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Fractionation and release of Cd, Cu, Pb, Mn, and Zn from historically contaminated river sediment in Southern China: Effect of time and pH. | The release of in situ heavy metals (cadmium [Cd], copper [Cu], lead [Pb], manganese [Mn], and zinc [Zn]) from contaminated river sediment near a Cu-iron mine in South China was experimentally studied. The effects of pH values and the kinetics of heavy metal release were investigated. In addition, species of the 5 metals in the sediment were determined as a function of pH and time. Rates and extents of metal desorption were studied over 30 d, and a 3-parameter, 2-compartment model was used to analyze the desorption kinetics. The rate constants (k<sub>s</sub> ) for the slowly desorbing fraction of heavy metals were found to be 5 to 6 orders of magnitude lower than the corresponding rate constants (k<sub>r</sub> ) for the rapidly desorbing fraction, suggesting that slow desorption is the rate-limiting step. The partition coefficients (K<sub>d</sub> ) varied significantly among metals, on the order Pb > Cu >Zn > Cd > Mn, indicating that the sediment had a much higher retention capability for strongly hydrolyzed metals than for weakly hydrolyzed ones. The amount of metals released from the sediment decreased dramatically at the final pH of 2 to 4 and leveled off in the pH range of 5 to 8. Release time and pH exhibited a varied influence on the fractionation of metals, and had a more remarkable influence on more mobile fractions and hardly any effect on the residual fraction during the desorption process. The fractionation of strongly adsorbing metals like Pb was not as dependent on release time and pH as it was for the weakly bonded metals like Mn and Cd. The results indicate that in situ heavy metals may exhibit a sustainable potential for release and may increase health risks when the pH of the river is lowered. Environ Toxicol Chem 2019;38:464-473. © 2018 SETAC. | Fractionation;Heavy metals;Release kinetics;Sediment;pH | pubmed |
FABP4 silencing ameliorates hypoxia reoxygenation injury through the attenuation of endoplasmic reticulum stress-mediated apoptosis by activating PI3K/Akt pathway. | Endoplasmic reticulum (ER) stress and subsequent apoptosis play a vital role in myocardial ischemia reperfusion (IR) injury. Fatty acid binding protein 4 (FABP4) may induce ER stress. The aim of this study was to investigate the mechanism and effect of FABP4 on IR injury in vitro. Rat H9c2 cells were exposed to hypoxia reoxygenation (HR) to create an IR model in vitro. FABP4 was overexpressed in HR-injured H9c2 cells. Transfection with FABP4 siRNA increased cell viability and decreased LDH upon HR stimulation. FABP4 cessation also suppressed apoptotic cells and caspase-3 activity after HR. Downregulation of FABP4 significantly inhibited ER stress by decreasing the protein expression of p-PERK, GRP78, and ATF6. FABP4 silencing also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins p-JNK, CHOP, Bax, and caspase-12, as well as upregulation of Bcl-2 during HR. Furthermore, FABP4 silencing activated the PI3K/Akt pathway. Blocking this pathway by the specific PI3K inhibitor-LY294002 restored HR-induced ER stress and subsequently reversed the protective effect of FABP4 silencing on HR injury. Taken together, our findings revealed that FABP4 silencing exerts protective effects against HR injury in H9c2 cells through inhibiting ER stress-induced cell apoptosis via activation of the PI3K/Akt pathway. | Apoptosis;Endoplasmic reticulum stress;FABP4;Hypoxia reoxygenation;PI3K/Akt | pubmed |
Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK. | To evaluate the appropriateness of the initial prescribed daily dose of non-vitamin K antagonist oral anticoagulants (NOACs) according to label in patients with non-valvular atrial fibrillation (NVAF) in the UK. Population-based cross-sectional study. UK primary care. 30 467 patients with NVAF and a first prescription for apixaban, dabigatran or rivaroxaban between January 2011 and December 2016. Percentage of patients prescribed a NOAC dose according to the European Union (EU) labels (appropriately dosed), and not according to the EU labels (inappropriately dosed-including both underdosed and overdosed patients); percentage of patients prescribed an initial NOAC dose according to renal function status. A total of 15 252 (50.1%) patients started NOAC therapy on rivaroxaban, 10 834 (35.6%) on apixaban and 4381 (14.4%) on dabigatran. Among patients starting NOAC therapy on rivaroxaban, 17.3% were eligible to receive a reduced dose compared with 12.8% of patients starting on apixaban and 53.8% of patients starting on dabigatran. The majority of patients were prescribed an appropriate dose according to the EU labels: apixaban 74.9 %, dabigatran, 74.4%; rivaroxaban, 84.2%. Underdosing occurred in 21.6% (apixaban), 8.7% (dabigatran), 9.1% (rivaroxaban). Overdosing was more frequent for dabigatran (16.9%) than for rivaroxaban (6.6%) or apixaban (3.5%). There was a trend towards dose reduction with increasing renal impairment. Among patients with severe renal impairment, the majority received a reduced dose NOAC: apixaban, 91.1%, dabigatran, 80.0%, rivaroxaban, 83.0%. Between 2011 and 2016, the majority of patients starting NOAC therapy in UK primary care were prescribed a daily dose in line with the approved EU drug label. Underdosing was more than twice as common among patients starting on apixaban than those starting on dabigatran or rivaroxaban. Research into the patient characteristics that may influence inappropriate underdosing of NOACs in UK primary care is warranted. | Cardiac Epidemiology;EPIDEMIOLOGY;Thromboembolism | pubmed |
Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective? | Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (-)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcumin + EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aβ40/Aβ42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (p < .0001) and hippocampal (p < .0001) areas of the Tg2576 mouse brain, along with lower Aβ<sub>40</sub>/Aβ<sub>42</sub> levels in the frontal cortex (p = .000129 and p = .000039, respectively) and Aβ<sub>42</sub> levels in the temporal lobe (p = .000082). A curcumin only diet was shown to lower amyloid plaque load (p = .028), but when combined with EGCG, DHA and ALA did not result in further decreases in amyloid plaque load. The EDA combination group showed the most prominent decrease in microglial activation (number of microglia around plaques: p < .05 and p < .0001, respectively, for the cortex and hippocampus). Analysing the hippocampal associated contextual fear conditioning revealed that both the curcumin+EDA (p < .0001) and EDA groups (p = .001) spent increased time on freezing compared to the control group. In addition, the curcumin+EDA group showed a significant increase in time spent freezing compared with the curcumin only group. In the amygdala associated cued test, all mice demonstrated the ability to associate the conditioned stimulus with the unconditioned stimulus as evidenced by a significant increase in freezing behaviour in response to the presentation of the cue (p < .0001). Post-hoc analysis showed that only curcumin+EDA (p < .0001) and EDA groups (p < .0001) developed a significant increase in freezing during the cue presentation. The results from this study show that the combination of EGCG, DHA and ALA (EDA) appeared to have the most potent anti-inflammatory and neuroprotective effect. Our results also demonstrate that interactions between nutraceutical products might result in counterproductive outcomes, highlighting the fact that manufacturers of nutraceuticals containing multiple compounds should be careful not to claim additive or synergistic effects of their combination products in vivo without having tested it in animal models and/or human clinical trials. | Amyloid plaque;Curcumin;Fish oil;Green tea;Inflammation;Lipoic acid;Microglia | pubmed |
Combining Wireless Technology and Behavioral Economics to Engage Patients (WiBEEP) with cardiometabolic disease: a pilot study. | The long-term management of cardiometabolic diseases, such as type 2 diabetes and hypertension, is complex and can be facilitated by supporting patient-directed behavioral changes. The concurrent application of wireless technology and personalized text messages (PTMs) based on behavioral economics in managing cardiometabolic diseases, although promising, has not been studied. The aim of this pilot study was to evaluate the feasibility and acceptability of the concurrent application of wireless home blood pressure (BP) monitoring (as an example of "automated hovering") and PTMs (as an example of "nudging") targeting pharmacotherapy and lifestyle habits in patients with cardiometabolic disease (type 2 diabetes and/or hypertension). The Wireless Technology and Behavioral Economics to Engage Patients (WiBEEP) with cardiometabolic disease study was a single-arm, open-label, 7-week-long pilot study in 12 patients (mean age 58.5 years) with access to a mobile phone. The study took place at Tufts Medical Center (Boston, MA) between March and September 2017. All patients received PTMs; nine patients received wireless home BP monitoring. At baseline, patients completed questionnaires to learn about their health goals and to assess medication adherence; at the end of week 7, all patients completed questionnaires to evaluate the feasibility and acceptability of the intervention and assess medication adherence. Hemoglobin A1c was ascertained from data collected during routine clinical care in 7 patients with available data. The majority of patients reported the text messages to be easy to understand (88%) and appropriate in frequency (71%) and language (88%). All patients reported BP monitoring to be useful. Mean arterial pressure was lower at the end-of-study compared to baseline (- 3.4 mmHg [95% CI, - 5 to - 1.8]. Mean change in hemoglobin A1c was - 0.31% [95% CI, - 0.56 to - 0.06]. Among patients with cardiometabolic disease, the combination of wireless BP monitoring and lifestyle-focused text messaging was feasible and acceptable. Larger studies will determine the long-term effectiveness of such an approach. | Blood pressure;Diabetes;Diet;Exercise;Text messages | pubmed |
Can the gut be the missing piece in uncovering PD pathogenesis? | It is now well established that Parkinson's disease (PD) is not only a movement disorder of the CNS but also a gastrointestinal disorder affecting the enteric nervous system (ENS). The gut-brain axis is a bidirectional communication between the brain and the gastrointestinal tract, which comprises besides the CNS and the ENS, the intestinal epithelial barrier, the intestinal microbiota and the enteroendocrine systems. In this review, we present the clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease. | Enteric nervous system;Gut microbiota;Gut-brain axis;Inflammation;Intestinal epithelial barrier;Parkinson's disease | pubmed |
Low partner testing in high HIV prevalence setting in Freetown, Sierra Leone: a retrospective study. | Despite a 1.5% National HIV prevalence, less than 40% of people living with HIV in Sierra Leone know their status. Limited activities on testing partners of HIV patients could be contributory to this substantial unawareness of HIV status. We carried out a retrospective study aimed at assessing partner testing and HIV prevalence among adults (≥ 15 years) tested using Determine™ and SD Bioline as recorded in the HIV testing registers from January to December 2017 at Connaught Hospital, an urban tertiary hospital in Sierra Leone. Of the 3808 clients tested for HIV, 2048 (53.8%) were females. The median age was 31 (IQR 24-42) years and 2104 (55.3%) were single. While 3014 (79.1%) had Provider-Initiated Testing and Counseling (PITC), 794 (20.9%) had Client-Initiated Testing and Counseling (CITC). HIV test was positive in 925 (24.3%) {CI 22.9-25.6, P < 0.001} clients. Of the 17 (0.4%) partners tested for HIV, 9 (52.9%) were positive. PITC yielded more HIV positive cases (760, 25.2%) than CITC (165, 20.8%). Partner testing (P = 0.007), female sex (P < 0.001) and PITC (P = 0.006) were associated with a positive HIV diagnosis. With high HIV prevalence and low partner testing, activities on partner testing are needed to improve the response to the epidemic. | Clients;Connaught Hospital;Counselling;Provider | pubmed |
Two new species of Batoctenus Sharp (Coleoptera: Staphylinidae: Pselaphinae) from French Guiana. | Two new species of the Neotropical pselaphine genus Batoctenus Sharp, 1887 are described from French Guiana, i.e., B. kawmontis sp. nov., and B. kociani sp. nov., with their habitus and major diagnostic characters illustrated. | Coleoptera, taxonomy, Batrisini, Batoctenus, new species, Neotropical region | pubmed |
Clinical outcome and toxicity after simultaneous integrated boost IMRT in head and neck squamous cell cancer patients. | A simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT) in patients with head and neck squamous cell carcinoma (HNSCC) allows to irradiate different target volumes to different dose levels within a single treatment session without increasing the toxicity. To analyze the outcome and toxicity of patients treated by definitive or postoperative SIB IMRT for HNSCC. 106 patients with HNSCC of the oral cavity (OC), oropharynx (OP), larynx (L) and hypopharynx (HP), consecutively treated at our cancer center between 3/2012 and 3/2014 were retrospectively analyzed. The prescribed SIB IMRT doses were in the postoperative setting (group A) 60-66 Gy and 53 Gy in 30-33 fractions for PTV high risk and PTV elective, respectively; and 70 Gy and 56 Gy in 35 fractions for PTV high risk and PTV elective, respectively when given as primary treatment (group B). Toxicity was consistently graded according to RTOG/EORTC scale. Median follow-up duration was 31 months. Thirty (28%) patients were postoperatively irradiated (group A) and 76 (72%) patients received definitive IMRT (group B). At 3 years, loco-regional control, distant control and overall survival were 78%, 78%, 57% and 64%, 76%, 52% in the postoperative (group A) and the definitive SIB IMRT group (group B), respectively. The observed acute grade 3 toxicities were dysphagia (44%), oral and/or oropharyngeal mucositis (40%) and dermatitis (21%). Late toxicity was predominantly clinically significant xerostomia (42%), dysgeusia (23%) and dysphagia (8%). SIB IMRT is feasible, safe and effective in the treatment of HNSCC patients. | Head and neck cancer;IMRT;Outcome;Radiotherapy;Simultaneous integrated boost;Squamous cell carcinoma | pubmed |
Functional transepithelial transport measurements to detect nephrotoxicity in vitro using the RPTEC/TERT1 cell line. | The kidney is a frequent target for organ-specific toxicity as a result of its primary function in controlling body fluids, for example, via resorption of amino acids, peptides, nutrients, ions, xenobiotics and water from the primary urine as well as excretion of metabolic waste products and hydrophilic and amphiphilic xenobiotics. Compounds exhibiting dose-limiting nephrotoxicity include drugs from highly diverse classes and chemical structures, e.g., antibiotics (gentamicin), chemotherapeutics (cisplatin), immunosuppressants (cyclosporine A and tacrolimus) or bisphosphonates (zoledronate). All of these compounds elicit nephrotoxicity primarily by injuring renal proximal tubule epithelial cells (RPTECs). However, prediction of a compound's nephrotoxic potential in humans to support early unmasking of risk-bearing drug candidates remains an unmet challenge, mainly due to the complex kidney anatomy as well as pronounced inter- and intraspecies differences and lack of relevant and validated human in vitro models. Accordingly, we used the recently established human RPTEC/TERT1 cell line to carry out toxicity studies with a focus on impairment of functional characteristics, i.e., transepithelial electrical resistance (TEER), vectorial transport of water, cations, and anions. Results were compared to real-time cytotoxicity assessments using cellular impedance (xCELLigence assay) and the routine cell viability readout (MTT). As expected, most toxins caused exposure time- and concentration-dependent cytotoxicity. However, for some compounds (cyclosporine A and tacrolimus), transport processes were strongly impaired in absence of a concomitant decrease in cell viability. In conclusion, these data demonstrate that functional parameters are important, highly sensitive and meaningful additional readouts for nephrotoxicity assessment in human renal proximal tubule epithelial cells. | Epithelial transport;In vitro;Kidney;Nephrotoxicity;Proximal tubule | pubmed |
Direct Feature Evaluation in Black-Box Optimization Using Problem Transformations. | Exploratory Landscape Analysis provides sample-based methods to calculate features of black-box optimization problems in a quantitative and measurable way. Many problem features have been proposed in the literature in an attempt to provide insights into the structure of problem landscapes and to use in selecting an effective algorithm for a given optimization problem. While there has been some success, evaluating the utility of problem features in practice presents some significant challenges. Machine learning models have been employed as part of the evaluation process, but they may require additional information about the problems as well as having their own hyper-parameters, biases and experimental variability. As a result, extra layers of uncertainty and complexity are added into the experimental evaluation process, making it difficult to clearly assess the effect of the problem features. In this article, we propose a novel method for the evaluation of problem features which can be applied directly to individual or groups of features and does not require additional machine learning techniques or confounding experimental factors. The method is based on the feature's ability to detect a prior ranking of similarity in a set of problems. Analysis of Variance (ANOVA) significance tests are used to determine if the feature has successfully distinguished the successive problems in the set. Based on ANOVA test results, a percentage score is assigned to each feature for different landscape characteristics. Experimental results for twelve different features on four problem transformations demonstrate the method and provide quantitative evidence about the ability of different problem features to detect specific properties of problem landscapes. | ANOVA;Black-box optimization;ELA features;evaluation criteria;linearity;neutrality;problem transformations;ruggedness;sample size. | pubmed |
Liddle's syndrome mechanisms, diagnosis and management. | Liddle's syndrome is a genetic disorder characterized by hypertension with hypokalemic metabolic alkalosis, hyporeninemia and suppressed aldosterone secretion that often appears early in life. It results from inappropriately elevated sodium reabsorption in the distal nephron. Liddle's syndrome is caused by mutations to subunits of the Epithelial Sodium Channel (ENaC). Among other mechanisms, such mutations typically prevent ubiquitination of these subunits, slowing the rate at which they are internalized from the membrane, resulting in an elevation of channel activity. A minority of Liddle's syndrome mutations, though, result in a complementary effect that also elevates activity by increasing the probability that ENaC channels within the membrane are open. Potassium-sparing diuretics such as amiloride and triamterene reduce ENaC activity, and in combination with a reduced sodium diet can restore normotension and electrolyte imbalance in Liddle's syndrome patients and animal models. Liddle's syndrome can be diagnosed clinically by phenotype and confirmed through genetic testing. This review examines the clinical features of Liddle's syndrome, the differential diagnosis of Liddle's syndrome and differentiation from other genetic diseases with similar phenotype, and what is currently known about the population-level prevalence of Liddle's syndrome. This review gives special focus to the molecular mechanisms of Liddle's syndrome. | ENaC;Liddle’s syndrome;blood pressure;distal nephron;hypertension | pubmed |
