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Wide-field Digital Ophthalmic Imaging in Infants using Nasal Endoscopic System. | To report the utility of nasal endoscopic system in viewing the iridocorneal angle and fundus using various nasal endoscopes and light sources and to determine which type suits best to image a given location in the eye. This is a prospective observational study of 20 eyes of 10 consecutive infants, who were scheduled for irrigation and probing for congenital nasolacrimal duct obstruction under general anesthesia. The pupils were dilated, viscoelastic gel was applied on the cornea and imaging was performed using nasal endoscopes. The endoscopes used were of 2.7 mm and 4 mm diameter, each with various angulations of 0(0), 30(0) and 70(0). Two different cold light illuminators (Xenon and Halogen) were used uniformly in all cases. Images were analyzed for their quality, clarity and extent of the fields captured. In all the 20 eyes, nasal endoscope provided a clear circular view of the iridocorneal angle and wide-field fundus view in a single glimpse. The 4 mm endoscope offered a wider view while in-air disc analysis was better with the 2.7 mm endoscope. Angulated endoscopes were more useful in imaging the iridocorneal angle, peripheral retina up to the ora serrata and ciliary body. The image quality with the xenon and halogen light sources were found to be comparable. The time taken for a single eye examination did not exceed 5 min. With good techniques and appropriate selection of nasal endoscopes, viewing of the iridocorneal angle and fundus is easy, possibly less expensive and very useful in infants. | Fundus;Imaging;Infants;Low cost;Nasal endoscope;Screening | pubmed |
Kinetic modeling and docking study of immobilized lipase catalyzed synthesis of furfuryl acetate. | The present work deals with the kinetic modeling and docking study for the furfuryl acetate synthesis using immobilized Burkholderia cepacia (BCL) lipase. Initially various lipases were immobilized on hydroxypropyl methyl cellulose (HPMC) and poly vinyl alcohol (PVA) base hybrid polymer matrix. After screening of various immobilized biocatalysts, HPMC:PVA:BCL was found to be a robust biocatalyst. Various reaction conditions were optimized using response surface methodology (RSM) based on a four-factor-three-level Box-Behnken design. The optimal conditions were obtained at molar ratio of 1:2 of furfuryl alcohol to acyl donor, temperature 50°C with catalyst loading of 30mg in 3mL of non-aqueous media toluene. Under these conditions 99.98% yield was obtained in 3h. The Arrhenius plot showed that the activation energy for furfuryl acetate synthesis was 10.68kcal/mol. The kinetics of reaction was studied close to optimized conditions which obey order bi-bi model. Molecular docking study was carried out to understand the active site of BCL which is responsible for the reaction. It was observed that the reaction proceeds via acylation of the active serine of BCL and demonstrating strong hydrogen bond between the substrate and histidine site. The catalyst recyclability study was carried up to five cycles. | Docking study;Furfuryl acetate;Immobilized lipase;Reaction kinetics | pubmed |
Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial. | This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality. | Antibacterial efficacy;Morinda citrifolia L;irreversible hydrocolloid | pubmed |
Does Place Attachment Predict Wildfire Mitigation and Preparedness? A Comparison of Wildland-Urban Interface and Rural Communities. | Wildfires are a common occurrence in many countries and are predicted to increase as we experience the effects of climate change. As more people are expected to be affected by fires, it is important to increase people's wildfire mitigation and preparation. Place attachment has been theorized to be related to mitigation and preparation. The present study examined place attachment and wildfire mitigation and preparation in two Australian samples, one rural and one on the wildland-urban interface. The study consisted of 300 participants who responded to questionnaires about their place attachment to their homes and local areas, as well as describing their socio-demographic characteristics and wildfire mitigation and preparedness. Hierarchical regression showed that place attachment to homes predicted wildfire mitigation and preparedness in the rural sample but not in the wildland-urban interface sample. The results suggest that place attachment is a motivator for mitigation and preparation only for people living rurally. Reminding rural residents of their attachment to home at the beginning of wildfire season may result in greater mitigation and preparedness. Further research focusing on why attachment does not predict mitigation and preparedness in the wildland-urban interface is needed. | Place attachment;Place dependence;Place identity;Rural communities;Wildfire mitigation;Wildland–urban interface | pubmed |
Strain distribution in the proximal Human femur during in vitro simulated sideways fall. | This study assessed: (i) how the magnitude and direction of principal strains vary for different sideways fall loading directions; (ii) how the principal strains for a sideways fall differ from physiological loading directions; (iii) the fracture mechanism during a sideways fall. Eleven human femurs were instrumented with 16 triaxial strain gauges each. The femurs were non-destructively subjected to: (a) six loading configurations covering the range of physiological loading directions; (b) 12 configurations simulating sideways falls. The femurs were eventually fractured in a sideways fall configuration while high-speed cameras recorded the event. When the same force magnitude was applied, strains were significantly larger in a sideways fall than for physiological loading directions (principal compressive strain was 70% larger in a sideways fall). Also the compressive-to-tensile strain ratio was different: for physiological loading the largest compressive strain was only 30% larger than the largest tensile strain; but for the sideways fall, compressive strains were twice as large as the tensile strains. Principal strains during a sideways fall were nearly perpendicular to the direction of principal strains for physiological loading. In the most critical regions (medial part of the head-neck) the direction of principal strain varied by less than 9° between the different physiological loading conditions, whereas it varied by up to 17° between the sideways fall loading conditions. This was associated with a specific fracture mechanism during sideways fall, where failure initiated on the superior-lateral side (compression) followed by later failure of the medially (tension), often exhibiting a two-peak force-displacement curve. | Direction of principal strain;Hip fractures;Physiological loading;Sideways fall;Strain distribution;Structural optimization | pubmed |
The efficacy of intrauterine injection of human chorionic gonadotropin before embryo transfer in assisted reproductive cycles: Meta-analysis. | A systematic review and meta-analysis to evaluate the effect of human chorionic gonadotropin (hCG) intrauterine injection before embryo transfer on the outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Searches of PubMed®, EMBASE®, EBSCO, Web of Science®, SCOPUS® and Cochrane Central Register of Controlled Trials were conducted to retrieve relevant randomized controlled trials (RCTs). Data were extracted and analysed. The meta-analysis included five RCTs (hCG group n = 680; control group n = 707). Intrauterine hCG injection significantly increased rates of biochemical, clinical and ongoing pregnancy compared with controls. There were no between-group differences in implantation or miscarriage rates. Women undergoing IVF/ICSI may benefit from intrauterine hCG injection before embryo transfer. | Intrauterine injection;embryo transfer;endometrial infusion;hCG;human chorionic gonadotropin;intracytoplasmic sperm injection;in vitro fertilization;meta-analysis | pubmed |
Long-Term Care and Humanbecoming. | humanbecoming;listening;long-term care | pubmed |
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Interactions between innate immunity genes and early-life risk factors in allergic rhinitis. | Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated. A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three early-life factors and AR were assessed by a questionnaire. Skin prick tests were done. Polymorphisms of TLR4 (rs1927911) and CD14 (rs2569190) were genotyped. Use of antibiotics during infancy increased the risk of AR (aOR [95% CI] 1.511 [1.222-2.037]) and atopic AR (aOR [95% CI], 1.565 [1.078-2.272]). There were synergistic interactions between caesarean delivery, formula feeding, and use of antibiotics in the rate of atopic AR (aOR [95% CI], 3.038 [1.256-7.347]). Additional analyses revealed that the risk for the development of AR or atopic AR subjects with the TLR4 CC genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.127 [1.265-20.780] for AR; 6.078 [1.499-24.649] for atopic AR). In addition, the risk for the development of AR or atopic AR in subjects with the CD14 TT genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.960 [1.421-15.002] for AR; 6.714 [1.440-31.312] for atopic AR). Delivery mode, feeding method, and use of antibiotics during infancy appeared to have synergistic interactions in the development of AR. Gene-environment interactions between polymorphism of innate genes and early- life risk factors might affect the development of AR. | Obstetric delivery;antibiotics;gene-environment interaction, allergic rhinitis;infant food | pubmed |
Pancreatic Endotherapy for Chronic Pancreatitis. | Extracorporeal shock wave lithotripsy is recommended as the first-line therapy for large (>5-mm) obstructive pancreatic ductal stones. Dominant pancreatic duct strictures should be initially managed with a wide-bore single plastic stent with 3 monthly exchanges for a year, even in asymptomatic patients. Recent studies have evaluated multiple plastic and self-expanding covered metal stents for refractory pancreatic ductal stricture. Pancreatic pseudocysts should be treated endoscopically with or without endoscopic ultrasound guidance. | Endoscopic retrograde cholangiopancreatography;Extracorporeal shock wave lithotripsy;Metal stents;Multiple plastic stent;Painful chronic pancreatitis;Pancreatic calculi;Pseudocyst;Stricture | pubmed |
Effect of chemical interaction on the bonding strengths of self-etching adhesives to deproteinised dentine. | The present study examined (1) the chemical interaction between three self-etching adhesives and sodium hypochlorite (NaOCl)-deproteinised dentine, and (2) the influence of NaOCl treatment on bond strength of self-etching adhesives with/without adhesive functional monomers to dentine. Caries-free dentine disks (control) and those treated with 5.25% NaOCl for 60s were prepared. Xeno V (no functional monomers), G-Bond (containing 4-MET) or S3 Bond (containing 10-MDP) were applied to the NaOCl-treated dentine and either left without further treatment, or rinsed with 100% ethanol or distilled water. Attenuated total reflection (ATR) spectroscopy and field-emission scanning electron microscopy (FE-SEM) were used to evaluate the affinity of functional monomers with deproteinised dentine. Chemical interaction between the functional monomers and deproteinised dentine was evaluated using thin-film X-ray diffraction (TF-XRD). Microtensile bond strength (MTBS) was used to evaluate the mechanical property of the adhesives, either immediately or after thermo-cycling (5-55°C) for 10,000 cycles. According to the ATR and FE-SEM results, G-Bond and S3 Bond showed stronger affinity to deproteinised dentine than Xeno V even after rinsing with water. TF-XRD showed that chemical interaction between S3 Bond and deproteinised dentine occurred by formation of 10-MDP-Ca salt. Both deproteinisation and thermo-cycling adversely affected the MTBS of Xeno V (P<0.05) but deproteinisation had no significant influence on S3 Bond. When bonding to NaOCl-treated dentine, self-etch adhesives containing functional monomers (10-MDP) can maintain immediate and aged bond strengths after 10,000 thermal cycles. | Adhesive;Functional monomer;Microtensile bond strengths;Sodium hypochlorite, Self-etching | pubmed |
Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants. | The use of nanoparticles for delivery of vaccine antigens and as vaccine adjuvants is appealing because their size allows efficient uptake by dendritic cells and their biological properties can be tailored to the desired function. Here, we report the effect of chemically modified phytoglycogen, a dendrimer-like α-d-glucan nanoparticle, on dendritic cells in vitro, and the utility of this type of nanoparticle as a vaccine adjuvant in vivo. The modified phytoglycogen nanoparticle, termed Nano-11, has a positive surface charge which enabled electrostatic adsorption of negatively charged protein antigens. The Nano-11-antigen complexes were efficiently phagocytized by dendritic cells. Nano-11 induced increased expression of costimulatory molecules and the secretion of IL-1β and IL-12p40 by dendritic cells. Intramuscular injection of Nano-11-antigen formulations induced a significantly enhanced immune response to two different protein antigens. Examination of the injection site revealed numerous monocytes and relatively few neutrophils at one day after injection. The inflammation had nearly completely disappeared by 2 weeks after injection. These studies indicate that Nano-11 is an effective vaccine delivery vehicle that significantly enhances the immune response. This type of plant based nanoparticle is considered highly cost-effective compared with fully synthetic nanoparticles and appears to have an excellent safety profile making them an attractive adjuvant candidate for prophylactic vaccines. | Adjuvants;Dendritic cells;IL-1β;Inflammation;Nanoparticles;Vaccines | pubmed |
Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study. | We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19-20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients. | 2009 A/H1N1 influenza pandemic;UCBL, Université Claude Bernard Lyon 1;WHO, World Health Organization;influenza vaccination;university staff | pubmed |
Recent advances in the elucidation of enzymatic function in natural product biosynthesis. | With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed. | combinatorial biosynthesis;natural product biosynthesis;plant-derived drugs | pubmed |
Organellar non-coding RNAs: emerging regulation mechanisms. | Originally focused on the nuclear and cytosolic compartments, the concept of regulation driven by non-coding RNAs (ncRNAs) is extending to mitochondria and chloroplasts. These organelles have distinct genetic systems that need coordination with cellular demands. In mammals, nuclear-encoded microRNAs were found associated with the mitochondria. Some of these contribute to the regulation of mitochondrial transcription and translation. Others were proposed to be stored in the organelles and to be released for regulation of nuclear transcripts. Further ncRNAs of various sizes derive from the mitochondrial genome and it was speculated that organelles host antisense or RNA interference pathways. Long ncRNAs mapping to the mitochondrial DNA seem to operate in the nucleus. Altogether, the origin and trafficking of ncRNAs categorized as mitochondrial in mammals raise questions far beyond the current knowledge. In protozoa, hundreds of guide RNAs specify editing events needed to generate functional messenger RNAs. Only few ncRNAs have been reported in plant mitochondria, but editing sites were revealed in non-coding regions of the organellar genome, suggesting that the corresponding transcripts have a function. Conversely, numerous ncRNA candidates were identified in chloroplasts, essentially mapping to the plastid genome. A synthetic view of the data with their functional implications is given here. | Antisense regulation;Chloroplasts;Mitochondria;Non-coding RNA;RNA interference;RNA trafficking | pubmed |
Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. | Breast cancer is a common diagnosis in women. Breast radiation has become critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation-induced heart disease (RIHD) comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation. | breast cancer;radiation fibrosis;radiation side effects;radiation therapy | pubmed |
Introduction of an update system for vaccine strains of veterinary influenza vaccines in Japan. | The basic countermeasures used to control highly pathogenic avian influenza (HPAI) are early detection procedures and the culling of affected chickens. However, if successive HPAI outbreaks occur, the vaccination may be an option for controlling HPAI. Therefore, avian influenza (AI) vaccines are stocked by the Japanese government. By contrast, equine influenza (EI) vaccine is an effective tool for preventing or controlling EI. Because antigenic drifts affect the efficacy of AI and EI vaccines, the vaccine strains should be updated rapidly. However, the development and registration of veterinary vaccines usually takes several years. In response to this issue, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) established a system that allows AI and EI vaccine strains to be updated rapidly. National Veterinary Assay Laboratory, MAFF, established a vaccine strains selection committee for veterinary influenza vaccine. The main agendas involve determining whether the current vaccine strains need to be updated and selecting the most appropriate vaccine strains. The committee concluded that A/duck/Hokkaido/Vac-3/2007(H5N1) was added to the strains of stockpiled AI vaccines and that the EI vaccine strains did not need to be changed, but that the clade 2 viruses of the Florida sub-lineage strain, A/equine/Yokohama/aq13/2010(H3N8) was added to the EI vaccine strain. | Avian influenza;Equine influenza;Veterinary vaccine | pubmed |
