Orexins and gastrointestinal functions.
Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep-wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointestinal functions: animal studies have indeed demonstrated that centrally-injected orexins or endogenously released orexins in the brain stimulates gastric secretion and influence gastrointestinal motility. The subsequent identification of orexins and their receptors in the enteric nervous system (including the myenteric and the submucosal plexuses) as well as in mucosa and smooth muscles has suggested that these neuropeptides may also play a local action. In this view, emerging studies indicate that orexins also exert region-specific contractile or relaxant effects on isolated gut preparations. The aim of the proposed review is to summarize both centrally- and peripherally-mediated actions of orexins on gastrointestinal functions and to discuss the related physiological role on the basis of the most recent findings.


Hazards for Women and Children in Rural Settings.
a) To identify possible risk factors associated with rural accidents in women, b) to describe women's knowledge about zoonosis, c) to describe women's risk perception about farming, d) to describe mothers' risk perception about children's activities in rural settings, e) to estimate the initial age of exposure to the rural setting and its dangers, and f) to identify possible risk factors associated with rural accidents in children. Cross-sectional design. Women with children that live in the countryside were surveyed (n=24). Structured questionnaire. χ2, Student's t-test, Pearson's correlation coefficient and logistic regression. Many women had suffered an accident in the countryside (65.6 %). Farm worker usually did not use personal protective equipment (PPE). Hearing protection, gloves, and safety goggles were rarely used. Working women showed a high risk perception for urban driving, the handling of agrochemicals, and driving on main roads (85.7 %, 70 % and 66.7 %). There was no significant association between risk perception and PPE use. Most mothers (87.5 %) thought that was good for children to learn how to perform farm chores starting at a young age. Children started to drive tractors at 9 years of age; 12.23 years on average. More than 7 % of the children (7.14 %) have suffered an accident on the farm. The most frequent accidents were being trapped in machinery (60 %). No association was found between the independent variables and the dependent variable; farm-related accidents in children (p>0.2). Risk communication is necessary to inform people involved and to reduce exposure.


Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding.
Basement membranes (BMs) are supramolecular matrices built on laminin and type IV collagen networks that provide structural and signaling support to tissues. BM complexity, however, has hindered an understanding of its formation, dynamics, and regulation. Using genome editing, we tagged 29 BM matrix components and receptors in C. elegans with mNeonGreen. Here, we report a common template that initiates BM formation, which rapidly diversifies during tissue differentiation. Through photobleaching studies, we show that BMs are not static-surprisingly, many matrix proteins move within the laminin and collagen scaffoldings. Finally, quantitative imaging, conditional knockdown, and optical highlighting indicate that papilin, a poorly studied glycoprotein, is the most abundant component in the gonadal BM, where it facilitates type IV collagen removal during BM expansion and tissue growth. Together, this work introduces methods for holistic investigation of BM regulation and reveals that BMs are highly dynamic and capable of rapid change to support tissues.


Vibegron: a β3-adrenergic agonist for the treatment of overactive bladder.
Overactive bladder (OAB) is an extremely common condition in adults of both sexes. It is characterized by an urgent need to micturate often accompanied by incontinence. The condition may also increase the number of micturitions in a 24-hour period as well as nocturia. The syndrome is not due to a urinary infection or other obvious pathology. In terms of drug treatment of OAB, there are two main approaches. One is the use of anticholinergic drugs that reduce the effect of the parasympathetic nervous system on the bladder. The other involves the use of drugs that are agonists at β3-adrenergic receptors in the bladder. These drugs increase the capacity of the bladder and cause reductions in the number of daily micturitions and nocturia and also importantly reduce the frequency of urinary urgency and urinary urgency incontinence. Vibegron is the second β3-adrenergic agonist to be approved for the treatment of OAB.


Protective Mechanism of Berberine on Human Retinal Pigment Epithelial Cells against Apoptosis Induced by Hydrogen Peroxide via the Stimulation of Autophagy.
Age-related macular degeneration (AMD) is a major cause of severe and irreversible vision loss with limited effective therapies. Diminished autophagy and increased oxidative damage caused by ROS in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of AMD, and strategies aimed at enhancing autophagy are likely to protect these cells from oxidative damage. We have previously shown that berberine (BBR), an isoquinoline alkaloid isolated from Chinese herbs, was able to protect human RPE cells from H2O2-induced oxidative damage through AMPK activation. However, the precise mechanisms behind this protective effect remain unclear. Given the essential role of AMPK in autophagy activation, we postulated that BBR may confer protection against H2O2-induced oxidative damage by stimulating AMPK-dependent autophagy. Our results showed that BBR was able to induce autophagy in D407 cells, whereas autophagy inhibitor PIKIII or silencing of LC3B blocked the protective effect of BBR. Further analysis showed that BBR activated the AMPK/mTOR/ULK1 signaling pathways and that both pharmacological and genetic inhibitions of the AMPK pathway abolished the autophagy-stimulating effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrate that BBR is able to stimulate autophagy in D407 cells via the activation of AMPK pathway and that its protective effect against H2O2-induced oxidative damage relies on its autophagy-modulatory effect. Our findings also provide evidence to support the potential application of BBR in preventing and treating AMD.


Assessment of early language development in Turkish children with a cochlear implant using the TEDIL test.
To analyse language development of children with a cochlear implant (CI) in relation to length of CI use and age at implantation and to examine the suitability of the TEDIL as an assessment tool for measuring early language development in Turkish children. A total of 119 children implanted with a CI before 5 years of age were assessed acutely on sound field thresholds, speech recognition thresholds, open-set and closed-set monosyllabic word tests, the TEDIL, categories of auditory performance (CAP), and speech intelligibility rating (SIR). The outcome scores were analysed in relation to length of CI use (3, 4, and 5 years) and age at implantation (<24 months vs. >24 months). The TEDIL scores were compared to all other outcome measures. Scores significantly increased with CI experience. CAP and SIR were significantly higher in the younger implanted group. No significant difference was observed between the younger and older implanted group on the closed-set and open-set monosyllabic tests and the TEDIL. The TEDIL scores significantly correlated with CAP, SIR, and the closed-set and open-set word scores. The mean TEDIL standard score was close to average. Performance of CI users improves with increased CI experience. CI users implanted <24 months tend to have better auditory skills and clearer speech than CI users implanted >24 months. CI users implanted between 24 months and 60 months tend to develop language similarly to CI users implanted <24 months. The TEDIL is a suitable tool for assessing early receptive and expressive language development in Turkish children.


A novel index to aid in prioritizing habitats for site-based conservation.
Funding biodiversity conservation strategies are usually minimal, thus prioritizing habitats at high risk should be conducted. We developed and tested a conservation priority index (CPI) that ranks habitats to aid in prioritizing them for conservation. We tested the index using 1897 fish species from 273 African inland lakes and 34 countries. In the index, lake surface area, rarity, and their International Union for Conservation of Nature (IUCN) Red List status were incorporated. We retrieved data from the Global Biodiversity Information Facility (GBIF) and IUCN data repositories. Lake Nyasa had the highest species richness (424), followed by Tanganyika (391), Nokoué (246), Victoria (216), and Ahémé (216). However, lakes Otjikoto and Giunas had the highest CPI of 137.2 and 52.1, respectively. Lakes were grouped into high priority (CPI > 0.5; n = 56) and low priority (CPI < 0.5; n = 217). The median surface area between priority classes was significantly different (W = 11,768, p < .05, effect size = 0.65). Prediction accuracy of Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) for priority classes were 0.912 and 0.954, respectively. Both models exhibited lake surface area as the variable with the highest importance. CPI generally increased with a decrease in lake surface area. This was attributed to less ecological substitutability and higher exposure levels of anthropogenic stressors such as pollution to a species in smaller lakes. Also, the highest species richness per unit area was recorded for high-priority lakes. Thus, smaller habitats or lakes may be prioritized for conservation although larger waterbodies or habitats should not be ignored. The index can be customized to local, regional, and international scales as well as marine and terrestrial habitats.


Study of the interactions between proximal femur 3d bone shape, cartilage health, and biomechanics in patients with hip Osteoarthritis.
In this study quantitative MRI and gait analysis were used to investigate the relationships between proximal femur 3D bone shape, cartilage morphology, cartilage biochemical composition, and joint biomechanics in subject with hip Osteoarthritis (OA). Eighty subjects underwent unilateral hip MR-imaging: T1ρ and T2 relaxation times were extracted through voxel based relaxometry and bone shape was assessed with 3D MRI-based statistical shape modeling. In addition, 3D gait analysis was performed in seventy-six of the studied subjects. Associations between shape, cartilage lesion presence, severity, and cartilage T1ρ and T2 were analyzed with linear regression and statistical parametric mapping. An ad hoc analysis was performed to investigate biomechanics and shape associations. Our results showed that subjects with a higher neck shaft angle in the coronal plane (higher mode 1, coxa valga), thicker femoral neck and a less spherical femoral head (higher mode 5, pistol grip) exhibited more severe acetabular and femoral cartilage abnormalities, showing different interactions with demographics factors. Subjects with coxa valga also demonstrated a prolongation of T1ρ and T2. Subjects with pistol grip deformity exhibited reduced hip internal rotation angles and subjects with coxa valga exhibited higher peak hip adduction moment and moment impulse. The results of this study establish a clear relationship between 3D proximal femur shape variations and markers of hip joint degeneration-morphological, compositional, well as insight on the possible interactions with demographics and biomechanics, suggesting that 3D MRI-based bone shape maybe a promising biomarker of early hip joint degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:330-341, 2018.