Hypertension and Cardiovascular Morbidity Following Surgery for Kidney Cancer. | Despite better renal function following nephron-sparing surgery (NSS) relative to radical nephrectomy (RN), there is no consensus with respect to the long-term sequelae associated with surgery. To investigate the effect of surgery and the temporal pattern of two different cardiovascular event (CVe) categories after NSS versus RN. We collected data of 898 patients with cT1-2 N0 M0 renal mass and no history of CVe treated with NSS versus RN. CVe categories were dichotomised in (1) de novo hypertension (HT) and (2) other major cardiovascular events (MCEs). Multivariable competing regression analyses (MVAs) tested the adjusted effect of surgery type on each CVe category. Among patients treated with RN, 38% of HT events occurred immediately after surgery. Conversely, in NSS counterparts, the onset of HT was diluted over the years after surgery (10% of HT events in the first 6 mo). When an MCE was considered, an increasing long-term time-dependent prevalence of the outcome was observed in both groups, with no statistically significantly difference between NSS and RN. At MVA, RN was associated with a higher HT risk (hazard ratio [HR] 2.89; p=0.006) than but a similar MCE risk (HR 0.85; p=0.6) to NSS. Relative to RN, NSS showed an independent protective effect on HT but not on MCEs. In patients with no history of preoperative HT or MCEs, the onset of HT after RN is a very early event, due probably to the acute loss of renal parenchyma. This is not the case for the other cardiovascular morbidity, which develops in the long-term period, regardless of the type of surgery performed. In renal cancer patients without a medical history of cardiopathy, preserving healthy kidney tissue at surgery is associated with a decreased risk of developing postoperative hypertension. | Cardiovascular events;Hypertension;Kidney cancer;Partial nephrectomy;Radical nephrectomy;Renal cancer | pubmed |
Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny. | Comparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. Here, in an effort to improve our understanding of the human microbiome, we compare gut microbiome composition and functional potential in 14 populations of humans from ten nations and 18 species of wild, non-human primates. Contrary to expectations from host phylogenetics, we find that human gut microbiome composition and functional potential are more similar to those of cercopithecines, a subfamily of Old World monkey, particularly baboons, than to those of African apes. Additionally, our data reveal more inter-individual variation in gut microbiome functional potential within the human species than across other primate species, suggesting that the human gut microbiome may exhibit more plasticity in response to environmental variation compared to that of other primates. Given similarities of ancestral human habitats and dietary strategies to those of baboons, these findings suggest that convergent ecologies shaped the gut microbiomes of both humans and cercopithecines, perhaps through environmental exposure to microbes, diet, and/or associated physiological adaptations. Increased inter-individual variation in the human microbiome may be associated with human dietary diversity or the ability of humans to inhabit novel environments. Overall, these findings show that diet, ecology, and physiological adaptations are more important than host-microbe co-diversification in shaping the human microbiome, providing a key foundation for comparative analyses of the role of the microbiome in human biology and health. | Cercopithecine;Human evolution;Human gut microbiome;Primate gut microbiome | pubmed |
The interplay between substance use and intimate partner violence perpetration: A meta-ethnography. | The relationship between intimate partner violence (IPV) perpetration and substance use is not well understood. We conducted a meta-ethnography of qualitative studies to explore how substance use features in survivors' and perpetrators' accounts of IPV perpetration. Qualitative studies from 1995 to 2016 were identified from PsycINFO, ASSIA and Web of Science, with an update in PsycINFO and ASSIA to December 2017. 7654 abstracts were screened for accounts of heterosexual IPV perpetration, then full-texts were screened for mentions of substance use. Key concepts from 26 qualitative studies (363 female survivors' and 219 male perpetrators' views) were synthesised to develop a grounded theory that put similarities and differences between studies into an interpretive order. Six themes emerged: five related to the complex interplay between substance use and IPV perpetration in the context of intoxication, withdrawal and addiction, impact on relationship and wider dynamics of power and control and psychological vulnerabilities; a final theme related to survivors' agency and resistance to IPV perpetration. Survivors and perpetrators noted how both intoxication and withdrawal could pre-empt IPV perpetration. Survivors, however, were more likely to see intoxication and withdrawal as part of a pattern of abusive behaviour, whereas perpetrators tended to describe a causal relationship between intoxication and discrete incidents of IPV perpetration. Irritability and frustration during withdrawal from or craving alcohol, heroin and stimulants, and/or a failure or partner refusal to procure money for drugs increased the likelihood of violence. Survivors were more likely than perpetrators to identify abuse in relation to the impact of substance use on their relationship and dynamics of power and control. The interplay between substance use and IPV perpetration occurs at numerous contextual levels and is perceived differently by perpetrators and survivors. Behaviour change interventions must address the meanings behind divergent narratives about IPV perpetration and substance use. | Alcohol;Intimate partner violence;Meta-ethnography;Perpetrator;Qualitative research;Substance use;Survivor;Victim | pubmed |
Relation between adaptive function and IQ among youth with histories of heavy prenatal alcohol exposure. | Adaptive function and general intellectual function are two important and often correlated domains. While youth with prenatal alcohol exposure frequently demonstrate impairments in both domains, it is not clear whether the relation between these domains is consistent across levels of ability or whether, for example, adaptive function is less affected by intellectual function at higher ability levels. The aim of the current study was to test this relation in youth with and without prenatal alcohol exposure. As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phase II, subjects with heavy prenatal alcohol exposure (AE) and nonexposed subjects with and without other clinical conditions or concerns (CON) completed a comprehensive neurobehavioral battery. Multiple regression analyses tested the relation between full scale IQ (FSIQ) and overall adaptive function. Interaction terms between Group and each variable were created to formally test for group differences. Three subsequent regression analyses tested which adaptive function domains (Communication, Daily Living Skills, Socialization) significantly contributed to results. Follow-up analyses examined correlations based on IQ range (low IQ <85; high IQ ≥85). The interaction between FSIQ and Group on overall adaptive function was significant; the relationship between FSIQ and adaptive function was weaker in the AE group than in the CON group. Regarding specific adaptive function domains, the interaction between FSIQ and Group was significant only in the Communication domain. Follow-up analyses showed, within the low IQ range, the correlation between FSIQ and Communication was stronger in the CON group than the AE group. Within the high IQ range, the correlation between FSIQ and Communication was significant only in the CON group. Although higher intellectual functioning was associated with better adaptive function ability among controls, this was not found among the alcohol-exposed youth where a general dampening of adaptive ability was noted. Further, the differential relationship between IQ and adaptive function between groups appears to be driven by communication abilities. These findings suggest that level of intellectual functioning of children with prenatal alcohol exposure does not fully account for caregiver-reported communication and overall adaptive function deficits particularly at higher levels of functioning. | adaptive function;fetal alcohol spectrum disorders (FASD);fetal alcohol syndrome (FAS);intellectual functioning | pubmed |
Clinical retrospective analysis of long-pulsed 1064-nm Nd:YAG laser in the treatment of onychomycosis and its effect on the ultrastructure of fungus pathogen. | The objective of this study was to analyze retrospectively the clinical efficacy and fungal clearance of long-pulsed 1064-nm Nd:YAG laser for treating onychomycosis and explore the inhibitory effects of laser on the fungus pathogen-induced onychomycosis in vitro. We performed a systematic retrospective analysis of clinical patients (162 effected nails) of onychomycosis treatment applying laser with or without topical ketoconazole ointment and followed up 3 months after treatment. Trichophyton rubrum- and Trichophyton mentagrophytes-induced onychomycosis was irradiated with laser superimposed for different cumulative energy, respectively; then, the areas of fungus colonies and growth curve in different days were showed, and changes in ultrastructures were observed under SEM and TEM. The clinical effective rate and fungal clearance rate in the combined group were higher than those in the laser group; however, there was no significant difference between the two groups. In vitro, the areas of T. rubrum colonies were significantly reduced at days 1, 3, and 5 after irradiation with cumulative laser energy ≥ 6400 J/cm<sup>2</sup>. When irradiated with cumulative laser energy ≥ 25600 J/cm<sup>2</sup>, significant difference in the areas of T. mentagrophytes colonies was found at day 5. And ultrastructure of the two strains before and after laser irradiation was damaged at different degrees. This study confirmed that long-pulsed 1064-nm Nd:YAG laser is effective for treating onychomycosis, and the laser irradiation can inhibit the colony growth of T. rubrum and T. mentagrophytes and change their cellular ultrastructures. The mechanism of laser treatment of onychomycosis may be related to direct damage of fungus pathogen. | Electron microscopy;Irradiation;Long-pulsed 1064-nm Nd:YAG laser;Onychomycosis;Trichophyton mentagrophytes;Trichophyton rubrum | pubmed |
Factors Associated with Mammographic Density in Postmenopausal Women. | Breast density increases the risk of breast cancer, but also in the interpretation of mammography is also important. This study examine the risk factors affecting breast density in postmenopausal women. Between January 2013 and January 2014, 215 patients admitted to The Clinics of Gynecology and Obstetrics with complaints of menopause were taken. According to the results of mammography, Group I (non-dense, n = 175) and Group II (dense, n = 40) were created. The informations of the caseswere analyzed retrospectively. In Group I, body mass index (BMI), number of pregnancies, parity were significantly higher than group II (P < 0.05). In group II, the withdrawal period of menstruation and progesterone levels were significantly higher (P < 0.05). In logistic regression analysis, BMI for dense breasts and number of pregnancies were found to be an independent risk factor (P < 0.05). Increased BMI, pregnancy and parity, result of reduction in density , but longer duration of menopause and increased progesterone cause an increase in density. BMI and the number of pregnancy was found to be independent risk factors for reducing breast density. | Mammary glands human;Mammography;Postmenopause | pubmed |
A proton current associated with sour taste: distribution and functional properties. | Sour taste is detected by taste receptor cells that respond to acids through yet poorly understood mechanisms. The cells that detect sour express the protein PKD2L1, which is not the sour receptor but nonetheless serves as a useful marker for sour cells. By use of mice in which the PKD2L1 promoter drives expression of yellow fluorescent protein, we previously reported that sour taste cells from circumvallate papillae in the posterior tongue express a proton current. To establish a correlation between this current and sour transduction, we examined its distribution by patch-clamp recording. We find that the current is present in PKD2L1-expressing taste cells from mouse circumvallate, foliate, and fungiform papillae but not in a variety of other cells, including spinal cord neurons that express PKD2L1. We describe biophysical properties of the current, including pH-dependent Zn(2+) inhibition, lack of voltage-dependent gating, and activation at modest pH values (6.5) that elicit action potentials in isolated cells. Consistent with a channel that is constitutively open, the cytosol of sour taste cells is acidified. These data define a functional signature for the taste cell proton current and indicate that its expression is mostly restricted to the subset of taste cells that detect sour. | PKD2L1;acid;ion channel;pH;sensory transduction | pubmed |
Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches. | Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. | Plasmodium falciparum;cerebral malaria;diagnostic;new therapies;pathophysiology;research tools | pubmed |
Larvicidal activity of catechin isolated from Leucas aspera against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus (Diptera: Culicidae). | Vector control is facing a threat due to the emergence of resistance to synthetic insecticides. Insecticides of plant origin my serve as an alternative biocontrol technique in the future. The aim of the present study was to evaluate the larvicidal activity of fractions and compounds from the whole-plant methanol extracts of Leucas aspera on the fourth-instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. The larvae were exposed to fractions with concentrations ranging from 1.25, 2.25, 5, 10, and 20 ppm and isolated compounds. After 24 h exposure, larval mortality was assessed. Among the eight fractions, four from hexane extractions showed potent larvicidal activity against tested mosquito species at 20 ppm concentration. The isolated compound catechin showed pronounced larvicidal activity at very low concentrations. The LC50 and LC90 values of catechin were 3.05 and 8.25 ppm against Ae. aegypti, 3.44 and 8.89 ppm against An. stephensi, and 3.76 and 9.79 ppm against C. quinquefasciatus, respectively. The isolated compound was subjected to spectral analyses (GC-MS, FTIR, (1)H NMR, and (13)C NMR) to elucidate the structure and to compare with spectral data literature. | Aedes aegypti;Anopheles stephensi;Catechin;Culex quinquefasciatus;Larvicidal activity;Leucas aspera | pubmed |
Prediction of the thickness of the compensator filter in radiation therapy using computational intelligence. | In this study, artificial neural networks (ANNs) and adaptive neuro-fuzzy inference system (ANFIS) are investigated to predict the thickness of the compensator filter in radiation therapy. In the proposed models, the input parameters are field size (S), off-axis distance, and relative dose (D/D0), and the output is the thickness of the compensator. The obtained results show that the proposed ANN and ANFIS models are useful, reliable, and cheap tools to predict the thickness of the compensator filter in intensity-modulated radiation therapy. | Computational intelligence;Filter in radiation therapy;Radiation therapy;Thickness of the compensator | pubmed |
Higher breastfeeding performance index is associated with lower risk of illness in infants under six months in Ethiopia. | Breastfeeding performance index is an explanatory attempt to summarize key breastfeeding practices by summarizing the different dimensions of breastfeeding practices into a single summary variable. Breastfeeding performance index is used to assess optimal breastfeeding practices by constructing a single composite index that includes timely initiation of breastfeeding, prelacteal feeding, current breastfeeding status, bottle feeding, any liquid given(except medicine) in the last 24 h, formula given in the last 24 h, any solid food given in the last 24 h. This study aimed to assess optimal breastfeeding practices of 0-6 month infants using breastfeeding performance index (BPI) and its association with childhood illness in Ethiopia. A secondary data analysis was carried out based on the Ethiopia Demographic and Health Survey (EDHS) 2011 data. The BPI was created using seven components by giving equal weight for all components during scoring. The data were described using descriptive statistics and analyzed using multivariable logistic regression. The prevalence of low, medium, and high BPI was 18.41, 57.96 and 23.63 % respectively. The mean BPI score was 4.38 (SD 1.25; 95 % CI 4.31, 4.45). Multivariable logistic regression analysis showed that those infants who had low BPI score were 2.22 times (AOR = 2.22; 95 % CI 1.20, 4.11) and medium BPI category had 2.15 times at higher odds (AOR = 2.15; 95 % CI 1.23, 3.75) of developing diarrhea compared to infants in the highest BPI category. Being in the lower BPI category was significantly associated with higher odds of having fever (AOR = 1.73; 95 % CI 1.06, 2.80). Being in the medium index category was also associated with higher odds of having short and rapid breaths (AOR = 2.02; 95 % CI 1.01, 4.04). More than 80 % of the infants did not receive optimal breastfeeding practices based on the Breastfeeding Performance Index. Lower BPI was statistically associated with diarrhea, fever and short and rapid breaths illness in the last 2 weeks. This study implicates the importance of optimal breastfeeding to reduce childhood illness. | Breastfeeding;DHS;Ethiopia;Index;Infants | pubmed |
Crystal structure of 1-(2-amino-phen-yl)-3-phenyl-urea. | In the title compound, C13H13N3O, the phenyl ring makes a dihedral angle of 47.0 (1)° with the mean plane of the -NC(=O)N- unit, while the dihedral angle between the latter mean plane and the amino-phenyl ring is 84.43 (7)°. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds involving the central -NHC(=O)NH- units, forming chains running parallel to the b axis. These chains associate with one another via N-H⋯O and N-H⋯N hydrogen bonds, from the pendant amino groups to the -NHC(=O)NH- units of adjacent mol-ecules, forming columns propagating along [010]. The structure was refined as a two-component twin with a 0.933 (3):0.067 (3) domain ratio. | N—H⋯N hydrogen bonds;N—H⋯O hydrogen bonds;crystal structure;twinned structure;urea derivatives | pubmed |
