Increased expression of transcription factor TFAP2α correlates with chemosensitivity in advanced bladder cancer.
The standard treatment for patients with advanced transitional cell carcinoma of the bladder is platin based chemotherapy. Only approximately 50% of the patients respond to chemotherapy. Therefore, molecular predictive markers for identification of chemotherapy sensitive subgroups of patients are highly needed. We selected the transcription factor TFAP2α from a previously identified gene expression signature for chemotherapy response. TFAP2α expression and localization was assessed by immunohistochemistry using a tissue microarray (TMA) containing 282 bladder cancer tumors from patients with locally advanced (pT2-T4(b) and N(1-3)) or metastatic (M(1)) disease. All patients had received cisplatin containing chemotherapy. Furthermore, QPCR analysis of three TFAP2α isoforms was performed on tumor specimens of advanced muscle invasive bladder cancers (T2-4). Using the bladder cell lines T24 and SW780 the relation of TFAP2α and cisplatin and gemcitabine sensitivity as well as cell proliferation was examined using siRNA directed TFAP2α knockdown. TFAP2α protein expression was analyzed on a TMA with cores from 282 advanced bladder cancer tumors from patients treated with cisplatin based combinational chemotherapy. TFAP2α was identified as a strong independent predictive marker for a good response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer. Strong TFAP2α nuclear and cytoplasmic staining predicted good response to chemotherapy in patients with lymph node metastasis, whereas weak TFAP2α nuclear staining predicted good response in patients without lymph node metastasis. In vitro studies showed that siRNA mediated knockdown of TFAP2α increased the proliferation of SW780 cells and rendered the cells less sensitive to cisplatin and gemcitabine. In contrast to that T24 bladder cells with mutated p53 showed to be more drug sensitive upon TFAP2α depletion. High levels of nuclear and cytoplasmic TFAP2α protein were a predictor of increased overall survival and progression free survival in patients with advanced bladder cancer treated with cisplatin based chemotherapy. TFAP2α knockdown increased the proliferation of the SW780 bladder cells and reduced cisplatin and gemcitabine induced cell death. The inverse effect was observed in the TP53 mutated T24 cell line where TFAP2α silencing augmented cisplatin and gemcitabine sensitivity and did not stimulate proliferation.


Effects of susceptor, coating and conventional browning applications on color and crust formation during microwave baking.
The effects of different browning treatments on the crust color and crust hardness of microwave baked breads were investigated. Microwave oven was operated at 20%, 30% and 40% powers for 3.5-5.5 minutes. As a control, breads were baked in a conventional oven at 200 degrees C for 12 minutes. After microwave baking, breads were browned or conventional browning times increased, crust hardness and weight loss of breads increased. When susceptors were used, desired browning and hardness were obtained on the bottom surfaces of the breads. However, they did not affect top surface color significantly. The optimum microwave baking conditions for safety susceptor and standard susceptor were found as 5.0 minutes at 20% power and 4.5 minutes at 20% power, respectively. Breads coated with a solution composed of 10.5% sodium bicarbonate, 31.6% glucose, 5.3% glycine and 52.6% water (by weight) did not have the desired crust color and hardness. Conventional browning at 200 degrees C for 8 minutes was an alternative to achieve browning on top and bottom surfaces and crust formation on the bottom surface.


Expression and characterization of novel chimeric endolysin CHAPk-SH3bk against biofilm-forming methicillin-resistant Staphylococcus aureus.
The continuous evolution of antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) due to the misuse of antibiotics lays out the need for the development of new antimicrobials with higher activity and lower resistance. In this study, we have expressed novel chimeric endolysin CHAPk-SH3bk derived from LysK to investigate its antibacterial activity against planktonic and biofilm-forming MRSA. The molecular docking and MD simulation results identified critical amino acids (ASP47, ASP56, ARG71, and Gly74) of CHAPk domain responsible for its catalytic activity. Chimeric endolysin CHAPk-SH3bk showed an effective binding to peptidoglycan fragment using 14 hydrogen bonds. The in-vitro antibacterial assays displayed higher activity of CHAPk against planktonic MRSA with 2-log10 reduction in 2 h. Both CHAPk and CHAPk-SH3bk displayed bactericidal activity against MRSA with ∼4log10 and ∼3.5log10 reduction in 24 h. Biofilm reduction activity displayed CHAPk-SH3bk reduced 33 % and 60 % of hospital-associated ATCC®BAA-44™ and bovine origin SA1 respectively. The CHAPk treatment reduced 47 % of the preformed biofilm formed by bovine-origin MRSA SA1. This study indicates an effective reduction of preformed MRSA biofilms of human and animal origin using novel chimeric construct CHAPk-SH3bk. Stating that the combination and shuffling of different domains of phage endolysin potentially increase its bacteriolytic effectiveness against MRSA.


Dynamic regulation of the Kv2.1 voltage-gated potassium channel during brain ischemia through neuroglial interaction.
The physiological significance of neuroglial interactions in the CNS has been emphasized in neurological conditions such as epilepsy and brain ischemia. The Kv2.1 voltage-gated potassium channel is unique in its ability to form large clusters in the plasma membrane of neuronal cell bodies. We have previously shown that brain ischemia causes rapid dephosphorylation of Kv2.1 subunits and resultant activation of the ion channel function. However, the physiological significance of the channel clustering is unknown. Here we present evidence that clustered Kv2.1 channels in the neuronal plasma membrane are juxtaposed to axosomatic synapses and associated with astrocytic processes expressing high levels of glutamate transporters. In acute cortical slices, ischemic stress rapidly resulted in the dephosphorylation and dispersion of Kv2.1. Selective inhibition of metabolism in astrocytes was sufficient to induce Kv2.1 dephosphorylation in neurons. Interestingly, these effects were blocked by the antagonists of ionotropic glutamate receptors, indicating the involvement of glutamate as the signal mediator between astrocytes and neurons. Furthermore, the pharmacological inhibition of glial glutamate transporter GLT-1 induced the similar Kv2.1 dephosphorylation, whereas exogenous glutamate alone was not efficacious. These results suggest that ischemic stress rapidly causes the dysfunction of glutamate transporters in astrocytes and resultant accumulation of glutamate in the extracellular space. The elevated glutamate may subsequently activate ionotropic glutamate receptors and result in the dephosphorylation of Kv2.1 in neurons. These findings implicate that Kv2.1 clusters are strategically situated at neuroglial junctions to achieve the rapid modulation after ischemic stress via glutamate signaling.


Constructing neural networks for multiclass-discretization based on information entropy.
Cios and Liu (1992) proposed an entropy-based method to generate the architecture of neural networks for supervised two-class discretization. For multiclass discretization, the inter-relationship among classes is reduced to a set of binary relationships, and an independent two-class subnetwork is created for each binary relationship. This two-class-based method ends up with the disability of sharing hidden nodes among different classes and a low recognition rate. We keep the interrelationship among classes when training a neural network. Entropy measure is considered in a global sense, not locally in each independent subnetwork. Consequently, our method allows hidden nodes and layers to be shared among classes, and presents higher recognition rates than the two-class-based method.


The biocompatibility of bone cements: progress in methodological approach.
The ideal bone graft substitute should have certain properties and there are many studies dealing with mixture of polymethylmetacrilate (PMMA) and β-tricalciumphospate (β-TCP) presenting the best characteristics of both. Scanning Electron Microscopy (SEM), for ultra-structural data, resulted a very reliable in vivo model to better understand the bioactivity of a cement and to properly evaluate its suitability for a particular purpose. The present study aims to further improve the knowledge on osteointegration development, using both parameters obtained with the Environmental Scanning Electron Microscopy (ESEM) and focused histological examination. Two hybrid bone graft substitute were designed among ceramic and polymer-based bone graft substitutes. Based on β-TCP granules sizes, they were created with theoretical different osteoconductive properties. An acrylic standard cement was chosen as control. Cements were implanted in twelve New Zealand White (NZW) rabbits, which were sacrificed at 1, 2, 3, 6, 9 and 12 months after cement implantation. Histological samples were prepared with an infiltration process of LR white resin and then specimens were studied by X-rays, histology and Environmental Scanning Electron Microscopy (ESEM). Comparing the resulting data, it was possible to follow osteointegration's various developments resulting from different sizes of β-TCP granules. In this paper, we show that this evaluation process, together with ESEM, provides further important information that allows to follow any osteointegration at every stage of develop.


Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents.
The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. Wistar rats, wild type and AMPKalpha(2) (-/-) mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. First, in vitro luminal leptin activating its receptors coupled to PKCbetaII and AMPKalpha, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious.


Simultaneous modeling of multiple end points in life-cycle toxicity tests.
Standard toxicity tests do not allow extrapolations to the population level, mainly because these tests apply a short, fixed exposure time and focus on a single end point only. These limitations can be overcome by (partial) life-cycle toxicity testing, although these test results are harder to analyze. DEBtox is an existing software tool for the process-based analysis of standardized bioassays, and this paper presents two extensions of this method, making it applicable to life-cycle tests: the simultaneous assessment of end points and the description of aging (senescence) of the animals. We demonstrate these adaptations by describing life-cycle tests with the springtail Folsomia candida, exposed to cadmium and triphenyltin in their food. The extended model is able to describe the data for all end points simultaneously overtime with few, physiologically relevant parameters. Furthermore, the analysis reveals these chemicals to have distinctly different modes of action: cadmium apparently decreases the assimilation of energy from the food whereas triphenyltin increases the maintenance costs. The model fit allows calculation of the intrinsic rate of population increase, integrating effects on survival and reproduction. As the analysis is process based, population responses under food limitation can be explored, which depends critically on the selected mode of action.


