SARS-CoV-2 virus which caused the global pandemic the Coronavirus Disease- 2019 (COVID-2019) has infected about 1,203,959 patients and brought forth death rate about 64,788 among 206 countries as mentioned by WHO in the month of April 2020. The clinical trials are underway for Remdesivir, an investigational anti-viral drug from Gilead Sciences. Antimalarial drugs such as Chloroquine and Hydroxychloroquine derivatives are being used in emergency cases; however, they are not suitable for patients with conditions like diabetes, hypertension and cardiac issues. The lack of availability of approved treatment for this disease calls forth the scientific community to find novel compounds with the ability to treat it. This paper evaluates the compound Andrographolide from Andrographis paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction and ADME prediction. Andrographolide was docked successfully in the binding site of SARS-CoV-2 Mpro. Computational approaches also predicts this molecule to have good solubility, pharmacodynamics property and target accuracy. This molecule also obeys Lipinski's rule, which makes it a promising compound to pursue further biochemical and cell based assays to explore its potential for use against COVID-19.Communicated by Ramaswamy H. Sarma.

Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network.

The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Diosignin and 4-hydroxy-L-isulosine (4-OH-Ile) are the two active ingredients of Fenugreek (Trigonella foenumgraecum). Thus, in this study, we examined the effects of hydroalcoholic extract of fenugreek seeds (HEFS), diosgenin and 4-OH-Ile on the expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ) and low-density lipoprotein (LDL) receptor (LDLR) which are involved in lipid metabolism in SW480 cell line.

MicroRNAs (miRNAs) are short, noncoding RNAs that play vital roles in gene regulation. It has been shown that storage has an effect on platelet miRNAs. MiR-16 is highly expressed in platelets and it appears to target the genes involved in cell death. It has been shown that platelets could be stored in Composol for a longer period of time. The aim of the present study was to assess and compare the expression pattern of miR-16 in platelet concentrates (PCs) in plasma and Composol media.

von Frey Filament (vFF) is an aesthesiometer to measure paw withdrawal thresholds. Our aim was to validate the manually von Frey test technique for assessing neuropathic pain behavioral signs in a sciatic nerve ligation model.

In the cerebellum of neonatal mice, multiple climbing fibers (CFs) form excitatory synapses on each Purkinje cell (PC). Only one CF is strengthened in each PC from postnatal day 3 (P3) to P7, whereas the other weaker CFs are eliminated progressively from ∼P7 to ∼P11 (early phase of CF elimination) and from ∼P12 to ∼P17 (late phase of CF elimination). Type 1 metabotropic glutamate receptor (mGluR1) triggers a canonical pathway in PCs for the late phase of CF elimination. Among downstream signaling molecules of mGluR1, phospholipase C β3 (PLCβ3) and β4 (PLCβ4) are expressed complementarily in PCs of aldolase C (Aldoc)-positive (+) and Aldoc-negative (-) cerebellar compartments, respectively. PLCβ4 is reported to mediate the late phase of CF elimination in the anterior half of the cerebellar vermis which corresponds to the Aldoc (-) region. However, roles of PLCβ3 and Aldoc in CF synapse elimination are unknown. Here, we investigated CF innervation of PCs in Aldoc-tdTomato knock-in mice that underwent lentivirus-mediated knockdown (KD) of PLCβ3 in PCs during postnatal development. By recording CF-mediated excitatory postsynaptic currents from PCs and immunostaining CF synaptic terminals, we found that significantly higher percentage of PCs with PLCβ3-KD remained multiply innervated by CFs in Aldoc (+) compartments after P12, which was accompanied by impaired elimination of somatic CF synapses and reduced dendritic CF translocation. In contrast, deletion of Aldoc had no effect on CF synapse elimination. These results suggest that PLCβ3 is required for the late phase of CF elimination in Aldoc (+) PCs.

The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar, is poorly understood. The pulvinar is thought to modulate information flow between cortical areas, and has been implicated in cognitive tasks like directing visually guided actions. In order to better understand the underlying circuitry, we performed retrograde injections of modified rabies virus in the visual cortex and pulvinar of the Long-Evans rat. We found a relatively small population of cells projecting to primary visual cortex (V1), compared to a much larger population projecting to higher visual cortex. Reciprocal corticothalamic projections showed a similar result, implying that pulvinar does not play as big a role in directly modulating rodent V1 activity as previously thought.

