Adult Exposure Research Articles

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 μg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 μg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Chronic, episodic nicotine exposure enhances the hypoxic ventilatory response in adult female rats

It is well known that cigarette smoking causes lung disease and damages the airways. However, we know little about the direct role of nicotine, the primary addictive component of tobacco, in the development of smoking- related diseases. Along with promoting cancer cell proliferation and airway inflammation, nicotine can modulate central respiratory control, increasing the rate and depth of breathing through mechanisms that are not well understood. In addition, cigarette smoking is associated with obstructive sleep apnea, a sleep-related breathing disorder that is marked by reduced brainstem respiratory motor output. Despite these examples indicating that chronic nicotine exposure in adulthood may alter central respiratory control, there is no published research that directly tests this hypothesis. We exposed male and female adult rats to nicotine for four weeks through their drinking water and then used whole body plethysmography to test the hypothesis that chronic, episodic nicotine exposure alters restful breathing and the hypoxic ventilatory response (HVR), a critical respiratory chemoreflex. We measured tidal volume (TV) and frequency of breathing at rest, and during a 5- minute episode of hypoxia (10% oxygen/balance nitrogen). Total ventilation (VE/VCO2) was calculated as TV X Frequency and normalized to carbon dioxide production, to account for changes in metabolism, and body weight. For both males and females, comparisons were made between groups and across trials using a 2-way ANOVA and Tukey’s post-hoc test. In male rats, nicotine exposure significantly decreased overall ventilation at rest in one of three trials (Trial 1 VE/VCO2: Nicotine exposed, 30.7±7.5 mL/min/100g, Control, 44.3±6.4 mL/min/100g, p=0.0183), but had no effect on breathing during hypoxia. In female rats, nicotine exposure had no effect on breathing at rest, however, overall ventilation during hypoxia was enhanced in nicotine exposed rats compared to controls in two of three trials (Trial 1 VE/VCO2: Nicotine exposed, 106.8±20.6 mL/min/100g, Control, 79.8±5.1 mL/min/100g, p=0.049; Trial 3 VE/VCO2: Nicotine exposed, 101.6±9.9 mL/min/100g, Control, 68.1±10.9 mL/min/100g, p=0.007). Overall, these results suggest that chronic nicotine exposure triggers plasticity in the chemoreflex pathway mediating the HVR in a sex specific manner and further studies are warranted to understand the implications of this finding. 1K99HL164973-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Poor Sleep Quality Contributes to Vascular Endothelial Dysfunction in Young Adults with Adverse Childhood Experiences

Introduction: Adverse childhood experiences (ACEs) represent severe psychosocial stressors during the first 18 years of life that promote a dose-dependent, lifetime increase in cardiovascular disease risk. ACEs have been associated with impaired vascular endothelial function and poor sleep quality in young adults. However, whether poor sleep quality influences the association between ACEs and vascular endothelial function is unclear. We hypothesized that sleep quality would mediate the association of ACE exposure with impaired vascular function. Purpose: To examine the contribution of sleep quality to ACEs-related impairments in vascular endothelial function in young adults. Methods: We used a cross-sectional cohort study (Study 1) and a single-arm intervention (Study 2) to test our hypothesis. Sleep quality was characterized as sleep effciency (SE%) and calculated as total sleep duration relative to time-in-bed. Vascular endothelial function was assessed using the brachial artery flow mediated dilation technique (FMD). In Study 1, we examined the mediation effect of SE% in the association of ACE exposure with FMD in a cohort of young adults (n=56; age = 25 ± 5 y, BMI = 26 ± 5 kg/m2) using the bootstrapped (1,000 replications) bias-corrected percentile confidence interval method adjusted for sex, and depression and anxiety symptomology. The variance accounted for (VAF) was calculated as the ratio of the indirect effect to total effect β-coeffcients. In Study 2, with a separate sample (n=12; age = 21 ± 2 y, BMI = 23 ± 4 kg/m2) of young adults with high ACE exposure (5 ± 2 ACEs) and poor sleep quality (SE ≤ 90%), we manipulated SE% using 6-weeks of cognitive-behavioral therapy for insomnia (CBTi) and measured FMD before (PRE) and after (POST) the intervention. Change in weekly SE% from daily consensus sleep diary entries was analyzed using a one-way ANOVA with Tukey post hoc comparisons. PRE to POST change in FMD was analyzed with a paired samples t-test. The association between the change (Δ; POST-PRE) in SE% and FMD was examined using a Spearman’s correlation coeffcient (ρ). Results: In Study 1, SE% significantly, partially mediated the association between ACE exposure and FMD (indirect effect standardized β-estimate = -0.11 [95% CI = -0.29 – -0.02]; VAF = 27.4%). In Study 2, there was a treatment effect of CBTi on SE% ( p < 0.001) where SE% improved from baseline to weeks 3, 4, 5, and 6 (weekly improvement range = 8.8 – 10.1%; all p ≤ 0.002). FMD increased PRE to POST (2.85 ± 0.58 to 3.65 ± 1.0 %/SR AUC·104; p = 0.017). There was a moderate, non-significant association between ΔSE% and ΔFMD (ρ = 0.46, p = 0.13). Conclusions: Our findings provide initial evidence that poor sleep quality may contribute to the previously described impairment in vascular endothelial dysfunction observed with increasing ACE exposure in young adults. Funding provided by a grant from the Injury Prevention Research Center through the CDC (R49 CE003095; NDMJ). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Muscle Sympathetic Action Potential Firing Patterns Following Intranasal Insulin Administration in Healthy Adults

