• Winstead Slot posted an update 1 week, 3 days ago

    The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. read more These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and e efforts should be directed to improve treatment in this important group.To compare the outcomes of non-operative versus operative treatment for distal radius fractures in patients aged from 18 to 64 years, we performed a retrospective analysis using the OptumLabs® Data Warehouse using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes of distal radius fracture. Of the 34,184 distal radius fractures analysed, 11,731 (34%) underwent operative management. Short-term complications within 90 days of fracture identified an overall complication rate of 16.6 per 1000 fractures and the 1-year upper extremity-specific complication rate was 287 per 1000 fractures. Overall, post-injury stiffness was the most common 1-year upper extremity-specific complication and was associated with operative management (202.8 vs. 123.4 per 1000 fractures, operative vs. non-operative, p  less then  0.01). Secondary procedures were significantly more common following non-operative management (8.7% vs. 43%, operative vs. non-operative, p  less then  0.01) with carpal tunnel release representing the most common secondary procedure. Operative management of distal radius fractures resulted in significantly fewer secondary procedures at the expense of increased overall 1-year complication rates, specifically stiffness.Level of evidence III.Tobacco products contain thousands of chemicals, including addictive and toxic chemicals. We utilized in silico toxicology tools to predict in a validation test and in a separate screening test, the mutagenic potential of chemicals reported in tobacco products and tobacco smoke. Different publicly available (quantitative) structure-activity relationship (Q)SAR software platforms were used in this study. The models were validated against 900 chemicals relevant to tobacco for which experimental Ames mutagenicity data are available from public sources. The predictive performance of the individual and combined (Q)SAR models was evaluated using various performance metrics. All the (Q)SAR models represented >95% of the tobacco chemical space indicating a high potential for screening tobacco products. All the models performed well and predicted mutagens and nonmutagens with 75-95% accuracy, 66-94% sensitivity and 73-97% specificity. Subsequently, in a screening test, a combination of complementary SAR-based and QSAR-based models was used to predict the mutagenicity of 6820 chemicals catalogued in tobacco products and/or tobacco smoke. More than 1200 chemicals identified in tobacco products are predicted to have mutagenic potential, with 900 potential mutagens in tobacco smoke. This research demonstrates the validity of in silico (Q)SAR tools to make mutagenicity predictions for chemicals in tobacco products and/or tobacco smoke, and suggest they hold utility as screening tools for hazard identification to inform tobacco regulatory science.Obesity and its related diseases have been associated with oxidative stress. Thus, the search for nutritional strategies to ameliorate oxidative stress in obese individuals seems important. We hypothesized that the supplementation with monounsaturated (2-hydroxyoleic acid (2-OHOA)) and with combined n-3 polyunsaturated (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) fatty acids would ameliorate oxidative stress in different organs, including brain, liver, lungs, and kidneys of adult diet-induced obese (DIO) mice. Adult female ICR-CD1 mice were fed a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of DIO mice received the same HFD, supplemented with 1500 mg of 2-OHOA per kg of HFD and another group with 1500 mg of EPA and 1500 mg of DHA per kg of HFD. At the end of the experiment, several parameters of oxidative stress were assessed. The supplementation with 2-OHOA or with EPA and DHA in DIO mice was able to revert oxidative stress, enhancing the activities of catalase and glutathione reductase, as well as diminishing the activity of xanthine oxidase, the concentration of thiobarbituric acid reactive substances (TBARS) and the ratio between oxidized glutathione and reduced glutathione in several organs.