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Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

BackgroundHispanics/Latinos are purportedly at increased risk for neurocognitive decline and dementias. Without dementia cures, low-cost, well-tolerated public health means for mitigating neurocognitive decline are needed.ObjectiveWe examined associations between neurocognition and cardiovascular health (CVH) metrics (Life's Simple 7; LS7) among diverse Hispanics/Latinos. We hypothesized that higher LS7 would be associated with healthier brain function (neurocognitive performance).MethodsWe used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N = 9,623; ages 45-74 years) to examine neurocognition in relation to CVH LS7 scores.ResultsIn age and sex adjusted models, a one unit LS7 score increase (range = 0-14) was associated with higher neurocognitive function on the B-SEVLT sum (0.23 [p

BackgroundCurrently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms.MethodsWe conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score,

Background & aimsNonalcoholic fatty liver disease (NAFLD) was shown to disproportionally affect Hispanic persons. We examined the prevalence of suspected NAFLD in Hispanic/Latino persons with diverse backgrounds.MethodsWe studied the prevalence of suspected NAFLD among 12,133 persons included in the Hispanic Community Health Study/Study of Latinos. We collected data on levels of aminotransferase, metabolic syndrome (defined by National Cholesterol Education Program-Adult Treatment Panel III guidelines), demographics, and health behaviors. Suspected NAFLD was defined on the basis of increased level of aminotransferase in the absence of serologic evidence for common causes of liver disease or excessive alcohol consumption. In multivariate analyses, data were adjusted for metabolic syndrome, age, acculturation, diet, physical activity, sleep, and levels of education and income.ResultsIn multivariate analysis, compared with persons of Mexican heritage, persons of Cuban (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.57-0.85), Puerto Rican (OR, 0.67; 95% CI, 0.52-0.87), and Dominican backgrounds (OR, 0.71; 95% CI, 0.54-0.93) had lower rates of suspected NAFLD. Persons of Central American and South American heritage had a similar prevalence of suspected NAFLD compared with persons of Mexican heritage. NAFLD was less common in women than in men (OR, 0.49; 95% CI, 0.40-0.60). Suspected NAFLD associated with metabolic syndrome and all 5 of its components.ConclusionsOn the basis of an analysis of a large database of health in Latino populations, we found the prevalence of suspected NAFLD among Hispanic/Latino individuals to vary by region of heritage.

Background Dementia severity is unavailable in administrative claims data. We examined whether a claims-based frailty index (CFI) can measure dementia severity in Medicare claims. Methods This cross-sectional study included the National Health and Aging Trends Study Round 5 participants with possible or probable dementia whose Medicare claims were available. We estimated the Functional Assessment Staging Test (FAST) scale (range: 3 [mild cognitive impairment] to 7 [severe dementia]) using information from the survey. We calculated CFI (range: 0–1, higher scores indicating greater frailty) using Medicare claims 12 months prior to the participants' interview date. We examined C-statistics to evaluate the ability of the CFI in identifying moderate-to-severe dementia (FAST stage 5–7) and determined the optimal CFI cut-point that maximized both sensitivity and specificity. Results Of the 814 participants with possible or probable dementia and measurable CFI, 686 (72.2%) patients were ≥75 years old, 448 (50.8%) were female, and 244 (25.9%) had FAST stage 5–7. The C-statistic of CFI to identify FAST stage 5–7 was 0.78 (95% confidence interval: 0.72–0.83), with a CFI cut-point of 0.280, achieving the maximum sensitivity of 76.9% and specificity of 62.8%. Participants with CFI ≥0.280 had a higher prevalence of disability (19.4% vs 58.3%) and dementia medication use (6.0% vs 22.8%) and higher risk of mortality (10.7% vs 26.3%) and nursing home admission (4.5% vs 10.6%) over 2 years than those with CFI <0.280. Conclusions Our study suggests that CFI can be useful in identifying moderate-to-severe dementia from administrative claims among older adults with dementia. [ABSTRACT FROM AUTHOR]