Porcine reproductive and respiratory syndrome virus vaccine does not fit in classical vaccinology. | All vaccines are developed to elicit an effective immune response in vaccinated animals such as innate, humoral and cell mediated response to protect animal health. Quality and intensity of the immune responses are differing by characteristics of the vaccine formulation and nature of the infectious agent. Modified live virus vaccines showed advantages over killed vaccines in terms of rapid immune response, duration of the immunity and better cell mediated protection mechanism. The porcine reproductive and respiratory syndrome virus (PRRSV) is relatively newly emerging (1986 in United States, 1990 in Europe) viral pathogen in pigs and tremendous effort has been made to protect pigs from this economically devastating disease such as developing killed, modified live, recombinant protein based and DNA vaccines. However, only cell culture attenuated virus vaccine is practiced with arguably limited efficacy. The PRRSV vaccine did not clear virus from infected pigs nor prevent re-infection of the virus. The vaccine showed very limited innate immune response, low anamnestic immune response and negligible cell mediated immune response. Despite of the current developed scientific technology, there still remain many questions to solve a most important pig disease worldwide. | Immunity;Porcine respiratory and reproductive syndrome virus;Vaccines | pubmed |
The felt presence of other minds: Predictive processing, counterfactual predictions, and mentalising in autism. | The mental states of other people are components of the external world that modulate the activity of our sensory epithelia. Recent probabilistic frameworks that cast perception as unconscious inference on the external causes of sensory input can thus be expanded to enfold the brain's representation of others' mental states. This paper examines this subject in the context of the debate concerning the extent to which we have perceptual awareness of other minds. In particular, we suggest that the notion of perceptual presence helps to refine this debate: are others' mental states experienced as veridical qualities of the perceptual world around us? This experiential aspect of social cognition may be central to conditions such as autism spectrum disorder, where representations of others' mental states seem to be selectively compromised. Importantly, recent work ties perceptual presence to the counterfactual predictions of hierarchical generative models that are suggested to perform unconscious inference in the brain. This enables a characterisation of mental state representations in terms of their associated counterfactual predictions, allowing a distinction between spontaneous and explicit forms of mentalising within the framework of predictive processing. This leads to a hypothesis that social cognition in autism spectrum disorder is characterised by a diminished set of counterfactual predictions and the reduced perceptual presence of others' mental states. | Active inference;Autism;Counterfactuals;Mentalising;Predictive coding;Presence;Social cognition;Theory of mind;Veridicality | pubmed |
ASD, ADHD, mental health conditions and psychopharmacology in neurogenetic syndromes: parent survey. | There are a number of neurogenetic syndromes with well described behavioural phenotypes including fragile X syndrome, Prader-Willi syndrome, Williams syndrome and velo-cardio-facial syndrome (VCFS). Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and psychiatric conditions are often associated with the syndromes. Parents (n = 381) of school-aged children with one of the four syndromes in the UK and Ireland were asked whether their child had been professionally diagnosed with ASD, ADHD or a mental health condition. Parents were also asked whether their child had been prescribed medication for behavioural or psychiatric reasons. The highest level of reported diagnoses of ASD and ADHD was in fragile X syndrome. In all syndrome groups, lower rates of diagnosis were reported in comparison to previously published research. Prescribing of medication for behavioural/psychiatric reasons was highest in fragile X syndrome although the highest usage of melatonin was in Williams syndrome. Reasons for a lower recognition of ASD, ADHD and mental health conditions in clinical practice compared with research studies may include 'diagnostic overshadowing' due to presence of intellectual disability and a genetic syndrome. However, there may also be a lack of belief in the utility of such diagnoses in neurogenetic syndromes among relevant professionals and/or lack of access to professionals with sufficient expertise in the recognition of such diagnoses in those with neurogenetic syndromes. The low rates of prescribing of medication for behavioural/psychiatric reasons may reflect the low level of clinical diagnoses or lack of belief in the utility of psychopharmacology in this population. | ADHD;Prader-Willi syndrome;Williams syndrome;autism spectrum disorder (ASD);fragile X syndrome;velo-cardio-facial syndrome (VCFS) | pubmed |
Imaging characteristics and embolus burden of unreported pulmonary embolism in oncologic patients. | The present study sought to estimate the frequency of overseen and unreported (i.e., false negative) pulmonary embolism (PE) events in oncologic patients. In a retrospective analysis, 3270 patients (6780 computed tomography examinations) were reviewed. Unreported PE was found in 74 patients (2.3%). It was particularly frequent in follow-up staging examinations in patients with metastasized malignancies of the lung and kidney. The present data support the thesis that the search error (thrombus was never fixed by the eyes of the reviewer) was the most common reason why PE was overseen. | Computed tomography;Embolus burden;Incidental pulmonary embolism;Medical imaging perception;Quality assurance;Unreported pulmonary embolism | pubmed |
Detection of unruptured intracranial aneurysms on noninvasive imaging. Is there still a role for digital subtraction angiography? | To determine the utility of digital subtraction angiography (DSA) in patients with unruptured intracranial aneurysms (UIA) detected on noninvasive imaging, such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA). The follow-up of patients with untreated UIAs involves serial imaging; however, this diagnosis may be based on false positive (FP) results. We examined the incidence of FPs in our institutional series. DSAs performed at our institution from January 2011 to June 2014 were retrospectively reviewed and patients referred with UIA detected on noninvasive imaging were selected. Clinical presentation as well as aneurysm location, size, and number reported on DSA and noninvasive imaging were assessed. Two hundred and eighty six patients (mean age 56.8 years, female 74.8%) with a total of 355 UIA were included. Thirty-one patients had a symptomatic presentation. Analysis per patient showed the pooled FP rate of noninvasive imaging was 15%. MRA FP was 13% (22/171) and CTA FP was 18% (22/120). FP increased significantly with aneurysm size < 3.5 mm on MRA (P < 0.001) and <4.0 mm on CTA (P = 0.01). Mean aneurysm size among symptomatic patients was significantly larger (P < 0.001) as compared to the incidental group (17.8 vs. 7.7 mm). No location was significantly susceptible to false detection of aneurysms. DSA detection of FP UIA diagnosed on noninvasive imaging is significantly higher for aneurysms <4.0 mm. Accurate diagnosis with DSA may eliminate the need for further follow-up and its associated negative psychological and economic effects. Within the limitations of this retrospective study, we conclude that DSA has a diagnostic role in small aneurysms detected on noninvasive imaging. | Angiography;cerebral aneurysm;computed tomography;digital subtraction angiography;magnetic resonance imaging | pubmed |
Fit-for-purpose chromatographic method for the determination of amikacin in human plasma for the dosage control of patients. | In this paper, a simple, rapid and sensitive method based on liquid chromatography with fluorimetric detection (HPLC-FLD) for the determination of amikacin (AMK) in human plasma is developed. Determination is performed by pre-column derivatization of AMK with ortho-phtalaldehyde (OPA) in presence of N-acetyl-L-cysteine (NAC) at pH 9.5 for 5 min at 80 °C. In our knowledge, this is the first time that NAC has been used in AMK derivatization. Derivatization conditions (pH, AMK/OPA/NAC molar ratios, temperature and reaction time) are optimized to obtain a single and stable, at room temperature, derivative. Separation of the derivative is achieved on a reversed phase LC column (Kromasil C18, 5 μm, 150 × 4.6 i.d. mm) with a mobile phase of 0.05 M phosphate buffer:acetonitrile (80:20, v/v) pumped at flow rate of 1.0 mL/min. Detection is performed using 337 and 439 nm for excitation and emission wavelengths, respectively. The method is fitted for the purpose of being a competitive alternative to the currently used method in many hospitals for AMK dosage control: fluorescence polarization immunoassay (FPIA). The method exhibits linearity in the 0.17-10 µg mL(-1) concentration range with a squared correlation coefficient higher than 0.995. Trueness and intermediate precision are estimated using spiked drug free plasma samples, which fulfill current UNE-EN ISO15189:2007 accreditation schemes. Finally, for the first time, statistical comparison against the FPIA method is demonstrated using plasma samples from 31 patients under treatment with AMK. | Amikacin;Fit-for-purpose;Fluorescence detection;Liquid chromatography;Ortho-phtalaldehyde/N-acetyl-L-cysteine derivatization;Plasma samples | pubmed |
The efficient hemostatic effect of Antarctic krill chitosan is related to its hydration property. | Antarctic krill chitosan (A-Chitosan) was first evaluated in its hemostatic effect in this study. The prepared A-Chitosan powder showed low level of crystallinity and significantly high water binding capacity as 1293% (w/w). By mice tail amputation model and blood coagulation timing experiment, it is showed that this chitosan accelerated the tail hemostasis by 55% and shortened the blood clotting time by 38%. This efficacy was better than two other commercial chitosans investigated and was corresponding to their water binding capacities. Through examining the effect of chitosan on blood components, it could be found that platelets adhesion was mainly affected by the water binding capacity, and red blood cells aggregation was dependent on their deacetylation degree. The physicochemical properties resulted in better hydration property of chitosan would improve its hemostatic effect. These results suggested that Antarctic krill chitosan is a good candidate for hemostatic application. | Antarctic krill;CaCl2 (PubChem CID:5284359);Calcein AM (PubChem CID:4126474);Chitosan;HCl (PubChem CID:313);Hemostatic agent;NaOH (PubChem CID:14798);acetic acid (PubChem CID:176);chloral hydrate (PubChem CID:2707);deuterium chloride (PubChem CID:522634);deuterium oxide (PubChem CID:24602);socium acetate (PubChem CID:517045);sodium citrate (PubChem CID:6224) | pubmed |
Integrated parasite management: path to sustainable control of fishborne trematodes in aquaculture. | Fishborne zoonotic trematodes (FZT) are an emerging problem and there is now a consensus that, in addition to wild-caught fish, fish produced in aquaculture present a major food safety risk, especially in Southeast Asia where aquaculture is important economically. Current control programs target communities at risk through mass drug administration. However, we argue that treatment alone will not reduce the risk from eating infected fish and that sustainable effective control must adopt an integrated FZT control approach based on education, infrastructure improvements, and management practices that target critical control points in the aquaculture production cycle identified from a thorough understanding of FZT and host biology and epidemiology. We present recommendations for an integrated parasite management (IPM) program for aquaculture farms. | aquaculture;control;fish;fishborne;parasites;prevention | pubmed |
Prevalence of hyperglycaemia in singleton versus twin pregnancy. | There is conflicting information regarding the risk of gestational diabetes mellitus in twin pregnancies. This study was conducted to determine whether the risk of gestational diabetes mellitus is higher in pregnant Japanese women with twin versus singleton pregnancy. The prevalence of gestational diabetes mellitus was studied in two different populations: 144 589 women registered with the Japan Society of Obstetrics and Gynecology (JSOG cohort) over 3 years between 2007 and 2009 in which patient selection bias was unavoidable; and 430 Japanese women who gave birth at a single centre over 5 years between 2008 and 2012 (single-centre cohort), consisting of 86 women with twins and 344 women with singletons matched for maternal age and prepregnancy body mass index. The gestational diabetes mellitus was diagnosed on the basis of the previous criteria in the JSOG cohort. The gestational diabetes mellitus was screened in a stepwise method and diagnosed on the basis of the new criteria in the single-centre cohort. In the single-centre cohort, neither frequency of random glucose level ≥105 mg/dL in the first trimester [9.0% (31/344) vs 5.8% (5/86)], positive result (≥140 mg/dL) on 50 g glucose challenge test in the second trimester [26.5% (90/339) vs 26.7% (23/86)], nor women diagnosed with GDM [8.4% (29/344) vs 9.3% (8/86)] differed between the two groups. The prevalence of hyperglycaemia was higher in singleton than in twin pregnancies in the JSOG cohort (2.6% vs 1.8%, p < 0.001). The risk of gestational diabetes mellitus may be similar between Japanese women with singleton and twin pregnancies. Difference in the risk of hyperglycaemia in the JSOG cohort may have been due to selection bias. | glucose metabolism;maternal body mass index;twin pregnancy | pubmed |
The Downregulation of MicroRNA-146a Modulates TGF-β Signaling Pathways Activity in Glioblastoma. | Transforming growth factor-β (TGF-β) is considered to be one of the main factors responsible for glioblastoma tumorigenesis. MicroRNAs have recently been shown to regulate cell proliferation, differentiation, and apoptosis. However, the involvement of miRNA-146a in TGF-β1-induced glioblastoma development remains largely unknown. Here, miRNA-164a transfection was used to overexpress miRNA-164a in U87, and then real-time quantitative PCR and Western blot were applied to detect the gene transcription and protein expression. In addition, MTT and wound healing assay were also used to observe cell proliferation and migration. Our data revealed that miRNA-146a was downregulated by TGF-β1 treatment, but upregulated by miRNA-164a transfection. MiRNA-146a overexpression significantly reduced SMAD4 protein expression instead of p-SMAD2. Besides, miRNA-146a overexpression also decreased the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9 as well as the p-ERK1/2 level. Furthermore, the upregulation of miRNA-146a suppressed TGF-β1-mediated U87 proliferation and migration. These results demonstrate that miRNA-146a acts as a novel regulator to modulate the activity and transduction of TGF-β signaling pathways in glioblastoma, and the downregulation of miRNA-146a is required for overexpression of EGFR and MMP9, which can be considered an efficiently therapeutic target and a better understanding of glioblastoma pathogenesis. | Glioblastoma;MiRNA-146a;Regulation;TGF-β Signaling | pubmed |
Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells. | Baicalein (BA), isolated from the Chinese medicinal herb Scutellariae radix (Huangqin in Chinese), is a flavonoid with various pharmacological effects. Herein, we found that BA only slightly reduced the cell viability on HepG2 cells after 24-h treatment as determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. However, BA (50 μM) effectively blocked the colony formation. Meanwhile, BA remarkably induced the formation of autophagosomes after 24-h treatment as determined by immunofluorescence with monodansylcadaverine staining as well as transmission electron microscopy, respectively. Moreover, BA obviously up-regulated the expression of microtubule-associated protein 1A/1B-light chain 3-II in concentration-dependent and time-dependent manners in HepG2 cells. When combined with the autophagy inhibitor chloroquine and BA, the cell viability and colony formation were significantly decreased, indicating that BA triggered protective autophagy, which prevented cell death. Further study showed that BA concentration-dependently and time-dependently decreased the expression of p-AKT (S473), p-ULK1 (S757) and p-4EBP1 (T37 and S65), suggesting the involvement of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) in BA-triggered autophagy. | AKT;ULK1;autophagy;baicalein;hepatocellular carcinoma | pubmed |
DNA electrochemical sensor for detection of PRSS1 point mutation based on restriction endonuclease technique. | To construct a restriction endonuclease based biosensor technology for PRSS1 genotyping. We designed a thiol-modified hairpin probe where the neck has EcoRI endonuclease recognition sites according to the PRSS1 gene c.410 C>T (p.T137 M) mutation and it was fixed on the gold electrode. Different charge generated by the binding of MB to phosphate groups of DNA before and after hybridization was used for distinguishing the different genotypes and quantity. This showed that the novel sensor can better distinguish the complementary sequence, single-base mismatches, and completely noncomplementary sequences, and the linear range for the logarithm was Y=-0.0242 X+0.1574, R=0.9912(Y=current, X=log target DNA concentration); the detection limit for DNA detection is estimated to be 50 fM. | DNA biosensors;digestion;genotyping;hairpin probe | pubmed |