A dual-valve system to minimize loss of pneumoperitoneum in laparoscopic surgery. | Loss of visualization of the surgical field due to pneumoperitoneum deflation when CO2 insufflator cylinders become empty can occur at key moments during laparoscopic surgery. The purpose of this study was to examine the incidence of intraoperative cylinder exhaustion in the United Kingdom, determine its impact on patient safety, and design and test a novel device to minimize the phenomenon. We performed a national cross-sectional survey of U.K. surgeons, inviting all members of the Association of Surgeons of Great Britain and Ireland (ASGBI) and the Association of Upper GI Surgeons (AUGIS) to participate. We designed and tested a novel dual-valve system to allow rapid intraoperative exchange of CO2 cylinders. Eighty-five percent of the U.K. surgeons surveyed reported loss of surgical visualization at critical times during laparoscopic surgery, caused by the decrease in pneumoperitoneum during CO2 cylinder exchange. Eighty-four percent said that the process contributed to the surgeon's stress, and 63% said that a device that maintains uninterrupted pneumoperitoneum would reduce the risk of intraoperative complications. In our locale, a timed cylinder exchange was, on average, 30 times quicker with the novel dual valve than by conventional cylinder exchange (mean conventional exchange time, 61.3 ± 7.3 s vs. novel device, 2.0 ± 0.2 s; P ≤ .0001) and could be performed just as rapidly by staff unfamiliar with the device (2.2 ± 0.3 s vs. 1.9 ± 0.4 s P = .1945). We suggest that this simple, low-cost system could be developed for use in a clinical setting to enhance patient safety. | CO2 cylinder exchange;Loss of insufflation | pubmed |
Fall risk is associated with amplified functional connectivity of the central executive network in patients with Parkinson's disease. | Falls are debilitating problems that markedly impact the health-related quality of life of many patients with Parkinson's disease (PD). Numerous studies point to the role of executive function and attention in falls; however, the brain mechanisms underlying these relationships are less clear. Here, we aim to evaluate the brain mechanisms underlying the role of executive function in falls. Patients with PD who were fallers (n = 27) or non-fallers (n = 53) and 27 healthy older adults were examined in a cross-sectional study. Gray matter volumes of the caudate head and posterior putamen were evaluated, as these striatal regions play a role in the executive and the sensorimotor cortico-striatal networks, respectively. The functional connectivity of the central executive network and of the sensorimotor network was measured using intrinsic brain connectivity during resting state functional magnetic resonance imaging. Compared to non-fallers and healthy controls, fallers had lower gray matter volume in the caudate head, but not in the posterior putamen, and increased connectivity between posterior partial regions of the central executive network, with no difference within the sensorimotor network. Mediation analysis demonstrated that the relationships between caudate head gray matter volume and fall history and risk were mediated by increased connectivity within the central executive network, apparently via attentional changes. The above findings provide additional converging evidence for the involvement of executive-related brain changes in falls in PD and support the important role of attention and executive function in fall risk. | Caudate;Central executive network;Falls;Function connectivity;Parkinson’s disease | pubmed |
Causes and consequences of habitat fragmentation in river networks. | Increases in river fragmentation globally threaten freshwater biodiversity. Rivers are fragmented by many agents, both natural and anthropogenic. We review the distribution and frequency of these major agents, along with their effects on connectivity and habitat quality. Most fragmentation research has focused on terrestrial habitats, but theories and generalizations developed in terrestrial habitats do not always apply well to river networks. For example, terrestrial habitats are usually conceptualized as two-dimensional, whereas rivers often are conceptualized as one-dimensional or dendritic. In addition, river flow often leads to highly asymmetric effects of barriers on habitat and permeability. New approaches tailored to river networks can be applied to describe the network-wide effects of multiple barriers on both connectivity and habitat quality. The net effects of anthropogenic fragmentation on freshwater biodiversity are likely underestimated, because of time lags in effects and the difficulty of generating a single, simple signal of fragmentation that applies to all aquatic species. We conclude by presenting a decision tree for managing freshwater fragmentation, as well as some research horizons for evaluating fragmented riverscapes. | barrier;biodiversity;connectivity;defragmentation;edge effect;matrix permeability | pubmed |
Amnesia in an actor: Learning and re-learning of play passages despite severe autobiographical amnesia. | We describe the case of an accomplished actor, whom we term AB, who suffered severe amnesia following a cardiac arrest and hypoxic brain damage, affecting medial temporal and thalamic structures. His performance on standard episodic memory tests, and on measures of retrograde amnesia, including autobiographical memory, was severely impaired. When presented with passages from plays he had not appeared in, AB showed a severe impairment at the first learning trial, but thereafter showed a 'normal' learning curve for this semantically and syntactically complex material. On being presented with passages from plays he had performed in the past, AB did not show any recognition of them whatsoever, as one might expect from his severe episodic memory impairment. However, AB showed a striking benefit (savings score) in relearning passages he had previously performed, compared with new passages, despite not having any autobiographical recall of having performed the relearned passages before. Moreover, although his initial recall performance in learning these passages was impaired compared with healthy control actors of similar age and experience, AB demonstrated the same incremental learning rate on subsequent learning trials of the passages as did the controls. We conclude that, although severely impaired at the first learning trial (on both 'new' and 'old' passages), AB was able to employ his long-established semantic and procedural skills to attempt the task, and that thereafter he showed a 'normal' rate of incremental learning from a lower baseline. | Actor;Autobiographical amnesia;Episodic memory;Semantic learning | pubmed |
Relationship between echocardiographic and cardiac magnetic resonance imaging-derived measures of right ventricular function in patients with chronic thromboembolic pulmonary hypertension. | Echocardiography is widely used to evaluate right ventricular (RV) function. However, the value of echocardiographic parameters to assess RV function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. In this study, we analyzed the correlations between echocardiographic parameters and the RV ejection fraction (RVEF) as measured by cardiac magnetic resonance (CMR) imaging to systematically elucidate the role of echocardiographic parameters in the assessment of RV function in patients with CTEPH. Echocardiography was used to measure the tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), fractional area change (FAC), myocardial performance index (MPI), and tricuspid annular plane systolic excursion (TAPSE). CMR was used to measure the RV end-diastolic volume (RVEDV) and end-systolic volume (RVESV), and the RVEF was calculated. A significant positive correlation was found between S' and RVEF (r=0.689, P<0.0001) and between FAC and RVEF (r=0.423, P=0.022), a significant negative correlation was found between MPI and RVEF (r=-0.387, P=0.048), and no correlation was found between TAPSE and RVEF (r=0.451, P=0.22). Echocardiography can be routinely used in the clinical setting to measure S', FAC, and MPI for the evaluation of right heart function in patients with CTEPH. | CMR;chronic thromboembolic pulmonary hypertension;echocardiography;right ventricular function | pubmed |
The growth of computer-assisted (robotic) surgery in urology 2000-2014: The role of Asian surgeons. | A major role in the establishment of computer-assisted robotic surgery (CARS) can be traced to the work of Mani Menon at Vattikuti Urology Institute (VUI), and of many surgeons of Asian origin. The success of robotic surgery in urology has spurred its acceptance in other surgical disciplines, improving patient comfort and disease outcomes and helping the industrial growth. The present paper gives an overview of the progress and development of robotic surgery, especially in the field of Urology; and to underscore some of the seminal work done by the VUI and Asian surgeons in the development of robotic surgery in urology in the US and around the world. PubMed/Medline and Scopus databases were searched for publications from 2000 through June 2014, using algorithms based on keywords "robotic surgery", "prostate", "kidney", "adrenal", "bladder", "reconstruction", and "kidney transplant". Inclusion criteria used were published full articles, book chapters, clinical trials, prospective and retrospective series, and systematic reviews/meta-analyses written in English language. Studies from Asian institutions or with the first/senior author of Asian origin were included for discussion, and focused on techniques of robotic surgery, relevant patient outcomes and associated demographic trends. A total of 58 articles selected for final review highlight the important strides made by robots in urology, from robotic radical prostatectomy in 2000 to robotic kidney transplant in 2014. In the hands of an experienced robotic surgeon, it has been demonstrated to improve functional patient outcomes and minimize perioperative complications compared to open surgery, especially in urologic oncology and reconstructive urology. With increasing surgeon proficiency, the benefits of robotic surgery were consistently seen across different surgical disciplines, patient populations, and strata. The addition of robot to the surgical armamentarium has allowed better patient care and improved disease outcomes. VUI and surgeons of Asian origin have played a pioneering role in dissemination of computer-assisted surgery. | Asian;IDEAL;Kidney transplant;Nephrectomy;Radical cystectomy;Radical prostatectomy;Reconstructive urology;Robotic surgery | pubmed |
Stressful life events and leukocyte telomere attrition in adulthood: a prospective population-based cohort study. | Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL). Participants were 1094 adults (mean age 53.1, range 33-79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education. Recent life events significantly predicted telomere attrition prospectively (B = -0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood. Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively. | Adversity;life events;observational cohort study;prospective;stress;telomere | pubmed |
Structural characterization and anti-tumor activity of polysaccharide produced by Hirsutella sinensis. | HSP-III, a novel homogeneous polysaccharide with 513.89 kDa molecular weight, was fractionated from submerged cultures of Hirsutella sinensis by Sevag and chromatography on Sephadex G-100 column. The total sugar content of HSP-III was amounted to 89.87%. Based on the results of high performance gel permeation chromatogram (HPGPC), FT-IR, NMR spectroscopy, GC, periodate oxidation-smith degradation and methylation analysis, it showed that HSP-III was mainly composed of mannose and galactose, and a small amount of rhamnose, arabinose, xylose, and glucose. The molar ratio of Rha:Ara:Xyl:Man:Glu:Gal was 1.00:2.44:13.11:74.13:13.80:54.39. The main chain of HSP-III was majorly composed of (1→3) glucose. The tumor inhibition ratio on H22 cell was 79.04% at 100 μg/mL of HSP-III. | Anti-tumor activity;Polysaccharide;Structure | pubmed |
Complete annotated genome sequence of Mycobacterium tuberculosis (Zopf) Lehmann and Neumann (ATCC35812) (Kurono). | We report the completely annotated genome sequence of Mycobacterium tuberculosis (Zopf) Lehmann and Neumann (ATCC35812) (Kurono), which is a used for virulence and/or immunization studies. The complete genome sequence of M. tuberculosis Kurono was determined with a length of 4,415,078 bp and a G+C content of 65.60%. The chromosome was shown to contain a total of 4,340 protein-coding genes, 53 tRNA genes, one transfer messenger RNA for all amino acids, and 1 rrn operon. Lineage analysis based on large sequence polymorphisms indicated that M. tuberculosis Kurono belongs to the Euro-American lineage (lineage 4). Phylogenetic analysis using whole genome sequences of M. tuberculosis Kurono in addition to 22 M. tuberculosis complex strains indicated that H37Rv is the closest relative of Kurono based on the results of phylogenetic analysis. These findings provide a basis for research using M. tuberculosis Kurono, especially in animal models. | Complete genome;Kurono;PE-PPE;PacBio sequencer;Phyrogenetic tree | pubmed |
Adverse childhood experiences and substance use among Hispanic emerging adults in Southern California. | Emerging adults who experienced stressful childhoods may engage in substance use as a maladaptive coping strategy. Given the collectivistic values Hispanics encounter growing up, adverse childhood experiences may play a prominent role in substance use decisions as these events violate the assumptions of group oriented cultural paradigms. Alternatively, adverse childhood events might not increase the risk of substance use because strong family ties could mitigate the potential maladaptive behaviors associated with these adverse experiences. This study examined whether adverse childhood experiences were associated with substance use among Hispanic emerging adults. Participants (n = 1420, mean age = 22, 41% male) completed surveys indicating whether they experienced any of 8 specific adverse experiences within their first 18 years of life, and past-month cigarette use, marijuana use, hard drug use, and binge drinking. Logistic regression models examined the associations between adverse childhood experiences and each category of substance use, controlling for age, gender, and depressive symptoms. The number of adverse childhood experiences was significantly associated with each category of substance use. A difference in the number of adverse childhood experiences, from 0 to 8, was associated with a 22% higher probability of cigarette smoking, a 24% higher probability of binge drinking, a 31% higher probability of marijuana use, and a 12% higher probability of hard drug use respectively. These findings should be integrated into prevention/intervention programs in hopes of quelling the duration and severity of substance use behaviors among Hispanic emerging adults. | Adverse childhood experiences;Emerging adults;Hispanics;Prevention;Substance use;Young adults | pubmed |
Sodium bicarbonate ingestion augments the increase in PGC-1α mRNA expression during recovery from intense interval exercise in human skeletal muscle. | We tested the hypothesis that ingestion of sodium bicarbonate (NaHCO3) prior to an acute session of high-intensity interval training (HIIT) would augment signaling cascades and gene expression linked to mitochondrial biogenesis in human skeletal muscle. On two occasions separated by ∼1 wk, nine men (mean ± SD: age 22 ± 2 yr, weight 78 ± 13 kg, V̇O(2 peak) 48 ± 8 ml·kg(-1)·min(-1)) performed 10 × 60-s cycling efforts at an intensity eliciting ∼90% of maximal heart rate (263 ± 40 W), interspersed with 60 s of recovery. In a double-blind, crossover manner, subjects ingested a total of 0.4 g/kg body weight NaHCO3 before exercise (BICARB) or an equimolar amount of a placebo, sodium chloride (PLAC). Venous blood bicarbonate and pH were elevated at all time points after ingestion (P < 0.05) in BICARB vs. PLAC. During exercise, muscle glycogen utilization (126 ± 47 vs. 53 ± 38 mmol/kg dry weight, P < 0.05) and blood lactate accumulation (12.8 ± 2.6 vs. 10.5 ± 2.8 mmol/liter, P < 0.05) were greater in BICARB vs. PLAC. The acute exercise-induced increase in the phosphorylation of acetyl-CoA carboxylase, a downstream marker of AMP-activated protein kinase activity, and p38 mitogen-activated protein kinase were similar between treatments (P > 0.05). However, the increase in PGC-1α mRNA expression after 3 h of recovery was higher in BICARB vs. PLAC (approximately sevenfold vs. fivefold compared with rest, P < 0.05). We conclude that NaHCO3 before HIIT alters the mRNA expression of this key regulatory protein associated with mitochondrial biogenesis. The elevated PGC-1α mRNA response provides a putative mechanism to explain the enhanced mitochondrial adaptation observed after chronic HIIT supplemented with NaHCO3 in rats. | glycogen;high-intensity interval training;mitochondria;supplementation | pubmed |
Glucagon-like polypeptide agonists in type 2 diabetes mellitus: efficacy and tolerability, a balance. | Glucagon-like polypeptide (GLP-1) receptor agonist treatment has multiple effects on glucose metabolism, supports the β cell, and promotes weight loss. There are now five GLP-1 agonists in clinical use with more in development. GLP-1 treatment typically can induce a lowering of hemoglobin A1c (HbA1c) of 0.5-1.5% over time with weight loss of 2-5%. In some individuals, a progressive loss of weight occurs. There is evidence that GLP-1 therapy opposes the loss of β cells which is a feature of type 2 diabetes. The chief downside of GLP-1 treatment is the gastrointestinal motility disturbance which is one of the modes of action of the hormone; significant nausea, vomiting, and diarrhea may lead to discontinuation of treatment. Although daily injection of GLP-1 agents is successful, the development of extended release preparations allows for injection once weekly, and perhaps much longer in the future. The indication for GLP-1 use is diabetes, but now, liraglutide has been approved for primary treatment of obesity. When oral agents fail to control glucose levels in type 2 diabetes, there is a choice between long-acting insulin and GLP-1 agonists as additional treatments. The lowering of HbA1c by either modality is equivalent in most studies. Patients lose weight with GLP-1 treatment and gain weight on insulin. There is a lower incidence of hypoglycemia with GLP-1 therapy but a much higher incidence of gastrointestinal complaints. Insulin dosing is flexible while GLP-1 agents have historically been administered at fixed dosages. Now, the use of combined long-acting insulin and GLP-1 agonists is promising a major therapeutic change. Combined therapy takes advantage of the benefits of both insulin and GLP-1 agents. Furthermore, direct admixture of both in the same syringe will permit flexible dosing, improvement of glucose levels, and reduction of both hypoglycemia and gastrointestinal side effects. | albiglutide;dulaglutide;exenatide;liraglutide;lixisenatide | pubmed |
Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. | We describe a novel nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum among 30 children (ages 1.0 to 28 years) from diverse Amish demes. Children with nephrocerebellar syndrome had progressive microcephaly, visual impairment, stagnant psychomotor development, abnormal extrapyramidal movements and nephrosis. Fourteen died between ages 2.7 and 28 years, typically from renal failure. Post-mortem studies revealed (i) micrencephaly without polymicrogyria or heterotopia; (ii) atrophic cerebellar hemispheres with stunted folia, profound granule cell depletion, Bergmann gliosis, and signs of Purkinje cell deafferentation; (iii) selective striatal cholinergic interneuron loss; and (iv) optic atrophy with delamination of the lateral geniculate nuclei. Renal tissue showed focal and segmental glomerulosclerosis and extensive effacement and microvillus transformation of podocyte foot processes. Nephrocerebellar syndrome mapped to 700 kb on chromosome 15, which contained a single novel homozygous frameshift variant (WDR73 c.888delT; p.Phe296Leufs*26). WDR73 protein is expressed in human cerebral cortex, hippocampus, and cultured embryonic kidney cells. It is concentrated at mitotic microtubules and interacts with α-, β-, and γ-tubulin, heat shock proteins 70 and 90 (HSP-70; HSP-90), and the carbamoyl phosphate synthetase 2/aspartate transcarbamylase/dihydroorotase multi-enzyme complex. Recombinant WDR73 p.Phe296Leufs*26 and p.Arg256Profs*18 proteins are truncated, unstable, and show increased interaction with α- and β-tubulin and HSP-70/HSP-90. Fibroblasts from patients homozygous for WDR73 p.Phe296Leufs*26 proliferate poorly in primary culture and senesce early. Our data suggest that in humans, WDR73 interacts with mitotic microtubules to regulate cell cycle progression, proliferation and survival in brain and kidney. We extend the Galloway-Mowat syndrome spectrum with the first description of diencephalic and striatal neuropathology. | cerebellar hypoplasia;mTOR;mitosis;nephrosis;progressive microcephaly | pubmed |
