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Resistance to Streptomyces turgidiscabies in potato involves an early and sustained transcriptional reprogramming at initial stages of tuber formation. | Common scab, caused by species from the bacterial genus Streptomyces, is an important disease of potato (Solanum tuberosum) crops worldwide. Early tuberization is a critical period for pathogen infection; hence, studies of host gene expression responses during this developmental stage can be important to expand our understanding of the infection process and to identify putative resistance genes. In an infection experiment with the highly susceptible potato cultivar Saturna and the relatively resistant cultivar Beate, transcription profiles were obtained by RNA sequencing at two developmental stages: the early hook stage and the early tuber formation stage. Our results indicate that 'Beate' mounts an early and sustained response to infection by S. turgidiscabies, whereas the defence response by 'Saturna' ceases before the early tuber formation stage. Most pronounced were the putative candidate defence-associated genes uniquely expressed in 'Beate'. We observed an increase in alternative splicing on pathogen infection at the early hook stage for both cultivars. A significant down-regulation of genes involved in the highly energy-demanding process of ribosome biogenesis was observed for the infected 'Beate' plants at the early hook stage, which may indicate an allocation of resources that favours the expression of defence-related genes. | Solanum tuberosum;common scab;transcriptomics | pubmed |
The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis. | Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan. Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration. Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009). | Anemia management;ESA;Erythropoiesis-stimulating agents;Myelofibrosis;Ruxolitinib | pubmed |
Palliative and end-of-life care in pediatric solid organ transplantation. | End-of-life care is a component of palliative care and takes a holistic, individualized approach to patients, focusing on the assessment of quality of life and its maintenance until the end of life, and beyond, for the patient's family. Transplant teams do not always make timely referrals to palliative care teams due to various clinician and perceived family barriers, an important one being the simultaneous, active care plan each patient would have alongside an end-of-life plan. Application of findings and further research specific to the pediatric solid organ population would be of significant benefit to guide transplant teams as to the most effective time to introduce end-of-life care, who to involve in ongoing discussions, and important ethical and cultural considerations to include in care planning. Attention must also be paid to clinician training and support in this challenging area of health care. | advanced care planning;end-of-life care;ethics;palliative care;pediatric transplantation;quality of life | pubmed |
Quantitative variability of 342 plasma proteins in a human twin population. | The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2-7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis-SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood-based biomarker studies. | SWATH‐MS;heritability;longitudinal variability;plasma biomarkers;twin study | pubmed |
Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation. | By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. | Atomic force microscopy;Computational simulations;Early-stage aggregation;Interfaces;Prion protein | pubmed |
Variations in Metformin Prescribing for Type 2 Diabetes. | Reasons for suboptimal metformin prescribing are unclear, but may be due to perceived risk of lactic acidosis. The purpose of this study is to describe provider attitudes regarding metformin prescribing in various patient situations. An anonymous, electronic survey was distributed electronically to 76 health care providers across the nation. The 14-item survey contained demographic questions and questions related to prescribing of metformin for T2DM in various patient situations, including suboptimal glycemic control, alcohol use, history of lactic acidosis, and varying degrees of severity for certain health conditions, including renal and hepatic dysfunction, chronic obstructive pulmonary disease, and heart failure. There were a total of 100 respondents. For suboptimal glycemic control, most providers (75%) would increase metformin from 1500 to 2000 mg daily; however, 25% would add an alternate agent, such as a sulfonylurea (18%) or dipeptidyl peptidase-4 inhibitor (7%). Although 51% of providers would stop metformin based on serum creatinine thresholds, the remainder would rely on glomerular filtration rate thresholds of <60 mL/min (15%), <30 mL/min (33%), or <15 mL/min (1%) to determine when to stop metformin. For heart failure, 45% of providers would continue metformin as currently prescribed regardless of severity. Most providers would adjust metformin for varying severity of hepatic dysfunction (74%) and alcohol abuse (40%). Despite evidence supporting the cardiovascular benefits of metformin, provider attitudes toward prescribing metformin are suboptimal in certain patient situations and vary greatly by provider. | Health Care Surveys;Lactic Acidosis;Metformin;Physician's Practice Patterns;Type 2 Diabetes Mellitus | pubmed |
Impact of classic and paradoxical low flow on survival after aortic valve replacement for severe aortic stenosis. | Low flow (LF) can occur with reduced (classic) or preserved (paradoxical) left ventricular ejection fraction (LVEF). The objective of this study was to compare outcomes of patients with low ejection fraction (LEF), paradoxical low flow (PLF), and normal flow (NF) after aortic valve replacement (AVR). We examined 1,154 patients with severe aortic stenosis (AS) who underwent AVR with or without coronary artery bypass grafting. Among these patients, 206 (18%) had LEF as defined by LVEF of <50%; 319 (28%) had PLF as defined by LVEF of ≥50% but stroke volume indexed to body surface area (SVi) of ≤35 ml ∙ m(-2); and 629 (54%) had NF, as defined by LVEF of ≥50% and SVi of >35 ml ∙ m(2). Aortic valve area was lower in low flow/LVEF groups (LEF: 0.71 ± 0.20 cm(2) and PLF: 0.65 ± 0.23 cm(2) vs. NF: 0.77 ± 0.18 cm(2); p < 0.001). The 30-day mortality was higher (p < 0.001) in LEF and PLF groups than in the NF group (6.3% and 6.3% vs. 1.8%, respectively). SVi and PLF group were independent predictors of operative mortality (odds ratio [OR]: 1.18, p < 0.05; and OR: 2.97, p = 0.004; respectively). At 5 years after AVR, overall survival was 72 ± 4% in LEF group, 81 ± 2% in PLF group, and 85 ± 2% in NF group (p < 0.0001). Patients with LEF or PLF AS have a higher operative risk, but pre-operative risk score accounted only for LEF and lower LVEF. Patients with LEF had the worst survival outcome, whereas patients with PLF and normal flow had similar survival rates after AVR. As a major predictor of perioperative mortality, SVi should be integrated in AS patients' pre-operative evaluation. | aortic stenosis;low flow;low ejection fraction;survival | pubmed |
Solution-Processed Dielectrics Based on Thickness-Sorted Two-Dimensional Hexagonal Boron Nitride Nanosheets. | Gate dielectrics directly affect the mobility, hysteresis, power consumption, and other critical device metrics in high-performance nanoelectronics. With atomically flat and dangling bond-free surfaces, hexagonal boron nitride (h-BN) has emerged as an ideal dielectric for graphene and related two-dimensional semiconductors. While high-quality, atomically thin h-BN has been realized via micromechanical cleavage and chemical vapor deposition, existing liquid exfoliation methods lack sufficient control over h-BN thickness and large-area film quality, thus limiting its use in solution-processed electronics. Here, we employ isopycnic density gradient ultracentrifugation for the preparation of monodisperse, thickness-sorted h-BN inks, which are subsequently layer-by-layer assembled into ultrathin dielectrics with low leakage currents of 3 × 10(-9) A/cm(2) at 2 MV/cm and high capacitances of 245 nF/cm(2). The resulting solution-processed h-BN dielectric films enable the fabrication of graphene field-effect transistors with negligible hysteresis and high mobilities up to 7100 cm(2) V(-1) s(-1) at room temperature. These h-BN inks can also be used as coatings on conventional dielectrics to minimize the effects of underlying traps, resulting in improvements in overall device performance. Overall, this approach for producing and assembling h-BN dielectric inks holds significant promise for translating the superlative performance of two-dimensional heterostructure devices to large-area, solution-processed nanoelectronics. | Density gradient ultracentrifugation;density differentiation;graphene;h-BN;heterostructure;isopycnic sorting | pubmed |
Clinical audit of patients hospitalized due to COPD exacerbation. MAG-1 Study. | Hospitalizations for acute exacerbation of COPD (AECOPD) generate high consumption of health resources, frequent readmissions and high mortality. The MAG -1 study aims to identify critical points to improve the care process of severe AECOPD requiring hospitalization. Observational study, with review of clinical records of patients admitted to hospitals of the Catalan public network for AECOPD. The centers were classified into 3 groups according to the number of discharges/year. Demographic and descriptive data of the previous year, pharmacological treatment, care during hospitalization and discharge process and follow-up, mortality and readmission at 30 and 90 days were analyzed. A total of 910 patients (83% male) with a mean age of 74.3 (+10.1) years and a response rate of 70% were included. Smoking habit was determined in only 45% of cases, of which 9% were active smokers. In 31% of cases, no previous lung function data were available. Median hospital stay was 7 days (IQR 4-10), increasing according the complexity of the hospital. Mortality from admission to 90 days was 12.4% with a readmission rate of 49%. An inverse relationship between length of hospital stay and readmission within 90 days was observed. In a large number of medical records, smoking habit and lung function tests were not appropriately reported. Average hospital stay increases with the complexity of the hospital, but longer stays appear to be associated with lower mortality at follow-up. | Audit;Auditoría;Chronic obstructive pulmonary disease;Enfermedad pulmonar obstructiva crónica;Hospitalización;Hospitalization;Mortalidad;Mortality;Readmissions;Reingresos | pubmed |
Analysis of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours. | The aim of this study was to determine the type and frequency of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours (GISTs) and investigate the association between the c-KIT mutation status and KIT immunohistochemical staining pattern. Mutations in exon 11 of c-KIT were examined in 46 formalin-fixed paraffin-embedded canine GISTs using PCR of genomic DNA and reverse transcription-PCR (RT-PCR) of cDNA. Exon 11 c-KIT mutations were detected in 15/46 (32.6%) cases by conventional PCR and 34/46 (73.9%) cases by RT-PCR; the mutation detection rate was significantly higher for RT-PCR (P = 0.004, Fisher's exact test). Ten different mutations, including deletion, internal tandem duplication and point mutations, were identified by RT-PCR. Immunohistochemistry was performed using an anti-KIT antibody; diffuse KIT staining was detected in the tumour cell cytoplasm in 32/46 (69.6%) cases and partial or stippled cytoplasmic staining of KIT was observed in 14/46 (30.4%) cases. Neither pattern was significantly associated with c-KIT exon 11 mutation status (P = 1.000, chi-square test). These data indicate that c-KIT exon 11 mutations occur frequently in canine GISTs, similar to human GISTs; however, there is no association between c-KIT mutations and the KIT expression pattern in canine GISTs. This study suggests that RT-PCR is more sensitive than conventional PCR for the detection of c-KIT mutations in canine GISTs. | Canine;Gastrointestinal stromal tumours;Immunohistochemistry;Mutation;c-KIT | pubmed |
Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience. | Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. This study was conducted as part of the service evaluation audit. Tertiary referral centre. All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. Fifty patients were analysed; median age 73 years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high-incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise. | BARRETT'S CARCINOMA;ENDOSCOPIC PROCEDURES | pubmed |
Changing trends of hospitalisation of liver cirrhosis in Beijing, China. | To examine if the hospitalisation trends of liver cirrhosis are changing with the changes of risk factors of the disease in China. Secondary analysis of hospitalisation records in the 31 top-ranking hospitals in Beijing. Between 2006 and 2010, hospitalisation from viral hepatitis cirrhosis (VHC) decreased by 10% (95% CI=5-14%, p<0.001), but non-viral hepatitis cirrhosis (NVHC) and alcoholic cirrhosis (AC) increased by 35% (26-46%, p<0.001) and 33% (19%- 47%, p<0.001), respectively. The age patterns of hospitalisation varied with different types of liver cirrhosis. The hospitalisation risks for patients with VHC and AC were significantly high in the age groups 40-49 and 50-59 years, but risks for those with NHVC were high in all age groups of 40 years or above. Overall male-to-female hospitalisation ratios for VHC, NVHC and AC were 2.71, 1.14 and 59.9, respectively. The sex ratio became smaller with time from 2006 to 2010 in hospitalised patients with VHC, but it substantially increased in those with NVHC during the same period. Hospitalisation rates for liver cirrhosis in Beijing are changing with time. The changes of viral hepatitis infection and alcohol consumption in the general population may cause these changes. | ALCOHOL;HEPATITIS;LIVER CIRRHOSIS | pubmed |
The Impact of Population, Contact, and Spatial Heterogeneity on Epidemic Model Predictions. | Our objective was to evaluate the effect that complexity in the form of different levels of spatial, population, and contact heterogeneity has in the predictions of a mechanistic epidemic model. A model that simulates the spatiotemporal spread of infectious diseases between animal populations was developed. Sixteen scenarios of foot-and-mouth disease infection in cattle were analyzed, involving combinations of the following factors: multiple production-types (PT) with heterogeneous contact and population structure versus single PT, random versus actual spatial distribution of population units, high versus low infectivity, and no vaccination versus preemptive vaccination. The epidemic size and duration was larger for scenarios with multiple PT versus single PT. Ignoring the actual unit locations did not affect the epidemic size in scenarios with multiple PT/high infectivity, but resulted in smaller epidemic sizes in scenarios using multiple PT/low infectivity. In conclusion, when modeling fast-spreading epidemics, knowing the actual locations of population units may not be as relevant as collecting information on population and contact heterogeneity. In contrast, both population and spatial heterogeneity might be important to model slower spreading epidemic diseases. Our findings can be used to inform data collection and modeling efforts to inform health policy and planning. | Disease modeling;health policy;parsimony | pubmed |
Regional Differential Genetic Response of Human Articular Cartilage to Impact Injury. | Normal physiological movement creates different weightbearing zones within a human knee: the medial condyle bearing the highest and the trochlea bearing the lowest weight. Adaptation to different physiological loading conditions results in different tissue and cellular properties within a knee. The objective of this study was to use microarray analysis to examine gene expression differences among three anatomical regions of human knee articular cartilage at baseline and following induction of an acute impact injury. Cartilage explants were harvested from 7 cadaveric knees (12 plugs per knee). A drop tower was utilized to introduce injury. Plugs were examined 24 hours after impact for gene expression using microarray. The primary analysis is the comparison of baseline versus impacted samples within each region separately. In addition, pairwise comparisons among the three regions were performed at baseline and after impact. False discovery rate (FDR) was used to evaluate significance of differential gene expression. In the comparison of before and after injury, the trochlear had 130 differentially expressed genes (FDR ≤ 0.05) while the condyles had none. In the comparison among regions, smaller sets of differentially expressed genes (n ≤ 21) were found, with trochlea being more different than the condyles. Most of more frequently expressed genes in trochlea are developmental genes. Within the experimental setup of this study, only the trochlea was displaying an acute genetic response on injury. Our data demonstrated the regional-specific response to injury in human articular cartilage. | articular cartilage;human knee;impact injury;regional genetic expression | pubmed |
