Residential Density Is Associated With BMI Trajectories in Children and Adolescents: Findings From the Moving to Health Study.

Introduction: This study investigates the associations between built environment features and 3-year BMI trajectories in children and adolescents. Methods: This retrospective cohort study utilized electronic health records of individuals aged 5-18 years living in King County, Washington, from 2005 to 2017. Built environment features such as residential density; counts of supermarkets, fast-food restaurants, and parks; and park area were measured using SmartMaps at 1,600-meter buffers. Linear mixed-effects models performed in 2022 tested whether built environment variables at baseline were associated with BMI change within age cohorts (5, 9, and 13 years), adjusting for sex, age, race/ethnicity, Medicaid, BMI, and residential property values (SES measure). Results: At 3-year follow-up, higher residential density was associated with lower BMI increase for girls across all age cohorts and for boys in age cohorts of 5 and 13 years but not for the age cohort of 9 years. Presence of fast food was associated with higher BMI increase for boys in the age cohort of 5 years and for girls in the age cohort of 9 years. There were no significant associations between BMI change and counts of parks, and park area was only significantly associated with BMI change among boys in the age cohort of 5 years. Conclusions: Higher residential density was associated with lower BMI increase in children and adolescents. The effect was small but may accumulate over the life course. Built environment factors have limited independent impact on 3-year BMI trajectories in children and adolescents.

Neighborhood built and food environment in relation to glycemic control in people with type 2 diabetes in the moving to health study.

OBJECTIVE: To examine whether built environment and food metrics are associated with glycemic control in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We included 14,985 patients with type 2 diabetes using electronic health records from Kaiser Permanente Washington. Patient addresses were geocoded with ArcGIS using King County and Esri reference data. Built environment exposures estimated from geocoded locations included residential unit density, transit threshold residential unit density, park access, and having supermarkets and fast food restaurants within 1600-m Euclidean buffers. Linear mixed effects models compared mean changes of HbA1c from baseline at 1, 3 (primary) and 5 years by each built environment variable. RESULTS: Patients (mean age = 59.4 SD = 13.2, 49.5% female, 16.6% Asian, 9.8% Black, 5.5% Latino/Hispanic, 57.1% White, 20% insulin dependent, mean BMI = 32.7±7.7) had an average of 6 HbA1c measures available. Participants in the 1st tertile of residential density (lowest) had a greater decline in HbA1c (-0.42, -0.43, and -0.44 in years 1, 3, and 5 respectively) than those in the 3rd tertile (HbA1c = -0.37 at 1- and 3-years and -0.36 at 5-years; all p-values <0.05). Having any supermarkets within 1600 m of home was associated with a greater decrease in HbA1c at 1-year and 3-years compared to having none (all p-values <0.05). CONCLUSIONS: Lower residential density and better proximity to supermarkets may benefit HbA1c control in people with people with type 2 diabetes. However, effects were small and indicate limited clinical significance.

The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Stability of Suicide Risk Prediction Models During Changes in Health Care Delivery.

OBJECTIVE: The authors aimed to use health records data to examine how the accuracy of statistical models predicting self-harm or suicide changed between 2015 and 2019, as health systems implemented suicide prevention programs. METHODS: Data from four large health systems were used to identify specialty mental health visits by patients ages ≥11 years, assess 311 potential predictors of self-harm (including demographic characteristics, historical risk factors, and index visit characteristics), and ascertain fatal or nonfatal self-harm events over 90 days after each visit. New prediction models were developed with logistic regression with LASSO (least absolute shrinkage and selection operator) in random samples of visits (65%) from each calendar year and were validated in the remaining portion of the sample (35%). RESULTS: A model developed for visits from 2009 to mid-2015 showed similar classification performance and calibration accuracy in a new sample of about 13.1 million visits from late 2015 to 2019. Area under the receiver operating characteristic curve (AUC) ranged from 0.840 to 0.849 in the new sample, compared with 0.851 in the original sample. New models developed for each year for 2015-2019 had classification performance (AUC range 0.790-0.853), sensitivity, and positive predictive value similar to those of the previously developed model. Models selected similar predictors from 2015 to 2019, except for more frequent selection of depression questionnaire data in later years, when questionnaires were more frequently recorded. CONCLUSIONS: A self-harm prediction model developed with 2009-2015 visit data performed similarly when applied to 2015-2019 visits. New models did not yield superior performance or identify different predictors.

