Correction of Brassiere Strap Grooving with Injectable Poly-L-Lactic Acid in Plastic Surgery Resident Filler and Neuromodulator Clinic.

Poly-L-lactic acid (PLLA) is a biocompatible synthetic polymer that induces neocollagenesis by fibroblasts after placement into the reticular dermis and subcutaneous plane. We present an innovative use of this product to treat brassiere strap grooves. The size and weight of hypertrophied breasts can cause physical and psychological problems that can be corrected with reduction mammaplasty. However, bra strap grooving remains an unsightly consequence of brassiere use with large and heavy breasts. PLLA provides an innovative way to treat this deformity in a minimally invasive way, while maintaining relatively long-term results of two years or more. We studied 10 patients who presented to resident filler and neuromodulator clinic to help improve the bra strap groove deformity. The average number of clinic visits was 3.1. The average total number of vials injected was 2.58 on the right and 2.92 on the left. There were no complications or side effects, apart from one patient who reported injection site bruising. Patient surveys demonstrated 70% satisfied with the results and 30% very satisfied. We also discuss resident filler and neuromodulator clinic as an opportunity for resident research.

Targeting the 'DNA methylation mark': Analysis of early epigenetic-alterations in children chronically exposed to arsenic.

Chronic exposure to arsenic causes adverse health effects in children. Aberrant epigenetic modifications including altered DNA methylation pattern are one of the major steps towards malignant transformation of cells. Our group has previously identified significant alteration in DNA methylation mark in arsenic exposed adults, affecting major biological pathways. Till date, no information is available exploring the altered DNA methylation mark in telomere regulation and altered mitochondrial functionality in association with DNA damage in arsenic-exposed children. Our study aims in identifying signature epigenetic pattern associated with telomere lengthening, mitochondrial functionality and DNA damage repair in children with special emphasis on DNA methylation. Biological samples (blood and urine) and drinking water were collected from the children aged between 5 and 16 years of arsenic exposed areas (N = 52) of Murshidabad district and unexposed areas (N = 50) of East Midnapur districts, West Bengal, India. Methylation-specific PCR was performed to analyse subtelomeric methylation status and promoter methylation status of target genes. Results revealed altered DNA methylation profile in the exposed children compared to unexposed. Promoter hypermethylation was observed in MLH1 and MSH2 (p < 0.05 and p < 0.001) indicating inefficiency in DNA damage repair. Hypomethylation in mitochondrial D-loop (p < 0.05) and TFAM promoter region (p < 0.05) along with increased mitochondrial DNA copy number among exposed children was also observed. Significant increase in telomere length and region specific subtelomeric hypermethylation (XpYp, p < 0.05) was found. Analysis of S-Adenosyl Methionine (SAM) and 8-oxoDG level revealed significant depletion of SAM (p < 0.001) and elevated oxidative DNA damage (p < 0.001) respectively in arsenic toxicity. Our study identified key methylation patterns in arsenic-exposed children which may act as an early predictive biomarker in the near future. Further in-depth studies involving large sample size and transcriptomic analysis are required for understanding the mechanistic details.

Diminished Adaptation, Satisfaction, and Neural Responses to Advantageous Social Signals in Anorexia Nervosa and Bulimia Nervosa.

BACKGROUND: Development and recurrence of 2 eating disorders (EDs), anorexia nervosa and bulimia nervosa, are frequently associated with environmental stressors. Neurobehavioral responses to social learning signals were evaluated in both EDs. METHODS: Women with anorexia nervosa (n = 25), women with bulimia nervosa (n = 30), or healthy comparison women (n = 38) played a neuroeconomic game in which the norm shifted, generating social learning signals (norm prediction errors [NPEs]) during a functional magnetic resonance imaging scan. A Bayesian logistic regression model examined how the probability of offer acceptance depended on cohort, block, and NPEs. Rejection rates, emotion ratings, and neural responses to NPEs were compared across groups. RESULTS: Relative to the comparison group, both ED cohorts showed less adaptation (p = .028, ηp2 = 0.060), and advantageous signals (positive NPEs) led to higher rejection rates (p = .014, ηp2 = 0.077) and less positive emotion ratings (p = .004, ηp2 = 0.111). Advantageous signals increased neural activations in the orbitofrontal cortex for the comparison group but not for women with anorexia nervosa (p = .018, d = 0.655) or bulimia nervosa (p = .043, d = 0.527). More severe ED symptoms were associated with decreased activation of dorsomedial prefrontal cortex for advantageous signals. CONCLUSIONS: Diminished neural processing of advantageous social signals and impaired norm adaptation were observed in both anorexia nervosa and bulimia nervosa, while no differences were found for disadvantageous social signals. Development of neurocognitive interventions to increase responsivity to advantageous social signals could augment current treatments, potentially leading to improved clinical outcomes for EDs.