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) in healthy adults by augmenting firing frequency of medium-sized sympathetic action potentials (AP) and recruiting previously latent, larger axons. Whether these neural coding patterns are due to central or peripheral effects of insulin is unclear. We examined the impact of elevated central insulin on AP firing patterns in healthy adults. We hypothesized intranasal insulin administration, which increases central insulin levels, would increase MSNA via elevated firing frequency of APs and recruitment of previously latent, larger axons. Methods: Ten participants were assigned to time control [TC, n=6 (3M/3F)] or 160 IU of intranasal insulin [n=4 (3M/1F)] administered over 5 min. MSNA (fibular microneurography) was assessed at baseline and for 30 min following insulin administration. Sympathetic APs were identified using a matched mother wavelet and continuous wavelet transform. APs were divided into the proportion of those firing in small, medium, or large amplitude clusters. AP firing frequency, percent of APs firing within an MSNA burst (synchronous), and the probability of clusters firing more than once within an MSNA burst were identified. Data are reported as median (interquartile range). Results: MSNA burst frequency increased 15 min after intranasal insulin administration [24(20) to 31(23) bursts/min, p=0.03]. At this time, the percent of synchronous APs [72(27) to 90(24)%, p=0.02] and the probability of medium-sized AP clusters firing more than once within an MSNA burst [13(14) to 19(17)%, p=0.03] increased. No changes in MSNA burst frequency [23(14) to 25(13) bursts/min, p=0.27], percent of synchronous APs [74(15) to 75(34), p=0.48], nor firing probability of medium-sized AP clusters [6(12) to 8(7)%, p=0.97] occurred in TC. The total number of detected clusters did not change in either group (p>0.05). Conclusions: Intranasal insulin increases MSNA burst frequency due to a higher percent of synchronous APs, particularly medium-sized AP clusters; however, we did not observe recruitment of latent, larger axons. These exploratory data highlight potential differences in the sympathetic response to central versus peripheral insulin exposure in healthy adults. CAFNR Joy of Discovery (JKL, JP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of home-based heat therapy on thermal and cardiovascular strain during passive heat exposure in older adults

