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Item A cross-sectional study of latent tuberculosis infection, insurance coverage, and usual sources of health care among non-US-born persons in the United States(Wolters Kluwer Health, Inc., 2021-02-19) Annan, Esther; Stockbridge, Erica L.; Katz, Dolly; Mun, Eun-Young; Miller, Thaddeus L.ABSTRACT: More than 70% of tuberculosis (TB) cases diagnosed in the United States (US) occur in non-US-born persons, and this population has experienced less than half the recent incidence rate declines of US-born persons (1.5% vs 4.2%, respectively). The great majority of TB cases in non-US-born persons are attributable to reactivation of latent tuberculosis infection (LTBI). Strategies to expand LTBI-focused TB prevention may depend on LTBI positive non-US-born persons' access to, and ability to pay for, health care.To examine patterns of health insurance coverage and usual sources of health care among non-US-born persons with LTBI, and to estimate LTBI prevalence by insurance status and usual sources of health care.Self-reported health insurance and usual sources of care for non-US-born persons were analyzed in combination with markers for LTBI using 2011-2012 National Health and Nutrition Examination Survey (NHANES) data for 1793 sampled persons. A positive result on an interferon gamma release assay (IGRA), a blood test which measures immunological reactivity to Mycobacterium tuberculosis infection, was used as a proxy for LTBI. We calculated demographic category percentages by IGRA status, IGRA percentages by demographic category, and 95% confidence intervals for each percentage.Overall, 15.9% [95% confidence interval (CI) = 13.5, 18.7] of non-US-born persons were IGRA-positive. Of IGRA-positive non-US-born persons, 63.0% (95% CI = 55.4, 69.9) had insurance and 74.1% (95% CI = 69.2, 78.5) had a usual source of care. IGRA positivity was highest in persons with Medicare (29.1%; 95% CI: 20.9, 38.9).Our results suggest that targeted LTBI testing and treatment within the US private healthcare sector could reach a large majority of non-US-born individuals with LTBI. With non-US-born Medicare beneficiaries' high prevalence of LTBI and the high proportion of LTBI-positive non-US-born persons with private insurance, future TB prevention initiatives focused on these payer types are warranted.Item A Machine Learning Approach to Identify Predictors of Potentially Inappropriate Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Use in Older Adults with Osteoarthritis(MDPI, 2020-12-28) Patel, Jayeshkumar; Ladani, Amit; Sambamoorthi, Nethra; LeMasters, Traci; Dwibedi, Nilanjana; Sambamoorthi, UshaEvidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics((R)) Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual's CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02-1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20-1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34-1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.Item A Tutorial on Cognitive Diagnosis Modeling for Characterizing Mental Health Symptom Profiles Using Existing Item Responses(Springer Nature, 2022-02-04) Tan, Zhengqi; de la Torre, Jimmy; Ma, Wenchao; Huh, David; Larimer, Mary E.; Mun, Eun-YoungIn research applications, mental health problems such as alcohol-related problems and depression are commonly assessed and evaluated using scale scores or latent trait scores derived from factor analysis or item response theory models. This tutorial paper demonstrates the use of cognitive diagnosis models (CDMs) as an alternative approach to characterizing mental health problems of young adults when item-level data are available. Existing measurement approaches focus on estimating the general severity of a given mental health problem at the scale level as a unidimensional construct without accounting for other symptoms of related mental health problems. The prevailing approaches may ignore clinically meaningful presentations of related symptoms at the item level. The current study illustrates CDMs using item-level data from college students (40 items from 719 respondents; 34.6% men, 83.9% White, and 16.3% first-year students). Specifically, we evaluated the constellation of four postulated domains (i.e., alcohol-related problems, anxiety, hostility, and depression) as a set of attribute profiles using CDMs. After accounting for the impact of each attribute (i.e., postulated domain) on the estimates of attribute profiles, the results demonstrated that when items or attributes have limited information, CDMs can utilize item-level information in the associated attributes to generate potentially meaningful estimates and profiles, compared to analyzing each attribute independently. We introduce a novel visual inspection aid, the lens plot, for quantifying this gain. CDMs may be a useful analytical tool to capture respondents' risk and resilience for prevention research.Item Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype(MDPI, 2020-12-25) Harrison, Mark A. A.; Wise, Rachel M.; Benjamin, Brooke P.; Hochreiner, Emily M.; Mohiuddin, Omair A.; Bunnell, Bruce A.Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.Item Analysis of the Patient-Physician Relationship, Race, and Pain Control and Physical Function Among Adults With Chronic Low Back Pain(American Medical Association, 2022-06-01) Licciardone, John C.; Ganta, Sweta; Goehring, Leah; Wallace, Kendall; Pu, RyanImportance: Racial and ethnic disparities in pain outcomes are widely reported in the United States. However, the impact of the patient-physician relationship on such outcomes remains unclear. Objective: To determine whether the patient-physician relationship mediates the association of race with pain outcomes. Design, Setting, and Participants: This cross-sectional study uses data from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation, collected from April 2016 to December 2021. All registry enrollees who identified as Black or White with chronic low back pain who had a regular physician who provided pain care were included. Data were analyzed during December 2021. Exposures: Participant-reported aspects of their patient-physician relationship, including physician communication, physician empathy, and satisfaction with physician encounters. Main Outcomes and Measures: The primary outcomes included low back pain intensity, measured with a numerical rating scale and physical function, measured with the Roland-Morris Disability Questionnaire. Mediator variables were derived from the Communication Behavior Questionnaire, Consultation and Relational Empathy measure, and Patient Satisfaction Questionnaire. Results: Among 1177 participants, the mean (SD) age was 53.5 (13.1) years, and there were 876 (74.4%) women. A total of 217 participants (18.4%) were Black, and 960 participants (81.6%) were White. The only difference between Black and White participants in the patient-physician relationship involved effective and open physician communication, which favored Black participants (mean communication score, 72.1 [95% CI, 68.8-75.4] vs 67.9 [95% CI, 66.2-69.6]; P = .03). Black participants, compared with White participants reported worse outcomes for pain intensity (mean pain score, 7.1 [95% CI, 6.8-7.3] vs 5.8 [95% CI, 5.7-6.0]; P < .001) and back-related disability (mean disability score, 15.8 [95% CI, 15.1-16.6] vs 14.1 [95% CI, 13.8-14.5]; P < .001). In mediation analyses that controlled for potential confounders using disease risk scores, virtually none of the associations of race with each outcome was mediated by the individual or combined factors of physician communication, physician empathy, and patient satisfaction. Similarly, no mediation was observed in sensitivity analyses that included only participants with both chronic low back pain and the same treating physician for more than 5 years. Conclusions and Relevance: These findings suggest that factors other than the patient-physician relationship were important to pain disparities experienced by Black participants. Additional research on systemic factors, such as access to high-quality medical care, may be helpful in identifying more promising approaches to mitigating racial pain disparities.Item Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia(BioMed Central Ltd., 2021-11-02) Booz, George W.; Kennedy, Daniel; Bowling, Michael; Robinson, Taprieka; Azubuike, Daniel; Fisher, Brandon; Brooks, Karen; Chinthakuntla, Pooja; Hoang, Ngoc H.; Hosler, Jonathan P.; Cunningham, Mark W., Jr.Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence ('n7AAc') improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + 'n7AAc' (n = 16). Gestational day 14, RUPP surgery was performed and 'n7AAc' (144 mug/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 +/- 4 vs. 116 +/- 3 mmHg, p < 0.05), but was normalized in in RUPP + 'n7AAc' (109 +/- 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + 'n7AAc' vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with 'n7AAc'. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.Item Association of Magnesium Intake with Liver Fibrosis among Adults in the United States(MDPI, 2021-01-02) Tao, Meng-Hua; Fulda, Kimberly G.Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations differ by alcohol drinking status. Based on the National Health and Nutrition Examination Survey (NHANES) 2017–2018, the study included 4166 participants aged >18 years who completed the transient elastography examination and had data available on magnesium intake. The median liver stiffness of 8.2 kPa was used to identify subjects with significant fibrosis (≥F2). The age-adjusted prevalence of significant fibrosis was 12.81%. Overall total magnesium intake was marginally associated with reduced odds of significant fibrosis (p trend = 0.14). The inverse association of total magnesium intake with significant fibrosis was primarily presented among those who had daily calcium intake <1200 mg. There were no clear associations for significant fibrosis with calcium intake. Findings suggest that high total magnesium alone may reduce risk of significant fibrosis. Further studies are needed to confirm these findings.Item At the intersection of precision