Perfluoroalkyl substances (PFAS) and lead (Pb) as "cardiovascular disruptors" in 9-11-year-old children living in Syracuse, New York, United States.

OBJECTIVE: Per- and polyfluoro-alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). METHODS: We assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9-11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). RESULTS: Significant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater "vascular reactivity" (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (ß = 0.21, p = 0.010). CONCLUSION: To our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as "cardiovascular disruptors" in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Race, cortisol, and subclinical cardiovascular disease in 9- to 11-year-old children.

BACKGROUND: Non-Hispanic Black Americans have a greater risk for certain subtypes of cardiovascular disease (CVD; e.g., stroke and heart failure) relative to non-Hispanic White Americans. Moreover, Black relative to White adults consistently show elevated cortisol, a CVD risk. The impact of race, environmental stress, and cortisol on subclinical CVD has yet to be fully researched in children. METHOD: We assessed diurnal salivary cortisol slopes and hair cortisol in a sample of 9- to 11-year-old children (N = 271; 54% female) with roughly half self-identifying as either Black (57%) or White (43%). Two subclinical CVD indicators were assessed: carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). We assessed numerous environmental stress indicators. RESULTS: After adjusting for covariates, we found that Black children had significantly flatter diurnal cortisol slopes, higher hair cortisol, and thicker IMT than White children. Significant pathways were found: race → salivary cortisol slope → cfPWV (effect = -0.059, 95% CI [-0.116, -0.002]) and race → hair cortisol → cIMT (effect = -0.008, [-0.016, -0.002]). Black children also experienced significantly more environmental stress than White children; however, only income inequality served as a significant indirect pathway from race to salivary cortisol (effect = 0.029, [0.003, 0.060]). CONCLUSIONS: Relative to White children, Black children had significantly greater hair cortisol and flatter diurnal slopes which, in turn, were associated with greater subclinical CVD. As suggested by a significant indirect pathway, income inequality might partially explain the race-cortisol association. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exposure to Arsenic and Subclinical Cardiovascular Disease in 9- to 11-Year-Old Children, Syracuse, New York.

Importance: Studies in adults have demonstrated associations between arsenic exposure and clinical and subclinical cardiovascular disease (CVD). No studies to date have considered potential associations in children. Objective: To examine the association between total urinary arsenic levels in children and subclinical indicators of CVD. Design, Setting, and Participants: This cross-sectional study considered 245 children, a subset from the Environmental Exposures and Child Health Outcomes (EECHO) cohort. Children from the Syracuse, New York, metropolitan area were recruited from August 1, 2013, until November 30, 2017, with enrollment throughout the year. Statistical analysis was performed from January 1, 2022, to February 28, 2023. Exposures: Total urinary arsenic was measured using inductively coupled plasma mass spectrometry. Creatinine concentration was used to adjust for urinary dilution. In addition, potential exposure routes (eg, diet) were measured. Main Outcomes and Measures: Three indicators of subclinical CVD were assessed: carotid-femoral pulse wave velocity, carotid intima media thickness, and echocardiographic measures of cardiac remodeling. Results: The study sample included 245 children aged 9 to 11 years (mean [SD] age, 10.52 [0.93] years; 133 [54.3%] female). The geometric mean of the creatinine-adjusted total arsenic level in the population was 7.76 µg/g creatinine. After adjustment for covariates, elevated total arsenic levels were associated with significantly greater carotid intima media thickness (ß = 0.21; 95% CI, 0.08-0.33; P = .001). In addition, echocardiography revealed that elevated total arsenic was significantly higher for children with concentric hypertrophy (indicated by greater left ventricular mass and greater relative wall thickness; geometric mean, 16.77 µg/g creatinine; 95% CI, 9.87-28.79 µg/g) relative to the reference group (geometric mean, 7.39 µg/g creatinine; 95% CI, 6.36-8.58 µg/g). With respect to exposure source, significant geographic clustering of total arsenic was found in 1 urban area of Syracuse, New York. Conclusions and Relevance: These findings suggest a significant association between arsenic exposure and subclinical CVD in children. Elevated total arsenic levels were found in an area of Syracuse with known elevations of toxic metals from industrial waste, suggesting historical pollution as a possible source. Given the novelty and potential importance of this association, further research is needed to confirm our findings. Any potential effect of urinary arsenic exposure in childhood on actual clinical CVD outcomes in adulthood remains to be determined.

