Determination of personal exposure to volatile organic compounds and their health risks after the use of mosquito repellents in residential environments using passive sampling.

The ubiquitous use of mosquito repellents in homes across Asia, Africa, and South America is related with human exposure to indoor volatile organic compounds (VOCs). There are three primary types of mosquito repellents: those in the form of coils, mats, and liquids. The repellent mechanisms of these products are distinct, resulting in the generation of varying types of VOCs during the repellent process. In this study, the emission characteristics of commercial coil-, mat-, and liquid-type mosquito repellents were observed in a laboratory chamber using real-time measurement. A previously developed personal passive sampler, ePTFE PS, was used to quantify personal exposure to indoor VOCs while 86 volunteers habitually used those three representative types for 3 h in their residence. Notable increase of indoor benzene was observed for coil- and mat-type mosquito repellents, while α-pinene concentration increased significantly following the use of liquid-type mosquito repellent. The average incremental cancer risks for benzene were 10-6 to 10-4 for adults following the use of coil- and mat-type mosquito repellents. The average non-cancer risks for all chemicals were <1 after the use of three types of mosquito repellents. Considering the potential human health risks associated with byproducts (e.g., particulate matter or carbon monoxide from incomplete combustion) emitted after mosquito coil use, further research on this topic is warranted.

Adverse effects of meteorological factors and air pollutants on dry eye disease: a hospital-based retrospective cohort study.

Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.

Solanidine Metabolites as Diet-Derived Biomarkers of CYP2D6-Mediated Tamoxifen Metabolism in Breast Cancer Patients.

Tamoxifen is an important antiestrogen for the treatment of hormone receptor-positive breast cancer and undergoes bioactivation by CYP2D6 to its active metabolite endoxifen. Genetic variation in CYP2D6 has been linked to endoxifen levels during tamoxifen therapy. Recent studies have suggested solanidine, a glycoalkaloid phytochemical in potatoes, undergoes CYP2D6-mediated metabolism to 4-OH-solanidine (m/z 414) and 3,4-seco-solanidine-3,4-dioic acid (SSDA; m/z 444). Using a retrospective cohort of 1,032 breast cancer patients on tamoxifen therapy, we examined the association of solanidine metabolites with CYP2D6 activity and its correlation with tamoxifen metabolism. Solanidine, 4-OH-solanidine, or SSDA was detected in 99.7% (N = 1,029) of plasma samples. Decreased solanidine metabolite ratios were found in CYP2D6 intermediate and poor metabolizers (P < 0.0001). Patients on CYP2D6 strong inhibitors had a 77.6% and 94.2% decrease in 4-OH-solandine/solanidine (P < 0.0001) and SSDA/solanidine (P < 0.0001), respectively. The ratio of endoxifen to tamoxifen was highly correlated with both 4-OH-solandine/solanidine (ρ = 0.3207, P < 0.0001) and SSDA/solanidine (ρ = 0.5022, P < 0.0001) ratios. Logistic regression modeling was used to determine that 4-OH-solanidine/solanidine and SSDA/solanidine ratios below 2.1 and 0.8, respectively, predicted endoxifen concentrations of <16 nM. In conclusion, solanidine, 4-OH-solanidine, and SSDA are diet-derived biomarkers of CYP2D6 activity. Moreover, in patients on tamoxifen therapy, 4-OH-solanidine/solanidine and SSDA/solanidine predicted endoxifen levels including the inhibitory effects of concomitantly prescribed CYP2D6-interacting medications. Accordingly, 4-OH-solanidine/solanidine or SSDA/solanidine ratio has the potential to be particularly useful prior to initiation of tamoxifen or for determining the impact of CYP2D6 drug interactions, as well as prior to switching from an aromatase inhibitor to tamoxifen.

Extending the DeLong algorithm for comparing areas under correlated receiver operating characteristic curves with missing data.

A nonparametric method proposed by DeLong et al in 1988 for comparing areas under correlated receiver operating characteristic curves is used widely in practice. However, the DeLong method as implemented in popular software quietly deletes individuals with any missing values, yielding potentially invalid and/or inefficient results. We simplify the DeLong algorithm using ranks and extend it to accommodate missing data by using a mixed model approach for multivariate data. Simulation results demonstrate the validity and efficiency of our procedure for data missing at random. We illustrate our proposed procedure in SAS, Stata, and R using the original DeLong data.

Evaluation of a unique and innovative diabetes care model in primary care in Ontario, Canada: protocol for a multiple-methods study with a convergent parallel design.