Paroxysmal atrial fibrillation and clinically reversible cor pulmonale in a horse with complicated recurrent airway obstruction. | Cor pulmonale is considered an uncommon complication in horses with recurrent airway obstruction (RAO). This case report describes the history, clinical and further examination findings, treatment, progression and outcome of a horse diagnosed with cor pulmonale and paroxysmal atrial fibrillation of 2 days duration due to a severe exacerbation of RAO. To our best knowledge, this is the first report of RAO induced pulmonary hypertension in a horse causing atrial fibrillation. However, even severe cardiac changes due to respiratory dysfunction seem to be largely reversible in horses. | Pulmonary hypertension;cardiac disease;heart catheterization;heaves | pubmed |
Small molecule therapeutics targeting F-box proteins in cancer. | The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein equilibrium mainly through proteolytic degradation of targeted substrates. The archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition subunit F-box protein that recruits substrates to the catalytic ligase core for its polyubiquitylation and subsequent proteasomal degradation. Several well-characterized F-box proteins have been demonstrated that are tightly linked to neoplasia. There is mounting information characterizing F-box protein-substrate interactions with the rationale to develop unique therapeutics for cancer treatment. Here we review that how F-box proteins function in cancer and summarize potential small molecule inhibitors for cancer therapy. | Cancer;E3 ligase;F-box protein;Small molecule inhibitor;Ubiquitin | pubmed |
Structure-5-HT receptor affinity relationship in a new group of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione. | In our previous paper, we have reported that some 8-alkoxy-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic activity for the serotonin 5-HT1A receptor. In order to examine the influence of the substituent in the position 8 of the purine moiety on the affinity for the serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors, a series of 7-arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl (THIQ) derivatives of 8-amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds were investigated in in vitro competition binding experiments for serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors. The structure-affinity relationships for this group of compounds were discussed. For selected compounds, functional assays for the 5-HT1A receptor were carried out. The results of the assays indicated that these groups of derivatives possessed antagonistic activity for this receptor. | 5-HT1A;5-HT2A;5-HT7;LCAPs;Theophylline | pubmed |
Delineation of somatosensory finger areas using vibrotactile stimulation, an ECoG study. | In surgical planning for epileptic focus resection, functional mapping of eloquent cortex is attained through direct electrical stimulation of the brain. This procedure is uncomfortable, can trigger seizures or nausea, and relies on subjective evaluation. We hypothesize that a method combining vibrotactile stimulation and statistical clustering may provide improved somatosensory mapping. Seven pediatric candidates for surgical resection underwent a task in which their fingers were independently stimulated using a custom designed finger pad, during electrocorticographic monitoring. A cluster-based statistical analysis was then performed to localize the elicited activity on the recording grids. Mid-Gamma clusters (65-115 Hz) arose in areas consistent with anatomical predictions as well as clinical findings, with five subjects presenting a somatotopic organization of the fingers. This process allowed us to delineate finger representation even in patients who were sleeping, with strong interictal activity, or when electrical stimulation did not successfully locate eloquent areas. We suggest that this scheme, relying on the endogenous neural response rather than exogenous electrical activation, could eventually be extended to map other sensory areas and provide a faster and more objective map to better anticipate outcomes of surgical resection. | Electroencephalography;epilepsy;event‐related potentials;evoked potentials;fingers;somatosensory cortex | pubmed |
Blood monitoring of perfluorocarbon compounds (F-tert-butylcyclohexane, perfluoromethyldecalin and perfluorodecalin) by headspace-gas chromatography-tandem mass spectrometry. | A headspace-gas chromatography-tandem mass spectrometry (HS-GC-MS/MS) method for the trace measurement of perfluorocarbon compounds (PFCs) in blood was developed. Due to oxygen carrying capabilities of PFCs, application to doping and sports misuse is speculated. This study was therefore extended to perform validation methods for F-tert-butylcyclohexane (Oxycyte(®)), perfluoro(methyldecalin) (PFMD) and perfluorodecalin (PFD). The limit of detection of these compounds was established and found to be 1.2 µg/mL blood for F-tert-butylcyclohexane, 4.9 µg/mL blood for PFMD and 9.6 µg/mL blood for PFD. The limit of quantification was assumed to be 12 µg/mL blood (F-tert-butylcyclohexane), 48 µg/mL blood (PFMD) and 96 µg/mL blood (PFD). HS-GC-MS/MS technique allows detection from 1000 to 10,000 times lower than the estimated required dose to ensure a biological effect for the investigated PFCs. Thus, this technique could be used to identify a PFC misuse several hours, maybe days, after the injection or the sporting event. Clinical trials with those compounds are still required to evaluate the validation parameters with the calculated estimations. | F-tert-butylcyclohexane;Perfluoro(methyldecalin);Perfluorocarbons;Perfluorodecalin;Tandem mass spectrometry | pubmed |
Spectroscopic properties of transparent Er-doped oxyfluoride glass-ceramics with GdF₃. | Optically active glass-ceramics (GC) with the low-phonon phases of fluorides, doped with Er(3+) was studied. Glass based on SiO₂-Al₂O₃-Na₂F₂-Na₂O-GdF₃-BaO system was obtained. Dopant were introduced to the glass in an amount of 0.01 mol Er₂O₃ per 1 mol of glass. DTA/DSC study shows multi-stage crystallization. XRD identification of obtained phases did not confirm the presence of pure GdF₃ phase. Instead of that ceramization process led to formation of NaGdF₄ and BaGdF₅. The structural changes were studied using FT-IR spectroscopic method. The study of luminescence of the samples confirmed that optical properties of the obtained GC depend on crystallizing phases during ceramization. Time resolved spectroscopy of Er-doped glass showed the 3 and 8 times increase of lifetime of emission from (4)S₃/₂ and (4)F₉/₂ states, respectively. It confirms the erbium ions have ability to locate in the low phonon gadolinium-based crystallites. The results give possibility to obtain a new material for optoelectronic application. | Er;FTIR;GdF(3);Oxyfluoride glass;Time-resolved spectroscopy;Transparent glass–ceramics | pubmed |
The impact of childhood adversity on the persistence of psychotic symptoms: a systematic review and meta-analysis. | Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time. A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup. A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine studies yielded a weighted odds ratio of 1.76 [95% confidence interval (CI) 1.19-2.32, p < 0.001] for general population studies and 1.55 (95% CI 0.32-2.77, p = 0.007) for studies conducted using clinical populations. The available evidence is limited but tentatively suggests that reported exposure to adverse events in childhood is associated with persistence of PE and clinically relevant psychotic symptoms. This partially strengthens the case for addressing the consequences of early adversity in individuals presenting with psychotic phenomena to improve long-term outcomes. However, the heterogeneity of studies was high which urges caution in interpreting the results and highlights the need for more methodologically robust studies. | Adversity;course;meta-analysis;persistence;psychosis;psychotic symptoms | pubmed |
Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation. | Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved in the dexmedetomidine-induced contraction remains unknown. The goal of this in vitro study was to examine the specific PKC isoform that contributes to the dexmedetomidine-induced contraction in the isolated rat aorta. The endothelium-denuded rat aorta was suspended for isometric tension recording. Dexmedetomidine dose-response curves were generated in the presence or absence of the following inhibitors: the pan-PKC inhibitor, chelerythrine; the PKC-α and -β inhibitor, Go6976; the PKC-α inhibitor, safingol; the PKC-β inhibitor, ruboxistaurin; the PKC-δ inhibitor, rottlerin; the c-Jun NH2-terminal kinase (JNK) inhibitor, SP600125; and the myosin light chain kinase inhibitor, ML-7 hydrochloride. Western blot analysis was used to examine the effect of rottlerin on dexmedetomidine-induced PKC-δ expression and JNK phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) and to investigate the effect of dexmedetomidine on PKC-δ expression in VSMCs transfected with PKC-δ small interfering RNA (siRNA) or control siRNA. Chelerythrine as well as SP600125 and ML-7 hydrochloride attenuated the dexmedetomidine-induced contraction. Go6976, safingol, and ruboxistaurin had no effect on the dexmedetomidine-induced contraction, whereas rottlerin inhibited the dexmedetomidine-induced contraction. Dexmedetomidine induced PKC-δ expression, whereas rottlerin and PKC-δ siRNA transfection inhibited dexmedetomidine-induced PKC-δ expression. Dexmedetomidine also induced JNK phosphorylation, which was inhibited by rottlerin. Taken together, these results suggest that the dexmedetomidine-induced contraction involves PKC-δ-dependent JNK phosphorylation in the isolated rat aorta. | aorta;c-Jun NH2-terminal kinase;dexmedetomidine;protein kinase C;protein kinase C-δ;vasoconstriction | pubmed |
Validation of the Spanish version of the Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) in a population of Hispanic children. | The Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) is intended to measure the impact of children's asthma on their parents/caregiver's QoL. However, there are no formal validation studies of the Spanish version of PACQLQ. In a prospective cohort validation study, asthmatic children aged between 7 and 17 years and their parents, attended both a baseline and a follow-up visit 2-6 weeks later. In these two visits, we gathered the necessary data for assessing the criterion validity, construct validity, test-retest reliability, sensitivity to change, internal consistency and usability of the PACQLQ. At baseline, PACQLQ scores were significantly different between patients with controlled, partly controlled and uncontrolled asthma (median [IQR] 78.0 [61.0-85.0], 71.0 [37.0-76.0] and 48.0 [40.7-55.0], respectively, p < 0.001), and also between patients for whom this visit resulted in a step-up versus no change or a step-down in therapy (50.0 [40.0-60.0] versus 78.0 [61.0-85.0]; p < 0.001). PACQLQ scores at baseline were significantly lower than those obtained in the follow-up visit in patients with change for the better in the global rating of change questionnaire (median [IQR] 50.0 [42.5-56.0] versus 80.0 [78.5-85.0]; p < 0.001). The intraclass correlation coefficient of the measurements was 0.839 (95%CI: 0.735-0.902). The Cronbach α was 0.914 for the questionnaire as a whole. The Spanish version of the PACQLQ has adequate construct validity, adequate sensitivity to change, good internal consistency, excellent test-retest reliability and good usability when employed in children aged between 7 and 17 years with physician-diagnosed asthma. | Asthma;health-related quality of life;pediatrics;reliability;validation studies;validity | pubmed |
Etiology of distinct membrane excitability in pre- and posthearing auditory neurons relies on activity of Cl- channel TMEM16A. | The developmental rehearsal for the debut of hearing is marked by massive changes in the membrane properties of hair cells (HCs) and spiral ganglion neurons (SGNs). Whereas the underlying mechanisms for the developing HC transition to mature stage are understood in detail, the maturation of SGNs from hyperexcitable prehearing to quiescent posthearing neurons with broad dynamic range is unknown. Here, we demonstrated using pharmacological approaches, caged-Ca(2+) photolysis, and gramicidin patch recordings that the prehearing SGN uses Ca(2+)-activated Cl(-) conductance to depolarize the resting membrane potential and to prime the neurons in a hyperexcitable state. Immunostaining of the cochlea preparation revealed the identity and expression of the Ca(2+)-activated Cl(-) channel transmembrane member 16A (TMEM16A) in SGNs. Moreover, null deletion of TMEM16A reduced the Ca(2+)-activated Cl(-) currents and action potential firing in SGNs. To determine whether Cl(-) ions and TMEM16A are involved in the transition between pre- and posthearing features of SGNs we measured the intracellular Cl(-) concentration [Cl(-)]i in SGNs. Surprisingly, [Cl(-)]i in SGNs from prehearing mice was ∼90 mM, which was significantly higher than posthearing neurons, ∼20 mM, demonstrating discernible altered roles of Cl(-) channels in the developing neuron. The switch in [Cl(-)]i stems from delayed expression of the development of intracellular Cl(-) regulating mechanisms. Because the Cl(-) channel is the only active ion-selective conductance with a reversal potential that lies within the dynamic range of SGN action potentials, developmental alteration of [Cl(-)]i, and hence the equilibrium potential for Cl(-) (ECl), transforms pre- to posthearing phenotype. | action potentials;calcium-activated chloride channels;development;hearing;spiral ganglion neurons | pubmed |
Is the "Heart Age" Concept Helpful or Harmful Compared to Absolute Cardiovascular Disease Risk? An Experimental Study. | Cardiovascular disease (CVD) prevention guidelines are generally based on the absolute risk of a CVD event, but there is increasing interest in using 'heart age' to motivate lifestyle change when absolute risk is low. Previous studies have not compared heart age to 5-year absolute risk, or investigated the impact of younger heart age, graphical format, and numeracy. Compare heart age versus 5-year absolute risk on psychological and behavioral outcomes. 2 (heart age, absolute risk) × 3 (text only, bar graph, line graph) experiment. Online. 570 Australians aged 45-64 years, not taking CVD-related medication. CVD risk assessment. Intention to change lifestyle, recall, risk perception, emotional response, perceived credibility, and lifestyle behaviors after 2 weeks. Most participants had lifestyle risk factors (95%) but low 5-year absolute risk (94%). Heart age did not improve lifestyle intentions and behaviors compared to absolute risk, was more often interpreted as a higher-risk category by low-risk participants (47% vs 23%), and decreased perceived credibility and positive emotional response. Overall, correct recall dropped from 65% to 24% after 2 weeks, with heart age recalled better than absolute risk at 2 weeks (32% vs 16%). These results were found across younger and older heart age results, graphical format, and numeracy. Communicating CVD risk in a consultation rather than online may produce different results. There is no evidence that heart age motivates lifestyle change more than 5-year absolute risk in individuals with low CVD risk. Five-year absolute risk may be a better way to explain CVD risk, because it is more credible, does not inflate risk perception, and is consistent with clinical guidelines that base lifestyle and medication recommendations on absolute risk. | behaviour change;cardiovascular disease;lifestyle change;prevention;risk assessment;risk communication;risk perception | pubmed |
Stage IB2 adenosquamous cervical cancer diagnosed at 19-weeks' gestation. | Neoadjuvant chemotherapy (NACT) for advanced cervical cancer in pregnancy has been shown to increase operability and be effective against spread of disease. In all reported cases of advanced disease, residual tumour has been found at surgery following NACT. We present a case of a 27-year old diagnosed with stage IB2 adenosquamous cervical carcinoma at 19-weeks' gestation who was treated with NACT. Following caesarean section and radical hysterectomy, histopathology showed no evidence of residual tumour in the cervix and negative pelvic lymph nodes. | cervical cancer;neoadjuvant chemotherapy;pregnancy | pubmed |
Flaxseed flour (Linum usitatissinum) consumption improves bone quality and decreases the adipocyte area of lactating rats in the post-weaning period. | The aim of this work was to evaluate the effects of flaxseed flour in the intake on adiposity and femur structure of the lactating rats during the post-weaning period. After weaning, the lactating rats were divided into control (C, n = 6) and experimental (F, n = 6) groups treated with a diet containing flaxseed flour. Serum hormone and fatty acids composition, morphology of intra-abdominal adipocytes, computed tomography and biomechanical analyses of femur were determined. Food intake, body mass and hormone analysis have shown similar results. The F group showed the following (p < 0.05): lower arachidonic acid (-60%), total polyunsaturated fatty acids (-30%) and retroperitoneal adipocytes (-36%) area. Higher radiodensity of femoral head region (+29%) and higher maximum force (+18%), breaking strength (+18%) and rigidity (+31%). Fatty acid composition of flaxseed flour decreased the area of adipocytes and improved the bone quality, which may be associated with lower serum levels of arachidonic acid levels, during the post-weaning period. | Biomechanical;chromatography;diet;femur;polyunsaturated fatty acids | pubmed |
Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes. | A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation. | alkoxylation;alkylation;copper catalysis;difunctionalization;radicals | pubmed |
Effects of hearing and vision impairments on the Montreal Cognitive Assessment. | Many standardized measures of cognition include items that must be seen or heard. Nevertheless, it is not uncommon to overlook the possible effects of sensory impairment(s) on test scores. In the current study, we investigated whether sensory impairments could affect performance on a widely used screening tool, the Montreal Cognitive Assessment (MoCA). Three hundred and one older adults (mean age = 71 years) completed the MoCA and also hearing and vision tests. Half of the participants had normal hearing and vision, 38% impaired hearing, 5% impaired vision, and 7% had dual-sensory impairment. More participants with normal sensory acuity passed the MoCA compared to those with sensory loss, even after modifying scores to adjust for sensory factors. The results suggest that cognitive abilities may be underestimated if sensory problems are not considered and that people with sensory loss are at greater risk of cognitive decline. | Montreal Cognitive Assessment;cognitive screening;dual-sensory loss;hearing loss;vision loss | pubmed |
Effects of aging on strategic-based visuomotor learning. | There are different kinds of visuomotor learnings. One of the most studied is error-based learning where the information about the sign and magnitude of the error is used to update the motor commands. However, there are other instances where subjects show visuomotor learning even if the use of error sign and magnitude information is precluded. In those instances subjects could be using strategic instead of procedural adaptation mechanisms. Here, we present the results of the effect of aging on visuomotor strategic learning under a reversed error feedback condition, and its contrast with procedural visuomotor learning within the same participants. A number of measures were obtained from a task consisting of throwing clay balls to a target before, during and after wearing lateral displacing or reversing prisms. The displacing prism results show an age dependent decrease on the learning rate that corroborates previous findings. The reversing prism results also show significant adaptation impairment in the aged population. However, decreased reversing learning in the older group was the result of an increase in the number of subjects that could not adapt to the reversing prism, and not on a reduction of the learning capacity of all the individuals of the group. These results suggest a significant deleterious effect of aging on visuomotor strategic learning implementation. | Aging;Prism adaptation;Procedural learning;Strategic-based learning;Visual reversing;Visuomotor learning | pubmed |
F-18 fluorodeoxyglucose positron emission tomography for differential diagnosis of pancreatic tumors. | Positron emission tomography with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG-PET) has been proven useful for differentiating pancreatic ductal cancer from mass-forming chronic pancreatitis. However, there are particular pancreatic tumors having various grades of malignancy such as intraductal papillary mucinous neoplasm (IPMN) or pancreatic neuroendocrine tumor. We examined whether the cut-off value of maximum standardized uptake value (SUVmax) determined by pancreatic ductal cancers is also applicable for other pancreatic tumors. One hundred thirty six patients with pancreatic tumors underwent FDG-PET imaging. We first analyzed the cut-off value to differentiate pancreatic ductal cancers from mass-forming chronic pancreatitis. Secondly, we determined the cut-off value between malignant IPMN and benign IPMN. Thirdly, we computed a cut-off value between malignant pancreatic tumors and benign tumors irrespective of tumor type. The optimal cut-off value to differentiate ductal cancers from mass-forming chronic pancreatitis was 2.5. The optimal cut-off value for differentiating malignant IPMN from benign IPMN was also 2.5, similar to that of reported studies. In all types of pancreatic tumors, the cut-off value was also 2.5. The accuracy for detecting malignancy was 93.4% for all tumors. In the FDG-PET study for pancreatic tumors, an SUVmax of 2.5 would be justified as a cut-off value to differentiate malignant lesions. | Cut-off;FDG-PET;IPMN;Non-ductal pancreatic cancer;SUV | pubmed |
Breakdowns of eye movement control toward smoking cues in young adult light smokers. | Many studies suggest that dependent smokers have a preference or attentional bias toward smoking cues. The purpose of this study was to test the ability of infrequent non-dependent light smokers to control their eye movements by look away from smoking cues. Poor control in the lightest of smokers would suggest nicotine cue-elicited behavior occurring even prior to nicotine dependency as measured by daily smoking. 17 infrequent non-dependent light smokers and 17 lifetime non-smokers performed an antisaccade task (look away from suddenly appearing cue) on smoking, alcohol, neutral, and dot cues. The light smokers, who were confirmed light smokers and non-dependent (MFaegerström Dependency Score=0.35), were significantly worse at controlling their eye movements to smoking cues relative to both neutral cues (p<.04) and alcohol cues (p<.02). Light smokers made significantly more errors to smoking cues than non-smokers (p<.004). These data suggest that prior to developing clinical symptoms of severe dependence or progressing to heavier smoking (e.g., daily smoking), the lightest of smokers are showing a specific deficit in control of nicotine cue-elicited behavior. | Antisaccade;Control;Light smokers;Nicotine;Smoking;Young adults | pubmed |
The relationship between deferred imitation, associative memory, and communication in 14-months-old children. Behavioral and electrophysiological indices. | The present study combines behavioral observations of memory (deferred imitation, DI, after a brief delay of 30 min and after a long delay of 2-3 weeks) and electrophysiological (event-related potentials, ERPs) measures of associative memory, as well as parental reports of non-verbal and verbal communication in sixteen 14-months-old children. Results show that for DI, the children remembered the stimulus after the brief but not after the long delay. There was a clear electrophysiological response indicating associative memory. Furthermore, a correlation between DI and ERP suggests that both measures of memory (DI and associative memory) tap into similar mechanisms in 14-months-old children. There was also a statistically significant relation between parental report of receptive (verbal) language and the ERP, showing an association between receptive language skills and associative memory. | associative memory;communication;deferred imitation;event-related potentials;infant;memory | pubmed |
Cardiac Troponin and its Relationship to Cardiovascular Outcomes in Community Populations - A Systematic Review and Meta-analysis. | The clinical relevance of minor elevations of cardiac troponin (cTn) in the general population remains uncertain. The objective of this systematic review was to examine the literature and evaluate the prevalence of raised cTn in asymptomatic, community populations and explore the strength of the relationship between cTn and cardiovascular mortality amongst those studied. Studies were identified by searching Medline, Embase, CINAHL, EBM Reviews, Cochrane Library and using the "related citation" search tool in PubMed from inception through August 2014. Prospective cohort studies of asymptomatic individuals recruited from the community (age ≥ 18 years) that assessed the relationship between cTn levels and mortality or cardiovascular events were included. Twenty-one prospective studies involving 64,855 participants were identified. An elevated cTn measurement (>99th percentile) occurred in 5% of individuals and was associated with a tripling of risk of mortality (adjusted RR 3.07, 95% confidence interval [CI] 2.32-4.06) and cardiovascular mortality (adjusted RR 3.30, 95% CI 1.77-6.12). In studies including high sensitivity assays, cTn was detectable in 58% of individuals. A detectable cardiac troponin T (cTnT) was also associated with an increased risk of cardiovascular mortality (adjusted RR 1.32, 95% CI 1.10 - 1.59). The risk increased with increasing cTnT level. Elevated troponin in asymptomatic individuals in the community is associated with a tripling of risk of all-cause and cardiovascular mortality. Cardiac troponin T (cTnT) is generally not measured in this group of patients, but may potentially have utility in predicting risk in this population. Further research is required to assess if this risk is modifiable with usual primary prevention treatments. | Cardiovascular diseases;Epidemiology;Meta-analysis;Systematic Review;Troponin | pubmed |
Children's Lung Health Improves With Reduced Air Pollution. | Air pollution;Asthma;Children | pubmed |
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Lack of timely follow-up of abnormal imaging results and radiologists' recommendations. | Abnormal imaging results may not always lead to timely follow-up. We tested whether certain aspects of communication in radiology reports influence the response of the referring providers, and hence follow-up on abnormal findings. We focused on 2 communication-related items that we hypothesized could affect follow-up: expressions of doubt in the radiology report, and recommendations for further imaging. After institutional review board approval, we conducted a retrospective review of 250 outpatient radiology reports from a multispecialty ambulatory clinic of a tertiary-care Veterans Affairs facility. The selected studies included 92 cases confirmed to lack timely follow-up (ie, further tests or consultations, treatment, and/or communication to the patient within 4 weeks), as determined in a previous study. An additional 158 cases with documented timely follow-up served as controls. Doubt in the narrative was measured by the presence of key phrases (eg, "unable to exclude," "cannot exclude," "cannot rule out," "possibly," and "unlikely"), in the absence of which we used reviewer interpretation. A physician blinded to follow-up outcomes collected the data. Patients whose reports contained recommendations for further imaging were more likely to have been lost to follow-up at 4 weeks compared with patients without such recommendations (P = .01). Language in the report suggestive of doubt did not affect the timeliness of follow-up (P = .59). Abnormal imaging results with recommendations for additional imaging may be more vulnerable to lack of timely follow-up. Additional safeguards, such as tracking systems, should be developed to prevent failure to follow up on such results. | Follow-up;abnormal tests;diagnostic error;doubt;radiology reporting | pubmed |
Does training with traditionally presented and virtually simulated tasks elicit differing changes in object interaction kinematics in persons with upper extremity hemiparesis? | To contrast changes in clinical and kinematic measures of upper extremity movement in response to virtually simulated and traditionally presented rehabilitation interventions in persons with upper extremity hemiparesis due to chronic stroke. Non-randomized controlled trial. Ambulatory research facility. Subjects were a volunteer sample of twenty one community-dwelling adults (mean age: 51 ± 12 years) with residual hemiparesis due to stroke more than 6 months before enrollment (mean: 74 ± 48 months), recruited at support groups. Partial range, against gravity shoulder movement and at least 10° of active finger extension were required for inclusion. All subjects completed the study without adverse events. A 2 weeks, 24-hour program of robotic/virtually simulated, arm and finger rehabilitation activities was compared to the same dose of traditionally presented arm and finger activities. Subjects in both groups demonstrated statistically significant improvements in the ability to interact with real-world objects as measured by the Wolf Motor Function Test (P = 0.01). The robotic/virtually simulated activity (VR) group but not the traditional, repetitive task practice (RTP) group demonstrated significant improvements in peak reaching velocity (P = 0.03) and finger extension excursion (P = 0.03). Both groups also demonstrated similar improvements in kinematic measures of reaching and grasping performance such as increased shoulder and elbow excursion along with decreased trunk excursion. Kinematic measurements identified differing adaptations to training that clinical measurements did not. These adaptations were targeted in the design of four of the six simulations performed by the simulated activity group. Finer grained measures may be necessary to accurately depict the relative benefits of dose matched motor interventions. | Kinematic measurements;Robotics,;Stroke,;Virtual reality, | pubmed |
Rehabilitation of hypomimia in Parkinson's disease: a feasibility study of two different approaches. | Parkinson's disease (PD) patients frequently have an impairment of facial expression both in voluntary and spontaneous emotional expression. Aim of this study was to evaluate the feasibility of a rehabilitation program for hypomimia in patients with PD, comparing two different approaches. Thirty-six patients with PD were included: 20 patients received a rehabilitative intervention for hypomimia either with a DVD showing exercises focused on facial muscles (PD-group-A) or with a therapist-guided facial rehabilitation with a proprioceptive/recognition approach (PD-group-B). Sixteen patients (PD-Ctrl group) did not receive any treatment and served as control group. The feasibility of the proposed rehabilitation techniques was the main focus of this evaluation. We also evaluate the efficacy of the treatments by means of the sub-item 19 of the Unified Parkinson's disease Rating Scale motor score (UPDRS-III) and by a computerized analysis of facial expression (E-Motion), which was assessed prior to (T0) and after therapy (T1). The proposed rehabilitative program for the treatment of hypomimia was shown to be feasible. Our data show a significant improvement in UPDRS-III sub-item 19 in PD-group-B compared to PD-group-A, (p = 0.005) and to PD-Ctrl (p = 0.003) and in expressivity of fear in PD-group-B compared to PD-Ctrl (p = 0.01). The proposed rehabilitative program showed to be feasible. A larger multi-center trial is now warranted to establish its efficacy to improve facial expression over long time period. | Facial expression;Geriatrics;Hypomimia;Parkinson’s disease;Randomized controlled trial;Rehabilitation | pubmed |
Hydrogenated TiO2 nanobelts as highly efficient photocatalytic organic dye degradation and hydrogen evolution photocatalyst. | TiO2 nanobelts have gained increasing interest because of its outstanding properties and promising applications in a wide range of fields. Here we report the facile synthesis of hydrogenated TiO2 (H-TiO2) nanobelts, which exhibit excellent UV and visible photocatalytic decomposing of methyl orange (MO) and water splitting for hydrogen production. The improved photocatalytic property can be attributed to the Ti(3+) ions and oxygen vacancies in TiO2 nanobelts created by hydrogenation. Ti(3+) ions and oxygen vacancies can enhance visible light absorption, promote charge carrier trapping, and hinder the photogenerated electron-hole recombination. This work offers a simple strategy for the fabrication of a wide solar spectrum of active photocatalysts, which possesses significant potential for more efficient photodegradation, photocatalytic water splitting, and enhanced solar cells using sunlight as light source. | Hydrogen production;Hydrogenation;Photocatalytic;TiO(2) nanobelts;UV–visible | pubmed |
Diet, Microbiota and Immune System in Type 1 Diabetes Development and Evolution. | Type 1 diabetes (T1D) is the second most frequent autoimmune disease in childhood. The long-term micro- and macro-vascular complications of diabetes are associated with the leading causes of disability and even mortality in young adults. Understanding the T1D etiology will allow the design of preventive strategies to avoid or delay the T1D onset and to help to maintain control after developing. T1D development involves genetic and environmental factors, such as birth delivery mode, use of antibiotics, and diet. Gut microbiota could be the link between environmental factors, the development of autoimmunity, and T1D. In this review, we will focus on the dietary factor and its relationship with the gut microbiota in the complex process involved in autoimmunity and T1D. The molecular mechanisms involved will also be addressed, and finally, evidence-based strategies for potential primary and secondary prevention of T1D will be discussed. | Bacteroides;Type 1 diabetes;autoimmunity;diet;dysbiosis;gut microbiota | pubmed |