Factors associated with post-traumatic stress disorder of nurses exposed to corona virus disease 2019 in China.
Quantitative studies using validated questionnaires on post-traumatic stress disorder (PTSD) of Nurses exposed to corona virus disease 2019 (COVID-19) in China are rare and the baseline PTSD must first be evaluated before prevention. This study aimed to investigate the factors potentially involved in the level of PTSD of Nurses exposed to COVID-19 in China.In this cross-sectional study, male and female Nurses (n = 202) exposed to COVID-19 from HuBei China were included in the final sample. The PTSD Checklist-Civilian (PCL-C) questionnaire and Simplified Coping Style Questionnaire (SCSQ) were used for evaluation. Multivariate stepwise linear regression analysis and spearman correlation test were performed to assess the association between various factors associated with PTSD.The incidence of PTSD in Nurses exposed to COVID-19 was 16.83%, the PCL-C score was 27.00 (21.00-34.00), and the highest score in the three dimensions was avoidance dimension 9.50 (7.00-13.25); multivariable stepwise linear regression analysis showed that job satisfaction and gender were independently associated with lower PCL-C scores (both P < .001); PCL-C scores were correlated with positive coping (r = -0.151, P = .032), negative coping (r = 0.154, P = .029).Nurses exposed to COVID-19 from HuBei China with job satisfaction, male and positive coping had low PCL-C scores which necessitate reducing the PTSD level by ways of improving job satisfaction, positive response, and strengthening the psychological counseling of female nurses in order to reduce the risk of psychological impairment.


Synergistic induction of the senescence-associated genes by 5-bromodeoxyuridine and AT-binding ligands in HeLa cells.
5-Bromodeoxyuridine induces a senescence-like phenomenon in mammalian cells. This effect was dramatically potentiated by AT-binding ligands such as distamycin A, netropsin, and Hoechst 33258. The genes most remarkably affected by these ligands include the widely used senescence-associated genes and were located on or nearby Giemsa-dark bands of human chromosomes. We hypothesize that AT-rich scaffold/nuclear matrix attachment region sequences are involved in this phenomenon. In fact, upon substitution of thymine with 5-bromouracil, a rat S/MAR sequence reduced its degree of bending and became insensitive to cancellation of the bending by distamycin A. The S/MAR sequence containing 5-bromouracil also bound more tightly to nuclear scaffold proteins in vitro and this binding was not inhibited by distamycin A. Under the same conditions, the S/MAR sequence containing thymine easily dissociated from the nuclear scaffold proteins. Taken together, the synergistic induction of the genes may be explained not only by opening of condensed chromatin by distamycin A but also by increase in the binding of 5-bromouracil-containing S/MAR sequences to the nuclear scaffolds.


Who's counting now? ROI for patient safety IT initiatives.
The impact and expectation of cost-justifying patient safety IT initiatives using a traditional ROI must evolve to focus beyond the financial benefit. It must encompass overall patient safety, patient satisfaction, and employee and physician satisfaction benefit categories. Computerized physician order entry (CPOE) and bar code medication administration (BCMA) systems are two particular clinical point-of-care products that will play a key role in addressing patient safety objectives. Integrating the two technologies can bring both financial and clinical benefits.


Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland.
While acute respiratory tract infections can trigger cardiovascular events, the differential effect of specific organisms is unknown. This is important to guide vaccine policy.Using national infection surveillance data linked to the Scottish Morbidity Record, we identified adults with a first myocardial infarction or stroke from January 1, 2004 to December 31, 2014 and a record of laboratory-confirmed respiratory infection during this period. Using self-controlled case series analysis, we generated age- and season-adjusted incidence ratios (IRs) for myocardial infarction (n=1227) or stroke (n=762) after infections compared with baseline time.We found substantially increased myocardial infarction rates in the week after Streptococcus pneumoniae and influenza virus infection: adjusted IRs for days 1-3 were 5.98 (95% CI 2.47-14.4) and 9.80 (95% CI 2.37-40.5), respectively. Rates of stroke after infection were similarly high and remained elevated to 28 days: day 1-3 adjusted IRs 12.3 (95% CI 5.48-27.7) and 7.82 (95% CI 1.07-56.9) for S. pneumoniae and influenza virus, respectively. Although other respiratory viruses were associated with raised point estimates for both outcomes, only the day 4-7 estimate for stroke reached statistical significance.We showed a marked cardiovascular triggering effect of S. pneumoniae and influenza virus, which highlights the need for adequate pneumococcal and influenza vaccine uptake. Further research is needed into vascular effects of noninfluenza respiratory viruses.


Dietary fiber modulates gut microbiome and metabolome in a host sex-specific manner in a murine model of aging.
Emerging evidence reveals the fundamental role of the gut microbiome in human health. Among various factors regulating our gut microbiome, diet is one of the most indispensable and prominent one. Inulin is one of the most widely-studied dietary fiber for its beneficial prebiotic effects by positively modulating the gut microbiome and microbial metabolites. Recent research underscores sexual dimorphism and sex-specific disparities in microbiome and also diet-microbiome interactions. However, whether and how the prebiotic effects of dietary fiber differ among sexes remain underexplored. To this end, we herein examine sex-specific differences in the prebiotic effects of inulin on gut microbiome and metabolome in a humanized murine model of aging i.e., aged mice carrying human fecal microbiota. The findings demonstrate that inulin exerts prebiotic effects, but in a sex-dependent manner. Overall, inulin increases the proportion of Bacteroides, Blautia, and glycine, while decreasing Eggerthella, Lactococcus, Streptococcus, trimethylamine, 3-hydroxyisobutyrate, leucine and methionine in both sexes. However, we note sex-specific effects of inulin including suppression of f_Enteroccaceae:_, Odoribacter, bile acids, malonate, thymine, valine, acetoin, and ethanol while promotion of Dubosiella, pyruvate, and glycine in males. Whereas, suppression of Faecalibaculum, Lachnoclostridium, Schaedlerella, phenylalanine and enhancement of Parasutterella, Phocaeicola, f_Lachnospiraceae;_, Barnesiella, Butyricimonas, glycine, propionate, acetate and glutamate are observed in females. Altogether, the study reveals that prebiotic mechanisms of dietary fiber vary in a sex-dependent manner, underscoring the importance of including both sexes in preclinical/clinical studies to comprehend the mechanisms and functional aspects of dietary interventions for effective extrapolation and translation in precision nutrition milieus.


Revision in sequence of CAD aspartate transcarbamylase domain of Drosophila.
The Drosophila CAD gene, also known as rudimentary, encodes a protein that carries out the first three enzymatic steps of de novo pyrimidine biosynthesis. The sequence for this gene, as previously published, appears to contain several errors. The correction of six bases in a 250 bp stretch encoding the aspartate transcarbamylase domain leads to changes of frame in two areas of the predicted amino acid sequence, consisting of lengths of 30 and 15 amino acid residues, respectively. The revised sequence shows significantly improved positional identity with both Syrian hamster and Escherichia coli aspartate transcarbamylases.


Brief Mindfulness Practices for Healthcare Providers - A Systematic Literature Review.
Mindfulness practice, where an individual maintains openness, patience, and acceptance while focusing attention on a situation in a nonjudgmental way, can improve symptoms of anxiety, burnout, and depression. The practice is relevant for health care providers; however, the time commitment is a barrier to practice. For this reason, brief mindfulness interventions (eg, ≤ 4 hours) are being introduced. We systematically reviewed the literature from inception to January 2017 about the effects of brief mindfulness interventions on provider well-being and behavior. Studies that tested a brief mindfulness intervention with hospital providers and measured change in well-being (eg, stress) or behavior (eg, tasks of attention or reduction of clinical or diagnostic errors) were selected for narrative synthesis. Fourteen studies met inclusion criteria; 7 were randomized controlled trials. Nine of 14 studies reported positive changes in levels of stress, anxiety, mindfulness, resiliency, and burnout symptoms. No studies found an effect on provider behavior. Brief mindfulness interventions may be effective in improving provider well-being; however, larger studies are needed to assess an impact on clinical care.


Screening for gestational diabetes; past, present and future.
Gestational diabetes is carbohydrate intolerance, with onset or first recognition of hyperglycaemia during pregnancy. Several studies have suggested that gestational hyperglycaemia is associated with adverse maternal and fetal outcomes, promoting the case for screening. Conversely, others argue that screening for gestational diabetes may colour the clinical judgement, influencing further management, e.g. more 'unjustified' caesarean sections. Additionally, the lack of definitive data either on a clear-cut glycaemic threshold for the development of adverse outcomes or on the impact of intervention is emphasized by opponents of screening. This review attempts to evaluate the available data on screening for gestational diabetes. Oral glucose tolerance test is promoted on the basis that the diabetogenic stress of pregnancy is encountered during late gestation and is best recognized in the fed state. There are different tests, including the 1 h/50-g, 2 h/75-g and 3 h/100-g tests, with practical limitations, including the time and cost involved and the unpleasant supra-physiological glucose load that is unrelated to body weight, and issues of reproducibility and sensitivity/specificity profiles. Despite its convenience, the poor sensitivity of random glucose has precluded its routine use for screening. Fasting glucose appears to be promising but further testing is required to ensure satisfactory sensitivity/specificity in different populations. Despite its limitations, the oral glucose tolerance test has become established as the 'most acceptable' diagnostic test for gestational diabetes. More convenient methods, e.g. fasting or random or post-load glucose, have to be validated therefore against the oral glucose tolerance test to gain acceptance for routine screening.