medicine and population health: an implementation-effectiveness study of family health history based systematic risk assessment in primary care(BioMed Central Ltd., 2020-11-07) Orlando, Lori A.; Wu, R. Ryanne; Myers, Rachel A.; Neuner, Joan; McCarty, Catherine; Haller, Irina V.; Harry, Melissa; Fulda, Kimberly G.; Dimmock, David; Rakhra-Burris, Teji; Buchanan, Adam; Ginsburg, Geoffrey S.Background: Risk assessment is a precision medicine technique that can be used to enhance population health when applied to prevention. Several barriers limit the uptake of risk assessment in health care systems; and little is known about the potential impact that adoption of systematic risk assessment for screening and prevention in the primary care population might have. Here we present results of a first of its kind multi-institutional study of a precision medicine tool for systematic risk assessment. Methods: We undertook an implementation-effectiveness trial of systematic risk assessment of primary care patients in 19 primary care clinics at four geographically and culturally diverse healthcare systems. All adult English or Spanish speaking patients were invited to enter personal and family health history data into MeTree, a patient-facing family health history driven risk assessment program, for 27 medical conditions. Risk assessment recommendations followed evidence-based guidelines for identifying and managing those at increased disease risk. Results: One thousand eight hundred eighty-nine participants completed MeTree, entering information on N = 25,967 individuals. Mean relatives entered = 13.7 (SD 7.9), range 7-74. N = 1443 (76.4%) participants received increased risk recommendations: 597 (31.6%) for monogenic hereditary conditions, 508 (26.9%) for familial-level risk, and 1056 (56.1%) for risk of a common chronic disease. There were 6617 recommendations given across the 1443 participants. In multivariate analysis, only the total number of relatives entered was significantly associated with receiving a recommendation. Conclusions: A significant percentage of the general primary care population meet criteria for more intensive risk management. In particular 46% for monogenic hereditary and familial level disease risk. Adopting strategies to facilitate systematic risk assessment in primary care could have a significant impact on populations within the U.S. and even beyond.Item Bacterial microbiomes of Ixodes scapularis ticks collected from Massachusetts and Texas, USA(BioMed Central Ltd., 2019-06-24) Thapa, Santosh; Zhang, Yan; Allen, Michael S.BACKGROUND: The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease spirochete Borrelia burgdorferi in North America. Though the tick is found across the eastern United States, Lyme disease is endemic to the northeast and upper midwest and rare or absent in the southern portion of the vector's range. In an effort to better understand the tick microbiome from diverse geographic and climatic regions, we analysed the bacterial community of 115 I. scapularis adults collected from vegetation in Texas and Massachusetts, representing extreme ends of the vector's range, by massively parallel sequencing of the 16S V4 rRNA gene. In addition, 7 female I. scapularis collected from dogs in Texas were included in the study. RESULTS: Male I. scapularis ticks had a more diverse bacterial microbiome in comparison to the female ticks. Rickettsia spp. dominated the microbiomes of field-collected female I. scapularis from both regions, as well as half of the males from Texas. In addition, the male and female ticks captured from Massachusetts contained high proportions of the pathogens Anaplasma and Borrelia, as well as the arthropod endosymbiont Wolbachia. None of these were found in libraries generated from ticks collected in Texas. Pseudomonas, Acinetobacter and Mycobacterium were significantly differently abundant (p < 0.05) between the male ticks from Massachusetts and Texas. Anaplasma and Borrelia were found in 15 and 63% of the 62 Massachusetts ticks, respectively, with a co-infection rate of 11%. Female ticks collected from Texas dogs were particularly diverse, and contained several genera including Rickettsia, Pseudomonas, Bradyrhizobium, Sediminibacterium, and Ralstonia. CONCLUSIONS: Our results indicate that the bacterial microbiomes of I. scapularis ticks vary by sex and geography, with significantly more diversity in male microbiomes compared to females. We found that sex plays a larger role than geography in shaping the composition/diversity of the I. scapularis microbiome, but that geography affects what additional taxa are represented (beyond Rickettsia) and whether pathogens are found. Furthermore, recent feeding may have a role in shaping the tick microbiome, as evident from a more complex bacterial community in female ticks from dogs compared to the wild-caught questing females. These findings may provide further insight into the differences in the ability of the ticks to acquire, maintain and transmit pathogens. Future studies on possible causes and consequences of these differences will shed additional