Accelerated Longitudinal Glycemic Changes in Relation to Urinary Toxic/Essential Metals and Metal Mixtures Among Mexican Americans Living in Starr County, Texas.

OBJECTIVE: Metal and metalloid exposures (hereafter "metals") are associated with adverse health outcomes, including type 2 diabetes; however, previous studies were largely cross- sectional or underpowered. Furthermore, underserved racial/ethnic groups are underrepresented in environmental health research despite having higher rates of type 2 diabetes and a greater risk of metal exposures. Consequently, we evaluated continuous glycemic traits in relation to baseline urinary toxic metal, essential metal, and metal mixtures in a cohort of Mexican American adults. RESEARCH DESIGN AND METHODS: A total of 510 participants were selected based upon self-reported diabetes status and followed over 3 years. Urinary metals were assessed at baseline. Linear mixed-effects models were used to estimate per-month changes in hemoglobin A1c, fasting plasma glucose, and postload glucose in relation to urinary metal levels. Multiple statistical approaches were used to assess the associations between glycemic traits and metal mixtures. RESULTS: After adjustment, higher urinary levels of arsenic, selenium, copper, molybdenum, nickel, and tin were associated with faster increases in measures of glycemia. The toxic metal mixture composed of arsenic, lead, cadmium, nickel, and tin was associated with faster increases in postload glucose. Using postload glucose criteria, highest versus lowest arsenic was predicted to accelerate conversion of normoglycemia to prediabetes and diabetes by 23 and 65 months, respectively. CONCLUSIONS: In this underrepresented, high-risk Mexican American population, exposure to toxic metals and alterations in essential metal homeostasis were associated with faster increases in glycemia over time that may accelerate type 2 diabetes development.

Predictors of Toxic Metal/Metalloid Exposures Among Mexican Americans in Starr County, Texas.

BACKGROUND: Arsenic, cadmium, and lead are toxic elements that widely contaminate our environment. These toxicants are associated with acute and chronic health problems, and evidence suggests that minority communities, including Hispanic/Latino Americans, are disproportionately exposed. Few studies have assessed culturally specific predictors of exposure to understand the potential drivers of racial/ethnic exposure disparities. OBJECTIVE: We sought to evaluate acculturation measures as predictors of metal/metalloid (hereafter "metal") concentrations among Mexican American adults to illuminate potential exposure sources that may be targeted for interventions. METHODS: As part of a longitudinal cohort, 510 adults, aged 35 to 69 years, underwent baseline interview, physical examination, and urine sample collection. Self-reported acculturation was assessed across various domains using the Short Acculturation Scale for Hispanics (SASH). Multivariable linear regression was used to assess associations between acculturation and urinary concentrations of arsenic, cadmium, and lead. Ordinal logistic regression was utilized to assess associations between acculturation and a metal mixture score. Lastly, best subset selection was used to build a prediction model for each toxic metal with a combination of the acculturation predictors. RESULTS: After adjustment, immigration factors were positively associated with arsenic and lead concentrations. For lead alone, English language and American media and food preferences were associated with lower levels. Immigration and parental heritage from Mexico were positively associated with the metal mixture, while preferences for English language, media, and food were negatively associated. CONCLUSION: Acculturation-related predictors of exposure provide information about potential sources of toxic metals, including international travel, foods, and consumer products. The findings in this research study provide information to empower future efforts to identify and address specific acculturation-associated toxicant exposures in order to promote health equity through clinical guidance, patient education, and public policy.

A Scoping Review of the Intersectionality of Autism and Intellectual and Developmental Disability with Social Inequity on Diagnosis and Treatment of Youth.