The health-related quality of life in eating disorders.
This study investigated the perception of health-related quality of life (HRQoL) in ambulatory patients with eating disorders in relation to the severity of eating symptomatology and psychological comorbidity. One hundred ninety-seven study patients were consecutively recruited at the Eating Disorders Outpatient Clinic. Short Form-36 items (SF-36), a generic HRQoL questionnaire, the Eating Attitudes Test (EAT-40), and the Hospital Anxiety and Depression Scale (HAD) were used to measure different aspects of HRQoL. The results of the SF-36 were compared with the norms of the Spanish general population for women 18-34 years of age. Patients with eating disorders were more dysfunctional in all areas of the SF-36 compared with women in the general population. There were no differences among the eating disorder diagnostic groups. Higher scores on the EAT-40 and the HAD were associated with a perception of greater impairment on all SF-36 subscales. The evaluation of HRQoL in these patients confirms the impact of these disorders on daily life in areas not directly related to eating disorders. The SF-36 is useful for discriminating among different levels of severity of eating disorders and other psychological comorbidities of these patients.


Gastrointestinal bleeding associated with rivaroxaban administration in a treated patient infected with human immunodeficiency virus.
The use of rivaroxaban in fixed dosing regimens without need for routine coagulation monitoring may lead to the misconception that there is a minimal risk of drug-drug interactions. We describe the case of a patient infected with human immunodeficiency virus (HIV) on salvage therapy who developed gastrointestinal bleeding while receiving the standard dose of rivaroxaban for the prevention of venous thromboembolism after surgery. This case clearly sends a warning that protease inhibitors should not be co-administered with rivaroxaban. Furthermore, it highlights the importance of clinicians' caution about potential drug-drug interactions.


[Prophylactic use of prostatilen in rats prior to exposure to +Gz loads as a way of reducing changes in urogenital organs].
Experimental verification of prostatilen prophylactics of changes in the urogenital organs consequent to g-loads was the idea of the work. The experiment was performed with 37 mongrel white male rats weighing 200-250 g who were exposed to the head-pelvis g-loads (+Gl) at 10 units. Behavior reactions of the rats were assessed with the "open field" technique immediately after centrifugation; weighing coefficients of the urogenital organs (the organ/body mass relation) were determined, and histological and morphometric analyses of prostate, testis and kidney were made. A significant moderating effect of prophylactic prostatilen on the stress-reactions in animals was first revealed; prostatilen was also found to speed up adaptation. This was concluded from normalization of the hemodynamics, a decrease in venous plethora and epithelial dystrophy, absence of basophilia in conjunctive tissue of the urogenital organs. Distention and overfilling of acini by secret and the number of epithelial acinus hulled into the lumen were markedly less in prostate. Spermatogenesis in testis was normalized, too. The histological profile of kidney approached the norm. Results of the experiment showed that prostatilen is a promising preparation from the standpoint of moderation of stress-reactions and counteraction of disorders in the urogenital organs caused by g-loads.


Sequence confirmation of the EWS-WT1 fusion gene transcript in the peritoneal effusion of a patient with desmoplastic small round cell tumor.
Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated neoplasm. The prognosis is poor, even if therapy is instituted promptly, and thus it is important to differentiate it from other histologically and cytologically similar-looking malignancies of the young adult. We present a case of DSRCT in a 17-yr-old male with disseminated peritoneal disease and peritoneal effusion. The cytology sample showed a malignant small round cell tumor, the classical cytological features of DSRCT, and immunohistochemistry performed in the prepared cell block exhibited an antibody expression profile in keeping with DSRCT. Further material from the effusion was prepared for RNA extraction, following which a reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing of the t(11;22)(p13;q11 or q12) were carried out. The result showed the presence of the reciprocal translocation and thus confirmed the diagnosis of DSRCT. This case shows how molecular techniques (including sequencing) can be applied to cytology in clarifying and confirming certain difficult diagnosis of undifferentiated neoplasms, DSRCT in this particular case.


Strain-dependent differences in corticolimbic processing of aversive or rewarding stimuli.
Aberrations in the elaboration of both aversive and rewarding stimuli characterize several psychopathologies including anxiety, depression and addiction. Several studies suggest that different neurotrasmitters, within the corticolimbic system, are critically involved in the processing of positive and negative stimuli. Individual differences in this system, depending on genotype, have been shown to act as a liability factor for different psychopathologies. Inbred mouse strains are commonly used in preclinical studies of normal and pathological behaviors. In particular, C57BL/6J (C57) and DBA/2J (DBA) strains have permitted to disclose the impact of different genetic backgrounds over the corticolimbic system functions. Here, we summarize the main findings collected over the years in our laboratory, showing how the genetic background plays a critical role in modulating amminergic and GABAergic neurotransmission in prefrontal-accumbal-amygdala system response to different rewarding and aversive experiences, as well as to stress response. Finally, we propose a top-down model for the response to rewarding and aversive stimuli in which amminergic transmission in prefrontal cortex (PFC) controls accumbal and amygdala neurotransmitter response.


Kasabach-merritt syndrome arising from tufted angioma successfully treated with systemic corticosteroid.
We report a case of Kasabach-Merritt syndrome arising from a tufted angioma successfully treated with systemic corticosteroid. A 2-month-old male infant presented with a palm-sized, erythematous induration on his left pubis. The lesion was diagnosed as tufted angioma histopathologically. After 1 month, the lesion suddenly expanded to the abdomen and scrotum. Initial laboratory tests were consistent with consumptive coagulopathy. He was diagnosed with Kasabach-Merritt syndrome and treated with intravenous dexamethasone at 0.32 mg/kg/day (equivalent to prednisolone 2.0 mg/kg/day). Two days after initiating the treatment, his platelet counts recovered and the lesion ceased to expand. Steroid therapy was converted to oral prednisolone and the dosage was subsequently tapered, and the lesion gradually involuted with no signs of recurrence for a year.


Anatomy of the cavernous sinus. A microsurgical study.
Fifty cavernous sinuses from cadavers were studied in detail using magnification, with special attention to the relationships important in surgical approaches on the intracavernous structures, and to understanding arterial contributions to arteriovenous fistulas involving the cavernous sinus. Significant findings were: 1) The three main branches of the intracavernous portion of the carotid artery were the meningohypopyseal artery, present in 100% of the specimens, the artery of the inferior cavernous sinus (84%), and McConnell's capsular arteries (28%). In addition, the ophthalmic and dorsal meningeal arteries arose from the carotid artery within the cavernous sinus in 8% and 6%, respectively. The three main branches of the meningohypopyseal trunk were the tentorial artery, present in 100%, the dorsal meningeal (90%), and the inferior hypophyseal (80%). 2) The carotid artery was separated from the trigeminal nerve just proximal to the sinus by only dura in 84% of the specimens, and the artery was exposed in the floor of the middle fossa lateral to the trigeminal nerve in 38%. 3) The intracavernous portion of the carotid artery indented the lateral side of the pituitary gland in 28% of dissections but could be as far as 7 mm from it. 4) A triangular area, described by Parkinson, through which the intracavernous portion of the carotid artery could be exposed surgically was found in all specimens. 5) The sixth cranial nerve may split into as many as five rootlets as it passes lateral to the intracavernous portion of the carotid artery. 6) The three major venous spaces within the sinus were posterosuperior, anteroinferior, and medial to the intracavernous portion of the carotid artery.


Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections.
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, and its subsequent variants has underscored the importance of understanding the host-viral molecular interactions to devise effective therapeutic strategies. A significant aspect of these interactions is the role of alternative splicing in modulating host responses and viral replication mechanisms. Our study sought to delineate the patterns of alternative splicing of RNAs from immune cells across different SARS-CoV-2 variants and vaccination statuses, utilizing a robust dataset of 190 RNA-seq samples from our previous studies, encompassing an average of 212 million reads per sample. We identified a dynamic alteration in alternative splicing and genes related to RNA splicing were highly deactivated in COVID-19 patients and showed variant- and vaccination-specific expression profiles. Overall, Omicron-infected patients exhibited a gene expression profile akin to healthy controls, unlike the Alpha or Beta variants. However, significantly, we found identified a subset of infected individuals, most pronounced in vaccinated patients infected with Omicron variant, that exhibited a specific dynamic in their alternative splicing patterns that was not widely shared amongst the other groups. Our findings underscore the complex interplay between SARS-CoV-2 variants, vaccination-induced immune responses, and alternative splicing, emphasizing the necessity for further investigations into these molecular cross-talks to foster deeper understanding and guide strategic therapeutic development.


Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in epilepsy.
Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy and is not rare. The NIH and National Institute of Neurological Disorders and Stroke sponsored a 3-day multidisciplinary workshop to advance research into SUDEP and its prevention. Parallel sessions were held: one with a focus on the science of SUDEP, and the other with a focus on issues related to the education of health care practitioners and people with epilepsy. This report summarizes the discussions and recommendations of the workshop, including lessons learned from investigations of sudden infant death syndrome (SIDS), sudden cardiac death, autonomic and respiratory physiology, medical devices, genetics, and animal models. Recommendations include educating all people with epilepsy about SUDEP as part of their general education on the potential harm of seizures, except in extenuating circumstances. Increasing awareness of SUDEP may facilitate improved seizure control, possibly decreasing SUDEP incidence. There have been significant advances in our understanding of the clinical and physiologic features of SIDS, sudden cardiac death, and SUDEP in both people and animals. Research should continue to focus on the cardiac, autonomic, respiratory, and genetic factors that likely contribute to the risk of SUDEP. Multicenter collaborative research should be encouraged, especially investigations with direct implications for the prevention of SUDEP. An ongoing SUDEP Coalition has been established to facilitate this effort. With the expansion of clinical, genetic, and basic science research, there is reasonable hope of advancing our understanding of SUDEP and ultimately our ability to prevent it.


A key sphingolipid pathway gene, MoDES1, regulates conidiation, virulence and plasma membrane tension in Magnaporthe oryzae.
Rice blast, caused by the plant pathogenic fungus Magnaporthe oryzae, is a destructive disaster all over the earth that causes enormous losses in crop production. Sphingolipid, an important biological cell membrane lipid, is an essential structural component in the plasma membrane (PM) and has several biological functions, including cell mitosis, apoptosis, stress resistance, and signal transduction. Previous studies have suggested that sphingolipid and its derivatives play essential roles in the virulence of plant pathogenic fungi. However, the functions of sphingolipid biosynthesis-related proteins are not fully understood. In this article, we identified a key sphingolipid synthesis enzyme, MoDes1, and found that it is engaged in cell development and pathogenicity in M. oryzae. Deletion of MoDES1 gave rise to pleiotropic defects in vegetative growth, conidiation, plant penetration, and pathogenicity. MoDes1 is also required for lipid homeostasis and participates in the cell wall integrity (CWI) and Osm1-MAPK pathways. Notably, our results showed that there is negative feedback in the TORC2 signaling pathway to compensate for the decreased sphingolipid level due to the knockout of MoDES1 by regulating the phosphorylated Ypk1 level and PM tension. Furthermore, protein structure building has shown that MoDes1 is a potential drug target. These findings further refine the function of Des1 and deepen our understanding of the sphingolipid biosynthesis pathway in M. oryzae, laying a foundation for developing novel and specific drugs for rice blast control.


MicroRNA-146a downregulates NFκB activity via targeting TRAF6 and functions as a tumor suppressor having strong prognostic implications in NK/T cell lymphoma.
We investigated prognostic implications of microRNAs in extranodal NK/T cell lymphoma (NKTL). We measured miRNA expression in NKTL tissues and cell lines, using real-time PCR, and analyzed its role in NKTL, using cell lines. Multivariate analysis showed low miR-146a expression (P < 0.001; HR = 13.110), primary non-upper aerodigestive tract lesion (non-UAT; P = 0.008; HR = 5.376) and high International Prognostic Index (IPI; ≥3; P = 0.013; HR = 3.584) to be independent poor prognostic factors. miR-146a expression could subdivide UAT-NKTL into 2 prognostic groups, resulting in the following prognostic groups: (i) UAT(Low-146a), (ii) UAT(High-146a), and (iii) non-UAT. Compared with UAT(High-146a), UAT(Low-146a) showed distinctively poor prognosis (P < 0.001; HR = 15.620), similar to the non-UAT group. In vitro, miR-146a overexpression in NKTL cell lines, SNK6 and YT, inhibited nuclear factor κB (NFκB) activity, suppressed cell proliferation, induced apoptosis, and enhanced chemosensitivity. TNF receptor-associated factor 6, a target of miR-146a and a known NFκB activator, was downregulated by miR-146a in SNK6 and YT cells. Promoter methylation of miR-146a gene was observed in SNK6 and YT cells, as well as in NKTL tissues with low miR-146a expression, and miR-146a expression was induced by the conversion of methylation status with a demethylating agent in SNK6 and YT cells. These results suggest that miR-146a might function as a potent tumor suppressor in NKTL and be useful for patient assessment and therapeutic targeting.


The Role of Birds of Prey in West Nile Virus Epidemiology.
Reported human cases of West Nile virus (WNV) in Europe increased dramatically in 2018. Lineage 1 strains had been circulating in Euro-Mediterranean countries since the early 1990s. The subsequent introduction of WNV lineage 2 has been responsible for the remarkable upsurge of European WNV outbreaks since 2004, including the dramatic increase in human cases observed since 2018. The virus exists in a natural cycle between mosquitoes and wild birds, with humans and horses acting as dead-end hosts. As the key vertebrate hosts in the transmission cycle of WNV, avian species have been the focus of surveillance across many countries. Raptors appear particularly susceptible to WNV infection, resulting in higher prevalence, and in some cases exhibiting neurological signs that lead to the death of the animal. In addition, birds of prey are known to play an important role as WNV reservoir and potentially amplifying hosts of infection. Importantly, raptor higher susceptibility/prevalence may indicate infection through predation of infected prey. Consequently, they are considered important target species when designing cost-effective surveillance for monitoring both seasonal WNV circulation in endemic countries and its emergence into new areas, where migrating raptors may play a critical role in virus introduction. This review summarizes the different aspects of the current knowledge of WNV infection in birds of prey and evaluates their role in the evolution of the epizootic that is spreading throughout Europe.


Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states.
Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer's disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, 'shape connections' between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.


Accounting for Delayed Entry in Analyses of Overall Survival in Clinico-Genomic Databases.
Clinico-genomic databases favor inclusion of long-term survivors, leading to potentially biased overall survival (OS) analyses. Risk set adjustments relying on the independent delayed entry assumption may mitigate this bias. We aimed to determine whether this assumption is satisfied in a dataset of patients with advanced non-small cell lung cancer (aNSCLC), and to give guidance for clinico-genomic OS analyses when the assumption is not satisfied. We analyzed the association of timing of next-generation sequencing (NGS) testing with real-world OS (rwOS) in patient data from a United States-based nationwide longitudinal deidentified electronic health records-derived database. Estimates of rwOS using risk set adjustment were compared with estimates computed with respect to all patients, regardless of NGS testing. The independent delayed entry assumption was not satisfied in this database, and later sequencing had a negative association with the hazard of death after sequencing. In a model adjusted for relevant characteristics, each month delay in sequencing was associated with a 2% increase in the hazard of death. However, until the median survival time, estimates of OS using risk set adjustment are similar to estimates computed for all patients, regardless of NGS testing. rwOS analyses in clinico-genomic databases should assess the independent delayed entry assumption. Comparisons versus broader population may be useful to evaluate the rwOS differences between calculations using risk set adjustment and patient cohorts where the bias relates to overrepresentation of long survivors. This study illustrates practices that can increase the interpretability of findings from OS analyses in clinico-genomic databases.


Using automated voice messages linked to telephone counselling to increase post-menstrual regulation contraceptive uptake and continuation in Bangladesh: study protocol for a randomised controlled trial.
Adoption of modern contraceptive methods after menstrual regulation (MR) is thought to reduce subsequent unwanted pregnancy and abortion. Long-acting reversible contraceptives (LARCs) are highly effective at reducing unintended pregnancy, but uptake in Bangladesh is low. Providing information on the most effective methods of contraception increases uptake of more effective methods. This protocol describes a randomised controlled trial of an intervention delivered by mobile phone designed to support post-MR contraceptive use in Bangladesh. This is a multi-site single blind individual randomised controlled trial. At least 960 women undergoing MR procedures at selected facilities will be recruited after their procedure by female research assistants. Women will be randomised into the control or intervention group with a 1:1 ratio. All participants will receive usual clinic care, including contraceptive counselling and the telephone number of a non-toll-free call centre which provides counselling on MR and contraception. During the 4 months after their MR procedure, intervention participants will be sent 11 recorded interactive voice messages to their mobile phone about contraception with a focus on their chosen method and LARCs. Each message allows the participant to connect directly to the call centre. The intervention is free to the user. The control group will receive no messages delivered by mobile phone. All participants will be asked to complete an in-person questionnaire at recruitment and follow-up questionnaires by telephone at 2 weeks, 4 months and 12 months after their MR. The primary outcome for the trial will be self-reported LARC use 4 months post-MR. Secondary outcomes include LARC use at 2 weeks and 12 months post-MR, use of any effective modern contraceptive method at 2 weeks, 4 months and 12 months post-MR, and contraceptive discontinuation, contraceptive method switching, pregnancy, subsequent MR and experience of violence during the 12 month study period. Mobile phones offer a low-cost mechanism for providing individualised support to women with contraception outside of the clinic setting. This study will provide information on the effects of such an intervention among MR clients in Bangladesh. Trial registered with clinicaltrials.gov Registration number: NCT02579785 Date of registration: 16th October 2015.


Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment.
Four coumarin-containing telodendrimers (denoted as P-I, P-II, P-III and P-IV) were designed and synthesized to self-assemble into the corresponding nanoparticles. Of those, two nanoparticles (P-II and P-IV micelles) were screened and selected for targeted drug delivery of 7-ethyl-10-hydroxy camptothecin (SN-38), a prominent and efficacious anticancer agent, for the treatment of colon cancers. The nanoparticle encapsulation significantly increased the solubility of SN-38 in aqueous solution. Dynamic light scattering (DLS) showed the size of these SN-38 nanoparticles to be around 50 nm, and rod-shaped micelles were observed using transmission electron microscopy (TEM). These two novel nanoformulations of SN-38/P-II and SN-38/P-IV were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug (SN-38 in DMSO) and were 500-fold more potent than irinotecan (a prodrug of SN-38). In addition, near infrared fluorescent (NIRF) optical imaging was utilized to monitor the tumor targeted delivery of SN-38/NPs via co-loading a NIRF dye. It was demonstrated that these NPs preferentially accumulated in tumors when compared to healthy tissue. A pharmacokinetics study showed that SN-38 micelle formulations had a longer circulating time in blood than irinotecan. Furthermore, SN-38 loaded nanoformulations exhibit superior anti-tumor efficacy when compared with irinotecan at equivalent SN-38 dose in HT-29 human colon cancer xenograft models.


Tularemia in Germany: the tip of the iceberg?
Tularemia is a rare, notifiable zoonosis in Germany. Since November 2004, several lines of evidence including outbreaks in humans or animals and confirmed infections in indigenous hare and rodent populations have indicated a re-emergence of tularemia in different German federal states. Unfortunately, reliable basic information on the seroprevalence in different geographical regions, permitting the identification of risk factors, does not exist. Combining a sensitive screening assay with a highly specific confirmative immunoblot test, we performed a serological investigation on 2416 sera from a population-based, cross-sectional health survey of the city population of Leutkirch, Baden-Wuerttemberg. A total of 56 sera gave positive results indicating a seroprevalence of 2.32%. Thus, the seroprevalence is tenfold higher than that previously reported in a nationwide study in 2004. Francisella tularensis can cause a wide variety of clinical syndromes including severe, sometimes fatal disease. Missing epidemiological data on its spatial and temporal distribution in an endemic country complicate an appropriate risk assessment necessary for public health authorities to be prepared for an adequate outbreak management. This is of special concern regarding the extraordinary potential of F. tularensis as an agent of bioterrorism. Our investigation performed in a presumed low-risk area demonstrated that tularemia might be seriously underestimated in Germany and probably in other central European countries as well.


Impacts of mustard gas exposure on veterans mental health: A study on the role of education.
The mustard gas (MG) exposure can impair physical health and therefore increase the probability of the posttraumatic stress disorder (PTSD) and psychological disorders. The aim of this study was to investigate long-term effects of MG exposure on veterans' mental health. This was a cross-sectional study. In order to assess prevalence of mental health and PTSD of 100 MG victims 25 years after the exposure to MG in Iran-Iraq conflict, the general health questionnaire (GHQ-28) and Impact of Event Scale-Revised, respectively was administered. The mean (±standard deviation (SD)) age of participants was 40.63 (±5.86) years. The mean GHQ-28 (47.34) of the study group was higher compared to standardized cutoff point (23) of the Iranian community. Also, it was found that 38 participants (38%) suffer from PTSD. The results of this study showed that academic education in the PTSD group was less than that in the non-PTSD group (P=0.03). In addition, in multivariate analysis it was found that only education level of the veterans and their wives were effective on the mental health score (adjusted P=0.036 and 0.041, respectively). The mean score of depression and psychosocial activity subscale in patients at higher education level was lower than patients at lower education level (P<0.05). This study found that sulfur mustard (SM) exposure can be effect on mental health even 25 years after exposure. Therefore, the psychological state should be more considered in chemical injured veterans and it is important that providing more mental health centers for this community.


Helmet use in equestrian athletes: opportunities for intervention.
Equestrian athletes (horse riders) are at high risk for head injury, including concussions. Adults riders were recruited via social media posting to complete a branching survey collecting data on demographics, riding experience, helmet use, injury history and concussion symptom knowledge. Results are reported as frequencies and percentages, with associations tested using chi-square with significance level p < 0.05. Of the 2598 subjects, about 75% reported always wearing a helmet. Of those who did not, the most common reasons were that helmets are unnecessary (57.4%) or do not fit well (48.6%). Many indicated improper storage conditions and/or did not follow manufacturer's replacement recommendations. Most (75.4%) reported a high level of comfort with recognizing concussion signs, with half experiencing a prior head injury. This information suggests opportunities for intervention to improve helmet use through increased fit, while the responses indicate a need for further education on proper helmet use.


Gene expression profiling in the developing prostate.
Gene expression profiling has proven to be an effective tool for characterizing genes and molecular pathways operative at key stages of organogenesis. Temporal profiling of RNA transcripts can provide valuable insights into mechanisms of differentiation and lay a foundation for characterizing molecular aspects of development. Descriptive and functional experiments have demonstrated critical roles for androgenic hormones and mesenchymal-epithelial interactions during prostate organogenesis. These studies have uncovered roles for members of several growth factor pathways--primarily using a candidate gene approach--but it is likely that critical molecular determinants of prostate organogenesis remain to be defined. Despite the potential for expression profiling to uncover novel genes and pathways, only a limited number of gene profiling studies have focused on the developing prostate. Among these are studies based on the generation of cDNA libraries and expressed sequence tags (ESTs) and other tag counting strategies such as serial analysis of gene expression (SAGE). Recently, microarray-based assays have provided more comprehensive time-course studies of molecular pathways associated with induction, branching morphogenesis, and secretory differentiation. Several profiling methods have also been used to characterize the influences of androgenic hormones on different tissue compartments including the urogenital sinus mesenchyme (UGM) and urogenital sinus epithelium (UGE) in order to define paracrine mediators operative in early morphogenesis. While hypothesis-driven candidate gene studies remain the gold standard for delineating cause-and-effect relationships dictating the complex biological regulators of the developing prostate, gene profiling provides a valuable adjunct, and is especially useful as an unbiased first step for generating new hypotheses. This review will focus on detailing the methods and results of profiling strategies in the context of normal prostate gland development, with implications for alterations in conserved pathways that may contribute to prostatic diseases.


TIMP3 expression associates with prognosis in colorectal cancer and its novel arylsulfonamide inducer, MPT0B390, inhibits tumor growth, metastasis and angiogenesis.
Tissue inhibitors of metalloproteinase 3 (TIMP3) are a major endogenous inhibitor of matrix metalloproteinase (MMPs) that inhibit tumor growth, invasion, metastasis and angiogenesis. In this study, we found that TIMP3 expression is associated with positive prognosis of colorectal cancer (CRC) clinicopathologically. Therefore, we developed a series of arylsulfonamide derivatives as TIMP3 inducers in order to define potential colorectal cancer therapeutic agent. Among these, MPT0B390 was selected for anti-tumor, anti-metastasis, and anti-angiogenesis property determination. Methods: The relationship between TIMP3 expression and clinical pathological features in colorectal patients and cell lines were determined by immunohistochemistry, bioinformatics analysis and western blotting. The anti-tumor function was validated by using MTT, apoptosis pathway detection and in vivo xenograft model for tumor growth inhibition determination. The anti-metastatic function was validated using a transwell migration assay, and using in vivo lung metastasis and liver metastasis models. The mechanism of MPT0B390-induced TIMP3 expression was further tested using qPCR and Chromatin IP assay. The anti-angiogenesis function was examined by using transwell migration assay, and in vivo Matrigel plug assay. Results: After screening candidate compounds, we identified MPT0B390 as an effective inducer of TIMP3. We showed that MPT0B390 induces TIMP3 expression significantly and inhibits CRC cell growth in vitro and in vivo. By inducing TIMP3 expression, MPT0B390 can also exert its anti-metastasis effect to inhibit CRC cell migration and invasion and downregulates migration markers such as uPA, uPAR, and c-Met. Subsequent Chromatin immunoprecipitation assay revealed that MPT0B390 can significantly inhibit EZH2 expression as well as its binding to TIMP3 promoter region to regulate TIMP3 induction. In addition to the anti-tumor and anti-metastasis capability, MPT0B390 can also induce TIMP3 expression in endothelial cells to inhibit tumor angiogenesis. Conclusion: These data suggest the potential therapeutic applications of the TIMP3 inducer, MPT0B390, for colorectal cancer treatment.


Identification of Persistent Sulfidogenic Bacteria in Shale Gas Produced Waters.
Produced waters from hydraulically fractured shale formations give insight into the microbial ecology and biogeochemical conditions down-well. This study explores the potential for sulfide production by persistent microorganisms recovered from produced water samples collected from the Marcellus shale formation. Hydrogen sulfide is highly toxic and corrosive, and can lead to the formation of "sour gas" which is costly to refine. Furthermore, microbial colonization of hydraulically fractured shale could result in formation plugging and a reduction in well productivity. It is vital to assess the potential for sulfide production in persistent microbial taxa, especially when considering the trend of reusing produced waters as input fluids, potentially enriching for problematic microorganisms. Using most probable number (MPN) counts and 16S rRNA gene sequencing, multiple viable strains of bacteria were identified from stored produced waters, mostly belonging to the Genus Halanaerobium, that were capable of growth via fermentation, and produced sulfide when supplied with thiosulfate. No sulfate-reducing bacteria (SRB) were detected through culturing, despite the detection of relatively low numbers of sulfate-reducing lineages by high-throughput 16S rRNA gene sequencing. These results demonstrate that sulfidogenic produced water populations remain viable for years post production and, if left unchecked, have the potential to lead to natural gas souring during shale gas extraction.


