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Introduction Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use. Aims and Methods EARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up. Results Current smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking <10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men. Conclusions Our project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people. Implications This study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people. [ABSTRACT FROM AUTHOR]

A study to differentiate the advancement of subclinical atherosclerotic disease in patients with type 2 diabetes is conducted. Results conclude that treatment of low-density lipoprotein (LDL) cholesterol and systolic blood pressure bettered alternate measures of cardiovascular disease.

BACKGROUND: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. OBJECTIVES: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). METHODS: We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography--inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum x 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing. RESULTS: Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MTand 10q24 were most significant (p < 9.33 x [10.sup.-5]). CONCLUSIONS: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. http://dx.doi.org/ 10.1289/EHP251., Introduction Inorganic arsenic (iAs) is a toxic and carcinogenic metalloid that is found in groundwater, soil, food, and air (Welch et al. 1988). Experimental and epidemiological studies support the role [...]

Introduction: Identifying the most effective ways to support career development of early stage investigators in clinical and translational science should yield benefits for the biomedical research community. Institutions with Clinical and Translational Science Awards (CTSA) offer KL2 programs to facilitate career development; however, the sustained impact has not been widely assessed. Methods: A survey comprised of quantitative and qualitative questions was sent to 2144 individuals that had previously received support through CTSA KL2 mechanisms. The 547 responses were analyzed with identifying information redacted. Results: Respondents held MD (47%), PhD (36%), and MD/PhD (13%) degrees. After KL2 support was completed, physicians' time was divided 50% to research and 30% to patient care, whereas PhD respondents devoted 70% time to research. Funded research effort averaged 60% for the cohort. Respondents were satisfied with their career progression. More than 95% thought their current job was meaningful. Two-thirds felt confident or very confident in their ability to sustain a career in clinical and translational research. Factors cited as contributing to career success included protected time, mentoring, and collaborations. Conclusion: This first large systematic survey of KL2 alumni provides valuable insight into the group's perceptions of the program and outcome information. Former scholars are largely satisfied with their career choice and direction, national recognition of their expertise, and impact of their work. Importantly, they identified training activities that contributed to success. Our results and future analysis of the survey data should inform the framework for developing platforms to launch sustaining careers of translational scientists. [ABSTRACT FROM AUTHOR]

Introduction: A national survey characterized training and career development for translational researchers through Clinical and Translational Science Award (CTSA) T32/TL1 programs. This report summarizes program goals, trainee characteristics, and mentorship practices. Methods: A web link to a voluntary survey was emailed to 51 active TL1 program directors and administrators. Descriptive analyses were performed on aggregate data. Qualitative data analysis used open coding of text followed by an axial coding strategy based on the grounded theory approach. Results: Fifty out of 51 (98%) invited CTSA hubs responded. Training program goals were aligned with the CTSA mission. The trainee population consisted of predoctoral students (50%), postdoctoral fellows (30%), and health professional students in short-term (11%) or year-out (9%) research training. Forty percent of TL1 programs support both predoctoral and postdoctoral trainees. Trainees are diverse by academic affiliation, mostly from medicine, engineering, public health, non-health sciences, pharmacy, and nursing. Mentor training is offered by most programs, but mandatory at less than one-third of them. Most mentoring teams consist of two or more mentors. Conclusions: CTSA TL1 programs are distinct from other NIH-funded training programs in their focus on clinical and translational research, cross-disciplinary approaches, emphasis on team science, and integration of multiple trainee types. Trainees in nearly all TL1 programs were engaged in all phases of translational research (preclinical, clinical, implementation, public health), suggesting that the CTSA TL1 program is meeting the mandate of NCATS to provide training to develop the clinical and translational research workforce. [ABSTRACT FROM AUTHOR]