Findings from a community-based asthma education fair for Latino caregivers. | To assess limited English proficiency (LEP) asthma caregiver quality of life (QoL), skills retention and healthcare utilization after an asthma education fair (AEF). A language concordant AEF was conducted at a Latino community center. LEP caregivers of children 1-12 years old and an established asthma diagnosis participated in three skill stations: (a) medication recognition and administration, (b) peak flow use (if child ≥ 5 years) and (c) action plan dissemination. Spacers, peak flow meters and individualized action plans were distributed. A validated, pediatric asthma caregiver quality of life questionnaire (PACQLQ-Spanish version) was administered. Baseline data was compared to follow-up interview data at three and six months after the AEF. Mean PACQLQ scores were analyzed with Wilcoxon signed-rank test and nominal paired data with McNemar's test. We analyzed data from 18 caregivers able to speak English well (22%), not well (28%) or not at all (50%). After three months, improved caregiver QoL was experienced (51 vs. 72, p<0.01). No differences were observed in medication recognition, spacer and peak flow use or peak flow interpretation. After six months, mean school days missed due to asthma decreased (4.1 vs. 0.4, p<0.01). Mean clinic visits, emergency department visits and hospitalizations remained unchanged. Implementation of a community-based AEF with action plan administration can be beneficial for LEP caregivers and their children. QoL improvements to emotional wellbeing and activity limitations were observed, and lower rates of school absenteeism were reported. Caregiver ability to accurately identify medications was not enhanced. | Asthma;Latino health;community-based participator research;pediatrics;quality of life | pubmed |
Biological characteristics of tracheal smooth muscle cells regulated by NK-1R in asthmatic rat with airway remodeling. | This study aims to investigate the biological characteristic changes of infant rat tracheal smooth muscle cells in asthma airway remodeling and the impact of NK-1R on the mechanism. Ovalbumin (OVA) was used to excited juvenile SD rats by 8 w. Immunofluorescence, MTT assay, transwell chambers, real time quantitative PCR, Western blot and other methods were used to observe the proliferation, migration, synthesis and secretion changes of infant airway remodeling in rat tracheal smooth muscle cell and the Neurokinin 1 receptor (NK-1R) expression. 1. NK-1R mRNA, protein expression of airway smooth muscle cell (ASMC) of each asthma group were higher than that of the control group, especially the asthma 8 w group had highest expression (P<0.01). 2. The average A value of 8 w asthma group measured by MTT method were significantly higher than that of the control group (P<0.05), WIN62577 10(-8) mol/L group had the strongest inhibition of ASMC proliferation (P<0.01). 3. The number of cell migration in the asthma group significantly increased than that in the control group. The number of migrating cells in the NK-1R antagonist group significantly reduced compared with the asthma 8 w group (P<0.05). 4. The average gray value of type III collagen in each asthma group were higher than that of the control group, and the asthma 8 w group had the highest (P<0.01). After NK-1R blocking, the average gray value of type III collagen was significantly lower (P<0.05). ASMC proliferation, migration, synthesis and secretion function increased in the airway remodeling group, and NK-1R played an important role. | Airway remodeling;NK-1R;migration;proliferation;smooth muscle cells | pubmed |
Some Like it High! Phylogenetic Diversity of High-Elevation Cyanobacterial Community from Biological Soil Crusts of Western Himalaya. | The environment of high-altitudinal cold deserts of Western Himalaya is characterized by extensive development of biological soil crusts, with cyanobacteria as dominant component. The knowledge of their taxonomic composition and dependency on soil chemistry and elevation is still fragmentary. We studied the abundance and the phylogenetic diversity of the culturable cyanobacteria and eukaryotic microalgae in soil crusts along altitudinal gradients (4600-5900 m) at two sites in the dry mountains of Ladakh (SW Tibetan Plateau and Eastern Karakoram), using both microscopic and molecular approaches. The effects of environmental factors (altitude, mountain range, and soil physico-chemical parameters) on the composition and biovolume of phototrophs were tested by multivariate redundancy analysis and variance partitioning. Both phylogenetic diversity and composition of morphotypes were similar between Karakorum and Tibetan Plateau. Phylogenetic analysis of 16S rRNA gene revealed strains belonging to at least five genera. Besides clusters of common soil genera, e.g., Microcoleus, Nodosilinea, or Nostoc, two distinct clades of simple trichal taxa were newly discovered. The most abundant cyanobacterial orders were Oscillatoriales and Nostacales, whose biovolume increased with increasing elevation, while that of Chroococales decreased. Cyanobacterial species richness was low in that only 15 morphotypes were detected. The environmental factors accounted for 52 % of the total variability in microbial data, 38.7 % of which was explained solely by soil chemical properties, 14.5 % by altitude, and 8.4 % by mountain range. The elevation, soil phosphate, and magnesium were the most important predictors of soil phototrophic communities in both mountain ranges despite their different bedrocks and origin. The present investigation represents a first record on phylogenetic diversity of the cyanobacterial community of biological soil crusts from Western Himalayas and first record from altitudes over 5000 m. | Cyanobacterial diversity;Desert;High-elevation;Phosphorus;Soil crusts;Western Himalayas | pubmed |
Is the noun ending a cue to grammatical gender processing? An ERP study on sentences in Italian. | Gender-to-ending consistency has been shown to influence grammatical gender retrieval in isolated word presentation. Notwithstanding the wealth of evidence, the exact role and the time course of processing of this distributional information remain unclear. This ERP study investigated if and when the brain detects gender-to-ending consistency in sentences containing Italian determiner-noun pairs. Determiners either agreed or disagreed in gender with the nouns whose endings were reliable or misleading cues to gender (transparent and irregular nouns). Transparent nouns elicited an increased frontal negativity and a late posterior positivity compared to irregular nouns (350-950 ms), suggesting that the system is sensitive to gender-to-ending consistency from relatively early stages of processing. Gender agreement violations evoked a similar LAN-P600 pattern for both types of nouns. The present findings provide evidence for an early detection of reliable gender-related endings during sentence reading. | Agreement;ERPs;Gender-to-ending consistency;Grammatical gender;Language processing | pubmed |
Optimal performance of networked control systems with bandwidth and coding constraints. | The optimal tracking performance of multiple-input multiple-output (MIMO) discrete-time networked control systems with bandwidth and coding constraints is studied in this paper. The optimal tracking performance of networked control system is obtained by using spectral factorization technique and partial fraction. The obtained results demonstrate that the optimal performance is influenced by the directions and locations of the nonminimum phase zeros and unstable poles of the given plant. In addition to that, the characters of the reference signal, encoding, the bandwidth and additive white Gaussian noise (AWGN) of the communication channel are also closely influenced by the optimal tracking performance. Some typical examples are given to illustrate the theoretical results. | Bandwidth;Coding constraints;Networked control systems;Optimal tracking performance | pubmed |
Beyond the vascular endothelial growth factor axis: update on role of imaging in nonantiangiogenic molecular targeted therapies in oncology. | This article provides a comprehensive review of molecular targeted therapies that do not act directly through vascular endothelial growth factor pathways, highlighting the role of imaging in assessment of treatment response and drug toxicities. A substantial number of molecular targeted therapies act on nonantiangiogenic pathways. Familiarity with these drugs, their personalized tumor response criteria, and class- and drug-specific toxicities will help radiologists to be an integral part of the multi-disciplinary oncology team. | alternate tumor response criteria;anaplastic lymphoma kinase inhibitors;epidermal growth factor receptor inhibitors;immune modulators;mammalian target of rapamycin inhibitors;molecular targeted therapies | pubmed |
Speckle noise reduction in ultrasound images using a discrete wavelet transform-based image fusion technique. | Here, the speckle noise in ultrasonic images is removed using an image fusion-based denoising method. To optimize the denoising performance, each discrete wavelet transform (DWT) and filtering technique was analyzed and compared. In addition, the performances were compared in order to derive the optimal input conditions. To evaluate the speckle noise removal performance, an image fusion algorithm was applied to the ultrasound images, and comparatively analyzed with the original image without the algorithm. As a result, applying DWT and filtering techniques caused information loss and noise characteristics, and did not represent the most significant noise reduction performance. Conversely, an image fusion method applying SRAD-original conditions preserved the key information in the original image, and the speckle noise was removed. Based on such characteristics, the input conditions of SRAD-original had the best denoising performance with the ultrasound images. From this study, the best denoising technique proposed based on the results was confirmed to have a high potential for clinical application. | SRAD;Ultrasound imaging;discrete wavelet transform;image fusion;speckle noise | pubmed |
New reassortant H5N8 highly pathogenic avian influenza virus from waterfowl in Southern China. | New reassortant H5N8 highly pathogenic avian influenza viruses were isolated from waterfowl in Southern China. Blast analysis demonstrated that the PB2 gene in these viruses were most closely related to A/wild duck/Shangdong/628/2011 (H5N1), while their NP genes were both more closely related to A/wild duck/Shandong/1/2011 (H5N1) and A/duck/Jiangsu/k1203/2010 (H5N8). However, the HA, NA, PB1, PA, M, and NS genes had the highest identity with A/duck/Jiangsu/k1203/2010 (H5N8). Phylogenetic analysis revealed that their HA genes belonged to the same GsGd H5 clade 2.3.4.4 detected in China in 2010. Therefore, we supposed that these H5N8 viruses might be novel reassortant viruses that have a H5N8 backbone while acquiring PB2 and NP genes from H5N1 viruses. This study is useful for better understanding the genetic and antigenic evolution of H5 avian influenza viruses in Southern China. | H5N8;Southern China;highly pathogenic avian influenza virus;reassortant;waterfowl | pubmed |
RstA is required for the virulence of an avian pathogenic Escherichia coli O2 strain E058. | Certain strains of avian pathogenic Escherichia coli (APEC) cause severe extraintestinal infections in poultry, including acute fatal septicemia, subacute pericarditis, and airsacculitis. These bacteria contain an RstA/RstB regulatory system, a two-component system that may help APEC strains adapt to the extra-intestinal environment and survive under stressful conditions. Whether RstA correlates with APEC pathogenesis or acts as an APEC virulence factor has not been established. Here we provide the first evidence for an important role of rstA in APEC virulence. We generated an rstA-deficient mutant from the highly virulent APEC strain E058. Virulence of the mutant strain was evaluated in vivo and in vitro through bird infection assays, a cytotoxicity assay on chicken macrophage cell line HD-11, and a bactericidal assay to serum complement. Based on lethality assays in 1-day-old birds, rstA deletion from APEC E058 reduced the bacterial virulence in birds. The deletion also deeply impaired the capacity of APEC E058 to colonize deeper tissues of 5-week-old specific pathogen free chickens. No obvious gross or histopathological lesions were observed in the visceral organs of chickens challenged with the rstA-deficient strain. Also, rstA inactivation reduced the survival of APEC E058 within chicken macrophages. However, no significant differences were observed between the mutant and the wild-type strain in resistance to serum. Our data collectively show that the rstA gene functions in the pathogenesis of diseases caused by avian pathogenic E. coli. | Avian pathogenic Escherichia coli;Mutant;RstA;Virulence | pubmed |
The critical molecular interconnections in regulating apoptosis and autophagy. | Apoptosis and autophagy are both highly regulated biological processes that have important roles in development, differentiation, homeostasis, and disease. These processes may take place independently, with autophagy being cytoprotective for preventing cells from apoptosis and apoptosis blocking autophagy. But in most circumstances, both may be induced sequentially with autophagy preceding apoptosis. The simultaneous activation of both processes has been observed not only in experimental settings but also in pathophysiological conditions. In fact, these two pathways are tightly connected with each other by substantial interplays between them, enabling the coordinated regulation of cell fates by these two pathways. They share some common upstream signaling components, and some components of one pathway may play important roles in the other, and vice versa. Such proteins represent the critical interconnections of the two pathways, which seem to determine the cell for survival or death. Here several critical molecular interconnections between apoptosis and autophagy pathways are reviewed, with their action mechanisms being highlighted. | Apoptosis;Bcl-2;Beclin 1;PI3K/Akt/mTOR signaling;autophagy;caspases;cell death;cross-talk;p53 | pubmed |
In vitro dermal penetration of nickel nanoparticles. | Nickel nanoparticles (NiNPs) represent a new type of occupational exposure because, due to the small size/high surface, they can release more Ni ions compared to bulk material. It has been reported a case of a worker who developed sensitization while handling nickel nanopowder without precautions. Therefore there is the need to assess whether the skin absorption of NiNPs is higher compared to bulk nickel. Two independent in vitro experiments were performed using Franz diffusion cells. Eight cells for each experiment were fitted using intact and needle-abraded human skin. The donor phase was a suspension of NiNPs with mean size of 77.7 ± 24.1 nm in synthetic sweat. Ni permeated both types of skin, reaching higher levels up to two orders of magnitude in the damaged skin compared to intact skin (5.2 ± 2.0 vs 0.032 ± 0.010 μg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 ± 11.2 μg cm(-2) in damaged skin and 9.67 ± 2.70 μg cm(-2) in intact skin (mean and SD, p = 0.006). Skin abrasions lead to doubling the Ni amount in the epidermis and to an increase of ten times in the dermis. This study demonstrated that NiNPs applied on skin surface cause an increase of nickel content into the skin and a significant permeation flux through the skin, higher when a damaged skin protocol was used. Preventive measures are needed when NiNPs are produced and used due to their higher potential to enter in our body compared to bulk nickel. | Damaged skin;In vitro;Nanoparticles;Nickel;Skin penetration | pubmed |
Enzymatic activities and arbuscular mycorrhizal colonization of Plantago lanceolata and Plantago major in a soil root zone under heavy metal stress. | The objectives of the present field study were to examine the soil enzyme activities in the soil root zones of Plantago lanceolata and Plantago major in different heavy metal contaminated stands. Moreover, the investigations concerned the intensity of root endophytic colonization and metal bioaccumulation in roots and shoots. The investigated Plantago species exhibited an excluder strategy, accumulating higher metal content in the roots than in the shoots. The heavy metal accumulation levels found in the two plantain species in this study were comparable to other plants suggested as phytostabilizers; therefore, the selected Plantago species may be applied in the phytostabilization of heavy metal contaminated areas. The lower level of soil enzymes (dehydrogenase, urease, acid, and alkaline phosphatase) as well as the higher bioavailability of metals in the root zone soil of the two plantain species were found in an area affected by smelting activity, where organic matter content in the soil was also the smallest. Mycorrhizal colonization on both species in the contaminated area was similar to colonization in non-contaminated stands. However, the lowest arbuscule occurrence and an absence of dark septate endophytes were found in the area affected by the smelting activity. It corresponded with the lowest plant cover observed in this stand. The assessment of enzyme activity, mycorrhizal colonization, and the chemical and physical properties of soils proved to be sensitive to differences between sites and between Plantago species. | Heavy metals;Mycorrhiza;Plantago;Soil enzymes | pubmed |