[Dupuytren disease].
Dupuytren disease (DD) is a connective tissue disorder that consists in fibromatosis of the palmar and digital fascia (in form of nodules or flanges) that leads to the development of flexion contractures of the palm and fingers. The little and ring finger are particularly affected. The disease can limit hand function, reducing the quality of life. The disease can have a traumatic origin and is also associated with conditions such as diabetes mellitus, alcoholism, dyslipidemia, epilepsy and AIDS, among others. However, none of these conditions can fully explain the genesis of DD. A hereditary component is described in 40% of patients and is attributed to an autosomal dominant gene of variable penetrance, probably related to collagen synthesis. However there are also spontaneous and recessive inheritance cases. The diagnosis is clinical and based on physical examination. Treatment ranges from observation or use of injectable collagenase to the surgical option in cases with significant functional limitations.


The postoperative analgesic efficacy and safety of piroxicam (FDDF) and naproxen sodium.
The aim of the present study was to compare the analgesic efficacy of piroxicam-FDDF (fast dissolving dosage form) with naproxen sodium, following bilateral removal of impacted third molars. A double-blind, randomized, crossover, analgesic trial was carried out on 40 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a single dose regimen of piroxicam-FDDF (40 mg, Feldene Flash, Pfizer, Turkey) was compared with naproxen sodium (550 mg, Anaprotab, Sanli, Turkey). Pain intensity was measured on a category-rating scale during the 8-h period after drug administration. Each patient evaluated the efficacy of the study medication at 15, 30, 45, 60, 90 and 120 min, and then hourly for up to 8 h of drug ingestion. Additional key efficacy measures were also determined (pain intensity difference [PID], sums of pain intensity difference [SPID], total pain relief [TOTPAR], peak pain relief, number of observations at which pain was half-relieved, overall evaluation of study medication effectiveness, and time to medication with a back-up analgesic). The data were analyzed by paired Student's t-test and one-way analysis of variance (ANOVA). Results are expressed as means +/- SEM, and p < 0.05 was taken as statistically significant. The PID and pain relief scores of the piroxicam-FDDF group were significantly greater than those for the naproxen sodium group at 15, 30, 45 and 60 min (p < 0.01). After 90 min to 8 h, no statistical significance was revealed among the two test groups (p > 0.05). The peak pain relief, maximal analgesic effect, SPID, TOTPAR values, adjusted mean number of observations with pain at least half-relieved, and the final overall evaluation records were all superior for piroxicam-FDDF (p < 0.05). The results of this study clearly show that the analgesic efficacy of piroxicam-FDDF is superior to naproxen sodium in the treatment of pain following oral surgery for the removal of impacted third molars.


Water-based chitosan/melamine polyphosphate multilayer nanocoating that extinguishes fire on polyester-cotton fabric.
Polyester-cotton (PECO) blends are widely used in the textile industry because they combine the softness of cotton and the strength and durability of polyester. Unfortunately, both fiber types share the disadvantage of being flammable. The layer-by-layer coating technique was used to deposit a highly effective flame retardant (melamine polyphosphate) from water onto polyester-cotton fabric. Soluble melamine and sodium hexametaphosphate form this water-insoluble flame retardant during the coating procedure. This unique nanocoating imparts self-extinguishing properties to PECO with only 12% relative coating weight. Vertical flame testing, pyrolysis combustion flow calorimetry (PCFC), thermogravimetric analysis (TGA), and scanning electron microscopy were used to evaluate the quality of the coating as well as its flame retardant performance. A combination of both condensed and gas-phase activity appears to be the reason for this effective flame retardancy. Degradation pathways of both cotton and polyester are affected by the applied coating, as shown by PCFC and TGA. Use of environmentally benign and non-toxic chemicals, and the ease of layer-by-layer deposition, making this coating an industrially feasible alternative to render polyester-cotton fabric self-extinguishing.


[Pharmacoeconomy in acne--evaluation of benefit and economics].
Acne belongs to the most common skin diseases and has a prevalence in the adolescence of nearly 100% and in adults of about 4%. The quality of life indes is significantly reduced und has impact on daily activities and social life and physical and psychological well being as well. The socioeconomic relevance is based not only on its prevalence but on direct and indirect costs. For acne therapy the knowledge on therapeutic costs is of importance but the cost benefit ratio as well. Evidence of therapeutic costs in acne and economic benefit of the therapy. Systematic review of Cochrane data. Calculations reveal general costs of acne treatment in Germany over 400 Mill.Euro per year. For the treatment with topical retinoids, BPO and antibiotics as well as systemic drugs only a few studies on costeffectiveness are available. For topical treatments results are not conclusive and dependent on the different health systems. New topical combinations may have a better economic outcome, however, more studies are needed. With regard to systemic therapies of moderate to severe acne based on the international references the costbenefit ratio favours the treatment with oral isotretinoin on the longterm outcome. Superiority is based on the relationship of costs and clinical outcome and the increased quality of life as well (cost-benefit ratio). It has to be emphazised that only longterm observations over years will lead to a valid calculation of costs and benefit. FACIT: Taking the high social and quality of life impact into consideration an early, well targeted and effective therapy is prevailing. Initial higher cost are balanced by a high quality of outcome under experienced dermatological supervision. The patients benefit is ranked over the final costs because of its medical, social and ethical aspects. To sample more differentiated data on pharmacoeconomic aspects well designed new clinical studies are to be set up.


Transmissible Burkholderia cepacia genomovar IIIa strains bind and convert monomeric iron(III) protoporphyrin IX into the mu-oxo oligomeric form.
Burkholderia cepacia isolates of genomovar III are highly transmissible amongst patients with cystic fibrosis (CF) and express a 97 kDa putative haem-binding protein (HBP) [Smalley, J. W., Charalabous, P., Birss, A. J. & Hart, C. A. (2001). Clin Diagn Lab Immunol 8, 509-514]. An investigation of the interactions of iron(III) protoporphyrin IX with epidemic and non-epidemic strains of B. cepacia to determine the role of the above protein in haem acquisition and binding is reported herein. Spectrophotometric titrations of cell suspensions of genomovar IIIa strains BC7 and C5424 with iron(III) protoporphyrin IX, at pH 7.0, resulted in the depletion of Fe(III)PPIX.OH monomers and formation of the micro -oxo oligomeric species, [Fe(III)PPIX](2)O. Difference spectroscopy indicated a continuous conversion of the monomeric iron(III) protoporphyrin IX into micro -oxo oligomers. Incubations with Fe(III)PPIX.OH monomers at pH 6.5 also showed that cells could shift the equilibrium to generate the micro -oxo oligomeric form. Genomovar I strains ATCC 25416 and LMG 17997 were unable to mediate this conversion. SDS-PAGE of genomovar IIIa strains exposed to Fe(III)PPIX.OH at pH 6.5 followed by tetramethylbenzidine/H(2)O(2) staining revealed, in addition to the 97 kDa HBP, two proteins of 77 and 149 kDa located in the outer membrane which bound Fe(III)PPIX.OH monomers. These proteins were absent from the genomovar I strains. Genomovar IIIa strains BC7 and C5424 showed increased cellular binding of [Fe(III)PPIX](2)O, and as a consequence, displayed increased catalase activities compared to cells of the genomovar I isolates. It is concluded that, in addition to the putative 97 kDa HBP, B. cepacia genomovar IIIa strains express two outer-membrane proteins which function to bind and convert Fe(III)PPIX.OH monomers into the micro -oxo oligomeric form, [Fe(III)PPIX](2)O. The ability to perform this conversion at both neutral and slightly acidic pHs may enable epidemic strains to withstand attack from neutrophil-derived H(2)O(2) in the inflamed CF lung.


1-(4-[18F]Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine: A Novel Suitable Radioligand with Low Lipophilicity for Imaging σ1 Receptors in the Brain.
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine (10) possessed a low nanomolar σ1 receptor affinity and a high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), and adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2, and serotonin 5-HT1 receptors. The corresponding radiotracer [18F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice. Pretreatment with the selective σ1 receptor agonist SA4503 significantly reduced the level of accumulation of the radiotracer in the brain. No radiometabolite of [18F]10 was observed to enter the brain. Positron emission tomography and magnetic resonance imaging confirmed suitable kinetics and a high specific binding of [18F]10 to σ1 receptors in rat brain. Ex vivo autoradiography showed a reduced level of binding of [18F]10 in the cortex and hippocampus of the senescence-accelerated prone (SAMP8) compared to that of the senescence-accelerated resistant (SAMR1) mice, indicating the potential dysfunction of σ1 receptors in Alzheimer's disease.


