Association of Neighborhood Recreation Centers and Poststroke Outcomes in a Population-Based Cohort.

BACKGROUND: Higher neighborhood socioeconomic status has been favorably associated with stroke outcomes. This may be due to these areas having more beneficial resources such as recreational centers. We aimed to determine if neighborhood density of recreation centers is favorably associated with stroke outcomes. METHODS: We conducted analyses of data from the Brain Attack Surveillance in Corpus Christi project, a cohort of stroke survivors ≥45 years of age residing in Nueces County, TX (2009-2020). We included non-Hispanic White and Mexican American incident stroke survivors, who were not institutionalized prestroke and completed baseline and follow-up assessments (N=1392). We calculated the density of fitness and recreational sports centers within their residential census tract during the year of their stroke. Outcomes included function (self-ratings on activities of daily living and instrumental activities of daily living), cognition (modified mini-mental state exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life Scale). We fit confounder-adjusted gamma-distributed mixed generalized linear models with a log link for each outcome and considered interaction with stroke severity. RESULTS: On average, participants were 65 years old, 53% male, and 63% Mexican American. Median recreational centers were 1.60 per square mile (interquartile range, 0.41-3.06). Among moderate-severe stroke survivors, greater density of recreation centers (75th versus 25th percentile) was associated with more favorable function and possibly quality of life (activities of daily living/instrumental activities of daily living, 4.8% change [95% CI, -0.11% to -9.27%]; Stroke-Specific Quality of Life Scale, 3.7% change [95% CI, -0.7% to 8.2%]). Minimal nonsignificant differences were observed among the overall stroke population and those with mild stroke. CONCLUSIONS: The availability of recreation centers may be beneficial for poststroke function and quality of life among those with moderate-severe stroke. If further research confirms recreation centers to be beneficial, this could inform rehabilitation following stroke.

Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology.

We investigate the role of the mitochondrion, an organelle highly sensitive to environmental agents, in the influence of prenatal air pollution exposure on neurodevelopment and behavior in 96 children with autism spectrum disorder (ASD) [45 with neurodevelopmental regression (NDR); 76% Male; mean (SD) age 10 y 9 m (3 y 9 m)]. Mitochondrial function was assessed using the Seahorse XFe96 in fresh peripheral blood mononuclear cells. Second and third trimester average and maximal daily exposure to fine air particulate matter of diameter ≤2.5 µm (PM2.5) was obtained from the Environmental Protection Agency's Air Quality System. Neurodevelopment was measured using the Vineland Adaptive Behavior Scale 2nd edition and behavior was assessed using the Aberrant Behavior Checklist and Social Responsiveness Scale. Prenatal PM2.5 exposure influenced mitochondrial respiration during childhood, but this relationship was different for those with (r = 0.25-0.40) and without (r = -0.07 to -0.19) NDR. Mediation analysis found that mitochondrial respiration linked to energy production accounted for 25% (SD = 2%) and 10% (SD = 2%) of the effect of average prenatal PM2.5 exposure on neurodevelopment and behavioral symptoms, respectively. Structural equation models estimated that PM2.5 and mitochondrial respiration accounted for 34% (SD = 4%) and 36% (SD = 3%) of the effect on neurodevelopment, respectively, and that behavior was indirectly influenced by mitochondrial respiration through neurodevelopment but directly influenced by prenatal PM2.5. Our results suggest that prenatal exposure to PM2.5 disrupts neurodevelopment and behavior through complex mechanisms, including long-term changes in mitochondrial respiration and that patterns of early development need to be considered when studying the influence of environmental agents on neurodevelopmental outcomes.

The difference between hypertension determined by self-report versus examination in the adult population of the USA: Continuous NHANES 1999-2016.

