Process Evaluation of Two Interventions to Improve Health Environments in Family Child Care Homes.

Early care and education (ECE) environments influence children's lifelong health behaviors, growth, and development. Although the number of interventions to improve health in ECE environments is increasing, few have been designed for and tested in family child care homes (FCCHs). This study reports the process evaluation of two interventions to improve FCCH health environments, both part of Happy Healthy Homes, a matched-attention randomized-controlled intervention trial conducted in Oklahoma FCCHs. Participating child care providers received one of two multicomponent interventions: (a) an intervention focused on enhancing the quality of the nutrition environment, self-efficacy, and practices or (b) an intervention focused on improving providers' environmental health literacy, self-efficacy, and practices. Guided by "Implementation" constructs of the RE-AIM framework (i.e., reach, effectiveness, adoption, implementation, maintenance), intervention report forms and participant tracking were used to assess intervention dose delivered and interventionist-perceived challenges and successes to implementation. Interviews were conducted to obtain participant feedback after the intervention. Dose delivered was high for both interventions overall and across individual sessions, and provider feedback was positive. Implementation challenges and strengths identified for both interventions may be useful for further enhancing intervention appropriateness and success, particularly for interventions with FCCHs. Process evaluation findings indicate that the two Happy Healthy Home interventions can be conducted with high delivery and are well attended and considered to be valuable to FCCH providers.

Family child care home providers' self-reported nutrition and physical activity practices, self-efficacy, barriers and knowledge: baseline findings from happy healthy homes.

OBJECTIVE: Describe nutrition and physical activity practices, nutrition self-efficacy and barriers and food programme knowledge within Family Child Care Homes (FCCH) and differences by staffing. DESIGN: Baseline, cross-sectional analyses of the Happy Healthy Homes randomised trial (NCT03560050). SETTING: FCCH in Oklahoma, USA. PARTICIPANTS: FCCH providers (n 49, 100 % women, 30·6 % Non-Hispanic Black, 2·0 % Hispanic, 4·1 % American Indian/Alaska Native, 51·0 % Non-Hispanic white, 44·2 ± 14·2 years of age. 53·1 % had additional staff) self-reported nutrition and physical activity practices and policies, nutrition self-efficacy and barriers and food programme knowledge. Differences between providers with and without additional staff were adjusted for multiple comparisons (P < 0·01). RESULTS: The prevalence of meeting all nutrition and physical activity best practices ranged from 0·0-43·8 % to 4·1-16·7 %, respectively. Average nutrition and physical activity scores were 3·2 ± 0·3 and 3·0 ± 0·5 (max 4·0), respectively. Sum nutrition and physical activity scores were 137·5 ± 12·6 (max 172·0) and 48·4 ± 7·5 (max 64·0), respectively. Providers reported high nutrition self-efficacy and few barriers. The majority of providers (73·9-84·7 %) felt that they could meet food programme best practices; however, knowledge of food programme best practices was lower than anticipated (median 63-67 % accuracy). More providers with additional staff had higher self-efficacy in family-style meal service than did those who did not (P = 0·006). CONCLUSIONS: Providers had high self-efficacy in meeting nutrition best practices and reported few barriers. While providers were successfully meeting some individual best practices, few met all. Few differences were observed between FCCH providers with and without additional staff. FCCH providers need additional nutrition training on implementation of best practices.

Oversampling of Minority Populations Through Dual-Frame Surveys.

Previous studies have shown disparities in health conditions and behaviors among different ethnic groups. Sampling designs that do not consider oversampling certain minority populations, such as American Indians or African Americans, may not produce sufficient sample sizes for estimating health parameters for minority populations. Oversampling is one of the most common approaches that researchers use to achieve required precision levels for small domain estimation. However, it has not been rigorously investigated in dual-frame survey settings. To take advantage of extra information for minority populations in the Marketing Systems Group database, we propose a novel optimal oversampling strategy that minimizes the domain variance subject to total cost restriction or vice versa. We further extend the method to oversample multiple minorities simultaneously. Empirical study using a population-based community survey shows the benefits of our proposed methods compared with traditional methods in terms of statistical efficiency and cost balance.

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study.

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58-3.77) and MMA% (aOR = 1.95 (95% CI 0.81-4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25-1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

A systematic literature review of Native American and Pacific Islanders' perspectives on health data privacy in the United States.

