Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in infants and older adults. A safe and effective RSV vaccine for older adults represents a serious unmet medical need due to higher morbidity and mortality in this age group. In this randomized, partially double-blind, placebo-controlled, phase 1 dose-escalation study, we evaluated the safety, tolerability and immunogenicity of an investigational messenger ribonucleic acid (mRNA) vaccine encoding the RSV fusion protein (F) stabilized in the prefusion conformation. The study was conducted in healthy younger adults (ages ≥18 and ≤49 years) and healthy older adults (ages ≥60 and ≤79 years). Participants received mRNA-1777 (V171) or placebo as a single intramuscular dose. For each dose level, three sentinel participants were administered open-label mRNA-1777 (V171). Seventy-two younger adults were randomized and administered 25, 100, or 200 µg mRNA-1777 (V171) or placebo, and 107 older adults were randomized and administered 25, 100, 200 or 300 µg mRNA-1777 (V171) or placebo. Primary objectives were safety and tolerability and secondary objectives included humoral and cell-mediated immunogenicity. All dose levels of mRNA-1777 (V171) were generally well tolerated and no serious adverse events related to the vaccine were reported. Immunization with mRNA-1777 (V171) elicited a humoral immune response as measured by increases in RSV neutralizing antibody titers, serum antibody titers to RSV prefusion F protein, D25 competing antibody titers to RSV prefusion F protein, and cell-mediated immune responses to RSV-F peptides.

Using a hierarchical model with an adjustment for sample selection, we estimate the overweight prevalence for adults, by states, using data from the Third National Health and Nutrition Examination Survey (NHANES III). A two‐stage hierarchical model was selected to account for geographic variability of outcomes and to model possible overdispersion of estimates due to cluster sampling. We compare our model‐based estimates with design‐based estimates at the national level and obtain excellent agreement. We also provide a check of our model at the state level by comparing estimates with design‐based and synthetic estimates. Copyright © 1999 John Wiley & Sons, Ltd.

Background We report on the safety and immunogenicity of V591, a measles vector-based SARS-CoV-2 vaccine candidate. Methods In this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial, healthy adults with no history of COVID-19 disease were assigned to intramuscular injection of V591 or placebo (4:1 ratio). In part 1, younger adults (18-55 years) received V591 median tissue culture infectious dose (TCID 50 )-levels of 1×10 5 or 1×10 6 or placebo, 56 days apart. In part 2, younger and older (>55 years) adults received a single dose of one of four (10 4 /10 5 /10 6 /10 7 ) or one of two (10 5 /10 6 ) V591 TCID 50 levels, respectively, or placebo. Primary outcome: safety/tolerability. Secondary outcome: humoral immunogenicity. ClinicalTrials.gov: NCT04498247. Findings From August–December 2020, 444 participants were screened and 263 randomised (210 V591; 53 placebo); 262 received at least one and 10 received two doses of V591 or placebo. Adverse events were experienced by 140/209 (67.0%) V591 dose-group participants and 37/53 (69.8%) placebo-group participants following injection 1; most frequent were fatigue (57 [27.3%] vs 20 [37.7%]), headache (57 [27.3%] vs 19 [35.8%]), myalgia (35 [16.7%] vs 10 [18.9%]), and injection-site pain (35 [16.7%] vs 4 [7.5%]). No deaths nor vaccine-related serious adverse events occurred. At Day 29, no anti-SARS-CoV-2 spike serum neutralising antibody and IgG-responses were identified in placebo or the three lower V591 dose-groups; responses were detected with V591 1×10 7 TCID 50 , although titres were lower than convalescent serum. Interpretation V591 was generally well tolerated, but immunogenicity was insufficient to warrant continued development. Funding Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Background It has been reported that diabetic nephropathy and diabetic retinopathy are associated with each other through a shared pathophysiological mechanism. However, it is quite difficult to differentiate diabetic nephropathy from other glomerular diseases if diabetic retinopathy is absent in patients, and the only way to do this is to perform renal biopsies. The objective of this study was to test the hypothesis that diabetic nephropathy patients with and without diabetic retinopathy have different clinical and laboratory profiles. Material/Methods Medical records of type 2 diabetes mellitus patients with confirmed diabetic nephropathy were reviewed and analyzed with appropriate statistical modalities. Presence of arteriolar sclerosis of the carotid artery, abdominal aorta, upper extremities, and first-order aortic branches was regarded as a peripheral vascular disease. Results Out of 217 type 2 diabetes mellitus patients with confirmed diabetic nephropathy, retinopathy was present in 106 (48.8%), while 111 (51.2%) had no evidence of retinopathy. About 45% of patients had pure diabetic nephropathy without any diagnosis of non-diabetic renal diseases, of which membranous nephropathy was most common. Diabetic nephropathy patients with retinopathy and those without retinopathy differed in duration of hypertension ( p =0.041), serum creatinine ( p =0.031), albumin ( p =0.001), and erythrocyte sedimentation rate ( p =0.001). Moreover, male preponderance ( p <0.001), older age ( p =0.033), and increased levels of albumin ( p =0.033) were significantly associated with pure diabetic nephropathy without retinopathy. Conclusions Diabetic nephropathy patients with and without diabetic retinopathy have different clinical and laboratory profiles.

BackgroundDuring the COVID-19 pandemic, the frontline medical staff faced more workload and heavier physical and mental stress, which increased their job burnout and negative emotions. However, little is known about the potential factors mediating and moderating these relations. This study investigates the association between long working hours and depressive symptoms among frontline medical staff in China, and explores the potential mediating effect of job burnout, and moderating effect of family and organizational support on these associations.MethodsData of 992 frontline medical staff who participated in the prevention and control of COVID-19 was obtained from the online survey conducted in November to December 2021 in China. Depressive symptoms were evaluated using the Patient Health Questionaire-9 (PHQ-9). Moderated mediating model was employed to understand the relationship between long working hours (X), depressive symptoms (Y) mediated through job burnout (M), moderated by family support (W1) and organizational support (W2), while controlling all possible covariates.Results56.96% of participants worked more than 8 h per day. 49.8% of them had depressive symptoms (PHQ-9 ≥ 5) and 65.8% experienced job-related burnout. Long working hours was positively associated with depressive symptoms score (β = 0.26, 95% CI:0.13 ~ 0.40). Mediation analyses revealed that job burnout significantly mediated this relationship (indirect effect = 0.17, 95% CI: 0.08 ~ 0.26). Moderated mediation further indicated that both two interactions of social support (family support W1, organizational support W2) and job burnout were negatively related to depressive symptoms among frontline medical staff, indicating that higher social support being less job burnout with lower depressive symptoms.ConclusionLonger working hours and higher job burnout may contribute to worse mental health among frontline medical staff. Social support could buffer the detrimental effects by reducing their job burnout.ContributionThe main contribution of this study was to estimate the negative effect of long working hours on depressive symptoms among frontline medical staff and explore the potential mediating role of job burnout and moderating role of social support on these associations.