The prehospital management of traumatic brain injury. | Traumatic brain injury (TBI) is an important cause of death and disability, particularly in younger populations. The prehospital evaluation and management of TBI is a vital link between insult and definitive care and can have dramatic implications for subsequent morbidity. Following a TBI the brain is at high risk for further ischemic injury, with prehospital interventions targeted at reducing this secondary injury while optimizing cerebral physiology. In the following chapter we discuss the prehospital assessment and management of the brain-injured patient. The initial evaluation and physical examination are discussed with a focus on interpretation of specific physical examination findings and interpretation of vital signs. We evaluate patient management strategies including indications for advanced airway management, oxygenation, ventilation, and fluid resuscitation, as well as prehospital strategies for the management of suspected or impending cerebral herniation including hyperventilation and brain-directed hyperosmolar therapy. Transport decisions including the role of triage models and trauma centers are discussed. Finally, future directions in the prehospital management of traumatic brain injury are explored. | Airway management;emergency medical services;traumatic brain injury | pubmed |
Bile acid accelerates erbB2-induced pro-tumorigenic activities in biliary tract cancer. | Although very few studies have addressed the molecular and cellular mechanisms underlying the development of biliary tract cancer (BTC), several lines of evidence suggest a role for the erbB receptor family. Overexpression and activation of erbB2 has been reported in a significant percentage of human BTC. Further, we previously reported that overexpression of erbB2 basal epithelial cells of the biliary tract (BK5.erbB2 mouse) led to the development of BTC. However, the mechanisms by which erbB2 overexpression led to the spontaneous development of tumors specifically in the biliary tract are not completely understood. The goals of the current study were to (1) determine whether a cooperative relationship between bile acid exposure and erbB2 activation exists during biliary tract carcinogenesis and (2) to characterize the mechanism(s) underlying bile acid-mediated biliary tract carcinogenesis in cells with activated erbB2. In this study, we demonstrated that the secondary conjugated bile acid, taurochenodeoxycholic acid (TCDC), increased proliferation of primary cultured gallbladder epithelial cells from BK5.erbB2 mice and human BTC cells. TCDC treatment activated EGFR/erbB2 and downstream signaling molecules in both primary cultured cells and human BTC cells. TCDC also increased the expression of epidermal growth factor receptor (EGFR) ligands and TACE activity in human BTC cells. Inhibition of src activation led to attenuation of bile-induced upregulation of TACE activity as well as signaling through the EGFR/erbB2, suggesting that during the development of BTC erbB2 overexpression/activation accelerates the bile acid-induced signaling cascade: bile acid → src → TACE → EGFR/erbB2 → downstream signaling. We also provide direct evidence that bile acids possess tumor promoting capacity in epithelial cells overexpressing erbB2 using the two-stage skin carcinogenesis model. Collectively these findings suggest cooperative roles for bile acid and erbB2 activation in epithelial cell proliferation; bile acid appears to accelerate erbB2-induced pro-tumorigenic activities in the biliary tract and skin. | bile acid;biliary tract cancer;erbB2 | pubmed |
The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. | Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders. | core needle biopsy;forceps biopsy;locally advanced rectal cancer;neoadjuvant chemoradiotherapy | pubmed |
Heart failure patients' descriptions of participation in structured home care. | To strengthen the patient's position in health care, patient participation has been decreed in policy documents and legalizations. For patients suffering from heart failure, self-care is an important part of disease management and participation is crucial to succeed with this. To examine how heart failure patients receiving structured home care described participation in the care. Qualitative study. Thirteen men and six women, aged between 63 and 90 years, were interviewed. The informants received structured home care at four home care units in Sweden. The interviews were analysed using qualitative content analysis. Five categories with associated subcategories describing participation in care were identified: communication between patients and health-care professionals (HCPs) including time and space for dialogue and exchange of care-related information, accessibility to care through awareness of the plan for home visits or feasibility to initiate home visits, active involvement in care by engaging in self-care and collaboration with HCPs, trustful relation with HCPs, with confidence in competence and individually adapted care, options for decision making, by making decisions or entrusting decisions. Patient participation could be strengthened through structured home care. Participation was facilitated when there was a balance between the patient's own preferences to influence care and the health-care professional's actions and values and the organization of care. Barriers to participation could depend on the health-care organization, lack of continuity and confidence in HCPs. | decision making;heart failure;home care;involvement;patient participation;qualitative method | pubmed |
Evaluation of hydrogel matrices for vessel bioplotting: Vascular cell growth and viability. | Developing matrices biocompatible with vascular cells is one of the most challenging tasks in tissue engineering. Here, we compared the growth of vascular cells on different hydrogels as potential materials for bioplotting of vascular tissue. Formulations containing alginate solution (Alg, 2%, w/v) blended with protein solutions (silk fibroin, gelatin, keratin, or elastin) at 1% w/v were prepared. Human umbilical vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts were cultivated on hydrogels for 7 days. Cell number and morphology was visualised using fluorescent staining at day 3 and 7. Cell metabolic activity was analysed using WST assay. Compared to pure Alg, Alg/keratin, Alg/gelatin and Alg/silk fibroin provided superb surfaces for ECs, supporting their attachment, growth, spreading and metabolic activity. SMCs showed best colonization and growth on Alg/silk fibroin and Alg/keratin hydrogels, whereas on elastin-containing hydrogels, cell clustering was observed. Fibroblasts growth was enhanced on Alg/elastin, and strongly improved on silk fibroin- and keratin-containing hydrogels. In contrast to the previous studies with alginate dialdehyde-gelatin crosslinked gels, Alg/gelatin blend hydrogels provided a less favourable scaffold for fibroblasts. Taken together, the most promising results were obtained with silk fibroin- and keratin-containing hydrogels, which supported the growth of all types of vascular cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 577-585, 2016. | alginate-protein hydrogels;biocompatibility;fibroblasts;scaffold endothelialisation;smooth muscle cells | pubmed |
From Clinical Misdiagnosis to Electrophysiological Diagnosis: Two Male Asystole Cases. | Differential diagnosis of epilepsy and syncope may be difficult. Arrhythmias such as asystole, or ventricular fibrillation, may lead to cerebral hypoperfusion mimicking partial or secondary generalized tonic-clonic seizures. While performing an electroencephalogram (EEG) for epilepsy diagnosis, simultaneous electrocardiogram (ECG) recording may detect cardiac pathology. In this article, through 2 cases, who had cardiac asystole during the EEG, we demonstrate the importance of ECG during EEG. To rule out cardiac pathology in syncope cases, all necessary investigations must be done. | EEG;asystole;diagnosis;epilepsy;syncope | pubmed |
Influence of natural zeolite and nitrification inhibitor on organics degradation and nitrogen transformation during sludge composting. | Sludge composting is one of the most widely used treatments for sewage sludge resource utilization. Natural zeolite and nitrification inhibitor (NI) are widely used during composting and land application for nitrogen conservation, respectively. Three composting reactors (A--the control, B--natural zeolite addition, and C--3,4-dimethylpyrazole phosphate (DMPP) addition) were established to investigate the influence of NI and natural zeolite addition on organics degradation and nitrogen transformation during sludge composting conducted at the lab scale. The results showed that, in comparison with the control, natural zeolite addition accelerated organics degradation and the maturity of sludge compost was higher, while the DMPP addition slowed down the degradation of organic matters. Meanwhile, the nitrogen transformation functional genes including those responses for nitrification (amoA and nxrA) and denitrification (narG, nirS, nirK, and nosZ) were quantified through quantitative PCR (qPCR) to investigate the effects of natural zeolites and DMPP addition on nitrogen transformation. Although no significant difference in the abundance of nitrogen transformation functional genes was observed between treatments, addition of both natural zeolite and DMPP increases the final total nitrogen content by 48.6% and 23.1%, respectively. The ability of natural zeolite for nitrogen conservation was due to the absorption of NH3 by compost, and nitrogen conservation by DMPP was achieved by the source reduction of denitrification. Besides, it was assumed that the addition of natural zeolite and DMPP may affect the activity of these genes instead of the abundance. | 3,4-Dimethylpyrazole phosphate (DMPP);Composting;Natural zeolite;Nitrification inhibitor (NI);Nitrogen transformation functional genes;Sewage sludge | pubmed |
Clinical manifestations of pneumonia according to the causative organism in patients in the intensive care unit. | Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug-resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. Neither the causative micro-organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification. | Drug resistance, multiple;Intensive care units;Pathogenicity;Pneumonia | pubmed |
The urothelium of a hibernator: the American black bear. | The American black bear undergoes a 3-5 month winter hibernation during which time bears do not eat, drink, defecate, or urinate. During hibernation renal function (GFR) is 16-50% of normal but urine is reabsorbed across the urinary bladder (UB) urothelium thus enabling metabolic recycling of all urinary constituents. To elucidate the mechanism(s) whereby urine is reabsorbed, we examined the UBs of five nonhibernating wild bears using light, electron (EM), and confocal immunofluorescent (IF) microscopy-concentrating on two components of the urothelial permeability barrier - the umbrella cell apical membranes and tight junctions (TJ). Bear UB has the same tissue layers (serosa, muscularis, lamina propria, urothelia) and its urothelia has the same cell layers (basal, intermediate, umbrella cells) as other mammalians. By EM, the bear apical membrane demonstrated a typical mammalian scalloped appearance with hinge and plaque regions - the latter containing an asymmetric trilaminar membrane and, on IF, uroplakins Ia, IIIa, and IIIb. The umbrella cell TJs appeared similar to those in other mammals and also contained TJ proteins occludin and claudin - 4, and not claudin -2. Thus, we were unable to demonstrate urothelial apical membrane or TJ differences between active black bears and other mammals. Expression and localization of UT-B, AQP-1 and -3, and Na(+), K(+)-ATPase on bear urothelial membranes was similar to that of other mammals. Similar studies of urothelia of hibernating bears, including evaluation of the apical membrane lipid bilayer and GAGs layer are warranted to elucidate the mechanism(s) whereby hibernating bears reabsorb their daily urine output and thus ensure successful hibernation. | Black bear;hibernation;urinary bladder microscopy;urine reabsorption;urothelium | pubmed |
Nurses' and personal care assistants' role in improving the relocation of older people into nursing homes. | This article presents findings from a study that explored nurses' and personal care assistants' role in improving the relocation of older people into a nursing home. Suggestions for improving the relocation process for older people moving into a nursing home have been the outcomes of studies that have interviewed residents and their families. However, the views of nurses and personal care assistants working in nursing homes have not been previously explored. An exploratory, descriptive qualitative research design. Individual interviews were conducted with 20 care staff (seven registered nurses, five enrolled nurses and eight personal care assistants) employed at four nursing homes. Using thematic analysis, two key themes were identified: 'What it's like for them' - highlighted staffs' awareness of the advantages, disadvantages and meaning of relocation, and focused on staffing and nursing care; other services provided and the environment. The second theme - 'We can make it better', revealed suggestions for improving the relocation process, and included spending time with new residents and the importance of a person-centred approach to care. Care staff have an important role in improving the relocation process of older people into a nursing home, as well as contributing to the discussion on this important clinical topic. Challenging care staff to acknowledge the importance of their role in helping older people settle into a nursing home is a key requirement of nursing practice in aged care. Nursing practice guidelines, with a focus on person-centred care, on how to manage the relocation process for an older person and their family are required for this aspect of nursing home care. Education of staff on relocation policies and procedures is essential to ensure that residents and their families are supported through this process. | aged care;aged care facilities;enrolled nurses;nursing homes;older people;personal care assistants;registered nurses;relocation | pubmed |
Improved Bacterial 16S rRNA Gene (V4 and V4-5) and Fungal Internal Transcribed Spacer Marker Gene Primers for Microbial Community Surveys. | Designing primers for PCR-based taxonomic surveys that amplify a broad range of phylotypes in varied community samples is a difficult challenge, and the comparability of data sets amplified with varied primers requires attention. Here, we examined the performance of modified 16S rRNA gene and internal transcribed spacer (ITS) primers for archaea/bacteria and fungi, respectively, with nonaquatic samples. We moved primer bar codes to the 5' end, allowing for a range of different 3' primer pairings, such as the 515f/926r primer pair, which amplifies variable regions 4 and 5 of the 16S rRNA gene. We additionally demonstrated that modifications to the 515f/806r (variable region 4) 16S primer pair, which improves detection of <i>Thaumarchaeota</i> and clade SAR11 in marine samples, do not degrade performance on taxa already amplified effectively by the original primer set. Alterations to the fungal ITS primers did result in differential but overall improved performance compared to the original primers. In both cases, the improved primers should be widely adopted for amplicon studies. <b>IMPORTANCE</b> We continue to uncover a wealth of information connecting microbes in important ways to human and environmental ecology. As our scientific knowledge and technical abilities improve, the tools used for microbiome surveys can be modified to improve the accuracy of our techniques, ensuring that we can continue to identify groundbreaking connections between microbes and the ecosystems they populate, from ice caps to the human body. It is important to confirm that modifications to these tools do not cause new, detrimental biases that would inhibit the field rather than continue to move it forward. We therefore demonstrated that two recently modified primer pairs that target taxonomically discriminatory regions of bacterial and fungal genomic DNA do not introduce new biases when used on a variety of sample types, from soil to human skin. This confirms the utility of these primers for maintaining currently recommended microbiome research techniques as the state of the art. | 16S;ITS;marker genes;microbial ecology;primers | pubmed |
Chokeberry attenuates the expression of genes related to de novo lipogenesis in the hepatocytes of mice with nonalcoholic fatty liver disease. | Nonalcoholic fatty liver disease (NAFLD), which is characterized by steatosis, is a major public health concern. Previous studies have shown that chokeberry has anti-inflammatory, antimutagenic, hepatoprotective, cardioprotective, and antidiabetic effects. In this study, we hypothesized that chokeberry powder can attenuate the expression of genes related to de novo lipogenesis and the triglyceride levels in the hepatocytes of mice with high-fat diet-induced NAFLD. After coadministering chokeberry powder for 8weeks (0.5% and 1% powder) with a high-fat diet, mice that consumed chokeberry powder diets, regardless of the dose, had significantly lower liver triglyceride levels than control mice that were fed a high-fat diet (P=.0145 and P<.0012, respectively). Compared with mice that were fed a high-fat diet, mice that were given 1% chokeberry powder exhibited significantly decreased mRNA expression of sterol regulatory element-binding protein (P=.009) and acetyl-CoA carboxylase (P=.0032) in the liver. Compared with mice in the control group, fatty acid synthase (FAS) expression significantly increased in the mice that were fed a high-fat diet, but both chokeberry powder-treated groups had significantly decreased FAS expression (P=.0157 and P<.0001, respectively). The size of the fat droplets was decreased in the livers of the chokeberry-supplemented groups. In summary, the administration of chokeberry powder may help attenuate high-fat diet-induced NAFLD by regulating the expression levels of sterol regulatory element-binding protein, acetyl-CoA carboxylase, and FAS and by decreasing the size of the fat droplets in the liver. | Aronia melanocarpa;Chokeberry;De novo lipogenesis;High-fat diet;Lipid metabolism;Nonalcoholic fatty liver disease | pubmed |
