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Background Patients with peripheral artery disease (PAD) present a high prevalence of obesity and metabolic syndrome, as well as diseases related to cardiovascular dysfunction. However, whether obesity influences walking capacity and cardiovascular function in patients with PAD is poorly understood. Objectives The objective of this study was to analyze the impact of obesity on walking capacity and cardiovascular parameters in patients with PAD. Design This is a cross-sectional study. Setting Patients were recruited from public hospitals of São Paulo. Methods One-hundred two patients with PAD and symptoms of intermittent claudication were recruited and divided into 2 groups according to their body mass index normal weight ( less then 25 kg/m2) and overweight/obese (≥25 kg/m2). Patients were submitted to objective (6-minute walk test) and subjective measurements of walking capacity (Walking Impairment Questionnaire). In addition, cardiovascular parameters (office blood pressure, resting heart rate, arterial stiffness, vascular function, and heart rate variability) were obtained. Results The speed domain of the Walking Impairment Questionnaire was lower in the overweight/obese group compared to the normal weight group (32 ± 20 vs 21 ± 16, respectively, P less then .01). Resting heart rate was higher in overweight/obese patients (61 ± 10 vs 70 ± 12, respectively, P less then .01). However, no other walking capacity or cardiovascular parameter variables were related to obesity in patients with PAD. Conclusion Obesity influences resting heart rate and walking speed in patients with PAD.Neisseria meningitidis is an obligate human commensal bacterium that frequently colonises the upper respiratory tract. Person-to-person transmission occurs via direct contact or through dispersion of respiratory droplets from a carrier of the bacteria, and can lead to invasive meningococcal disease. Rare sporadic cases of meningococcal urogenital and anorectal infections, including urethritis, proctitis, and cervicitis, have been reported, typically following orogenital contact with an oropharyngeal meningococcal carrier. [https://www.selleckchem.com/products/picropodophyllin-ppp.html AXL1717] The resulting infections were clinically indistinguishable from infections caused by Neisseria gonorrhoeae. Over the past two decades, there have also been multiple outbreaks across North America and Europe of invasive meningococcal disease among men who have sex with men (MSM). The responsible meningococci belong to a highly virulent and predominantly serogroup C lineage, including strains that are able to express nitrite reductase and grow in anaerobic environments, such as the urogenital and anorectal tracts. More recently, a distinct clade within this lineage has expanded to cause urethritis predominantly among men who have sex with women. Evolutionary events giving rise to this clade included the loss of the ability to express a capsule, and acquisition of several gonococcal alleles, including one allele encoding a highly efficient gonococcal nitrite reductase. Members of the clade continue to acquire gonococcal alleles, including one allele associated with decreased antibiotic susceptibility. This evolution has implications for the clinical and public health management of those who are infected and their close contacts, in terms of both antibiotic treatment, and prevention through vaccination.Background Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population. Methods In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [ less then 1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancand an incidence rate ratio of 0·50 (0·31-0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43-0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously. Interpretation The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results. Funding Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.Background IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAFV600 mutation-positive advanced or metastatic melanoma. Methods IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAFV600 mutation-positive melanoma were randomly assigned 11 to 28-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cycle 2 onward. Randomisation was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by means of an identical intravenous placebo, and blinding for vemurafenib was achieved by means of a placebo tablet. The primary outcome was investigator-assessed progression-free survival. Thof atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAFV600 mutation-positive advanced melanoma. Funding F Hoffmann-La Roche and Genentech.The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. link2 In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.Background In animal models, immunity to mosquito salivary proteins protects animals against mosquito-borne disease. These findings provide a rationale to vaccinate against mosquito saliva instead of the pathogen itself. To our knowledge, no vector salivary protein-based vaccine has been tested for safety and immunogenicity in humans. We aimed to assess the safety and immunogenicity of Anopheles gambiae saliva vaccine (AGS-v), a peptide-based vaccine derived from four A gambiae salivary proteins, in humans. Methods In this randomised, placebo-controlled, double-blind, phase 1 trial, participants were enrolled at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Participants were eligible if they were healthy adults, aged 18-50 years with no history of severe allergic reactions to mosquito bites. link3 Participants were randomly assigned (111), using block randomisation and a computer-generated randomisation sequence, to treatment with either 200 nmol of AGS-v vaccine alone, 200 nmol of AGS-v webo group (absolute difference of log10 ratio of vaccine peptide-stimulated vs negative control 0·17 [95% CI 0·061 to 0·27]; p=0·009) but we saw no difference between the IFN-γ production in the vaccine only group compared with the placebo group (0·022 [-0·072 to 0·116]; p=0·63). Interpretation AGS-v was well tolerated, and, when adjuvanted, immunogenic. These findings suggest that vector-targeted vaccine administration in humans is safe and could be a viable option for the increasing burden of vector-borne disease. Funding Office of the Director and the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases, and National Institutes of Health.Background Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic. Methods The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesiant that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over less then 2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5-9 years and adults older than 65 years, compared with those aged 10-64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission. Funding Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.