Objective: To describe how the intersectionality of race, ethnicity, and language with autism and intellectual and developmental disability (IDD) impacts mental health inequities in psychopharmacological management of youth. Method: This was a scoping review in which a series of searches were conducted in PubMed, Web of Science, Google Scholar, and manual review of the articles collected. Results: Although autism and/or IDD increases the risk for poor physical and mental health, social determinants of health such as race, ethnicity, and language account for approximately a third of poor outcomes. Minoritized children with autism/IDD experience significantly greater delays to diagnosis and misdiagnosis and are less likely to receive appropriate services. Access to psychological testing and psychosocial services is often limited by availability, skilled practitioners, a shortage of non-English-language providers or interpreters, and poor reimbursement. Conclusion: The intersectionality of autism and/or IDD with race, ethnicity, and language compounds the health inequities associated with either of these challenges independently.

Sleep, executive functions, and functional impairment in children with specific learning disorder: An investigation of the mediating pathways.

OBJECTIVE: Sleep problems and executive dysfunction are associated with functional impairment in children with neurodevelopmental disorders. In this study, we aimed to investigate these aspects in children with Specific Learning Disorders (SLD) and SLD with comorbid Attention-Deficit Hyperactivity Disorder (ADHD), while also evaluating differences with typically developing (TD) children. Our study hypothesizes that children with SLD, especially those with comorbid ADHD, face greater sleep disturbances and executive function challenges compared to TD peers. We also propose that sleep disturbances aggravate functional impairment and that executive functions mediate this relationship. METHOD: The data obtained from psychiatric evaluations, semi-structured interviews and questionnaires filled out by parents were analyzed. RESULTS: SLD + ADHD group had worse scores in all scales, followed by SLD and TD groups. Mediator analysis demonstrated that executive functions had a mediator role in the relationship between sleep problems and functional impairment. CONCLUSION: Our findings suggest that children with SLD experience more significant difficulties in daily living than their typically developing peers and having ADHD comorbidity, poor executive functions, and additional sleep problems can further exacerbate impairment. Notably, our mediation analysis suggests that executive functions mediate the relationship between sleep disturbances and the severity of functional impairments.

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

An Open-Label Study of a Wearable Device Targeting ADHD, Executive Function, and Academic Performance.

OBJECTIVE: This was an open-label pilot study to test the feasibility and preliminary efficacy of a wearable digital intervention developed to improve on-task behavior. This was an exploratory study to test for specificity of response on parent- and teacher-reported symptom outcomes in attention and hyperactive/impulsive symptoms, as well as domains of functional impairment, including school behavior and learning and executive function. METHOD: Participants included 38 children aged 8-12 years with a parent-reported past diagnosis of ADHD. Following baseline ratings from parents (N = 38) and teachers (N = 26), participants wore the device to school for four weeks. Parent and teacher ratings of ADHD symptoms, executive function, and functional impairment were repeated at the end of the four-week intervention period. RESULTS: Statistically significant improvement was seen in the total scores for all parent and nearly all teacher outcomes, with moderate effect size improvements in attention, organization and planning, self-monitoring, school functioning, and teacher-reported academic performance. CONCLUSIONS: Preliminary evidence from this open-label pilot study suggests that having a child interact with a wearable device to self-monitor attention is feasible. This exploratory, open-label pilot study found real-world improvement in functional domains, including academic performance. Future research will require a blinded, randomized, controlled trial using an appropriate sham comparator to confirm these findings.

Receiver operating characteristic curve analysis of the Weiss Functional Impairment Rating Scale-Parent Report for screening children with ADHD: Looking beyond symptoms in ADHD diagnosis.