Mal control y elevado riesgo cardiovascular en hipertensos de una universidad

Introducción: La hipertensión arterial es una enfermedad de alta prevalencia y complicaciones mortales. Debido a ello, se necesitan un adecuado manejo en la atención primaria y estrategias preventivas y de intervención, como la iniciativa HEARTS en las Américas. Se sabe también que entre los trabajadores de la Universidad de Ciencias Médicas de Matanzas existe una elevada prevalencia de hipertensos. Objetivo: Identificar el comportamiento del control de la enfermedad y la estratificación de riesgo cardiovascular global. Materiales y métodos: Estudio descriptivo transversal en el que se incluyeron los primeros 80 pacientes hipertensos valorados en la consulta de la mencionada institución. Los métodos empleados fueron el analítico-sintético, el inductivo-deductivo, el histórico-lógico y los estadísticos. Resultados: De 808 trabajadores, 276 eran hipertensos, para una prevalencia de 34,1 %. Dentro de los inadecuados estilos de vida, predominó el sedentarismo, con 59 pacientes (73,7 %); 40 de los 80 pacientes estudiados tenían un riesgo cardiovascular cuantitativo igual o mayor del 10 %, mientras que el riesgo cardiovascular cualitativo mostró que 68 (85 %) tenían un riesgo medio o alto. Dentro del daño en órganos diana predominaron las enfermedades cardiovasculares, con un 16,2 %. Conclusiones: La hipertensión arterial sigue siendo uno de los factores de riesgo más importantes de enfermedad cardiovascular y cerebrovascular. Su pesquisa, control y estimación del riesgo constituyen una prioridad de la atención médica a nivel primario.

Introduction: Arterial hypertension is a disease of high prevalence and fatal complications. Due to this, an adequate management is needed in the primary care, and also preventive and intervention strategies, as the HEARTS initiative in the Americas. It is also known that there is a high prevalence of hypertensive patients among the working staff of the Matanzas University of Medical Sciences. Objective: To identify the behavior of disease control and global cardiovascular risk stratification. Materials and methods: Cross-sectional descriptive study in which the first 80 hypertensive patients evaluated in the consultation of the aforementioned institution were included. The methods used were analytical-synthetic, inductive-deductive, historical-logical and statistical. Results: Of 808 workers, 276 were hypertensive, for a prevalence of 34.1%. Among the inadequate lifestyles, sedentary lifestyle predominated, with 59 patients (73.7%); 40 of the 80 patients studied had a quantitative cardiovascular risk equal to or greater than 10%, while qualitative cardiovascular risk showed that 68 (85%) had a medium or high risk. Cardiovascular diseases predominated within target organ damage, with 16.2%. Conclusions: Arterial hypertension continuous to be one of the most important risk factors for cardiovascular and cerebrovascular diseases. Its screening, control and risk assessment are a priority of the medical care at the primary level.

Necesidad de calcular el riesgo cardiovascular global en pacientes hipertensos

Ante la amenaza para la salud que representan las enfermedades cardiovasculares, la iniciativa HEARTS, de la Organización Mundial de Salud, brinda apoyo a los países para que fortalezcan las medidas destinadas a prevenir las enfermedades cardiovasculares, como la estratificación del riesgo cardiovascular. Los autores proponen como objetivo fundamentar la necesidad del cálculo del riesgo cardiovascular global en la atención primaria de salud. Para estimar el riesgo cardiovascular global se utilizan dos formas: la cualitativa y la cuantitativa. En esta última, se consideran determinados factores de riesgo cardiovascular, que se expresa en términos de bajo, medio y alto. Existen varios sistemas en diferentes soportes que permiten su uso en diversos escenarios; además, posibilitan planificar el seguimiento y el tratamiento de acuerdo al riesgo. Aunque tienen desventajas, su uso es recomendable para prevenir complicaciones y muerte. El cálculo del riesgo cardiovascular global en pacientes hipertensos es una medida de gran valor para predecir mortalidad, establecer la estrategia terapéutica y planificar el seguimiento de los pacientes. Su uso debe extenderse y consolidarse a todos los niveles de la atención de salud.