Outcomes Among Children Who Received a Kidney Transplant in the United States From a Hepatitis B Core Antibody-Positive Donor, 1995-2010. | Accepting kidneys for transplant from donors with a history of hepatitis B virus infection may increase the availability of organs for those with end-stage kidney disease. In adult recipients, kidney transplants from hepatitis B virus core antibody-positive donors have resulted in favorable graft and patient survival rates. However, pediatric organ transplant recipients have developing immune systems and a higher risk of infectious complications than adults. Accordingly, little is known about the outcomes of children who have received a kidney transplant from a hepatitis B virus core antibody-positive donor. We included 11 898 children ≤18 years of age who received a first kidney transplant in the United States between January 1, 1995, and December 31, 2010, and who were recorded in the Scientific Registry of Transplant Recipients. We examined differences in graft and patient survival rates among children who received a kidney transplant from a hepatitis B virus core antibody-positive donor. There were 199 children (1.7%) who received a kidney transplant from a hepatitis B virus core antibody-positive donor. More than 80% of these transplants occurred in recipients who were hepatitis B virus core antibody and surface antigen negative. After a median follow-up of 7.9 years, there were no significant differences in the adjusted graft (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.80-1.31]) or patient (HR, 1.12 [95% CI, 0.73-1.73]) survival rates according to donor core antibody status. It may be acceptable, on a case-by-case basis, to consider hepatitis B virus core antibody-positive donors for kidney transplants to seroprotected children with end-stage kidney disease. | children;hepatitis B;kidney transplant | pubmed |
Laryngoscopic and spectral analysis of laryngeal and pharyngeal configuration in non-classical singing styles. | The present study aimed to assess three different singing styles (pop, rock, and jazz) with laryngoscopic, acoustic, and perceptual analysis in healthy singers at different loudness levels. Special emphasis was given to the degree of anterior-posterior (A-P) laryngeal compression, medial laryngeal compression, vertical laryngeal position (VLP), and pharyngeal compression. Prospective study. Twelve female trained singers with at least 5 years of voice training and absence of any voice pathology were included. Flexible and rigid laryngeal endoscopic examinations were performed. Voice recording was also carried out. Four blinded judges were asked to assess laryngoscopic and auditory perceptual variables using a visual analog scale. All laryngoscopic parameters showed significant differences for all singing styles. Rock showed the greatest degree for all of them. Overall A-P laryngeal compression scores demonstrated significantly higher values than overall medial compression and VLP. High loudness level produced the highest degree of A-P compression, medial compression, pharyngeal compression, and the lowest VLP for all singing styles. Additionally, rock demonstrated the highest values for alpha ratio (less steep spectral slope), L1-L0 ratio (more glottal adduction), and Leq (more vocal intensity). Statistically significant differences between the three loudness levels were also found for these acoustic parameters. Rock singing seems to be the style with the highest degree of both laryngeal and pharyngeal activity in healthy singers. Although, supraglottic activity during singing could be labeled as hyperfunctional vocal behavior, it may not necessarily be harmful, but a strategy to avoid vocal fold damage. | Laryngeal hyperfunction;Laryngoscopy;Nonclassical singers;Singing voice;Supraglottic activity | pubmed |
Classic thrombophilic gene variants. | Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagulable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review. | ABO blood group;Inherited thrombophilia;factor V Leiden;natural anticoagulants;prothrombin mutation | pubmed |
EA versus sham acupuncture and no acupuncture for the control of acute and delayed chemotherapy-induced nausea and vomiting: a pilot study. | To assess the feasibility of undertaking a high-quality randomised controlled study to determine whether EA gives better control of delayed chemotherapy-induced nausea and vomiting (CINV) than sham EA or standard antiemetic treatment alone. Patients having their first cycle of moderately or highly emetogenic chemotherapy were randomised to EA, sham EA or standard care. EA was given for 30 min on day 1 at the time of chemotherapy and on day 3 using standard acupuncture points bilaterally. Sham EA was given to points adjacent to true EA points. All patients received usual care, comprising antiemetics, according to hospital guidelines. The primary outcomes related to study feasibility, and the clinical outcome measure was the change in Functional Living Index Emesis (FLIE) score captured on days 1 and 7. 153 participants were screened between April 2009 and May 2011. Eighteen patients did not meet the inclusion criteria, 37 declined to participate and the absence of an acupuncturist or lack of consent from the treating oncologist excluded a further 38 patients; 60 patients were recruited. The FLIE was completed on day 7 by 49 participants; 33 of 40 patients returned on day 3 for treatment. The nausea and vomiting scores were low in all three arms. Adverse events were generally mild and infrequent. It was feasible to undertake a randomised EA trial on a busy day oncology unit. As few patients experienced nausea with their first cycle of chemotherapy, it was not possible to determine whether EA improves CINV over standard care. An enriched enrolment strategy is indicated for future studies. A simple numerical rating scale may prove a better objective nausea measure than the FLIE. ACTRN12609001054202. | ACUPUNCTURE;ONCOLOGY | pubmed |
Consistencies of 3D TTE global longitudinal strain of both ventricles between assessors were worse for 2D, but better for 3D ventricular EF. | We evaluated the consistency of different-assessors in estimating three-dimensional (3D) global-longitudinal-strain (GLS) of left (LV) and right ventricle (RV) using transthoracic-echocardiography (TTE) for LV and RV systolic-function. We compared results from two-independent-specialists using this-approach for 3D LV and RV parameters in a population with 74% hypertrophic-cardiomyopathy (HCM) patients. 58 patients (43 HCM (32 male; 62 ± 15 years) and 15 controls (5 male; 53 ± 22 years)) underwent TTE (Vivid-E9) to measure 2D and 3D GLS of the LV and RV by two-independent-specialists. Consistencies of estimates of 3D LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection-fraction (EF) between the two-assessors were 0.872 (3D LVEDV, P<0.001), 0.797 (3D LVESV, P<0.001), and 0.215 (3D LVEF, P=0.105). Consistencies of 2D and 3D LV GLS between two-assessors were 0.900 (2D LVGLS, P<0.001) and 0.874 (3D LVGLS, P<0.001). Consistencies of estimates of 3D RVEDV, RVESV, and RVEF between two assessors were 0.781 (3D RVEDV, P<0.001), 0.755 (3D RVESV, P<0.001), and 0.26 (3D RVEF, P=0.049). Consistencies of 2D and 3D GLS of whole RV and those of RV free wall only between two-assessors were 0.886 (2D GLS of whole RV, P<0.001), 0.687 (3D GLS of whole RV, P<0.001), 0.707 (2D GLS of RV free wall, P<0.001), and 0.630 (3D GLS of RV free wall, P<0.001). Consistencies of independent-estimates of 3D GLS of the LV and RV using TTE between two-assessors were worse than for 2D GLS of the LV and RV, but better than for 3D LVEF and RVEF in a population with 74% HCM patients. | 2D and 3D ventricular EF;3D TTE global longitudinal strain;Assessors;Both ventricles;Consistencies of independent estimates;HCM | pubmed |
Oxytocin decreases sweet taste sensitivity in mice. | Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. | Brief-access test;Gustation;Licking;Oxytocin;Sweet | pubmed |
Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O<sup>6</sup>-methylguanine-DNA methyltransferase. | The cytotoxicity of the monofunctional alkylator, temozolomide (TMZ), is known to be mediated by mismatch repair (MMR) triggered by O<sup>6</sup>-alkylguanine. By contrast, the cytotoxicity of bifunctional alkylators, including carmustine (BCNU) and melphalan (MEL), depends on interstrand crosslinks formed through O<sup>6</sup>-alkylguanine, which is repaired by nucleotide excision repair and recombination. O<sup>6</sup>-alkylguanine is removed by O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT). The aim of the present study was to evaluate the cytotoxicity of TMZ, BCNU and MEL in two different leukemic cell lines (HL-60 and MOLT-4) in the context of DNA repair. The transcript levels of MGMT, ERCC1, hMLH1 and hMSH2 were determined using reverse transcription-quantitative polymerase chain reaction. In addition, the proliferation was measured using the trypan blue exclusion assay. Drug sensitivity was found to vary between the two cell lines. Treatment of the cells with TMZ, BCNU or MEL in combination with O<sup>6</sup>-benzylguanine, an MGMT inhibitor, was demonstrated to sensitize the two cell lines to these agents. However, the extent of sensitization was not found to be correlated with the expression levels of MGMT transcripts. Furthermore, the drug sensitivity was also not associated with the transcript levels of ERCC1, hMLH1 and hMSH2. Thus, leukemic cells were sensitized to alkylating agents by the inhibition of MGMT. | DNA repair;O6-benzylguanine;carmustine;melphalan;temozolomide | pubmed |
Sustaining "meaningful use" of health information technology in low-resource practices. | The implementation of electronic health records (EHRs) has been extensively studied, but their maintenance once implemented has not. The Regional Extension Center (REC) program provides implementation assistance to priority practices-those with limited financial, technical, and organizational resources-but the assistance is time limited. Our objective was to identify potential barriers to maintenance of meaningful use of EHRs in priority primary care practices using a qualitative observational study for federally qualified health centers (FQHCs) and priority practices in Michigan. We conducted cognitive task analysis (CTA) interviews and direct observations of health information technology implementation in FQHCs. In addition, we conducted semistructured interviews with implementation specialists serving priority practices to detect emergent themes relevant to maintenance. Maintaining EHR technology will require ongoing expert technical support indefinitely beyond implementation to address upgrades and security needs. Maintaining meaningful use for quality improvement will require ongoing support for leadership and change management. Priority practices not associated with larger systems lack access to the necessary technical expertise, financial resources, and leverage with vendors to continue alone. Rural priority practices are particularly challenged, because expertise is often not available locally. Priority practices, especially in rural areas, are at high risk for falling on the wrong side of a "digital divide" as payers and regulators enact increasing expectations for EHR use and information management. For those without affiliation to maintain the necessary expert staff, ongoing support will be needed for those practices to remain viable. | American Recovery and Reinvestment Act;electronic health records;health information technology;meaningful use;primary health care;regional extension centers;rural health services;safety-net providers | pubmed |
Efficiency of selenium in attenuating epididymal histopathological changes in hypercholesterolaemic adult rat. | Studies on sperm maturation, epididymal histology, or epididymal tubule physiology are significant parts in reproductive researches. The present study was aimed to evaluate the effect of induced hypercholesterolaemia on the epididymis of adult albino rats and to clarify the possible protective role of selenium. Forty adult albino Wistar rats were divided into four groups; untreated control group (group I), sham control (group II), group with induced hypercholesterolaemia (group III), group with induced hypercholesterolaemia treated with selenium 0.25 mg/kg/day (group IV). Histological and ultrastructural examination of the epididymal epithelial cells of hypercholesterolaemic rats (group III) showed loss of cilia with many vacuolations, fatty degenerative changes and increased collagen fibres. Morphometrically significant increase (p < 0.0001) in the per cent area of collagen fibres with no significant change in the optical density of periodic acid Schiff reaction (p > 0.05). Selenium treated group (group IV) produced marked improvement in histological, ultrastructural and morphometric results as compared with group III. It could be concluded that hypercholesterolaemia produced deleterious effects to the epididymis and selenium could attenuate these effects. | epididymis;histopathology;hypercholesterolaemia;selenium | pubmed |
Using performance reference compound-corrected polyethylene passive samplers and caged bivalves to measure hydrophobic contaminants of concern in urban coastal seawaters. | Low-density polyethylene (PE) passive samplers containing performance reference compounds (PRCs) were deployed at multiple depths in two urban coastal marine locations to estimate dissolved concentrations of hydrophobic organic contaminants (HOCs), including dichlorodiphenyltrichloroethane (DDT) and its metabolites, polychlorinated biphenyl (PCB) congeners, and polybrominated flame retardants. PE samplers pre-loaded with PRCs were deployed at the surface, mid-column, and near bottom at sites representing the nearshore continental shelf off southern California (Santa Monica Bay, USA) and a mega commercial port (Los Angeles Harbor). After correcting for fractional equilibration using PRCs, concentrations ranged up to 100 pg L(-1) for PCBs and polybrominated diphenyl ethers (PBDEs), 500 pg L(-1) for DDMU and 300 pg L(-1) for DDNU, and to 1000 pg L(-1) for p,p'-DDE. Seawater concentrations of DDTs and PCBs increased with depth, suggesting that bed sediments serve as the source of water column HOCs in Santa Monica Bay. In contrast, no discernable pattern between surface and near-bottom concentrations in Los Angeles Harbor was observed, which were also several-fold lower (DDTs: 45-300 pg L(-1), PCBs: 5-50 pg L(-1)) than those in Santa Monica Bay (DDTs: 2-1100 pg L(-1), PCBs: 2-250 pg L(-1)). Accumulation by mussels co-deployed with the PE samplers at select sites was strongly correlated with PE-estimated seawater concentrations, providing further evidence that these samplers are a viable alternative for monitoring of HOC exposure. Fractional equilibration observed with the PRCs increased with decreasing PRC molar volume indicating the importance of target compound physicochemical properties when estimating water column concentrations using passive samplers in situ. | Bivalves;DDTs;PBDEs;PCBs;Passive samplers;Seawater | pubmed |
Effect of Prematurity on Cerebellar Growth. | The aim of this study was to evaluate cerebellar growth of preterm infants. Vermis height and transverse cerebellar diameter were measured by cranial ultrasonography in 38 preterm infants (27-32 weeks) at birth and term equivalent age. Measurements were compared with 40 term appropriate-for-gestational-age infants. Preterms at term equivalent age had larger vermis height than term infants (2.39 ± 0.25 cm vs 2.25 ± 0.18 cm, P = .005), whereas no significant difference was found in the transverse cerebellar diameter (5.32 ± 0.38 cm vs 5.44 ± 0.23 cm, P = .13). Vermis height and transverse cerebellar diameter of appropriate-for-gestational-age preterm infants (n = 29) were found larger than small-for-gestational-age ones (n = 9). Vermis height and transverse cerebellar diameter at term equivalent age of appropriate-for-gestational-age preterm infants born before and after 29 weeks of age showed no significant difference. Cerebellar growth is preserved in extreme preterms. However, being small for gestational age may have deleterious effects on cerebellar development. | cerebellum;preterm;supratentorial lesion;transverse cerebellar diameter;vermis height | pubmed |