BACKGROUND: Privacy-related concerns can prevent equitable participation in health research by US Indigenous communities. However, studies focused on these communities' views regarding health data privacy, including systematic reviews, are lacking. METHODS: We conducted a systematic literature review analyzing empirical, US-based studies involving American Indian/Alaska Native (AI/AN) and Native Hawaiian or other Pacific Islander (NHPI) perspectives on health data privacy, which we define as the practice of maintaining the security and confidentiality of an individual's personal health records and/or biological samples (including data derived from biological specimens, such as personal genetic information), as well as the secure and approved use of those data. RESULTS: Twenty-one studies involving 3234 AI/AN and NHPI participants were eligible for review. The results of this review suggest that concerns about the privacy of health data are both prevalent and complex in AI/AN and NHPI communities. Many respondents raised concerns about the potential for misuse of their health data, including discrimination or stigma, confidentiality breaches, and undesirable or unknown uses of biological specimens. CONCLUSIONS: Participants cited a variety of individual and community-level concerns about the privacy of their health data, and indicated that these deter their willingness to participate in health research. Future investigations should explore in more depth which health data privacy concerns are most salient to specific AI/AN and NHPI communities, and identify the practices that will make the collection and use of health data more trustworthy and transparent for participants.

Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections.

Movement, behavioral, and neuropsychiatric disorders in children have been linked to infections and a group of anti-neuronal autoantibodies, implying dopamine receptor-mediated encephalitis within the basal ganglia. The purpose of this study was to determine if anti-neuronal biomarkers, when used as a group, confirmed the acute disease in Sydenham chorea (SC) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). IgG autoantibodies against four neuronal autoantigens (tubulin, lysoganglioside GM1, and dopamine receptors D1 and D2) were detected in SC sera (N=8), sera and/or cerebrospinal fluid (CSF) from two groups of PANDAS cases (N=25 first group and N=35 second group), sera from Tourette's syndrome (N=18), obsessive-compulsive disorder (N=25), attention deficit hyperactivity disorder (N=18), and healthy controls (N=28) by direct enzyme-linked immunosorbent assay (ELISA). IgG specific for neuronal autoantigens was significantly elevated during the acute symptomatic phase, and the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) pathway was significantly elevated in human neuronal cells. Five assays confirmed the disease in SC and in two groups of children with PANDAS. In 35 acute onset PANDAS patients, 32 sera (91.4%) were positive for one or more of the anti-neuronal autoantibodies compared with 9 of 28 healthy controls (32.1%, p<0.0001). Importantly, CSF of 32 (91.4%) PANDAS patients had one or more detectable anti-neuronal autoantibody titers and CaMKII activation. Among healthy control subjects with elevated serum autoantibody titers for individual antigens, none (0%) were positively associated with elevated positive CaMKII activation, which was a striking contrast to the sera of PANDAS subjects, who had 76-89% positive association with elevated individual autoantibody titers and positive CaMKII activity. At 6 months follow-up, symptoms improved for more than 80% of PANDAS subjects, and serum autoantibody titers also significantly decreased. Results reported herein and previously published studies in our laboratory suggest the antibody biomarkers may be a useful adjunct to clinical diagnosis of SC, PANDAS, and related disorders and are the first known group of autoantibodies detecting dopamine receptor-mediated encephalitis in children.

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

OBJECTIVES: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF. BACKGROUND: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown. METHODS: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively. RESULTS: Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed. CONCLUSIONS: Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754).

Diabetes among Hispanics in Oklahoma: Assessing Disparities to Guide Basic and Applied Research.

Background ­: Diabetes, a leading cause of morbidity and mortality in the United States, disproportionally affects minority populations. In 2015, Hispanics, the largest minority in the country, had the third highest rate of diabetes prevalence and the third highest age-adjusted rate of diabetes-related mortality. Substantial progress in understanding diabetes disparities nationally and in many areas of the country has been made. However, little is known about diabetes and related mortality among Hispanics in Oklahoma, which is known as a Hispanic "new Settlement" state due to the relatively recent and substantial growth of this population. Methods ­: We used Oklahoma Behavioral and Risk Factor Surveillance Survey data (2011-2016) to calculate population estimates of diabetes prevalence and selected sociodemographic characteristics for Hispanic and Non-Hispanic adults in the state. We used Oklahoma Death Registry data to estimate diabetes-related mortality rates for Hispanic and Non-Hispanic adults for the same five-year period. We examined differences in diabetes prevalence and diabetes-related mortality across selected sociodemographic characteristics. Results ­: Hispanics are the largest minority group in Oklahoma. Spanish is the most common non-English language spoken in the state. Hispanics are younger, poorer, less educated and experience less access to health care compared to other populations in Oklahoma. While Hispanics had the fifth highest reported diabetes prevalence rate during the five-year period examined, they had the third highest diabetes-related mortality rate in the state. Discussion and Conclusions ­: There is a need for community engagement and basic and applied research to help identify and reduce diabetes disparities in the growing Hispanic population in Oklahoma.