Faced with the global health threat posed by cardiovascular diseases, the HEARTS initiative of the World Health Organization supports countries to strengthen measures to prevent cardiovascular diseases, such as cardiovascular risk stratification. The authors propose as an objective to substantiate the need of calculating global cardiovascular risk in primary health care. Two forms are used to estimate global cardiovascular risk: qualitative and quantitative. In the latter, certain cardiovascular risk factors are considered and expressed in terms of low, medium, and high risk. There are several systems and in different supports that allow their use in various scenarios; in addition they make it possible to plan the follow-up and treatment according to risk. Although they have disadvantages, their use is recommended to prevent complications and death. The calculation of global cardiovascular risk in hypertensive patients is a measure of great value for predicting mortality, establishing the therapeutic strategy, and planning patient follow-up. Its use should be extended and consolidated at all levels of health care.

Predicting Outcomes of Antidepressant Treatment in Community Practice Settings.

OBJECTIVE: The authors examined whether machine-learning models could be used to analyze data from electronic health records (EHRs) to predict patients' responses to antidepressant medications. METHODS: EHR data from a Washington State health system identified patients ages ≥13 years who started an antidepressant medication in 2016 in a community practice setting and had a baseline Patient Health Questionnaire-9 (PHQ-9) score of ≥10 and at least one PHQ-9 score recorded 14-180 days later. Potential predictors of a response to antidepressants were extracted from the EHR and included demographic characteristics, psychiatric and substance use diagnoses, past psychiatric medication use, mental health service use, and past PHQ-9 scores. Random-forest and penalized regression analyses were used to build models predicting follow-up PHQ-9 score and a favorable treatment response (≥50% improvement in score). RESULTS: Among 2,469 patients starting antidepressant medication treatment, the mean±SD baseline PHQ-9 score was 17.3±4.5, and the mean lowest follow-up score was 9.2±5.9. Outcome data were available for 72% of the patients. About 48% of the patients had a favorable treatment response. The best-fitting random-forest models yielded a correlation between predicted and observed follow-up scores of 0.38 (95% CI=0.32-0.45) and an area under the receiver operating characteristic curve for a favorable response of 0.57 (95% CI=0.52-0.61). Results were similar for penalized regression models and for models predicting last PHQ-9 score during follow-up. CONCLUSIONS: Prediction models using EHR data were not accurate enough to inform recommendations for or against starting antidepressant medication. Personalization of depression treatment should instead rely on systematic assessment of early outcomes.

Drug use and spending under a formulary informed by cost-effectiveness.

BACKGROUND: The National Academy of Medicine has called for value-based drug formularies to address health plan prescription drug spending while maintaining access to high-value medicines. Thirty employer-sponsored plans implemented a "Value-Based Formulary-essentials" (VBF-e) program that uses cost-effectiveness evidence to inform cost-sharing and coverage exclusion. OBJECTIVE: To evaluate if the VBF-e was associated with changes in medication use and patient out-of-pocket spending and health plan spending on prescription drugs and other health care. METHODS: This was a cohort study using a difference-in-differences design from 2015 through 2019 with 1 year of follow-up after VBF-e implementation at Premera Blue Cross, the largest nonprofit health plan in the Pacific Northwest. The VBF-e exposure group was composed of all individuals aged younger than 65 years and enrolled at least 12 months prior to their employer group's VBF-e implementation date. The contemporaneous control group was composed of propensity score-matched individuals with the same inclusion criteria but their employer group that did not implement VBF-e. We prespecified the following outcomes: days of medication on hand overall and by VBF-e tier (high-value generic, brand, and specialty drugs were in tiers 1 to 3, respectively, and low-value drugs were in tier 4 or excluded from coverage); prescription drug spending; and other health care use (emergency department visits, hospital days, and outpatient visits). RESULTS: Comparing 12,111 exposed (mean age = 36.0; 49.8% female sex) participants with 24,222 control participants (mean age = 34.7; 49.6% female sex), VBF-e reduced use of low-value drugs by 0.3 days per member per month (PMPM) (95% CI = -0.5 to -0.1; 17% decrease) for tier 4 drugs and 0.4 days PMPM (95% CI = -0.5 to -0.4; 83% decrease) for excluded drugs. High-value specialty drug use increased by 0.1 days PMPM (95% CI = 0.0-0.1; 123% increase). Health plan spending decreased by $14 PMPM (95% CI = -26 to -4) and member out-of-pocket spending increased by $1 PMPM (95% CI = 1-2). Other health care use did not change significantly. CONCLUSIONS: An exclusion formulary informed by cost-effectiveness evidence reduced low-value drug use, increased high-value specialty drug use, reduced health plan spending, and increased member out-of-pocket spending without increasing acute care use. DISCLOSURES: This research was supported by a grant from the Patrick and Catherine Weldon Donaghue Medical Research Foundation's Greater Value Portfolio Program. Study Registration Number: NCT04904055.

Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial.

BACKGROUND: N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE: To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS: This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES: Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS: LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION: At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).

Circulating Nrf2, Glutathione, and Malondialdehyde Correlate with Disease Severity in Duchenne Muscular Dystrophy.

Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl concentrations change according to the disease severity in DMD patients. Moreover, we assessed whether OS correlated with muscle injury, clinical characteristics, physical activity, and antioxidant food consumption (AFC). A total of 28 DMD patients participated in this study. OS markers, metabolic indicators, and enzymatic markers of muscle injury were measured in circulation. Muscle injury was measured with clinical scales, and physical activity and AFC were evaluated with questionnaires. Nrf2 concentration was lower (p ≤ 0.01), and malondialdehyde concentration was higher (p < 0.05) in non-ambulatory patients than in ambulatory patients. Nrf2 correlated with age (rho = -0.387), Vignos scale (rho = -0.328), GMFCS scale (rho = -0.399), and Brooke scale scores (rho = -0.371) (p < 0.05). MDA correlated with Vignos (rho = 0.317) and Brooke scale scores (rho = 0.414) (p ≤ 0.05). In conclusion, DMD patients with the worst muscle function had more significant oxidative damage and lower antioxidant function than DMD patients with better muscle function.

Complex modeling with detailed temporal predictors does not improve health records-based suicide risk prediction.

Suicide risk prediction models can identify individuals for targeted intervention. Discussions of transparency, explainability, and transportability in machine learning presume complex prediction models with many variables outperform simpler models. We compared random forest, artificial neural network, and ensemble models with 1500 temporally defined predictors to logistic regression models. Data from 25,800,888 mental health visits made by 3,081,420 individuals in 7 health systems were used to train and evaluate suicidal behavior prediction models. Model performance was compared across several measures. All models performed well (area under the receiver operating curve [AUC]: 0.794-0.858). Ensemble models performed best, but improvements over a regression model with 100 predictors were minimal (AUC improvements: 0.006-0.020). Results are consistent across performance metrics and subgroups defined by race, ethnicity, and sex. Our results suggest simpler parametric models, which are easier to implement as part of routine clinical practice, perform comparably to more complex machine learning methods.

Machine Learning Prediction of Suicide Risk Does Not Identify Patients Without Traditional Risk Factors.

Objective: To determine whether predictions of suicide risk from machine learning models identify unexpected patients or patients without medical record documentation of traditional risk factors.Methods: The study sample included 27,091,382 outpatient mental health (MH) specialty or general medical visits with a MH diagnosis for patients aged 11 years or older from January 1, 2009, to September 30, 2017. We used predicted risk scores of suicide attempt and suicide death, separately, within 90 days of visits to classify visits into risk score percentile strata. For each stratum, we calculated counts and percentages of visits with traditional risk factors, including prior self-harm diagnoses and emergency department visits or hospitalizations with MH diagnoses, in the last 3, 12, and 60 months.Results: Risk-factor percentages increased with predicted risk scores. Among MH specialty visits, 66%, 88%, and 99% of visits with suicide attempt risk scores in the top 3 strata (respectively, 90th-95th, 95th-98th, and ≥ 98th percentiles) and 60%, 77%, and 93% of visits with suicide risk scores in the top 3 strata represented patients who had at least one traditional risk factor documented in the prior 12 months. Among general medical visits, 52%, 66%, and 90% of visits with suicide attempt risk scores in the top 3 strata and 45%, 66%, and 79% of visits with suicide risk scores in the top 3 strata represented patients who had a history of traditional risk factors in the last 12 months.Conclusions: Suicide risk alerts based on these machine learning models coincide with patients traditionally thought of as high-risk at their high-risk visits.

Natural history of circulating miRNAs in Duchenne disease: Association with muscle injury and metabolic parameters.