Enamel matrix derivative, inflammation and soft tissue wound healing. | Over 15 years have now passed since enamel matrix derivative (EMD) emerged as an agent capable of periodontal regeneration. Following thorough investigation, evidenced-based clinical application is now established for a multitude of clinical settings to promote regeneration of periodontal hard tissues. Despite the large number of studies and review articles written on this topic, no single review has compiled the influence of EMD on tissue inflammation, an area of research that merits substantial attention in periodontology. The aim of the present review was to gather all studies that deal with the effects of EMD on tissue inflammation with particular interest in the cellular mechanisms involved in inflammation and soft tissue wound healing/resolution. The effects of EMD on monocytes, macrophages, lymphocytes, neutrophils, fibroblasts and endothelial cells were investigated for changes in cell behavior as well as release of inflammatory markers, including interleukins, prostaglandins, tumor necrosis factor-α, matrix metalloproteinases and members of the OPG-RANKL pathway. In summary, studies listed in this review have reported that EMD is able to significantly decrease interleukin-1b and RANKL expression, increase prostaglandin E2 and OPG expression, increase proliferation and migration of T lymphocytes, induce monocyte differentiation, increase bacterial and tissue debris clearance, as well as increase fibroplasias and angiogenesis by inducing endothelial cell proliferation, migration and capillary-like sprout formation. The outcomes from the present review article indicate that EMD is able to affect substantially the inflammatory and healing responses and lay the groundwork for future investigation in the field. | Emdogain;enamel matrix proteins;inflammation;periodontal regeneration;periodontal wound healing | pubmed |
P < 5 × 10(-8) has emerged as a standard of statistical significance for genome-wide association studies. | In genome-wide association studies (GWASs), the practice regarding the choice of thresholds of significance and of thresholds used to include single nucleotide polymorphisms (SNPs) in a further validation stage is not well known. Here, we performed a systematic analysis of all GWASs published in two recent but nonconsecutive periods to assess whether any consensus was emerging regarding the choice of these thresholds. We identified 167 GWASs published during the first semester of 2011 and 105 published in the third trimester of 2012 and retrieved the genome-wide threshold of significance and the thresholds to include SNPs in a replication stage if applicable. The proportion of studies using 5 × 10(-8) as a genome-wide significance threshold increased between 2011 and 2012 (40% vs. 64%, P < 0.001), whereas the proportion of articles that gave a justification for this threshold decreased. The distribution of thresholds used to include SNPs in the replication stage remained stable over time (median 10(-5)), and the variance remained large [interquartile range (10(-6), 10(-4))]. Although 5 × 10(-8) has become the de facto standard genome-wide threshold, practice regarding the choice of inclusion threshold for the replication step remains heterogeneous and did not ensure the best trade-off between power and type 1 error. | Evaluation studies as topic;False discovery rate;Genome-wide association study;Multiple testing;Significance thresholds;Validation studies | pubmed |
Impact of regional femoral nerve block during general anesthesia for hip arthoplasty on blood pressure, heart rate and pain control: A randomized controlled study. | Adequate pain management is essential for preventing hemodynamic instability which can affect the perfusion of vital organs during the perioperative period, particularly in geriatric patients. For hip arthroplasty, peripheral nerve block is frequently used, limiting the adverse effects of opioid and non-opioid analgesics. The aim was to survey the impact of a supplementary single shot femoral nerve block (FNB) on hemodynamic stability and pain level. After registration at German Clinical Trial Register (DRKS-ID): DRKS00000752. and Ethics Committee approval (University Hospital of Marburg), 80 patients who underwent elective hip surgery were included. Half of them were randomly assigned to receive a FNB followed by general anesthesia; a control group received only general anesthesia as standard procedure (STD). Blood pressure and heart rate were measured and recorded every five minutes during surgery and stay at the postanesthesia care unit (PACU). Fifty-two patients were included for statistical analysis. The FNB group had significantly lower systolic blood pressures during and after surgery and lower diastolic blood pressure postoperatively, heart rate, as well as opioid and non-steroidal anti-inflammatory consumption. Femoral nerve block improved perioperative hemodynamic stability mostly likely attributable to an overall reduced sympathico adrenergic tone. | Femoral nerve block;hemodynamic control;hip arthroplasty;postoperative analgesics | pubmed |
Co-operative intermolecular kinetics of 2-oxoglutarate dependent dioxygenases may be essential for system-level regulation of plant cell physiology. | Can the stimulus-driven synergistic association of 2-oxoglutarate dependent dioxygenases be influenced by the kinetic parameters of binding and catalysis?In this manuscript, I posit that these indices are necessary and specific for a particular stimulus, and are key determinants of a dynamic clustering that may function to mitigate the effects of this trigger. The protein(s)/sequence(s) that comprise this group are representative of all major kingdoms of life, and catalyze a generic hydroxylation, which is, in most cases accompanied by a specialized conversion of the substrate molecule. Iron is an essential co-factor for this transformation and the response to waning levels is systemic, and mandates the simultaneous participation of molecular sensors, transporters, and signal transducers. Here, I present a proof-of-concept model, that an evolving molecular network of 2OG-dependent enzymes can maintain iron homeostasis in the cytosol of root hair cells of members of the family Gramineae by actuating a non-reductive compensatory chelation by the phytosiderophores. Regression models of empirically available kinetic data (iron and alpha-ketoglutarate) were formulated, analyzed, and compared. The results, when viewed in context of the superfamily responding as a unit, suggest that members can indeed, work together to accomplish system-level function. This is achieved by the establishment of transient metabolic conduits, wherein the flux is dictated by kinetic compatibility of the participating enzymes. The approach adopted, i.e., predictive mathematical modeling, is integral to the hypothesis-driven acquisition of experimental data points and, in association with suitable visualization aids may be utilized for exploring complex plant biochemical systems. | 2-oxoglutarate;co-operative kinetics;facial triad;iron deficiency;non-linear regression;system-level | pubmed |
Learning curve for endoscopic submucosal dissection of esophageal neoplasms. | There is a significant learning curve for endoscopic submucosal dissection of esophageal neoplasms that has not been fully characterized. This retrospective study included 33 consecutive superficial esophageal neoplasms for analysis of the learning curve for esophageal endoscopic submucosal dissection based on a single, novice endoscopist's experience. The study was divided into three periods (T1, T2, and T3) of 10 endoscopic submucosal dissection procedures in chronological order, with 13 procedures in the last period. Patient factors (age, sex, coexistent esophageal varices, or submucosal fibrosis) and tumor factors (location at upper esophagus, involving >3/4 esophageal circumference) for endoscopic submucosal dissection were not statistically different between the periods. The mean procedure time was 74.6 min/cm(2) , 23.4 min/cm(2) , and 10.5 min/cm(2) for T1, T2, and T3, respectively. The procedure time decreased over time (P = 0.02) and post hoc test revealed significant difference was only between T3 and T1 (P = 0.019). The en bloc resection rate was 50%, 100%, and 92.3% for T1, T2, and T3, respectively (P for trend = 0.015). R0 resection rate was 40%, 100%, and 84.6% for T1, T2, and T3, respectively (P for trend = 0.023). Two patients had complications: each one patient in T1 and T3 period experienced major bleeding during the procedure (P for trend = 0.875). None of the patients had esophageal perforation. The results of the study concluded that at least 30 cases of endoscopic submucosal dissection of esophageal neoplasms are needed for a novice endoscopist to gain early proficiency in this technique. | endoscopic submucosal dissection;learning curve;superficial esophageal neoplasm | pubmed |
Situational analysis and future directions of AYUSH: An assessment through 5-year plans of India. | AYUSH is an acronym for Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy. These are the six indigenous systems of medicine practiced in India. A department called Department of Indian System of medicine was created in March 1995 and renamed to AYUSH in November 2003 with a focus to provide increased attention for the development of these systems. Very recently, in 2014, a separate ministry was created under the union Government of India, which is headed by a minister of state. Planning regarding these systems of medicine was a part of 5-year planning process since 1951. Since then many developments have happened in this sector albeit the system was struggling with a great degree of uncertainty at the time of 1(st)5-year plan. A progressive path of development could be observed since the first to the 12(th)5-year plan. It was up to the 7(th)plan the growth was little sluggish and from 8(th)plan onward the growth took its pace and several innovative development processes could be observed thereafter. The system is gradually progressing ahead with a vision to be a globally accepted system, as envisaged in 11(th)5-year plan. Currently, AYUSH system is a part of mainstream health system implemented under National Rural Health Mission (NRHM). NRHM came into play in 2005 but implemented at ground level in 2006 and introduced the scheme of "Mainstreaming of AYUSH and revitalization of local health traditions" to strengthen public health services. This scheme is currently in operation in its second phase, since 1(st)April 2012, with the 12(th)5-year plan. The scheme was primarily brought in to operation with three important objectives; choice of treatment system to the patients, strengthen facility functionally and strengthen the implementation of national health programmes, however, in some places it seems to be a forced medical pluralism owing to a top-down approach by the union government without considerable involvement of the concerned community. In this study, the 5-year planning documents have been reviewed, from the 1(st)plan to 12(th)plan, to enable reflection and throw some light into the future directions of AYUSH system. | Ancient medical manuscripts;Indian systems of medicine;Indian systems of medicine informatics;Sidha and Homeopathy;Unani;Yoga and Naturopathy;mainstreaming of Ayurveda;medical tourism | pubmed |
The Tolerance and Accumulation of Miscanthus Sacchariflorus (maxim.) Benth., an Energy Plant Species, to Cadmium. | Miscanthus sacchariflorus (Maxim.) Benth. is a metallophyte suitable for the phytoremediation of mine wastes. The tolerance and accumulation of M. sacchariflorus to cadmium was studied by pot experiments. The results showed that O2·- generation rate, plasma membrane permeability and MDA content of M. sacchariflorus leaves increased with increasing Cd concentrations in soil, but significant effect was only observed when Cd concentrations were ≥50 mg·kg(-1). SOD and POD activities increased initially but decreased later on, whereas CAT activity only increased significantly at higher Cd concentrations, 50-100 mg·kg(-1). The content of photosynthetic pigment and growth of M. sacchariflorus were both not significantly affected when Cd concentration was ≤25 mg·kg(-1). In contrast, both parameters were significantly affected when Cd concentration was ≥50 mg·kg(-1). M. sacchariflorus could accumulate much Cd, but most of the Cd assimilated was retained in the belowground part, suggesting that M. sacchariflorus has poor ability to translocate Cd to the aboveground part. Our results suggested that although M. sacchariflorus was not a hyper-accumulator, it has a strong capacity to tolerate and stabilize the Cd. Therefore, M. sacchariflorus has a certain potential in the phytostabilization of Cd-contaminated soils. | Miscanthus sacchariflorus (Maxim.) Benth.;cadmium stress;energy plant;phytostabilization;tolerance | pubmed |
Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery. | Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. Twenty children ages 12-17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(-0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1) kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23 litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics. The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading dose and 40 mg kg(-1) h(-1) infusion; weight ≤25 kg-<50 kg, 100 mg kg(-1) loading dose and 35 mg kg(-1) h(-1) infusion; and weight ≥50 kg, 100 mg kg(-1) loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this dosing strategy is warranted. NCT01408823. | antifibrinolytic agents;paediatrics;pharmacology;scoliosis;spinal fusion | pubmed |
Blockade of Extracellular HMGB1 Suppresses Xenoreactive B Cell Responses and Delays Acute Vascular Xenogeneic Rejection. | Blockade of extracellular high mobility group box 1 (HMGB1) can significantly prolong murine cardiac allograft survival. Here, we determined the role of HMGB1 in xenotransplantation. Sprague-Dawley rat hearts were transplanted heterotopically into BALB/c mice. Xenografts without any treatment developed predominant acute vascular rejection within 6 days. Both passively released HMGB1 from xenografts and actively secreted HMGB1 from infiltrated immune cells were significantly increased after xenotransplantation. HMGB1-neutralizing antibody treatment significantly prolonged xenograft survival and attenuated pathologic damage, immune cell infiltration, and HMGB1 expression and release in the xenografts. Compared to control IgG treatment evaluated at study endpoint, treatment with HMGB1-neutralizing antibody markedly suppressed xenoreactive B cell responses, as evidenced by the significant inhibition of anti-rat antibody production and deposition in xenografts at Day 6 posttransplant. Furthermore, treatment with anti-HMGB1 antibody suppressed B cell activation and reduced IFN-γ and IL-17A production after xenotransplantation. These results demonstrate for the first time that HMGB1 plays an important role in mediating acute xenograft rejection. Thus, we have shown that neutralization of extracellular HMGB1 can significantly inhibit xenoreactive B cell responses and delay xenograft rejection in a rat-to-mouse model of xenotransplantation, uncovering new insights in the role of HMGB1 in transplantation. | Animal models: murine;basic (laboratory) research/science, heart transplantation/cardiology;immunobiology;innate immunity;rejection: vascular;xenoantibody;xenotransplantation | pubmed |
Biomarker-based drug safety assessment in the age of systems pharmacology: from foundational to regulatory science. | Improved biomarker-based assessment of drug safety is needed in drug discovery and development as well as regulatory evaluation. However, identifying drug safety-related biomarkers such as genes, proteins, miRNA and single-nucleotide polymorphisms remains a big challenge. The advances of 'omics' and computational technologies such as genomics, transcriptomics, metabolomics, proteomics, systems biology, network biology and systems pharmacology enable us to explore drug actions at the organ and organismal levels. Computational and experimental systems pharmacology approaches could be utilized to facilitate biomarker-based drug safety assessment for drug discovery and development and to inform better regulatory decisions. In this article, we review the current status and advances of systems pharmacology approaches for the development of predictive models to identify biomarkers for drug safety assessment. | biomarker;drug safety assessment;regulatory science;systems biology;systems pharmacology | pubmed |
The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide. | Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue. | Ethanol;Gastric mucosal damage;Inflammation;Nitric oxide;Thalidomide | pubmed |
CONTROLLING ANTLER GROWTH IN A CASTRATED INDOCHINESE SIKA DEER CERVUS NIPPON PSEUDAXIS USING A COMMERCIALLY AVAILABLE TRENBOLONE ACETATE AND ESTRADIOL IMPLANT. | A captive Indochinese sika deer (Cervus nippon pseudaxis) was castrated at the age of 5 yr. The resultant abnormal antler growth over the next few years became difficult to manage from both the veterinary and husbandry standpoints. Using a commercially available trenbolone acetate and estradiol implant marketed for domestic cattle heifers, normal mineralization of the abnormal antlers was achieved along with the expected normal casting. The deer was then maintained for 6 yr using an annual implant regimen. | Antler;castrated deer;hormone implant;perruque;sika deer | pubmed |
Vertical transmission in experimentally infected sheep despite previous inoculation with Neospora caninum NcNZ1 isolate. | Recent reports indicate N. caninum has a possible role in causing abortions in sheep in New Zealand. Knowledge about the mode of transmission of neosporosis in sheep in New Zealand is limited. This study aimed to determine the rate of vertical transmission that would occur in lambs born from experimentally inoculated ewes and to determine if previous inoculation would protect the lambs from N. caninum infection. A group of 50 ewes was divided into 2 groups with one group being inoculated with 5×10(6) N. caninum tachyzoites prior to pregnancy in Year 1. In Year 2, each of these groups was subdivided into 2 groups with one from each original group being inoculated with 1×10(7) N. caninum tachyzoites on Day 120 of gestation. Inoculation of N. caninum tachyzoites into ewes prior to mating resulted in no congenital transmission in lambs born in Year 1 but without further inoculation, 7 out of 11 lambs in Year 2 were positive for N. caninum infection. Ewes that were inoculated in both years resulted in all 12 lambs born in Year 2 being positive for N. caninum infection. This indicates that previous inoculation in Year 1 did not result in any vertical transmission in that year but did not provide any protection against vertical transmission in Year 2. These results suggest that vertical transmission occurs readily once the ewe is infected. | Lambs;N. caninum;Sheep;Vertical transmission | pubmed |
Triple positive breast cancer: a distinct subtype? | Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets. | Anti-HER-2 agents;Breast cancer;Chemotherapy;Hormonal therapy;Triple positive | pubmed |