Molecular assays for detection of falcon adenovirus.
Falcon adenovirus is a newly recognized member of the family Aviadenoviridae and includes 2 closely related strains that are pathogenic to several species of falcons. Peregrine falcons appear to be one of the primary reservoirs, but recent outbreaks suggest that other carrier species probably exist. To allow screening of captive birds for virus shedding and investigations of disease outbreaks, conventional and real-time, quantitative polymerase chain reaction (PCR) assays and an in situ hybridization technique were developed. The diagnostic protocols were used on tissue and fecal samples from 7 species or subspecies of falcons infected with adenovirus as well as adenoviruses from other birds and mammals. The assays were specific for falcon adenovirus and detected both strains of virus in fecal samples from living animals or frozen and formalin-fixed, paraffinized tissues. Together with established serologic tests for falcon adenovirus, these molecular assays are valuable tools for management and conservation of falcons in captivity and the wild.


Quantitative concentration measurements of creatinine dissolved in water and urine using Raman spectroscopy and a liquid core optical fiber.
We describe the use of a Teflon-AF liquid core optical fiber (LCOF) geometry to enhance the collection of Raman scattering from the biochemical creatinine, dissolved in water and in urine. At short integration times, where shot noise is most troublesome, the enhanced signal leads to greater accuracy in estimating the creatinine concentration from the spectrum. At longer integration times, instabilities in the LCOF geometry manifest themselves, and the predictions are the same as or worse than those from standard cuvette-based spectral measurements. Photobleaching of fluorescence from urine is more extensive and more stable in the LCOF as well. Starting from the measured enhancement of a major creatinine Raman band, we calculate the expected ratio of prediction errors obtained using the two geometries, and it agrees closely with the observed ratio. These results indicate that Raman spectroscopy with these Teflon-AF LCOFs is stable enough for quantitative concentration predictions, accurate to a few percent of the concentration range spanned.


Mercury/silver resistance genes and their association with antibiotic resistance genes and microbial community in a municipal wastewater treatment plant.
Municipal wastewater treatment plants (WWTPs) are an important reservoir for heavy metal (e.g., Hg and Ag) resistance genes and antibiotic resistance genes (ARGs). However, current knowledge on Hg/Ag resistance genes and their association with ARGs in WWTPs remains largely unknown. In this study, the fates of five Hg/Ag resistance genes (merB, merD, merR, silE, and silR), five ARGs (sulI, sulII, tetO, tetQ, tetW), and class 1 integrase (intI1) in a WWTP were investigated. Results show that the absolute abundances of all target genes were greatly reduced through the treatment systems. The dynamics of merB, merD and silE were significantly correlated with tetW and sulII. Based on network analysis, Hg/Ag resistance genes might share the same microbial hosts with tetQ and tetW, implying the potential importance of Hg/Ag in ARGs evolution and spread. These findings advanced our understanding of the occurrence of Hg/Ag resistance genes and ARGs in WWTPs.


Will antimicrobial resistance of BRD pathogens impact BRD management in the future?
Resistance is a qualitative interpretation of antimicrobial activity in vitro. Critical to management of bovine respiratory disease (BRD) is the clinical response in vivo. Attempts to connect activity in vitro to response in vivo have been complicated by the complexity of BRD, interpretation of antimicrobial activity in vitro, and inconsistent measures of clinical success or failure. During recent history, the discovery, development, and commercialization of antimicrobials have decreased. In response to resistance, voluntary and imposed restrictions on use of antimicrobials have been implemented. Resistance can be reversed using technology and knowledge of mechanisms of resistance. Perhaps approaches that reverse resistance will be used in clinical management of BRD in the future. The short answer to the question posed in the title is, 'yes.' Since antimicrobial drugs were discovered, resistance has been a consideration for selection of treatment of any infectious disease and BRD is not unique. In the opinion of the author, the more important question is, 'How will antimicrobial resistance of BRD pathogens impact BRD management in the future?'


Cultural factors that affected the spatial and temporal epidemiology of kuru.
Kuru is a prion disease which became epidemic among the Fore and surrounding linguistic groups in Papua New Guinea, peaking in the late 1950s. It was transmitted during the transumption (endocannibalism) of dead family members at mortuary feasts. In this study, we aimed to explain the historical spread and the changing epidemiological patterns of kuru by analysing factors that affected its transmission. We also examined what cultural group principally determined a family's behaviour during mortuary rituals. Our investigations showed that differences in mortuary practices were responsible for the initial pattern of the spread of kuru and the ultimate shape of the epidemic, and for subsequent spatio-temporal differences in the epidemiology of kuru. Before transumption stopped altogether, the South Fore continued to eat the bodies of those who had died of kuru, whereas other linguistic groups, sooner or later, stopped doing so. The linguistic group was the primary cultural group that determined behaviour but at linguistic boundaries the neighbouring group's cultural practices were often adopted. The epidemiological changes were not explained by genetic differences, but genetic studies led to an understanding of genetic susceptibility to kuru and the selection pressure imposed by kuru, and provided new insights into human history and evolution.


Wnt/β-catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c-Myc and cyclin D1 via the p38 MAPK-dependent pathway.
Airway remodeling is the main characteristic of asthma; however, the mechanisms underlying this pathophysiological change have not been fully elucidated. Previous studies have indicated that the Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling pathway are involved in the development of airway remodeling during asthma. Therefore, the present study established an airway remodeling rat model, after which β-catenin, cyclin D1 and c-Myc protein expressions were analyzed via western blotting in the lung tissue and airway smooth muscle cells (ASMCs) of rats. The mRNA expression of the aforementioned proteins were evaluated via reverse transcription-quantitative PCR. β-catenin, cyclin D1 and c-Myc are core transcription factors and target genes of the Wnt/β-catenin and MAPK signaling pathways. Furthermore, β-catenin, c-Myc and cyclin D1 protein expression were determined following blocking of the p38 MAPK signaling pathway in vitro. The results demonstrated that higher expressions of β-catenin, cyclin D1 and c-Myc were detected in lung tissues and ASMCs in the asthma group compared with the control. Blocking the p38 MAPK signaling pathway with a specific inhibitor SB203580 also downregulated the expressions of β-catenin, cyclin D1 and c-Myc in vitro. Taken together, these results indicated that the Wnt/β-catenin signaling pathway may regulate the process of airway remodeling via the p38 MAPK-dependent pathway.


Bovine coronavirus in neonatal calf diarrhoea in Iran.
Partial gene sequencing for the bovine coronavirus at the World Genebank is available for many countries, which are distributed unevenly in five continents, but so far, no sequencing of strains has been recorded in Iran. One hundred ninety-four stool samples from calves with diarrhoea less than one-month old were collected from five different geographical regions of country in order to detect coronavirus and characterize it if coronavirus was found. Samples were screened for the presence of BCoV by using a commercially available ELISA kit. Furthermore, RT-PCR was carried out on positive samples for confirmation of the presence of N and S specific genes. Sequencing and phylogenetic analysis was carried out following RT-PCR tests. 7.2% of samples, were positive for BCoV and all stool samples from the South-West, Northeast and West regions of Iran were negative. The results showed that all the strains of coronavirus identified in Iran were completely in independent clusters and that they did not stand in the same cluster as any of the strains identified in other parts of the world. The strains from Iran were quite different from strains in other parts of the world but from the point of similarity these viruses showed some similarities to the European strains, such as those found in France, Croatia, Denmark and Sweden.


Viscoelastic Methods of Blood Clotting Assessment - A Multidisciplinary Review.
Viscoelastic methods (VEM) made available the bedside assessment of blood clotting. Unlike standard laboratory tests, the results are based on the whole blood coagulation and are available in real time at a much faster turnaround time. In combination with our new knowledge about pathophysiology of the trauma-induced coagulopathy, the goal-oriented treatment protocols have been recently proposed for the initial management of bleeding in trauma victims. Additionally, the utility of viscoelastic monitoring devices has been proved even outside this setting in cardiosurgical patients or those undergoing liver transplantation. Many other situations were described in literature showing the potential use of bedside analysis of coagulation for the management of bleeding or critically ill patients. In the near future, we may expect further improvement in current bedside diagnostic tools enabling not only the assessment of secondary hemostasis but also the platelet aggregation. More sensitive assays for new anticoagulants are underway. Aim of this review is to offer the reader a multidisciplinary overview of VEM and their potential use in anesthesiology and critical care.


Discovery of aromatic components with excellent fragrance properties and biological activities: β-ionols with antimelanogenetic effects and their asymmetric syntheses.
Both enantiomers of dihydro-β-ionol and β-ionol, contained in the aromatic components of Osmanthus flower and of Hakuto peach, were obtained with high optical purity by lipase-catalyzed kinetic resolution of the racemates. It was found that all these enantiomers had different characteristic favorable scents and high antimelanogenetic effects. The absolute configuration and the enantiomer ratios of dihydro-β-ionol in the aromatic components of Osmanthus flower and of Hakuto peach were determined. The asymmetric synthesis of (R)-dihydro-β-ionol, one of the most valuable raw materials for fragrance and flavor, was performed from inexpensive β-ionone via lipase-catalyzed dynamic kinetic resolution followed by reduction.


