The Shape of Things to Come: Obesity, Aging, and Disability

Rising obesity represents one of the most disturbing health trends in the U.S. and elsewhere. Obese people are at greater risk for diabetes, cardiovascular disease, disability, and mortality. However, recent studies also suggest that the obese population has grown “healthier” since the 1960s, probably due to improved medical care for cardiovascular disease. It isunclear whether these improvements have resulted in more or less disability in obese people as they age. This Issue Brief summarizes two studies that examine the prevalence of obesity over time in the elderly and disabled, and the changing relationship of obesity and disability

Home Exercise DVD Promotes Exercise Accuracy by Caregivers of Children and Adolescents With Brachial Plexus Palsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147221/1/pmr2924.pd

Prevalence of Posterior Shoulder Subluxation in Children With Neonatal Brachial Plexus Palsy After Early Full Passive Range of Motion Exercises

BackgroundChildren with neonatal brachial plexus palsy (NBPP) are often prescribed shoulder range of motion (ROM) exercises; however, the extent and timing of exercise implementation remains controversial in the context of shoulder joint integrity. The association of ROM exercises to delayed posterior shoulder subluxation (PSS) is unknown.ObjectiveTo determine prevalence of PSS in children with NBPP who began full passive ROM exercises before 6 months of age, and characteristics associated with development or absence of PSS in children.DesignCrossâ sectional study.SettingTertiary care NBPP referral center.ParticipantsFortyâ six children with NBPP, aged 24â 57 months, who began full ROM exercises before 6 months of age.MethodsOne radiologist conducted bilateral shoulder ultrasound (US) on each child to evaluate for PSS. One occupational therapist evaluated each child clinically for PSS using defined parameters without knowledge of US results.Main Outcome MeasuresBy US, 20% of children had PSS; 46% had PSS by clinical examination. Shoulder active ROM limitations and history of shoulder surgery were associated with presence of PSS. Extent of NBPP was not associated with PSS.ResultsNine of 46 children (20%) met US criteria for PSS; α angle was 58° ± 21° (mean ± standard deviation [SD]). Twentyâ one children (46%) met clinical criteria. Mean age at examination was 35 ± 10 months. Shoulder active ROM (P â ¤ .004) was associated with PSS, whereas passive ROM was not (P â ¥ .08). History of secondary shoulder surgery and primary nerve graft repair were associated with PSS (P = .04). Extent of NBPP by Narakas classification was not associated with PSS (P = .48).ConclusionsEarly use of fullâ arc passive ROM home exercise program is not associated with increased prevalence of PSS in children with NBPP compared to prevalence of PSS in published literature. We suggest careful clinical examination, based on defined criteria, provides a reasonable screening examination for evaluating PSS that can be confirmed by noninvasive US.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147125/1/pmr21235.pd

Mortality Attributable to Low Levels of Education in the United States

BackgroundEducational disparities in U.S. adult mortality are large and have widened across birth cohorts. We consider three policy relevant scenarios and estimate the mortality attributable to: (1) individuals having less than a high school degree rather than a high school degree, (2) individuals having some college rather than a baccalaureate degree, and (3) individuals having anything less than a baccalaureate degree rather than a baccalaureate degree, using educational disparities specific to the 1925, 1935, and 1945 cohorts.MethodsWe use the National Health Interview Survey data (1986–2004) linked to prospective mortality through 2006 (N=1,008,949), and discrete-time survival models, to estimate education- and cohort-specific mortality rates. We use those mortality rates and data on the 2010 U.S. population from the American Community Survey, to calculate annual attributable mortality estimates.ResultsIf adults aged 25–85 in the 2010 U.S. population experienced the educational disparities in mortality observed in the 1945 cohort, 145,243 deaths could be attributed to individuals having less than a high school degree rather than a high school degree, 110,068 deaths could be attributed to individuals having some college rather than a baccalaureate degree, and 554,525 deaths could be attributed to individuals having anything less than a baccalaureate degree rather than a baccalaureate degree. Widening educational disparities between the 1925 and 1945 cohorts result in a doubling of attributable mortality. Mortality attributable to having less than a high school degree is proportionally similar among women and men and among non-Hispanic blacks and whites, and is greater for cardiovascular disease than for cancer.ConclusionsMortality attributable to low education is comparable in magnitude to mortality attributable to individuals being current rather than former smokers. Existing research suggests that a substantial part of the association between education and mortality is causal. Thus, policies that increase education could significantly reduce adult mortality

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi Infection by Recruiting Suppressive IL-10-Producing Neutrophils

Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed

Maternal Undernutrition Significantly Impacts Ovarian Follicle Number and Increases Ovarian Oxidative Stress in Adult Rat Offspring

BACKGROUND: We have shown recently that maternal undernutrition (UN) advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of maternal UN potentially contributing to premature ovarian ageing in offspring