CTLA4-Ig suppresses development of experimental autoimmune uveitis in the induction and effector phases: Comparison with blockade of interleukin-6. | Recently, a number of biologics have been used in the treatment of autoimmune diseases. However, in the treatment of severe autoimmune uveitis, only TNF-alpha inhibitors are preferably used and the effect of other biologics such as interleukin-6 (IL-6) signaling blockade or cytotoxic T-lymphocyte antigen-4-immunoglobulin fusion protein (CTLA4-Ig) has not been well studied. Previously, we reported that IL-6 blockade effectively suppresses the development of experimental autoimmune uveitis (EAU), a mouse model for uveitis, by inhibiting Th17 cell development. In this study, we investigated the effect of CTLA4-Ig on EAU development and compared it with the effect of anti-IL-6 receptor monoclonal antibody (MR16-1). C57BL/6J mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and treated once with CTLA4-Ig or MR16-1. Both CTLA4-Ig and MR16-1 administered in the induction phase (the same day as immunization) significantly reduced the clinical and histopathological scores of EAU. Fluorescence-activated cell sorting studies using draining lymph node (LN) cells from EAU mice 10 days after immunization showed that CTLA4-Ig can suppress early T-helper cell activation. CTLA4-Ig administered in the effector phase of the disease (one week after immunization), when IRBP-reactive T cells have been primed, also significantly reduced the clinical and histopathological scores of EAU. In contrast, MR16-1 administered in the effector phase did not ameliorate EAU. To investigate the differences between these biologics in the effector phase, in vitro restimulation analysis of LN cells obtained from EAU mice one week after immunization was performed and revealed that CTLA4-Ig, but not MR16-1, added to culture media could inhibit the proliferation of IRBP-specific CD4(+) T cells which possessed capacities of producing IFN-gamma and/or IL-17. Collectively, CTLA4-Ig ameliorated EAU through preventing initial T-cell activation in the induction phase and suppressing proliferation of IRBP-specific T cells in the effector phase. Blockade of IL-6 signaling did not have such inhibitory effects after T-cell priming. CTLA4-Ig may have therapeutic effects on human chronic uveitis. | Biologic;CTLA4;Cytokine;Experimental autoimmune uveitis;T cell;Uveitis | pubmed |
Single pyruvate intake induces blood alkalization and modification of resting metabolism in humans. | Three separate studies were performed with the aim to 1) determine the effect of a single sodium pyruvate intake on the blood acid-base status in males and females; 2) compare the effect of sodium and calcium pyruvate salts and establish their role in the lipolysis rate; and 3) quantify the effect of single pyruvate intake on the resting energy metabolism. In all, 48 individuals completed three separate studies. In all the studies, participants consumed a single dose of pyruvate 0.1 g/kg 60 min before commencing the measurements. The whole blood pH, bicarbonate concentration, base excess or plasma glycerol, free fatty acids, glucose concentrations, or resting energy expenditure and calculated respiratory exchange ratio were determined. The analysis of variance for repeated measurements was performed to examine the interaction between treatment and time. The single dose of sodium pyruvate induced blood alkalization, which was more marked in the male than in the female participants. Following the ingestion of sodium or calcium pyruvate, the blood acid-base parameters were higher than in the placebo trial. Furthermore, 3-h postingestion glycerol was lower in both pyruvate trials than in placebo. Resting energy expenditure did not differ between the trials; however, carbohydrate oxidation was increased after sodium pyruvate ingestion. Pyruvate intake induced mild alkalization in a sex-dependent fashion. Moreover, it accelerated carbohydrate metabolism and delayed the rate of glycerol appearance in the blood, but had no effect on the resting energy expenditure. Furthermore, sodium salt seems to have had a greater effect on the blood buffering level than calcium salt. | Acid-base status;Base excess;Blood bicarbonate;Free fatty acids;Glycerol;Respiratory exchange ratio;Resting energy expenditure | pubmed |
Clinical outcomes following collagenase injections compared to fasciectomy in the treatment of Dupuytren's contracture. | The aim of this study is to compare the efficacy of collagenase injections with that of fasciectomy in the treatment of Dupuytren's contracture. This is a case-control retrospective study. We reviewed the electronic medical records from January 2009 through January 2013, identifying 142 consecutive patients who underwent either fasciectomy or collagenase injection. Exclusion criteria for both groups were age <18 years, pregnant women, and arthroplasty or arthrodesis of the treated joint. Follow-up data beyond 1-year duration was available for 117 of the patients: 44 patients who had undergone fasciectomy, and 73 patients who had received collagenase injection. The primary outcome measure in this study was resolution of joint contracture to 0-5° deficit of full extension. Data was analyzed using two-sample t tests for continuous data and chi-square test for categorical data. A significant P value was set at <0.05. At the latest follow-up, significantly more joints treated with fasciectomy met the primary outcome measure. Metacarpophalangeal (MP) joints responded better than the proximal interphalangeal (PIP) joints for both treatments. At the latest follow-up (14.2 months for collagenase, 16.3 months for fasciectomy), 46 % of MP joints treated with collagenase and 68 % of MP joints treated with fasciectomy maintained resolution of joint contracture. Sub-analysis of the affected joints based on the severity of initial contracture demonstrated that MP and PIP joints with contractures <45° responded better than more severely contracted joints (>45°). Fasciectomy yields a greater mean magnitude of correction for digital contractures at the latest follow-up when compared to collagenase. Both treatments were more effective for treatment of MP joint contracture compared to PIP joint contracture. Level III, therapeutic. | Collagenase;Dupuytren’s disease;Faciectomy;Finger joint contracture;Xiaflex | pubmed |
Effect of minodronate on the speed of sound of the calcaneus in postmenopausal women with an increased risk of fractures: A clinical practice-based observational study. | We previously reported that alendronate and risedronate reduce the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) by 44.9% and 34.7%, respectively, at 3 months after the start of treatment, and increase the speed of sound (SOS) of the calcaneus by 0.6% and 0.65%, respectively, at 12 months after the start of treatment in postmenopausal women with osteoporosis. The aim of the present clinical practice-based observational study was to examine the effect of treatment with minodronate for 12 months on the SOS of the calcaneus and on bone turnover markers in postmenopausal women with an increased risk of fractures. Forty-two postmenopausal women with osteoporosis or osteopenia with a clinical risk factor for fractures who had been treated with minodronate for > 12 months were enrolled in the study. The SOS and bone turnover markers were monitored during treatment with minodronate for 12 months. Compared to their baseline values, the urinary levels of NTX at 3 months and the serum levels of alkaline phosphatase at 12 months were significantly decreased at 47.5% and 25.8%, respectively. At 12 months, the SOS increased modestly, but significantly, by 0.47%, compared to the baseline value. The present study confirmed that minodronate suppressed bone turnover and modestly increased the SOS of the calcaneus in postmenopausal women with an increased risk of fractures. | bone turnover;minodronate;postmenopausal women;quantitative ultrasound;speed of sound | pubmed |
Pentoxifylline as a modulator of anticancer drug doxorubicin. Part I: Reduction of doxorubicin DNA binding. | Pentoxifylline--biologically active aromatic compound--has a well established capability to sequester aromatic ligands, such as an anticancer drug--doxorubicin--in mixed stacking aggregates. Formation of such hetero-complexes may influence biological activity of secluded drug. Presented work shows assessment of pentoxifylline influence on doxorubicin direct interactions with DNA employing biophysical methods. Achievement of this goal required statistical-thermodynamical model allowing numerical four-parameter analysis of experimental mixture--an issue that was successfully tackled by merging McGhee--von Hippel and Kapuscinski--Kimmel models. Results obtained with new model are well in agreement with data obtained with separate experiments with each of these two models and show reduction of doxorubicin in free (monomeric, dimeric) and complexed with DNA forms in favor of doxorubicin-pentoxifylline complexes with increasing pentoxifylline concentration. Developed model appears to be a universal tool allowing numerical analysis of mixtures containing self-aggregating ligand, DNA, and modulating agent. | De-intercalation;Hetero-aggregation;Stacking complexes | pubmed |
The yeast chromatin remodeler Rsc1-RSC complex is required for transcriptional activation of autophagy-related genes and inhibition of the TORC1 pathway in response to nitrogen starvation. | The yeast RSC, an ATP-dependent chromatin-remodeling complex, is essential for mitotic and meiotic growth. There are two distinct isoforms of this complex defined by the presence of either Rsc1 or Rsc2; however, the functional differences between these complexes are unclear. Here we show that the RSC complex containing Rsc1, but not Rsc2, functions in autophagy induction. Rsc1 was required not only for full expression of ATG8 mRNA but also for maintenance of Atg8 protein stability. Interestingly, decreased autophagic activity and Atg8 protein stability in rsc1Δ cells, but not the defect in ATG8 mRNA expression, were partially suppressed by deletion of TOR1. In addition, we found that rsc1Δ impaired the binding between the Rho GTPase Rho1 and the TORC1-specific component Kog1, which is required for down-regulation of TORC1 activity. These results suggest that the Rsc1-containing RSC complex plays dual roles in the proper induction of autophagy: 1) the transcriptional activation of autophagy-related genes independent of the TORC1 pathway and 2) the inactivation of TORC1, possibly through enhancement of Rho1-Kog1 binding. | Autophagy induction;Chromatin remodeling;RSC;Saccharomyces cerevisiae;TORC1 | pubmed |
How Much In-Kind Support Do Low-Income Nonresident Fathers Provide? A Mixed-Method Analysis. | Past child support research has largely focused on cash payments made through the courts (formal support) or given directly to the mother (informal support), almost to the exclusion of a third type: non-cash goods (in-kind support). Drawing on repeated, semistructured interviews with nearly 400 low-income noncustodial fathers, the authors found that in-kind support constitutes about one quarter of total support. Children in receipt of some in-kind support receive, on average, $60 per month worth of goods. Multilevel regression analyses demonstrated that children who are younger and have more hours of visitation, as well as those whose father has a high school education and no current substance abuse problem, receive in-kind support of greater value. Yet children whose fathers lack stable employment, or are Black, receive a greater proportion of their total support in kind. A subsequent qualitative analysis revealed that fathers' logic for providing in-kind support is primarily relational, and not financial. | child support;family policy—child-related;low-income families;noncustodial parents | pubmed |
Microbial surfactants: fundamentals and applicability in the formulation of nano-sized drug delivery vectors. | Microbial surfactants, so-called biosurfactants, comprise a wide variety of structurally distinct amphipathic molecules produced by several microorganisms. Besides exhibiting surface activity at the interfaces, these molecules present powerful characteristics including high biodegradability, low toxicity and special biological activities (e.g. antimicrobial, antiviral, anticancer, among others), that make them an alternative to their chemical counterparts. Several medical-related applications have been suggested for these molecules, including some reports on their potential use in the formulation of nano-sized drug delivery vectors. However, despite their promises, due to the generalized lack of knowledge on microbial surfactants phase behavior and stability under diverse physicochemical conditions, these applications remain largely unexplored, thus representing an exciting field of research. These nano-sized vectors are a powerful approach towards the current medical challenges regarding the development of efficient and targeted treatments for several diseases. In this review, a special emphasis will be given to nanoparticles and microemulsions. Nanoparticles are very auspicious as their size, shape and stability can be manipulated by changing the environmental conditions. On the other hand, the easiness of formulation, as well as the broad possibilities of administration justifies the recent popularity of the microemulsions. Notwithstanding, both vector types still require further developments to overcome some critical limitations related with toxicity and costs, among others. Such developments may include the search for other system components, as the microbial surfactants, that can display improved features. | Biosurfactants;Drug delivery systems;Microemulsions;Nanoparticles;Self-aggregation | pubmed |
Revision of the Massarineae (Pleosporales, Dothideomycetes). | We here taxonomically revise the suborder Massarineae (Pleosporales, Dothideomycetes, Ascomycota). Sequences of SSU and LSU nrDNA and the translation elongation factor 1-alpha gene (tef1) are newly obtained from 106 Massarineae taxa that are phylogenetically analysed along with published sequences of 131 taxa in this suborder retrieved from GenBank. We recognise 12 families and five unknown lineages in the Massarineae. Among the nine families previously known, the monophyletic status of the Dictyosporiaceae, Didymosphaeriaceae, Latoruaceae, Macrodiplodiopsidaceae, Massarinaceae, Morosphaeriaceae, and Trematosphaeriaceae was strongly supported with bootstrap support values above 96 %, while the clades of the Bambusicolaceae and the Lentitheciaceae are moderately supported. Two new families, Parabambusicolaceae and Sulcatisporaceae, are proposed. The Parabambusicolaceae is erected to accommodate Aquastroma and Parabambusicola genera nova, as well as two unnamed Monodictys species. The Parabambusicolaceae is characterised by depressed globose to hemispherical ascomata with or without surrounding stromatic tissue, and multi-septate, clavate to fusiform, hyaline ascospores. The Sulcatisporaceae is established for Magnicamarosporium and Sulcatispora genera nova and Neobambusicola. The Sulcatisporaceae is characterised by subglobose ascomata with a short ostiolar neck, trabeculate pseudoparaphyses, clavate asci, broadly fusiform ascospores, and ellipsoid to subglobose conidia with or without striate ornamentation. The genus Periconia and its relatives are segregated from the Massarinaceae and placed in a resurrected family, the Periconiaceae. We have summarised the morphological and ecological features, and clarified the accepted members of each family. Ten new genera, 22 new species, and seven new combinations are described and illustrated. The complete ITS sequences of nrDNA are also provided for all new taxa for use as barcode markers. | Aquastroma Kaz. Tanaka & K. Hiray.;Aquastroma magniostiolata Kaz. Tanaka & K. Hiray.;Aquilomyces rebunensis Kaz. Tanaka & K. Hiray.;Clypeoloculus Kaz. Tanaka & K. Hiray.;Clypeoloculus akitaensis Kaz. Tanaka & K. Hiray.;Clypeoloculus hirosakiensis Kaz. Tanaka & K. Hiray.;Clypeoloculus microsporus Kaz. Tanaka & K. Hiray.;Clypeoloculus towadaensis Kaz. Tanaka & K. Hiray.;Coelomycetes;Dictyosporium pseudomusae Kaz. Tanaka, G. Sato & K. Hiray.;Freshwater ascomycetes;Fuscostagonospora Kaz. Tanaka & K. Hiray.;Fuscostagonospora sasae Kaz. Tanaka & K. Hiray.;Gregarithecium Kaz. Tanaka & K. Hiray.;Gregarithecium curvisporum Kaz. Tanaka & K. Hiray.;Helminthosporium;Helminthosporium massarinum Kaz. Tanaka, K. Hiray. & Shirouzu;Holomorph;Hyphomycetes;Keissleriella breviasca Kaz. Tanaka & K. Hiray.;Keissleriella quadriseptata Kaz. Tanaka & K. Hiray.;Keissleriella yonaguniensis Kaz. Tanaka & K. Hiray.;Lentithecium clioninum (Kaz. Tanaka, Sat. Hatak. & Y. Harada) Kaz. Tanaka & K. Hiray.;Lentithecium pseudoclioninum Kaz. Tanaka & K. Hiray.;Magnicamarosporium Kaz. Tanaka & K. Hiray.;Magnicamarosporium iriomotense Kaz. Tanaka & K. Hiray.;Massarina;Neoophiosphaerella Kaz. Tanaka & K. Hiray.;Neoophiosphaerella sasicola (Nagas. & Y. Otani) Kaz. Tanaka & K. Hiray.;Parabambusicola Kaz. Tanaka & K. Hiray.;Parabambusicola bambusina (Teng) Kaz. Tanaka & K. Hiray.;Parabambusicolaceae Kaz. Tanaka & K. Hiray.;Periconia;Periconia homothallica Kaz. Tanaka & K. Hiray.;Periconia pseudodigitata Kaz. Tanaka & K. Hiray.;Phaeosphaeria arundinacea var. brevispora Nagas. & Y. Otani;Phaeosphaeria sasicola Nagas. & Y. Otani;Pseudocoleophoma Kaz. Tanaka & K. Hiray.;Pseudocoleophoma calamagrostidis Kaz. Tanaka & K. Hiray.;Pseudocoleophoma polygonicola Kaz. Tanaka & K. Hiray.;Pseudoxylomyces Kaz. Tanaka & K. Hiray.;Pseudoxylomyces elegans (Goh, W.H. Ho, K.D. Hyde & K.M. Tsui) Kaz. Tanaka & K. Hiray.;Setoseptoria arundinacea (Sowerby) Kaz. Tanaka & K. Hiray.;Setoseptoria magniarundinacea (Kaz. Tanaka & Y. Harada) Kaz. Tanaka & K. Hiray.;Spegazzinia;Stagonospora bicolor (D. Hawksw., W.J. Kaiser & Ndimande) Kaz. Tanaka & K. Hiray;Stagonospora pseudoperfecta Kaz. Tanaka & K. Hiray.;Sulcatispora Kaz. Tanaka & K. Hiray;Sulcatispora acerina Kaz. Tanaka & K. Hiray.;Sulcatispora berchemiae Kaz. Tanaka & K. Hiray;Sulcatisporaceae Kaz. Tanaka & K. Hiray | pubmed |
Hyperactive RAS/PI3-K/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem/Progenitor Cells. | Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutations in the NF1 tumor suppressor gene, which affect approximately 1 out of 3000 individuals. Patients with NF1 suffer from a range of malignant and nonmalignant manifestations such as plexiform neurofibromas and skeletal abnormalities. We previously demonstrated that Nf1 haploinsufficiency in mesenchymal stem/progenitor cells (MSPCs) results in impaired osteoblastic differentiation, which may be associated with the skeletal manifestations in NF1 patients. Here we sought to further ascertain the role of Nf1 in modulating the migration and adhesion of MSPCs of the Nf1 haploinsufficient (Nf1(+/-)) mice. Nf1(+/-) MSPCs demonstrated increased nuclear-cytoplasmic ratio, increased migration, and increased actin polymerization as compared to wild-type (WT) MSPCs. Additionally, Nf1(+/-) MSPCs were noted to have significantly enhanced cell adhesion to fibronectin with selective affinity for CH271 with an overexpression of its complimentary receptor, CD49e. Nf1(+/-) MSPCs also showed hyperactivation of phosphoinositide 3-kinase (PI3-K) and mitogen activated protein kinase (MAPK) signaling pathways when compared to WT MSPCs, which were both significantly reduced in the presence of their pharmacologic inhibitors, LY294002 and PD0325901, respectively. Collectively, our study suggests that both PI3-K and MAPK signaling pathways play a significant role in enhanced migration and adhesion of Nf1 haploinsufficient MSPCs. | mesenchymal stem/progenitor cells;neurofibroma;neurofibromatosis 1;oncogene protein p21 (ras) | pubmed |
Amadori albumin in diabetic nephropathy. | Nonenzymatic glycation of macromolecules in diabetes mellitus (DM) is accelerated due to persistent hyperglycemia. Reducing sugar such as glucose reacts non enzymatically with free €-amino groups of proteins through series of reactions forming Schiff bases. These bases are converted into Amadori product and further into AGEs. Non enzymatic glycation has the potential to alter the biological, structural and functional properties of macromolecules both in vitro and in vivo. Studies have suggested that amadori as well as AGEs are involved in the micro-macro vascular complications in DM, but most studies have focused on the role of AGEs in vascular complications of diabetes. Recently putative AGE-induced patho-physiology has shifted attention from the possible role of amadori-modified proteins, the predominant form of the glycated proteins in the development of the diabetic complications. Human serum albumin (HSA), the most abundant protein in circulation contains 59 lysine and 23 arginine residues that could, in theory be involved in glycation. Albumin has dual nature, first as a marker of intermediate glycation and second as a causative agent of the damage of tissues. Among the blood proteins, hemoglobin and albumin are the most common proteins that are glycated. HSA with a shorter half life than RBC, appears to be an alternative marker of glycemic control as it can indicate blood glucose status over a short period (2-3 weeks) and being unaffected by RBCs life span and variant haemoglobin, anemia etc which however, affect HbA1c. On the other hand, Amadori albumin may accumulate in the body tissues of the diabetic patients and participate in secondary complications. Amadori-albumin has potential role in diabetic glomerulosclerosis due to long term hyperglycaemia and plays an important role in the pathogenesis of diabetic nephropathy. This review is an approach to compile both the nature of glycated albumin as a damaging agent of tissues and as an intermediate diagnostic marker and its potential role in diabetic nephropathy. | Amadori albumin;diabetic nephropathy;glycated albumin | pubmed |