Adipose-derived mesenchymal stem cells markedly attenuated brain infarct size and improved neurological function in rats. The mechanisms for neuronal cell death have previously been defined in stress states to suggest that an influx of calcium ions into the neurons activates calpain cleavage of p35 into p25 forming a hyperactive complex that induces cell death. Now we report that p5, a 24-residue peptide derived from p35, offers protection to neurons and endothelial cells in vitro. In vivo administration of human adipose-derived mesenchymal stem cells (hADMSCs) loaded with this therapeutic peptide to post-stroke rats had no effect on the infarct volume. Nevertheless, the treatment led to improvement in functional recovery in spatial learning and memory (water maze), bilateral coordination and sensorimotor function (rotating pole), and asymmetry of forelimb usage (cylinder test). However, the treatment may not impact on cutaneous sensitivity (adhesive tape removal test). In addition, the double immunofluorescence with human cell-specific antibodies revealed that the number of surviving transplanted cells was higher in the peri-infarcted area of animals treated with hADMSCs + P5 than that in hADMSC-treated or control animals, concomitant with reduced number of phagocytic, annexin3-positive cells in the peri-infarcted region. However, the combination therapy did not increase the vascular density in the peri-infarcted area after stroke. In conclusion, administration of hADMSC-loaded p5 peptide to post-stroke rats created conditions that supported survival of drug-loaded hADMSCs after cerebral ischemia, suggesting its therapeutic potential in patients with stroke.

Cognitive impairment and dementia are predicted to undergo a dramatic increase in the following years with more than 131.5 million people being affected by 2030. Although vascular diseases play the most important role in the pathogenesis of memory impairment in aging men, some pre-clinical and clinical evidence has suggested a possible contribution of the age-dependent reduction of testosterone (T). In this paper we have summarized and discussed all the information derived from available animal and experimental studies. In addition, we meta-analyzed data rising from all randomized placebo controlled trials (RCTs) published so far. Only limited preclinical and clinical evidence can support a possible contribution of T in the pathogenesis of the age-dependent impairment of cognitive functions. In addition, our meta-analysis did not support the use of T replacement therapy for the improvement of several cognitive domains analyzed including attention/working memory, executive function, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability. However, it is important to recognize that the vast majority of available RCTs included mixed populations of subjects with eugonadism and hypogonadism preventing any final conclusion being drawn on these issues.

Somatic structural variants (SVs), which are variants that typically impact >50 nucleotides, play a significant role in cancer development and evolution but are notoriously more difficult to detect than small variants from short-read next-generation sequencing (NGS) data. This is due to a combination of challenges attributed to the purity of tumour samples, tumour heterogeneity, limitations of short-read information from NGS and sequence alignment ambiguities. In spite of active development of SV detection tools (callers) over the past few years, each method has inherent advantages and limitations. In this review, we highlight some of the important factors affecting somatic SV detection and compared the performance of seven commonly used SV callers. In particular, we focus on the extent of change in sensitivity and precision for detecting different SV types and size ranges from samples with differing variant allele frequencies and sequencing depths of coverage. We highlight the reasons for why some SV callers perform well in some settings but not others, allowing our evaluation findings to be extended beyond the seven SV callers examined in this paper. As the importance of large SVs become increasingly recognized in cancer genomics, this paper provides a timely review on some of the most impactful factors influencing somatic SV detection that should be considered when choosing SV callers.

There is no evidence supporting intubation for a Glasgow Coma Scale (GCS) of 8. We investigated the effect of intubation in trauma patients with a GCS 6-8, with the hypothesis that intubation would increase mortality and length of stay.

Professional identities research in medical education has made significant contributions to the field. However, what comprises professional identities is rarely interrogated. This research tackles this relatively understudied component of professional identities research by understanding emergency medicine physicians' perspectives on the important elements that comprise their professional identities. Q-methodology was used to identify different clusters of viewpoints on professional identities; by extension, the core components that comprise emergency medicine physicians' professional identities are disclosed. Thirty-three emergency medicine physicians were recruited, through purposive sampling, from five hospitals across Taiwan. R software was used to analyse the Q-sorts, determine loadings on each viewpoint and formulate the viewpoint array. Analysis of interview data enhanced our understanding of these viewpoints. In total, twenty-five emergency medicine physicians loaded onto four distinct viewpoints, reflecting dominant perspectives of emergency medicine physicians' understanding of their professional identities. These distinct viewpoints demonstrated what emergency medicine physicians deemed significant in how they understood themselves. The viewpoints comprised: skills acquisition, capabilities and practical wisdom; coping ability and resilience; professional recognition and self-esteem; and wellbeing and quality of life. All viewpoints stressed the importance of trust between colleagues. These findings demonstrate the multitude of ways in which seemingly unified professional identities diverge across groups of individuals. An enhanced understanding of speciality work culture is gained. By understanding facets of professional identities, the development of future educational interventions and departmental initiatives, which might support key components of professional identities, can be explored.