Survival Benefit of Treatment at or Transfer to a Tertiary Trauma Center among Injured Older Adults.

Objective: It is well established that seriously injured older adults are under-triaged to tertiary trauma centers. However, the survival benefit of tertiary trauma centers (TC) compared to a non-tertiary trauma centers (Non-TCs) remains unclear for this patient population. Using improved methodology and a larger sample, we hypothesized that there was a difference in hospital mortality between injured older adults treated at TCs and those treated at Non-TCs. Methods: This was a retrospective cohort study of injured older adults (> =55 years) reported to the Oklahoma statewide trauma registry between 2005 and 2014. The outcome of interest was 30-day in-hospital mortality and the exposure variable of interest was level of definitive trauma care (TC vs Non-TC). Overall survival benefit of treatment at a TC as well as the survival benefit of transferring injured older adults to a TC were evaluated using multivariable survival analyses as well as propensity score-adjusted analyses. Results: Of the 25,288 patients eligible for analysis, 43% (10,927) were treated at TCs. Multivariable Cox regression analyses revealed effect modification by age group and time. After adjusting for potential confounders within the age strata, overall, patients treated at TCs were significantly less likely to die within 7 days of admission and this effect was stronger for patients aged 55-64 years (HR 0.41, 95% CI 0.31-0.52) compared to those > =65 years (HR 0.62, 95% CI 0.55-0.70). Overall survival benefit of TCs beyond 7 days was also observed (HR 0.68, 95% CI 0.56-0.83). Similarly, for the survival benefit of transferring injured older adults, after adjusting for the propensity to be transferred and other confounders, transfer to a TC was associated with lower 30-day mortality both for patients less than 65 years old (HR 0.36, 95% CI: 0.27-0.49) and those 65 years and older (HR 0.55, 95% CI: 0.48-0.64). Conclusions: Our results suggest a survival benefit for injured older adults treated at TCs. This benefit was also observed for patients transferred from non-tertiary trauma centers. Further research should focus on identifying specific subgroups of patients who would especially benefit from this level of care to minimize trauma triage inefficiencies.

Distribution of congenital anomalies by race/ethnicity and geospatial location in Oklahoma, 1997-2009.

INTRODUCTION: Congenital anomalies were the leading cause of infant mortality, responsible for 23 and 21% of deaths in Oklahoma and the USA, respectively, in 2016. We aimed to determine the prevalence by race/ethnicity and spatial distribution of congenital anomalies to identify geographic and racial/ethnic disparities, particularly among American Indian/Alaska Natives (AI/AN). METHODS: We evaluated the prevalence of anomalies by type and race/ethnicity among 648,074 live births in Oklahoma from 1997 to 2009. Prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. We used Moran's I and Getis-Ord Gi* to evaluate spatial clustering for neural tube defects, critical congenital heart defects (CCHDs), and oral clefts among births whose residence geocoded to the ZIP code or finer level. RESULTS: Overall prevalence of anomalies among live births was 3.9%. Non-Hispanic (NH) African American (PPR: 0.87, 95% CI: 0.83, 0.91), Asian/Pacific Islander (PPR: 0.70, 95% CI: 0.63, 0.78), and Hispanic (PPR: 0.87, 95% CI: 0.83, 0.91) children had a lower prevalence of anomalies compared to NH whites. The prevalence in NH AI/AN children was similar to NH whites (PPR: 1.01, 95% CI: 0.97, 1.05). However, differences in specific types of anomalies were observed by race/ethnicity. We observed no spatial autocorrelation for CCHD and oral clefts. Neural tube defects demonstrated spatial autocorrelation (p < .0001). Local hot spots varied by anomaly. DISCUSSION: The prevalence of anomalies by race/ethnicity and geography differed by race/ethnicity and region, though this varied by anomaly. Additional research is needed to identify behavioral or environmental factors to target for prevention.