AIM: The current study aimed at examining the ability of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) to discriminate between children with ADHD and controls in functional impairment and identifying optimal cutoff scores for the WFIRS-P subscales and total scale. METHODS: Parents of 51 children with ADHD (90.2% male; grades 1-6) and 51 gender/grade matched controls (90.2% male; grades 1-6) completed the WFIRS-P. Receiver operating characteristic (ROC) curve analysis was used to examine the ability of the WFIRS-P to differentiate children with ADHD from controls and to determine optimal cutoff scores of the WFIRS-P. RESULTS: Area under the curve (AUC) was 0.98 for the WFIRS-P total scale, indicating excellent ability to differentiate children with ADHD from controls. The score of 0.45 with 0.88 for sensitivity and 0.96 for specificity was determined as the optimal cutoff score for the total scale of the WFIRS-P. AUC was 0.73 to 0.97 for the WFIRS-P subscales, suggesting good to excellent ability for discriminating between children with ADHD and controls. Among the subscales, the family subscale score of 0.42 with 0.92 for sensitivity and 0.96 for specificity showed the highest discriminating power. The self-concept and life skills subscales had low sensitivity, suggesting Iranian mothers do not identify problems with self-concept or difficulty with life skills as particularly problematic in ADHD. CONCLUSIONS: The WFIRS-P is a sensitive and specific measure of the functional impairment associated with ADHD in Iranian children. Our sample was predominantly male, limiting the generalizability of results to females.

Hormonal Injustice: Environmental Toxicants as Drivers of Endocrine Health Disparities.

The toll of multiple endocrine disorders has increased substantially in recent decades, and marginalized populations bear a disproportionate burden of disease. Because of the significant individual and societal impact of these conditions, it is essential to identify and address all modifiable risk factors contributing to these disparities. Abundant evidence now links endocrine dysfunction with exposure to endocrine-disrupting chemicals (EDCs), with greater exposures to multiple EDCs occurring among vulnerable groups, such as racial/ethnic minorities, those with low incomes, and others with high endocrine disease burdens. Identifying and eliminating EDC exposures is an essential step in achieving endocrine health equity.

Arsenic metabolism, diabetes prevalence, and insulin resistance among Mexican Americans: A mendelian randomization approach.

Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas. Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. To further assess mechanisms for diabetes pathogenesis, proportions of the urinary arsenic metabolites were employed to assess the association between arsenic metabolism and insulin resistance among participants without diabetes. Urinary biomarkers of arsenic metabolites were modeled as individual proportions of the total. Arsenic metabolism was evaluated both with a static outcome of insulin resistance, homeostatic measure of assessment (HOMA-IR), and a dynamic measure of insulin sensitivity, Matsuda Index. Results: Among 475 Mexican American participants from Starr County, higher metabolism capacity for arsenic is associated with higher diabetes prevalence driven by worse insulin resistance. Presence of the minor T allele of rs9527 is independently associated with an increase in the proportion of monomethylated arsenic (MMA%) and is associated with an odds ratio of 0.50 (95% CI: 0.24, 0.90) for type 2 diabetes. This association was conserved after potential covariate adjustment. Furthermore, among participants without type 2 diabetes, the highest quartile of MMA% was associated with 22% (95% CI: -33.5%, -9.07%) lower HOMA-IR and 56% (95% CI: 28.3%, 91.3%) higher Matsuda Index for insulin sensitivity. Conclusions: Arsenic metabolism capacity, indicated by a lower proportion of monomethylated arsenic, is associated with increased diabetes prevalence driven by an insulin resistant phenotype among Mexican Americans living in Starr County, Texas.

Transportation-related Environmental Mixtures and Diabetes Prevalence and Control in Urban/Metropolitan Counties in the United States.

Diabetes rates in the United States are staggering and climbing. Importantly, traditional risk factors fail to completely account for the magnitude of the diabetes epidemic. Environmental exposures, including urban and metropolitan transportation quality, are implicated as contributors to disease. Using data from the county-level Environmental Quality Index (EQI) developed for the United States, we analyzed associations between transportation and air quality environmental metrics with overall diabetes prevalence and control within urban/metropolitan counties in the United States from 2006 to 2012. Additionally, we examined effect modification by race/ethnicity through stratification based on the county-level proportion of minority residents. Last, we applied mixture methods to evaluate the effect of simultaneous poor transportation factors and worse air quality on the same outcomes. We found that increased county-level particulate matter air pollution and nitrogen dioxide along with reduced public transportation usage and lower walkability were all associated with increased diabetes prevalence. The minority proportion of the population influences some of these relationships as some of the effects of air pollution and the transportation-related environment are worse among counties with more minority residents. Furthermore, the transportation and air quality mixtures were found to be associated with increased diabetes prevalence and reduced diabetes control. These data further support the burgeoning evidence that poor environments amplify diabetes risk. Future cohort studies should explore the utility of environmental policies and urban planning as tools for improving metabolic health.