Tibial Bone Strength is Enhanced in the Jump Leg of Collegiate-Level Jumping Athletes: A Within-Subject Controlled Cross-Sectional Study. | An efficient method of studying skeletal adaptation to mechanical loading is to assess side-to-side differences (i.e., asymmetry) within individuals who unilaterally exercise one side of the body. Within-subject controlled study designs have been used to explore skeletal mechanoadaptation at upper extremity sites; however, there is no established model in the lower extremities. The current study assessed tibial diaphysis and distal tibia asymmetry in collegiate-level jumping athletes (N = 12). To account for normal crossed asymmetry, data in jumping athletes were compared to asymmetry in a cohort of athletic controls not routinely exposed to elevated unilateral lower extremity loading (N = 11). Jumpers exhibited side-to-side differences between their jump and lead legs at both the tibial diaphysis and distal tibia, with differences at the former site persisting following comparison to dominant-to-nondominant leg differences in controls. In particular, jump-to-lead leg differences for cortical area and thickness at the tibial diaphysis in jumpers were 3.6% (95% CI 0.5-6.8%) and 3.5% (95% CI 0.4-6.6%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Similarly, jump-to-lead leg differences in jumpers for tibial diaphysis maximum second moment of area and polar moment of inertia were 7.2% (95% CI 1.2-13.2%) and 5.7% (95% CI 1.7-9.8%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Assessment of region-specific differences of the tibial diaphysis in jumpers indicated that the jump leg had greater pericortical radii on the medial and posterior sides and greater radial cortical thickness posteromedially when compared to the lead leg. These data suggest that athletes who perform repetitive and forceful unilateral jumping may be a useful and efficient within-subject controlled model for studying lower extremity skeletal mechanoadaptation. | Adaptation;Bone;Exercise;Mechanical loading;Physical activity;Tibia | pubmed |
Methods in plant foliar volatile organic compounds research. | Plants are a major atmospheric source of volatile organic compounds (VOCs). These secondary metabolic products protect plants from high-temperature stress, mediate in plant-plant and plant-insect communication, and affect our climate globally. The main challenges in plant foliar VOC research are accurate sampling, the inherent reactivity of some VOC compounds that makes them hard to detect directly, and their low concentrations. Plant VOC research relies on analytical techniques for trace gas analysis, usually based on gas chromatography and soft chemical ionization mass spectrometry. Until now, these techniques (especially the latter one) have been developed and used primarily by physicists and analytical scientists, who have used them in a wide range of scientific research areas (e.g., aroma, disease biomarkers, hazardous compound detection, atmospheric chemistry). The interdisciplinary nature of plant foliar VOC research has recently attracted the attention of biologists, bringing them into the field of applied environmental analytical sciences. In this paper, we review the sampling methods and available analytical techniques used in plant foliar VOC research to provide a comprehensive resource that will allow biologists moving into the field to choose the most appropriate approach for their studies. | gas chromatography–mass spectrometry (GC-MS);leaf cuvette;plant volatile organic compound (VOC);proton transfer reaction–mass spectrometry (PTR-MS);selected ion flow tube–mass spectrometry (SIFT-MS);thermal desorption–gas chromatography–mass spectrometry (TD-GC-MS) | pubmed |
Inter-study reproducibility of left ventricular torsion and torsion rate quantification using MR myocardial feature tracking. | To determine the inter-study reproducibility of MR feature tracking (MR-FT) derived left ventricular (LV) torsion and torsion rates for a combined assessment of systolic and diastolic myocardial function. Steady-state free precession (SSFP) cine LV short-axis stacks were acquired at 9:00 (Exam A), 9:30 (Exam B), and 14:00 (Exam C) in 16 healthy volunteers at 3 Tesla. SSFP images were analyzed offline using MR-FT to assess rotational displacement in apical and basal slices. Global peak torsion, peak systolic and peak diastolic torsion rates were calculated using different definitions ("twist", "normalized twist" and "circumferential-longitudinal (CL) shear angle"). Exam A and B were compared to assess the inter-study reproducibility. Morning and afternoon scans were compared to address possible diurnal variation. The different methods showed good inter-study reproducibility for global peak torsion (intraclass correlation coefficient [ICC]: 0.90-0.92; coefficient of variation [CoV]: 19.0-20.3%) and global peak systolic torsion rate (ICC: 0.82-0.84; CoV: 25.9-29.0%). Conversely, global peak diastolic torsion rate showed little inter-study reproducibility (ICC: 0.34-0.47; CoV: 40.8-45.5%). Global peak torsion as determined by the CL shear angle showed the best inter-study reproducibility (ICC: 0.90;CoV: 19.0%). MR-FT results were not measurably affected by diurnal variation between morning and afternoon scans (CL shear angle: 4.8 ± 1.4°, 4.8 ± 1.5°, and 4.1 ± 1.6° for Exam A, B, and C, respectively; P = 0.21). MR-FT based derivation of myocardial peak torsion and peak systolic torsion rate has high inter-study reproducibility as opposed to peak diastolic torsion rate. The CL shear angle was the most reproducible parameter independently of cardiac anatomy and may develop into a robust tool to quantify cardiac rotational mechanics in longitudinal MR-FT patient studies. | cardiovascular magnetic resonance;circumferential longitudinal shear angle;feature tracking;inter-study reproducibility;torsion;twist | pubmed |
Resistance exercise induces a greater irisin response than endurance exercise. | We determined detailed time-course changes in the irisin response to acute exercise using different exercise modes. In experiment 1, seven healthy males rested for 12h (8:00-20:00) to determine the diurnal variation in plasma irisin concentration. In experiment 2, 10 healthy males conducted three exercises to clarify time-course changes in plasma irisin concentration over 6h, using a randomized crossover design. The resistance exercise (R) trial consisted of eight exercises of 12 repetitions with 3-4 sets at 65% of one repetition maximum (1RM). The endurance exercise (E) trial consisted of 60 min of pedaling at 65% of maximal oxygen uptake (VO2max). In the combined mode (R+E) trial, 30 min of endurance exercise was preceded by 30 min of resistance exercise. In experiment 1, no significant changes in plasma irisin concentration were observed over 12h. In experiment 2, the R trial showed a marked increase in plasma irisin concentration 1h after exercise (P<0.05), but not in the E or R+E trials. The area under the curve (AUC) for irisin concentrations for 6h after exercise was significantly higher in the R trial than in the R+E trial (P<0.05). The AUC for irisin concentrations was significantly correlated with AUC values for blood glucose, lactate, and serum glycerol (r=0.37, 0.45, 0.45, respectively. P<0.05). Resistance exercise resulted in significantly greater irisin responses compared with endurance exercise alone, and resistance and endurance exercises combined. | Exercise mode;FNDC5;Irisin;PGC-1α;Time-course change | pubmed |
Antigenic validation of recombinant hemagglutinin-neuraminidase protein of Newcastle disease virus expressed in Saccharomyces cerevisiae. | The outer membrane glycoprotein, hemagglutinin-neuraminidase (HN) of Newcastle disease virus (NDV) is important for virus infection and subsequent immune response by host, and offers target for development of recombinant antigen-based immunoassays and subunit vaccines. In this study, the expression of HN protein of NDV is attempted in yeast expression system. Yeast offers eukaryotic environment for protein processing and posttranslational modifications like glycosylation, in addition to higher growth rate and easy genetic manipulation. Saccharomyces cerevisiae was found to be better expression system for HN protein than Pichia pastoris as determined by codon usage analysis. The complete coding sequence of HN gene was amplified with the histidine tag, cloned in pESC-URA under GAL10 promotor and transformed in Saccharomyces cerevisiae. The recombinant HN (rHN) protein was characterized by western blot, showing glycosylation heterogeneity as observed with other eukaryotic expression systems. The recombinant protein was purified by affinity column purification. The protein could be further used as subunit vaccine. | Newcastle disease virus; glycoprotein; codon usage; yeast expression. | pubmed |
Adaptation by macrophytes to inorganic carbon down a river with naturally variable concentrations of CO2. | The productivity and ecological distribution of freshwater plants can be controlled by the availability of inorganic carbon in water despite the existence of different mechanisms to ameliorate this, such as the ability to use bicarbonate. Here we took advantage of a short, natural gradient of CO2 concentration, against a background of very high and relatively constant concentration of bicarbonate, in a spring-fed river, to study the effect of variable concentration of CO2 on the ability of freshwater plants to use bicarbonate. Plants close to the source, where the concentration of CO2 was up to 24 times air equilibrium, were dominated by Berula erecta. pH-drift results and discrimination against (13)C were consistent with this and the other species being restricted to CO2 and unable to use the high concentration of bicarbonate. There was some indication from stable (13)C data that B. erecta may have had access to atmospheric CO2 at low water levels. In contrast, species downstream, where concentrations of CO2 were only about 5 times air-equilibrium were almost exclusively able to use bicarbonate, based on pH-drift results. Discrimination against (13)C was also consistent with bicarbonate being the main source of inorganic carbon for photosynthesis in these species. There was, therefore, a transect downstream from the source of increasing ability to use bicarbonate that closely matched the decreasing concentration of CO2. This was produced largely by altered species composition, but partly by phenotypic changes in individual species. | Bicarbonate;Fontaine de Vaucluse;Photosynthesis;River Sorgue;Stable carbon isotope | pubmed |
The Role of CDK4/6 Inhibition in Breast Cancer. | Imbalance of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may result in diversion away from a pathway to senescence and toward a more proliferative phenotype. Cancer cells may increase cyclin D-dependent activity through a variety of mechanisms. Therapeutic inhibition of CDKs in tumors to negate their evasion of growth suppressors has been identified as a key anticancer strategy. In this review, we outline the development of CDK inhibitory therapy in breast cancer, including the initial experience with the pan-CDK inhibitor flavopiridol and the next generation of oral highly selective CDK4 and CDK6 inhibitors PD0332991 (palbociclib), LEE011 (ribociclib), and LY2835219 (abemaciclib). Data from phase I and II studies in estrogen receptor-positive (ER+) breast cancer demonstrate promising efficacy with manageable toxic effects, chiefly neutropenia. We discuss these studies and the phase III studies that are accruing or nearing completion. We describe the application of such therapy to other breast cancer settings, including HER2-positive breast cancer and the adjuvant treatment of early breast cancer. We also discuss potential concerns surrounding the combination of CDK inhibitors with chemotherapy and their effects on repair of double-strand DNA breaks in cancer cells. Oral highly selective CDK inhibitors show great promise in improving the outcomes of patients with ER+ breast cancer, although caution must apply to their combination with other agents and in the early breast cancer setting. | Abemaciclib;Breast neoplasms;Flavopiridol;Inhibitors of cyclin-dependent kinase 4 proteins;LEE011;Palbociclib | pubmed |
Impulsivity and risky decision making among taxi drivers in Hong Kong: An event-related potential study. | Taxi drivers play an important role in providing safe and professional public transport services. However, they tend to be more involved than other professional driver groups in accidents caused by deliberate recklessness. This study used an event-related potential (ERP) experiment to examine risk-taking behavior arising from impulsivity by comparing the underlying neural processes of taxi drivers with and without traffic offence records in Hong Kong. A sample of 15 traffic offenders and 15 nonoffenders, matched by sociodemographic characteristics, was recruited. The results show that the offender group demonstrated significantly less negative-going (less negative) feedback-related negativity but more positive-going (more positive) feedback-related P300 when than with their nonoffending counterparts. These findings show that taxi drivers with traffic offence records were less sensitive to the consequences of behavior and more attuned to the magnitude of potential reward. In addition, behavioral data revealed that they were more willing to make risky decisions. All these characteristics pertain to impulsive personality traits. Based on these findings, we can conclude that the offenders in this sample were more impulsive than their nonoffending counterparts. | Event-related potentials;Impulsivity;Risk-taking behavior;Taxi driver;Traffic offence | pubmed |
Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer cells. | Osteopontin (OPN) is a phosphoprotein that activates several aspects of tumor progression. Alternative splicing of the OPN primary transcript generates three splicing isoforms, OPNa, OPNb and OPNc. In this report, we investigated some cellular mechanisms by which OPN splice variants could mediate PC3 prostate cancer (PCa) cell survival and growth in response to docetaxel (DXT)-induced cell death. Cell survival before and after DXT treatment was analyzed by phase-contrast microscopy and crystal-violet staining assays. Quantitative real-time PCR and immunocytochemical staining assays were used to evaluate the putative involvement of epithelial-mesenchymal transition (EMT) and OPN isoforms on mediating PC3 cell survival. Upon DXT treatment, PC3 cells overexpressing OPNb or OPNc isoforms showed higher cell densities, compared to cells overexpressing OPNa and controls. Notably, cells overexpressing OPNb or OPNc isoforms showed a downregulated pattern of EMT epithelial cell markers, while mesenchymal markers were mostly upregulated in these experimental conditions. We concluded that OPNc or OPNb overexpression in PC3 cells can mediate resistance and cell survival features in response to DXT-induced cell death. Our data also provide evidence the EMT program could be one of the molecular mechanisms mediating survival in OPNb- or OPNc-overexpressing cells in response to DXT treatment. These data could further contribute to a better understanding of the mechanisms by which PCa cells acquire resistance to DXT treatment. | Cell survival;Docetaxel;Osteopontin;Prostate cancer;Splicing isoforms | pubmed |
The phage Mu middle promoter Pm contains a partial UP element. | There are three phases of transcription during lytic development of bacteriophage Mu: early, middle, and late. Transcription from the middle phase promoter Pm requires the activator protein Mor. In the presence of Mor, transcription from Pm is carried out by the Escherichia coli RNA polymerase holoenzyme containing σ(70). A Mor dimer binds to two 5-bp inverted repeats within a 16-bp element centered at -43.5 in Pm, replacing the normal -35 element contacted by RNA polymerase (RNAP). In this study random and targeted mutagenesis of the sequence upstream (-88 to -52) of the Mor binding site was performed to determine whether Pm also contains an UP element for binding of the RNAP α subunit, thereby stimulating transcription. The results demonstrated that mutations upstream of -57 had no effect on Pm activity in vivo, assayed by expression of lacZ fused downstream of a wild-type or mutant Pm. Mutations at positions -57 through -52 led to decreased transcription from Pm, consistent with the presence of an UP element. In DNase I footprinting and gel mobility shift assays, paired mutations at positions -55 and -54 did not affect Mor binding but decreased the synergistic binding of Mor with histidine tagged α (His-α), indicating that His-α binds to Pm in a sequence- and/or structure-specific manner. Taken together, these results demonstrate that Pm has a strong proximal UP element subsite, but lacks a distal subsite. | Mu promoter Pm;UP element;bacteriophage Mu;prokaryotic transcription;regulation of gene expression | pubmed |
Management of hepatocellular carcinoma with portal vein thrombosis. | Management of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) is complex and requires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival. | Hepatocellular carcinoma;Management;Portal vein thrombosis;Selective internal radiation therapy;Yttrium 90 | pubmed |