Trends in Cardiovascular Disease Morbidity and Mortality in American Indians Over 25 Years: The Strong Heart Study.

Background American Indians experience high rates of cardiovascular disease. We evaluated whether cardiovascular disease incidence, mortality, and prevalence changed over 25 years among American Indians aged 30 to 85. Methods and Results The SHS (Strong Heart Study) and SHFS (Strong Heart Family Study) are prospective studies of cardiovascular disease in American Indians. Participants enrolled in 1989 to 1990 or 2000 to 2003 with birth years from 1915 to 1984 were followed for cardiovascular disease events through 2013. We used Poisson regression to analyze data for 5627 individuals aged 30 to 85 years during follow-up. Outcomes reflect change in age-specific cardiovascular disease incidence, mortality, and prevalence, stratified by sex. To illustrate generational change, 5-year relative risk compared most recent birth years for ages 45, 55, 65, and 75 to same-aged counterparts born 1 generation (23-25 years) earlier. At all ages, cardiovascular disease incidence was lower for people with more recent birth years. Cardiovascular disease mortality declined consistently among men, while prevalence declined among women. Generational comparisons were similar for women aged 45 to 75 (relative risk, 0.39-0.46), but among men magnitudes strengthened from age 45 to 75 (relative risk, 0.91-0.39). For cardiovascular disease mortality, risk was lower in the most recent versus the earliest birth years for women (relative risk, 0.56-0.83) and men (relative risk, 0.40-0.54), but results for women were inconclusive. Conclusions Cardiovascular disease incidence declined over a generation in an American Indian cohort. Mortality declined more for men, while prevalence declined more for women. These trends might reflect more improvement in case survival among men compared with women.

Interventions to promote healthy environments in family child care homes in Oklahoma-Happy Healthy Homes: study protocol for a randomized controlled trial.

BACKGROUND: Early childhood is a critical period of development. Caregivers, including providers of early care and education (ECE), have a substantial influence on the health of young children. Family child care homes (FCCHs), which are small, licensed ECE businesses operated out of the residences of providers, are important settings for promoting child health. However, to date, few interventions to promote the health of children have been developed for FCCHs. The purpose of this article is to describe the protocol for Happy Healthy Homes, a pilot interdisciplinary, community-based study to improve FCCH environments and the health of children in Oklahoma. We describe the development and evaluation of two interventions to be tested in a matched attention randomized controlled trial: 1) a nutrition intervention aimed at enhancing the nutritional quality of meals served to young children, incorporating the Child and Adult Care Food Program best practices, and improving nutritional self-efficacy of providers; and 2) an environmental intervention aimed at increasing providers' environmental health literacy, self-efficacy for integrated pest management (IPM), and awareness of less toxic cleaning practices and FCCH provider cleaning behaviors. METHODS: Both interventions are informed by common theoretical principles and are matched in attention (i.e., 6 h), format (i.e., two individual 90-min educational home visits and a 3-h small group class) and materials (i.e., tool kit of educational materials and supplies tailored to the allocated intervention). A randomized trial of both interventions is currently underway with 52 FCCH providers in the Oklahoma City metropolitan area who participate in the Child and Adult Care Food Program. Observed and self-reported measures will be collected at baseline, and 3 months and 12 months after baseline measurements. Randomization to one of the two interventions will occur after baseline data collection. DISCUSSION: This study aims to support FCCH providers in creating healthier FCCH environments for nutrition and environmental health. Successful completion will provide critical information about the nutritional quality and the environmental health of children in FCCHs, as well as much needed evidence about the efficacy of two community-based interventions to improve the nutrition and environmental health of children in home-based ECE settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03560050 . Retrospectively registered on 23 May 2018.

Higher Coated-Platelet Levels in Acute Stroke are Associated with Lower Cognitive Scores at Three Months Post Infarction.