BACKGROUND: Studies have considered the validity of self-reported hypertension relative to hypertension detected by examination; no study has explored trends in the difference between these two measures. Our objective was to calculate these differences overtime within subpopulations of the USA. METHODS: We included non-Hispanic white, non-Hispanic black and Hispanic adults who participated in the National Health and Nutrition Examination Surveys from 1999 to 2016, in the analysis (N = 44 333). We subtracted self-reported hypertension from hypertension detected by examination to calculate blood pressure difference (BPD). We fit weighted linear regression models that included important covariates along with all combination of two- and three-way interactions to predict the BPD. We used the fitted lines of the models to depict the patterns of differences in the different subpopulations. RESULTS: Age ≥ 45 years, lack of annual clinical visit, body mass index (BMI) < 25 and time were important factors associated with increased BPD. CONCLUSIONS: People who are ≥ 45 years, have normal BMI, or do not have annual medical visits are more likely to have a bigger BPD. We can use the calculated BPD, to adjust estimates of the prevalence of self-reported hypertension.

The Relationship between Insulin Resistance and Spatial QRS-T Angle in American Adults.

BACKGROUND: Insulin resistance can impair the electrical conductivity of the heart. Spatial QRS-T axis reflects ventricular depolarization and repolarization. The relationship between insulin resistance and spatial QRS-T angle has not been examined in the general population. OBJECTIVE: We examined the relationship between insulin resistance and spatial QRS-T angle in an American population-based sample. METHODS: We used data collected from the National Health and Nutrition Examination Survey III (NHANES III), and a directed acyclic graph to select confounders. We fitted logistic regression models and adjusted for the effect of the confounders. We stratified all analyses by gender. RESULTS: The odds ratios (OR) of the abnormal QRS-T angle and their 95% confidence intervals (CI) for females and males were 1.08 (1.03-1.16) and 1.03 (0.96-1.11), respectively. A 5-unit increase in insulin resistance in females increased the odds of an abnormal QRS-T angle by 47% (OR = 1.47, 95% CI, 1.10-2.10); in males, a 5-unit increase in insulin resistance increased the OR by 17% (OR = 1.17, 95% CI, 0.82-1.70). CONCLUSIONS: Spatial QRS-T angle may be associated with insulin resistance, especially in women. The individuals with a higher insulin resistance value had higher odds for major adverse cardiovascular events. Nevertheless, the results of this study should be verified in prospective studies.

The association of metabolic syndrome and QRS|T angle in US adults (NHANES III).

BACKGROUND: Spatial QRS|T angle is a predictor of cardiovascular events. Those with metabolic syndrome have an increased risk of cardiovascular morbidity and mortality. This study investigated the association between metabolic syndrome and spatial QRS|T angle. METHODS: We obtained data from the National Health and Nutritional Examination Survey III on 6,249 adults. We calculated spatial QRS|T angle from the standard 12-lead electrocardiogram and classified it as abnormal, borderline, or normal. We identified metabolic syndrome if at least three of the following were present: abdominal obesity, elevated blood pressure, elevated triglycerides, decreased high-density lipoprotein (HDL), and impaired fasting glucose. We used weighted logistic regression to estimate the effect of metabolic syndrome and its components on QRS|T angle while stratifying by gender and adjusting for age, race, smoking status, heart rate, PR, QT, and QRS interval, and QRS amplitude. RESULTS: Among men and women, metabolic syndrome, the number of components present, elevated blood pressure, and impaired fasting glucose were positively associated with QRS|T angle. Among women, decreased HDL and abdominal obesity were also positively associated with QRS|T angle. CONCLUSIONS: This study suggests that persons with metabolic syndrome may be at increased risk for ventricular arrhythmias. The use of spatial QRS|T angle to assess this cardiovascular risk is warranted.

Bioenergetic variation is related to autism symptomatology.