INTRODUCTION: The growth and complexity of diabetes are exceeding the capacity of family physicians, resulting in the demand for community-based, interprofessional, primary care-led transition clinics. The Primary Care Diabetes Support Programme (PCDSP) in London, Ontario, is an innovative approach to diabetes care for high-risk populations, such as medically or socially complex and unattached patients. In this study, we will employ a quadruple-aim approach to evaluate the health system impacts of the PCDSP. METHODS AND ANALYSIS: We will use multiple methods through a convergent parallel design in this project across five unique studies: a case study, a patient study, a provider study, a complications study and a cost-effectiveness study. The project will be conducted in a dedicated stand-alone clinic specialising in chronic disease management, specifically focusing on diabetes care. Participants will include clinic staff, administrators, family physicians, specialists and patients with type 1 or type 2 diabetes who received care at the clinic between 2011 and 2023. The project design will define the intervention, support replication at other sites or for other chronic diseases and address each of the quadruple aims and equity. Following the execution of the five individual studies, we will build a business case by integrating the results. Data will be analysed using both qualitative (content analysis and thematic analysis) and quantitative techniques (descriptive statistics and multiple logistic regression). ETHICS AND DISSEMINATION: We received approval from the research ethics boards at Western University (reference ID: 2023-1 21 766; 2023-1 22 326) and Lawson Health Research Institute (reference ID: R-23-202). A privacy review was completed by St. Joseph's Healthcare Corporation. The findings will be shared among PCDSP staff and patients, stakeholders, academic researchers and the public through stakeholder sessions, conferences, peer-reviewed publications, infographics, posters, media interviews, social media and online discussions. For the patient and provider study, all participants will be asked to provide consent and are free to withdraw from the study, without penalty, until the data are combined. Participants will not be identified in any report or presentation except in the case study, for which, given the number of PCDSP providers, we will seek explicit consent to identify them.

Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer. METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 µm, and fine particulate matter with a diameter < 2.5 µm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality. RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30). CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.

Associations of minimally processed and ultra-processed food intakes with cardiovascular health in Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES VI), 2013-2015.

BACKGROUND: Although recent studies have suggested the adverse effects of processed foods on cardiovascular disease, few studies have been conducted on the effects of food processing on cardiovascular health (CVH) in Koreans. OBJECTIVE: This study aimed to investigate the associations of minimally processed foods (MPF) and ultra-processed foods (UPF) intakes with CVH. METHODS: We used the data of 6945 adults (≥19) from the sixth Korea National Health and Nutrition Examination Survey. MPF and UPF intakes were based on the NOVA food classification. Using Life's simple 7 (LS7) proposed by the American Heart Association, the CVH indicator was estimated as the sum (0-12) of the scores of six components. Multiple linear and multinomial logistic regressions were used to estimate the associations between processed food intakes and CVH. RESULTS: The mean (standard error) of MPF and UPF intake was 61.28 (0.28) and 20.27 (0.24) %kcal/day, respectively. After adjusting for sex, age, household income, educational attainment, family history of CVD, and stress, we found significant positive associations between MPF intake and CVH (p value < 0.001), while associations between UPF intake and CVH were significantly negative (p value < 0.001). Moreover, the magnitude of the observed association was more distinctive in females (p-interaction < 0.01) and with increasing age (p-interaction < 0.001). CONCLUSIONS: A high intake of MPF is associated with improved CVH, while a high intake of UPF is associated with poorer CVH in Korean adults. Therefore, public health policies should be established to promote the choice of less processed foods to improve CVH among South Korean adults. IMPACT STATEMENT: In modern society, processed foods have become ubiquitous and South Korea's consumption of processed foods is very high. This study had shown that the more processed a food is, the more negative impact it can have on cardiovascular health. Therefore, researching the effects of processed foods on the human body can increase understanding of population health and aid in the development of prevention and treatment strategies.

Association between oil spill clean-up work and thyroid cancer: Nine years of follow-up after the Hebei Spirit oil spill accident.

In 2007, an unprecedented oil spill occurred in Taean, Korea. Although crude oil contains chemicals that could increase thyroid cancer risk, few studies have examined the long-term effects of oil exposure during clean-up and thyroid cancer incidence. We investigated the long-term thyroid cancer incidence among participants involved in clean-up work. 1798 participants engaged in at least two surveys since the baseline was tracked from 2008 to 2018. Participants reported the days they participated in oil clean-up works and cancer diagnoses. Cox proportional hazard models were used to estimate the hazard ratios between clean-up work duration and thyroid cancer. Over the 9-year follow-up, 30 thyroid cancer cases were diagnosed. A positive association was observed between clean-up duration and thyroid cancer risk. This effect was more pronounced among residents living <50 m from traffic roads. Our results indicate that crude oil clean-up work participation may increase the thyroid cancer risk.

Exposure to biocides and its association with atopic dermatitis among children and adolescents: A population-based cross-sectional study in South Korea.