BACKGROUND: Coated-platelets are a subset of highly procoagulant platelets observed after dual agonist stimulation with collagen and thrombin. Coated-platelet levels are increased in acute stroke compared to controls, and higher levels are associated with stroke recurrence. We examined whether coated-platelet levels measured at the time of the stroke correlate with cognitive scores at 3 months following the brain infarction. METHODS: Coated-platelets were assayed in consecutive patients with nonlacunar stroke. Cognitive screening was performed using the Mini-Mental State Examination (MMSE) at 3 months after discharge. Linear regression, with adjustment for individual covariates, was used to model the association between coated-platelet levels and MMSE scores. RESULTS: One hundred and twenty-eight patients with a mean MMSE score of 26 points (range 14-30, standard deviation [SD] 3.1) and mean coated-platelet levels of 40.9% (range 5.2-76.2, SD 13.3), completed cognitive screening. An inverse linear association was found between coated-platelet levels and MMSE score, with higher levels seen in patients with lower MMSE scores (r = -.34, R2 = .12, P < .0001). This association remained despite adjustment for potential confounding factors. In the final model, higher coated-platelet levels (coefficient -.078, 95% confidence interval [CI]: -.12 to -.041, P < .0001), presence of hypertension (coefficient -2.42, 95% CI: -3.90 to -.95, P = .0015), and anticoagulant use at discharge (coefficient -1.48, 95% CI: -2.56 to -.39, P = .0079) were predictive of lower MMSE. CONCLUSIONS: These findings support a link between increased platelet procoagulant potential at the time of the stroke and development of cognitive impairment following cerebral infarction.

Conducting a formative evaluation of an intervention promoting mammography screening in an American Indian community: The Native Women's Health Project.

BACKGROUND: Breast cancer is an important public health issue among American Indian/Alaska Native (AI/AN) women. However, there are very few published studies describing the evaluation of breast health promotion programs among AI/AN women. PURPOSE: To describe the formative evaluation of a multi-component intervention to promote mammography screening in an AI community in rural Oklahoma. METHODS: A comprehensive process evaluation plan with emphasis on context, reach, dose received, dose delivered, and fidelity was developed. Data collection included mixed research methodology and impact was assessed via one group pre/post research design. Data analysis consisted of descriptive statistical analysis and content analysis. The study utilized a community-based participatory research (CBPR) approach. RESULTS: Process evaluation revealed a relatively high reach within the priority population for both components (clinic and community) and a moderate implementation. Focus group research showed that participants were overall satisfied with program implementation. The intervention was feasible to implement in real-world settings. TRANSLATION TO HEALTH EDUCATION PRACTICE: Community-based evaluation of breast health promotion programs among AI communities is challenging, as one has to balance methodological rigor with practical constraints. The use of an evaluation plan, mixed methods and a collaborative approach are useful tools in conducting the evaluation.

Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of cardiovascular events in T1D.

APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.

Loss of alveolar bone density in postmenopausal, osteopenic women is associated with circulating levels of gelatinases.

OBJECTIVE: To determine whether circulating levels of two matrix metalloproteinases, MMP-2 and MMP-9, are associated with loss of alveolar bone density (ABD) or height (ABH), or with progression of periodontitis (relative clinical attachment level [RCAL]), among postmenopausal women with local and systemic bone loss. BACKGROUND: This study was planned as part of a 2-year randomized, double-blind, placebo-controlled, clinical trial examining efficacy/safety of subantimicrobial dose doxycycline (20 mg bid) in postmenopausal osteopenic women. This study examines whether serum levels of gelatinases are associated with local changes in the periodontium. METHODS: A sample of 113 women received periodontal maintenance for moderate to advanced chronic periodontitis and consented to analysis of stored serum biomarkers. Posterior vertical bitewings were taken, and serum collected, at baseline, one, and 2 years. ABD was determined by computer-assisted densitometric image analysis (CADIA), ABH by the Hausmann et al (1992, J Periodontol 63, 657) method, and RCAL by Florida Probe (every 6 months). MMPs were measured densitometrically on gelatin zymograms using denatured type I collagen as substrate and purified MMP-2 (72 kDa) and MMP-9 (92 kDa) as standards. Evidence of worsening in the periodontium at a tooth site was defined as a change from baseline of, for ABD, at least 14 densitometric units (for subcrestal locations) or 17 units (for crestal locations); of at least 0.4 mm for ABH; and of at least 1.5 mm for RCAL. Logistic regression models, while accounting for clustering, compared the odds of worsening in ABD, ABH, or RCAL, after 2 years of observation, between groups defined by baseline and concurrent levels of serum gelatinases. RESULTS: Changes in ABH and RCAL were not associated with circulating levels of MMP-2 or MMP-9. However, elevated odds of ABD loss over 24 months were associated, among smokers, with both baseline and concurrent levels of MMP-9 in the middle and highest tertile, and with concurrent levels of MMP-2 in the middle (but not the highest) tertile. Elevated odds of ABD loss were also associated, among women within 5 years of menopause, with baseline levels of MMP-2 in the highest tertile. CONCLUSION: Among postmenopausal osteopenic women, loss of ABD was associated, in smokers, with elevated circulating levels of MMP-9 and MMP-2. In those within 5 years of menopause, ABD loss was associated with elevated circulating levels of MMP-2.