A universal approach to determine footfall timings from kinematics of a single foot marker in hoofed animals. | The study of animal movement commonly requires the segmentation of continuous data streams into individual strides. The use of forceplates and foot-mounted accelerometers readily allows the detection of the foot-on and foot-off events that define a stride. However, when relying on optical methods such as motion capture, there is lack of validated robust, universally applicable stride event detection methods. To date, no method has been validated for movement on a circle, while algorithms are commonly specific to front/hind limbs or gait. In this study, we aimed to develop and validate kinematic stride segmentation methods applicable to movement on straight line and circle at walk and trot, which exclusively rely on a single, dorsal hoof marker. The advantage of such marker placement is the robustness to marker loss and occlusion. Eight horses walked and trotted on a straight line and in a circle over an array of multiple forceplates. Kinetic events were detected based on the vertical force profile and used as the reference values. Kinematic events were detected based on displacement, velocity or acceleration signals of the dorsal hoof marker depending on the algorithm using (i) defined thresholds associated with derived movement signals and (ii) specific events in the derived movement signals. Method comparison was performed by calculating limits of agreement, accuracy, between-horse precision and within-horse precision based on differences between kinetic and kinematic event. In addition, we examined the effect of force thresholds ranging from 50 to 150 N on the timings of kinetic events. The two approaches resulted in very good and comparable performance: of the 3,074 processed footfall events, 95% of individual foot on and foot off events differed by no more than 26 ms from the kinetic event, with average accuracy between -11 and 10 ms and average within- and between horse precision ≤8 ms. While the event-based method may be less likely to suffer from scaling effects, on soft ground the threshold-based method may prove more valuable. While we found that use of velocity thresholds for foot on detection results in biased event estimates for the foot on the inside of the circle at trot, adjusting thresholds for this condition negated the effect. For the final four algorithms, we found no noteworthy bias between conditions or between front- and hind-foot timings. Different force thresholds in the range of 50 to 150 N had the greatest systematic effect on foot-off estimates in the hind limbs (up to on average 16 ms per condition), being greater than the effect on foot-on estimates or foot-off estimates in the forelimbs (up to on average ±7 ms per condition). | Biomechanics;Contact;Event detection;Footfall events;Footfall timings;Horse;Kinematics;Motion capture;Stride cutting;Stride segmentation | pubmed |
HIV and Nurses: A Focus Group on Task Shifting in Uganda. | The HIV prevalence rate is 7.4% in Uganda, where the HIV-related President's Emergency Plan for AIDS Relief and United Nations millennial development goals have not been met. This is partially due to a critical shortage of nurses and other health care providers. Task shifting is a World Health Organization strategy to address the shortage of human resources for health by shifting work from one cadre of health care worker to another, often less-trained, cadre. We conducted three focus groups with nurses in Uganda to better understand perceptions of their preparation for and implementation of task shifting. The focus group included nurses from diverse work settings. Data analysis revealed that nurses were proud of the work they were doing but were challenged by the lack of consistent and appropriate support. We found a need for additional policies, regulations, and consistent preparation for nurses who work in environments with task shifting. | HIV;Uganda;focus group;human resources for health;sustainable development goals;task shifting | pubmed |
Microwave Assisted Synthesis, Physicochemical, Photophysical, Single Crystal X-ray and DFT Studies of Novel Push-Pull Chromophores. | Two push-pull chromophores were synthesized by knoevenagel condensation under microwave irradiation. The structure of synthesized chromophores were established by spectroscopic (FT-IR, (1)H NMR, (13)C NMR, EI-MS) and elemental analysis. Structure of the chromophores was further conformed by X-ray crystallographic. UV-Vis and fluorescence spectroscopy measurements provided that chromophores were good absorbent and fluorescent properties. Fluorescence polarity studies demonstrated that chromophores were sensitive to the polarity of the microenvironment provided by different solvents. Physicochemical parameters, including singlet absorption, extinction coefficient, stokes shift, oscillator strength, dipole moment and flurescence quantum yield were investigated in order to explore the analytical potential of the synthesized chromophores. In addition, the total energy, frontier molecular orbitals, hardness, electron affinity, ionization energy, electrostatic potential map were also studied computationally by using density functional theoretical method. | Chromophore;DFT;Flurescence quantum yield;Knoevenagel condensation;X-ray | pubmed |
Initial test of an emotional avoidance model of restriction in anorexia nervosa using ecological momentary assessment. | It has been hypothesized that restrictive eating allows individuals with anorexia nervosa (AN) to avoid contact with negative emotions; however, this presumption has not been directly tested. In this study, we conducted an initial investigation examining whether restrictive eating serves an emotional avoidance function among individuals with AN. Females with AN (n = 118) reported on negative and positive affect, anxiety/tension, and eating behaviors at multiple time points daily over a 2-week period using ecological momentary assessment methodology. Affective patterns were compared using generalized estimating equation models between days in which participants reported either: (1) relatively high restriction (without binge eating); (2) relatively low restriction (without binge eating); (3) binge eating; or (4) no restriction or binge eating. We hypothesized that, if restriction were functioning to avoid negative affect, average negative affect and anxiety/tension, as well as average negative and positive affect lability, would be lower and average positive affect would be higher on days characterized by high levels of restriction compared to other eating patterns. Contrary to hypotheses: (1) average negative affect, anxiety/tension, and positive affect were not significantly different between days characterized by high restriction and those characterized by low or no restriction; (2) Negative affect and anxiety/tension lability were higher on days characterized by high restriction compared to no restriction or binge eating days; (3) Anxiety/tension lability was higher on days characterized by high versus low levels of restriction. This patterns of findings does not support an avoidance model of restrictive eating for individuals with AN. | Anorexia nervosa;Avoidance;Emotion regulation;Restrictive eating | pubmed |
Management of Elbow Trauma: Anatomy and Exposures. | The elbow is a complex joint from the anatomic and biomechanical point of view. A thorough understanding of elbow anatomy greatly aids the surgeon in dealing with elbow trauma. The close vicinity of neurovascular structures should always be kept in mind when selecting a surgical approach. Any approach to the elbow needs to be safe and versatile. Knowledge of the attachment and orientation of elbow ligaments reduces the risk of inadvertent intraoperative injury and/or postoperative instability. Surgeons dealing with elbow trauma should have a good working understanding of elbow anatomy and the available approaches to effectively and efficiently conduct the surgical procedure to maximize outcomes and minimize complications. | Anatomy;Dislocation;Elbow;Exposures;Fracture;Surgical approaches | pubmed |
A role for panendoscopy? Second primary tumour in early stage squamous cell carcinoma of the oral tongue. | Panendoscopy is routinely used for the identification of occult second primary tumours in head and neck squamous cell carcinoma. However, its role in low risk subgroups, particularly non-smoking, non-drinking patients and patients presenting with early stage oral cavity lesions, is debatable. The records of 112 patients with T₁ or T₂ oral tongue squamous cell carcinoma were retrospectively reviewed. Demographic, disease characteristics and survival data were collected. Average follow-up duration was 71.7 months (range, 3.6-238.3 months). Thirty-five patients died within this period. Thirteen second primary events were identified in 11 patients, with all but 2 tumours in the oral cavity or oropharynx. There was a single synchronous primary - a lung adenocarcinoma; all other events were metachronous. No non-smoking, non-drinking patients re-presented with a second primary tumour; tobacco and alcohol use are clearly risk factors for development of a second primary tumour. The role of panendoscopy for identifying synchronous primary tumours in patients with early stage oral tongue squamous cell carcinoma should be re-evaluated, particularly in non-smoking, non-drinking patients who are at low risk of second primary development. Close follow up with regular clinical examination including flexible fibre-optic endoscopy may be sufficient in this subgroup. | Drinking | pubmed |
On-Tip Photo-Modulated Molecular Printing. | The concept of using cantilever-free scanning probe arrays as structures that can modulate nanoscale ink flow and composition with light is introduced and evaluated. By utilizing polymer pen arrays with an opaque gold layer surrounding the base of the transparent polymer pyramids, we show that inks with photopolymerizable or isomerizable constituents can be used in conjunction with light channelled through the pyramids to control ink viscosity or composition in a dynamic manner. This on-tip photo-modulated molecular printing provides novel chemically and mechanically controlled approaches to regulating ink transport and composition in real time and could be useful not only for rapidly adjusting feature size but also for studying processes including photoreactions and mass transport at the nanoscale, self-assembly, and cell-material interactions. | molecular printing;photochemistry;photocontrol;polymer pen lithography;scanning probe lithography | pubmed |
Clinical contraindications to allergen immunotherapy: an EAACI position paper. | Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient. | allergen immunotherapy;contraindications | pubmed |
A multi-center randomized controlled trial to compare a self-ligating bracket with a conventional bracket in a UK population: Part 1: Treatment efficiency. | To use a two-arm parallel trial to compare treatment efficiency between a self-ligating and a conventional preadjusted edgewise appliance system. A prospective multi-center randomized controlled clinical trial was conducted in three hospital orthodontic departments. Subjects were randomly allocated to receive treatment with either a self-ligating (3M SmartClip) or conventional (3M Victory) preadjusted edgewise appliance bracket system using a computer-generated random sequence concealed in opaque envelopes, with stratification for operator and center. Two operators followed a standardized protocol regarding bracket bonding procedure and archwire sequence. Efficiency of each ligation system was assessed by comparing the duration of treatment (months), total number of appointments (scheduled and emergency visits), and number of bracket bond failures. One hundred thirty-eight subjects (mean age 14 years 11 months) were enrolled in the study, of which 135 subjects (97.8%) completed treatment. The mean treatment time and number of visits were 25.12 months and 19.97 visits in the SmartClip group and 25.80 months and 20.37 visits in the Victory group. The overall bond failure rate was 6.6% for the SmartClip and 7.2% for Victory, with a similar debond distribution between the two appliances. No significant differences were found between the bracket systems in any of the outcome measures. No serious harm was observed from either bracket system. There was no clinically significant difference in treatment efficiency between treatment with a self-ligating bracket system and a conventional ligation system. | Bond failure;Self-ligating;SmartClip;Treatment efficiency;Treatment time | pubmed |
Supplementation of α-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. | ω-3 Polyunsaturated α-linolenic acid (ALA) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity (IS) improvements in patients with type 2 diabetes mellitus (T2DM) by hyperinsulinemic-euglycemic clamp (HEC). The aim of this study was to examine the influence of ω-3 ALA on IS and adiponectin. We conducted a randomized study in patients with T2DM and assessed IS using HEC. Twenty patients with T2DM were included and randomly assigned to receive 3 g/d of ALA or placebo for 60 d, in a double-blind design. The assessment of IS by HEC was performed at baseline and after 60 d in all patients; blood samples were taken for the measurement of serum lipids, glucose, insulin, adiponectin, and cytokines. The primary outcome variables were an increase of both glucose infusion rate (GIR) in steady state and glucose metabolization (M) by HEC. The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose, glycated hemoglobin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, lipids and cytokines. The study was conducted at an academic medical center. The ALA group improved IS corrected for fat-free mass (M/FFM; P = 0.04). Both groups showed increased adiponectin after 60 d (P = 0.01), however, the increase for the ALA group was greater (P = 0.04). In the ALA group, adiponectin was positively correlated with GIR (r = 0.76; P = 0.01) and M/FFM (r = 0.62; P = 0.06), and negatively correlated with HOMA-IR (r = -0.61; P = 0.03). ω-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin. Improvement in the overall metabolic profile with ω-3 ALA suggests a potential clinical utility for this agent and requires further investigation. | Adiponectin;Hyperinsulinemic-euglycemic clamp;Insulin resistance;Type 2 diabetes mellitus;α-Linolenic acid | pubmed |
Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer. | The role of Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) in tumorigenesis has been previously identified. However, the exact role and mechanism of these proteins in progression of colorectal cancer (CRC) are controversial. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling was involved in CRC cell invasion and migration. Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC. | Snail;colorectal cancer;fibronectin;prognosis;serpinA1 | pubmed |
Cardiovascular disease in systemic sclerosis. | Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc. | Atherosclerosis (ATS);cardiovascular (CV) disease;systemic sclerosis (SSc) | pubmed |
Differentiation and characterization of human facial subcutaneous adipocytes. | Aging is associated with the loss of facial subcutaneous fat and with increased abdominal subcutaneous fat. Site specific differences in adipocyte phenotype and/or gene expression may play a role in these age-related changes. In this study, we isolated and characterized human facial preadipocytes and investigated distinct metabolic properties such as a differentiation pattern in relation to abdominal preadipocytes. Subcutaneous preadipocytes were isolated from human facial and abdominal skin and cultured in the presence of differentiation factors including rosiglitazone, a known peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, isobutyl-methyl xanthine (IBMX) and insulin. Differentiation was characterized microscopically and by quantitative real-time PCR. Unexpected superior adipogenic capacity of facial preadipocytes was observed; more facial preadipocytes differentiated in response to rosiglitazone than abdominal preadipocytes and facial preadipocytes retained their ability to differentiate through passage 11 compared with passage 5 for abdominal preadipocytes. Experiments confirmed a reduced lipolysis response in facial versus abdominal adipocytes after exposure to isoproterenol, which was consistent with the reduced β2-adrenergic receptor expression by 60% in the facial cells. The expression of other lipid metabolic gene markers was similar in both facial and abdominal adipocytes with the exception of β3-adrenergic receptor which was only found in abdominal adipose tissue. Gene profiling, by microarray analysis, identified that several HOX genes are robustly reduced in facial adipocytes compared to abdominal adipocytes, suggesting different characteristics between the 2 fat depots. These differences may have implications for development of treatments for facial fat loss during aging. | CD, control differentiated;CDR, control differentiated plus rosiglitazone;FDR, false discovery rate;HOX, homeobox;PCA, principal component analysis;PPAR, peroxisome proliferating activated receptor;UD, undifferentiated;adipocyte;cell culture;differentiation;facial;gene expression;qPCR, quantitative polymerase chain reaction;β adrenergic receptor | pubmed |