Conductive Inorganic-Organic Hybrid Distributed Bragg Reflectors. | A conductive hybrid distributed Bragg reflector (DBR) is demonstrated, consisting of inorganic and organic semiconductor films and assembled by a thermal deposition technique. A maximum reflectance of 92.2% and a wide spectral width of more than 70 nm are achieved. The hybrid DBR shows good electrical conductivity, which provides the possibility of practical applications in novel optoelectronic devices, such as electrically pumped organic vertical-cavity surface-emitting lasers. | distributed Bragg reflectors;electrical conductivity;inorganic-organic semiconductors | pubmed |
Separation of phenolic acids and flavonoids from Trollius chinensis Bunge by high speed counter-current chromatography. | In this work, eleven compounds were successfully separated from Trollius chinensis Bunge by using a two-step high-speed counter-current chromatography (HSCCC) method. NRTL-SAC (nonrandom two-liquid segment activity coefficient) method, a newly developed solvent system selection strategy, was applied to screening the suitable biphasic liquid systems. Hexane/ethyl acetate/ethanol/water (3:7:3:7, v/v) solvent system was used in the first step, while the hexane/ethyl acetate/methanol/water (1:2:1:2, 1:4:1:4, 1:9:1:9, v/v) systems were employed in the second step. The chemical structures of the separated compounds were identified by UV, high resolution ESI-MS and MS/MS data. The separated compounds are 3,4-dihydroxyphenylethanol (1), vanillic acid (2), orientin (3), vitexin (4), veratric acid (5), 2″-O-(3‴, 4‴-dimethoxybenzoyl) orientin (6), 2″-O-feruloylorientin (7), 2″-O-feruloylvitexin (8), 2″-O-(2‴-methylbutyryl) vitexin (9), 2″-O-(2‴-methylbutyryl) isoswertiajaponin (10), 2″-O-(2‴-methylbutyryl) isoswertisin (11). The results demonstrate that HSCCC is a powerful tool for the separation of compounds from extremely complex samples. | Flavonoids;HSCCC;Phenolic acids;Separation;Trollius chinensis Bunge | pubmed |
Antioxidant activity and kinetics studies of eugenol and 6-bromoeugenol. | In this work, we report the antioxidant and free radical scavenging activity of 6-bromoeugenol and eugenol. EC50, the concentration providing 50% inhibition, is calculated and the antioxidant activity index (AAI) is evaluated. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging method. EC50 values of 6-bromoeugenol, ascorbic acid and eugenol were 34.270 μg/mL, 54.888 μg/mL and 130.485 μg/mL, respectively. 6-Bromoeugenol showed higher AAI value (1.122) followed by ascorbic acid (0.700), then by eugenol (0.295). We also investigate the kinetics of DPPH radical scavenging activity of our products to determine the useful parameter TEC50 to evaluate their antiradical efficiency (ARE). Our results have shown high ARE. This study has provided the following ARE ( × 10(-3)) order for the tested antioxidants: ascorbic acid (70.119)>6-bromoeugenol (34.842) > eugenol (21.313). Finally, we classify ascorbic acid and eugenol as fast kinetics reaction (TEC50 8.82 and 11.38 min, respectively) and 6-bromoeugenol as medium kinetics reaction (TEC50 39.24 min). | antioxidant activity;antiradical efficiency;eugenol derivatives;kinetic study | pubmed |
Relationship between gene polymorphisms and prostate cancer risk. | To investigate the relationship between genetic factor and prostate cancer (Pca) risk and the possible cause in it. The polymorphisms of cytochrome P450 family 17 (CYPl7) rs743572, p27 V109G and androgen receptor (AR) gene CAG repeat length in peripheral blood from 70 cases and 70 controls were detected through the polymerase chain reaction-restriction fragment length polymorphism technique or short tandem repeat-polymerase chain reaction technique. Then, according to the results of case-control study, the recombinant plasmids containing the wild/mutant p27 gene were constructed and transfected Pca LNcap cells. After 24 and 72 h of transfection, the cell proliferative activity was determined by MTT method, cell cycle distribution and apoptosis was detected by flow cytometry, and the expression level of bcl-2, caspase-3 and p27 protein was determined by Western-blot. In three target polymorphisms, only p27 V109G polymorphism was related to Pca risk (P = 0.030, OR = 0.202, 95% CI = 0.042-0.973). Pca risk of p27-109G allele was lower than -109V allele (P = 0.006, OR = 0.285, 95% CI = 0.110-0.737). Cells transfected with wild/mutant p27 gene both showed the higher cells apoptosis rate and the lower cell proliferative activity than mock cells (P < 0.05 or 0.01), the regulatory effect of mutant p27 on cell proliferation and apoptosis was stronger than the wild p27 (P < 0.05). p27-109G allele that could cause higher p27 protein expression than -109V allele in LNcap cells, maybe is the protective factor of Pca. | Case–control study;LNcap cells;Prostate cancer;p27 V109G polymorphism | pubmed |
Comparison of immunosuppressive therapies for IgA nephropathy after tonsillectomy: three-course versus one-course steroid pulse combined with mizoribine. | It has been reported that steroid pulse therapy for IgA nephropathy improves renal prognosis. However, because of the side effects, steroid dose must be restricted to some cases. Treatment effects of steroid on cases already presenting with reduced renal function are unknown. In this study, we performed tonsillectomy in patients with IgA nephropathy and conducted a comparative study about subsequent immunosuppressive therapy. Subjects were patients younger than 70 years of age diagnosed with IgA nephropathy by renal biopsy. Treatment protocols were a single-course steroid pulse combined with mizoribine during a period from August 2006 to June 2010 (Group A; n = 34) and a three-course steroid pulse during a period from July 2010 to March 2013 (Group B; n = 32). Primary end points were excretory amounts of proteinuria, disappearance of proteinuria and hematuria, and exacerbation of renal function. In both the groups, proteinuria decreased significantly 12 months after treatment, and no significant difference in alleviation effects on proteinuria was found between groups. eGFR increased significantly 12 months after treatment in Group A, whereas it tended to decrease in Group B. As for the preservation effect on eGFR, Group A showed significantly higher preservation of eGFR. Similar results were shown in the patients whose eGFR at the start of the treatment was less than 60 mL/min/1.73 m(2). Single-course steroid pulse therapy combined with mizoribine was considered to have a protective effect on the renal function in IgA nephropathy, especially accompanying renal dysfunction. | IgA nephropathy;Mizoribine;Steroid pulse;Tonsillectomy | pubmed |
Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease. | Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2) IU/μgDNA) compared to the IM (median, 10(2.1) IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0) IU/μgDNA and 10(3.2) IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients. | CAEBV;Chronic active Epstein–Barr virus disease;Diagnosis;Peripheral blood mononuclear cells;Viral load | pubmed |
Collecting in collections: a PCR strategy and primer set for DNA barcoding of decades-old dried museum specimens. | Natural history museums are vastly underutilized as a source of material for DNA analysis because of perceptions about the limitations of DNA degradation in older specimens. Despite very few exceptions, most DNA barcoding projects, which aim to obtain sequence data from all species, generally use specimens collected specifically for that purpose, instead of the wealth of identified material in museums, constrained by the lack of suitable PCR methods. Any techniques that extend the utility of museum specimens for DNA analysis therefore are highly valuable. This study first tested the effects of specimen age and PCR amplicon size on PCR success rates in pinned insect specimens, then developed a PCR primer set and amplification strategy allowing greatly increased utilization of older museum specimens for DNA barcoding. PCR success rates compare favourably with the few published studies utilizing similar aged specimens, and this new strategy has the advantage of being easily automated for high-throughput laboratory workflows. The strategy uses hemi-nested, degenerate, M13-tailed PCR primers to amplify two overlapping amplicons, using two PCRs per amplicon (i.e. four PCRs per DNA sample). Initial PCR products are reamplified using an internal primer and a M13 primer. Together the two PCR amplicons yield 559 bp of the COI gene from Coleoptera, Lepidoptera, Diptera, Hemiptera, Odonata and presumably also other insects. BARCODE standard-compliant data were recovered from 67% (56 of 84) of specimens up to 25 years old, and 51% (102 of 197) of specimens up to 55 years old. Given the time, cost and specialist expertise required for fieldwork and identification, 'collecting in collections' is a viable alternative allowing researchers to capitalize on the knowledge captured by curation work in decades past. | COI;DNA barcodes;DNA sequencing;insect | pubmed |
Understanding How Sexual and Gender Minority Stigmas Influence Depression Among Trans Women and Men Who Have Sex with Men in India. | Few studies have assessed how sexual and gender minority stigmas affect the mental health of trans women and self-identified men who have sex with men (MSM) in India, populations with a high HIV burden. We tested whether social support and resilient coping act as mediators of the effect of sexual and gender minority stigmas on depression as proposed by Hatzenbuehler's psychological mediation framework, or as moderators based on Meyer's minority stress theory. We conducted a cross-sectional survey among trans women (n = 300) and MSM (n = 300) recruited from urban and rural sites in India. Standardized scales were used to measure depression (outcome variable), transgender identity stigma/MSM stigma (predictor variables), and social support and resilient coping (tested as moderators and parallel mediators). The mediation and moderation models were tested separately for trans women and MSM, using Hayes' PROCESS macro in SPSS. Participants' mean age was 29.7 years (standard deviation 8.1). Transgender identity stigma and MSM stigma were significant predictors (significant total and direct effects) of depression, as were social support and resilient coping. Among trans women and MSM, social support and resilient coping mediated (i.e., significant specific indirect effects), but did not moderate, the effect of stigma on depression, supporting the psychological mediation framework. Sexual and gender minority stigmas are associated with depression, with social support and resilient coping as mediators. In addition to stigma reduction interventions at the societal level, future interventions should focus on improving social support and promoting resilience among trans women and MSM in India. | India;depression;gender minority stigma;men who have sex with men;sexual stigma;social support;trans women | pubmed |
Validation of a quantitative method to measure neural respiratory drive in children during sleep. | Quantitatively measure and validate analysis of neural respiratory drive (NRD) using a commercial polysomnography system in children during sleep. Surface electromyogram of the diaphragm (sEMGdi) recorded from primary snoring children were analysed. A subset was re-analysed to assess intra- and inter-investigator reproducibility. Effects of different band pass filter settings (20-100Hz vs 10-1000Hz) on sEMGdi amplitude were evaluated. Mean sEMGdi from 45 children aged 4.38 years (median; IQR 3.00-7.96) was 5.05μV (SD 2.73). The sEMGdi had a high intra-subject intraclass correlation coefficient (ICC) of 0.88. sEMGdi analysis was reproducible with high ICC between occasions (0.99; 95% CI 0.98-0.99) and between investigators (0.98; 95% CI 0.97-0.99). There was also a high ICC (0.99, 95% CI 0.96-1.00) between the sEMGdi measured using different band-pass filter settings. Age and BMI were negative predictors of sEMGdi (p<0.0001 and p=0.0004 respectively). NRD in children during sleep as assessed by sEMGdi can be quantified in a reliable and reproducible fashion. | Child;Diaphragm EMG;Physiology;Polysomnography;Reproducibility;Sleep | pubmed |
Quality of life of patients with locally advanced head and neck cancer treated with induction chemotherapy followed by cisplatin-containing chemoradiotherapy in the Dutch CONDOR study: a randomized controlled trial. | The CONDOR study showed that docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with cisplatin 100 mg/m<sup>2</sup> on days 1, 22, and 43 (cis100 + RT; n = 27)) versus accelerated radiotherapy with cisplatin weekly 40 mg/m<sup>2</sup> (cis40 + ART; n = 29) in locally advanced head and neck cancer (LAHNC) patients was not feasible. Here, we report the analysis of health-related quality of life (HRQOL) of the patients entered in this study. HRQOL was assessed at baseline, after two TPF, before start of chemoradiotherapy, and 1, 4, 8, 12, and 24 months after completion of chemoradiotherapy using the EORTC-QLQ-C30 and QLQ-H&N35 in 62 patients. Compliance with the QOL questionnaires was 94% (59/62) at baseline and 61% (30/49) at 12 months, respectively. HRQOL decreased after TPF and further decreased during chemoradiohteray in both arms equally. Pain and swallowing dysfunction improved significantly during TPF but deteriorated below baseline levels during chemoradiotherapy, cis40 + ART > cis100 + RT (p < 0.05). HRQOL and symptoms restored to baseline within 12 months in both arms and remained at that level until 24 months. After TPF, cis40 + ART had a larger negative impact on symptoms than cis100 + RT, probably due to the ART. HRQOL and symptoms restored to baseline levels within 12 months after end of treatment in both arms, which is an important perspective for patients during the phase of most serious acute side effects of treatment. NCT00774319. | Chemoradiotherapy;Induction chemotherapy;Locally advanced head and neck cancer;Quality of life;Symptoms | pubmed |
Characterization, survival analysis, and expression of IGFR in tumor samples from patients diagnosed with Ewing family tumors treated at the Barretos Cancer Hospital. | Study the clinical characteristics of patients diagnosed with Ewing family tumors (EFTs) and survival analysis based on risk criteria and expression of the surface protein known as insulin-like growth factor (IGFR). This was a retrospective cohort study based on clinical data from 77 patients diagnosed with EFTs treated by the Department of Pediatric Oncology at the Barretos Cancer Hospital in a period between 2003 and 2012. Biological samples of patients were examined for the presence of the surface receptor IGFR. The overall survival rate (OSR) of patients included in the study was 45% at five years, and EFS was 30% at five years. Metastasis at diagnosis was present in 44.2% of the sample; 88.2% of the sample was male (<i>p</i> < 0.001). The evaluation of the expression of IGFR in biological samples of patients was associated with the variable metastasis at diagnosis (<i>p</i> < 0.001). Worse prognosis was observed in patients with extrapulmonary metastasis (<i>p</i> = 0.009). The local treatment of neoplasia presented better prognosis in patients undergoing local surgical treatment (<i>p</i> < 0.001). These results showed a higher incidence of metastasis at diagnosis in patients with EFTs treated at the Barretos Cancer Hospital (BCH). Extrapulmonary metastases were a negative prognostic factor in this study. Surgical treatment of the primary tumor was a factor for better prognosis. Strong expression of IGFR was more frequent in patients with metastases at diagnosis, but did not represent a prognostic factor for EFTs. | Bone neoplasms;Ewing;Insulin-like growth factor I;Neuroectodermal tumors;Oncology;Peripheral;Primitive;Sarcoma;Survival analysis | pubmed |
<i>ALK</i> Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy. | Genomic fusions of the anaplastic lymphoma kinase gene (<i>ALK</i>) are a well-established therapy target in non-small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of <i>ALK</i> rearrangements (r<i>ALK</i>) in non-NSCLC tumors and report their responsiveness to therapies targeting ALK. Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. Of 114,200 clinical samples, 21,522 (18.8%) were NSCLC and 92,678 (81.2%) were other tumor types. Of the 876 (0.8%) cases with <i>ALK</i> fusions (f<i>ALK</i>) or rALK, 675 (77.1%) were NSCLC and 201 (22.9%) were other tumor types. <i>ALK</i> fusions were significantly more frequent in NSCLC (3.1%) than non-NSCLC (0.2%; <i>p</i> < .0001). Patients with non-NSCLC tumors harboring f<i>ALK</i> were significantly younger (<i>p</i> < .0001) and more often female (<i>p</i> < .0001) than patients with f<i>ALK</i>-positive NSCLC. <i>EML4</i> was more often the fusion partner in NSCLC (83.5%) versus non-NSCLC tumors (30.9%; <i>p</i> < .0001). <i>ALK</i> rearrangements can be identified in a wide variety of epithelial and mesenchymal malignancies beyond NSCLC. Anti-ALK therapies can be effective in non-NSCLC tumors driven by f<i>ALK</i>, and further study of therapies targeting <i>ALK</i> in clinical trials involving a wider variety of cancer types appears warranted. Rearrangements involving the <i>ALK</i> gene have been detected in dozens of cancer types using next-generation sequencing. Patients whose tumors harbor <i>ALK</i> rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with <i>ALK</i> mutations, such as non-Langerhans cell histiocytosis or renal cell carcinoma. Comprehensive genomic profiling using next-generation sequencing can detect targetable <i>ALK</i> fusions irrespective of tumor type or fusions partner. | ALK;Alectinib;Comprehensive genomic profiling;Crizotinib;Fusion;Rearrangement | pubmed |
Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis. | Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro. The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo. | IKKα pathway;Mouse model;NAPA;Osteoarthritis | pubmed |
Developing standards for the development of glaucoma virtual clinics using a modified Delphi approach. | To obtain consensus opinion for the development of a standards framework for the development and implementation of virtual clinics for glaucoma monitoring in the UK using a modified Delphi methodology. A modified Delphi technique was used that involved sampling members of the UK Glaucoma and Eire Society (UKEGS). The first round scored the strength of agreement to a series of standards statements using a 9-point Likert scale. The revised standards were subjected to a second round of scoring and free-text comment. The final standards were discussed and agreed by an expert panel consisting of seven glaucoma subspecialists from across the UK. A version of the standards was submitted to external stakeholders for a 3-month consultation. There was a 44% response rate of UKEGS members to rounds 1 and 2, consisting largely of consultant ophthalmologists with a specialist interest in glaucoma. The final version of the standards document was validated by stakeholder consultation and contains four sections pertaining to the patient groups, testing methods, staffing requirements and governance structure of NHS secondary care glaucoma virtual clinic models. Use of a modified Delphi approach has provided consensus agreement for the standards required for the development of virtual clinics to monitor glaucoma in the UK. It is anticipated that this document will be useful as a guide for those implementing this model of service delivery. | Delphi;glaucoma;standards;virtual clinic | pubmed |
