Notes

Multidrug Efflux Pumps and also the Two-Faced Janus involving Substrates and also Inhibitors.
Kobuvirus infections are common among humans, rodents, carnivores, pigs, and ruminants. We report herein the complete genome sequence of a novel caprine kobuvirus (MN604700) from diarrheic kids in Minnesota. Whole-genome sequencing revealed a kobuvirus genome of 8,139 nt with a single ORF region encoding a polyprotein of 2,480 amino acids. Further analysis revealed nt substitutions along the genome compared with that of the caprine kobuvirus reference strain, with 93% identity. Phylogenetic analysis indicated that the clade of the caprine kobuvirus was most closely related to porcine kobuviruses rather than bovine or ovine kobuviruses. Using primers designed from this genome, caprine kobuvirus was identified in the stools of other goats. Sanger sequencing of PCR products indicated 3D and VP1 gene nucleotides of this latter strain were 95% and 91% identical with those of MN604700, respectively. There were 35 and 101 nt substitutions in 3D and VP1 genes, respectively. Findings of kobuvirus over a 2-y period may indicate an endemic state, which needs further research. In addition, screening for kobuviruses over large geographic areas is needed to identify the evolutionary connections among different strains.Two horses that consumed well water with high fluoride content exhibited clinical signs of chronic dental and skeletal fluoride toxicosis and were later euthanized and autopsied. Both horses had degenerative disease of multiple joints and multiple dental defects. Elevated fluoride concentrations were found in bone and tooth samples of both horses, well water, and feed. Microscopically, abnormalities were noted in bone and tooth samples, and consisted mostly of foci of cement necrosis and hypercementosis. Horses exhibiting bilateral, highly symmetrical dental and/or skeletal lesions, with chronic lameness, should be evaluated for the possible presence of fluoride toxicosis.The global spread of the coronavirus infections disease - 2019 (COVID-19) and the search for new drugs from natural products particularly from plants are receiving much attention recently. In this study, the therapeutic potential of a new iridoid glycoside isolated from the leaves of Clerodendrum volubile against COVID-19 was investigated. Harpagide 5-O-β-D-glucopyranoside (HG) was isolated, characterised and investigated for its druglikeness, optimized geometry, and pharmacokinetics properties. Its immunomodulatory was determined by chemiluminescence assay using polymorphonuclear neutrophils (PMNs) in addition to T-cell proliferation assay. In silico analysis was used in determining its molecular interaction with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). HG displayed potent druglikeness properties, with no inhibitory effect on cytochrome P450 (1A2, 2C19, 2C9, 2D6 and 3A4) and a predicted LD50 of 2000 mg/kg. Its 1H-NMR chemical shifts showed a little deviation of 0.01 and 0.11 ppm for H-4 and H-9, respectively. HG significantly suppressed oxidative bursts in PMNs, while concomitantly inhibiting T-cell proliferation. It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor. These results suggest the immunomodulatory properties and anti-SARS-COV-2 potentials of HG which can be explored in the treatment and management of COVID-19. Communicated by Ramaswamy H. Sarma.
Doctors who research and provide abortion care have had their work characterized as a conflict of interest. We investigated whether surgeons who perform medical procedures other than abortion also routinely conduct research on that procedure and whether they disclose this as a relevant "conflict of interest."

We conducted a two-step literature review of five medical procedures-abortion, rhinoplasty, Mohs micrographic surgery, transurethral resection of the prostate, and laminectomy. We identified articles published between June 2011 and May 2012, and we calculated the proportion of articles authored by clinicians who also perform that procedure as well as the percentage that reported clinical care as a conflict of interest. We then screened conflict of interest statements on publications on said procedures from the same journals between 2012 and 2019 and calculated the proportion of publications that reported clinical work as a conflict of interest.