OBJECTIVES: This study aimed to evaluate whether the expression of circulating dystromiRs and a group of oxidative stress-related (OS-R) miRNAs is associated with muscle injury and circulating metabolic parameters in Duchenne muscular dystrophy (DMD) patients. METHODS: Twenty-four DMD patients were included in this cross-sectional study. Clinical scales to evaluate muscle injury (Vignos, GMFCS, Brooke, and Medical Research Council), enzymatic muscle injury parameters (CPK, ALT, and AST), anthropometry, metabolic indicators, physical activity, serum dystromiRs (miR-1-3p, miR-133a-3p, and miR-206), and OS-R miRNAs (miR-21-5p, miR-31-5p, miR-128-3p, and miR-144-3p) levels were measured in ambulatory and non-ambulatory DMD patients. RESULTS: DystromiRs (except miR-1-3p) and miRNAs OS-R levels were lower (p-value <.05) in the non-ambulatory group than the ambulatory group. The expression of those miRNAs correlated with Vignos scale score (For instance, rho = -0.567, p-value <0.05 for miR-21-5p) and with other scales scores of muscle function and strength. CPK, AST, and ALT concentration correlated with expression of all miRNAs (For instance, rho = 0.741, p-value <.05 between miR-206 level and AST concentration). MiR-21-5p level correlated with glucose concentration (rho = -0.369, p-value = .038), and the miR-1-3p level correlated with insulin concentration (rho = 0.343, p-value = .05). CONCLUSIONS: Non-ambulatory DMD patients have lower circulating dystromiRs and OS-R miRNAs levels than ambulatory DMD patients. The progressive muscle injury is associated with a decrease in the expression of those miRNAs, evidencing DMD progress. These findings add new information about the natural history of DMD.

Influence of Maternal Body Fat on Levels of Insulin, Insulin-Like Growth Factor-1, and Obestatin.

BACKGROUND: Insulin, insulin-like Growth Factor-1 (IGF-1), and obestatin in human milk originate from the circulation. There is also limited knowledge about the influence of body fat on the levels of these hormones in human milk. RESEARCH AIM: To determine (1) the influence of body fat on levels of insulin, IGF-1, and obestatin in human milk and serum/plasma during the postpartum period; (2) the changes in the levels of these hormones in human milk and serum/plasma postpartum; and (3) the presence of IGF-1 mRNA in human milk. METHODS: In this prospective, longitudinal, observational cohort study, levels of insulin, IGF-1, and obestatin were measured up to 30 days postpartum in milk and serum/plasma of 58 participants with adequate (≤ 32%) or excess (> 32%) total body fat determined by electrical bioimpedance. Student's t test and repeated-measures analysis of variance were used to evaluate the differences between groups. Pearson's test was used to analyze the associations. RESULTS: The milk from participants with excess body fat had higher insulin and IGF-1 levels and lower obestatin levels than that of participants with adequate body fat at 3-7, 14-15, and 30 days postpartum (adjusted p < .001). The levels of insulin, IGF-1, and obestatin were significantly higher in human milk than in serum/plasma (p < .05) and correlated with maternal body fat (p < .001). CONCLUSIONS: Maternal body fat was associated with elevated insulin and IGF-1 levels and decreased obestatin levels in human milk up to 30 days postpartum.

Genetic determination and JARID2 over-expression in a thermal incubation experiment in Casque-Headed Lizard.

Non-avian reptiles, unlike mammals and birds, have undergone numerous sex determination changes. Casque-Headed Lizards have replaced the ancestral XY system shared across pleurodonts with a new pair of XY chromosomes. However, the evolutionary forces that triggered this transition have remained unclear. An interesting hypothesis suggests that species with intermediate states, with sex chromosomes but also thermal-induced sex reversal at specific incubation temperatures, could be more susceptible to sex determination turnovers. We contrasted genotypic data (presence/absence of the Y chromosome) against the histology of gonads of embryos from stages 35-37 incubated at various temperatures, including typical male-producing (26°C) and female-producing (32°C) temperatures. Our work apparently reports for the first time the histology of gonads, including morphological changes, from stages 35-37 of development in the family Corytophanidae. We also observed that all embryos developed hemipenes, suggesting sex-linked developmental heterochrony. We observed perfect concordance between genotype and phenotype at all temperatures. However, analysis of transcriptomic data from embryos incubated at 26°C and 32°C identified transcript variants of the chromatin modifiers JARID2 and KDM6B that have been linked to temperature-dependent sex determination in other reptiles. Our work tested the validity of a mixed sex determination system in the family Corytophanidae. We found that XY chromosomes are dominant; however, our work supports the hypothesis of a conserved transcriptional response to incubation temperatures across non-avian reptiles that could be a reminiscence of an ancestral sex determination system.