F2-isoprostanes affect macrophage migration and CSF-1 signalling.
F2-isoprostanes (F2-IsoP) are formed in vivo via free radical peroxidation of arachidonic acid. Enhanced oxidative stress is implicated in the development of atherosclerosis in humans and F2-IsoP have been detected in atherosclerotic plaque. Colony stimulating factor-1 (CSF-1) is essential to macrophage survival, proliferation and differentiation and has been detected in human atherosclerotic plaques. Accumulation of macrophages within the vascular wall is an important component of atherosclerosis but little is known about the effect of F2-IsoP on the migration of these cells. Our aim was to examine the effect of free and lipid-bound 15-F2t-isoprostane (15-F2t-IsoP) on macrophage migration and investigate the signalling pathways involved. Mouse macrophages (cell line BAC1.2F5) were pre-incubated with 15-F2t-IsoP (free, bound to cholesterol or monoacylglycerol or within oxidized phospholipid) and cell migration was assessed using chemotaxis towards CSF-1 in Boyden chambers. Migration was also measured using the wound healing assay with primary mouse bone marrow derived macrophages. We showed that 15-F2t-IsoP dose-dependently inhibited BAC1.2F5 macrophage spreading and adhesion but stimulated their migration towards CSF-1, with maximum effect at 10 µM. Analysis of CSF-1 stimulated signalling pathways in BAC1.2F5 macrophages showed that phosphorylation of Akt, a key mediator of cell migration, and one of its regulators, the mTORC2 component, Rictor, was significantly decreased. In contrast, phosphorylation of the adhesion kinases, FAK and Pyk2, and the adhesion scaffold protein, paxillin, was enhanced after treatment with 15-F2t-IsoP. Mouse bone marrow macrophages were transfected with FAK or Pyk2 small interfering RNA (siRNA) to examine the role of FAK and Pyk2 in 15-F2t-IsoP signalling. Pyk2 silencing inhibited 15-F2t-IsoP-induced reduction in cell area and phospho-paxillin adhesion numbers. The size distribution of adhesions in the presence of 15-F2t-IsoP was also affected by Pyk2 silencing and there was a trend for Pyk2 silencing to reduce 15-F2t-IsoP-stimulated macrophage migration. These results demonstrate that 15-F2t-IsoP affects macrophage adhesions and migration, which are integral components of macrophage involvement in atherosclerosis.


Dietary tryptophan-rich protein hydrolysate can acutely impact physiological and psychological measures of mood and stress in healthy adults.
Tryptophan is the precursor to the mood regulating neurotransmitter serotonin. Its brain bioavailability from food can be dependent on the dietary source. Egg protein hydrolysate (EPH), a dietary supplement rich in tryptophan, has previously shown to acutely impact cognition, mood and stress benefits at 2 g dose. No data exist on the acute effects of lower doses in a food matrix. This exploratory study tested the acute effects of low-doses EPH (0.5, 1 g) in a food matrix on cognition, mood and stress. The study employed a double-blinded randomized controlled parallel design in 45 participants with three arms. The effects of the interventions were measured after a multi-task cognitive stressor on blood biomarkers, self-reported mood states, performances of attention, autonomic parameters and, emotional reactivity responses from electroencephalographic recording. As compared to the reference, the 1 g EPH dose increased tryptophan bioavailability from baseline, and, both doses improved heart rate variability parameters related to parasympathetic activation while showing differences in the late neural response to negative versus neutral emotions. Post-hoc analyses indicated a gender difference in the baseline tryptophan bioavailability and further examination suggested the change in mood rating depends on the interaction between gender and change from baseline of tryptophan bioavailability. Overall, this study suggests that low levels of tryptophan rich EPH in a food matrix positively impact mood or stress in acute settings and adds to the body of evidence linking tryptophan and dietary sources thereof with these benefits. Confirmatory randomized controlled trials are needed to confirm these findings.Trial registration number: CER-VD N°2019-00218.


MR molecular imaging of tumors based on an optimal hTERT promoter tyrosinase expression system.
The early diagnosis and treatment of tumors is of vital significance to increase patient survival. Therefore, we constructed a lentiviral vector expressing tyrosinase (TYR) driven by an optimized human telomerase reverse transcriptase (hTERT) promoter or a cytomegalovirus(CMV) promoter in the hopes of performing noninvasive and real-time tumor-specific imaging. First, hTERT-TYR and CMV-TYR were constructed to infect cancer cell lines (telomerase-negative cell line: U2OS; telomerase-positive cell lines: SGC-7901, SW480 and HepG2). Subsequently, stable tyrosinase-expressing cell lines were sorted by flow cytometry out of these infected cancer cell lines. Then, the mRNA and protein levels of tyrosinase were analyzed. Thetyrosinase activity, melanin production and ferric ion adsorption were measured followed by an MR scan. Consequently the results showed that tyrosinase was only expressed in telomerase-positive tumor cells infected by hTERT-TYR, whereas tyrosinase was expressed in both telomerase-negative and telomerase-positive tumor cells infected by CMV-TYR. Finally, we performed in vivo tumor MR using a clinical 3T MR scanner and found increased signals at T1W1 from telomerase-positive cells infected by hTERT-TYR, which revealed that MR scanning could distinguish cells with hTERT -positive cells from hTERT-negative cells infected with the optimized lentivirus. The mechanism underlying this effect is that tyrosinase promotes melanin production and ferric ion adsorption only in hTERT-expressing cells. Taken together, these data show that this optimized hTERT promoter-driving tyrosinase expression system might be a useful diagnostic tool for the detection of tumors using MR imaging.


Rapid discovery and identification of the prototypes and their metabolites of Da-Huang-Xiao-Shi decoction in rat plasma by an integrative strategy based on liquid chromatography coupled with mass spectrometry.
Da-Huang-Xiao-Shi decoction has been used to treat damp-heat jaundice for centuries in China. However, the absorbed components of the decoction and their related metabolites are little known until now. In this work, an integrative strategy based on liquid chromatography coupled with mass spectrometry (time-of-flight/triple-quadruple tandem) was adopted to effectively identify the prototypes and their metabolites and to speculate the possible transformation pathways among these compounds. Using pattern recognition approaches, the exogenous compounds in rat plasma were screened out from endogenous compounds and then distinguished into prototypes and metabolites according to the characteristic information from the self-building database of Da-Huang-Xiao-Shi decoction. On this basis, the metabolic profiles of main prototypes (such as iridoid glycosides, alkaloids, and anthraquinones) were proposed. As a result, a total of 62 related prototypes and their metabolites were detected and tentatively identified in rat plasma after administration, and among them, three prototypes were found for the first time. Glucuronidation and sulfation were deduced to be the main metabolic pathways of alkaloids, iridoid glycosides, and anthraquinones. The integrative strategy used in this study was an effective approach to rapidly discover and characterize the prototypes and their metabolites from a complex bio-sample without the use of standard substances.


Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics.
The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.


Receptor-based targeting of therapeutics.
Receptor-based targeting of therapeutics may be a fascinating proposition to improve the therapeutic efficacy of encapsulated drugs. The development of safe and effective nanomedicines is a prerequisite in the current nanotechnological scenario. Currently, the surface engineering of nanocarriers has attracted great attention for targeted therapeutic delivery by selective binding of targeting ligand to the specific receptors present on the surface of cells. In this review, we have discussed the current status of various receptors such as transferrin, lectoferrin, lectin, folate, human EGF receptor, scavenger, nuclear and integrin, which are over-expressed on the surface of cancer cells; along with the relevance of targeted delivery systems such as nanoparticles, polymersomes, dendrimers, liposomes and carbon nanotubes. The review also focuses on the effective utilization of receptor-based targeted delivery systems for the management of cancer in effective ways by minimizing the drug-associated side effects and improving the therapeutic efficacy of developed nano-architectures.


Demonstration of nucleolar organizer regions in intrahepatic bile duct carcinoma by the silver-staining technique.
A silver colloid technique to identify argyrophilic nucleolar organizer region associated protein (AgNOR) was applied to 43 cases of intrahepatic bile duct carcinoma (cholangiocarcinoma, CC), 2 with bile duct adenoma (BDA), 5 with focal duct epithelial hyperplasia (FEH) associated with hepatolithiasis, 15 with posthepatitic ductular proliferation (PHDP) associated with massive or submassive hepatic necrosis and 20 of normal liver. In the present study, only discrete, easily counted black dots within nuclei and silver-stained nucleolus were counted under a magnification of x 400 without oil-immersion objectives. The mean AgNOR count of CC was significantly higher than those of BDA, FEH, PHDP and normal controls (P less than 0.05, P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Among CCs the mean AgNOR numbers of papillary adenocarcinoma (pap), moderately (tub2) and poorly differentiated (por) adenocarcinoma, and adenosquamous carcinoma (as) were significantly higher than that of normal controls (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.001, respectively), and those of tub2, por and as were also significantly higher than those of BDA, FEH and PHDP, whereas that of well differentiated tubular adenocarcinoma (tub1) was not different from those of BDA, FEH, PHDP and normal controls, and that of pap was not different from those of BDA, FEH and PHDP. The mean numbers of AgNORs of BDA and FEH were not different from that of normal controls, whereas that of PHDP was significantly higher than that of normal controls (P less than 0.01). Interestingly, the mean AgNOR counts of tubular adenocarcinoma were increased with histologic tumor grades.(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of Outcome in Conservative and Minimally Invasive Surgical Management of Pain Originating From the Sacroiliac Joint: A Pooled Analysis.
A pooled patient-level analysis of two multicenter randomized controlled trials and one multicenter single-arm prospective trial. The aim of this study was to identify predictors of outcome of conservative and minimally invasive surgical management of pain originating from the sacroiliac joint (SIJ). Three recently published prospective trials have shown that minimally invasive SIJ fusion (SIJF) using triangular titanium implants produces better outcomes than conservative management for patients with pain originating from the SIJ. Due to limitations in individual trial sample size, analyses of predictors of treatment outcome were not conducted. We pooled individual patient data from the three trials and used random effects models with multivariate regression analysis to identify predictors for treatment outcome separately for conservative and minimally invasive surgical treatment. Outcome was measured using visual analogue scale (VAS), Oswestry Disability Index (ODI), and EuroQOL-5D (EQ-5D). We included 423 patients assigned to either nonsurgical management (NSM, n = 97) or SIJF (n = 326) between 2013 and 2015. The reduction in SIJ pain was 37.9 points larger [95% confidence interval (95% CI) 32.5-43.4, P < 0.0001] in the SIJF group than in the NSM group. Similarly, the improvement in ODI was 18.3 points larger (95% CI 14.3-22.4), P < 0.0001). In NSM, we found no predictors of outcome. In SIJF, a reduced improvement in outcome was predicted by smoking (P = 0.030), opioid use (P = 0.017), lower patient age (P = 0.008), and lower duration of SIJ pain (P = 0.028). Our results support the view that SIJF leads to better treatment outcome than conservative management of SIJ pain and that a higher margin of improvement can be predicted in nonsmokers, nonopioid users, and patients of increased age and with longer pain duration. 1.


