Search

While frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems-wide phenotypes to define potential novel, clinically relevant frailty biology. Proteomic signatures (specifically of physical function) were related to post-intervention outcome in AS, specifying pathways of innate immunity, cell growth/senescence, fibrosis/metabolism, and a host of proteins not widely described in human aging. In published cohorts, the frailty proteome displayed heterogeneous trajectories across age (20-100 years, age only explaining a small fraction of variance) and were associated with cardiac and non-cardiac phenotypes and outcomes across two broad validation cohorts (N > 35,000) over ≈2-3 decades. These findings suggest the importance of precision biomarkers of underlying multi-organ health status in age-related morbidity and frailty.

Service-learning (S-L) was adopted as a signature pedagogy in Ngee Ann Polytechnic in 2016. The present study investigated students' civic and academic learning, personal growth, and career preparation in S-L at the School of Humanities & Social Sciences, using mixed methods. The scales and subscales used in this study had acceptable internal consistency (Cronbach's alpha ranged from 0.71 to 0.93). Results showed that students perceived significant improvement to their civic outcomes when they participated in S-L compared to when they did not (n = 351), strong academic connection and career preparation development through the S-L experience (n = 832), and growth in interpersonal and personal development. Significant relationships were found between the student outcomes and S-L design and delivery features, such as perceived impact of S-L, preparedness for S-L, quality of reflection prompts, and amount of interaction with community. Frequency of reflection activities was significantly related to academic connection and career preparation but not civic outcomes. The findings suggest that student outcomes can be optimized through improvements in S-L course design and hold implications for faculty training and development.

Background GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with age-related diseases including cancer and cardiovascular diseases. However, the associations between GAA and muscle mass and function are unknown. Methods We estimated measures of GAA in 1 118 Black and White participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at exam years (Y) 15 (2000–2001) and 20 (2005–2006). Abdominal muscle composition was measured using CT scans at the Y25 (2010–2011) visit. We used multivariate regression models to examine associations of GAA estimates with muscle imaging measurements. Results In the CARDIA study, each 1-year higher GAA was associated with an average 1.1% (95% confidence interval [CI]: 0.6%, 1.5%) higher intermuscular adipose tissue (IMAT) volume for abdominal muscles. Each 1-year higher GAA was associated with an average −0.089 Hounsfield unit (HU; 95% CI: −0.146, −0.032) lower lean muscle attenuation and an average −0.049 HU (95% CI: −0.092, −0.007) lower IMAT attenuation for abdominal muscles. Stratified analyses showed that GAA was more strongly associated with higher abdominal muscle IMAT volume in females and significantly associated with lower lean muscle attenuation for White participants only. Conclusions Higher GAA is associated with higher abdominal muscle IMAT volume and lower lean muscle attenuation in a midlife population. [ABSTRACT FROM AUTHOR]

Introduction: Plasma levels of themetabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. Methods: We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individualswith treatedHIV, with orwithout T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. Results and discussion: We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with bodymass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations. [ABSTRACT FROM AUTHOR]

Background African Caribbeans have higher levels of myosteatosis than other populations; however, little is known about the impact of myosteatosis on physical function in African Caribbeans. Herein, we examined the association between regional myosteatosis of the calf, thigh, and abdomen versus physical function in 850 African-Ancestry men aged 64.2 ± 8.9 (range 50–95) living on the Caribbean Island of Tobago. Methods Myosteatosis was measured using computed tomography and included intermuscular adipose tissue (IMAT) and muscle density levels of the thigh, calf, psoas, and paraspinous muscles. Outcomes included grip strength, time to complete 5 chair-rises, and 4-meter gait speed. Associations were quantified using separate linear models for each myosteatosis depot and were adjusted for age, height, demographics, physical activity, and chronic diseases. Beta coefficients were presented per standard deviation of each myosteatosis depot. Results Higher thigh IMAT was the only IMAT depot significantly associated with weaker grip strength (β = −1.3 ± 0.43 kg, p =.003). However, lower muscle density of all 4 muscle groups was associated with weaker grip strength (all p <.05). Calf and thigh myosteatosis (IMAT and muscle density) were significantly associated with both worse chair rise time and gait speed (all p <.05), whereas psoas IMAT and paraspinous muscle density were associated with gait speed. Conclusion Myosteatosis of the calf and thigh―but not the abdomen―were strongly associated with grip strength and performance measures of physical function in African Caribbean men. However, posterior abdominal myosteatosis may have some utility when abdominal images are all that are available. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-[[alpha].sup.-308], interleukin-1 [[beta].sup.+3953], and interleukin-[6.sup.-174], in susceptibility to recurrent otitis media in childhood. Key Words otitis media, gene polymorphism, acutephase cytokines METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-[[alpha].sup.-308] and interleukin[6.sup.-174] heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-[[alpha].sup.-308] and interleukin-[6.sup.-174] polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-[[alpha].sup.-308] polymorphism and were breastfed for < 1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-[[alpha].sup.-308] and interleukin[6.sup.-174] polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals., UP TO 19% of children are susceptible to recurrent otitis media (OM). (1-3) The long-term sequelae of chronic and recurrent OM include delayed language development and learning difficulty. The cause [...]