We identified 135 publications that met inclusion criticine, they alone face accusations that their clinical expertise is a potential conflict of interest. This stigmatizing practice could have wide-ranging consequences including delegitimization of the scientific method and peer review process broadly.In the Dominican Republic (DR), high rates of intimate partner violence (IPV) coexist with low rates of support for IPV. This raises questions about the actual underlying preferences for justifying IPV in the DR. We expect marriage to be influential in this relationship insofar as it reinforces gendered norms that may rationalize IPV apart from legal proscriptions against it. Our analysis of survey data finds that wives are less likely to justify IPV, but recently married husbands are more likely to justify it. Marriage seems more of a conduit for justifications of IPV whose roots lie in institutions throughout DR society.The outbreak of COVID-19 caused by SARS-CoV-2 virus continually led to infect a large population worldwide. Currently, there is no specific viral protein-targeted therapeutics. The Nucleocapsid (N) protein of the SARS-CoV-2 virus is necessary for viral RNA replication and transcription. The C-terminal domain of N protein (CTD) involves in the self-assembly of N protein into a filament that is packaged into new virions. In this study, the CTD (PDB ID 6WJI) was targeted for the identification of possible inhibitors of oligomerization of N protein. Herein, multiple computational approaches were employed to explore the potential mechanisms of binding and inhibitor activity of five antiviral drugs toward CTD. The five anti-N drugs studied in this work are 4E1RCat, Silmitasertib, TMCB, Sapanisertib, and Rapamycin. Among the five drugs, 4E1RCat displayed highest binding affinity (-10.95 kcal/mol), followed by rapamycin (-8.91 kcal/mol), silmitasertib (-7.89 kcal/mol), TMCB (-7.05 kcal/mol), and sapanisertib (-6.14 kcal/mol). Subsequently, stability and dynamics of the protein-drug complex were examined with molecular dynamics (MD) simulations. Overall, drug binding increases the stability of the complex with maximum stability observed in the case of 4E1RCat. The CTD-drug complex systems behave differently in terms of the free energy landscape and showed differences in population distribution. Overall, the MD simulation parameters like RMSD, RMSF, Rg, hydrogen bonds analysis, PCA, FEL, and DCCM analysis indicated that 4E1RCat and TMCB complexes were more stable as compared to silmitasertib and sapanisertib and thus could act as effective drug compounds against CTD. Communicated by Ramaswamy H. Sarma.
The systematic review aims to investigate the effect of sampling source on activated clotting time (ACT) measurement within cardiovascular surgery and cardiac catheterisation. It also examines the evidence surrounding novel clot assessment techniques and associated sampling variation.

A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar until 20th June 2020. All studies reporting sampling source variability of ACT in cardiac surgery, vascular surgery and cardiac catheterisation were included.

Fourteen studies were included in the systematic review. Inconsistent reports of variability were seen in cardiac surgery and cardiac catheterisation. There were no studies directly examining ACT variability in vascular surgery. Novel clot assessment techniques have been validated in cardiac surgery, but measurements vary depending on sampling source.

Sampling source should be kept consistent to facilitate effective haemostatic strategies. More research is needed regarding variability in vascular surgery and novel clot assessment techniques.
Sampling source should be kept consistent to facilitate effective haemostatic strategies. More research is needed regarding variability in vascular surgery and novel clot assessment techniques.Occupational Applications This paper provides a historical overview of the rise of Work-Related Musculoskeletal Disorders (WMSDs) in the U.S. from the 1980s to the present, with a special focus on the two industries with the highest recorded rates Meatpacking and Auto Assembly. The activities underlying this account amount to a major occupational health success story (although still incomplete) in the recognition of these disorders and the development of a nation-wide effort for prevention. An obstacle in creating the data presented here was that the system of recordkeeping changed in multiple ways, making it difficult to compare WMSD rates over time. The work summarized here evaluated the effect of these changes and combined temporal segments that were judged to be the most accurate to create an overall trend line. These results can aid in 1) showing the overall history of the recognition and prevention of WMSDs, 2) understanding the effects of the recordkeeping changes, and 3) allowing international comparisons of the trends.Systemic antineoplastic treatment agents represent one of the fastest developing medical fields. Oncological treatment is becoming increasingly individualized and new targets with corresponding agents, are constantly being developed. In tandem with this progress, new combinations and algorithms have evolved and patient's outcome have improved. Expanding tumors rely on a growing neovascular network to maintain their increased metabolism, which is caused by an accelerated reproduction rate. Accordingly, interrupting this supply mechanism is a major component of antineoplastic pharmaceutics and is a hallmark of cancer treatment. With advances in cancer treatment, long-term side effects have become an important consideration, especially in cases of neoplasia in young patients. While neuropathy and cardiotoxicity are well documented, vascular adverse events remain poorly understood. The mutual risk factors, like smoking and increased age, complicate the association between the vascular pathology and the earlier antineoplastic therapy. A deeper understanding of the effects of chemotherapy on peripheral arterial disease could lead to more detailed pathophysiological insight into both maladies and to new treatment options.Much of the global burden of disease is attributable to unhealthy behaviour, including excessive consumption of alcohol and sugar-sweetened beverages. Developing effective methods to change these drinking behaviours could inform policies to improve population health. In line with an increasing interest in environmental-level interventions - i.e., changing the environment in which a behaviour occurs in order to change the behaviour of interest - this review first describes the existing evidence of the impact of glassware design (including capacity and shape) on drinking behaviours (e.g., at the 'micro' level - including sip size, as well as at the macro level - including amount consumed). The roles of two sets of possible underlying mechanisms - perception and affordance - are also explored. Finally, this review sets out a provisional typology of drinking behaviours to enable more systematic approaches to the study of these behaviours. While there is a paucity of evidence - in particular on measures of consumption - this growing evidence base suggests promising targets for novel interventions involving glassware design to reduce the consumption of drinks that harm health.
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