light on tick microbiome biology and vector competence.Item C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia/reperfusion injury(BioMed Central Ltd., 2016-03-24) Silverman, Sean M.; Kim, Byung-Jin; Howell, Garreth R.; Miller, Joselyn; John, Simon W. M.; Wordinger, Robert J.; Clark, Abbot F.BACKGROUND: C1q represents the initiating protein of the classical complement cascade, however recent findings indicate pathway independent roles such as developmental pruning of retinal ganglion cell (RGC) axons. Furthermore, chronic neuroinflammation, including increased expression of C1q and activation of microglia and astrocytes, appears to be a common finding among many neurodegenerative disease models. Here we compare the effects of a retinal ischemia/reperfusion (I/R) injury on glial activation and neurodegeneration in wild type (WT) and C1qa-deficient mice in the retina and superior colliculus (SC). Retinal I/R was induced in mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. Glial cell activation and population changes were assessed using immunofluorescence. Neuroprotection was determined using histological measurements of retinal layer thickness, RGC counts, and visual function by flash electroretinography (ERG). RESULTS: Retinal I/R injury significantly upregulated C1q expression in the retina as early as 72 h and within 7 days in the superficial SC, and was sustained as long as 28 days. Accompanying increased C1q expression was activation of microglia and astrocytes as well as a significantly increased glial population density observed in the retina and SC. Microglial activation and changes in density were completely ablated in C1qa-deficient mice, interestingly however there was no effect on astrocytes. Furthermore, loss of C1qa significantly rescued I/R-induced loss of RGCs and protected against retinal layer thinning in comparison to WT mice. ERG assessment revealed early preservation of b-wave amplitude deficits from retinal I/R injury due to C1qa-deficiency that was lost by day 28. CONCLUSIONS: Our results for the first time demonstrate the spatiotemporal changes in the neuroinflammatory response following retinal I/R injury at both local and distal sites of injury. In addition, we have shown a role for C1q as a primary mediator of microglial activation and pathological damage. This suggests developmental mechanisms of C1q may be re-engaged during injury response, modulation of which may be beneficial for neuroprotection.Item Cholinergic agonists reduce blood pressure in a mouse model of systemic lupus erythematosus(Wiley Periodicals, Inc., 2017-04-10) Fairley, Amber S.; Mathis, Keisa W.Increased inflammation arising from an abnormal immune response can damage healthy tissue and lead to disease progression. An important example of this is the accumulation of inflammatory mediators in the kidney, which can subsequently lead to hypertension and renal injury. The origin of this inflammation may involve neuro-immune interactions. For example, the novel vagus nerve-to-spleen mechanism known as the "cholinergic anti-inflammatory pathway" controls inflammation upon stimulation. However, if this pathway is dysfunctional, inflammation becomes less regulated and chronic inflammatory diseases such as hypertension may develop. Systemic lupus erythematosus (SLE) is an autoimmune disease with aberrant immune function, increased renal inflammation, and prevalent hypertension. We hypothesized that the cholinergic anti-inflammatory pathway is impaired in SLE and that stimulation of this pathway would protect from the progression of hypertension in SLE mice. Female SLE (NZBWF1) and control (NZW) mice were administered nicotine or vehicle for 7 days (2 mg/kg/day, subcutaneously) in order to stimulate the cholinergic anti-inflammatory pathway at the level of the splenic nicotinic acetylcholine receptor (alpha7-nAChR). Blood pressure was assessed posttreatment. Nicotine-treated SLE mice did not develop hypertension and this lower blood pressure (compared to saline-treated SLE mice) coincided with lower splenic and renal cortical expression of pro-inflammatory cytokines. These data provide evidence that the cholinergic anti-inflammatory pathway is impaired in SLE In addition, these data suggest that stimulation of the cholinergic anti-inflammatory pathway can protect the kidney by dampening inflammation and therefore prevent the progression of hypertension in the setting of SLE.Item Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans(PLoS, 2019-03-12) Silzer, Talisa K.; Barber, Robert C.; Sun, Jie; Pathak, Gita A.; Johnson, Leigh A.; O'Bryant, Sid E.; Phillips, NicoleMitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.Item Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients(PLOS, 2016-11-29) Smith, Ashley D.; Zhang, Yan; Barber, Robert C.; Minshall, Christian T.; Huebinger, Ryan M.; Allen, Michael S.The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients.Item Comparison of Dietary Micronutrient Intakes by Body Weight Status among Mexican-American and Non-Hispanic Black Women Aged 19-39 Years: An Analysis of NHANES 2003-2014(MDPI, 