Metalloproteinase-9 in the ocular surface of patients with implanted Boston type 1 keratoprosthesis.

PURPOSE: To characterize the presence of ocular surface inflammation, using matrix metalloproteinase 9 (MMP-9) as a marker, in the ocular surface of eyes with implanted Boston Keratoprosthesis type 1 (KPro). METHODS: Patients with implanted KPro at a single tertiary center were recruited to assess ocular inflammation. MMP-9 was measured using InflammaDry® test in both eyes of each patient. The non-KPro eye served as control. Rate of positivity of MMP-9 was compared between groups. Possible associations between ocular surface inflammation and the development of postoperative complications were evaluated using univariate statistical analysis. RESULTS: Fifty eyes from 25 patients were included. The mean age was 50 years old. Non-inflammatory indications for KPro were predominant among patients. Eighty eight percent of KPro eyes had a positive test for MMP-9 while only 25% of control eyes were positive (p<001). The most common complications were retroprosthetic membrane, epithelial defects, and sterile corneal melt. The presence of a strong positive result was associated to a higher frequency of complications (80% of eyes) compared to a faint positive test (54%) and a negative test (33%). CONCLUSION: The KPro device appears to increase MMP-9 levels in the ocular surface. High MMP-9 levels may be associated with higher risk of complications. MMP-9 testing can be useful to assess subclinical ocular surface inflammation with a potential role in the postoperative care of KPro patients.

The Impact of School Closures on Service Utilization in School-Based Health Centers.

BACKGROUND: The pandemic was followed by a severe mental health crisis in youth with both an increase in the prevalence of mental health problems and a decrease in requests for and access to care. METHODS: data were extracted from the school-based health center records in three large public high schools that include under-resourced and immigrant communities. Data from 2018/2019 (pre-pandemic), 2020 during the pandemic, and then in 2021 after the return to in-person school were compared regarding the impact of in-person, telehealth, and hybrid care. RESULTS: Despite the increase in mental health needs globally, there was a dramatic decrease in referrals, evaluations, and the total number of students seen for behavioral health care. The time course of this decrease in care was specifically associated with the transition to telehealth, although treatment did not return to pre-pandemic levels, even after in-person care became available. CONCLUSIONS: Despite ease of access and increased need, these data suggest that telehealth has unique limitations when delivered in school-based health centers.

Editorial: Longitudinal Associations Between Sleep and ADHD Symptoms: ADHD Is a 24-Hour Disorder.

There is a robust literature of predominantly cross-sectional studies demonstrating an association between attention-deficit/hyperactivity disorder (ADHD) and sleep quality in childhood and adolescence, measured by subjective as well as objective measures, dimensional and categorical variables, and controlling for a wide range of confounders such as other disorders.1 Moreover, ADHD symptoms and sleep problems are independently associated with adverse functional outcome and quality of life.2 As a result, these are viewed as common and mutually exacerbating conditions, likely mediated by common neuropathways.3-5.

Relationships Between Urinary Metals and Diabetes Traits Among Mexican Americans in Starr County, Texas, USA.