Unhealthy food consumption in adolescence: role of sedentary behaviours and modifiers in 11-, 13- and 15-year-old Italians.
Unhealthy eating behaviours increase with age and have been associated with adverse health consequences in adulthood. We examined the influence of screen-based sedentary behaviours (SBs) on unhealthy food consumption, such as energy-dense foods and sweetened drinks, among a representative sample of nearly 60 000 adolescents and assessed the role of possible modifiers. Data come from the Italian 2009-10 Health Behaviour in School-aged Children (HBSC) survey. Data on Eating patterns, SBs, physical activity, peers network, BMI and socio-economic status (SES) were collected following the HBSC study protocol. Hierarchical logistic regression models were used. Unhealthy food consumption was significantly associated with a lower intake of fruit and vegetables and with the increase of SBs in both sexes and in all ages. The risk was interestingly higher in normal weight adolescents, in those with wider relationships with peers and in low SES children. This study adds evidence to support the importance of investing more resources in educational initiatives both to increase parents' awareness to support adolescents on dietary choices and on time spent in screen-based behaviours, independently of their adiposity status; and to develop youth's ability to access and appropriately use media and technologies. Policy makers should also increase their attention on introducing regulatory policies on television food advertising to which youth are exposed.


Change in the natural head-neck orientation momentarily altered sensorimotor control during sensory transition.
Achilles tendon vibration generates proprioceptive information that is incongruent with the actual body position; it alters the perception of body orientation leading to a vibration-induced postural response. When a person is standing freely, vibration of the Achilles tendon shifts the internal representation of the verticality backward thus the vibration-induced postural response realigned the whole body orientation with the shifted subjective vertical. Because utricular otoliths information participates in the creation of the internal representation of the verticality, changing the natural orientation of the head-neck system during Achilles tendon vibration could alter the internal representation of the earth vertical to a greater extent. Consequently, it was hypothesized that compared to neutral head-neck orientation, alteration in the head-neck orientation should impair balance control immediately after Achilles tendon vibration onset or offset (i.e., sensory transition) as accurate perception of the earth vertical is required. Results revealed that balance control impairment was observed only immediately following Achilles tendon vibration offset; both groups with the head-neck either extended or flexed showed larger body sway (i.e., larger root mean square scalar distance between the center of pressure and center of gravity) compared to the group with the neutral head-neck orientation. The fact that balance control was uninfluenced by head-neck orientation immediately following vibration onset suggests the error signal needs to accumulate to a certain threshold before the internal representation of the earth vertical becomes incorrect.


Relation between Proepileptic Activity of Indomethacin and AdrenalGland Hormones.
The role of inflammation has been shown in the pathogenesis of epilepsy, while glucocorticoids and adrenaline have anti-inflammatory effects. The aim of the present study was to investigate the effects of adrenaline, prednisolone, and indomethacin on caffeine-induced epilepsy (epileptiform activity) in rats and to examine the mechanism of the pro-epileptic effect of indomethacin. The adrenalectomized rats that had been given only adrenaline (the control group) did not die; however, adrenaline did not prevent the adrenalectomized rats which were given prazosin, phenoxybenzamine, yohimbine, metoprolol, and propranolol from dying. In the rats given propranolol + adrenaline, the rate of death was 100%, while this rate was 50% in the groups receiving prazosin + adrenaline, phenoxybenzamine + adrenaline, and metoprolol + adrenaline. The rate was 75% in the group given yohimbine + adrenaline. Prednisolone increased the degree of convulsion in adrenalectomized rats. Over-reduction in the blood catecholamine level made epileptogenesis more severe. It was observed that adrenaline pressed epileptogenesis via its own receptors (α - 1, α - 2, β - 1, β - 2). It was also revealed that all of the adrenergic receptors were responsible due to antiepileptic activity; β - 2 receptors played the most important role. It was observed that both acute and chronic indomethacin administration reduced the catecholamine levels. The situation in which acute administration of indomethacin did not affect epileptogenesis might originate from the fact that the structure of indomethacin did not significantly increase the corticosterone level.


Location of the chronic subdural haematoma: role of the gravity and cranial morphology.
Chronic subdural haematoma (SDH) frequently originates from subdural hygroma (SDG). The cranial morphology can determine the location of SDG. Since SDG is the precursor of chronic SDH, the shapes of the cranium wall act an important role in location of chronic SDH. The authors tried to test this hypothesis. The computed tomographic scans or magnetic resonance images of 118 consecutive patients with chronic SDH were re-evaluated, and the symmetry of the cranium and location of the lesion were checked. The cranium was symmetrical in 55 patients (47%) and asymmetrical in 63 patients (53%). Chronic SDH was bilateral in 25 patients (21%) and unilateral in 93 patients (79%). It was more commonly bilateral in symmetrical craniums than in asymmetrical craniums (29.1% vs. 14.3%) (p = 0.0496). In 63 patients with asymmetric cranium, the chronic SDH was bilateral in nine patients, located on the opposite side of the flat side in 38 patients, and located on the same side of the flat side in 17 patients. This unequal distribution was statistically significant (p = 0.03). In four patients, the haematoma originated from the acute SDH located on the same side of the flat side. No reason could be found in the remaining 13 patients. Chronic SDH originating from SDG usually locates on the opposite to the flat side of the skull. The shape and posture of the cranium can predict the location of chronic SDH, as in the SDG.


Hip fracture risk and cadmium in erythrocytes: a nested case-control study with prospectively collected samples.
Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study's biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95% confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95% CI 0.77-2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95% CI 1.18-3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95% CI 1.29-8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.


Molecular and cellular programs underlying the development of bovine pre-implantation embryos.
Early embryonic mortality is a major cause of infertility in cattle, yet the underlying molecular causes remain a mystery. Over the past half century, assisted reproductive technologies such as in vitro fertilisation and somatic cell nuclear transfer have been used to improve cattle reproductive efficiency; however, reduced embryo developmental potential is seen compared to their in vivo counterparts. Recent years have seen exciting progress across bovine embryo research, including genomic profiling of embryogenesis, new methods for improving embryo competence, and experimenting on building bovine embryos from stem cell cultures. These advances are beginning to define bovine embryo molecular and cellular programs and could potentially lead to improved embryo health. Here, I highlight the current status of molecular determinants and cellular programs of bovine embryo development and new opportunities to improve the bovine embryo health.


MONOCRYL and DERMABOND vs Staples in Total Hip Arthroplasty Performed Through a Lateral Skin Incision: A Randomized Controlled Trial Using a Patient-Centered Assessment Tool.
There are various possible methods of skin closure in total hip arthroplasty (THA) through a lateral skin incision. The cost and time required for each can vary between techniques. The objective of this study was to determine whether there is a difference in patient and surgeon rating of scar outcome using a combination of subcuticular suture and skin adhesive (subcuticular MONOCRYL and DERMABOND [SMD]) vs staples for skin closure after THA. Patients undergoing THA were recruited from a university hospital. Patients were randomized to staples or SMD. Patient and Observer Scar Assessment Scale data were collected postoperatively. In addition, visual analog scale pain scores, wound drainage, length of stay, time to closure, and total cost were collected. One hundred twenty-nine patients were available for final analysis. There was no significant difference in Patient and Observer Scar Assessment Scale scores at 6 weeks or 3 months (P = .71). There was no difference in visual analog scale pain scores (P = .64, P = .49). The staple group had a higher rate of discharge on postoperative days 1 and 3 (P < .001, P < .001) but had a 1.6-minute shorter time of closure (P < .001). There was no significant difference in length of stay or total cost (P = .5). Although there are some small initial advantages to each method of skin closure, there is little difference in scar outcome when comparing SMD and staples.


[Biological characteristics of the variants of Bacillus thuringiensis subsp. galleriae formed during continuous culture].
Bacillus thuringiensis subsp. galleriae S. variants formed during continuous cultivation differ from the parent culture in certain properties. In contrast to the parent R form, their growth in the chemostat does not yield virulent mutants which can cause their lysis on solid media. The chemostat S forms are resistant against virulent phage mutants produced when the R variants are grown under the conditions of continuous cultivation and against a virulent phage obtained from the parent culture 69-6 under the action of vancomycin. The R forms are sensitive to these phages. When the S forms are grown under the chemostat conditions, they do not revert to the R forms. The R and S forms do not differ noticeably in the character of their growth, formation of spores and crystals, and biological activity.


Regulation of Mitochondrial Respiratory Chain Complex Levels, Organization, and Function by Arginyltransferase 1.
Arginyltransferase 1 (ATE1) is an evolutionary-conserved eukaryotic protein that localizes to the cytosol and nucleus. It is the only known enzyme in metazoans and fungi that catalyzes posttranslational arginylation. Lack of arginylation has been linked to an array of human disorders, including cancer, by altering the response to stress and the regulation of metabolism and apoptosis. Although mitochondria play relevant roles in these processes in health and disease, a causal relationship between ATE1 activity and mitochondrial biology has yet to be established. Here, we report a phylogenetic analysis that traces the roots of ATE1 to alpha-proteobacteria, the mitochondrion microbial ancestor. We then demonstrate that a small fraction of ATE1 localizes within mitochondria. Furthermore, the absence of ATE1 influences the levels, organization, and function of respiratory chain complexes in mouse cells. Specifically, ATE1-KO mouse embryonic fibroblasts have increased levels of respiratory supercomplexes I+III2+IVn. However, they have decreased mitochondrial respiration owing to severely lowered complex II levels, which leads to accumulation of succinate and downstream metabolic effects. Taken together, our findings establish a novel pathway for mitochondrial function regulation that might explain ATE1-dependent effects in various disease conditions, including cancer and aging, in which metabolic shifts are part of the pathogenic or deleterious underlying mechanism.