2019-11-20) Liu, Jialiang; Zhu, Xiangzhu; Fulda, Kimberly G.; Chen, Shande; Tao, Meng-HuaThe objective of the current study was to examine micronutrient intake from foods in women of childbearing age and to better understand potential nutritional problems varied by body weight status in minority women. A sample of women aged 19-39 years from the National Health and Nutrition Examination Surveys (NHANES) 2003-2014 was analyzed. Dietary intakes of 13 micronutrients were estimated using the National Cancer Institute method. Mexican-American and non-Hispanic Black women were categorized into normal/under-weight, overweight, or obese groups according to their body mass index (BMI). Mexican-American and non-Hispanic Black women had lower dietary intakes for vitamins A, B2, B6, B12, and D, folate, calcium, and magnesium than non-Hispanic Whites. Among Mexican-Americans, obese women had the lowest dietary intake of vitamins A, B2, C and D. Obese non-Hispanic Black women had significantly lower dietary intakes of iron and zinc than their normal/under-weight counterparts. Comparable percentages (>30%) of Mexican-American and non-Hispanic Black women had dietary intake less than the Estimated Average Requirements (EARs) for several key nutrients including vitamin A, C and D, folate, calcium and magnesium, and the percentages varied by body weight status. These results indicate micronutrient inadequacies persist among and within racial/ethnic and body weight groups.Item Dengue Seroprevalence and Seroconversion in Urban and Rural Populations in Northeastern Thailand and Southern Laos(MDPI, 2020-12-07) Doum, Dyna; Overgaard, Hans J.; Mayxay, Mayfong; Suttiprapa, Sutas; Saichua, Prasert; Ekalaksananan, Tipaya; Tongchai, Panwad; Rahman, Md. Siddikur; Haque, Ubydul; Phommachanh, Sysavanh; Pongvongsa, Tiengkham; Rocklov, Joacim; Paul, Richard; Pientong, ChamsaiDengue is the most rapidly spreading mosquito-borne viral disease in the world. The detection of clinical cases enables us to measure the incidence of dengue infection, whereas serological surveys give insights into the prevalence of infection. This study aimed to determine dengue seroprevalence and seroconversion rates in northeastern Thailand and southern Laos and to assess any association of mosquito control methods and socioeconomic factors with dengue virus (DENV) infection. Cross-sectional seroprevalence surveys were performed in May and November 2019 on the same individuals. Blood samples were collected from one adult and one child, when possible, in each of 720 randomly selected households from two urban and two rural sites in both northeastern Thailand and southern Laos. IgG antibodies against DENV were detected in serum using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Overall, 1071 individuals participated in the study. The seroprevalence rate was high (91.5%) across all 8 study sites. Only age and province were associated with seroprevalence rates. There were 33 seroconversions during the period from May to November, of which seven reported fever. More than half of the seroconversions occurred in the rural areas and in Laos. Dengue seroconversion was significantly associated with young age (<15 years old), female gender, province, and duration of living in the current residence. No socioeconomic factors or mosquito control methods were found to be associated with seroprevalence or seroconversion. Notably, however, the province with most seroconversions had lower diurnal temperature ranges than elsewhere. In conclusion, our study has highlighted the homogeneity of dengue exposure across a wide range of settings and most notably those from rural and urban areas. Dengue can no longer be considered to be solely an urban disease nor necessarily one linked to poverty.Item Depression, inflammation, and memory loss among Mexican Americans: analysis of the HABLE cohort(Cambridge University Press, 2017-06-20) Johnson, Leigh A.; Edwards, Melissa; Gamboa, Adriana; Hall, James R.; Robinson, Michelle; O'Bryant, Sid E.Background: This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders. Methods: Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFɑ levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI. Results: Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9-11.2, p < 0.001). Conclusion: Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.Item Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm(PLOS, 2020-06-11) Chaudhari, Kiran; Wang, Jianmei; Xu, Yong; Winters, Ali; Wang, Linshu; Dong, Xiaowei; Cheng, Eric Y.; Liu, Ran; Yang, ShaohuaMetformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.Item Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer(MDPI, 2020-02-11) Sridharan, Savitha; Basu, AlakanandaThe mechanistic target of rapamycin (mTOR) is a master regulator of protein translation, metabolism, cell growth and proliferation. It forms two complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 is frequently deregulated in many cancers, including breast cancer, and is an important target for cancer therapy. The immunosuppressant drug rapamycin and its analogs