Compact tomato seedlings and plants upon overexpression of a tomato chromatin remodelling ATPase gene. | Control of plant growth is an important aspect of crop productivity and yield in agriculture. Overexpression of the AtCHR12/23 genes in Arabidopsis thaliana reduced growth habit without other morphological changes. These two genes encode Snf2 chromatin remodelling ATPases. Here, we translate this approach to the horticultural crop tomato (Solanum lycopersicum). We identified and cloned the single tomato ortholog of the two Arabidopsis Snf2 genes, designated SlCHR1. Transgenic tomato plants (cv. Micro-Tom) that constitutively overexpress the coding sequence of SlCHR1 show reduced growth in all developmental stages of tomato. This confirms that SlCHR1 combines the functions of both Arabidopsis genes in tomato. Compared to the wild type, the transgenic seedlings of tomato have significantly shorter roots, hypocotyls and reduced cotyledon size. Transgenic plants have a much more compact growth habit with markedly reduced plant height, severely compacted reproductive structures with smaller flowers and smaller fruits. The results indicate that either GMO-based or non-GMO-based approaches to modulate the expression of chromatin remodelling ATPase genes could develop into methods to control plant growth, for example to replace the use of chemical growth retardants. This approach is likely to be applicable and attractive for any crop for which growth habit reduction has added value. | SWI/SNF2;chromatin remodelling;growth;plant habit;tomato | pubmed |
Abnormalities of vascular structure and function in pediatric hypertension. | Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage. | Arterial stiffness;Carotid artery;Hypertension;Pediatric | pubmed |
Relative Lability and Chemoselective Transmetallation of NHC in Hybrid Phosphine-NHC Ligands: Access to Heterometallic Complexes. | The relative lability and transmetallation aptitude of trialkylphosphine and NHC donors, integrated in semi-rigid hybrid ligands attached to [Ag4Br4] pseudo-cubanes, lies in favor of the NHC and is used to selectively access unprecedented NHC complexes with heterobimetallic cores, such as Ag-Cu (4(Cy)) and Ag-Ir (5(tBu)). These can be viewed as an arrested state before the full transmetallation of both donors, which gives the homodinuclear Cu (3(Cy)) and Ir (6(Cy)) complexes. The observed NHC transmetallation aptitude and reactivity urges caution in the common notion that views the NHC as a universal spectator. | N-heterocyclic carbene;chemoselectivity;hybrid ligands;phosphines;transmetallation | pubmed |
Position-specific isotope modeling of organic micropollutants transformation through different reaction pathways. | The degradation of organic micropollutants occurs via different reaction pathways. Compound specific isotope analysis is a valuable tool to identify such degradation pathways in different environmental systems. We propose a mechanism-based modeling approach that provides a quantitative framework to simultaneously evaluate concentration as well as bulk and position-specific multi-element isotope evolution during the transformation of organic micropollutants. The model explicitly simulates position-specific isotopologues for those atoms that experience isotope effects and, thereby, provides a mechanistic description of isotope fractionation occurring at different molecular positions. To demonstrate specific features of the modeling approach, we simulated the degradation of three selected organic micropollutants: dichlorobenzamide (BAM), isoproturon (IPU) and diclofenac (DCF). The model accurately reproduces the multi-element isotope data observed in previous experimental studies. Furthermore, it precisely captures the dual element isotope trends characteristic of different reaction pathways as well as their range of variation consistent with observed bulk isotope fractionation. It was also possible to directly validate the model capability to predict the evolution of position-specific isotope ratios with available experimental data. Therefore, the approach is useful both for a mechanism-based evaluation of experimental results and as a tool to explore transformation pathways in scenarios for which position-specific isotope data are not yet available. | CSIA;Isotope modeling;Organic micropollutants;Position-specific isotope fractionation;Transformation pathways | pubmed |
Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes. | In biology, redox reactions are essential and sometimes harmful, and therefore, iron metabolism is tightly regulated by cuproproteins. Since the state of copper in iron overload syndromes remains unclear, we investigated whether copper metabolism is altered in these syndromes. Eleven patients with iron overload syndromes participated in this study. The clinical diagnoses were aceruloplasminemia (n=2), hemochromatosis (n=5), ferroportin disease (n=2), and receiving excess intravenous iron supplementation (n=2). Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer. In addition to a large amount of iron associated with oxygen and phosphorus, the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur, regardless of disease etiology. Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins. Copper stasis was unlikely in noncirrhotic patients. The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins. In conclusion, we have demonstrated that copper accumulates in hemosiderins in iron overload conditions, perhaps due to alterations in copper metabolism. | Aceruloplasminemia;Cuproprotein induction;Ferroportin disease;Hemochromatosis;Hemosiderin;Iron copper interaction;Iron overload syndromes | pubmed |
The effect of ascorbic acid on the photophysical properties and photodynamic therapy activities of zinc phthalocyanine-single walled carbon nanotube conjugate on MCF-7 cancer cells. | Zinc mono carboxy phenoxy phthalocyanine (1) was chemical modified with ascorbic acid via an ester bond to give ZnMCPPc-AA (2). Complexes 2 and 1 were coordinated to single walled carbon nanotubes via π-π interaction to give ZnMCPPc-AA-SWCNT (3) and ZnMCPPc-SWCNT (4) respectively. Complexes 2, 3 and 4 showed better photophysical properties: with improved triplet lifetimes and quantum yields, and singlet oxygen quantum yields when compared to 1 alone. The photodynamic therapy activities of complexes 1, 2, 3 and 4 were tested in vitro on MCF-7 breast cancer cells. Ascorbic acid suppresses the photodynamic therapy effect of 1, due to its ability to reduce oxidative DNA damage as a result of its potent reducing properties. The highest phototoxicity was observed for 4 which resulted in 77% decrease in cell viability, followed by 3 which resulted in 67% decrease in cell viability. This shows the importance of combination therapy, where the phthalocyanines are the photodynamic therapy agents and single walled carbon nanotubes are the photothermal therapy agents. | Ascorbic acid;Photodynamic therapy;Single walled carbon nanotubes;Singlet oxygen quantum yield;Zinc carboxy phenoxy phthalocyanine | pubmed |
Healthcare Coordination and Transition for Individuals with Genetic Conditions. | This study aimed to examine insurance coverage, use of the healthcare system, satisfaction with care, transition from pediatric to adult healthcare services, and social and emotional support for individuals with genetic conditions. In June 2013, the National Genetics Education and Consumer Network surveyed US individuals with genetic conditions about their healthcare experiences. Chi square statistics were used to compare use of the healthcare system, satisfaction, social and emotional support of children (0-17 years) and adults (18 + years) with genetic conditions. There were 1895 valid responses (53.0 % individuals with genetic conditions, 47.0 % parents of these individuals). The findings suggest several potential areas to impact the quality of care received by this population. The majority of respondents reported that they had: (1) more than one health professional they considered to be their personal doctor or nurse (70.5 % children; 57.8 % adults); (2) providers that listened carefully to their needs always or most of the time (82.2 % children; 83.5 % adults); and (3) providers that usually or always involved them as partners in their care (78.4 % children; 66.6 % adults). However, several significant differences around care and support received between children versus adults and areas of need were reported. Most persons surveyed received care from a system of providers that was self- or parent- coordinated and lacked sufficient social and emotional support. Data from this study will inform practice and identifies further research needed to improve care provided to individuals with genetic conditions who require a combination of specialty and primary care. | Access;Care coordination;Genetic condition;Genetics;Transition | pubmed |
Measuring and mitigating agricultural greenhouse gas production in the US Great Plains, 1870-2000. | The Great Plains region of the United States is an agricultural production center for the global market and, as such, an important source of greenhouse gas (GHG) emissions. This article uses historical agricultural census data and ecosystem models to estimate the magnitude of annual GHG fluxes from all agricultural sources (e.g., cropping, livestock raising, irrigation, fertilizer production, tractor use) in the Great Plains from 1870 to 2000. Here, we show that carbon (C) released during the plow-out of native grasslands was the largest source of GHG emissions before 1930, whereas livestock production, direct energy use, and soil nitrous oxide emissions are currently the largest sources. Climatic factors mediate these emissions, with cool and wet weather promoting C sequestration and hot and dry weather increasing GHG release. This analysis demonstrates the long-term ecosystem consequences of both historical and current agricultural activities, but also indicates that adoption of available alternative management practices could substantially mitigate agricultural GHG fluxes, ranging from a 34% reduction with a 25% adoption rate to as much as complete elimination with possible net sequestration of C when a greater proportion of farmers adopt new agricultural practices. | Great Plains;agricultural management;biogeochemistry;greenhouse gases;modeling | pubmed |
SHH inhibitors for the treatment of medulloblastoma. | Medulloblastoma is the most common malignant brain tumor of childhood. It is currently stratified into four molecular variants through the advances in transcriptional profiling. They include: wingless, sonic hedgehog (SHH), Group III, and Group IV. The SHH group is characterized by constitutive activation of the SHH signaling pathway, and genetically characterized by mutations in patched homolog 1 (PTCH1) or other downstream pathway mutations. SHH inhibitors have become of great clinical interest in treating SHH-driven medulloblastoma. Many inhibitors are currently in different stages of development, some already approved for other SHH-driven cancers, such as basal cell carcinoma. In vitro and in vivo medulloblastoma studies have shown efficacy and these findings have been translated into Phase I and II clinical trials. In this review, we present an overview of SHH medulloblastoma, as well as a discussion of currently available SHH inhibitors, and the challenges associated with their use. | basal cell carcinoma;gorlin syndrome;medulloblastoma;smoothened;sonic hedghog;vismodegib | pubmed |
Pro: Should we move to more frequent haemodialysis schedules? | Most end-stage renal disease patients on maintenance haemodialysis follow the typical schedule of three sessions per week, and thus remain outside dialysis for two short intervals (∼2 days in duration) and for a longer interval (∼3 days) at the end of each week. This pattern was historically enforced more due to calendar logistics and less due to factors related to health and disease. Therefore, it is long hypothesized that the intermittent nature of haemodialysis and the consequent shifts and fluctuations in volume status and metabolic parameters during the dialysis-free periods may pre-dispose patients to several complications. Recent large-scale observational studies in haemodialysis patients link the first week-day (including the last hours of the long interval and the subsequent dialysis session) with increased risk of cardiovascular morbidity and mortality. Previous observational studies support that enhanced-frequency home haemodialysis is associated with reduced risk of all-cause mortality, while randomized studies suggest that short-daily or alternate-day in-centre haemodialysis offer improvements in left ventricular hypertrophy, blood pressure, phosphorous homeostasis and other intermediate end points when compared with conventional thrice-weekly in-centre haemodialysis. This article summarizes available evidence relating long inter-dialytic intervals with elevated cardiovascular risk, potential mechanisms for this association and the main benefits of more frequent dialytic modalities. | alternate-day dialysis;frequent dialysis;long inter-dialytic interval;morbidity;mortality | pubmed |
Mortality and major adverse cardiovascular events after transcatheter aortic valve replacement using Edwards valve versus CoreValve: A meta-analysis. | In patients with severe aortic stenosis who are at high risk for surgery, transcatheter aortic valve replacement (TAVR) has emerged as an alternative procedure using EV or CV. The objective of this meta-analysis is to compare 1-year mortality and major adverse cardiovascular and cerebrovascular events (MACCE) between Edwards valve (EV) and Medtronic CoreValve (CV). PubMed and the Cochrane Center Register of Controlled Trials were searched through December 2014. Twenty seven studies (n=12,249) comparing TAVR procedure that used EV (n=5745) and CV (n=6504) were included. End points were procedural success rates, post-procedural mortality, myocardial infarction (MI), stroke, major bleeding, major vascular complications, incidence of new permanent pacemaker (PPM) placement and new left bundle branch block (LBBB). The odds ratio (OR) with 95% confidence interval (CI) was computed and p<0.05 was considered for significance. There were no significant differences between EV and CV for post-procedural in-hospital, 30-day and 1-year all-cause mortality rates (p=0.53, 0.33 and 0.94 respectively), cardiovascular mortality (p=0.61), stroke (p=0.54), major bleeding (p=0.25) and major vascular complications (p=0.27). MI was significantly lower with EV compared to CV (OR: 0.56, CI: 0.35-0.89, p=0.01). Placement of new PPM and new onset LBBB were significantly higher in CV compared to EV (OR: 3.35, CI: 2.96-3.79, p<0.00001 and OR: 6.55, CI: 4.76-9.03, p<0.00001 respectively). The results of our meta-analysis suggest that TAVR procedure using CV may be associated with a higher incidence of MI, new PPM placement, and new onset LBBB compared to EV. However, the type of valve placed does not affect mortality. | CoreValve;Edwards valve;Major adverse cardiovascular and cerebrovascular events;Transcatheter aortic valve replacement | pubmed |
Temporal and spatial limits of pattern motion sensitivity in macaque MT neurons. | Many neurons in visual cortical area MT signal the direction of motion of complex visual patterns, such as plaids composed of two superimposed drifting gratings. To compute the direction of pattern motion, MT neurons combine component motion signals over time and space. To determine the spatial and temporal limits of signal integration, we measured the responses of single MT neurons to a novel set of "pseudoplaid" stimuli in which the component gratings were alternated in time or space. As the temporal or spatial separation of the component gratings increased, neuronal selectivity for the direction of pattern motion decreased. Using descriptive models of signal integration, we inferred the temporal and spatial structure of the mechanisms that compute pattern direction selectivity. The median time constant for integration was roughly 10 ms, a timescale characteristic of integration by single cortical pyramidal neurons. The median spatial integration field was roughly one-third of the MT receptive field diameter, suggesting that the spatial limits are set by stages of processing in earlier areas of visual cortex where receptive fields are smaller than in MT. Interestingly, pattern direction-selective neurons had shorter temporal integration times than component direction-selective neurons but similar spatial integration windows. We conclude that pattern motion can only be signaled by MT neurons when the component motion signals co-occur within relatively narrow spatial and temporal limits. We interpret these results in the framework of recent hierarchical models of MT. | extrastriate visual cortex;macaques;neural dynamics;receptive fields;visual motion processing | pubmed |
Sensory gating in subjects at ultra high risk for developing a psychosis before and after a first psychotic episode. | To explore sensory gating deficits in subjects at Ultra High Risk (UHR) for psychosis before and after transition to a first psychotic episode. Sensory gating was assessed with the paired click paradigm in 61 UHR subjects, of whom 18 (30%) made a transition to psychosis (UHR + T) over a 3-year follow-up period and 28 matched healthy controls. Subjects were assessed at inclusion and again after approximately 18 months. P50, N100 (N1) and P200 (P2) sensory gating was established using the amplitude on the first (S1) and second (S2) click, the ratio- (S2/S1) and the difference score (S1-S2). Psychopathology was also assessed. At baseline, UHR + T subjects presented smaller N1 difference scores compared to UHR + NT subjects and controls. The N1 difference score contributed modestly to the prediction of a first psychotic episode. Repeated measure analyses revealed smaller N1 and P2 S1 amplitudes, smaller P2 difference scores and larger P2 ratio's at follow-up compared to baseline in UHR + T subjects. The N1 difference score may be helpful in predicting a first psychosis. N1 and P2 sensory gating measures also showed alterations between the prodromal phase and the first psychosis, suggesting that these changes may relate to the onset of a frank psychotic episode. | Ultra High Risk subjects;psychopathology;psychosis prediction;schizophrenia;sensory gating | pubmed |