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of diabetes and diabetes-associated mortality. We used multivariable linear regression to quantify the differences in homeostatic model assessments for pancreatic ß-cell function, insulin resistance, and insulin sensitivity (HOMA-ß, HOMA-IR, HOMA-S, respectively), plasma insulin, plasma glucose, and hemoglobin A1c (HbA1c) associated with increasing urinary metal concentrations. Quantile-based g-computation was utilized to assess mixture effects. After multivariable adjustment, urinary arsenic and molybdenum were associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels and higher HOMA-S. Additionally, higher urinary copper levels were associated with a reduced HOMA-ß. Lastly, a higher concentration of the 8 metal mixtures was associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels as well as higher HOMA-S. Our data indicate that arsenic, molybdenum, copper, and this metal mixture are associated with alterations in measures of glucose homeostasis among non-diabetics in Starr County. This study is one of the first to comprehensively evaluate associations of urinary metals with glycemic measures in a high-risk Mexican American population.

A Paradigm for Targeting Functional Impairment as an Outcome in Attention-Deficit/Hyperactivity Disorder.

Although functional impairment is required for a diagnosis in the DSM 5, the time frame and definition of functional impairment is ambiguous. We present a conceptual review clarifying the difference between functional impairment as a stable trait representing strength or disability in various domains, and functional impairment as secondary to emotional or behavior problems, which is a state sensitive to change with treatment intervention. Functional impairment as a measure of treatment outcome includes both change from baseline and status at the endpoint of treatment. When using a validated measure of function, functional improvement can be defined as the percentage of patients who achieve the Minimal Important Clinical Difference (MCID) and functional remission as the percentage of patients who normalize at treatment endpoint. True treatment remission should be defined as both symptomatic and functional remission.

Measurement Informed Care in Attention-Deficit/Hyperactivity Disorder (ADHD).

Measurement-informed care is a cornerstone of evidence-based practice and shared decision-making. A structured diagnostic interview specific to ADHD provides a globally agreed-on standard of evaluation. These interviews are accessible in the public domain in multiple languages and are helpful to clinicians new to the diagnosis of ADHD. Broad-based rating scales looking at multiple domains of psychopathology are critical to assuring recognition of comorbid diagnoses, which might otherwise be missed, differential diagnoses, and identification of the most prominent or treatable diagnosis. Recent innovations in computerized adaptive testing have improved the efficiency and accuracy of diagnostic screening. Rating scales specific to ADHD and disruptive behavior disorders establish the severity of the disorder and response to intervention. Age- and gender-normed symptom rating scales for ADHD capture clinically salient differences between what is normative in different demographic groups. An evaluation of functional impairment in ADHD has been critical to understanding the patient's perspective of the presenting problem. Best practice care for ADHD treatment goes beyond improvement to well-defined standards for both symptom and functional remission. Studies of executive function, emotional regulation, mind-wandering, and sluggish cognitive tempo have led to a richer understanding of the breadth and depth of associated deficits commonly experienced by ADHD patients. Psychometrically validated tools are available to complement every aspect of ADHD care and provide global standards for research.

Clinical and Socio-Demographic Variables Associated with the Diagnosis of Long COVID Syndrome in Youth: A Population-Based Study.

This study examines the demographic, clinical and socioeconomic factors associated with diagnosis of long COVID syndrome (LCS). Data of 20,601 COVID-19-positive children aged 5 to 18 years were collected between 2020 and 2021 in an Israeli database. Logistic regression analysis was used to evaluate the adjusted odds ratio for the characteristics of the COVID-19 infection and pre-COVID-19 morbidities. Children with LCS were significantly more likely to have been severely symptomatic, required hospitalization, and experienced recurrent acute infection within 180 days. In addition, children with LCS were significantly more likely to have had ADHD, chronic urticaria, and allergic rhinitis. Diagnosis of LCS is significantly associated with pre-COVID-19 ADHD diagnosis, suggesting clinicians treating ADHD children who become infected with COVID-19 remain vigilant for the possibility of LCS. Although the risk of severe COVID-19 infection and LCS in children is low, further research on possible morbidity related to LCS in children is needed.