that inhibit mTOR are currently being evaluated for their potential as anti-cancer agents, albeit with limited efficacy. mTORC1 mediates its function via its downstream targets 40S ribosomal S6 kinases (S6K) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). There are two homologs of S6K: S6K1 and S6K2. Most of the earlier studies focused on S6K1 rather than S6K2. Because of their high degree of structural homology, it was generally believed that they behave similarly. Recent studies suggest that while they may share some functions, they may also exhibit distinct or even opposite functions. Both homologs have been implicated in breast cancer, although how they contribute to breast cancer may differ. The purpose of this review article is to compare and contrast the expression, structure, regulation and function of these two S6K homologs in breast cancer.Item Do Brief Alcohol Interventions Reduce Driving After Drinking Among College Students? A Two-step Meta-analysis of Individual Participant Data(Oxford University Press, 2021-02-16) Mun, Eun-Young; Li, Xiaoyin; Lineberry, Shelby; Tan, Zhengqi; Huh, David; Walters, Scott T.; Zhou, Zhengyang; Larimer, Mary E.; in Collaboration with Project, Integrate TeamAIMS: College students who drink are at an increased risk of driving after drinking and alcohol-involved traffic accidents and deaths. Furthermore, the persistence of driving after drinking over time underscores a need for effective interventions to prevent future drunk driving in adulthood. The present study examined whether brief alcohol interventions (BAIs) for college students reduce driving after drinking. METHODS: A two-step meta-analysis of individual participant data (IPD) was conducted using a combined sample of 6801 college students from 15 randomized controlled trials (38% male, 72% White and 58% first-year students). BAIs included individually delivered Motivational Interviewing with Personalized Feedback (MI + PF), Group Motivational Interviewing (GMI), and stand-alone Personalized Feedback (PF) interventions. Two outcome variables, driving after two+/three+ drinks and driving after four+/five+ drinks, were checked, harmonized and analyzed separately for each study and then combined for meta-analysis and meta-regression analysis. RESULTS: BAIs lowered the risk of driving after four+/five+ drinks (19% difference in the odds of driving after drinking favoring BAIs vs. control), but not the risk of driving after two+/three+ drinks (9% difference). Subsequent subgroup analysis indicated that the MI + PF intervention was comparatively better than PF or GMI. CONCLUSIONS: BAIs provide a harm reduction approach to college drinking. Hence, it is encouraging that BAIs reduce the risk of driving after heavy drinking among college students. However, there may be opportunities to enhance the intervention content and timing to be more relevant for driving after drinking and improve the outcome assessment and reporting to demonstrate its effect.Item Do physical activity levels differ by number of children at home in women aged 25-44 in the general population?(Sage Publications, 2019-09-09) Abell, Laura P.; Tanase, Kelly A.; Gilmore, Madison L.; Winnicki, Anna E.; Holmes, Victor L.; Hartos, Jessica L.OBJECTIVES: While physical activity is important for health, many women do not meet recommended levels, particularly mothers. The purpose of this study was to assess whether physical activity levels differ by number of children at home in women aged 25-44 in the general US population. METHODS: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance System data for females aged 25-44 (N = 6266) from California, Colorado, New York, Texas, and Utah. Ordered logistic regression analysis assessed the relationship between physical activity levels and number of children at home while controlling for state and demographic, socioeconomic, and health-related factors. RESULTS: About half of participants reported "inactive" or "insufficiently active" physical activity levels and about two-thirds reported having one or more children at home. The results of adjusted analysis indicated that physical activity level was significantly related to having one child (adjusted odds ratio = 0.75, 95% confidence interval = 0.63, 0.89), two children (adjusted odds ratio = 0.79; 95% confidence interval = 0.67, 0.93), and three or more children (adjusted odds ratio = 0.80, 95% confidence interval = 0.67, 0.94) at home. CONCLUSION: Overall, physical activity levels were significantly related to presence of children at home for women aged 25-44, but increasing number of children at home did not impact effect size. For women aged 25-44 in a primary care setting, a moderate prevalence of inactive or insufficiently active physical activity may be expected. Providers should address physical activity with all patients in this target population during well-visits, but particularly for women with children at home; educate patients about the health benefits of regular physical activity; and provide resources that will help them integrate physical activity into their daily lifestyles.