Dinitrogen fixation by legume shade trees and direct transfer of fixed N to associated cacao in a tropical agroforestry system. | Natural abundance of (15)N (δ (15)N) was determined in bulk soil, rhizospheric soil and vegetation in an organically managed cacao (Theobroma cacao L.) plantation with Inga edulis Mart. legume trees (inga) as the principal shade for studying the nitrogen (N) cycle in the system. Cacao without contact with legumes in an adjacent plantation was used as the reference for N2 fixation and direct N transfer calculations. Bulk and rhizospheric soils contained 72 and 20%, respectively, of whole- system N. No vegetation effect on δ (15)N in rhizospheric soil was detected, probably due to the high native soil N pool. Fine roots of the cacaos associated with inga contained ∼35% of N fixed from the atmosphere (Nf) out of the total N. Leaves of all species had significantly higher δ (15)N than fine roots. Twenty percent of system Nf was found in cacao suggesting direct N transfer from inga via a common mycelial network of mycorrhizal fungi or recycling of N-rich root exudates of inga. Inga had accumulated 98 kg [Nf] ha(-1) during the 14-year history of the plantation. The conservative estimate of current N2 fixation rate was 41 kg [Nf] ha(-1) year(-1) based on inga biomass only and 50 kg [Nf] ha(-1) year(-1) based on inga and associated trees. | 15N natural abundance;Inga edulis;N cycle;Theobroma cacao;isotopic fractionation;rhizosphere | pubmed |
Analogous synaptic plasticity profiles emerge from disparate channel combinations. | An open question within the Bienenstock-Cooper-Munro theory for synaptic modification concerns the specific mechanism that is responsible for regulating the sliding modification threshold (SMT). In this conductance-based modeling study on hippocampal pyramidal neurons, we quantitatively assessed the impact of seven ion channels (R- and T-type calcium, fast sodium, delayed rectifier, A-type, and small-conductance calcium-activated (SK) potassium and HCN) and two receptors (AMPAR and NMDAR) on a calcium-dependent Bienenstock-Cooper-Munro-like plasticity rule. Our analysis with R- and T-type calcium channels revealed that differences in their activation-inactivation profiles resulted in differential impacts on how they altered the SMT. Further, we found that the impact of SK channels on the SMT critically depended on the voltage dependence and kinetics of the calcium sources with which they interacted. Next, we considered interactions among all the seven channels and the two receptors through global sensitivity analysis on 11 model parameters. We constructed 20,000 models through uniform randomization of these parameters and found 360 valid models based on experimental constraints on their plasticity profiles. Analyzing these 360 models, we found that similar plasticity profiles could emerge with several nonunique parametric combinations and that parameters exhibited weak pairwise correlations. Finally, we used seven sets of virtual knock-outs on these 360 models and found that the impact of different channels on the SMT was variable and differential. These results suggest that there are several nonunique routes to regulate the SMT, and call for a systematic analysis of the variability and state dependence of the mechanisms underlying metaplasticity during behavior and pathology. | BCM plasticity rule;hippocampus;homeostasis;ion channels;metaplasticity;synaptic plasticity | pubmed |
Potential of copper-tolerant grasses to implement phytostabilisation strategies on polluted soils in South D. R. Congo : Poaceae candidates for phytostabilisation. | Phytostabilisation (i.e. using plants to immobilise contaminants) represents a well-known technology to hamper heavy metal spread across landscapes. Southeastern D.R. Congo, Microchloa altera, a tolerant grass from the copper hills, was recently identified as a candidate species to stabilise copper in the soil. More than 50 grasses compose this flora, which may be studied to implement phytostabilisation strategies. However, little is known about their phenology, tolerance, reproductive strategy or demography. The present study aims to characterize the Poaceae that may be used in phytostabilisation purposes based on the following criteria: their ecological distribution, seed production at two times, abundance, soil coverage and the germination percentage of their seeds. We selected seven perennial Poaceae that occur on the copper hills. Their ecological distributions (i.e. species response curves) have been modelled along copper or cobalt gradients with generalised additive models using logic link based on 172 presence-absence samples on three sites. For other variables, a total of 69 quadrats (1 m(2)) were randomly placed across three sites and habitats. For each species, we compared the number of inflorescence-bearing stems (IBS) by plot, the percentage of cover, the number of seeds by IBS and the estimated number of seeds by plot between sites and habitat. Three species (Andropogon schirensis, Eragrostis racemosa and Loudetia simplex) were very interesting for phytostabilisation programs. They produced a large quantity of seeds and had the highest percentage of cover. However, A. schirensis and L. simplex presented significant variations in the number of seeds and the percentage of cover according to site. | Cobalt;Copper;Cover;Generalised additive model;Poaceae;Seed production;Species response curve | pubmed |
P450s and UGTs: Key Players in the Structural Diversity of Triterpenoid Saponins. | The recent spread of next-generation sequencing techniques has facilitated transcriptome analyses of non-model plants. As a result, many of the genes encoding enzymes related to the production of specialized metabolites have been identified. Compounds derived from 2,3-oxidosqualene (the common precursor of sterols, steroids and triterpenoids), a linear compound of 30 carbon atoms produced through the mevalonate pathway, are called triterpenes. These include essential sterols, which are structural components of biomembranes; steroids such as the plant hormones, brassinolides and the toxin in potatoes, solanine; as well as the structurally diverse triterpenoids. Triterpenoids containing one or more sugar moieties attached to triterpenoid aglycones are called triterpenoid saponins. Triterpenoid saponins have been shown to have various medicinal properties, such as anti-inflammatory, anticancerogenic and antiviral effects. This review summarizes the recent progress in gene discovery and elucidates the biochemical functions of biosynthetic enzymes in triterpenoid saponin biosynthesis. Special focus is placed on key players in generating the structural diversity of triterpenoid saponins, cytochrome P450 monooxygenases (P450s) and the UDP-dependent glycosyltransferases (UGTs). Perspectives on further gene discovery and the use of biosynthetic genes for the microbial production of plant-derived triterpenoid saponins are also discussed. | Biosynthesis;Cytochrome P450 monooxygenase;Oxidosqualene cyclase;Plant specialized metabolites;Triterpenoid saponin;UDP-dependent glycosyltransferase | pubmed |
Identification of novel post-translational modifications in linker histones from chicken erythrocytes. | Chicken erythrocyte nuclei were digested with micrococcal nuclease and fractionated by centrifugation in low-salt buffer into soluble and insoluble fractions. Post-translational modifications of the purified linker histones of both fractions were analyzed by LC-ESI-MS/MS. All six histone H1 subtypes (H1.01, H1.02, H1.03, H1.10, H1.1L and H1.1R) and histone H5 were identified. Mass spectrometry analysis enabled the identification of a wide range of PTMs, including N(α)-terminal acetylation, acetylation, formylation, phosphorylation and oxidation. A total of nine new modifications in chicken linker histones were mapped, most of them located in the N-terminal and globular domains. Relative quantification of the modified peptides showed that linker histone PTMs were differentially distributed among both chromatin fractions, suggesting their relevance in the regulation of chromatin structure. The analysis of our results combined with previously reported data for chicken and some mammalian species showed that most of the modified positions were conserved throughout evolution, highlighting their importance in specific linker histone functions and epigenetics. Post-translational modifications of linker histones could have a role in the regulation of gene expression through the modulation of chromatin higher-order structure and chromatin remodeling. Finding new PTMs in linker histones is the first step to elucidate their role in the histone code. In this manuscript we report nine new post-translational modifications of the linker histones from chicken erythrocytes, one in H5 and eight in the H1 subtypes. Chromatin fractionated by centrifugation in low-salt buffer resulted in two fractions with different contents and compositions of linker histones and enriched in specific core histone PTMs. Of particular interest is the fact that linker histone PTMs were differentially distributed in both chromatin fractions, suggesting specific functions. Future studies are needed to establish the interplay between PTMs of linker and core histones in order to fully understand chromatin regulation. A protein sequence alignment summarizing the PTMs found to date in chicken, mouse, rat and humans showed that, while many of the modified positions were conserved between these species, the type of modification often varied depending on the species or the cellular type. This finding suggests an important role for the PTMs in the regulation of linker histone functions. | Chicken erythrocyte;Chromatin fractionation;Epigenetics;Linker histone PTMs;Mass spectrometry | pubmed |
Long-term independent brain-computer interface home use improves quality of life of a patient in the locked-in state: a case study. | Despite intense brain-computer interface (BCI) research for >2 decades, BCIs have hardly been established at patients' homes. The current study aimed at demonstrating expert independent BCI home use by a patient in the locked-in state and the effect it has on quality of life. In this case study, the P300 BCI-controlled application Brain Painting was facilitated and installed at the patient's home. Family and caregivers were trained in setting up the BCI system. After every BCI session, the end user indicated subjective level of control, loss of control, level of exhaustion, satisfaction, frustration, and enjoyment. To monitor BCI home use, evaluation data of every session were automatically sent and stored on a remote server. Satisfaction with the BCI as an assistive device and subjective workload was indicated by the patient. In accordance with the user-centered design, usability of the BCI was evaluated in terms of its effectiveness, efficiency, and satisfaction. The influence of the BCI on quality of life of the end user was assessed. At the patient's home. A 73-year-old patient with amyotrophic lateral sclerosis in the locked-in state. Not applicable. The BCI has been used by the patient independent of experts for >14 months. The patient painted in about 200 BCI sessions (1-3 times per week) with a mean painting duration of 81.86 minutes (SD=52.15, maximum: 230.41). BCI improved quality of life of the patient. In most of the BCI sessions the end user's satisfaction was high (mean=7.4, SD=3.24; range, 0-10). Dissatisfaction occurred mostly because of technical problems at the beginning of the study or varying BCI control. The subjective workload was moderate (mean=40.61; range, 0-100). The end user was highy satisfied with all components of the BCI (mean 4.42-5.0; range, 1-5). A perfect match between the user and the BCI technology was achieved (mean: 4.8; range, 1-5). Brain Painting had a positive impact on the patient's life on all three dimensions: competence (1.5), adaptability (2.17) and self-esteem (1.5); (range: -3 = maximum negative impact; 3 maximum positive impact). The patient had her first public art exhibition in July 2013; future exhibitions are in preparation. Independent BCI home use is possible with high satisfaction for the end user. The BCI indeed positively influenced quality of life of the patient and supports social inclusion. Results demonstrate that visual P300 BCIs can be valuable for patients in the locked-in state even if other means of communication are still available (eye tracker). | Amyotrophic lateral sclerosis;Brain-computer interfaces;Locked-in syndrome;Quality of life;Rehabilitation | pubmed |
Prognostic value of the second ictal intracranial pattern for the outcome of epilepsy surgery. | To investigate the prognostic value of the second ictal pattern (SIP) that follows the first ictal pattern (FIP) seen at seizure onset in order to predict seizure control after epilepsy surgery. SIPs were analysed in 344 electro-clinical and subclinical seizures recorded with intracranial electrodes in 63 patients. SIPs were classified as (a) electrodecremental event (EDE); (b) fast activity (FA); (c) runs of spikes; (d) spike-wave activity; (e) sharp waves; (f) alpha activity; (g) delta activity and (h) theta activity. Engel surgical outcome scale was used. The mean follow-up period was 42.1 months (SD=30.1). EDE was the most common SIP seen (41%), followed by FA (19%), spike-wave activity (18%), alpha activity (8%), sharp-wave activity (8%), delta activity (3%), runs of spikes (2%) and theta activity (2%). EDE as SIP was associated with favourable outcome when compared with FA (p=0.0044) whereas FA was associated with poor outcome when compared with any other pattern (p=0.0389). FA as SIP tends to occur after EDE (75%) whereas EDE tends to evolve from a FIP containing FA (77%). SIP extent was focal in 46% of patients, lobar in 24%, multilobar in 14% and bilateral in 16%. There is a gradual decrease in the proportion of Engel grade I with the extent of SIP. Focal and delayed (in temporal lobe epilepsy) SIPs appear to be associated with better outcome. As SIP, EDE was associated with favourable surgical outcome whereas FA was associated with poor outcome, probably because outcome is dominated by FIP. EDE as SIP should not discourage surgery. However, FA as SIP should be contemplated with caution. SIP focality and latency can have prognostic value in epilepsy surgery. | Epilepsy;Epilepsy surgery;Intracranial EEG;Invasive recordings;Second ictal pattern;Surgical outcome | pubmed |
Optimizing Performance in Adult Cochlear Implant Users through Clinician Directed Auditory Training. | Clinician-directed auditory training using the KTH Speech Tracking Procedure can be a powerful approach for maximizing outcomes with adult cochlear implant (CI) users. This article first reviews prior research findings from an 8-week clinician-directed auditory training (AT) program using speech tracking that yielded significant gains in speech tracking rate and sentence recognition scores following training. The second focus of the article is to illustrate the value of intensive face-to-face long-term AT using speech tracking with adult CI users. A detailed case study report is presented that demonstrates major ongoing and progressive gains in tracking rate, sentence recognition, and improvements in self-perceived competence and confidence over the course of intensive long-term training. Given the potential of both short- and long-term clinician-directed auditory training via KTH speech tracking to help CI users reach their optimal performance level, consideration for more widespread clinical use is proposed in the overall rehabilitation of adult CI users. | Auditory training;aural rehabilitation;cochlear implants;speech tracking | pubmed |
Enrichment of committed human nucleus pulposus cells expressing chondroitin sulfate proteoglycans under alginate encapsulation. | Intervertebral disc (IVD) degeneration is associated with a malfunction of the nucleus pulposus (NP). Alginate culturing provides a favorable microenvironment for the phenotypic maintenance of chondrocyte-like NP cells. However, NP cells are recently evidenced to present heterogeneous populations, including progenitors, fibroblastic cells and primitive NP cells. The aim of this study is to profile the phenotypic changes of distinct human NP cells populations and describe the dynamic expression of chondroitin sulfate glycosaminoglycans (CS-GAGs) in extended alginate encapsulation. Non-degenerated (ND-NPC) and degenerated (D-NPC) NP cells were expanded in monolayers, and subject to 28-day culture in alginate after serial passaging. CS-GAG compositional expression in monolayer-/alginate-cultured NP cells was evaluated by carbohydrate electrophoresis. Cellular phenotypic changes were assessed by immunologic detection and gene expression analysis. Relative to D-NPC, ND-NPC displayed remarkably higher expression levels of chondroitin-4-sulfate GAGs over the 28-day culture. Compared with monolayer culture, ND-NPC showed increased NP marker expression of KRT18, KRT19, and CDH2, as well as chondrocyte markers SOX9 and MIA in alginate culture. In contrast, expression of fibroblastic marker COL1A1, COL3A1, and FN1 were reduced. Interestingly, ND-NPC showed a loss of Tie2+ but gain in KRT19+/CD24+ population during alginate culture. In contrast, D-NPC showed more consistent expression levels of NP surface markers during culture. We demonstrate for the first time that extended alginate culture selectively enriches the committed NP cells and favors chondroitin-4-sulfate proteoglycan production. These findings suggest its validity as a model to investigate IVD cell function. | Alginate;Chondroitin sulfate;Intervertebral disc degeneration;Nucleus pulposus;Proteoglycan | pubmed |
Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses. | Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period. Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory. Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations. Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness. | Cognition;help-seeking;neuropsychology;prodrome;psychosis/bipolar | pubmed |
Transcanal endoscopic resection for leiomyoma of the external auditory canal and a review of the literature. | Leiomyoma usually originates from the uterus and alimentary tract, but in extremely rare cases leiomyoma can appear in the external auditory canal. Here we present a 37-year-old man with right auricular fullness. Preoperative findings suggested benign tumor or cholesteatoma in the right external auditory canal. We performed total resection using an endoauricular approach with transcanal endoscopic ear surgery. Histopathological and immunohistochemistry examination confirmed the diagnosis of leiomyoma of external auditory canal. Leiomyoma arising from soft tissue, including that in the external auditory canal, is classified into two types: that from the arrectores pilorum muscles and that from the muscle coats of blood vessels. Only four cases of leiomyoma of external auditor canal have been published in the English literature. The other four cases demonstrated vascular leiomyomas. This is the first report of leiomyoma of the EAC arising from arrectores pilorum muscles. | Arrectores pilorum muscles;Auricular fullness;External auditory canal;Leiomyoma;Transcanal endoscopic ear surgery | pubmed |
A retrospective study: Factors associated with the risk of abdominal aortic aneurysm rupture. | Literature regarding pharmacological manipulation of aneurysm development and progression is abundant; however studies looking at preventing rupture are sparse. Moreover, best medical therapy is ill-instituted, and continued in this high-risk cohort. This paper aims to identify factors which affect the risk of AAA-rupture. A retrospective review of patients undergoing non-screen detected AAA-repair at a single tertiary-referral centre was performed. Age, cardiovascular history, medication use and the nature of surgical repair (elective or emergency) were converted to binary characteristics and a binomial logistic regression performed. We included 315 admissions for ruptured AAA, and 668 referrals for elective repair of large aneurysms (n=983). Multifactorial analysis showed that the cohort which was prescribed statins experienced fewer ruptured AAA ([OR] 0.50, [95% CI] 0.32-0.77). Factors associated with increased risk of rupture include female gender (2.49, 1.63-3.80), history of hypertension (3.5, 1.6-3.8) or renal failure (8.08, 4.15-15.4), age over 80 (2.77, 1.79-4.27) and current smoking (1.80, 1.09-2.96). This is the largest study, interrogating individual patient data, to suggest an association between statins and prevention of large AAA-rupture. As patients with AAA are at high risk of cardiovascular events, and statins may decrease the risk of the devastating consequence of the condition, healthcare teams should maintain pharmaco-vigilance in instituting and continuing best medical therapy, including a statin. | AAA rupture risk;Risk factor;Statin therapy | pubmed |
Development of a reduced-graphene-oxide based superparamagnetic nanocomposite for the removal of nickel (II) from an aqueous medium via a fluorescence sensor platform. | Reduced-graphene-oxide based superparamagnetic nanocomposite (GC) was fabricated and applied for the remediation of Ni(II) from an aqueous medium. The as-prepared GC was extensively characterized by Raman, TEM, AFM, SEM-EDX, SQUID, and BET analyses. Quantitative immobilization of Ni(II) in an aqueous solution by the fluorescent sensor platform of GC was explored at varying pH, doses, contact times, and temperatures. The pseudo-second-order kinetics equation governed the overall sorption process at optimized pH of 5 (±0.2). The superior monolayer sorption capacity was 228mgg(-1) at 300K. Negative ΔG(0) indicated the spontaneous sorption nature, whereas the positive ΔH(0) resulted from an increase in entropy (positive ΔS(0)) at the solid-liquid interface during the endothermic reaction. The lower enthalpy agreed with the relatively high regeneration (approximately 91%) of the GC by 0.1M HCl, because of the formation of stable tetrahedral complex. The physisorption was well corroborated by calculated sorption energy (EDR ∼7kJmol(-1)) and the nature of the Stern-Volmer plot of the fluorescence-quenching data with reaction time. The GC played a pivotal role as a static fluorescent sensor platform (fluorophore) for Ni(II) adsorption. Magnetic property also indicated that GC could be easily separated from fluids by exploiting its superparamagnetic property. | Adsorption;Fluorescence sensing technology;Magnetic separation;Water purification | pubmed |
Chronic pesticide exposure: Health effects among pesticide sprayers in Southern India. | Occupational health has never been a priority for policy makers in India, despite 63% of the Indian population being in the economically productive age group. The study was designed to find out the morbidity as a result of long-term exposure to pesticides among professional pesticide sprayers in a rural block in Tamil Nadu. A cross-sectional study was done in Kaniyambadi block of Vellore district, Tamil Nadu, during July to October 2013. A total of 70 professional pesticide sprayers and 66 people engaged in other occupations were enrolled into the study. The participants were administered a standardized questionnaire apart from measuring pulmonary function and peripheral sensations. Venous blood samples were collected for measuring serum cholinesterase. The pesticide sprayers had higher prevalence of breathlessness on activities of daily living (odds ratio [OR]: 3.14, 95% confidence interval [CI]: 1.22-8.07), chronic cough/phlegm (OR: 3.53, 95% CI: 1.09-11.46), symptoms of peripheral sensory neuropathy (OR: 6.66, 95% CI: 2.53-17.51) and recurrent abdominal pain (OR: 3.05, 95% CI: 1.03-9.01), when compared to people engaged in other occupations. Pesticide sprayers also had significantly lower mean peak expiratory low rates and poor peripheral sensations. The serum cholinesterase levels were not statistically different between the groups. The pesticide sprayers had a higher morbidity when compared to people engaged in other occupations, and further research is needed to find out methods to prevent the same. Serum cholinesterase may not be a good marker for quantifying exposure to pesticide among sprayers, during a spraying season. | Cholinesterase;exposure;pesticides;sprayers;toxicity | pubmed |
CBCT in orthodontics: assessment of treatment outcomes and indications for its use. | Since its introduction into dentistry in 1998, CBCT has become increasingly utilized for orthodontic diagnosis, treatment planning and research. The utilization of CBCT for these purposes has been facilitated by the relative advantages of three-dimensional (3D) over two-dimensional radiography. Despite many suggested indications of CBCT, scientific evidence that its utilization improves diagnosis and treatment plans or outcomes has only recently begun to emerge for some of these applications. This article provides a comprehensive and current review of key studies on the applications of CBCT in orthodontic therapy and for research to decipher treatment outcomes and 3D craniofacial anatomy. The current diagnostic and treatment planning indications for CBCT include impacted teeth, cleft lip and palate and skeletal discrepancies requiring surgical intervention. The use of CBCT in these and other situations such as root resorption, supernumerary teeth, temporomandibular joint (TMJ) pathology, asymmetries and alveolar boundary conditions should be justified on the basis of the merits relative to risks of imaging. CBCT has also been used to assess 3D craniofacial anatomy in health and disease and of treatment outcomes including that of root morphology and angulation; alveolar boundary conditions; maxillary transverse dimensions and maxillary expansion; airway morphology, vertical malocclusion and obstructive sleep apnoea; TMJ morphology and pathology contributing to malocclusion; and temporary anchorage devices. Finally, this article utilizes findings of these studies and current voids in knowledge to provide ideas for future research that could be beneficial for further optimizing the use of CBCT in research and the clinical practice of orthodontics. | CBCT;cone beam computed tomography;evidence-based diagnosis;orthodontics;three-dimensional imaging;treatment planning and treatment outcomes | pubmed |
Salvage Conservation Laryngeal Surgery After Radiation Therapy Failure. | Conservation laryngeal surgery (CLS) includes time-honored approaches such as the vertical partial laryngectomy and the open horizontal supraglottic laryngectomy, as well as the supracricoid partial laryngectomy and transoral laser microsurgery. Carefully selected patients can undergo transoral endoscopic or open CLS for early to intermediate stage recurrent tumors of the glottic and supraglottic larynx. Patient factors, such as comorbid pulmonary disease, are essential in selecting patients for CLS, especially after previous radiation therapy. This article reviews the preoperative indications and postoperative management of salvage CLS after radiation therapy for laryngeal cancer. | Conservation laryngeal surgery;Larynx;Laser;Radiation;Salvage;Supracricoid | pubmed |
Development of biodegradable radiopaque microsphere for arterial embolization-a pig study. | To develop a new type of calibrated, biodegradable, and imaging detectable microsphere and evaluated its embolization safety and efficacy on pig's liver and spleen. Six kinds of pharmaceutical excipient were combined and atomized to form our microsphere. Twenty-four male Lanyu pigs weighing 25-30 kg were used. The arteries of spleen and liver were embolized with Gelfoam, Embosphere, or our microsphere. The serum biochemical tests, computed tomography (CT), liver perfusion scan, and tissue microscopy examination were done to evaluate the safety and efficacy of embolization. Radiopaque microspheres with a size ranging from 300 to 400 μm were produced. Embolization of hepatic and splenic artery of pigs with our microsphere significantly reduced the blood flow of liver and resulted in splenic infarction. The follow-up CT imaging and the microscopic examination showed intraarterial degradation of Gelfoam and microsphere. The blood tests demonstrated insignificant changes with regards to liver and renal functions. Our microspheres, with the unique characteristics, can be used for transcatheter arterial embolization with effects equivalent to or better than Gelfoam and Embosphere in pigs. | Arterial embolization;Atomization;Microsphere;Pharmaceutical excipient | pubmed |
Suicidal ideation: Are refugees more at risk compared to host population? Findings from a preliminary assessment in a refugee community in Nigeria. | Among the serious mental health problems that may be associated with being a refugee is suicidal behavior. This study aimed to assess the prevalence and correlates of suicidal ideation among African refugees in Oru-Ijebu Nigeria. Suicidal ideation was assessed using appropriate section in the Mini-International Neuropsychiatric Interview while the brief version of the WHO Quality of Life was used to assess quality of life as a clinical variable. Study involved 444 refugees and 527 non-refugee member of host community. Result showed that the prevalence of suicidal ideation was significantly higher among the refugees than the non-refugee comparison group (27.3% vs. 17.3%; p<0.001). Social status and quality of life was significantly poorer among the refugees compared with their non-refugee members of same community. Quality of life was the only factor independently associated with suicidal ideations among refugees. In conclusion, the study shows that the prevalence of suicidal ideation is significantly higher among the refugees than the non-refugee members of the host community and calls for innovative ways of extending mental health services to refugees at the study site. | Nigeria;Refugees;Suicidal ideation | pubmed |
Multi Drug Resistant Klebsiella Isolates in Burn Patients: A Comparative Study. | Infections are the most common complications in the burn patients admitted to the hospitals leading to high morbidity and mortality. Klebsiella is one of the most frequently isolated bacteria from burn wounds. We studied antimicrobial susceptibility patterns of Klebsiella isolates from burn patients. In this cross- sectional study wound swabs from 1294 patients hospitalized in burnward were collected for bacteriological examination. Antibiotic sensitivity testing of Klebsiella isolates was done by modified Stokes disc diffusion method. Out of 883 isolates from 1294 patients 195 were found to be Klebsiella spp. Based on the biochemical properties 153 isolates were Klebsiella pneumoniae, 37 were Klebsiella oxytoca and 5 were others species. In our study we found that 54% of the Klebsiella isolates were multidrug resistant as they were resistant to at least one antibiotic of three or more different groups of antibiotics. [Table: see text]. Rate of isolation of Klebsiella as well as its resistance for commonly used antibiotics is increasing over the time. | Antibiotic susceptibility;Prevalence;Wound swabs | pubmed |
Two different models to predict ionic-liquid diffraction patterns: fixed-charge versus polarizable potentials. | This study reports the performance of classical molecular dynamics (MD) in predicting the X-ray diffraction patterns of butylammonium nitrate (BAN) and two derivatives, 4-hydroxybutan-1-ammonium nitrate (4-HOBAN) and 4-methoxybutan-1-ammonium nitrate (4-MeOBAN). The structure functions and radial distribution functions obtained from energy-dispersive X-ray diffraction spectra, recorded newly for BAN and for the first time for 4-MeOBAN and 4-HOBAN, are compared with the corresponding quantities calculated from MD trajectories, to access information on the morphology of these liquids. The different behavior of two force fields, a polarizable multipole force field and a fixed-charge one supplemented by an explicit three-body term, is shown. The three-body force field proves to be superior in reproducing the intermediate q range, for which the polarizable force field gives the wrong peak position and intensities. In addition, both models can correctly account for the presence or absence of a low q peak in the scattering patterns. | X-ray diffraction;ionic liquids;molecular dynamics;polarizable force field;three-body force field | pubmed |
Exercise, cognitive function, and aging. | Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. | brain;cardiovascular;physical activity;physiology | pubmed |
TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. | Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor transient receptor potential vanilloid 1 (TRPV1); however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4)-positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, which were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw, and whisker pad). The TRPV1-selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6 but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared with BALB/c. | TRPV1;capsaicin;electrophysiological property;heat pain sensitivity;trigeminal ganglion | pubmed |
Weber-Christian disease presenting with lung nodules dramatically improved with corticosteroid therapy: one case report and literature review. | Weber-Christian disease (WCD) is a chronic recurrent organ disease characterized by the formation of painful dense nodes in subcutaneous fat tissues, free from suppuration and accompanied by episodic temperature changes, chills and muscular pain. Sometimes it can involve the visceral organs. WCD often relapses during irregular intervals. It is a rare autoimmune inflammatory disorder of subcutaneous adipose tissue. However, lung involvement in WCD is rare. Here we report a man presenting with lung nodules. He was diagnosed as having WCD and successfully treated by corticosteroid and immonosuppressive agents. A 53-year-old male presented with a 2.5-year history of painful subcutaneous nodules on his trunk and limbs, accompanied by fever, night sweats, fatigue and malaise. A skin biopsy showed fat degeneration with foamy cells and infiltration of mononuclear cells. He was diagnosed as panniculitis and effectively treated by corticosteroid therapy at first. However, symptoms relapsed when the dosage of corticosteroid was tapered, and multiple lung nodules were found with the symptom of dyspnea in chest computed tomography scan during the follow-up period. Histological examination of the biopsy specimens from the lung was compatible with panniculitis change in the subcutanous nodule. Combination therapy of corticosteroid with cyclophosphamide was effective during the following 27 months. | Weber-Christian disease;lung nodules;panniculitis;response | pubmed |