Objective: Comprehensive assessment of alterations in lipid species preceding type 2 diabetes (T2D) is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians.Research Design and Methods: Using untargeted liquid chromatography-mass spectrometry, we repeatedly measured 3,907 fasting plasma samples from 1,958 participants who attended two examinations (∼5.5 years apart) and were followed up to 16 years in the Strong Heart Family Study. Mixed-effects logistic regression was used to identify lipids associated with risk of T2D, adjusting for traditional risk factors. Repeated measurement analysis was performed to examine the association between change in lipidome and change in continuous measures of T2D, adjusting for baseline lipids. Multiple testing was controlled by false discovery rate at 0.05.Results: Higher baseline level of 33 lipid species, including triacylglycerols, diacylglycerols, phosphoethanolamines, and phosphocholines, was significantly associated with increased risk of T2D (odds ratio [OR] per SD increase in log2-transformed baseline lipids 1.50-2.85) at 5-year follow-up. Of these, 21 lipids were also associated with risk of T2D at 16-year follow-up. Aberrant lipid profiles were also observed in prediabetes (OR per SD increase in log2-transformed baseline lipids 1.30-2.19 for risk lipids and 0.70-0.78 for protective lipids). Longitudinal changes in 568 lipids were significantly associated with changes in continuous measures of T2D. Multivariate analysis identified distinct lipidomic signatures differentiating high- from low-risk groups.Conclusions: Lipid dysregulation occurs many years preceding T2D, and novel molecular lipids (both baseline level and longitudinal change over time) are significantly associated with risk of T2D beyond traditional risk factors. Our findings shed light on the mechanisms linking dyslipidemia to T2D and may yield novel therapeutic targets for early intervention tailored to American Indians. [ABSTRACT FROM AUTHOR]

A study was conducted to analyze the influence of activated human eosinophil supernatant, polycationic polypeptides and major basic protein on intracellular Ca2+ concentrations found in cultured bovine tracheal smooth muscle cells. Tissues were equilibrated to establish optimal and reproducible isometric contraction. Results suggested that the products of eosinophil activation may directly support airway smooth muscle responsiveness in inflammatory disease states.

Background: Alzheimer's disease (AD) is best defined in vivo using quantifiable, objective markers reflecting amyloid deposition (A), pathologic tau (T), and neurodegeneration (N). However, gold standards for ATN (imaging or cerebrospinal proteins) are expensive, invasive, and/or impractical in low resource settings. Circulating proteins offer a practical alternative. Candidate plasma markers include amyloid‐β (Aβ40&42), phosphorylated tau‐181 (ptau), glial fibrillary protein (GFAP), and neurofilament light chain (NfL). However, no such markers have been evaluated in American Indians. Method: The Strong Heart Study recruited 401 American Indians over 3 states in 2017‐2019 for MRI, cognitive testing, and clinical examination. MRI included T1 sequences, which were processed using FreeSurfer to quantify structural volumes. Neuropsychological testing incuded California Verbal Learning Test, which was operationalized into categories of memory impairment using indices of learning and recall. Plasma samples were sent to University of Gothenburg for Simoa Quanterix assay. Statistics included descriptive summary; multivariate regression; and receiver operating characteristic analysis. Result: The study population was mean age 78 (SD 4.7, range 70‐95); majority female (71%); and 21% APOE ε4 allele carriers. An estimated 31% had any memory impairment (13.8% retrieval, 6.5% storage, 10.7% encoding). Median plasma marker values were: ptau 5.0pg/mL (range: 1.5‐442), Aβ40 128pg/mL (116‐175), Aβ42 8.2pg/mL (6.7‐9.7), GFAP 150pg/mL (0‐651), and NfL 31.6pg/mL (9.7‐343); median Aβ42:40 ratio 0.06. Comparing APOEε4 carriers to non‐carriers (Table1), ptau was +12%, Aβ40 ‐0.8%, Aβ42 ‐8.4%, Aβ4240 ‐16.7% (P = 0.006), GFAP +16.1%, NfL +3.2%, but only Aβ4240 was significant. Linear regressions with brain volumes identified significant associations for Aβ42, Aβ40, GFAP, and NfL (but not ptau) with ventricle, cortical, and overall volume; NfL was also associated with entorhinal and hippocampal volume. GFAP and ptau were significantly higher in those with memory encoding deficit; NfL higher with encoding or retrieval deficit (Table2). Although not significant, Aβ40 was lower with storage deficit, and Aβ42 with encoding or storage deficit. AUC range for plasma markers to discriminate memory impaired from intact: 0.4‐0.6. Conclusion: These data are a first look at ATN plasma markers in a population‐based cohort of American Indians, an underrepresented group in AD research. Future research should address generalizability and measurement validity. [ABSTRACT FROM AUTHOR]