Heat waves are occurring more frequently and with greater intensity. In fact, 2023 marked the hottest summer ever recorded in the Northern Hemisphere. Heat waves increase the risk for heat-related morbidity and mortality, particularly for older adults who have a reduced ability to dissipate heat. Heat acclimation induces physiological adaptations that attenuate thermal and cardiovascular strain during subsequent heat exposures. However, traditional heat acclimation protocols require expensive equipment (e.g., climate chamber) and may be challenging for older adults with limited functional capacity. Home-based heat therapy provides a potentially safe and pragmatic option to induce heat acclimation. The purpose of this pilot study was to test the hypothesis that home-based heat therapy reduces thermal and cardiovascular strain in older adults during acute passive heat exposure. Six older adults (5 women; 67 ± 4 years) performed 8 weeks of home-based heat therapy by immersing their lower legs ~33 cm into a heated (~ 42°C) and circulated water bath 4 days per week, for 45 min per session. Intestinal temperature (telemetric pill) and heart rate were assessed before (pre) and after (post) the intervention during acute heat exposure (45 min lower leg water immersion). In addition, rate pressure product, an estimate of myocardial demand, was calculated as heart rate x systolic blood pressure. Resting intestinal temperature, heart rate, and rate pressure product did not differ from pre to post heat therapy (all P ≥ 0.6). However, the change in intestinal temperature during acute heat exposure was reduced after heat therapy (15 min: pre, Δ0.47 ± 0.17 °C vs. post, Δ0.33 ± 0.14 °C; 30 min: pre, Δ0.84 ± 0.29 °C vs. post, Δ0.72 ± 0.23 °C; 45 min: pre, Δ1.10 ± 0.27 °C vs. post, Δ1.07 ± 0.24 °C; P = 0.03 for main effect of time). Likewise, the change in heart rate was attenuated following the intervention (15 min: pre, Δ14 ± 9 bpm vs. post, Δ10 ± 5 bpm; 30 min: pre, Δ22 ± 13 bpm vs. post, Δ17 ± 6 bpm; 45 min: pre, Δ25 ± 9 bpm vs. post, Δ21 ± 6 bpm; P = 0.02 for main effect of time). Rate pressure product was also reduced following heat therapy (15 min: pre, Δ1280 ± 1636 bpm·mmHg vs. post, Δ322 ± 698 bpm·mmHg; 30 min: pre, Δ1800 ± 1573 bpm·mmHg vs. post, Δ1170 ± 450 bpm·mmHg; 45 min: pre, Δ2145 ± 593 bpm·mmHg vs. post, Δ840 ± 602 bpm·mmHg; P < 0.01 for main effect of time). Our preliminary data suggest that 8 weeks of home-based heat therapy elicits some adaptations that may reflect heat acclimation. However, further work is needed to confirm these initial findings. American Heart Association TPA958179. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Early life exposure to Candida albicans disrupts regulatory T cells

Abstract Fungal species are immunogenic members of the commensal microbiota, on the skin and the intestine. Opportunistic Candida albicans is associated with numerous allergic disorders, like atopic dermatitis, with ~90% of cases diagnosed by age 6. With an increased lifetime risk to other allergic disorders, C. albicans exposure in early life may contribute to the development of allergic-type responses. Premature infant stool sequencing found frequent C. albicans colonization suggesting colonization in the human GI tract. Previous observations found mice exposed to C. albicans prior to, but not post, weaning maintain colonization into adulthood. Neonatal colonization of C. albicans in the intestine, resulted in long term colonization and presented significantly decreased FoxP3+ T regulatory cells (Tregs) post-weaning in the mesenteric lymph nodes, small intestine, and colon lamina propria (LP). Additionally, RORγt+ and C-MAF+ Th17-cells were increased in the LP. By comparison, adult exposure to C. albicans through the skin or intestine, showed no disruption of FoxP3+ Tregs, suggesting neonatal exposure to C. albicans may be more disruptive to developing Tregs. Future research will focus on the impact of C. albicans presence to early microbiota complexity and diversity development. Treg establishment in early life is vital for tolerance and maintenance of commensal organisms, thus Treg disruption potentially links C. albicans colonization towards the development of allergic responses.