Impact of Age, Gender and Anesthesia Modality on Post-Operative Pain in Total Knee Arthroplasty Patients. | Optimizing pain control following total knee arthroplasty is of utmost importance to the immediate post-operative course. Various anesthesia modalities are available, but studies comparing multiple anesthesia modalities, patient age, and sex are limited. The purpose of our study was to examine the impact of patient age, gender, and perioperative anesthesia modality on postoperative pain following primary total knee arthroplasty. 443 patients who underwent primary total knee arthroplasty by 14 surgeons with some combination of general anesthesia, spinal anesthesia, femoral nerve block, and intrathecal morphine were identified. Anesthesia route and type, length of surgery, post-operative patient-reported pain measures using the Visual Analog Scale, opioid consumption, and length of hospital stay were recorded for each patient and used to compare differences among study groups. No significant differences were noted between anesthesia groups with regards to postoperative pain or length of hospital stay. Patients receiving spinal anesthesia and femoral nerve block without intrathecal morphine were significantly older than other groups. Patients receiving general anesthesia required significantly more daily intravenous morphine equivalents than patients receiving spinal anesthesia. Patients receiving spinal anesthesia with femoral nerve block and intrathecal morphine consumed the least amount of morphine equivalents. When comparing males and females among all groups, females had significantly higher pain ratings between 24-36 and 24-48 hours postoperatively. Although no significant differences were noted on pain scores, patients who received spinal anesthesia with intrathecal morphine and femoral nerve block used less narcotic pain medication than any other group. Females reported significantly higher pain between 24-48 hours post-op compared with males but not significantly greater anesthetic usage. Level III, Therapeutic Study, (Retrospective Comparative study). | Anesthesia;Gender;Pain control;Total knee arthroplasty | pubmed |
Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism. | Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds. | Alteraciones del metabolismo oseo-mineral en la enfermedad renal crónica;Chronic kidney disease;Chronic kidney disease-mineral and bone disorder;Enfermedad renal crónica;Haemodialysis;Hemodiálisis;Hiperparatiroidismo secundario;Inicio del tratamiento;Interrupción del tratamiento;Mantenimiento del tratamiento;Secondary hyperparathyroidism;Treatment discontinuation;Treatment initiation;Treatment persistence | pubmed |
Functional neuroimaging of acute oculomotor deficits in concussed athletes. | In the pursuit to better understand the neural underpinnings of oculomotor deficits following concussion we performed a battery of oculomotor tests while performing simultaneous functional magnetic resonance imaging (fMRI). Based on the increasing evidence that concussion can disrupt multiple brain functional networks, including the oculomotor control networks, a series of classic saccadic and smooth pursuit tasks were implemented. Nine concussed athletes were tested within seven days of injury along with nine age and sex matched healthy normal volunteers. Both behavioral and fMRI data revealed differential results between the concussed and normal volunteer groups. Concussed subjects displayed longer latency time in the saccadic tasks, worse position errors, and fewer numbers of self-paced saccades compared to normal volunteer subjects. Furthermore, the concussed group showed recruitment of additional brain regions and larger activation sites as evidenced by fMRI. As a potential diagnostic and management tool for concussion, oculomotor testing shows promise, and here we try to understand the reasons for this disrupted performance with the aide of advanced neuroimaging tools. | Concussion;Eye-Tracking;Mild traumatic brain injury;Oculomotor | pubmed |
Time-lapse recording of centrosomes and other organelles in Drosophila neuroblasts. | Drosophila larval neuroblasts (NBs) are an excellent model for asymmetric division and cell cycle studies in general. For decades, visualizing relevant structures like centrosomes, chromosomes, or the mitotic spindle relied exclusively on immunofluorescence on fix samples. More recently, improvements on sensitivity and acquisition speed of different confocal systems have made it possible to acquire time-resolved images of combined fluorescent reporters from single larval NBs. Here, we provide protocols to visualize centrosomes and other organelles from both primary cultures of isolated single NBs and ex vivo, whole-mounted larval brains. | Cell culture;Centriole;Centrosome;Drosophila;Microscopy;Neuroblast | pubmed |
Overview of Integrative Medicine Practices and Policies in NATO Participant Countries. | <b>Background:</b> CAMbrella is a European research network for complementary and alternative medicine (CAM). Between January 2010 and December 2013 the CAMbrella consortium reviewed the status of CAM in Europe from the perspectives of: (1) terminology for description; (2) citizens' needs and expectations; (3) patients' usage patterns; (4) providers' practice patterns; and (5) regulatory and legal status in Europe. Together, this data was used to form a set of recommendations to the European Commission, the European Parliament, and national policy makers and civil society stakeholders. These recommendations can serve as a roadmap for European CAM research. <b>Objective:</b> This article aims to inform the reader about CAM prevalence, usage perspectives, and the future roadmap for CAM practices and research within the European Union. <b>Method:</b> This overview describes CAM status in the European Union, using the CAMbrella consortium projects as the source of information. <b>Conclusions:</b> The North Atlantic Treaty Organization is positioned as a potential foundation for inclusion of CAM modalities within the militaries as well for as collaborative research on safe and cost-effective practices. | CAM;CAMbrella Pan-European Project;Legislation of CAM;Regulation;Reimbursement;Survey on Members of EU;Usage of CAM | pubmed |
A comprehensive analysis of membrane and morphology of erythrocytes from patients with glucose-6-phosphate dehydrogenase deficiency. | Acute hemolytic anemia could be triggered by oxidative stress in the patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, the underlying hemolytic mechanism is unknown. To make clear the hemolytic mechanisms, a systematic study on membrane ultrastructure had been undertaken. A comprehensive method was used including atomic force microscopy, scanning electron microscopy, flow cytometer and fluorescence microscopy to analyze the membrane ultrastructure, externalized phosphatidylserine (PS), intracellular Ca(2+) concentration, morphology and the distributions of band 3 protein in G6PD deficient red blood cells (RBCs) after tert-butyl-hydroperoxide (t-BHP) oxidation. The results showed that erythrocyte shrinkage, annexin-V binding to externalized PS on the membrane of early-stage apoptotic cells, the increased membrane roughness and intracellular Ca(2+) concentration, as well as the change of distributions of band 3 protein in RBCs. Compared with the control RBCs, as the concentration of t-BHP up to 0.1mM, the membrane roughness of G6PD deficient RBCs showed significant difference (p<0.05) and as the concentration of t-BHP up to 0.3mM, externalized PS showed significant difference (p<0.05). Furthermore, the population types of RBCs showed dramatic difference between control groups and G6PD deficient groups. Oxidative stress induced more serious erythrocyte apoptosis and resulted in increased roughness of erythrocyte membrane and abnormal distributed band 3 protein in G6PD deficient RBCs. Echinocytes are the predominant abnormal erythrocyte shape occurring in the peripheral blood from patients with G6PD deficiency, which may shorten the RBCs lifespan. The results in the present study will give an increased understanding for the hemolytic mechanism of G6PD deficiency. | G6PD deficiency;Hemolytic mechanism;Morphology;Oxidation;RBCs;Ultrastructure | pubmed |
Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools. | Diabetes and metabolic syndromes are chronic, devastating diseases with increasing prevalence. Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling. With recent rapid advances in genome editing tools, these cells can now be genetically manipulated with relative ease to study how genes and gene variants contribute to diabetes and metabolic syndromes. We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases. hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease. | CRISPR/Cas;Diabetes;Disease modeling;Genome editing;Metabolic disease;Pluripotent stem cells | pubmed |
Influenza vaccine efficacy trials: a simulation approach to understand failures from the past. | The success of a seasonal influenza vaccine efficacy trial depends not only upon the design but also upon the annual epidemic characteristics. In this context, simulation methods are an essential tool in evaluating the performances of study designs under various circumstances. However, traditional methods for simulating time-to-event data are not suitable for the simulation of influenza vaccine efficacy trials because of the seasonality and heterogeneity of influenza epidemics. Instead, we propose a mathematical model parameterized with historical surveillance data, heterogeneous frailty among the subjects, survey-based heterogeneous number of daily contact, and a mixed vaccine protection mechanism. We illustrate our methodology by generating multiple-trial data similar to a large phase III trial that failed to show additional relative vaccine efficacy of an experimental adjuvanted vaccine compared with the reference vaccine. We show that small departures from the designing assumptions, such as a smaller range of strain protection for the experimental vaccine or the chosen endpoint, could lead to smaller probabilities of success in showing significant relative vaccine efficacy. | clinical trials;seasonal influenza;simulation;vaccine efficacy | pubmed |
Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins. | Lamina-associated polypeptide 2α (LAP2α) localizes throughout the nucleoplasm and interacts with the fraction of lamins A/C that is not associated with the peripheral nuclear lamina. The LAP2α-lamin A/C complex negatively affects cell proliferation. Lamins A/C are encoded by LMNA, a single heterozygous mutation of which causes Hutchinson-Gilford progeria syndrome (HGPS). This mutation generates the lamin A variant progerin, which we show here leads to loss of LAP2α and nucleoplasmic lamins A/C, impaired proliferation, and down-regulation of extracellular matrix components. Surprisingly, contrary to wild-type cells, ectopic expression of LAP2α in cells expressing progerin restores proliferation and extracellular matrix expression but not the levels of nucleoplasmic lamins A/C. We conclude that, in addition to its cell cycle-inhibiting function with lamins A/C, LAP2α can also regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2α in cells expressing progerin. | A-type lamins;Hutchinson Gilford progeria;cell proliferation regulation;extracellular matrix;lamina-associated polypeptide;nuclear lamina;nucleoplasmic lamins | pubmed |
Effect of continuous oxygen insufflation on induced-gastric air volume during cardiopulmonary resuscitation in a cadaveric model. | The main objective of this study was to compare the volume of gas insufflated in the stomach with continuous external chest compressions plus continuous oxygen insufflation (C-CPR) versus standard-CPR (S-CPR) which alternates external chest compressions and synchronized positive insufflations through a bag-valve-mask with a 30/2 ratio. The secondary objective was to compare upper airway pressures (intratracheal and intramask) generated during continuous oxygen insufflation. Open, prospective, randomized, cross over, comparative, non-inferiority study. CPR was performed for six minutes periods, on seven fresh human corpses, with C-CPR or S-CPR in a random order. Before each CPR period, the stomach was completely emptied through the gastrostomy tube, and then 200 mL of air was injected in the stomach to be sure it was not collapsed. The gastric volume was measured at the end of each intervention. Intratracheal and intramask pressures were recorded continuously during C-CPR. Results were provided as mean ± standard deviation. Statistical analyses were done with a paired student t test. Induced-gastric inflation was lower with C-CPR (221 ± 130 mL) than with S-CPR (5401 ± 2208 mL, p = 0.001). Throughout C-CPR, no difference was found between the intratracheal and intramask pressures (4.4 ± 1.2; 4.0 ± 0.8 cmH2O, respectively, p = 0.45). This human cadaver study demonstrates that continuous oxygen insufflation induced less gastric inflation than intermittent insufflation during CPR. | *Insufflation;Cardiopulmonary resuscitation;Cardiopulmonary resuscitation/therapy;Continuous external chest compression, Continuous oxygen insufflation | pubmed |
Outcomes after heart transplantation for amyloid cardiomyopathy in the modern era. | We conducted a review of patients undergoing heart transplantation (HT) at our institution for amyloid cardiomyopathy (ACM) between 2008 and 2013. Complete follow-up was available for all patients. Nineteen patients with ACM underwent HT during the study period, accounting for 9.4% of all HT performed at our institution during this period. Amyloid subtype was light chain (AL) in 9 patients and transthyretin (ATTR) in 10 (2 wild-type, 7 familial, 1 unknown). Eight of nine patients with AL amyloidosis began chemotherapy prior to HT, six have resumed chemotherapy since HT, and five have undergone autologous stem cell transplantation. Most recent free light chain levels in AL patients decreased by a median of 85% from peak values. Only one patient developed recurrent graft amyloidosis, occurring at 3.5 years post-HT and asymptomatic. After a median follow-up of 380 days, 17 (89.5%) patients are alive. To our knowledge, this is the largest single-center series reported of ACM patients undergoing HT in the modern era. Our results suggest that acceptable outcomes following HT can be achieved in the short-to-intermediate term and that this is a feasible option for end-stage ACM with careful patient selection and aggressive control of amyloidogenic light chains in AL patients. | clinical research/practice;heart disease;heart transplantation/cardiology;organ procurement and allocation;patient characteristics;patient survival;recipient selection | pubmed |
Unprecedented ring-ring interconversion of N,P,C-cage ligands. | The novel N,P,C-cage complexes 5 a-f and 6 a-f have been obtained by the reaction of the P-pentamethylcyclopentadienylphosphinidene complex 2, generated thermally from 2H-azaphosphirene complex 1, with N-methyl-C-arylcarbaldimines 3 a-f. Li/Cl phosphinidenoid complex 8 reacted with 3 a,b to give N,P,C-cage complexes 6 a,b, whereas with 3 c-f, complexes 6 c-f were obtained in negligible amounts only. Both types of ligand N,P,C-cage structures 5 and 6 were found to be in an unprecedented equilibrium, with 5 a,f as the predominant species. Transient electrophilic terminal phosphinidene complexes 10 a-f serve as intermediates in both ligand interconversions (5 a,f↔6 a,f), as evidenced through trapping reactions with phenylacetylene and N-methyl-C-phenylcarbaldimine, thus leading to the novel N,P,C-cage complexes 13 b and 15. DFT calculations predicted a small difference in the relative energies of the two types of N,P,C-cage ligands, and a remarkable stabilisation of the aminophosphinidene complex 10 as the common precursor, thereby providing an insight into this surprising 5-ring-3-ring interconversion. In depth analysis of intermediate 10 revealed the occurrence of both through-bond (conventional inductive/mesomeric effects) and through-space (non-covalent interactions) mechanisms, which amount to 67.8 and 14.4 kcal mol(-1), respectively, and account for the remarkable stabilisation of this intermediate. | cage compounds;density functional calculations;phosphinidenes;rearrangement;tungsten | pubmed |
Percutaneous pars interarticularis screw fixation: a technical note. | A conventional midline posterior approach is used for most of the described surgical techniques. We describe a technique of percutaneous fixation of the pars interarticularis, augmented where necessary by grafting the defect, which minimises muscle injury. A 4.5 mm partially threaded dynamic compression screw is placed over a wire inserted percutaneously across the pars interarticularis defect. Compression is achieved across the pars interarticularis defect on placement of the screw. The screw is locked in a compressed state. The patient is mobilised the same day with a corset for comfort and discharged the following day. Aerobic fitness is maintained for 3 months; then, focused rehabilitation performed until a CT scan confirms healing at 5-6 months, at which stage full (sports) activity is resumed. The minimal tissue injury and small incision used allow for the minimising of complications and for a rapid recovery and discharge from hospital. With adolescents, we have the opportunity to treat symptomatic pars interarticularis defects with minimal disruption to their academic and physical development. | Minimally invasive;Percutaneous screw;Spondylolysis | pubmed |
