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However, study partners tend to report higher and increasing ECogSP scores on behalf of participants in the same diagnosis category; this would indicate a degradation in the participant's cognitive ability over time, consistent with the progress of Alzheimer's disease.Background Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. As no effective novel drugs are available currently, drug repurposing is an alternative intervention strategy. Here we present an in silico drug repurposing study that implements successful concepts of computer-aided drug design (CADD) technology for repurposing known drugs to interfere with viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates host cell entry via the hACE2 receptor. Methods A total of 4015 known and approved small molecules were screened for interaction with SARS-CoV-2-S through docking studies and 15 lead molecules were shortlisted. Additionally, streptomycin, ciprofloxacin, and glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability and affordability. The 18 molecules were subjected to molecular dynamics (MD) simulation. Results The MD simulation results indicate that GA of plant origin may be repurposed for SARS-CoV-2 intervention, pending further studies. Conclusions Repurposing is a beneficial strategy for treating COVID-19 with existing drugs. It is aimed at using docking studies to screen molecules for clinical application and investigating their efficacy in inhibiting SARS-CoV-2-S. SARS-CoV-2-S is a key pathogenic protein that mediates pathogen-host interaction. Hence, the molecules screened for inhibitory properties against SARS-CoV-2-S can be clinically used to treat COVID-19 since the safety profile is already known.Background Neonatal jaundice is a physiological process that occurs normally ‎for every infant to a varying degree. In some cases, this process becomes pathological ‎and imposes an increased risk of morbidity and mortality for the infant. The aim of this study was to assess the adherence level of various physicians to different guidelines ‎of management of neonatal hyperbilirubinemia in Iraq. Methods An observational cross-sectional study was conducted in ‎multiple outpatient clinics in various Iraqi provinces, from February ‎‎2018 to ‎February 2019. ‎The study involved 130 physicians, who were divided into emergency physicians (EPs), general practitioners (GPs), and pediatricians (PDs), and assessed their compliance to guidelines for management of neonatal hyperbilirubinemia using a questionnaire, which included providing the correct management for a test case scenario. Results PDs had significantly longer discharge times compared to EPs and GPs. In total, ‎91.7‎% of PDs always tested the neonate for bilirubin levels ‎before discharge, while 5.5‎% of GPs and 0% of EP did so. Regarding follow-up visits, 16.7‎%, 4.8% and 45.2% of PDs, EPs and GPs, respectively, scheduled a follow-up between 49-72 hours; ‎47.6‎% and 38.1% of EPs scheduled a follow-up at ≤24 hours and 25-48 hours, respectively‎‏. In addition, 91.7% of PDs gave the correct answer for the management of the test ‎case scenario, followed by 58.9% of GPs, and 38.1% of ‎EPs‎‏.‏ About half of ‎PDs extended neonates length of stay beyond 48 ‎hours. Conclusion GPs and EPs show lower adherence levels for the management of neonatal jaundice than PDs, which indicates that these physicians adhere well to current management guidelines from the WHO, ‎AAP, and NICE.Background The temporal envelope (ENV) plays a vital role in conveying inter-aural time difference (ITD) in many clinical populations. However, the presence of background noise and electronic features, such as compression, reduces the modulation depth of ENV to a different degree in both ears. The effect of ENV modulation depth differences between the ears on ITD thresholds is unknown; therefore, this was the aim of the current study's investigation. Methods Six normally hearing young adults (age range 20-30 years) participated in the current study. Six vowel-consonant-vowel (VCV) (/aka/, /aga/, /apa/, /aba/, /ata/, /ada/) tokens were used as the probe stimuli. ENV depth of VCV tokens was smeared by 0%, 29%, and 50%, which results in 100%, 71%, and 50% of the original modulation depth. ITD thresholds were estimated as a function of the difference in temporal ENV depth between the ears, wherein in one ear the modulation depth was retained at 100% and in the other ear, the modulation depth was changed to 100%, 71%, and 50%. Results Repeated measures of ANOVA revealed a significant main effect of interaural modulation depth differences on the ITD threshold (F(2,10)= 9.04, p= 0.006). ITD thresholds increased with an increase in the inter-aural modulation depth difference. Conclusion Inter-aural ENV depth is critical for ITD perception.Acute mechanical circulatory support (MCS) devices are widely used in cardiogenic shock (CS) despite a lack of high-quality clinical evidence to guide their use. Multiple devices exist across a spectrum from modest to complete support, and each is associated with unique risks. In this review, we summarize existing data on complications associated with the three most widely used acute MCS platforms the intra-aortic balloon pump (IABP), Impella systems, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We review evidence from available randomized trials and highlight challenges comparing complication rates from case series and comparative observational studies where a lack of granular data precludes appropriate matching of patients by CS severity. We further offer a series of best practices to help shock practitioners minimize the risk of MCS-associated complications and ensure the best possible outcomes for patients.Acromegaly is a complex disease with excessive growth hormone and insulin-like growth factor 1 (IGF-1) causing multisystem effects, particularly cardiovascular, respiratory, and metabolic. Psychological concerns and poor quality of