Assessment of Societal Health Risks: Spatial Distribution and Potential Hazards of Toxic Metals in Street Dust Across Diverse Communities

On a global scale, the urban design of city centers is a topic of discussion concerning various aspects such development and its impact on public health. This research examines the health effects of urban agglomeration in city centers with compact, close development. In this work, the potentially toxic metals in street dust were studied by collecting and measuring street dust samples, measuring trace metal concentrations, and using index assessment, spatial analysis, correlation analysis, and health risk assessment models. Eskişehir, located in the part of Central Anatolia close to the Aegean region, west Türkiye, has been widely recognized as one of the most popular, known for having many narrow and old buildings in urban environments. The present paper investigates the atmospheric dust-related chemical speciation, urban environmental pollution, and human health risks in Eskişehir City by studying 66 dust samples collected at 11 points in the selected streets in August 2023. the study found that the concentrations of trace elements followed the order Cr > Ni > Pb > Cd > Cu. The primary source of these high levels is believed to be traffic-related contamination involving Cd, Pb, and Ni. The assessment of non-carcinogenic health risks has shown that the significant sources of potential toxic metals exposure for both children and adults are i) through ingestion and ii) dermal contact. The Hazard index (HI) for selected metals decreased in the order Cr > Pb > Ni > Cd > Cu for both children and adults without imposing possible non-carcinogenic risk (HI<1). On the contrary, Cr posed cancer risks above the safety threshold (> 10-4) through ingestion. Based on the available findings, Eskişehir still suffers from considerable environmental and ecological degradation and severe health risks due to street dust contamination. However, while high pollution was detected in the city center, where there is commercial land use, low values were observed in the region, rich with the water surface, bicycle paths, landscape design, and where traffic is slowed down.

The Effects of Psychosocial and Traumatic Stressors on MCI Diagnosis

Background and Objective: Toxic stress exposure can have effects across the lifespan. Studies of civilians and veterans suggest a connection between psychosocial and traumatic stressor exposure in adulthood and a diagnosis of dementia later in life. The objective of this study was to investigate the impact of psychosocial and traumatic stressors on rates of MCI (Mild Cognitive Impairment) diagnosis in Vietnam Era Twin Study of Aging participants. Methods: 1,237 twin participants from the VETSA study were aged 61.72 ± 2.44 years at the time of data collection. Traumatic stress was measured by clinical interviewing, with psychosocial stressors quantified by self-report measures. Neuropsychological assessment determined MCI diagnosis. Previously conducted genotyping determined ApoE genotype. Mixed model analysis was used to determine effects on MCI diagnosis. Results: Our results from the mixed model analysis did not find a significant relationship between psychosocial and traumatic stress exposure and MCI diagnosis. PTSD diagnosis, measured by the DIS-III-R, collected for the Harvard Drug Study in 1996 (F = 0.249, p = 0.618) does not have a significant effect on MCI diagnosis. Life stress exposure, measured by the Holmes and Rahe (1967), (F = 0.249, p = 0.618) does not have a significant effect on MCI diagnosis. Significant associations were determined using the Type III fixed effects. Associations were considered statistically significant at p &lt; 0.05, two-tailed. Implications: Few subjects in Wave 2 of VETSA had MCI (n = 147), due in part to the age of the participants at the time (Mean 61.72 ± (2.44 years)). This led to a lack of power in our analysis. Future studies should examine all available VETSA data.

The association between short-term ozone exposure and fasting blood glucose levels in non-diabetic adults was more obvious in rural residents: the evidence from a typical “urban–rural dual structure” province in southwestern China

The association between short-term ozone exposure and fasting blood glucose levels in non-diabetic adults was more obvious in rural residents: the evidence from a typical “urban–rural dual structure” province in southwestern China

Aflatoxin M1 Exposure and Health Risk Assessment in Children and Adults due to Pasteurized Milk Consumption in Addis Ababa, Ethiopia

Milk and dairy products stand as essential sources of nutrition across all age groups. However, the presence of Aflatoxin M1, particularly common and risky for young children, necessitates careful assessment of milk. This study, conducted in Addis Ababa, Ethiopia, aimed to evaluate the prevalence of Aflatoxin M1 using High-Performance Liquid Chromatography in pasteurized milk and assess associated health risks using deterministic techniques. The prevalence of Aflatoxin M1 in pasteurized milk was 56.6%, with Aflatoxin M1 levels ranging from 0 to 6.27 μg/L and a mean value of 1.237 μg/L. The risk assessment revealed substantial Aflatoxin M1 exposure risk from pasteurized milk consumption, as reflected by margin of exposure values &lt;10,000, specifically 25.9, 109.6, and 380 for children aged 2–5, 6–9, and adults, respectively. The hazard index values for pasteurized milk consumers were 110, 26, and 7.5 for children aged 2–5, 6–9, and adults, respectively. Furthermore, cancer risk calculations yielded values of 0.18, 0.04, and 0.01 per 100,000 population for children aged 2–5, 6–9, and adults, respectively, with an average potency of 0.007978 cases per 100,000/yr ng Aflatoxin M1/kg bw/day. Notably, children aged 2–5 and 6–7 face elevated risks, whereas adults face relatively lower risks.