Autism spectrum disorder (ASD) has been associated with mitochondrial dysfunction but few studies have examined the relationship between mitochondrial function and ASD symptoms. We measured Complex I and IV and citrate synthase activities in 76 children with ASD who were not receiving vitamin supplementation or medication. We also measured language using the Preschool Language Scales or Clinical Evaluation of Language Fundamentals, adaptive behavior using the Vineland Adaptive Behavioral Scale, social function using the Social Responsiveness Scale and behavior using Aberrant Behavior Checklist, Childhood Behavior Checklist and the Ohio Autism Clinical Impression Scale. Children with ASD demonstrated significantly greater variation in mitochondrial activity compared to controls with more than expected ASD children having enzyme activity outside of the normal range for Citrate Synthase (24%), Complex I (39%) and Complex IV (11%). Poorer adaptive skills were associated with Complex IV activity lower or higher than average and lower Complex I activity. Poorer social function and behavior was associated with relatively higher Citrate Synthase activity. Similar to previous studies we find both mitochondrial underactivity and overactivity in ASD. This study confirms an expanded variation in mitochondrial activity in ASD and demonstrates, for the first time, that such variations are related to ASD symptoms.

Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity.

Background: Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c. Methods: A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis. Results: Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c. Conclusions: In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children. Trial registration: This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).

Neighborhood Resources and Health Outcomes Among Stroke Survivors in a Population-Based Cohort.

BACKGROUND: Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post-stroke outcomes. METHODS AND RESULTS: We included Mexican American and non-Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009-2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini-Mental State Exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56-73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini-Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate-severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=-0.156 [95% CI, -0.284 to 0.027]) and quality of life (abbreviated Stroke-Specific Quality of Life scale=0.194 [95% CI, 0.029-0.359]). CONCLUSIONS: We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate-severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.

A multicomponent motivational intervention to improve adherence among adolescents with poorly controlled type 1 diabetes: a pilot study.

OBJECTIVE: To adapt and pilot test a multicomponent motivational intervention that includes family-based contingency management (CM) for adolescents with poorly controlled type 1 diabetes. METHODS: A total of 17 adolescents, age 12-17 years (M = 14.8, SD = 1.5), with type 1 diabetes (duration M = 6.2 years, SD = 4.5) and mean HbA1c of 11.6% (SD = 2.5%) were enrolled. Adolescents and their parents received 14 weeks of motivational interviewing, clinic-based CM, and parent-directed CM that targeted increased blood glucose monitoring (BGM). RESULTS: Adolescents significantly increased their BGM (p < .001) and showed significantly improved HbA1c levels (glycemic control) from pre-to posttreatment (p < .0001). CONCLUSIONS: The magnitude of improvements in the frequency of BGM and glycemic control in adolescents with type 1 diabetes is encouraging and will be tested in a randomized controlled trial.

Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity.

AIMS: The increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. MATERIAL AND METHODS: Plasma miRNAs were measured in prepubertal children (n = 63, 5-9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. KEY FINDINGS: While no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. SIGNIFICANCE: The present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.

Metabolomic Signatures of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.

Effect of excess weight and insulin resistance on DNA methylation in prepubertal children.

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population.

Air Pollution and Maximum Temperature Are Associated with Neurodevelopmental Regressive Events in Autism Spectrum Disorder.

Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM2.5) may trigger NDR, especially in those children without an identified trigger. Average daily PM2.5, ozone, precipitation and maximum temperature (Tmax) were derived from Environmental Protection Agency models and National Oceanic and Atmospheric Administration monitors based on zip-code information from 83 ASD participants during the six-weeks following the onset month of an NDR event and a reference period defined as one year before and one year after the event. Seasonally adjusted logistic regression (LR) and linear mixed models (LMM) compared cases (with a history of NDR) and matched controls (without a history of NDR). LR models found that the risk of NDR was related to higher PM2.5 during 3 to 6 weeks of the NDR event period, particularly in those without a trigger. Overall, both models converged on NDR being related to a higher PM2.5 and lower Tmax both during the NDR event period as well as the reference period, particularly in those without a known trigger. This temporal pattern suggests that environmental triggers, particularly PM2.5, could be related to NDR, especially in those without an identifiable trigger. Further studies to determine the underlying biological mechanism of this observation could help better understand NDR and provide opportunities to prevent NDR.