Feasibility of remote self-collection of dried blood spots, hair, and nails among people with HIV with hazardous alcohol use.

BACKGROUND: The use of biomarkers in behavioral HIV research can help to address limitations of self-reported data. The COVID-19 pandemic forced many researchers to transition from standard in-person data collection to remote data collection. We present data on the feasibility of remote self-collection of dried blood spots (DBS), hair, and nails for the objective assessment of alcohol use, antiretroviral therapy adherence, and stress in a sample of people with HIV (PWH) who are hazardous drinkers. METHODS: Standardized operating procedures for remote self-collection of DBS, hair, and nails were developed for an ongoing pilot study of a transdiagnostic alcohol intervention for PWH. Prior to each study appointment, participants were mailed a kit containing materials for self-collection, instructions, a video link demonstrating the collection process, and a prepaid envelope for returning samples. RESULTS: A total of 133 remote study visits were completed. For DBS and nail collection at baseline, 87.5% and 83.3% of samples, respectively, were received by the research laboratory, of which 100% of samples were processed. Although hair samples were intended to be analyzed, most of the samples (77.7%) were insufficient or the scalp end of the hair was not marked. We, therefore, decided that hair collection was not feasible in the framework of this study. CONCLUSION: An increase in remote self-collection of biospecimens may significantly advance the field of HIV-related research, permitting the collection of specimens without resource-intensive laboratory personnel and facilities. Further research is needed on the factors that impeded participants' ability to complete remote biospecimen collection.

Airborne levels of cadmium are correlated with urinary cadmium concentrations among young children living in the New York state city of Syracuse, USA.

Air pollution is a serious public health issue with early childhood exposure being of high concern because of the greater risk that children might experience negative health outcomes. Industrial sources in and near communities are one potential path of exposure that children might face with greater levels of air pollution correlating with higher levels of toxicants detected in children. We compare estimated ambient air concentrations of Cadmium (Cd) to a cohort (n = 281) of 9 to 11-year old children during their early childhood years (0-5 years of age) in a mid-size city in Upstate New York. Levels of Cd air pollution are compared to children's urine-Cd levels. Urine has been shown to be a superior biomarker to blood for Cd exposure particularly for longer-term exposures. We find that participants who reside in households that faced greater Cd air pollution during the child's early years have higher urine-Cd levels. This association is stable and stronger than previously presented associations for blood-Cd. Findings support expanded use of air modelling data for risk screening to reduce the potential health burden that industrial pollution can have.

Twenty-Four-Hour Central Hemodynamic Load in Adults With and Without a History of COVID-19.