The excess burden of osteoarthritis in the province of Ontario, Canada.
Little is known about the burden of osteoarthritis (OA) in Canada. This study was undertaken to estimate the excess burden of OA in Ontario, the largest province in Canada. The records of Ontarian respondents to the Canadian Community Health Survey (CCHS) who provided consent to data linkage were linked to the Ontario Health Insurance Program physician claims database and the Discharge Abstract Database Inpatient and Day Procedure databases. Patients with OA (n = 1,474) were identified using CCHS 1.1 and the physician claims database. To determine the excess burden of OA, a control group matched by age, sex, and rural/urban status was created, with 3 controls per case (n = 4,422). Sociodemographic and medical characteristics, health-related quality of life, and 1-year physician, day (outpatient) procedure, and hospitalization costs were compared between the 2 groups. Regression analyses were performed to identify predictors of medical characteristics, health utility, and cost. The mean age of the OA patients and the control subjects was 66 years, and 74% of all study subjects were women. Several differences were observed between patients with OA and subjects without OA in terms of socioeconomic and medical characteristics. On a scale of 0-1, the mean utility value associated with OA was 0.68, compared to 0.84 for the control group (P < 0.0001), representing a utility decrement of 0.16. The 1-year physician, outpatient procedure, and hospitalization costs were significantly higher in the OA group than in the non-OA group ($2,233 Canadian versus $1,033 Canadian, respectively; P < 0.0001). These results indicate that the excess burden of OA in Ontario is considerable.


The biomechanical significance of the frontal sinus in Kabwe 1 (Homo heidelbergensis).
Paranasal sinuses are highly variable among living and fossil hominins and their function(s) are poorly understood. It has been argued they serve no particular function and are biological 'spandrels' arising as a structural consequence of changes in associated bones and/or soft tissue structures. In contrast, others have suggested that sinuses have one or more functions, in olfaction, respiration, thermoregulation, nitric oxide production, voice resonance, reduction of skull weight, and craniofacial biomechanics. Here we assess the extent to which the very large frontal sinus of Kabwe 1 impacts on the mechanical performance of the craniofacial skeleton during biting. It may be that the browridge is large and the sinus has large trabecular struts traversing it to compensate for the effect of a large sinus on the ability of the face to resist forces arising from biting. Alternatively, the large sinus may have no impact and be sited where strains that arise from biting would be very low. If the former is true, then infilling of the sinus would be expected to increase the ability of the skeleton to resist biting loads, while removing the struts might have the opposite effect. To these ends, finite element models with hollowed and infilled variants of the original sinus were created and loaded to simulate different bites. The deformations arising due to loading were then compared among different models and bites by contrasting the strain vectors arising during identical biting tasks. It was found that the frontal bone experiences very low strains and that infilling or hollowing of the sinus has little effect on strains over the cranial surface, with small effects over the frontal bone. The material used to infill the sinus experienced very low strains. This is consistent with the idea that frontal sinus morphogenesis is influenced by the strain field experienced by this region such that it comes to lie entirely within a region of the cranium that would otherwise experience low strains. This has implications for understanding why sinuses vary among hominin fossils.


Effects of glucocorticoid on brain acetylcholinesterase of developing chick embryos.
Fetal exposure to excessive or deficient glucocorticoids may alter the programming in differentiation and maturation of various tissues including the brain and nervous system, leading to dysfunctions later in life. For further exploration of this possibility, we established an animal model using developing chick embryos. (i) Reverse-transcription polymerase chain reaction was used to determine the expression of glucocorticoid receptor mRNA in the brain of chick embryos. (ii) Embryos on day 15 were administered betamethasone or mifepristone and their cerebrum, cerebellum and optic lobe were investigated to determine the activity of acetylcholinesterase. (i) Glucocorticoid receptor mRNA was shown to be present in the cerebrum, cerebellum and optic lobe. (ii) After the administration of betamethasone, acetylcholinesterase activities in the cerebrum, cerebellum and optic lobe on day 19 were 1.5- to 2-fold higher than those of untreated control. Weights of body and brain parts were 0.65-0.75-fold relative to control values. However, these differences were less noticeable on day 22. (iii) Administration of mifepristone before treatment with betamethasone prevented high-dose betamethasone-induced changes in acetylcholinesterase activity and bodyweights on day 19. Administration of mifepristone alone did not induce differences from the control. The cerebrum, cerebellum and optic lobe of chick embryos could be influenced by glucocorticoids because of the presence of glucocorticoid receptor mRNA. Although the effects observed after treatment with excess glucocorticoids (even no effects after mifepristone treatment) were transitory, they may alter the developmental program in ways that could result in lasting change and influence behavioral activities after hatching.


Fuzzy-Affine-Model-Based Sliding-Mode Control for Discrete-Time Nonlinear 2-D Systems via Output Feedback.
This work investigates the issue of output-feedback sliding-mode control (SMC) for nonlinear 2-D systems by Takagi-Sugeno fuzzy-affine models. Via combining with the sliding surface, the sliding-mode dynamical properties are depicted by a singular piecewise-affine system. Through piecewise quadratic Lyapunov functions, new stability and robust performance analysis of the sliding motion are carried out. An output-feedback dynamic SMC design approach is developed to guarantee that the system states can converge to a neighborhood of the sliding surface. Simulation studies are given to verify the validity of the proposed scheme.


The formation of ubiquitin rich condensates triggers recruitment of the ATG9A lipid transfer complex to initiate basal autophagy.
Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A or the lipid transfer protein ATG2 leads to the accumulation of phosphorylated p62 aggregates in the context of basal autophagy. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Lastly, we present evidence that poly-ubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.


Polyketide synthase pathways identified from a metagenomic library are derived from soil Acidobacteria.
Polyketides are structurally diverse secondary metabolites, many of which have antibiotic or anticancer activity. Type I modular polyketide synthase (PKS) genes are typically large and encode repeating enzymatic domains that elongate and modify the nascent polyketide chain. A fosmid metagenomic library constructed from an agricultural soil was arrayed and the macroarray was screened for the presence of conserved ketosynthase [β-ketoacyl synthase (KS)] domains, enzymatic domains present in PKSs. Thirty-four clones containing KS domains were identified by Southern hybridization. Many of the KS domains contained within metagenomic clones shared significant similarity to PKS or nonribosomal peptide synthesis genes from members of the Cyanobacteria or the Proteobacteria phyla. However, analysis of complete clone insert sequences indicated that the blast analysis for KS domains did not reflect the true phylogenetic origin of many of these metagenomic clones that had a %G+C content and significant sequence similarity to genes from members of the phylum Acidobacteria. This conclusion of an Acidobacteria origin for several clones was further supported by evidence that cultured soil Acidobacteria from different subdivisions have genetic loci closely related to PKS domains contained within metagenomic clones, suggesting that Acidobacteria may be a source of novel polyketides. This study also demonstrates the utility of combining data from culture-dependent and -independent investigations in expanding our collective knowledge of microbial genomic diversity.


Uncovering Survivorship Bias in Longitudinal Mental Health Surveys During the COVID-19 Pandemic.
Markedly elevated adverse mental health symptoms were widely observed early in the coronavirus disease 2019 (COVID-19) pandemic. Unlike the U.S., where cross-sectional data indicate anxiety and depression symptoms have remained elevated, such symptoms reportedly declined in the U.K., according to analysis of repeated measures from a largescale longitudinal study. However, nearly 40% of U.K. respondents (those who did not complete multiple follow-up surveys) were excluded from analysis, suggesting that survivorship bias might partially explain this discrepancy. We therefore sought to assess survivorship bias among participants in our longitudinal survey study as part of The COVID-19 Outbreak Public Evaluation (COPE) Initiative. Survivorship bias was assessed 4,039 U.S. respondents who completed surveys including the assessment of mental health as part of The COPE Initiative in April 2020 and were invited to complete follow-up surveys. Participants completed validated screening instruments for symptoms of anxiety, depression, and insomnia. Survivorship bias was assessed for (1) demographic differences in follow-up survey participation, (2) differences in initial adverse mental health symptom prevalences adjusted for demographic factors, and (3) differences in follow-up survey participation based on mental health experiences adjusted for demographic factors. Adjusting for demographics, individuals who completed only one or two out of four surveys had higher prevalences of anxiety and depression symptoms in April 2020 (e.g., one-survey versus four-survey, anxiety symptoms, adjusted prevalence ratio [aPR]: 1.30, 95% confidence interval [CI]: 1.08-1.55, P=0.0045; depression symptoms, aPR: 1.43, 95% CI: 1.17-1.75, P=0.00052). Moreover, individuals who experienced incident anxiety or depression symptoms had higher odds of not completing follow-up surveys (adjusted odds ratio [aOR]: 1.68, 95% CI: 1.22-2.31, P=0.0015, aOR: 1.56, 95% CI: 1.15-2.12, P=0.0046, respectively). Our findings revealed significant survivorship bias among longitudinal survey respondents, indicating that restricting analytic samples to only respondents who provide repeated assessments in longitudinal survey studies could lead to overly optimistic interpretations of mental health trends over time. Cross-sectional or planned missing data designs may provide more accurate estimates of population-level adverse mental health symptom prevalences than longitudinal surveys.