Clinical decision support system for end-stage kidney disease risk estimation in IgA nephropathy patients. | The progression of IgA nephropathy (IgAN) to end-stage kidney disease (ESKD) depends on several factors that are not quite clear and tangle the risk assessment. We aimed at developing a clinical decision support system (CDSS) for a quantitative risk assessment of ESKD and its timing using available clinical data at the time of renal biopsy. We included a total of 1040 biopsy-proven IgAN patients with long-term follow-up from Italy (N = 546), Norway (N = 441) and Japan (N = 53). Of these, 241 patients reached ESKD: 104 Italian [median time to ESKD = 5 (3-9) years], 134 Norwegian [median time to ESKD = 6 (2-11) years] and 3 Japanese [median time to ESKD = 3 (2-12) years]. We independently trained and validated two cooperating artificial neural networks (ANNs) for predicting first the ESKD status and then the time to ESKD (defined as three categories: ≤ 3 years, between > 3 and 8 years and over 8 years). As inputs we used gender, age, histological grading, serum creatinine, 24-h proteinuria and hypertension at the time of renal biopsy. The ANNs demonstrated high performance for both the prediction of ESKD (with an AUC of 89.9, 93.3 and 100% in the Italian, Norwegian and Japanese IgAN population, respectively) and its timing (f-measure of 90.7% in the cohort from Italy and 70.8% in the one from Norway). We embedded the two ANNs in a CDSS available online (www.igan.net). Entering the clinical parameters at the time of renal biopsy, the CDSS returns as output the estimated risk and timing of ESKD for the patient. This CDSS provides useful additional information for identifying 'high-risk' IgAN patients and may help stratify them in the context of a personalized medicine approach. | IgA nephropathy;artificial neural networks;clinical decision support system;end-stage kidney disease;risk stratification | pubmed |
A whole-killed, blood-stage lysate vaccine protects against the malaria liver stage. | Although the attenuated sporozoite is the most efficient vaccine to prevent infection with the malaria parasite, the limitation of a source of sterile sporozoites greatly hampers its application. In this study, we found that the whole-killed, blood-stage lysate vaccine could confer protection against the blood stage as well as the liver stage. Although the protective immunity induced by the whole-organism vaccine against the blood stage is dependent on parasite-specific CD4<sup>+</sup> T-cell responses and antibodies, in mice immunized with the whole-killed, blood-stage lysate vaccine, CD8<sup>+</sup> , but not CD4<sup>+</sup> effector T-cell responses greatly contributed to protection against the liver stage. Thus, our data suggested that the whole-killed, blood-stage lysate vaccine could be an alternative promising strategy to prevent malaria infection and to reduce the morbidity and mortality of patients with malaria. | T-cell response;antibody;blood stage;liver stage;whole-killed blood-stage lysate vaccine | pubmed |
The epidemiology of boys' youth lacrosse injuries in the 2015 season. | Participation in boys' youth lacrosse has dramatically increased in recent years. Yet, research on the incidence of youth lacrosse injuries is limited. This study describes the epidemiology of boys' youth lacrosse injuries. Aggregate injury and exposure data was collected from 550 boys' youth lacrosse players (aged 9-15 years) from eight leagues in four states. Injury frequencies and rates with 95 % confidence intervals (CI) were calculated. Rate ratios (RR) accounting for clustering within league compared game and practice injury rates. During the 2015 season, 155 injuries were reported for a rate of 12.98/1000AE (95 % CI:10.93-15.02). Most injuries occurred during games (60.0 %), resulted in time loss <24 h (83.9 %), and were in the U13/U15 divisions (69.0 %). Most injuries were to the lower extremity (45.2 %), and diagnosed as contusions (51.6 %). Ten concussions (6.5 %) were reported, with seven occurring in the U13/U15 divisions. All injuries resulting in time loss ≥24 h in the U9/U11 divisions were concussions. Most injuries were due to equipment contact, particularly stick contact (35.5 %) and ball contact (14.2 %). Injury rates were higher in games than practices overall (RR = 2.90; 95 % CI:1.81-4.89), and for concussions only (RR = 4.51; 95 % CI:1.89-11.03). Between the U9/U11 and U13/U15 divisions, the overall-injury rate was higher in U9/U11 (RR = 1.23; 95 % CI:1.05-1.44). Our boys' youth lacrosse injury rate was higher than those previously reported, but may be more precise given the larger sample. The large proportion of equipment contact injuries demonstrate the need to adopt currently available coaching instruction and age-appropriate US Lacrosse rules that could better protect youth players. | Epidemiology;Youth sports | pubmed |
Formation of Oxazoles from Elusive Gold(I) α-Oxocarbenes: A Mechanistic Study. | The gold(I) catalyzed reaction between phenylacetylene, pyridine N-oxide and acetonitrile leading, via a putative gold-α-oxocarbene intermediate, towards an oxazole product has been investigated. A novel mass spectrometric method called "delayed reactant labeling" is used to track consecutive and parallel reactions. It clearly shows that the intramolecular formation of a pyridine adduct of gold-α-oxocarbene is in competition with the formation of the oxazole product. The reaction mechanism most probably corresponds to competition between acetonitrile and pyridine in an almost barrierless reaction with putative gold-α-oxocarbene within the solvent cage. The detected ionic species have been characterized by helium tagging infrared photodissociation spectroscopy. | carbenes;gold catalysis;mass spectrometry;reaction intermediates;reaction mechanism | pubmed |
Evaluation of a peer mentoring program for early career gerontological nursing faculty and its potential for application to other fields in nursing and health sciences. | As the retirement rate of senior nursing faculty increases, the need to implement new models for providing mentorship to early career academics will become key to developing and maintaining an experienced faculty. This evaluation of a peer mentorship program for predoctoral and postdoctoral gerontological nurses examined its efficacy, utility, and potential for improvement. A web-based survey was developed, implemented, and completed by 22 mentees and 17 mentors (71% and 61% response rates, respectively) as part of the evaluation. The peer mentorship program was found to be valuable by both mentors (64.7%) and mentees (72.7%) in helping mentees further develop their careers and networks and providing mentors with supported mentorship experience. The peer mentorship program could serve as a model for other professional organizations, academic institutions, and consortiums to enhance and extend the formal vertical mentorship provided to early academic career individuals. | Faculty;Gerontological nursing;Leadership;Mentoring;Peer mentorship;Professional development | pubmed |
Facile Surfactant-Free Synthesis of p-Type SnSe Nanoplates with Exceptional Thermoelectric Power Factors. | A surfactant-free solution methodology, simply using water as a solvent, has been developed for the straightforward synthesis of single-phase orthorhombic SnSe nanoplates in gram quantities. Individual nanoplates are composed of {100} surfaces with {011} edge facets. Hot-pressed nanostructured compacts (Eg ≈0.85 eV) exhibit excellent electrical conductivity and thermoelectric power factors (S(2) σ) at 550 K. S(2) σ values are 8-fold higher than equivalent materials prepared using citric acid as a structure-directing agent, and electrical properties are comparable to the best-performing, extrinsically doped p-type polycrystalline tin selenides. The method offers an energy-efficient, rapid route to p-type SnSe nanostructures. | nanomaterials;structures;synthesis;thermoelectrics;tin selenide | pubmed |
Intraoperative diagnosis of sentinel lymph node metastases in breast cancer treatment with one-step nucleic acid amplification assay (OSNA). | The aim of the study was to evaluate the clinical usefulness of a one-step nucleic acid amplification assay (OSNA) for intraoperative detection of metastases to sentinel lymph nodes (SLNs) in comparison to examination of frozen sections, and to summarize the results of previous studies. We enrolled 98 patients aged 58.13 ±10.74 years treated surgically for breast cancer, and 99 biopsies of SLNs were followed by analysis of 105 SLNs. The central 1 mm slice of SLN was used for examination of frozen sections, whereas 2 outer slices of SLNs were analyzed intraoperatively with OSNA. Detection of isolated tumor cells (ITC), micrometastases or macrometastases with OSNA extended surgery to axillary lymph node dissection. Congruency of results was assessed between OSNA and examination of frozen sections. One-step nucleic acid amplification assay detected metastases in 29/105 SLNs in surgery of 27/99 breasts, including ITC in 3/29 SLNs, micrometastases in 12/29 and macrometastases in 14/29. One-step nucleic acid amplification assay detected significantly more metastases to SLNs than examination of frozen sections (<i>p</i> < 0.0001). All 8 inconsistent results were positive in OSNA and negative in examination of frozen sections; ITC were identified in 2/8 SLNs and micrometastases in 6/8 SLNs. Sensitivity for OSNA was calculated as 100%, specificity as 90.47%, and κ was 79.16%. One-step nucleic acid amplification assay analysis allows rapid and quantitative detection of mRNA CK19 with high specificity and a low rate of false positives. One-step nucleic acid amplification assay is a reliable tool for intraoperative diagnosis of whole SLNs during surgery of breast cancer. One-step nucleic acid amplification assay minimizes the need for secondary surgery and avoids delays in the adjuvant treatment. | breast cancer;cytokeratin 19;intraoperative molecular study;sentinel lymph node | pubmed |
Development of a novel magnetophoresis-assisted hydrophoresis microdevice for rapid particle ordering. | Focusing and ordering of micro- or nanoparticles is an essential ability in microfluidic platforms for bio-sample processing. Hydrophoresis is an effective method utilising hydrodynamic force to focus microparticles, but it is limited by the fixed operational range and the lack of flexibility. Here, we report a work to tune and improve the dynamic range of hydrophoresis device using magnetophoresis. In this work, a novel approach was presented to fabricate the lateral fluidic ports, which allow the flipped chip to remain stable on the stage of microscope. Diamagnetic polystyrene microparticles suspended in a ferrofluidic medium were repelled to the lower level of the channel by negative magnetophoretic force, and then interact with grooves of microchannel to obtain an excellent hydrophoretic ordering. The effects of (i) flow rate, (ii) particle size, (iii) magnetic susceptibility of the medium, and (iv) number of magnets on the particle focusing efficiency were also reported. As the proposed magnetophorsis-assisted hydrophoretic device is tuneable and simple, it holds great potential to be integrated with other microfluidic components to form an integrated sample-to-answer system. | Magnetophoresis hydrophoresis particle ordering tunable | pubmed |
A Microfluidic DNA Sensor Based on Three-Dimensional (3D) Hierarchical MoS₂/Carbon Nanotube Nanocomposites. | In this work, we present a novel microfluidic biosensor for sensitive fluorescence detection of DNA based on 3D architectural MoS₂/multi-walled carbon nanotube (MWCNT) nanocomposites. The proposed platform exhibits a high sensitivity, selectivity, and stability with a visible manner and operation simplicity. The excellent fluorescence quenching stability of a MoS₂/MWCNT aqueous solution coupled with microfluidics will greatly simplify experimental steps and reduce time for large-scale DNA detection. | DNA fluorometric detection;MoS2/MWCNT nanocomposites;microfluidic biosensing | pubmed |
NDH-Mediated Cyclic Electron Flow Around Photosystem I is Crucial for C4 Photosynthesis. | C<sub>4</sub> photosynthesis exhibits efficient CO<sub>2</sub> assimilation in ambient air by concentrating CO<sub>2</sub> around ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) through a metabolic pathway called the C<sub>4</sub> cycle. It has been suggested that cyclic electron flow (CEF) around PSI mediated by chloroplast NADH dehydrogenase-like complex (NDH), an alternative pathway of photosynthetic electron transport (PET), plays a crucial role in C<sub>4</sub> photosynthesis, although the contribution of NDH-mediated CEF is small in C<sub>3</sub> photosynthesis. Here, we generated NDH-suppressed transformants of a C<sub>4</sub> plant, Flaveria bidentis, and showed that the NDH-suppressed plants grow poorly, especially under low-light conditions. CO<sub>2</sub> assimilation rates were consistently decreased in the NDH-suppressed plants under low and medium light intensities. Measurements of non-photochemical quenching (NPQ) of Chl fluorescence, the oxidation state of the reaction center of PSI (P700) and the electrochromic shift (ECS) of pigment absorbance indicated that proton translocation across the thylakoid membrane is impaired in the NDH-suppressed plants. Since proton translocation across the thylakoid membrane induces ATP production, these results suggest that NDH-mediated CEF plays a role in the supply of ATP which is required for C<sub>4</sub> photosynthesis. Such a role is more crucial when the light that is available for photosynthesis is limited and the energy production by PET becomes rate-determining for C<sub>4</sub> photosynthesis. Our results demonstrate that the physiological contribution of NDH-mediated CEF is greater in C<sub>4</sub> photosynthesis than in C<sub>3</sub> photosynthesis, suggesting that the mechanism of PET in C<sub>4</sub> photosynthesis has changed from that in C<sub>3</sub> photosynthesis accompanying the changes in the mechanism of CO<sub>2</sub> assimilation. | ATP production;C4 photosynthesis;Chloroplast NADH dehydrogenase-like complex;Cyclic electron flow around PSI;Low-light condition;Proton translocation across the thylakoid membrane | pubmed |
A Method of Radial Nerve Length Measurement Based on Cadaveric Investigation. | To determine the most reliable method to measure the length of the radial nerve during a nerve conduction study (NCS). Cadaveric investigation. A practical anatomy research laboratory in a university. Fresh cadavers (N=10), with 1 cadaver for study design and 9 for data. Design of measurement methods using cadaver dissection and comparison of the measured values to the true length in 18 arms of 9 cadavers. Four points (A, B, C, D) were determined: (A) proximal stimulation point in NCS; (B) point at the elbow crease; (C) point in the midforearm; and (D) distal stimulation point 5cm above the extensor indicis. The true length of the radial nerve between the stimulus points (points A and D) in NCS was compared with the measured values by summation of the straight line segments between those points with various combinations. The difference in root mean square error (RMSE) of the distance measured by each method compared with the true length was calculated to determine the best measurement method. The closest distance to the true length (28.7±2.8cm) in the cadaveric investigation was obtained using the summation of straight line segments between points A, B, and D (A-B-D, RMSE=.72cm), followed by the A-B-C-D distance (RMSE=.87cm) and the A-D distance (RMSE=1.38cm) methods, in sequence. The former 2 distance measurements were relatively closer to the true length than the latter measurement method. Multiple segmentation measurement methods reflected the course of the radial nerve better than a single linear measurement method. We suggest that the distance measured using a stopover point near the lateral epicondyle between 2 stimulus points (A-B-D distance) is closer to the true length of the nerve. | Cadaver;Electrodiagnosis;Nerve conduction;Radial nerve;Rehabilitation | pubmed |
Erythrocyte invasion receptors for Plasmodium falciparum: new and old. | Understanding the complex process by which the invasive form of the Plasmodium falciparum parasite, the merozoite, attaches to and invades erythrocytes as part of its blood stage life cycle represents a key area of research in the battle to combat malaria. Central to this are efforts to determine the identity of receptors on the host cell surface, their corresponding merozoite-binding proteins and the functional relevance of these binding events as part of the invasion process. This review will provide an updated summary of studies identifying receptor interactions essential for or implicated in P. falciparum merozoite invasion of human erythrocytes, highlighting the recent identification of new receptors using groundbreaking high throughput approaches and with particular focus on the properties and putative involvement of the erythrocyte proteins targeted by these invasion pathways. | cytoskeleton;erythrocyte;invasion;malaria;membrane protein;plasmodium;receptor;red blood cell | pubmed |