BACKGROUND: Although hypertension is a risk factor for severe Coronavirus Disease 2019 (COVID-19) illness, little is known about the effects of COVID-19 on blood pressure (BP). Central BP measures taken over a 24-hour period using ambulatory blood pressure monitoring (ABPM) adds prognostic value in assessing cardiovascular disease (CVD) risk compared with brachial BP measures from a single time point. We assessed CVD risk between adults with and without a history of COVID-19 via appraisal of 24-hour brachial and central hemodynamic load from ABPM. METHODS: Cross-sectional analysis was performed on 32 adults who tested positive for COVID-19 (29 ± 13 years, 22 females) and 43 controls (28 ± 12 years, 26 females). Measures of 24-hour hemodynamic load included brachial and central systolic and diastolic BP, pulse pressure, augmentation index (AIx), pulse wave velocity (PWV), nocturnal BP dipping, the ambulatory arterial stiffness index (AASI), and the blood pressure variability ratio (BPVR). RESULTS: Participants who tested positive for COVID-19 experienced 6 ± 4 COVID-19 symptoms, were studied 122 ± 123 days after testing positive, and had mild-to-moderate COVID-19 illness. The results from independent samples t-tests showed no significant differences in 24-hour, daytime, or nighttime measures of central or peripheral hemodynamic load across those with and without a history of COVID-19 (P > 0.05 for all). CONCLUSIONS: No differences in 24-hour brachial or central ABPM measures were detected between adults recovering from mild-to-moderate COVID-19 and controls without a history of COVID-19. Adults recovering from mild-to-moderate COVID-19 do not have increased 24-hour central hemodynamic load.

Physical activity is associated with lower pulsatile stress but not carotid stiffness in children.

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African-American, 42.10% Caucasian, body mass index (BMI) 20.1 ± 4.7 kg/m2) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery ß-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r = -0.27), and BMI (r = -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B = -1.3 [95%CI, -2.4, -0.2], ß = -0.20, p < 0.05) after covariate adjustment for age, race, sex, pubertal stage, and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r = 0.45, p < 0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children.

Validation of the novel transdermal arterial gasotransmitter sensor (TAGS™) system in measuring transdermal hydrogen sulfide in human subjects.

A novel non-invasive system has been developed to measure transdermally emitted hydrogen sulfide (H2S) from the upper and lower limbs of human subjects. The transdermal arterial gasotransmitter sensor (TAGS™) has previously been shown to detect low levels of H2S ranging between 1 and 100 ppb considered relevant for physiological measurements (Shekarriz et al. 2020). This study was designed to compare its measurement precision in detecting transdermal H2S to a commercially available chemiluminescent device, the H2S-selective Ecotech Serinus 55 TRS™. Although TAGS™ does in-situ and real-time sampling, the comparative studies in this paper collected gases emitted from the lower arm of 10 heathy human subjects between the ages of 30 and 60. Three replicate samples of each individual were collected for 30 min in a sealed 10 L Tedlar® bag to allow readings from the same sample by both devices. Readings from the TAGS™ system correlated strongly with the values obtained from the Serinus™ device, both ranging between 0.31 ppb/min and 2.21 ppb/min, with a correlation coefficient of R2 = 0.8691, p < 0.0001. These results indicate that TAGS™ measures transdermal H2S specifically and accurately. Because vascular endothelial cells are a known source of H2S, TAGS™ measurements may provide a non-invasive means of detecting endothelial dysfunction, the underlying cause of peripheral artery disease (PAD) and microvascular disease. TAGS™ has potential clinical applications such as monitoring skin vascular perfusion in individuals with suspected vascular disease or to monitor progression of wound healing during treatment, which is of particular value in diabetic patients with calcified arteries limiting detection options.

Structural brain differences in recovering and weight-recovered adult outpatient women with anorexia nervosa.