A case of microstomia subsequent to toxic epidermal necrolysis surgically treated by simple technique.
Toxic epidermal necrolysis (TEN) is a rare but severe adverse dermatitis that is an autoimmune reaction to drugs such as nonsteroidal anti-inflammatory drugs. TEN most severely affects the mucous membranes including the mouth and could develop into microstomia; however, microstomia in relation to TEN has rarely been reported in the literature. We describe an adult female patient who developed microstomia due to scar contracture of the bilateral oral commissures subsequent to TEN and was successfully treated by a simple surgical technique consisting solely of transverse incision of the commissure and longitudinal closure.


Microbiota of Honeybees, <I>Apis mellifera Adansonii </I>(Hymenoptera: Apidae) from Selected Ecozones, South West Nigeria.
Honeybees explore their environment in search of nectar and pollens including water whose sources are contaminated by variety of microbes. This has both negative and positive economic implications on health status of honeybees, the consumers of the products including the quality of the products. Hence, the study was designed to investigate the effect of geographical locations on the occurrence and diversity of microbiota on the external integument and the digestive gut of adult worker honeybees, Apis mellifera adansonii. The honeybee samples were sourced from Ondo, Ogun, Oyo and Osun of South West Nigeria. The samples were subjected to microbiological analyses using standard techniques. Two-ways ANOVA was used for statistical test of the data. The microbiota of the studied samples includes Corynebacterium kutsceri, Corynebacterium xerosis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus fermentum, Micrococcus luteus, Micrococcus varians and Staphylococcus aureus which were gram-positive bacteria, while gram-negative bacteria include Aeromonas veronii, Citrobacter diversus, Citrobacter freundii, Klebsiella oxytoca, Klebsiella pneumonia and Pseudomonas aeruginosa. Fungi isolates include Aspergillus parasiticus, Aspergilus flavus, Aspergilus fumigatus, Aspergilus niger and Rhizopus stolonifer. Most microbiota were not cosmopolitan across selected ecozones of south west, Nigeria except for Aspergillus fumigatus. The number of identified species of microbiota either in the digestive guts or on the external integument of worker honeybees from selected ecozones varies from one ecozone to another. There was significant species diversity of microbiota on external integument than in digestive guts of adult workers of A. mellifera adansonii from selected ecozones in South West, Nigeria. The study showed that both the external integument and the digestive guts of A. mellifera adansonii exhibited variety of microbial flora providing research exploration opportunity for probable microbes of economic and geographical importance.


Angle Locking of a Levitating Diamond Using Spin Diamagnetism.
Nanodiamonds with embedded nitrogen-vacancy (NV) centers have emerged as promising magnetic field sensors, as hyperpolarizing agents in biological environments, as well as efficient tools for spin mechanics with levitating particles. These applications currently suffer from random environmental interactions with the diamond which implies poor control of the N-V direction. Here, we predict and report on a strong diamagnetism of a pure spin origin mediated by a population inversion close to a level crossing in the NV center electronic ground state. We show control of the sign of the magnetic susceptibility as well as angle locking of the crystalline axis of a microdiamond along an external magnetic field, with bright perspectives for these applications.


Biochemical characterization of familial amyloidotic polyneuropathy in various districts of Japan.
The purpose of this study is to disclose the molecular basis of type I familial amyloidotic polyneuropathy (FAP) in Japan. Amyloid fibril protein of type I FAP consists of a variant transthyretin (also called prealbumin) with one amino acid substitution of methionine-for-valine at position 30. This variant transthyretin is present in the serum as a precursor protein of amyloid. A radioimmunoassay (RIA) has been established to detect the variant transthyretin. All the 94 patients with FAP who originate from various districts in Japan have the variant transthyretin, but any one of 78 healthy adults of families with FAP do not have it. Half of the symptom-free children of FAP patients have the variant transthyretin even before clinical manifestations appear. The RIA is widely applicable for early diagnosis. The methionine-for-valine substitution is due to a base change from guanine to adenine at the first letter of the valine codon at position 30. Type I FAP in Japan is considered to be a molecular disorder of transthyretin. Since the age of onset ranges from twenties to forties, genetic counseling is recommended to prevent the transmission of this intractable disorder to the next generation.


Designing new lithium-excess cathode materials from percolation theory: nanohighways in Li(x)Ni(2-4x/3)Sb(x/3)O2.
Increasing lithium content is shown to be a successful strategy for designing new cathode materials. In layered Li(x)Ni(2-4x/3)Sb(x/3)O2 (x = 1.00-1.15), lithium excess improves both discharge capacity and capacity retention at 1C. Structural studies reveal a complex nanostructure pattern of Li-Sb and Ni-Sb ordering where the interface between these domains forms the correct local configuration for good lithium mobility. The <1 nm Li-Sb stripe domains and their interfaces thereby effectively act as nanohighways for lithium diffusion.


Telehealth for Children With Medical Complexity During the COVID Pandemic: A Qualitative Study Exploring Caregiver Experiences.
Children with medical complexity (CMC) receive care from many clinicians. Our objective is to describe caregivers' experiences about telehealth for CMC. This qualitative study conducted in North Carolina involves semistructured interviews with 23 caregivers of CMC (15 English; 8 Spanish). Data were analyzed using thematic content analysis. Five themes were identified: (1) telehealth allayed caregivers' fears about their children's exposure to COVID-19 and mitigated the challenges with in-person visits during the pandemic. (2) Telehealth reduced the logistical challenges of in-person visits for CMC, enabled providers to see children in their home environment, and prevented appointment cancelations. (3) System inaccessibility, technical problems, and providers' inability to deliver telehealth were challenges. (4) Inadequate evaluation of the child and caregiver-provider communication were limitations. (5) Caregivers were satisfied with telehealth, found variability in telehealth offering, and wished telehealth continued to remain an option. Telehealth is a viable option for outpatient care delivery for CMC.


Initiation of postpartum luteal function in primiparous restricted-suckled beef cows exposed to a bull or excretory products of bulls or cows.
The objective of this study was to evaluate the influence of bull excretory products on the resumption of postpartum luteal function in primiparous, restricted-suckled cows. Hypotheses tested were that resumption of luteal function or proportions of cows that initiate luteal cycling did not differ among cows exposed to a bull (BE), exposed to excretory products of bulls (EPB), not exposed to a bull (NE), or exposed to excretory products of cows (EPC). Two-year-old Angus x Hereford cows were assigned 35 d after calving to one of the four treatments (n = 15, 16, 16, and 15 for BE, EPB, NE, and EPC, respectively). Cows in the EPB and EPC treatments were placed in enclosures for 10 to 12 h, between 1830 and 0800 daily. Each enclosure was occupied by bulls (EPB) or left empty (EPC) for 10 to 12 h (0800 to 1830) daily. All cows were restricted to suckling twice daily (0800 and 1800) beginning on d 0. Blood samples were obtained from each cow on d -1 and every third day of the study thereafter. An increase in progesterone concentrations in three consecutive samples that exceeded 1.0 ng/mL was used as evidence of resumption of luteal function. Interval from d 0 to resumption of luteal activity was less for (P < 0.05) BE and EPB cows than for NE cows, but did not differ between BE and EPB cows. Interval for EPC cows did not differ from that for NE cows; however, interval for EPC cows was greater (P = 0.06) than that for BE cows and was longer (P < 0.05) than that of EPB cows. Proportions of cows that resumed luteal function by d 40 and 50 did not differ between NE and EPC cows; however, proportions of EPB and BE cows that resumed luteal function were greater (P < 0.05) than those for NE and EPC cows by d 40 and 50. Proportions of cows that resumed luteal function by d 70 were greater (P < 0.05) for BE, EPB, and EPC cows than for NE cows; however, proportions of BE and EPC cows did not differ. The proportion of EPB cows that resumed luteal function was greater (P = 0.058) than that of EPC cows, but the proportion of BE cows that resumed luteal function did not differ from that of EPC cows by d 70. We conclude that exposing primiparous restricted-suckled cows to excretory products of bulls or crowding estrus-cycling cows in an enclosure hastened postpartum resumption of luteal function. Therefore, the biostimulatory role of bulls and the crowding effect of cows seem to be mediated by a pheromone (or pheremones) present in their excretory products.