life (QoL) are also major disease consequences. This review is intended for clinicians and focuses on the latest developments related to respiratory and QoL effects of long-term growth hormone excess. Along with biochemical disease control, patient treatment satisfaction and outcomes have become major treatment objectives; current knowledge and tools to evaluate and manage this aspect of the disease are described. Sleep apnea syndrome and other derangements of lung function and apparatus, from pathophysiology to treatment, and evaluation tools and determinants of QoL in patients with acromegaly are discussed.Multidisciplinary investigations into the pathogenesis of acne have significantly progressed over the past three years. Studies of the etiology of acne from the perspectives, for example, of sebaceous gland biology, sebum, genetics, keratinization, differentiation, hair cycles, immunology, bacteriology, and wound healing have elucidated its pathogenesis. This has led to the development of new therapies and paved the way for advanced studies that will enable the further evolution of acne treatment.Sickle cell disease (SCD) afflicts millions of people worldwide but is referred to as an orphan disease in the United States. Over the past several decades, there has been an increasing understanding of the pathophysiology of SCD and its complications. While most individuals with SCD in resource-rich countries survive into adulthood, the life expectancy of patients with SCD remains substantially shorter than for the general African-American population. SCD can be cured using hematopoietic stem cell transplantation and possibly gene therapy, but these treatment approaches are not available to most patients, the majority of whom reside in low- and middle-income countries. Until relatively recently, only one drug, hydroxyurea, was approved by the US Food and Drug Administration to ameliorate disease severity. Multiple other drugs (L-glutamine, crizanlizumab, and voxelotor) have recently been approved for the treatment of SCD, with several others at various stages of clinical testing. The availability of multiple agents to treat SCD raises questions related to the choice of appropriate drug therapy, combination of multiple agents, and affordability of recently approved products. The enthusiasm for new drug development provides opportunities to involve patients in low- and middle-income nations in the testing of potentially disease-modifying therapies and has the potential to contribute to capacity building in these environments. Demonstration that these agents, alone or in combination, can prevent or decrease end-organ damage would provide additional evidence for the role of drug therapies in improving outcomes in SCD.Cough is a natural process that protects the airway. Cough can occur spontaneously or voluntarily. It is considered chronic when it is present for longer than 4 weeks in children or 8 weeks in adults. In both, chronic cough causes patient distress and increased healthcare utilization. Etiologies of pediatric chronic cough include asthma, protracted bacterial bronchitis, tracheomalacia, habit cough, and various systemic disorders. While some diagnoses are identifiable by careful history alone, others require testing guided by specific pointers. Flexible fiberoptic bronchoscopy has been an important tool to identify etiologies of chronic cough that were not otherwise apparent. In adults, asthma and bronchitis are well-defined etiologies of chronic cough, but much chronic cough in adults is largely a conundrum. Reviews of adult chronic cough report that at least 40% of adults with chronic cough have no medical explanation. Gastroesophageal reflux and upper airway cough syndrome (a.k.a. post-nasal drip) have been common diagnoses of chronic cough, but those diagnoses have no support from controlled clinical trials and have been subjected to multiple published critiques. Cough hypersensitivity is considered to be an explanation for chronic cough in adults who have no other confirmed diagnosis. Gabapentin, a neuromodulator, has been associated with a modest effect in adults, as has speech pathology. While habit cough has not generally been a diagnosis in adults, there is evidence for a behavioral component in adults with chronic cough. Treatment for a specific diagnosis provides a better outcome than trials of cough suppression in the absence of a specific diagnosis. More data are needed for chronic cough in adults to examine the hypothesized cough hypersensitivity and behavioral management. This article reviews etiologies and the treatment of chronic cough in children and the conundrum of diagnosing and treating chronic cough in adults.Diversity within the fungal kingdom is evident from the wide range of morphologies fungi display as well as the various ecological roles and industrial purposes they serve. Technological advances, particularly in long-read sequencing, coupled with the increasing efficiency and decreasing costs across sequencing platforms have enabled robust characterization of fungal genomes. These sequencing efforts continue to reveal the rampant diversity in fungi at the genome level. Here, we discuss studies that have furthered our understanding of fungal genetic diversity and genomic evolution. selleckchem These studies revealed the presence of both small-scale and large-scale genomic changes. In fungi, research has recently focused on many small-scale changes, such as how hypermutation and allelic transmission impact genome evolution as well as how and why a few specific genomic regions are more susceptible to rapid evolution than others. High-throughput sequencing of a diverse set of fungal genomes has also illuminated the frequency, mechanisms, and impacts of large-scale changes, which include chromosome structural variation and changes in chromosome number, such as aneuploidy, polyploidy, and the presence of supernumerary chromosomes.

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