Variation analysis of norovirus among children with diarrhea in rural Hebei Province, north of China. | To understand the distribution of genotyping, as well as evolution of norovirus circulating among children<5yrs., a population-based diarrhea surveillance targeted children<5yrs. was conducted in rural Zhengding County, Hebei Province, China between October 2011 and March 2012. RT-PCR was used to amplify the capsid-encoding region of GI and GII norovirus to identify norovirus infection. All PCR products were sequenced and analyzed for genotyping and constructing phylogenetic tree. Dynamic distribution network was constructed by TempNet to illustrate the genetic relationships at two different time points. Bayesian evolutionary inference techniques were applied by BEAST software to study the norovirus evolution rate. During the 6-month surveillance period, 1091 episodes of diarrhea were reported from 5633 children under 5years of age lived in catchment area. 115 of 1091 stool specimens were detected as norovirus positive (10.54%). Five genotypes based on capsid gene sequences were identified, including GII.2 (11), GII.3 (52), GII.4 (47), GII.6 (4) and GII.7 (1). An identical haplotype of GII.4 circulated between 2006 and 2011 in Hebei Province. A mean rate of 6.29×10<sup>-2</sup> nucleotide substitutions/site/year (s/s/y) was obtained for GII.3 viruses in Hebei, while the GII.4 viruses evolved at a mean rate of 3.67×10<sup>-2</sup>s/s/y. In conclusions, GII.3 (45.22%) and GII. 4(40.87%) are the predominant strain in Hebei Province in the winter season of 2011 and 2012. Different from the current consensus, our study shows that GII.3 noroviruses in Hebei Province evolved at a faster rate than GII.4 viruses. | China;Evolutionary rates;Genotyping;Haplotype network;Norovirus;Phylogenetic tree | pubmed |
Sphingobacterium corticis sp. nov., isolated from bark of Populus × euramericana. | A Gram-stain negative, aerobic, non-motile bacterial strain, 23D10-4-9<sup>T</sup>, was isolated from symptomatic canker bark tissue of Populus × euramericana. The isolate grew between 4 and 35 °C, with optimal growth occurring at 25 °C. The species was positive for catalase and negative for oxidase activity. Nitrate was not reduced to nitrite. It showed activities toward β-galactosidase and β-glucosidase. Citrate was not utilized. Acid was produced from d-glucose. The major fatty acids were iso-C15 : 0, C16 : 1ω7c and iso-C17 : 0 3-OH. The main polar lipid profiles of the novel isolate included phosphatidylethanolamine, phospholipids and seven unknown lipids. The predominant menaquinone of the novel isolate was MK-7. The DNA G+C content was 40.6 mol%. 16S rRNA gene data revealed that the novel isolate shares the greatest sequence similarity with Sphingobacterium populi 7Y-4<sup>T</sup> (96.1 %). Based on phenotypic and genotypic characteristics, the isolate represents a novel species within the genus Sphingobacterium, for which the name Sphingobacteriumcorticis sp. nov. is proposed. The type strain is 23D10-4-9<sup>T</sup> (=CFCC 12640<sup>T</sup>=KCTC 42248<sup>T</sup>). | Populus × euramericana;Sphingobacterium corticis sp. nov.;bark | pubmed |
Change-point analysis data of neonatal diffusion tensor MRI in preterm and term-born infants. | The data presented in this article are related to the research article entitled "Mapping the Critical Gestational Age at Birth that Alters Brain Development in Preterm-born Infants using Multi-Modal MRI" (Wu et al., 2017) [1]. Brain immaturity at birth poses critical neurological risks in the preterm-born infants. We used a novel change-point model to analyze the critical gestational age at birth (GAB) that could affect postnatal development, based on diffusion tensor MRI (DTI) acquired from 43 preterm and 43 term-born infants in 126 brain regions. In the corresponding research article, we presented change-point analysis of fractional anisotropy (FA) and mean diffusivities (MD) measurements in these infants. In this article, we offered the relative changes of axonal and radial diffusivities (AD and RD) in relation to the change of FA and FA-based change-points, and we also provided the AD- and RD-based change-point results. | Axial diffusivity;Change-point analysis;Neonatal brain MRI;Preterm-born infants;Radial diffusivity | pubmed |
Beyond Hygiene: Commensal Microbiota and Allergic Diseases. | Complex communities of microorganisms, termed commensal microbiota, inhabit mucosal surfaces and profoundly influence host physiology as well as occurrence of allergic diseases. Perturbing factors such as the mode of delivery, dietary fibers and antibiotics can influence allergic diseases by altering commensal microbiota in affected tissues as well as in intestine. Here, we review current findings on the relationship between commensal microbiota and allergic diseases, and discuss the underlying mechanisms that contribute to the regulation of allergic responses by commensal microbiota. | Asthma;Atopic dermatitis;Commensal microbiota;Food allergy | pubmed |
The component formula of <i>Salvia miltiorrhiza</i> and <i>Panax</i> ginseng induces apoptosis and inhibits cell invasion and migration through targeting PTEN in lung cancer cells. | Lung cancer still remains the leading cause of cancer-related death worldwide. It is an urgent need for development of novel therapeutic agents to improve current treatment of this disease. Here we investigate whether the effective component formula of traditional Chinese Medicine could serve as new potential therapeutic drugs to treat lung cancer. We optimize the most effective component formula of <i>Salvia miltiorrhiza</i> and <i>Panax</i> Ginseng (FMG), which is composed of Salvianolic acid A, 20(S)-Ginsenoside and Ginseng polysaccharide. We discovered that FMG selectively inhibited lung cancer cell proliferation and induced apoptosis but had no any cytotoxic effects on normal lung epithelial BEAS-2B cells. Moreover, FMG inhibited lung cancer cell migration and invasion. Mechanistically, we found that FMG significantly promoted p-PTEN expression and subsequently inhibited PI3K/AKT signaling pathway. The phosphatase activity of PTEN protein was increased after FMG bound to PTEN protein, indicating that PTEN is one of the FMG targeted proteins. In addition, FMG regulated expression of some marker proteins relevant to cell apoptosis, migration and invasion. Collectively, these results provide mechanistic insight into the anti-NSCLC of FMG by enhancing the phosphatase activity of PTEN, and suggest that FMG could be as a potential option for lung cancer treatment. | PI3K/AKT signaling pathway;PTEN phosphorylation;orthogonal array design;the component formula of Salvia miltiorrhiza and Panax ginseng (FMG) | pubmed |
Why georeferencing matters: Introducing a practical protocol to prepare species occurrence records for spatial analysis. | Species Distribution Models (SDMs) are widely used to understand environmental controls on species' ranges and to forecast species range shifts in response to climatic changes. The quality of input data is crucial determinant of the model's accuracy. While museum records can be useful sources of presence data for many species, they do not always include accurate geographic coordinates. Therefore, actual locations must be verified through the process of georeferencing. We present a practical, standardized manual georeferencing method (the Spatial Analysis Georeferencing Accuracy (SAGA) protocol) to classify the spatial resolution of museum records specifically for building improved SDMs. We used the high-elevation plant <i>Saxifraga austromontana</i> Wiegand (Saxifragaceae) as a case study to test the effect of using this protocol when developing an SDM. In MAXENT, we generated and compared SDMs using a comprehensive occurrence dataset that had undergone three different levels of georeferencing: (1) trained using all publicly available herbarium records of the species, minus outliers (2) trained using herbarium records claimed to be previously georeferenced, and (3) trained using herbarium records that we have manually georeferenced to a ≤ 1-km resolution using the SAGA protocol. Model predictions of suitable habitat for <i>S. austromontana</i> differed greatly depending on georeferencing level. The SDMs fitted with presence locations georeferenced using SAGA outperformed all others. Differences among models were exacerbated for future distribution predictions. Under rapid climate change, accurately forecasting the response of species becomes increasingly important. Failure to georeference location data and cull inaccurate samples leads to erroneous model output, limiting the utility of spatial analyses. We present a simple, standardized georeferencing method to be adopted by curators, ecologists, and modelers to improve the geographic accuracy of museum records and SDM predictions. | GIS;Species Distribution Models;biogeography;botany;georeferencing;herbarium records;museum collections | pubmed |
Can gaze-contingent mirror-feedback from unfamiliar faces alter self-recognition? | This study focuses on learning of the self, by examining how human observers update internal representations of their own face. For this purpose, we present a novel gaze-contingent paradigm, in which an onscreen face mimics observers' own eye-gaze behaviour (in the congruent condition), moves its eyes in different directions to that of the observers (incongruent condition), or remains static and unresponsive (neutral condition). Across three experiments, the mimicry of the onscreen face did not affect observers' perceptual self-representations. However, this paradigm influenced observers' reports of their own face. This effect was such that observers felt the onscreen face to be their own and that, if the onscreen gaze had moved on its own accord, observers expected their own eyes to move too. The theoretical implications of these findings are discussed. | Mirror recognition;Self-face learning;Self-face recognition;Self-face representation | pubmed |
A panel of microRNAs can be used to determine oral squamous cell carcinoma. | Subjective histopathology is currently used to diagnose oral squamous cell carcinoma (OSCC). We tested if abundances of a panel of microRNA could be an objective OSCC indicator. Literature review enabled identification of 10 microRNAs associated with oral and head and neck malignancies. We extracted RNA from formalin-fixed paraffin-embedded biopsies; 20 each with OSCC, dysplasia, or histologically normal epithelium (HNE) and 10 with oral lichen planus (OLP). Relative abundances of microRNAs in HNE and OSCC were determined using reverse transcription and then real-time PCR with global mean normalization. MicroRNAs differentially expressed (test microRNA, T-miR) and non-differentially expressed (normalization microRNA, N-miR) were identified. The raw microRNA Cq data were incorporated in a developed algorithm that output a T-miR expression value (T-miREV) score. Raw Cq data from HNE, OSCC, dysplasia, and OLP samples were then used to test the algorithm scoring and OSCC classification. Four test and normalization microRNAs were identified. Algorithm output of T-mirEV >1 or <-1 indicated high and low OSCC probability score, respectively, and gave 88.9% sensitivity, 100% specificity, and 93.5% accuracy. Grouping high and intermediate T-mirEV scores (T-miREV ≥-1) resulted in sensitivity of 90%, specificity of 65%, and accuracy of 77.5% in OSCC classification. All 20 dysplasias and eight of 10 OLP had T-miREV ≥-1 indicating intermediate to high probability of malignant changes. A microRNA panel combined with our algorithm can identify tissue with probable oncogenic changes. The developed algorithm serves as a baseline for prospective trials, which may result in potential clinical utility. | algorithm;diagnostic;microRNAs;oral cancer | pubmed |
Using the agricultural environment to select better surrogates for foodborne pathogens associated with fresh produce. | Despite continuing efforts to reduce foodborne pathogen contamination of fresh produce, significant outbreaks continue to occur. Identification of appropriate surrogates for foodborne pathogens facilitates relevant research to identify reservoirs and amplifiers of these contaminants in production and processing environments. Therefore, the objective of this study was to identify environmental Escherichia coli isolates from manures (poultry, swine and dairy) and surface water sources with properties similar to those of the produce associated foodborne pathogens E. coli O157:H7 and Salmonella enterica serotype Typhimurium. The most similar environmental E. coli isolates were from poultry (n=3) and surface water (n=1) sources. The best environmental E. coli surrogates had cell surface characteristics (zeta potential, hydrophobicity and exopolysaccharide composition) that were similar (i.e., within 15%) to those of S. Typhimurium and/or formed biofilms more often when grown in low nutrient media prepared from lettuce lysates (24%) than when grown on high nutrient broth (7%). The rate of attachment of environmental isolates to lettuce leaves was also similar to that of S. Typhimurium. In contrast, E. coli O157:H7, a commonly used E. coli quality control strain and swine isolates behaved similarly; all were in the lowest 10% of isolates for biofilm formation and leaf attachment. These data suggest that the environment may provide a valuable resource for selection of surrogates for foodborne pathogens. | Adhesion;Biofilm;E. coli;Environment;Lettuce;Salmonella | pubmed |
The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on K<sub>Ca</sub>2.3/K<sub>Ca</sub>3.1-EDH-type relaxation in rat small mesenteric arteries. | The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (K<sub>Ca</sub>2.3/K<sub>Ca</sub>3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of N<sup>ω</sup>-nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively). In normo- and hypertension the efficacy of EDH-type relaxation was similar and inhibition of K<sub>Ca</sub>2.3 and K<sub>Ca</sub>3.1 by UCL1684 and TRAM-34, respectively, given alone or in combination, attenuated EDH-mediated vasorelaxation. K<sub>Ca</sub>3.1 expression and NS309 (K<sub>Ca</sub>2.3/K<sub>Ca</sub>3.1 activator)-induced relaxation was reduced in sMAs of DOCA-salt rats. Endothelium denudation and incubation with UCL1684 and TRAM-34 attenuated the maximal NS309-evoked vasorelaxation in both groups. URB597 had no effect in functional studies, but increased the expression of K<sub>Ca</sub>3.1 in the sMAs. K<sub>Ca</sub>2.3/K<sub>Ca</sub>3.1-EDH-mediated relaxation was maintained in the sMAs of DOCA-salt rats despite endothelial dysfunction and down-regulation of K<sub>Ca</sub>3.1. Furthermore, K<sub>Ca</sub>3.1 played a key role in the EDH-type dilator response of sMAs in normo- and hypertension. The hypotensive effect of URB597 is independent of K<sub>Ca</sub>2.3/K<sub>Ca</sub>3.1-EDH-type relaxation. | DOCA-salt hypertension;EDH-type relaxation;FAAH inhibitor;K(Ca)2.3;K(Ca)3.1 | pubmed |
Reversible S<sup>0</sup> /MgS<sub>x</sub> Redox Chemistry in a MgTFSI<sub>2</sub> /MgCl<sub>2</sub> /DME Electrolyte for Rechargeable Mg/S Batteries. | The redox chemistry of magnesium and its application in rechargeable Mg batteries has received increasing attention owing to the unique benefits of Mg metal electrodes, namely high reversibility without dendrite formation, low reduction potentials, and high specific capacities. The Mg/S couple is of particular interest owing to its high energy density and low cost. Previous reports have confirmed the feasibility of a rechargeable Mg/S battery; however, only limited cycling stability was achieved, and the complicated procedure for the preparation of the electrolytes has significantly compromised the benefits of Mg/S chemistry and hindered the development of Mg/S batteries. Herein, we report the development of the first rechargeable Mg/S battery with a MgTFSI<sub>2</sub> /MgCl<sub>2</sub> /DME electrolyte (DME=1,2-dimethoxyethane, TFSI=bis(trifluoromethanesulfonyl)imide) and realize the best cycling stability among all reported Mg/S batteries by suppressing polysulfide dissolution. Mechanistic studies show that the battery works via S<sup>0</sup> /MgS<sub>x</sub> redox processes and that the large voltage hysteresis is mainly due to the Mg anode overpotential. | batteries;electrochemistry;magnesium;polysulfide;sulfur | pubmed |
Whole-Body Docosahexaenoic Acid Synthesis-Secretion Rates in Rats Are Constant across a Large Range of Dietary α-Linolenic Acid Intakes. | Docosahexaenoic acid (DHA) is an ω-3 (n-3) polyunsaturated fatty acid (PUFA) thought to be important for brain function. Although the main dietary source of DHA is fish, DHA can also be synthesized from α-linolenic acid (ALA), which is derived from plants. Enzymes involved in DHA synthesis are also active toward ω-6 (n-6) PUFAs to synthesize docosapentaenoic acid n-6 (DPAn-6). It is unclear whether DHA synthesis from ALA is sufficient to maintain brain DHA. The objective of this study was to determine how different amounts of dietary ALA would affect whole-body DHA and DPAn-6 synthesis rates. Male Long-Evans rats were fed an ALA-deficient diet (ALA-D), an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet for 8 wk from weaning. Dietary ALA concentrations were 0.07%, 3%, and 10% of the fatty acids, and ALA was the only dietary PUFA that differed between the diets. After 8 wk, steady-state stable isotope infusion of labeled ALA and linoleic acid (LA) was performed to determine the in vivo synthesis-secretion rates of DHA and DPAn-6. Rats fed the ALA-A diet had an ∼2-fold greater capacity to synthesize DHA than did rats fed the ALA-H and ALA-D diets, and a DHA synthesis rate that was similar to that of rats fed the ALA-H diet. However, rats fed the ALA-D diet had a 750% lower DHA synthesis rate than rats fed the ALA-A and ALA-H diets. Despite enrichment into arachidonic acid, we did not detect any labeled LA appearing as DPAn-6. Increasing dietary ALA from 3% to 10% of fatty acids did not increase DHA synthesis rates, because of a decreased capacity to synthesize DHA in rats fed the ALA-H diet. Tissue concentrations of DPAn-6 may be explained at least in part by longer plasma half-lives. | docosahexaenoic acid;kinetics;synthesis;α-linolenic acid;ω-3 PUFA | pubmed |
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SciDocs Keywords exKEYliWORD
Dataset Description
SciDocs2Keywords is a dataset consisting of scientific papers (title and abstract) and their associated author-provided keywords. It is designed for use in task of keyword extraction or abstraction.
Each entry in the dataset includes:
- Title: The title of the scientific paper.
- Abstract: A brief summary of the paper.
- Author Keywords: Keywords provided by the authors to highlight the main topics or concepts of the paper.
- Source: Paper provider source API.
Associated Model
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How to Use
To use this dataset for model training or evaluation, you can load it using the Hugging Face datasets library as follows:
from datasets import load_dataset
dataset = load_dataset("nicolauduran45/scidocs-keywords-exkeyliword")
print(dataset[0])
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