Commandeering Channel Voltage Sensors for Secretion, Cell Turgor, and Volume Control. | Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate turgor, mineral and water transport. Plants use strongly electrogenic H<sup>+</sup>-ATPases, and the substantial membrane voltages they foster, to drive solute accumulation and generate turgor pressure for cell expansion. Vesicle traffic adds membrane surface and contributes to wall remodelling as the cell grows. Although a balance between vesicle traffic and ion transport is essential for cell turgor and volume control, the mechanisms coordinating these processes have remained obscure. Recent discoveries have now uncovered interactions between conserved subsets of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that drive the final steps in secretory vesicle traffic and ion channels that mediate in inorganic solute uptake. These findings establish the core of molecular links, previously unanticipated, that coordinate cellular homeostasis and cell expansion. | K(+) channels;SNARE protein;Sec1-Munc18 protein;plant cell turgor;secretion;voltage-dependent;volume control | pubmed |
Selection of specific inhibitor peptides in enzyme-linked immunosorbent assay (ELISA) of cardiac troponin I using immuno-dominant epitopes as competitor. | Human cardiac troponin I (cTni) is the gold marker for early diagnosis of myocardial infarction. In this regard, four immune-dominant epitopes of cTni were predicted and their 3D structures were determined. Thereafter, the competitive performance of the peptides was monitored with the developed polyclonal antibody-based indirect competitive ELISA; a half-maximal inhibitory concentration (IC50) of 0.49 (µg/mL) and detection limit of 0.037 (µg/mL) were achieved for recombinant cTni. The competitive ELISA determined sensitivity levels of 0.306, 0.141, 0.960, and 0.155 (µg/mL), respectively, for each peptide as competitor. We indicated that two of the selected epitopes have significant sensitivity scales and inhibition ability. | 3D molecular structure;cardiac troponin I;enzyme-linked immunosorbent assay;immunodominant epitopes;molecular dynamics;polyclonal antibody | pubmed |
Scombroid Poisoning: A Practical Approach. | Scombroid poisoning is a common cause of food poisoning worldwide. It is caused by ingestion of oily fish contaminated with bacteria that trigger the formation of high concentrations of histamine. Scombroid poisoning manifests mainly as a skin complaint (flushing that spreads downward and/or an erythematous urticarial rash affecting the face and upper trunk). Although the clinical course is usually self-limiting and benign, vascular compromise, bronchospasm, and arrhythmias have been described. It is important to establish a differential diagnosis that includes conditions such as fish allergy. Oral antihistamines are the mainstay of treatment. Scombroid poisoning is best prevented by refrigerating fish properly. The practical review of scombroid poisoning provided here is intended for dermatologists. | Escombroidosis;Fish;Food poisoning;Histamine poisoning;Intoxicación histamínica;Pescado;Scombroid poisoning;Toxiinfección alimentaria | pubmed |
Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR. | Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM). | 15-Lipoxygenase inhibitors;Anti-inflammatory;Celecoxib analogues;Cyclooxygenase inhibitors;DMFDMA;Ethyl trifloroacetate;SO(2)NH(2) pharmacophores | pubmed |
Building a competent health manager at district level: a grounded theory study from Eastern Uganda. | Health systems in low-income countries are often characterized by poor health outcomes. While many reasons have been advanced to explain the persistently poor outcomes, management of the system has been found to play a key role. According to a WHO framework, the management of health systems is central to its ability to deliver needed health services. In this study, we examined how district managers in a rural setting in Uganda perceived existing approaches to strengthening management so as to provide a pragmatic and synergistic model for improving management capacity building. Twenty-two interviews were conducted with district level administrative and political managers, district level health managers and health facility managers to understand their perceptions and definitions of management and capacity building. Kathy Charmaz's constructive approach to grounded theory informed the data analysis process. An interative, dynamic and complex model with three sub-process of building a competent health manager was developed. A competent manager was understood as one who knew his/her roles, was well informed and was empowered to execute management functions. Professionalizing health managers which was viewed as the foundation, the use of engaging learning approaches as the inside contents and having a supportive work environment the frame of the model were the sub-processes involved in the model. The sub-processes were interconnected although the respondents agreed that having a supportive work environment was more time and effort intensive relative to the other two sub-processes. The model developed in our study makes four central contributions to enhance the WHO framework and the existing literature. First, it emphasizes management capacity building as an iterative, dynamic and complex process rather than a set of characteristics of competent managers. Second, our model suggests the need for professionalization of health managers at different levels of the health system. Third, our model underscores the benefits that could be accrued from the use of engaging learning approaches through prolonged and sustained processes that act in synergy. Lastly, our model postulates that different resource investments and a varied range of stakeholders could be required at each of the sub-processes. | Capacity building;District-level;Grounded theory method;Health management;Health systems;Low-income settings;Uganda | pubmed |
The role of testosterone in colorectal carcinoma: pathomechanisms and open questions. | Colorectal cancer (CRC) is the fourth commonest type of malignancy after breast, lung and prostate in the USA and accounts for approximately 49,190 deaths annually in USA alone. The 5-year survival rate of CRC has increased over the past decades, in part, due to greater awareness and the widespread implementation of national screening programmes. Recently, a number of studies reported that males have a higher risk of developing CRC due to the action of testosterone. Testosterone is an androgen that is responsible for the development of male secondary sex characteristics and for spermatogenesis. Studies on rats with mutated <i>Apc</i> tumour-suppressor gene subjected to either ovariectomy or orchidectomy exhibit different risks of CRC. Female rats subjected to ovariectomy are at higher risk of CRC, whereas orchidectomised male rats exhibit a lower risk of developing CRC. Sex hormones, in particular estrogen and testosterone, play a significant role in the development of CRC since the anti-neoplastic effect of estrogen lost during ovariectomy increases the risk of females developing CRC. Male mice exposed to testosterone after orchidectomy were also at greater risk than those who were orchidectomised but administered placebo only. Moreover, the recently established role of membrane androgen receptors in regression of CRC via non-genomic androgen-dependent action sets these receptors apart from intracellular androgen receptors (iARs) which themselves promote CRC development. In addition, testosterone-albumin conjugates are selective to membrane androgen receptors (mARs) and lead to apoptosis via caspase-3 activation. Akt kinases promote invasion of colon cancer cells when phosphorylated. These kinases are dephosphorylated upon activation of mARs, thereby reducing colon cancer cell motility and invasiveness. Testosterone similarly plays important roles in human CRC. Long cytosine-adenine-guanine (CAG) repeats in the gene for the androgen receptors have been associated with a poor 5-year survival compared to shorter CAG repeats. Very recently, the measurement of serum unbound testosterone has been suggested as a novel biomarker along with carcinoembryonic antigen in CRC. In conclusion, testosterone may promote the development of CRC via a number of pathways, which may place males at greater risk. Testosterone holds promise as a potential biomarker in CRC risk prediction; however, further studies are required to better define its role in colorectal neoplasia. | Androgen receptor repeats;Androgens;Biomarker;Colorectal cancer;Estrogen receptors;Risk prediction;Sertoli cells;Testosterone | pubmed |
No Evidence of Hendra Virus Infection in the Australian Flying-fox Ectoparasite Genus Cyclopodia. | Hendra virus (HeV) causes potentially fatal respiratory and/or neurological disease in both horses and humans. Although Australian flying-foxes of the genus Pteropus have been identified as reservoir hosts, the precise mechanism of HeV transmission has yet to be elucidated. To date, there has been limited investigation into the role of haematophagous insects as vectors of HeV. This mode of transmission is particularly relevant because Australian flying-foxes host the bat-specific blood-feeding ectoparasites of the genus Cyclopodia (Diptera: Nycteribiidae), also known as bat flies. Using molecular detection methods, we screened for HeV RNA in 183 bat flies collected from flying-foxes inhabiting a roost in Boonah, Queensland, Australia. It was subsequently demonstrated that during the study period, Pteropus alecto in this roost had a HeV RNA prevalence between 2 and 15% (95% CI [1, 6] to [8, 26], respectively). We found no evidence of HeV in any bat flies tested, including 10 bat flies collected from P. alecto in which we detected HeV RNA. Our negative findings are consistent with previous findings and provide additional evidence that bat flies do not play a primary role in HeV transmission. | Cyclopodia;Hendra virus;Nycteribiidae;Pteropus;flying-foxes | pubmed |
Cytotoxic 19-oxygenated steroids from the South China Sea gorgonian, Pacifigorgia senta. | Bioassay guided chemical investigation of the gorgonian Pacifigorgia senta led to the discovery of a new 19-oxygenated steroid, cholesta-5,24-diene-3β,7β,19-triol (1), as well as three known steroids (2-4). The structure of 1 was determined by extensive spectroscopic analysis, including NMR and MS spectra. All of the compounds exhibited cytotoxicities against HepG2, Hep3B, MCF-7/ADR, PC-3 and HCT-116 cell lines, with the IC50 values ranging from 7.0 to 29.7 μM. It is the first report on the chemical constituents of the coral species P. senta. | 19-oxygenated steroid;Gorgonian;Pacifigorgia senta;cytotoxicity | pubmed |
Survey of community pharmacists' perception of electronic cigarettes in London. | To seek community pharmacists' perception on use, safety and possible effectiveness of e-cigarettes as quit smoking tools, and their future regulation. A survey of a sample of 154 community pharmacies across London, UK. E-cigarettes have exclusively established themselves in the market through consumers-led demand. To date, e-cigarettes still remain unregulated and can be easily purchased in shops, over the internet, but more controversially also in pharmacies in the UK. Pharmacists find themselves with a shortage of information on their safety and efficacy, and may experience an ethical dilemma when consulted by patients/customers. Response rate: 60% (n=92). Independent pharmacies accounted for 90% of the sample. The majority of participants (73%) sell e-cigarettes. A minority of participants (20%) have been presented with adverse effects such as cough and dry mouth. As possible reasons for their use, pharmacists ranked 'aid in stop smoking' as the most important (56%), with 'cheaper alternative' (43%) and 'social/recreational use' (31%) being the least important ones. Safety issues were raised as statements such as 'e-liquid in cartridges may be toxic' were agreed by 52% of respondents. The majority of pharmacists (97%) were supportive of e-cigarettes being regulated, expressing current concerns regarding excipients (42%) and nicotine content (34%). Participants indicated that they would require training in the form of information packs (88%), online tutorials (67%), continuous professional development (CPD) workshops (43%) to cover safety, counselling, dosage instructions, adverse effects and role in the smoking cessation care pathway in the future. Pharmacists expressed concerns about the safety of e-cigarettes, especially regarding the amounts of excipients and nicotine as these still remain unregulated. Currently, there are no guidelines for pharmacists regarding e-cigarettes. Community pharmacists look forward to regulations so to conduct their duties in a more confident and legislated fashion. | community pharmacist;e-cigarettes;efficacy;perception;regulations;safety | pubmed |
A porcine reproductive and respiratory syndrome virus candidate vaccine based on the synthetic attenuated virus engineering approach is attenuated and effective in protecting against homologous virus challenge. | Current porcine reproductive and respiratory syndrome virus (PRRSV) vaccines sometimes fail to provide adequate immunity to protect pigs from PRRSV-induced disease. This may be due to antigenic differences among PRRSV strains. Rapid production of attenuated farm-specific homologous vaccines is a feasible alternative to commercial vaccines. In this study, attenuation and efficacy of a codon-pair de-optimized candidate vaccine generated by synthetic attenuated virus engineering approach (SAVE5) were tested in a conventional growing pig model. Forty pigs were vaccinated intranasally or intramuscularly with SAVE5 at day 0 (D0). The remaining 28 pigs were sham-vaccinated with saline. At D42, 30 vaccinated and 19 sham-vaccinated pigs were challenged with the homologous PRRSV strain VR2385. The experiment was terminated at D54. The SAVE5 virus was effectively attenuated as evidenced by a low magnitude of SAVE5 viremia for 1-5 consecutive weeks in 35.9% (14/39) of the vaccinated pigs, lack of detectable nasal SAVE5 shedding and failure to transmit the vaccine virus from pig to pig. By D42, all vaccinated pigs with detectable SAVE5 viremia also had detectable anti-PRRSV IgG. Anti-IgG positive vaccinated pigs were protected from subsequent VR2385 challenge as evidenced by lack of VR2385 viremia and nasal shedding, significantly reduced macroscopic and microscopic lung lesions and significantly reduced amount of PRRSV antigen in lungs compared to the non-vaccinated VR2385-challenged positive control pigs. The nasal vaccination route appeared to be more effective in inducing protective immunity in a larger number of pigs compared to the intramuscular route. Vaccinated pigs without detectable SAVE5 viremia did not seroconvert and were fully susceptible to VR2385 challenge. Under the study conditions, the SAVE approach was successful in attenuating PRRSV strain VR2385 and protected against homologous virus challenge. Virus dosage likely needs to be adjusted to induce replication and protection in a higher percentage of vaccinated pigs. | Attenuation;Efficacy;Porcine reproductive and respiratory syndrome virus (PRRSV);Synthetic attenuated virus engineering (SAVE);Vaccine | pubmed |
Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention. | Various clinical and epidemiologic studies show that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase inhibitors (COXIBs) help prevent cancer. Since eicosanoid metabolism is the main inhibitory targets of these drugs the resulting molecular and biological impact is generally accepted. As our knowledge base and technology progress we are learning that additional targets may be involved. This review attempts to summarize these new developments in the field. | Aspirin;Cancer prevention;Inflammation;Non-steroidal anti-inflammatory drugs (NSAID) | pubmed |
Pharmacokinetics and tissue distribution of two novel isomerism anticancer platinum compounds. | LLC-0601(S,S) and LLC-0601(R,R) are two novel synthesized isomerism platinum compounds both with encouraging anticancer activity. However, the previous study showed that toxicity of LLC-0601(R,R) was much higher than that of LLC-0601(S,S) with higher body weight loss and mortality rate of tested rats. This paper is focused on the comparison of the two compounds with their pharmacokinetic (PK) profiles in rats and tissue distribution in mice after intravenous administration. The atomic absorption spectrometry (AAS) method was successfully developed and applied for the determination of platinum in plasma and tissues. The results showed that main PK parameters such as half-life, AUC and MRT of the two compounds had no significant difference after intravenous administration to rats (p > 0.05). The tissue distribution after intravenous administration to mice showed that the concentration of LLC-0601(R,R) in heart at 0.083 h was higher than that of LLC-0601(S,S) (p < 0.05) and it was the same case for AUC5min-4 h (p < 0.05). Different distribution of the two compounds in heart was possibly the main reason of different toxicity and more in-depth research on the metabolites and other mechanism are needed to investigate the toxicity. | Isomerism antitumor platinum compounds;LLC-0601(R,R);LLC-0601(S,S);pharmacokinetics;tissue distribution | pubmed |
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