Redox Imbalance and Methylation Disturbances in Early Childhood Obesity.

Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur-containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one-carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z-scores and HOMA-IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high-density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S-adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.

Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.

Mitochondrial Fatty Acid ß-Oxidation and Resveratrol Effect in Fibroblasts from Patients with Autism Spectrum Disorder.

Patients with autism spectrum disorder (ASD) may have an increase in blood acyl-carnitine (AC) concentrations indicating a mitochondrial fatty acid ß-oxidation (mtFAO) impairment. However, there are no data on systematic mtFAO analyses in ASD. We analyzed tritiated palmitate oxidation rates in fibroblasts from patients with ASD before and after resveratrol (RSV) treatment, according to methods used for the diagnosis of congenital defects in mtFAO. ASD participants (N = 10, 60%; male; mean age (SD) 7.4 (3.2) years) were divided in two age-equivalent groups based on the presence (N = 5) or absence (N = 5) of elevated blood AC levels. In addition, electron transport chain (ETC) activity in fibroblasts and muscle biopsies and clinical characteristics were compared between the ASD groups. Baseline fibroblast mtFAO was not significantly different in patients in comparison with control values. However, ASD patients with elevated AC exhibited significantly decreased mtFAO rates, muscle ETC complex II activity, and fibroblast ETC Complex II/III activity (p < 0.05), compared with patients without an AC signature. RSV significantly increased the mtFAO activity in all study groups (p = 0.001). The highest mtFAO changes in response to RSV were observed in fibroblasts from patients with more severe symptoms on the Social Responsiveness Scale total (p = 0.001) and Awareness, Cognition, Communication and Motivation subscales (all p < 0.01). These findings suggested recognition of an ASD patient subset characterized by an impaired mtFAO flux associated with abnormal blood AC. The study elucidated that RSV significantly increased fibroblast mtFAO irrespective of plasma AC status, and the highest changes to RSV effects on mtFAO were observed in the more severely affected patients.

Metabolic syndrome and P-wave duration in the American population.

PURPOSE: Metabolic syndrome has a high prevalence in the United States. P-wave duration is a valuable indicator for atrial electrical conduction. Abnormalities in atrial electrical conduction can predispose to atrial fibrillation. Our objective was to estimate the effect of metabolic syndrome on P-wave duration in a nationally representative sample. METHODS: We included 6499 adults who participated in the National Health and Nutrition Examination Survey III (1988-1994). We estimated the effect of metabolic syndrome and its components on P-wave duration after adjusting for confounders such as demographic and lifestyle variables. We stratified the analyses by gender. RESULTS: Irrespective of gender, participants with metabolic syndrome had a longer P-wave duration than that of those without it. In addition, we observed a positive linear dose-response relation between metabolic syndrome components and P-wave duration. CONCLUSIONS: Patients with metabolic syndrome had a longer P-wave duration. They might have been at a higher risk for atrial fibrillation and mortality; they need to be periodically checked by their health care providers. However, the results of this study should be confirmed in prospective studies.

The Influence of Diabetes Status on the Rate of Cataract Surgery Following Pars Plana Vitrectomy.