Trend and seasonality in hospitalizations for pulmonary embolism: a time-series analysis. | The existence of seasonal variability in patients with acute pulmonary embolism (PE) has been debated for years, with contradictory results. The aim of this study was to identify the trend and possible existence of a seasonal pattern in hospitalizations for PE in Spain. We analyzed the hospital discharge database of the Spanish National Health System from 2001 to 2010. Patients aged > 14 years diagnosed with PE were selected and a time series was constructed considering mean daily admissions for PE by month. The trend and seasonality factor of the series were determined using time-series analysis, and time-series modeling was used for analysis. Exponential smoothing models and the autoregressive integrated moving average test were used to generate a predictive model. From 2001 to 2010, there were 162,032 diagnoses of PE (5.07 per 1000 hospitalizations). In 105,168 cases, PE was the reason for admission. The PE diagnosis rate ranged from 4.14 per 1000 in 2001 to 6.56 per 1000 in 2010; and hospital admissions due to PE ranged from 2.67 to 4.28 per 1000 hospital discharges. Time-series analysis showed a linear increase in the incidence and a significant seasonal pattern with 17% more admissions in February and 12% fewer in June-July with respect to the central tendency (difference from February to June, 29%). The incidence of hospitalizations for PE showed a linear increase and a seasonal pattern, with the highest number of admissions in winter and the lowest number in summer. | community health planning;inpatients;pulmonary embolism;seasonal variation;trends | pubmed |
Transcriptional profiling unravels potential metabolic activities of the olive leaf non-glandular trichome. | The olive leaf trichomes are multicellular peltate hairs densely distributed mainly at the lower leaf epidermis. Although, non-glandular, they have gained much attention since they significantly contribute to abiotic and biotic stress tolerance of olive leaves. The exact mechanisms by which olive trichomes achieve these goals are not fully understood. They could act as mechanical barrier but they also accumulate high amounts of flavonoids among other secondary metabolites. However, little is currently known about the exact compounds they produce and the respective metabolic pathways. Here we present the first EST analysis from olive leaf trichomes by using 454-pyrosequencing. A total of 5368 unigenes were identified out of 7258 high quality reads with an average length of 262 bp. Blast search revealed that 27.5% of them had high homologies to known proteins. By using Blast2GO, 1079 unigenes (20.1%) were assigned at least one Gene Ontology (GO) term. Most of the genes were involved in cellular and metabolic processes and in binding functions followed by catalytic activity. A total of 521 transcripts were mapped to 67 KEGG pathways. Olive trichomes represent a tissue of highly unique transcriptome as per the genes involved in developmental processes and the secondary metabolism. The results indicate that mature olive trichomes are trancriptionally active, mainly through the potential production of enzymes that contribute to phenolic compounds with important roles in biotic and abiotic stress responses. | Olea europaea;multicellular trichomes;next-generation sequencing;non-glandular trichomes;transcriptome | pubmed |
High mass accuracy assay for trimethylamine N-oxide using stable-isotope dilution with liquid chromatography coupled to orthogonal acceleration time of flight mass spectrometry with multiple reaction monitoring. | Trimethylamine N-oxide (TMAO) has attracted interest as circulating levels have reported prognostic value in patients with cardiovascular conditions, such as heart failure. With continual advances in accurate mass measurements, robust methods that can employ the capabilities of time of flight mass spectrometers would offer additional utility in the analysis of complex clinical samples. A Waters Acquity UPLC was coupled to a Waters Synapt G2-S high-resolution mass spectrometer. TMAO was measured in plasma by stable-isotope dilution-hydrophilic interaction liquid chromatography-time of flight mass spectrometry with multiple reaction monitoring (LC-ToF-MRM). Two transitions were monitored: m/z 76.1 to 58.066/59.073 and m/z 85.1 to 66.116/68.130. The method was assessed for linearity, lower limits of detection and quantitation, and reproducibility. A selected cohort of patients with systolic heart failure (SHF; n = 43) and healthy controls (n = 42) were measured to verify the assay is suitable for the analysis of clinical samples. Quantitative analysis of TMAO using LC-ToF-MRM enabled linearity to be established between 0.1 and 75 μmol/L, with a lower limit of detection of 0.05 μmol/L. Relative standard deviations reported an inter-day variation of ≤20.8% and an intra-day variation of ≤11.4% with an intra-study quality control variation of 2.7%. Run times were 2.5 min. Clinical application of the method reported that TMAO in SHF was elevated compared to that of healthy controls (p < 0.0005). LC-ToF-MRM offers a highly selective method for accurate mass measurement of TMAO with rapid and reproducible results. Applicability of the method was shown in a selected cohort of patient samples. | Heart failure;High-resolution mass spectrometry;LC-MS/MS;Multiple reaction monitoring;TMAO;Time of flight | pubmed |
University Students Intend to Eat Better but Lack Coping Self-Efficacy and Knowledge of Dietary Recommendations. | To assess university students' knowledge, intentions, and coping self-efficacy related to dietary recommendations. The study used a cross-sectional online survey. Large university campus. Students (n = 6,638; 22% response). Self-efficacy and intentions were measured using 11-point scales. Students' perceived dietary recommendations were evaluated as correct or incorrect. Categorical variables were analyzed using chi-square and continuous variables by t tests or ANOVAs. Significance was set at P ≤ .05 and multiple comparisons at P ≤ .01. Respondents believed that they need fewer vegetables and fruit and more milk or alternatives servings/d than recommended; eg, males aged ≥ 19 years perceived milk or alternatives recommendations to be 4.3 ± 2.1 servings/d, significantly more than the 2 servings/d recommended (P < .001). Students in health sciences or with a food or nutrition course were significantly more likely to claim that they met recommendations (eg, 56% with vs 47% without a food or nutrition course for vegetables and fruit; P < .001); however, they were no more likely to identify them correctly. Males aged < 19 years had higher coping self-efficacy than females aged < 19 years to consume vegetables (68.3 ± 24.2 vs 64.0 ± 24.7; P < .01) and avoid high-calorie foods and beverages (HCFB) (56.2 ± 27.2 vs 49.0 ± 25.2; P < .01) when under stress; however, they had significantly lower intentions to consume vegetables (72.1 ± 24.5 vs 80.9 ± 20.3; P < .01) and avoid HCFB (60.5 ± 30.3 vs 77.7 ± 22.8; P < .01). Students do not have adequate knowledge of age- and sex-specific food guide recommendations. Simpler food guide recommendations or age- and sex-targeted campaigns may enhance knowledge. Students intend to consume more vegetables and less HCFB; however, they have low coping self-efficacy, all of which could be targeted in nutrition interventions. | dietary recommendations;intentions;knowledge;self-efficacy;university students | pubmed |
Hemoparasites in a wild primate: Infection patterns suggest interaction of Plasmodium and Babesia in a lemur species. | Hemoparasites can cause serious morbidity in humans and animals and often involve wildlife reservoirs. Understanding patterns of hemoparasite infections in natural populations can therefore inform about emerging disease risks, especially in the light of climate change and human disruption of natural ecosystems. We investigated the effects of host age, sex, host group size and season on infection patterns of Plasmodium sp., Babesia sp. and filarial nematodes in a population of wild Malagasy primates, Verreaux's sifakas (Propithecus verreauxi), as well as the effects of these infections on hematological variables. We tested 45 blood samples from 36 individuals and identified two species of Plasmodium, one species of Babesia and two species of filarial nematodes. Plasmodium spp. and Babesia sp. infections showed opposite patterns of age-dependency, with babesiosis being prevalent among young animals, while older animals were infected with Plasmodium sp. In addition, Babesia sp. infection was a statistically significant negative predictor of Plasmodium sp. infection. These results suggest that Plasmodium and Babesia parasites may interact within the host, either through cross-immunity or via resource competition, so that Plasmodium infections can only establish after babesiosis has resolved. We found no effects of host sex, host group size and season on hemoparasite infections. Infections showed high prevalences and did not influence hematological variables. This preliminary evidence supports the impression that the hosts and parasites considered in this study appear to be well-adapted to each other, resulting in persistent infections with low pathogenic and probably low zoonotic potential. Our results illustrate the crucial role of biodiversity in host-parasite relationships, specifically how within-host pathogen diversity may regulate the abundance of parasites. | Babesia sp.;Cross-immunity;Hemoparasites;Parasite community;Plasmodium sp.;Propithecus verreauxi;Verreaux's sifakas | pubmed |
A novel Lozenge gene in silkworm, Bombyx mori regulates the melanization response of hemolymph. | Runt-related (RUNX) transcription factors are evolutionarily conserved either in vertebrate or invertebrate. Lozenge (Lz), a members of RUNX family as well as homologue of AML-1, functions as an important transcription factor regulating the hemocytes differentiation. In this paper, we identified and characterized RUNX family especially Lz in silkworm, which is a lepidopteran model insect. The gene expression analysis illustrated that BmLz was highly expressed in hemocytes throughout the whole development period, and reached a peak in glutonous stage. Over-expression of BmLz in silkworm accelerated the melanization process of hemolymph, and led to instantaneously up-regulation of prophenoloxidases (PPOs), which were key enzymes in the melanization process. Further down-regulation of BmLz expression by RNA interference resulted in the significant delay of melanization reaction of hemolymph. These findings suggested that BmLz regulated the melanization process of hemolymph by inducing PPOs expression, and played a critical role in innate immunity defense in silkworm. | Bombyx mori;Lozenge;Melanization;Prophenoloxidases;Runt-related transcription factor (RUNX) | pubmed |
The relative toxicity of Delphinium stachydeum in mice and cattle. | Larkspurs (Delphinium spp.) are poisonous plants on rangelands throughout the Western United States and Canada. Larkspur-induced poisoning in cattle is due to norditerpene alkaloids that are represented by two main structural groups of norditerpene alkaloids, the N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and the non-MSAL type. Information on the alkaloid composition and resulting toxicity in mice and cattle is lacking for a number of Delphinium species, including Delphinium stachydeum. The objective of this study was to determine the alkaloid composition of D. stachydeum and to characterize its relative toxicity in mice and cattle compared to two reference species Delphinium barbeyi and Delphinium occidentale. D. stachydeum contains the non-MSAL-type alkaloids but not the MSAL-type alkaloids. D. stachydeum was less toxic than D. barbeyi and D. occidentale in the mouse model. D. stachydeum was less toxic than the MSAL-containing D. barbeyi but much more toxic than the non-MSAL-containing D. occidentale in cattle as measured by heart rate and time of exercise. These results indicate that predictions of Delphinium toxicity can't be accurately made based solely on results from the mouse model or the absence of the MSAL-type alkaloids in the plant. | Cattle;Delphinium;Norditerpene alkaloids;Toxic plant | pubmed |
Neuropsychological Status and Structural Brain Imaging in Adolescents With Single Ventricle Who Underwent the Fontan Procedure. | Few studies have described the neuropsychological outcomes and frequency of structural brain or genetic abnormalities in adolescents with single ventricle who underwent the Fontan procedure. In a cross-sectional, single-center study, we enrolled 156 subjects with single ventricle, mean age 14.5±2.9 years, who had undergone the Fontan procedure. Scores in the entire cohort on a standard battery of neuropsychological tests were compared with those of normative populations or to those of a group of 111 locally recruited healthy adolescents. They also underwent brain magnetic resonance imaging and were evaluated by a clinical geneticist. Genetic abnormalities were definite in 16 subjects (10%) and possible in 49 subjects (31%). Mean Full-Scale IQ was 91.6±16.8, mean Reading Composite score was 91.9±17.2, and mean Mathematics Composite score was 92.0±22.9, each significantly lower than the population means of 100±15. Mean scores on other neuropsychological tests were similarly lower than population norms. In multivariable models, risk factors for worse neuropsychological outcomes were longer total support and circulatory arrest duration at first operation, presence of a genetic abnormality, more operations and operative complications, more catheterization complications, and seizure history. The frequency of any abnormality on magnetic resonance imaging was 11 times higher among Fontan adolescents than referents (66% versus 6%); 19 (13%) patients had evidence of a stroke, previously undiagnosed in 7 patients (40%). The neuropsychological deficits and high frequencies of structural brain abnormalities in adolescents who underwent the Fontan procedure highlight the need for research on interventions to improve the long-term outcomes in this high-risk group. | Fontan procedure;congenital heart defects;genetics;magnetic resonance imaging | pubmed |
Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum. | Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [(11) C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, 12 in the [(11) C]PHNO PET study, 8 of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. Using [(11) C]PHNO and PET brain imaging techniques we show that body mass index was positively associated with D2R/D3R availability in the dorsal striatum, but that functional MR BOLD response was unrelated to D2R/D3R availability. These results suggest the existence of a nonlinear relationship between D2R/D3R availability and body mass index and that the altered BOLD responses to food consumption seen in obesity are not directly related to D2R/D3R availability. | BMI;BOLD;PET;[11C]-(+)-PHNO;dopamine D2/3 receptor;fMRI;human | pubmed |
Emerging Vaccine Technologies. | Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The emergence of new technologies with a growing understanding of host-pathogen interactions and immunity may lead to efficacious vaccines against pathogens, previously thought impossible. | epitope-scaffold;immunoprophylaxis;reverse vaccinology;structural vaccinology;vaccine | pubmed |
Contrasting association of circulating sCD14 with insulin sensitivity in non-obese and morbidly obese subjects. | In experimental studies, moderate to high concentrations of sCD14 (serum cluster of differentiation 14 protein) prevent lipopolysaccharide (LPS)-induced systemic inflammation, while low concentrations may promote inflammation. Given that metabolic endotoxemia is thought to initiate high-fat diet-induced insulin resistance, we explored the association between sCD14 concentrations and insulin sensitivity in humans. Healthy non-obese (n = 12, BMI 26 ± 5y), obese (n = 11, BMI 33.45 ± 3.2) and morbidly obese participants (n = 38, BMI 45 ± 7) underwent measurement of body composition (dual energy X-ray absorptiometry) and a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity (M value). Circulating sCD14 concentrations were measured by ELISA. Non-obese participants had lower circulating sCD14 concentrations compared to obese (p = 0.03). Circulating sCD14 concentrations were positively associated with percent body fat, waist circumference and white blood cell count and negatively associated with insulin sensitivity. In contrast, circulating sCD14 were positively associated with insulin sensitivity in morbidly obese participants. In regression analysis, insulin sensitivity (r = 0.52, p = 0.004) and fasting triglycerides (r = 0.49, p = 0.005) contributed independently to circulating sCD14 variance after controlling for age, sex and BMI in these morbidly obese subjects. These findings suggest that circulating sCD14 concentrations, through its compensatory (in non-obese subjects) or buffering role (in morbidly obese subjects), could exert an important role in modulating insulin sensitivity. | Adiposity;CD14;Fitness;Insulin resistance;Obesity | pubmed |
Eosinophilia Associated with Disorders of Immune Deficiency or Immune Dysregulation. | Increased serum eosinophil levels have been associated with multiple disorders of immune deficiency or immune dysregulation. Although primary immunodeficiency diseases are rare, it is important to consider these in the differential diagnosis of patients with eosinophilia. In this review, the clinical features, laboratory findings, diagnosis, and genetic basis of disease of several disorders of immune deficiency or dysregulation are discussed. The article includes autosomal dominant hyper IgE syndrome, DOCK8 deficiency, phosphoglucomutase 3 deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and severe dermatitis, multiple allergies, and metabolic wasting syndrome. | Deficiency;Dysregulation;Eosinophilia;Immune | pubmed |
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