Differences in Weight Gain Following Residential Relocation in the Moving to Health (M2H) Study.

BACKGROUND: Neighborhoods may play an important role in shaping long-term weight trajectory and obesity risk. Studying the impact of moving to another neighborhood may be the most efficient way to determine the impact of the built environment on health. We explored whether residential moves were associated with changes in body weight. METHODS: Kaiser Permanente Washington electronic health records were used to identify 21,502 members aged 18-64 who moved within King County, WA between 2005 and 2017. We linked body weight measures to environment measures, including population, residential, and street intersection densities (800 m and 1,600 m Euclidian buffers) and access to supermarkets and fast foods (1,600 m and 5,000 m network distances). We used linear mixed models to estimate associations between postmove changes in environment and changes in body weight. RESULTS: In general, moving from high-density to moderate- or low-density neighborhoods was associated with greater weight gain postmove. For example, those moving from high to low residential density neighborhoods (within 1,600 m) gained an average of 4.5 (95% confidence interval [CI] = 3.0, 5.9) lbs 3 years after moving, whereas those moving from low to high-density neighborhoods gained an average of 1.3 (95% CI = -0.2, 2.9) lbs. Also, those moving from neighborhoods without fast-food access (within 1600m) to other neighborhoods without fast-food access gained less weight (average 1.6 lbs [95% CI = 0.9, 2.4]) than those moving from and to neighborhoods with fast-food access (average 2.8 lbs [95% CI = 2.5, 3.2]). CONCLUSIONS: Moving to higher-density neighborhoods may be associated with reductions in adult weight gain.

A generalized interrupted time series model for assessing complex health care interventions.

Assessing the impact of complex interventions on measurable health outcomes is a growing concern in health care and health policy. Interrupted time series (ITS) designs borrow from traditional case-crossover designs and function as quasi-experimental methodology able to retrospectively analyze the impact of an intervention. Statistical models used to analyze ITS designs primarily focus on continuous-valued outcomes. We propose the "Generalized Robust ITS" (GRITS) model appropriate for outcomes whose underlying distribution belongs to the exponential family of distributions, thereby expanding the available methodology to adequately model binary and count responses. GRITS formally implements a test for the existence of a change point in discrete ITS. The methodology proposed is able to test for the existence of and estimate the change point, borrow information across units in multi-unit settings, and test for differences in the mean function and correlation pre- and post-intervention. The methodology is illustrated by analyzing patient falls from a hospital that implemented and evaluated a new care delivery model in multiple units.

Pro-inflammatory monocytes are increased in Duchenne muscular dystrophy and suppressed with omega-3 fatty acids: A double-blind, randomized, placebo-controlled pilot study.

BACKGROUND: Omega-3 long chain polyunsaturated fatty acids (LCPUFA) reduce circulating cytokines produced by monocytes. Nevertheless, whether the omega-3 LCPUFA regulate the monocytes and their cytokines in Duchenne muscular dystrophy (DMD) is unknown. The aim of this study was to evaluate whether circulating pro-inflammatory monocytes are increased and whether omega-3 LCPUFA selectively suppress these monocytes and their cytokines in patients with DMD. METHODS: This was a double-blind, randomized, placebo-controlled pilot study carried out in patients with DMD supplemented with omega-3 LCPUFA (n = 6) or sunflower oils (placebo, n = 6) for 6 months. Monocytes and their cytokines were measured at baseline and after 1, 2, 3, and 6 months of supplementation. RESULTS: The anti-inflammatory monocytes (median, [95% CI]) are increased at month 3 (-0.46 [-13.5-9.5] vs. 8.4 [5.5-12.5], p = 0.05) in the omega-3 LCPUFA group compared with the placebo group. The pro-inflammatory monocytes (-5.7 [-63.8-114.1] vs. -51.9 [-91.2 to -25.4], p = 0.026 and -16.4 [-50.8-50.6] vs. -57.9 [-86.9 to -18.5], p = 0.045 at months 3 and 6, respectively) and their cytokine interleukin 6 (-11.9 [-93.5-148.9] vs. -64.7 [-77.8 to -42.6], p = 0.019 at month 6) decreased in the omega-3 LCPUFA group compared with the placebo group. Pro-inflammatory monocytes decreased and anti-inflammatory monocytes were augmented (p < 0.05) during the 6 months of supplementation with omega-3 LCPUFA. CONCLUSIONS: This pilot study suggests that supplementation with omega-3 LCPUFA could have a selective reductive effect on pro-inflammatory monocytes and their cytokines in patients with DMD. These findings also support the performance of studies in a significant population to explore the role of omega-3 LCPUFA on monocyte populations and their cytokines in patients with DMD. This research was registered at clinicaltrials.gov (NCT018264229).