The novel coronavirus disease 2019 (COVID-19) caused by SARS-COV-2 has raised myriad of global concerns. There is currently no FDA approved antiviral strategy to alleviate the disease burden. The conserved 3-chymotrypsin-like protease (3CLpro), which controls coronavirus replication is a promising drug target for combating the coronavirus infection. This study screens some African plants derived alkaloids and terpenoids as potential inhibitors of coronavirus 3CLpro using in silico approach. Bioactive alkaloids (62) and terpenoids (100) of plants native to Africa were docked to the 3CLpro of the novel SARS-CoV-2. The top twenty alkaloids and terpenoids with high binding affinities to the SARS-CoV-2 3CLpro were further docked to the 3CLpro of SARS-CoV and MERS-CoV. The docking scores were compared with 3CLpro-referenced inhibitors (Lopinavir and Ritonavir). The top docked compounds were further subjected to ADEM/Tox and Lipinski filtering analyses for drug-likeness prediction analysis. This ligand-protein interaction study revealed that more than half of the top twenty alkaloids and terpenoids interacted favourably with the coronaviruses 3CLpro, and had binding affinities that surpassed that of lopinavir and ritonavir. Also, a highly defined hit-list of seven compounds (10-Hydroxyusambarensine, Cryptoquindoline, 6-Oxoisoiguesterin, 22-Hydroxyhopan-3-one, Cryptospirolepine, Isoiguesterin and 20-Epibryonolic acid) were identified. Furthermore, four non-toxic, druggable plant derived alkaloids (10-Hydroxyusambarensine, and Cryptoquindoline) and terpenoids (6-Oxoisoiguesterin and 22-Hydroxyhopan-3-one), that bind to the receptor-binding site and catalytic dyad of SARS-CoV-2 3CLpro were identified from the predictive ADME/tox and Lipinski filter analysis. However, further experimental analyses are required for developing these possible leads into natural anti-COVID-19 therapeutic agents for combating the pandemic.Communicated by Ramaswamy H. Sarma.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

Across international contexts, people with serious mental illnesses (SMI) experience marked reductions in life expectancy at birth. The intersection of ethnicity and social deprivation on life expectancy in SMI is unclear. The aim of this study was to assess the impact of ethnicity and area-level deprivation on life expectancy at birth in SMI, defined as schizophrenia-spectrum disorders, bipolar disorders and depression, using data from London, UK.

General self-efficacy (GSE) encourages health-promoting behaviors in older adults. It is unsurprising then that older adults receiving health care services are reported to have a greater risk of low GSE than older adults who are not. Despite this, there is currently limited evidence investigating whether the effect differs based on the environment in which care is received. This review aims to determine whether the GSE of older adults is affected by the receipt of health care services and whether GSE varies based on the setting in which care is received.

To date, there is no standard tool to diagnose gastroesophageal reflux disease (GERD). Typically, GERD is a non-erosive reflux disease (NERD) that does not present endoscopic abnormalities. Confocal laser endomicroscopy (CLE) has been shown to be an effective tool to identify and diagnose GERD. We aimed to investigate the cellular and vascular changes in vivo and ex vivo through CLE in patients with GERD.

For more than 2000 years, the avian embryo has helped scientists understand questions of developmental and cell biology. As early as 350 BC Aristotle described embryonic development inside a chicken egg (Aristotle, Generation of animals. Loeb Classical Library (translated), vol. 8, 1943). In the seventeenth century, Marcello Malpighi, referred to as the father of embryology, first diagramed the microscopic morphogenesis of the chick embryo, including extensive characterization of the cardiovascular system (Pearce Eur Neurol 58(4):253-255, 2007; West, Am J Physiol Lung Cell Mol Physiol 304(6):L383-L390, 2016). The ease of accessibility to the embryo and similarity to mammalian development have made avians a powerful system among model organisms. Currently, a unique combination of classical and modern techniques is employed for investigation of the vascular system in the avian embryo. Here, we will introduce the essential techniques of embryonic manipulation for experimental study in vascular biology.

To assess personal, professional, medical, and scientific educational characteristics and issues reported by pediatricians.