Use of reverse osmosis membranes to remove perfluorooctane sulfonate (PFOS) from semiconductor wastewater.
Perfluorooctane sulfonate (PFOS) and related substances are persistent, bioaccumulative, and toxic, and thus of substantial environmental concern. PFOS is an essential photolithographic chemical in the semiconductor industry with no substitutes yet identified. The industry seeks effective treatment technologies. The feasibility of using reverse osmosis (RO) membranes for treating semiconductor wastewater containing PFOS has been investigated. Commercial RO membranes were characterized in terms of permeability, salt rejection, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and membrane surface zeta potential (streaming potential measurements). Filtration tests were performed to determine the membrane flux and PFOS rejection. Over a wide range of feed concentrations (0.5 - 1500 ppm), the RO membranes generally rejected 99% or more of the PFOS. Rejection was better for tighter membranes, but was not affected by membrane zeta potential. Flux decreased with increasing PFOS concentration. While the flux reduction was severe for a loose RO membrane probably due to its higher initial flux, very stable flux was maintained for tighter membranes. At a very high feed concentration (about 500 ppm), all the membranes exhibited an identical stable flux. Isopropyl alcohol, present in some semiconductor wastewaters, had a detrimental effect on membrane flux. Where present it needs to be removed from the wastewater prior to using RO membranes.


High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births.
A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies.


Multiple shifts in the representation of a motor sequence during the acquisition of skilled performance.
When do learning-related changes in performance occur? Here we show that the knowledge of a sequence of movements evolves through several distinctive phases that depend on two critical factors: the amount of practice as well as the passage of time. Our results show the following. (i) Within a given session, large performance gains constituted a signature for motor novelty. Such gains occurred only for newly introduced conditions irrespective of the absolute level of performance. (ii) A single training session resulted in both immediate but also time-dependent, latent learning hours after the termination of practice. Time in sleep determined the time of expression of these delayed gains. Moreover, the delayed gains were sequence-specific, indicating a qualitative change in the representation of the task within 24 h posttraining. (iii) Prolonged training resulted in additional between-session gains that, unlike the effects of a single training session, were confined to the trained hand. Thus, the effects of multisession training were qualitatively different than the immediate and time-dependent effects of a single session. Altogether, our results indicate multiple time-dependent shifts in the representation of motor experience during the acquisition of skilled performance.


Angioscopic observation during carotid angioplasty with stent placement.
This clinical report is the first to describe angioscopy during carotid angioplasty with stent placement. The average observation time was 3 minutes 43 seconds in 18 cases. The view was clear in 67% of cases. Lesions in the endothelium, rupture of the fibrous cap, clots, debris detaching from plaque, and stent struts were observed. No symptomatic ischemic complications occurred. Diffusion-weighted MR imaging after angioscopy showed asymptomatic ischemic lesions in 47% of cases.


Phagocytosis: dynamin's dual role in phagosome biogenesis.
Dynamins have a well-established role in the fission of vesicles at sites of endocytosis. In phagocytosis, however, a role for certain dynamin isoforms has been reported in the full extension of pseudopods during phagosome formation, not in fission of the phagocytic vacuole. Recent studies in Caenorhabditis elegans have now uncovered a new function of dynamin in phagosome maturation.


[Prevention and management of postoperative complications in pancreatic surgery].
During the last decades mortality after pancreatic surgery has decreased. Nevertheless, morbidity still remains at a high level. It is important to differentiate between pancreatic head resection and distal pancreatectomy. The complication rates of both procedures are high, however the need for intervention to manage perilous complications is higher after pancreaticoduodenectomy. The main complications after pancreatic surgery are delayed gastric emptying (DGE), pancreatic fistula, anastomotic leakage and bleeding. The current literature on the different techniques of pancreatic anastomosis and pancreatic remnant closure, respectively, does not show consistent results or an advantage for a particular technique. The same is true for the perioperative use of somatostatin and its analogues for the prevention of complications. It is widely agreed that the smooth texture of the pancreas and a small pancreatic duct < 3 mm are risk factors for pancreatic leakage or fistula. Today, the trend is more for conservative or interventional therapy for pancreatic fistulas or intraabdominal collections with, e. g., persisting intraoperative drain, TPN, somatostatin therapy or CT-controlled drainage. The opinions about the optimal treatment of the dreaded postoperative bleeding differ significantly in the surgical community. There are early and late bleedings and the management varies from endoscopical treatment or angiographic coiling / stenting to revision. Nevertheless, every bleeding is accompanied with high mortality. Here we present a review of literature and demonstrate the various strategies for the management of complications.


Rooting depth, water relations and non-structural carbohydrate dynamics in three woody angiosperms differentially affected by an extreme summer drought.
In 2012, an extreme summer drought induced species-specific die-back in woody species in Northeastern Italy. Quercus pubescens and Ostrya carpinifolia were heavily impacted, while Prunus mahaleb was largely unaffected. By comparing seasonal changes in isotopic composition of xylem sap, rainfall and deep soil samples, we show that P. mahaleb has a deeper root system than the other two species. This morphological trait allowed P mahaleb to maintain higher water potential (Ψ), gas exchange rates and non-structural carbohydrates content (NSC) throughout the summer, when compared with the other species. More favourable water and carbon states allowed relatively stable maintenance of stem hydraulic conductivity (k) throughout the growing season. In contrast, in Quercus pubescens and Ostrya carpinifolia, decreasing Ψ and NSC were associated with significant hydraulic failure, with spring-to-summer k loss averaging 60%. Our data support the hypothesis that drought-induced tree decline is a complex phenomenon that cannot be modelled on the basis of single predictors of tree status like hydraulic efficiency, vulnerability and carbohydrate content. Our data highlight the role of rooting depth in seasonal progression of water status, gas exchange and NSC, with possible consequences for energy-demanding mechanisms involved in the maintenance of vascular integrity.


Second-language experience modulates eye movements during first- and second-language sentence reading: evidence from a gaze-contingent moving window paradigm.
Eye movement measures demonstrate differences in first-language (L1) and second-language (L2) paragraph-level reading as a function of individual differences in current L2 exposure among bilinguals (Whitford & Titone, 2012). Specifically, as current L2 exposure increases, the ease of L2 word processing increases, but the ease of L1 word processing decreases. Here, we investigate whether current L2 exposure also relates to more general aspects of reading performance, including global eye movement measures and how bilinguals use parafoveal information to the right of fixation during L1 and L2 sentence-level reading, through use of a gaze-contingent moving window paradigm (McConkie & Rayner, 1975). We found that bilinguals with high versus low current L2 exposure exhibited increased L2 reading fluency (faster reading rates, shorter forward fixation durations), but decreased L1 reading fluency (slower reading rates, longer forward fixation durations). We also found that bilinguals with high versus low current L2 exposure were more affected by reductions in window size during L2 reading (indicative of a larger L2 perceptual span), but were less affected by reductions in window size during L1 reading (indicative of a smaller L1 perceptual span). Taken together, these findings suggest that individual differences in current L2 exposure among bilinguals also modulate more general aspects of reading behavior, including global measures of reading difficulty and the allocation of visual attention into the parafovea during both L1 and L2 sentence-level reading.


In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect-Exposure Relationship in Rat Plasma.
Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent.


Lifetime History of Concussion Among Youth With ADHD Presenting to a Specialty Concussion Clinic.
Child and adolescent student athletes with attention-deficit/hyperactivity disorder (ADHD) report a greater lifetime history of concussion than those without ADHD. This case-control study compared youth with and without ADHD presenting for care at a specialty concussion clinic on their lifetime history of concussion. We hypothesized that a greater proportion of youth with ADHD would report a history of prior concussion. Archival clinical data from patients presenting to a specialty concussion clinic in Montreal, Québec, Canada between September 2015 and August 2019 were analyzed. The sample included 2,418 children and adolescents (age: M = 13.6, SD = 2.7, range 5-18 years; 50.9% girls), including 294 (12.2%) with ADHD and 2,124 (87.8%) without ADHD. The proportion with prior concussion among youth with ADHD (43.9%) was significantly greater than youth without ADHD [37.5%, χ2 = 4.41, p = 0.04, OR = 1.30, 95% confidence interval (CI): 1.02-1.67]. A significantly higher proportion of boys with ADHD had a prior concussion history (48.1%) than boys without ADHD [38.4%, χ2 = 5.33, p = 0.02, OR = 1.48 (95% CI: 1.06-2.09)], but this difference was not observed for girls (χ2 = 0.31, p = 0.58). Youth with ADHD did not differ with regard to their estimated longest duration of symptoms from a prior concussion (Z = 1.52, p = 0.13) and the proportion who reported taking longer than 28 days to recover from a prior concussion did not differ between those with ADHD (15.3%) and without ADHD (12.2%), χ2 = 2.20, p = 0.14. Among youth presenting to a specialty clinic, ADHD was associated with greater lifetime history of concussion but not a greater duration of symptoms from a prior injury.


Transmitted Light as Attractant with Mechanical Traps for Collecting Nocturnal Mosquitoes in Urban Bangkok, Thailand.
Mosquito surveillance is the cornerstone for determining abundance, species diversity, pathogen infection rates, and temporal and spatial distribution of different life stages in an area. Various methods are available for assessing adult mosquito populations, including mechanical trap devices using different forms of attractant cues (chemical and visual) to lure mosquitoes to the trap. So-called "light traps" use various electromagnetic wavelengths to produce a variety of visible spectral colors to attract adult mosquitoes. However, this type of trapping technology has not been widely used in Thailand. This study compared the efficacy of 4 light-emitting diodes (LEDs) (blue, green, yellow, and red) and 2 fluorescent (ultraviolet [UV] and white) lights for collecting mosquitoes in urban Bangkok. Using a Latin square experimental design, 6 light traps equipped with different lights were rotated between 6 trap site locations within the Kasetsart University (KU) campus. Each location received 6 replicate collections (6 consecutive trap-nights represented 1 replicate) over 36 collection nights for a total of 216 trap-nights. Traps were operated simultaneously (1800 to 0600 h), with captured mosquitoes removed at 3-h intervals. In total, 2,387 mosquitoes consisting of 11 species across 5 genera (Aedes, Anopheles, Armigeres, Culex, and Mansonia) were captured. Collectively, Culex species represented the predominant group sampled (2,252; 94.4%). The UV light source captured 1,544 (64.7%) of the total mosquitoes collected, followed by white 389 (16.3%), with the 4 LED sources collecting between 6.8% (blue) and 1.9% (yellow). Traps equipped with UV light were clearly the most effective for capturing nocturnally active mosquito species on the KU campus.