High rates of undiagnosed vascular cognitive impairment among American Indian veterans.

As data on prevalence and etiology of dementia in American Indians are limited, we sought to determine rates and patterns of memory loss among American Indian veterans with vascular risk factors. Sixty consecutive outpatient American Indian veterans with a mean age of 64 years (range 50-86), without prior dementia or mild cognitive impairment (MCI), and with ≥ 2 vascular risk factors were enrolled. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were used to screen for cognitive impairment and depression. Patients with MoCA scores < 26 were referred for additional evaluation, including imaging, serology, and neuropsychological testing. Overall rates, types, and distribution of cognitive impairment were determined. Most prevalent vascular risk factors included hypertension (92%), hyperlipidemia (88%), diabetes (47%), and smoking (78%). Eight patients (13%) with severe depression were excluded, leaving 23/52 with abnormal MoCA scores (44%, 95%CI 30%-59%). Fifteen completed additional evaluation for memory loss, including four with normal MoCA scores who requested evaluation based on symptoms. Results were adjudicated as normal (4), non-amnestic MCI (4), vascular MCI (5), and vascular dementia (2). These results show that rates of undiagnosed cognitive impairment among American Indian veterans with vascular risk factors exceed rates previously published in non-American Indian cohorts. The most common etiology is vascular. Our findings support the need to improve vascular risk reduction in this understudied population.

Intensive glycemic control in gestational diabetes mellitus: a randomized controlled clinical feasibility trial.

BACKGROUND: Overweight and obese women with gestational diabetes mellitus are at increased risk for adverse perinatal outcomes, and they are also more likely to have suboptimal glycemic control. However, there is a paucity of data evaluating whether lower glycemic targets could improve outcomes. OBJECTIVE: To evaluate the feasibility of intensive glycemic control in overweight and obese women with gestational diabetes mellitus. MATERIALS AND METHODS: We randomized 60 overweight or obese women with gestational diabetes mellitus, diagnosed between 12 and 32 weeks' gestation to either intensive (fasting <90 mg/dL, 1 hour postprandial <120 mg/dL) or standard (fasting <95 mg/dL, 1 ho postprandial <140 mg/dL) glycemic targets. Maternal glucose was assessed in 2 ways: blinded continuous glucose monitors, worn for 5 days at 2 time points (at 12-32 weeks and again at 32-36 weeks), and self-monitored glucose measurement 4 times per day. All women underwent standardized dietary counseling, and medical therapy was prescribed as needed to achieve glycemic control. RESULTS: Between December 2015 and December 2017, we randomized 60 women to either intensive (n = 30) or standard (n = 30) glycemic control. Baseline characteristics including maternal age, body mass index, and gestational age at diagnosis were similar between the intensive and standard groups. Medical therapy was more common in women in the intensive group than those in the standard group (83 vs 57%, P = .02). Women in the intensive glycemic control group had lower glucose values as assessed by continuous glucose monitors at including 24-hour mean (-8.1; 95% confidence interval, -12.0 to -4.3 mg/dL; P < .0001) and 1-h postprandial (-11.8; 95% confidence interval, -19.7 to -3.9 mg/dL, P = .004) values. Hypoglycemia <60 mg/dL was uncommon and did not differ between groups. CONCLUSION: Intensive glycemic targets can be used in overweight and obese women with minimal hypoglycemia, and this approach results in improved glycemic control when compared to standard glycemic targets. Further studies are needed to determine whether intensive glycemic targets can improve maternal and neonatal outcomes in high-risk women with gestational diabetes mellitus. CLINICAL TRIAL IDENTIFIER: NCT02530866; clinicaltrials.gov.

The association between natural gas well activity and specific congenital anomalies in Oklahoma, 1997-2009.