Health and ecological risk assessment of heavy metals in water and sediments within a data scarce urban catchment in Tanzania – A case of Ngerengere River, Morogoro Municipality

Low-, middle- and high-income countries, exhibit indications of risks associated with water quality. The study investigated heavy metal concentrations in surface water and sediments within the Ngerengere River and its tributaries (Kikundi, Bigwa, and Morogoro) drain within in the Morogoro Municipality of Tanzania, an Urban Catchment Area (UCA) with limited available data mainly because of inadequate monitoring and reporting capabilities. Analysis of health and ecological risks associated with heavy metal pollution was also carried out using health risk assessments models, pollution indices, and multivariate analysis techniques. Between the dry and wet seasons of 2023, water and sediment samples from (13) sampling stations strategically established along the Ngerengere river and its tributaries were analyzed for six heavy metals (Pb, Cr, Ni, Cd, Cu and Zn) using the Atomic Absorption Spectrophotometer Model Perking Elmer 850 Graphite Furnace and Perking Elmer AS 800 Auto-sampler coupled with a computer interface for operational, displaying and reading the results. The calculated degree of water contamination (Cd) values in river water in both dry and wet seasons ranged from 0 to 6.803 indicating low and high degrees of contamination respectively. Heavy metal concentration in sediment decreases in the order of Zn&gt;Ni&gt;Cr&gt;Cu&gt;Cd&gt;Pb. The non-cancer risk index (HI) via ingestion and dermal pathways in dry and wet seasons for both children and adult groups was &lt;1 hence no non-cancer risk, However, cumulative dermal and ingestion exposure in both children and adults indicated potential cancer risk in dry and wet season. The analysis of ecological risks associated with heavy metal enrichment in the sediment indicated high enrichment of sediments with Cd, Ni and Zn. Conclusively, in wet months, risk indices tend to be low, while in dry months, they typically remain high.

Emerging nitrate contamination in groundwater: Changing phase in a fast-growing state of India

The consumption of nitrate-contaminated groundwater is often associated with potential health risks, particularly in children. This study aimed to assess the hydrochemistry and nitrate contamination in groundwater of Kerala state, India for the years 2010 and 2018 and evaluate the potential human health risks due to nitrate exposure in adults, and children through oral ingestion and dermal contact pathways. Nitrate-contaminated zones were identified by spatial mapping of nitrate concentration based on groundwater quality data of 324 wells. Groundwater is typically acidic to slightly alkaline, and the electrical conductivity (EC) varied from 33 to 1180 μS/cm in 2010 and 34.6–2500 mg/L in 2018 indicating a noticeable increase over the years. Most samples fall within low salt enrichment category. The nitrate concentration in groundwater varied from 0 to 173 mg/L with a mean of 15.4 mg/L during 2010 and 0 to 244 with a mean of 20.3 mg/L during 2018. Though nitrate concentrations show uneven spatial distributions due to both natural and anthropogenic sources, the spatial clustering of higher concentrations remains almost same in both periods. In 2010, non-carcinogenic risk, as measured by Health Index Total (HITotal) values in groundwater for the investigated region, ranged from 0.005 to 4.170 (mean of 0.349) for males, 0.005 to 4.928 (mean of 0.413) for females, and 0.008 to 7.243 (mean of 0.607) for children, while in 2018, the corresponding values varied from 0.001 to 5.881 (mean of 0.501) for males, 0.002 to 6.950 (mean of 0.592) for females, and 0.003 to 10.215 (mean of 0.870) for children, indicating a substantial increase in risk, for females and children. Greater health risk is observed in children during both the periods. The findings emphasize the need for proper water quality management, especially in regions with higher vulnerability to nitrate pollution, to safeguard human health and well-being.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