PURPOSE: We aimed to evaluate the association between diabetic status and the rates of cataract extraction (CE) following pars plana vitrectomy (PPV). DESIGN: Retrospective cohort, multicenter database study. PARTICIPANTS: Patients were selected from an insurance claims database (PharMetrics LifeLink) that included persons who had filed claims between 2006 and 2015 in the United States. METHODS: We analyzed the records of 22 146 patients who underwent PPV performed by 2705 retina physicians. The vitrectomy group included patients ≥18 years of age who had undergone PPV. The control group included patients who were matched to the vitrectomy group 1:2 based on sex, diabetes mellitus (DM) status, region of the United States, and Charleston Comorbidity Index. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and rates of cataract surgery in patients with and without diabetes who had undergone prior PPV. RESULTS: The hazard ratio for post-PPV CE was lower among patients with diabetes (3.307; 95% confidence interval [CI], 3.051-3.583) than among patients without diabetes (4.889; 95% CI, 4.670-5.119). This association was significant for all subgroups of patients with diabetes except in patients with diabetes and without retinopathy (4.086; 95% CI, 3.511-4.754). There was a significantly longer time between PPV and CE in patients with diabetes (537 days; 95% CI, 459-677 days) compared with those without diabetes (295 days; 95% CI, 278-312 days). The type of DM (type 1 vs. type 2) did not influence the rate of post-PPV cataract surgery. In persons with diabetes who underwent PPV, we observed a trend for a lower HR of cataract surgery in eyes with proliferative retinopathy (0.903; 95% CI, 0.725-1.124), and nonproliferative retinopathy (0.965; 95% CI, 0.721-1.290) compared with eyes with no retinopathy. CONCLUSIONS: Eyes of patients with diabetes had a significantly decreased risk of undergoing CE after PPV surgery compared with eyes of patients without diabetes.

Early life metal exposure dysregulates cellular bioenergetics in children with regressive autism spectrum disorder.

Neurodevelopmental regression (NDR) is a subtype of autism spectrum disorder (ASD) that manifests as loss of previously acquired developmental milestones. Early life dysregulation of nutritional metals and/or exposure to toxic metals have been associated with ASD, but the underlying biological mechanisms by which metals influence neurodevelopment remain unclear. We hypothesize that metals influences neurodevelopment through dysregulation of bioenergetics. Prenatal and early postnatal metal exposures were measured using validated tooth-matrix biomarkers in 27 ASD cases (13 with NDR) and 7 typically-developing (TD) controls. Mitochondrial respiration and glycolysis were measured in peripheral blood mononuclear cells using the Seahorse XF96. Children with ASD demonstrated lower prenatal and postnatal Copper (Cu) and prenatal Nickel concentrations and Copper-to-Zinc (Cu/Zn) ratio as compared with TD children. Children with ASD and NDR showed greater metal-related disruption of cellular bioenergetics than children with ASD without NDR. For children with ASD and NDR mitochondrial respiration decreased as prenatal Manganese concentration increased and increased as prenatal Zinc concentration increased; glycolysis decreased with increased exposure to prenatal Manganese and Lead and postnatal Manganese. For children with ASD without a history of NDR, glycolysis increased with increased postnatal exposure to Tin. Language and communication scores in children with ASD were positively related to prenatal Cu exposure and Cu/Zn ratio. This study suggests that prenatal nutritional metals may be important for neurodevelopment in children with ASD, and that exposure to toxic metals and differences in nutritional metal exposures is associated with dysregulation of cellular bioenergetics, particularly in the NDR subtype of ASD.

The relation of blood lead and QRS-T angle in American adults.

The QRS-T angle is a key ECG predictor for ventricular arrhythmia. Lead has a strong relation with cardiovascular diseases; however, no study has been conducted to investigate the association between lead exposure and QRS-T angle. Thus, we explored this association in a population-based representative sample: NHANES III. We used the standard 12-lead ECGs to calculate Spatial QRS-T angles. Blood lead concentration was measured using graphite furnace atomic absorption spectrophotometry method. We conducted multivariate weighted logistic regression to adjust for impaired fasting glucose, hypertension, poverty index, age, race, and smoking status. We found that when the log of blood lead increased by one unit, the odds of an abnormal QRS-T angle increased by 34% among men and 4% among women. We suggest the use of QRS-T angle deviation among those who are exposed to lead to detect individuals at risk for adverse cardiovascular outcomes such as arrhythmias.