BACKGROUND: Anorexia nervosa is a complex psychiatric illness that includes severe low body weight with cognitive distortions and altered eating behaviors. Brain structures, including cortical thicknesses in many regions, are reduced in underweight patients who are acutely ill with anorexia nervosa. However, few studies have examined adult outpatients in the process of recovering from anorexia nervosa. Evaluating neurobiological problems at different physiological stages of anorexia nervosa may facilitate our understanding of the recovery process. METHODS: Magnetic resonance imaging (MRI) images from 37 partially weight-restored women with anorexia nervosa (pwAN), 32 women with a history of anorexia nervosa maintaining weight restoration (wrAN), and 41 healthy control women were analyzed using FreeSurfer. Group differences in brain structure, including cortical thickness, areas, and volumes, were compared using a series of factorial f-tests, including age as a covariate, and correcting for multiple comparisons with the False Discovery Rate method. RESULTS: The pwAN and wrAN cohorts differed from each other in body mass index, eating disorder symptoms, and social problem solving orientations, but not depression or self-esteem. Relative to the HC cohort, eight cortical thicknesses were thinner for the pwAN cohort; these regions were predominately right-sided and in the cingulate and frontal lobe. One of these regions, the right pars orbitalis, was also thinner for the wrAN cohort. One region, the right parahippocampal gyrus, was thicker in the pwAN cohort. One volume, the right cerebellar white matter, was reduced in the pwAN cohort. There were no differences in global white matter, gray matter, or subcortical volumes across the cohorts. CONCLUSIONS: Many regional structural differences were observed in the pwAN cohort with minimal differences in the wrAN cohort. These data support a treatment focus on achieving and sustaining full weight restoration to mitigate possible neurobiological sequela of AN. In addition, the regions showing cortical thinning are similar to structural changes reported elsewhere for suicide attempts, anxiety disorders, and autistic spectrum disorder. Understanding how brain structure and function are related to clinical symptoms expressed during the course of recovering from AN is needed.

Anorexia nervosa is a life-threatening mental illness defined in part by an inability to maintain a body weight in the normal range. Malnutrition and low weight are factors typically present in the anorexia nervosa and can affect brain structure. We conducted a detailed analysis of brain structure using Freesurfer, focusing on regional cortical thicknesses, areas, and volumes, in adult outpatient women with anorexia nervosa. The study included both a partially weight-restored cohort with anorexia nervosa, a cohort sustaining a healthy body weight with history of anorexia nervosa, and a healthy comparison cohort. Reduced cortical thicknesses were observed in eight regions, primarily in the frontal lobe and cingulate for the cohort recently with anorexia nervosa but only one frontal region in the weight-maintained cohort. These data emphasize the importance of sustained weight-restoration for adult women with anorexia nervosa. Further, the impacted neural regions have been associated with impulsivity, attention, self-regulation, and social interactions in other clinical cohorts, suggesting that these neuropsychological processes may warrant study in patients recovering from anorexia nervosa. Future work should consider whether these factors have clinical relevance in the outpatient treatment of adults with anorexia nervosa.

Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective.

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-ß. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND AND OBJECTIVES: Approximately 10 years ago, "bath salts" became popular as legal alternatives to the psychostimulants cocaine and the amphetamines. These products contained synthetic cathinones, including 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). Most preclinical investigations have only assessed the effects of these synthetic cathinones independently; however, case reports and Drug Enforcement Administration (DEA) studies indicate that bath salts contain mixtures of these substances. In this study, we examine the pharmacokinetic interactions of the drug combination. We hypothesized that combined exposure to MDPV, mephedrone, and methylone would result in increased drug concentrations and enhanced total drug concentrations when compared to individual administration. METHODS: Adolescent male Swiss-Webster mice were injected intraperitoneally with either 10 mg/kg MDPV, 10 mg/kg mephedrone, 10 mg/kg methylone, or 10 mg/kg combined MDPV, mephedrone, and methylone. Following injection, brains and plasma were collected at 1, 10, 15, 30, 60, and 120 min. Drugs were extracted via solid-phase extraction, and concentrations were determined using a previously published high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. RESULTS: All drugs crossed the blood-brain barrier quickly. For methylone, the maximal concentration (Cmax) and the total drug exposure [as represented by the area under the concentration-time curve (AUC)] were significantly higher when combined with mephedrone and MDPV in both matrices (2.89-fold increase for both Cmax and AUC with combined treatment). For mephedrone, the Cmax was unchanged, but the AUC in brain was increased when in combination by approximately 34%. Interestingly, for MDPV, the Cmax was unchanged, yet the AUC was higher when MDPV was administered individually (there was a 62% decrease in AUC with combined treatment). CONCLUSIONS: The pharmacokinetics of methylone, mepedrone, and MDPV are altered when the drugs are used in combination. These data provide insight into the consequences of co-exposure to synthetic cathinones in popular bath salt products.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Effect of Chronic Methylphenidate Treatment in a Female Experimental Model of Parkinsonism.

Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD in males and females. However, a majority of previous studies investigated the effect of MPH in only males, and little is known regarding consequences of female exposure to MPH. This is unfortunate because the few studies that have been conducted indicate that females have a greater sensitivity to MPH. Previous research in male mice has shown that chronic exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, estrogen has been shown to protect dopaminergic neurons from MPTP neurotoxicity. Therefore, in this study, we test the hypothesis that chronic MPH exposure in female mice will render dopaminergic neurons in the nigrostriatal pathway more sensitive to MPTP, and that estrogen may play a protective role. Interestingly, proestrus females exhibited greater sensitivity to MPTP, with significantly reduced dopaminergic neurons in the SN and significant increases in DA quinone production. Chronic MPH exposure contributed to GSH depletion, but surprisingly, it did not increase dopamine quinone levels or dopaminergic cell loss. There were no significant differences in anestrus animals, with the exception of a depletion in GSH seen when animals received chronic high-dose (10 mg/kg) MPH followed by MPTP. Thus, estrogen may actually sensitize neurons to MPTP in this model, and chronic MPH may contribute to GSH depletion within the striatum. This study provides insight into how chronic psychostimulant use may affect males and females differently.

Association of Sleep Quality With Greater Left Ventricular Mass in Children Aged 9 to 11 Years.

OBJECTIVE: Research has consistently found associations between sleep characteristics and cardiovascular disease risk in children, adolescents, and adults. Although primarily investigated in clinical samples (e.g., in those with sleep disorders), greater left ventricular mass is associated with poor sleep quality in nonclinical adult populations as well; however, this has not been evaluated in children or adolescents. Our study aim was to consider the relationship between objectively measured sleep characteristics and left ventricular mass in children. METHODS: We assessed sleep and cardiac structure in a biracial sample of 9- to 11-year-old children (n = 176; 41% White, 59% Black; 50% female). Sleep was assessed with actigraphy for five nights. Cardiac dimensions were assessed using echocardiography. RESULTS: After adjusting for covariates, we found that poor sleep quality was associated with significantly greater left ventricular mass (ß = 0.13, t(167) = 2.14, p = .034, Cohen d = 0.16, for activity during sleep; ß = 0.15, t(167) = 2.43, p = .016, Cohen d = 0.18, for sleep fragmentation). Other cardiac dimensions (namely, relative wall thickness and right ventricular dimension) were also significantly associated with sleep characteristics. Notably, associations did not differ as a function of sex or race. CONCLUSIONS: The present findings are novel and unique because no prior reports have systematically documented the association between poor sleep quality with potentially detrimental cardiac remodeling in a nonclinical sample of children. However, the novelty and importance of these findings require additional research for confirmation.

Seroprevalence of hepatitis E virus antibodies in adults and children from upstate New York: A cross-sectional study.

Hepatitis E virus (HEV) is a major cause of viral hepatitis around the world, especially in developing countries. Recently, HEV has also been recognized as important cause of hepatitis in Europe and Japan, however, there is a paucity of clinical data from the United States. The overall seroprevalence of HEV antibodies is around 10% in the United States, but considerable variation is seen based on geographic location, year, and assay used. In this study, 63 adults and 417 children from New York State were tested for anti-HEV IgG antibodies using the commercially available Wantai IgG assay. The overall seroprevalence of HEV antibodies among adult participants was 9.52% (95% CI: 3.58-19.59%). Positive adults tended to be older than HEV negative adults, all positive adults were female. Only 3 (0.7%, 95% CI:: 0.15-2.09%) of the children were positive, all positive children were male. These results are consistent with global and United States trends in HEV seroprevalence.