Little research has examined associations of social support with diabetes (or other physical health outcomes) in Hispanics, who are at elevated risk. We examined associations between social support and diabetes prevalence in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Participants were 5,181 adults, 18-74 years old, representing diverse Hispanic backgrounds, who underwent baseline exam with fasting blood draw, oral glucose tolerance test, medication review, sociodemographic assessment, and sociocultural exam with functional and structural social support measures. In adjusted analyses, one standard deviation higher structural and functional social support related to 16 and 15% lower odds, respectively, of having diabetes. Structural and functional support were related to both previously diagnosed diabetes (OR = .84 and .88, respectively) and newly recognized diabetes prevalence (OR = .84 and .83, respectively). Higher functional and structural social support are associated with lower diabetes prevalence in Hispanics/Latinos. Keywords Diabetes * Hispanic * Latino * Prevalence * Risk factor * Social support, Introduction In the U.S., ethnic minorities including Hispanics (1) are at higher risk for diabetes than non-Hispanic whites. The landmark Hispanic Community Health Study/Study of Hispanics (HCHS/SOL), a prospective, population [...]

Introduction: Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown. Methods: In a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2 cost ). Paired t -tests examined pre- to post-stimulation differences in each fNIRS metric within each group. Results: The tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2 cost (p = 0.03). This mitigation of dual task "cost" to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2 cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16). Discussion: This preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking. [ABSTRACT FROM AUTHOR]

Background: After the first of three COVID‐19 vaccination clinics in U.S. nursing homes (NHs), the median vaccination coverage of staff was 37.5%, indicating the need to identify strategies to increase staff coverage. We aimed at comparing the facility‐level activities, policies, incentives, and communication methods associated with higher staff COVID‐19 vaccination coverage. Methods: Design. Case–control analysis. Setting. Nationally stratified random sample of 1338 U.S. NHs participating in the Pharmacy Partnership for Long‐Term Care Program. Participants. Nursing home leadership. Measurement. During February 4–March 2, 2021, we surveyed NHs with low (<35%), medium (40%–60%), and high (>75%) staff vaccination coverage, to collect information on facility strategies used to encourage staff vaccination. Cases were respondents with medium and high vaccination coverage, whereas controls were respondents with low coverage. We used logistic regression modeling, adjusted for county and NH characteristics, to identify strategies associated with facility‐level vaccination coverage. Results: We obtained responses from 413 of 1338 NHs (30.9%). Compared with facilities with lower staff vaccination coverage, facilities with medium or high coverage were more likely to have designated frontline staff champions (medium: adjusted odds ratio [aOR] 3.6, 95% CI 1.3–10.3; high: aOR 2.9, 95% CI 1.1–7.7) and set vaccination goals (medium: aOR 2.4, 95% 1.0–5.5; high: aOR 3.7, 95% CI 1.6–8.3). NHs with high vaccination coverage were more likely to have given vaccinated staff rewards such as T‐shirts compared with NHs with low coverage (aOR 3.8, 95% CI 1.3–11.0). Use of multiple strategies was associated with greater likelihood of facilities having medium or high vaccination coverage: For example, facilities that used ≥9 strategies were three times more likely to have high staff vaccination coverage than facilities using <6 strategies (aOR 3.3, 95% CI 1.2–8.9). Conclusions: Use of designated champions, setting targets, and use of non‐monetary awards were associated with high NH staff COVID‐19 vaccination coverage. [ABSTRACT FROM AUTHOR]

This study used longitudinal cross-lagged modeling to examine reciprocal relations between maternal depression and child behavior problems. Data were drawn from 3,119 children (40% Hispanic, 30% African American, 20% White, and 10% other) from the Family and Child Experiences Survey of 2009 (a nationally representative sample of children served by Head Start). Results documented reciprocal relations between maternal depression and child behavior problems across early childhood (i.e., child age 3-5). Furthermore, the effect of child behavior problems on maternal depression was moderated by child race/ethnicity during children's first year in Head Start, such that the negative effect of child behavior problems on African American mothers' depression was more pronounced compared to Hispanics and other racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Objective: Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life.Methods: Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task.Results: Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition.Interpretation: Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-83. [ABSTRACT FROM AUTHOR]