Exposure assessment and risk characterisation of aflatoxins in randomly collected rice samples from local markets of Hyderabad, India

Aflatoxin (AF) poisoning of staple foods, such as rice, is caused by fungal contamination by Aspergillus species. These AFs are genotoxic, carcinogenic and suppress the immune system. Hence, the present study was conducted to elucidate the prevalence of AF contamination in rice samples collected from local markets of Hyderabad, Telangana, India. The rice samples collected were analysed for AF by using HPLC-fluorescence detection (HPLC-FLD). Based on AF contamination levels and dietary intake of rice, the health risk was assessed by the margin of exposure (MOE) and liver cancer risk in adults, adolescence and children. The percentage detected contamination with AFB1 and AFB2 of rice samples was 54% and 34%, with the concentration ranging between 0–20.35 µg/kg and 0–1.54 µg/kg, respectively. Three rice samples exceeded the Food Safety and Standards Authority of India (FSSAI) total AF acceptable limit of 15 µg/kg. The average MOE values were 53.73, 50.58 and 35.69 (all <10,000) for adults, adolescence and children, respectively. The average liver cancer risk associated with rice consumption in the population of Hyderabad was found to be 0.27, 0.28 and 0.40 hepatocellular carcinoma (HCC) cases/year/100,000 individuals in adults, adolescence and children, respectively. This study revealed an adverse health risk to population of Hyderabad due to consumption of AF contaminated rice.

Exercise attenuates the association between pyrethroid exposure and sleep disorders in male adults

BackgroundPyrethroids are widely used in agriculture and household pest management as one of the top three insecticides globally, yet the neurobehavioral impacts of human exposure to these chemicals have attracted increasing concern. ObjectiveThe purpose of this study was to examine the associations between pyrethroid exposure and sleep disorders and whether exercise could attenuate these associations. MethodsWe analyzed cross-sectional data from the 2007-2014 National Health and Nutrition Examination Survey to study the association between pyrethroid pesticide exposure and sleep disorders. The exposure level of pyrethroid metabolites in urine samples was measured. Physician diagnosis of sleep disorders was used to determine sleep disorders. Exercise level was judged by self-reported physical activity from the interviews. ResultsOf the 5947 participants, sleep disorders had a weighted prevalence of 9.0 %, representing an approximation of 186,140,757 patients nationwide. We found a sex-specific association between high levels of 3-PBA and elevated risk of sleep disorders diagnosis in men (OR: 1.87; 95 % CI: 1.150–3.042; P = 0.01). In addition, less physical activity was associated with higher rates of sleep disorders as pyrethroid exposure levels increased (OR: 1.98; 95 % CI: 1.152–3.388; P = 0.02). ConclusionThis study further confirmed that pyrethroid exposure is associated with an elevated risk of sleep disorders in men. More importantly, we reported for the first time that vigorous physical activity attenuates the correlation between pyrethroid exposure and sleep disorders.

Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma

BackgroundChildhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. MethodsTwo weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. ResultsChildhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013–0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. ConclusionsAmygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Effect of loperamide on heart rhythm: Randomized, double-blind, controlled study in healthy adults

BackgroundExcessively high doses of loperamide (of up to 792 mg/day) have recently been associated with reports of cardiac events. However, no data currently demonstrate a direct effect of high doses of loperamide on the occurrence of cardiovascular abnormalities. ObjectivesThis study aimed to assess the effects of loperamide on QT/corrected QT (QTc) intervals, electrocardiogram (ECG) morphology, and overall safety and tolerability at therapeutic and supratherapeutic exposures in healthy adults. MethodsThis randomized, double-blind, 4-way-crossover study enrolled 65 healthy adults to receive loperamide 8 mg (therapeutic dose), loperamide 48 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), and placebo. Least square (LS) mean difference in change from baseline in Fridericia-corrected QT (ΔQTcF) intervals between loperamide (8 mg and 48 mg) and placebo with the 2-sided 90% CI was calculated for each time point. A noninferiority criterion of mean difference in ΔQTcF of 10 ms evaluated whether loperamide was noninferior to placebo. Treatment safety was assessed throughout the study. ResultsMost participants were female (66.2%) and white (95.4%). The age was 36.4 years (SD 9.77). The highest upper limit of the 2-sided 90% CI for LS mean difference in ΔQTcF between loperamide and placebo was 3.39 ms for the therapeutic dose and 9.28 ms for the supratherapeutic dose of loperamide, which were below the 10 ms threshold, thereby demonstrating noninferiority of loperamide to placebo. There were no statistically significant morphologic ECG changes after loperamide administration. There were no deaths, serious adverse events, or severe treatment-emergent adverse events. ConclusionSingle-dose loperamide at therapeutic (8 mg) and supratherapeutic (48 mg) doses do not show evidence of QTc prolongation of clinical concern in healthy participants. No new safety findings were identified.

Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis

BackgroundIvacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF. MethodsIn this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight. Because IVA is a sensitive CYP3A substrate and CYP3A maturation is uncertain in infants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements. ResultsSeven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (−40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed. ConclusionsIn this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.

Ecological momentary assessment of digital food and beverage marketing exposure and impact in young adults: A feasibility study

Unhealthy food marketing is contributing to the obesity epidemic, but real-time insights into the mechanisms of this relationship are under-studied. Digital marketing is growing and following food and beverage (F&B) brands on social media is common, but measurement of exposure and impact of such marketing presents novel challenges. Thus, this study aimed to evaluate the feasibility of collecting data on exposure and impact of digital F&B marketing (DFM) using a smartphone-based ecological momentary assessment (EMA) methodology. We hypothesized that DFM-induced food cravings would vary based on whether (or not) participants engaged with F&B brands online. Participants were Singapore residents (n = 95, 21–40 years), recruited via telephone from an existing cohort. Participants were asked to upload screenshots of all sightings of online F&B marketing messages for seven days, and answer in-app contextual questions about sightings including whether any cravings were induced. Participants provided a total of 1310 uploads (median 9 per participant, Q1-Q3: 4–21) of F&B marketing messages, 27% of which were provided on Day 1, significantly more than on other days (P < 0.001). Followers of food/beverage brands on social media encountered 25.6 percentage points (95% CI 11.4, 39.7) more marketing messages that induced cravings than participants who were not followers. University education was also associated with more (18.1 percentage points; 95% CI 3.1, 33.1) encounters with marketing messages that induced cravings. It was practical and acceptable to participants to gather insights into digital F&B marketing exposure and impact using EMA in young adults, although a shorter study period is recommended in future studies. Followers of food and beverage brands on social media appear to be more prone to experience cravings after exposure to digital F&B marketing.

Increasing severity of medical outcomes and associated substances in cases reported to United States poison centers

Introduction Poison centers provide free expert recommendations on the treatment of a wide variety of toxicological emergencies. Prior studies have called attention to the increasing complexity of cases reported to poison centers. We aimed first, to evaluate the trends in medical outcome severity, over a 15-year period in both the adult and pediatric populations. Second, we described the most frequently reported substances associated with major effect or death. Methods This is a retrospective review of exposures reported to the National Poison Data System from 1 January 2007 through 31 December 2021. All closed cases, for human exposures, reported during the study period were included. We assessed trends in frequencies and rates of medical outcomes and level of care received, among the adult (age greater than 19 years) and pediatric (age 19 years and younger) populations by reason for exposure. Results During the study period, the number of adult unintentional exposures resulting in major effect (37.4 percent) and death (65.3 percent) increased. The number of adult intentional exposures resulting in death increased by 233.9 percent and those resulting in a major effect increased by 133.1 percent. The rates of exposures resulting in major effect and death increased among both intentional and unintentional adult exposures. The number of pediatric unintentional exposures resulting in a major effect increased by 76.6 percent and the number of pediatric intentional exposures resulting in death and major effect increased by 122.7 and 190.1 percent, respectively. Moderate, major effect, and death rates increased in pediatric unintentional exposures and moderate and major effect rates increased in pediatric intentional exposures. Conclusions We found a worsening severity of medical outcomes in adult and pediatric cases reported to poison centers. Poison centers are increasingly managing complex cases. Monitoring trends in which substances are associated with severe outcomes is imperative for future strategic prevention efforts.