A novel fluorogenic reporter substrate for 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2): Application to high-throughput screening for activators to treat Alzheimer's disease.
A rare coding variant in PLCγ2 (P522R) expressed in microglia induces a mild activation of enzymatic activity when compared to wild-type. This mutation is reported to be protective against the cognitive decline associated with late-onset Alzheimer's disease (LOAD) and therefore, activation of wild-type PLCγ2 has been suggested as a potential therapeutic target for the prevention and treatment of LOAD. Additionally, PLCγ2 has been associated with other diseases such as cancer and some autoimmune disorders where mutations with much greater increases in PLCγ2 activity have been identified. Here, pharmacological inhibition may provide a therapeutic effect. In order to facilitate our investigation of the activity of PLCγ2, we developed an optimized fluorogenic substrate to monitor enzymatic activity in aqueous solution. This was accomplished by first exploring the spectral properties of various "turn-on" fluorophores. The most promising turn-on fluorophore was incorporated into a water-soluble PLCγ2 reporter substrate, which we named C8CF3-coumarin. The ability of PLCγ2 to enzymatically process C8CF3-coumarin was confirmed, and the kinetics of the reaction were determined. Reaction conditions were optimized to identify small molecule activators, and a pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC1280) was performed with the goal of identifying small molecule activators of PLCγ2. The optimized screening conditions allowed identification of potential PLCγ2 activators and inhibitors, thus demonstrating the feasibility of this approach for high-throughput screening.


MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview.
Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.


Virus-host interaction in chronic hepatitis B virus infection.
The clearance of HBV-infected cells from the liver is probably dependent on an interplay between the interferon system and the cellular limb of the host immune response. Although the importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells is established in chronic HBV infection, further studies are needed during the early phase of acute HBV infection. The relative importance of pre S sequences as inducers and targets of the virus neutralizing humoral immune response is becoming established, but their precise place will await the development of in vitro models of hepadnavirus infection and precise definition of the mechanism of viral uptake. Our understanding of the mechanisms underlying the development of chronic HBV infection is still incomplete. When this occurs in adult life, deficient production of alpha interferon and suppression of the ability of the host to respond to interferon are probably important factors, and the role of suppression of the humoral response remains to be determined. In the neonate, specific suppression of the cell-mediated immune response, perhaps because of exposure to soluble HBe antigen or to modulating quantities of maternally derived antinucleocapsid antibodies at a time when the immune system is "immature," may be involved. In each of these postulated mechanisms the virus has neutralized one important host defense. Increasing the response rate to therapy with interferon or synthetic antiviral compounds will depend on identifying the cause in each patient and devising specific therapies to reverse the host-virus balance in favor of the host defenses.


VARIABLE SELECTION ALONG A SUCCESSIONAL GRADIENT.
Patterns of selection were measured in populations of the perennial grass Danthonia spicata from a successional gradient in northern lower Michigan for a five-year period. Phenotypic variation was found both within and among populations for morphological, reproductive, and life-history traits. Two fitness components were measured: fecundity (total number of spikelets produced) and mortality (number of years an individual lived). Multiple-regression analysis of relative reproductive effort (percentage of culms that flowered), culm length, and leaf length against fitness showed substantial variation in the magnitude and direction of selection among the populations and among the fitness components. When three other reproductive traits were added to the analysis, there were no qualitative changes in estimates of directional selection coefficients, but there were pronounced changes in estimates of stabilizing/disruptive selection components. Patterns of selection were concordant with previously measured genetic changes in reproductive effort along the successional gradient but not concordant with genetic changes in culm length and leaf length. These same patterns were found in comparisons of Michigan and North Carolina populations.


Effect of anti-donor serum (ADS) and donor cells on renal allograft survival in DL-A tissue-typed littermate beagles.
The influence of passive and active immunization on kidney allograft survival was tested in littermate beagles differing in one and two DL-A haplotypes. Immunization by treatment of recipients with hyperimmune antidonor serum (ADS) prolonged graft survival only in a few donor-recipient combinations differing in one DL-A haplotype. All ADS batches that were tested in MLC reaction did block this reaction, but no correlation with its in vivo activities was found. Hyperimmunization of recipients with donor lymphoid cells before grafting caused a second-set rejection, whereas one injection with donor blood did so only in 14%, with antibody production and accelerated rejection. A short course of horse antidog lymphocyte serum (HADLS) prolonged kidney graft survival. The addition of intravenously given donor bone-marrow cells to this protocol did not lead to a further increase in graft survival.


Successful surgical repair of the parachute mitral valve with mitral valve regurgitation.
A 65-year-old woman with exercise-related dyspnea was admitted to our hospital. Transthoracic echocardiography demonstrated a large anomalous papillary muscle that originated from the posterior wall of the left ventricle and severe mitral valve regurgitation in systole. Cleft suture, 5-0 polytetrafluoroethylene sutures from a single papillary muscle to the anterior commissure leaflet (AC), 5-0 polypropylene sutures between AC and A1, and between A1 and A2, the double-orifice technique, and ring plasty with 32-mm semi-rigid ring was performed. Postoperative echocardiography showed an improvement in severe mitral valve regurgitation. At the 2-month follow-up, the patient was in good health. In the present case, the elderly patient with an isolated parachute mitral valve but without any other cardiac anomaly and presenting with mitral valve regurgitation is extremely rare. This case of mitral valvuloplasty for a parachute mitral valve with a single papillary muscle in an elderly woman has not been reported before.


[Use of metal stents in gastroenterology].
A variety of metal stents have been increasingly used for malignant esophageal, biliary and colorectal stenoses. Esophageal self-expandable stents significantly reduce the early morbidity after implantation compared to conventional plastic prostheses. However they offer no benefit in the long-term due to various late complications. Biliary stents offer a significantly longer patency than plastic devices. This advantage is however clinically relevant only for patients with a survival time of more than three months. Preliminary trials indicate promising results for palliation of colorectal stenoses with metal stents in selected cases. Due to a lack of comparative studies the different types of metal stents must be selected on basis of their physical characteristics and clinical experiences. Most of the prostheses are irremovable which is a limitation for use in benign stenoses of the gastrointestinal and biliary tract. In addition metal stents are extremely expensive so that carefully designed trials are warranted for evaluation of the cost-benefit ratio.


Healthy hospital food initiatives in the United States: time to ban sugar sweetened beverages to reduce childhood obesity.
While childhood obesity is a global problem, the extent and severity of the problem in United States, has resulted in a number of new initiatives, including recent hospital initiatives to limit the sale of sweetened beverages and other high calorie drinks in hospital vending machines and cafeterias. These proposed policy changes are not unique to United States, but are more comprehensive in the number of proposed hospitals that they will impact. Meanwhile, however, it is advised, that these initiatives should focus on banning sugar sweetened beverages, including sodas, 100% fruit juice and sports drinks, from hospital cafeterias and vending machines instead of limiting their presence, so as to ensure the success of these programs in reducing the prevalence of childhood obesity. If US hospitals comprehensively remove sugar sweetened beverages from their cafeterias and vending machines, these programs could subsequently become a model for efforts to address childhood obesity in other areas of the world. Hospitals should be a model for health care reform in their communities and removing sugar sweetened beverages is a necessary first step.


Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis.
Garcinol, an anti-inflammatory and anti-carcinogenic polyisoprenylated benzophenone isolated from Garcinia plants, stimulates tumor cell apoptosis and suicidal erythrocyte death, but supports the survival of hepatocytes and neurons. The present study explored whether the substance influences platelet function and/or apoptosis. To this end, we exposed murine blood platelets to garcinol (33 µM, 30 min) without and with activation by collagen-related peptide (CRP) (2-5 µg/mL) or thrombin (0.01 U/mL); flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, relative platelet volume from forward scatter, and aggregation utilizing staining with CD9-APC and CD9-PE. As a result, in the absence of CRP and thrombin, the exposure of the platelets to garcinol did not significantly modify [Ca2+]i, P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, cell volume, caspase activity, and aggregation. Exposure of platelets to CRP or thrombin was followed by a significant increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activity, annexin-V-binding, caspase activity, and aggregation, as well as significant cell shrinkage. All effects of CRP were strong and significant; those of thrombin were only partially and slightly blunted in the presence of garcinol. In conclusion, garcinol blunts CRP-induced platelet activity, apoptosis and aggregation.