Differential associations of the built environment on weight gain by sex and race/ethnicity but not age.

OBJECTIVE: To explore the built environment (BE) and weight change relationship by age, sex, and racial/ethnic subgroups in adults. METHODS: Weight trajectories were estimated using electronic health records for 115,260 insured Kaiser Permanente Washington members age 18-64 years. Member home addresses were geocoded using ArcGIS. Population, residential, and road intersection densities and counts of area supermarkets and fast food restaurants were measured with SmartMaps (800 and 5000-meter buffers) and categorized into tertiles. Linear mixed-effect models tested whether associations between BE features and weight gain at 1, 3, and 5 years differed by age, sex, and race/ethnicity, adjusting for demographics, baseline weight, and residential property values. RESULTS: Denser urban form and greater availability of supermarkets and fast food restaurants were associated with differential weight change across sex and race/ethnicity. At 5 years, the mean difference in weight change comparing the 3rd versus 1st tertile of residential density was significantly different between males (-0.49 kg, 95% CI: -0.68, -0.30) and females (-0.17 kg, 95% CI: -0.33, -0.01) (P-value for interaction = 0.011). Across race/ethnicity, the mean difference in weight change at 5 years for residential density was significantly different among non-Hispanic (NH) Whites (-0.47 kg, 95% CI: -0.61, -0.32), NH Blacks (-0.86 kg, 95% CI: -1.37, -0.36), Hispanics (0.10 kg, 95% CI: -0.46, 0.65), and NH Asians (0.44 kg, 95% CI: 0.10, 0.78) (P-value for interaction <0.001). These findings were consistent for other BE measures. CONCLUSION: The relationship between the built environment and weight change differs across demographic groups. Careful consideration of demographic differences in associations of BE and weight trajectories is warranted for investigating etiological mechanisms and guiding intervention development.

RITS: a toolbox for assessing complex interventions via interrupted time series models.

BACKGROUND: Various interacting and interdependent components comprise complex interventions. These components create difficulty in assessing the true impact of interventions designed to improve patient-centered outcomes. Interrupted time series (ITS) designs borrow from case-crossover designs and serve as quasi-experimental methodology able to retrospectively assess the impact of an intervention while accounting for temporal correlation. While ITS designs are aptly situated for studying the impacts of large-scale public health policies, existing ITS software implement rigid ITS methodology that often assume the pre- and post-intervention phases are fully differentiated (by a known change-point or set of time points) and do not allow for changes in both the mean functions and correlation structure. RESULTS: This article describes the Robust Interrupted Time Series (RITS) toolbox, a stand-alone user-friendly application researchers can use to implement flexible ITS models that estimate the lagged effect of an intervention on an outcome, level and trend changes, and post-intervention changes in the correlation structure, for single and multiple ITS. The RITS toolbox incorporates a formal test for the existence of a change in the outcome and estimates a change-point over a set of possible change-points defined by the researcher. In settings with multiple ITS, RITS provides a global over-all units change-point and allows for unit-specific changes in the mean functions and correlation structures. CONCLUSIONS: The RITS toolbox is the first piece of software that allows researchers to use flexible ITS models that test for the existence of a change-point, estimate the change-point (if estimation is desired), and allow for changes in both the mean functions and correlation structures at the change point. RITS does not require any knowledge of a statistical (or otherwise) programming language, is freely available to the community, and may be downloaded and used on a local machine to ensure data protection.