BACKGROUND: Natural gas drilling may pose multiple health risks, including congenital anomalies, through air pollutant emissions and contaminated water. Two recent studies have evaluated the relationship between natural gas activity and congenital anomalies, with both observing a positive relationship. OBJECTIVES: We aimed to evaluate whether residence near natural gas wells is associated with critical congenital heart defects (CCHD), neural tube defects (NTD), and oral clefts in Oklahoma, the third highest natural gas producing state in the US. METHODS: We conducted a retrospective cohort study among singleton births in Oklahoma (n = 476,600) to evaluate natural gas activity and congenital anomalies. We calculated an inverse distance-squared weighted (IDW) score based on the number of actively producing wells within a two-mile radius of the maternal residence during the month of delivery. We used modified Poisson regression with robust error variance to estimate prevalence proportion ratios (PPR) and 95% confidence intervals (CI) for the association between tertiles of natural gas activity (compared to no wells) and CCHD, NTD, and oral clefts adjusted for maternal education. RESULTS: We observed an increased, though imprecise, prevalence of NTDs among children with natural gas activity compared to children with no wells (2nd tertile PPR: 1.34, 95% CI: 0.93, 1.93; 3rd tertile PPR: 1.20, 95% CI: 0.82, 1.75). We observed no association with CCHD or oral clefts overall. Specific CCHDs of common truncus, transposition of the great arteries, pulmonary valve atresia and stenosis, tricuspid valve atresia and stenosis, interrupted aortic arch, and total anomalous pulmonary venous connection were increased among those living in areas with natural gas activity compared to those living in areas without activity, though not statistically significant. DISCUSSION: Our results were similar to previous studies for NTDs and specific CCHDs. Future directions include evaluating the association between specific phases of the drilling process and congenital anomalies to better refine the relevant exposure period.

Neuroinvasive Listeria monocytogenes Infection Triggers IFN-Activation of Microglia and Upregulates Microglial miR-155.

MicroRNA (miR) miR-155 modulates microglial activation and polarization, but its role in activation of microglia during bacterial brain infection is unclear. We studied miR-155 expression in brains of C57BL/6 (B6.WT) mice infected i.p. with the neuro-invasive bacterial pathogen Listeria monocytogenes (L. monocytogenes). Infected mice were treated with ampicillin starting 2 days (d) post-infection (p.i.) and analyzed 3d, 7d, and 14d p.i. Virulent L. monocytogenes strains EGD and 10403s upregulated miR-155 in whole brain 7 d p.i. whereas infection with avirulent, non-neurotropic Δhly or ΔactA L. monocytogenes mutants did not. Similarly, infection with virulent but not mutated bacteria upregulated IFN-γ mRNA in the brain at 7 d p.i. Upregulation of miR-155 in microglia was confirmed by qPCR of flow cytometry-sorted CD45intCD11bpos brain cells. Subsequently, brain leukocyte influxes and gene expression in sorted microglia were compared in L. monocytogenes-infected B6.WT and B6.Cg-Mir155tm1.1Rsky/J (B6.miR-155-/-) mice. Brain influxes of Ly-6Chigh monocytes and upregulation of IFN-related genes in microglia were similar to B6.WT mice at 3 d p.i. In contrast, by d 7 p.i. expressions of microglial IFN-related genes, including markers of M1 polarization, were significantly lower in B6.miR-155-/- mice and by 14 d p.i., influxes of activated T-lymphocytes were markedly reduced. Notably, CD45highCD11bpos brain cells from B6.miR-155-/- mice isolated at 7 d p.i. expressed 2-fold fewer IFN-γ transcripts than did cells from B6.WT mice suggesting reduced IFN-γ stimulation contributed to dampened gene expression in B6.miR-155-/- microglia. Lastly, in vitro stimulation of 7 d p.i. brain cells with heat-killed L. monocytogenes induced greater production of TNF in B6.miR-155-/- microglia than in B6.WT microglia. Thus, miR-155 affects brain inflammation by multiple mechanisms during neuroinvasive L. monocytogenes infection. Peripheral miR-155 promotes brain inflammation through its required role in optimal development of IFN-γ-secreting lymphocytes that enter the brain and activate microglia. Microglial miR-155 promotes M1 polarization, and also inhibits inflammatory responses to stimulation by heat-killed L. monocytogenes, perhaps by targeting Tab2.