Is brain perfusion correlated to switching mood states and cognitive impairment in bipolar disorder type I? A longitudinal study using perfusion imaging approach.
Type I Bipolar disorder (BD-I) is a neuropsychiatric disorder characterized by manic or mixed-featured episodes, impaired cognitive functioning, and persistent work and social functioning impairment. This study aimed to investigate within-subject; (i) differences in brain perfusion using Single-photon emission computed tomography (SPECT) between manic and euthymic states in BD-I patients; (ii) explore potential associations between altered brain perfusion and cognitive status; and (iii) examine the relationship between cerebral perfusion and mania symptom ratings. Seventeen adult patients diagnosed with BD-I in a manic episode were recruited, and clinical assessments, cognitive tests, and brain perfusion studies were conducted at baseline (mania state) and a follow-up visit 6 months later. The results showed cognitive impairment during the manic episode, which persisted during the euthymic state at follow-up. However, no significant changes in brain perfusion were observed between the manic and euthymic states. During mania, trends toward decreased perfusion in the left cerebellum and right superior parietal lobule were noted. Additionally, trends indicated a higher perfusion imbalance in the left superior and middle frontal gyrus during mania and the right superior and middle frontal gyrus during euthymia. No significant correlations existed between brain perfusion, mania symptom ratings, and cognitive performance, indicating that symptomatology might represent more than neural hemodynamics. These findings suggest that cognitive impairment may persist in BD-I patients and highlight the need for therapeutic interventions targeting cognitive deficits. More extensive studies with extended follow-up periods are warranted further to investigate brain perfusion and cognitive functioning in BD-I patients.


Quantifying inter-annual variability on the space-use of parental Northern Gannets (Morus bassanus) in pursuit of different prey types.
Spatial planning for marine areas of multi-species conservation concern requires in-depth assessment of the distribution of predators and their prey. Northern Gannets Morus bassanus are generalist predators that predate several different forage fishes depending on their availability. In the western North Atlantic, gannets employ different dive tactics while in pursuit of different prey types, performing deep, prolonged U-shaped dives when foraging on capelin (Mallotus villosus), and rapid, shallow, V-shaped dives when foraging on larger pelagic fishes. Therefore, much can be inferred about the distribution and abundance of key forage fishes by assessing the foraging behaviour and space-use of gannets. In this study, we aimed to quantify space-use and to determine areas of suitable foraging habitat for gannets in pursuit of different prey types using habitat suitability models and kernel density utilization distributions. We deployed 25 GPS/Time-depth recorder devices on parental Northern Gannets at Cape St. Mary's, Newfoundland, Canada from 2019 to 2021. To assess the influence of environmental variables on gannets foraging for different prey types, we constructed three different habitat suitability models: a U-shaped dive model, and two V-shaped dive models (early and late chick-rearing). Suitable foraging habitat for capelin, deduced by the U-shaped dive model, was defined by coastal, shallow waters with flat relief and sea surface temperatures (SST) of 11-15° C. Suitable habitat for early V-shaped dives was defined by shallow and coastal waters with steep slope and SST of 12-15°C and ~18°C, likely reflecting the variability in environmental preferences of different prey species captured when performing V-shaped dives. Suitable habitat for late V-shaped dives was defined by shallow coastal waters (<100m depth), as well as waters deeper than 200 m, and by SST greater than 16°C. We show that space-use by gannets can vary both within and between years depending on environmental conditions and the prey they are searching for, with consequences for the extent of potential interaction with anthropogenic activities. Further, we suggest regions defined as suitable for U-shaped dives are likely to be critical habitat of multi-species conservation concern, as these regions are likely to represent consistent capelin spawning habitat.


KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle.
KIF18A (kinesin-8) is required for mammalian mitotic chromosome alignment. KIF18A confines chromosome movement to the mitotic spindle equator by accumulating at the plus-ends of kinetochore microtubule bundles (K-fibers), where it functions to suppress K-fiber dynamics. It is not understood how the motor accumulates at K-fiber plus-ends, a difficult feat requiring the motor to navigate protein dense microtubule tracks. Our data indicate that KIF18A's relatively long neck linker is required for the motor's accumulation at K-fiber plus-ends. Shorter neck linker (sNL) variants of KIF18A display a deficiency in accumulation at the ends of K-fibers at the center of the spindle. Depletion of K-fiber-binding proteins reduces the KIF18A sNL localization defect, whereas their overexpression reduces wild-type KIF18A's ability to accumulate on this same K-fiber subset. Furthermore, single-molecule assays indicate that KIF18A sNL motors are less proficient in navigating microtubules coated with microtubule-associated proteins. Taken together, these results support a model in which KIF18A's neck linker length permits efficient navigation of obstacles to reach K-fiber ends during mitosis.


Dream-enacting behaviour is associated with impaired sleep and severe headache-related disability in migraine patients.
Sleep disorders, nightmares and visual hallucinations have been reported in migraine patients, which may suggest the involvement of rapid eye movement (REM) sleep regulation in migraine. However, the relationship between migraine and REM sleep behaviour disorder (RBD) remains unclear. To investigate the clinical correlates of dream-enacting behaviours (DEB) in migraine patients, we assessed episodic migraine patients ( N = 161, mean age 33.1 years) and headache-free control subjects ( N = 140, mean age 33.1 years) under 50 years of age in a cross-sectional, case-control study. The Japanese version of the RBD screening questionnaire was used, and subjects scoring 5 or higher were defined as having DEB. A significantly increased frequency of DEB was observed in migraine patients compared to controls (24.2% vs. 14.3%). Migraine patients with DEB presented higher scores on the Migraine Disability Assessment and Pittsburgh Sleep Quality Index and an increased rate of smoking compared to those without DEB. Duration of migraine and headache frequency and intensity were not different between migraine patients with or without DEB. DEB was associated with impaired sleep and severe headache-related disability in migraine patients and may reflect brainstem dysfunction and increased brain excitability in migraine patients.


Protective effects of IL-1 on human hematopoietic progenitor cells treated in vitro with 4-hydroperoxycyclophosphamide.
Based on recently published data, IL-1 has been shown to provide radioprotective effects when given to mice 20 h before a lethal dose of irradiation and to enhance granulocyte recovery in mice treated with cyclophosphamide. In this study, we have investigated whether IL-1 can provide protection for human bone marrow colony-forming cells treated with high doses of 4-hydroperoxycyclophosphamide (4-HC), a potent derivative of cyclophosphamide. We have established an in vitro model system which demonstrates that prior incubation with IL-1 protects early human hematopoietic progenitor cells from the lethal effects of high doses of 4-HC. These early progenitors give rise to blast cell colonies which appear late in the culture and are characterized by their ability to give rise to different types of secondary colonies when replated. Furthermore, prior incubation with IL-1 was shown not to protect HL-60 or K562 leukemic cells from the lethal effects of 4-HC. We conclude that IL-1 is able to protect early human hematopoietic progenitors from a non-cell cycle-specific chemotherapeutic agent such as 4-HC, whereas providing no protection for the leukemic cell lines HL-60 and K562.


Surgical treatment of a rare rosette-forming glioneuronal tumor in the pineal region.
Rosette-forming glioneuronal tumors (RGNTs) in the pineal region are rare. RGNTs have been described in the fourth ventricle, but rarely reported in other brain regions. Here, we report the radiological findings, surgical treatment, and short-term outcome of an RGNT found in the pineal region. We present a case of a 22-year-old medical student with a 4-month history of headaches and diplopia. A previous magnetic resonance imaging scan revealed a mass in the pineal region, with heterogeneous contrast enhancement and hydrocephalus. Three months prior, an endoscopic biopsy and third ventriculocisternostomy were performed elsewhere; the diagnosis was neurocytoma Grade I, and radiotherapy was planned. The patient presented at our hospital for a second opinion, and we suggested surgical treatment. A near-total resection was performed in sitting position using a supracerebellar infratentorial microsurgical approach. The tumor was very soft and not well vascularized. Diplopia was initially worsened after the tumor was removed and relieved completely after 2 weeks. An 8-week follow-up examination revealed that the patient was free of symptoms. Histological analysis confirmed it was an RGNT. Maximal safe resection in pineal region RGNTs is a feasible and recommended treatment option.


Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement.
The plastic-adherent cells isolated from BM and other sources have come to be widely known as mesenchymal stem cells (MSC). However, the recognized biologic properties of the unfractionated population of cells do not seem to meet generally accepted criteria for stem cell activity, rendering the name scientifically inaccurate and potentially misleading to the lay public. Nonetheless, a bona fide MSC most certainly exists. To address this inconsistency between nomenclature and biologic properties, and to clarify the terminology, we suggest that the fibroblast-like plastic-adherent cells, regardless of the tissue from which they are isolated, be termed multipotent mesenchymal stromal cells, while the term mesenchymal stem cells is used only for cells that meet specified stem cell criteria. The widely recognized acronym, MSC, may be used for both cell populations, as is the current practice; thus, investigators must clearly define the more scientifically correct designation in their reports. The International Society for Cellular Therapy (ISCT) encourages the scientific community to adopt this uniform nomenclature in all written and oral communications.


Combined effects of estrogen deficiency and cadmium exposure on calcified hard tissues: animal model relating to itai-itai disease in postmenopausal women.
Using ovariectomized rats as a model of postmenopausal women, we studied the effects of estrogen (Es) deficiency and in combination with cadmium (Cd) exposure on the calcified hard tissues related to the development of itai-itai disease. Es deficiency suppressed the synthesis of carbonic anhydrase required for the crystal nucleation process, causing the crystal structure defects in the tooth enamel. Regarding the combined effects of Es deficiency and Cd exposure on the bone, in which rats were given drinking water containing Cd ions, soft X-ray radiography revealed a development of labyrinthine pattern in the calvaria, and micro-computed tomography demonstrated the declining trabecular architecture of the tibia, suggesting Cd-induced osteoporotic change. Further, electron microscopy showed the increase of amorphous minerals in the calvaria. In conclusion, the combined effects of Es deficiency and Cd exposure can be responsible for accelerating the declining bone strength together with the crystal structure defects resulting in the preferential occurrence of itai-itai disease in postmenopausal women.(Communicated by Tatsuo SUDA, M.J.A.).