Mean platelet volume in nasal polyps.
Many studies in literature point out that inflammation related to nasal polyp is mostly dependent on eosinophils and their inflammatory products. Beside eosinophils, platelets may have a role in nasal polyp development. Platelets are involved in haemostasis, tissue repairing and inflammation. However, to our knowledge, there are no reports in the literature that study the association between platelet parameters and nasal polyps. Forty-three patients with nasal polyps and forty-nine healthy controls were enrolled in the study, retrospectively. Laboratory data of patients with nasal polyp were obtained at the time of diagnosis. There were no statistically significant differences between the two groups in terms of white blood count, haemoglobin, haematocrit and platelet count. The mean platelet volume (MPV) value of the nasal polyp group was significantly lower than the control group (p = 0.025). Mean eosinophil count was significantly elevated in the nasal polyp group compared to the control group (p < 0.001). Reduction in MPV may be an indicator for nasal polyp formation. Further studies with a larger study population are needed to detect the possible correlation between eosinophil count and MPV values in patients with nasal polyps.


Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that mediate glucocorticoid receptor coactivation independently of its effects on G(2) cell cycle arrest.
Human immunodeficiency virus type 1 (HIV-1) Vpr participates in nuclear targeting of the viral preintegration complex in nondividing cells and induces G(2) cell cycle arrest in proliferating cells, which creates an intracellular milieu favorable for viral replication. Vpr also activates the transcription of several promoters and enhancers by a poorly understood mechanism. Vpr enhances glucocorticoid receptor (GR) signaling and may mediate the effects of steroids on HIV replication. More specifically, recombinant Vpr can potentiate virion production from U937 cells, downregulate NF-kappaB induction, and enhance programmed cell death, all effects also mediated by glucocorticoids. Vpr has been proposed to act as a GR coactivator, although other studies suggest that these enhancing effects are merely a consequence of G(2) cell cycle arrest. We now demonstrate that Vpr functions as a GR coactivator and that this activity is independent of cell cycle arrest. In addition, we show that the Vpr-induced coactivation requires an intact glucocorticoid response element, that it is dependent on the presence of hormone and the corresponding receptor, and that it is mediated by the two highly conserved leucine-rich domains within Vpr that resemble the GR coactivator signature motif.


Psychosocial risk factors in coronary heart disease: beyond type A behavior.
From a broad perspective of psychocardiology, our aim is to give an overview of the role that psychosocial risk factors play in coronary artery disease. A review of the literature was made based on a systematic search of four databases: EBSCO, Proquest Psychology, Proquest Health and PubMed. In sample 1, two dependent (Coronary and Myocardial) and six independent variables (Type A, hostility, anger, depression, anxiety and psychosocial) were created. In sample 2, we searched directly for three descriptors (Type D personality, time urgency and coronary-prone behavior). Following this search, two sets of concepts were distinguished: (1) those relating to traditional research areas, and their critics, and (2) those included in the most recent trends, and their limitations. Research in psychocardiology has gone beyond the traditional concept of type A behavior pattern. The idea of a specific toxic component has been abandoned, in favor of a more holistic approach. The deleterious effects that negative emotions, particularly depression, as well as personality and socioeconomic status, may have on the functioning of various organs and psychosocial performance have now been recognized.


Projecting future complications of chronic hepatitis C in the United States.
Chronic hepatitis C virus (HCV) infection is common and often results in slowly progressive liver disease. Although acute hepatitis C is now uncommon, most patients with acute infection have developed chronic hepatitis, and, therefore, the pool of infected patients is large. We used a modification of a previously described natural history model for HCV infection to project the number of cases of HCV infection, cirrhosis, and liver failure over the next 40 years. The model estimated the prevalence of HCV infection in the United States was 3.07 x 10(6) in 1993 (compared with an adjusted National Health and Nutrition Evaluation Survey (NHANES) III estimate of 2.8 to 3.5 x 10(6)). A gradual decline in the prevalence of infection should occur by year 2040 because of aging and natural deaths among the infected pool. However, as the duration of infection increases in the surviving cohort, the proportion with cirrhosis will increase from 16% to 32% by 2020 in an untreated population. Complications of cirrhosis also will increase dramatically over the next 20 years: hepatic decompensation (up 106%), hepatocellular carcinoma (up 81%), and liver-related deaths (up 180%). Although current treatment regimens eradicate HCV in over 50% of cases, many more patients would need to be treated to significantly impact disease progression. Identification and treatment of every case of HCV infection (with or without cirrhosis) would reduce the number of cases of decompensated cirrhosis by almost half after 20 years. Despite the declining incidence of acute HCV infection, chronic hepatitis C is common. The prevalence of cirrhosis and the incidence of its complications will increase over the next 10 to 20 years, because the duration of infection increases among those with chronic hepatitis C. These data emphasize the need for greater access to transplantation by expansion of the donor pool, increasing use of split livers and living donors, and novel options such as xenotransplantation.


WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.
The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.


Post-traumatic stress disorder in healthcare workers of emergency departments during the pandemic: A cross-sectional study.
Emergency departments (EDs) were the first application center for Covid-19 patients, as in almost all diseases. For this reason, a serious mental burden has arisen for ED workers. This study was conducted to determine the possible rate of Posttraumatic Stress Disorder (PTSD) and factors that may be associated with PTSD symptom severity in physicians and nurses working in EDs. This cross-sectional study was conducted with a total of 783 participants, including 406 physicians and 377 nurses working in EDs. The PTSD Checklist for DSM-5; Depression, Anxiety and Stress Scale-21; and a structured questionnaire on sociodemographic and work-related characteristics were administered to the participants. The probable PTSD rate in the total sample was found to be 19.2%. The rate of probable PTSD in physicians (22.9%) was significantly higher than in nurses (15.1%). However, PTSD symptom total scores and PTSD symptom clusters were higher in physicians than in nurses, but there was no difference between the two groups in terms of depression, anxiety and stress levels. High anxiety level, being diagnosed with COVID-19, high depression level, female gender, and having additional chronic disease were predictors of high PTSD symptom severity in physicians. For nurses, high anxiety level, being diagnosed with COVID-19, working with 24-h shifts, high depression level, low work experience (years), low monthly income and having additional chronic disease were the predictors of high PTSD symptom severity. The results of our study showed that both profession groups are at risk for PTSD, and contrary to the existing literature, this rate may be higher in physicians than in nurses. HCWs in the EDs needed protective and supportive mental health models in terms of PTSD.


Impact of processing load on analogical mapping with visual sequences in children with developmental language disorders (DLD).
Analogical mapping is a domain-general cognitive process used notably in language development, and particularly in the abstraction of construction schemas. Children with developmental language disorders (DLD) display an impairment in linguistic productivity and creativity, which can be linked to a lack of generalization of construction schemas. To investigate analogical mapping in children with DLD, and especially the influence of processing load, as it could explain the lack of creativity observed in children with DLD. It was hypothesized that analogical mapping is altered in children with DLD and that greater cognitive load (sequential presentation and no perceptual support) would be linked to poorer performance in these children. Fifteen children with DLD and their age-matched peers were administrated a visual analogical reasoning task where they had to complete a sequence sharing the same relational structure as previously presented sequences. Two factors influencing processing load were studied: the modality of presentation (sequential versus simultaneous) and the perceptual support (with versus without). Results showed an expected group effect with poorer performance in children with DLD compared with children with typical language development (TLD). Results corroborated hypotheses according to which children with DLD have difficulties with analogical mapping, which could hinder their abstraction of construction schemas. Results about the influence of processing load were mixed. While the difference between the two groups was more marked for the items without perceptual support than for those with perceptual support, children with DLD were not more affected by the sequential presentation than children with TLD. Children with DLD have impaired analogical mapping competences, especially when the relational similarities are not supported by perceptual cues. This impairment may be the cause of their difficulties in abstracting construction schemas, thus provoking their poor linguistic productivity and creativity. However, more studies are needed to confirm this hypothesis, as the influence of analogical reasoning on language development could also be reversed or could be linked to another external factor.


Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice.
Brain natriuretic peptide (BNP) is a ventricular hormone with natriuretic, diuretic and vasodilatory actions. Acute infusion of BNP reduces cardiac pre- and after-load in healthy and diseased subjects, but its long-term therapeutic usefulness remains unclear. We prepared a monoclonal antibody specific to mouse BNP, and characterized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction. Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY-mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeostasis. We developed highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular BNP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, accompanied with marked reduction in the atrial natriuretic peptide (ANP) concentration, that may be due to binding of circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KYmBNP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systolic BP. These results suggested that biological actions of BNP last and reduce cardiac overload in its longterm overproduction in the transgenic mouse model.


[Participation of its reaction center in the electrochemical reduction of ferredoxin].
In the experiments with reaction center modification of ferredoxin its participation in reduction has been shown. Polarographic characteristics of ferredoxin and apoferredoxin have been compared. While removing iron and labile sulphur from ferredoxin reaction center the reduction wave of Fe-S bonds with E 1/2 = -0.33 V (N. H. E.) transforms into the reduction wave of S-S bonds with E 1/2 = -0,39 V at pH = 7.