BACKGROUND: Biocides have emerged as a contributor to the rising cases of atopic dermatitis among children and adolescents. Previous animal studies suggested that phenols, parabens, and pyrethroid insecticides present in these products might play a role in atopic dermatitis. However, there's limited epidemiological evidence confirming the individual or combined effects of exposure to these chemicals on atopic dermatitis in young populations. This study aimed to investigate the association between phenol, paraben, and pyrethroid metabolite levels in urine and atopic dermatitis among Korean children and adolescents METHODS: We analyzed 556 preschool children (3-5 years), 701 schoolchildren (6-11 years), and 731 adolescents (12-17 years) enrolled in the 4th Korean National Environmental Health Survey (KoNEHS) (2018-2020). We used logistic regression and Bayesian kernel machine regression to evaluate the association between atopic dermatitis and individual or mixed exposure to urinary triclosan (TCS), parabens (methylparaben, ethylparaben, propylparaben, and butylparaben), and 3-phenoxybenzoic acid (3-PBA) levels. RESULTS: Urinary TCS levels were positively associated with atopic dermatitis in schoolchildren. When stratified by sex, male schoolchildren exhibited an increasing prevalence of atopic dermatitis as their urinary TCS and 3-PBA levels increased. The combined effect of biocide mixtures on atopic dermatitis was also significantly increased in male schoolchildren, with TCS as the main contributor. CONCLUSIONS: These study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Association between environmental mercury exposure and allergic disorders in Korean children: Korean National Environmental Health Survey (KoNEHS) cycles 3-4 (2015-2020).

Although previous studies have suggested potential adverse effects of mercury on a child's immune system, the associations have been inconsistent. We aimed to determine the association between urinary mercury levels and allergic diseases in Korean children with high mercury exposure. Data from 853 and 710 children aged 6-11 years in the Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017) and cycle 4 (2018-2020) were analyzed. We examined the association between mercury exposure and the prevalence of atopic dermatitis (AD), asthma, allergic rhinitis (AR), and allergic multimorbidity. After adjusting for all covariates, the urinary mercury level was positively associated with AD in the 2015-2017 study (OR = 1.34, 95% CI = 1.01, 1.79) and AR in 2018-2020 study (OR = 1.46, 95% CI = 1.01, 2.10). Pooled effects showed OR of 1.34 (95% CI = 1.01, 1.79) for AD and 1.47 (95% CI = 1.01, 2.12) for allergic multimorbidity. The association with allergic multimorbidity was greater in boys (OR = 1.88, 95% CI = 1.01, 3.49) than in girls (OR = 1.25, 95% CI = 0.73, 2.14). These results suggest that environmental mercury exposure may exacerbate symptoms of atopic dermatitis and allergic multimorbidity in children.

Evaluation and Classification of Supraorbital Nerve Emerging Patterns.

BACKGROUND: Numerous significant variations in the supraorbital nerve (SON) pass through the notches and foramina. During endoscopic forehead lifting, the passage and the location of the nerve against the frontal bone render it susceptible to injury, resulting in diminished or absent sensation in the corresponding location. We attempted to obtain accurate knowledge of the SON emergence routes. METHODS: Data of patients who underwent an endoscopic forehead lift in a plastic surgery clinic between November 2015 and August 2021 were retrospectively analyzed. Deep and superficial branch pathways of SONs were identified and compared according to side and gender. We also classified the nerve patterns into six types. RESULTS: Altogether, 942 patients (1884 SON cases) were evaluated. Out of the patients, 86 patients were male, and 856 were female. The overall mean age was 48.6 (± 13.1) years. In the deep branches, 49% came from the notch, and 51% came from the foramen. In the superficial branches, 67% came from the notch, and 33% of superficial branches came from the foramen. Unlike the deep branch, superficial branches from the notch were significant. Deep and superficial branches of male patients were much more notched than those of female patients. Branches emerged together in 56% and separately in 44% of the cases. CONCLUSION: The absolute number of SON notches was higher than that of SON foramina. This study with the largest number of SON cases will help surgeons understand the variation and course of SON. LEVEL OF EVIDENCE IV: This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Sociodemographic Factors and the Risk of Pediatric Out-of-Hospital Cardiac Arrest in Ontario, Canada: A Province-Wide Case-Control Study.

BACKGROUND: Pediatric out-of-hospital cardiac arrest (POHCA) is associated with significant mortality and poor neurological outcomes. We aimed to describe the association between sociodemographic factors and POHCA risk in Ontario, Canada. METHODS AND RESULTS: We conducted a province-wide case-control study at ICES, where patient records are linked across administrative databases. The case group included children (aged 1 day to 17 years) who experienced an out-of-hospital cardiac arrest between 2004 and 2020. Controls were matched up to 1:4 on age, sex, index date, and key comorbidities. We used conditional logistic regression to measure the association between sociodemographic indicators and POHCA risk. The case and control groups included 1826 and 7254 children, respectively. Children living in areas with the highest levels of material deprivation (adjusted odds ratio [aOR], 2.35 [95% CI, 1.94-2.85]) and dependency (aOR, 1.22 [95% CI, 1.01-1.48]) had a higher odds of POHCA, relative to children living in regions with the lowest levels of material deprivation and dependency, respectively. Children living in neighborhoods with the lowest levels of ethnic diversity had a higher odds of POHCA (aOR, 1.62 [95% CI, 1.30-2.01]), relative to children living in neighborhoods with the highest levels of ethnic diversity. The odds of POHCA were lower in immigrants (aOR, 0.67 [95% CI, 0.47-0.95]), relative to the general population. Northern urban residence was associated with a higher odds of POHCA (aOR, 1.45 [95% CI, 1.13-1.87]), relative to southern urban residence. CONCLUSIONS: Children living in neighborhoods with high levels of marginalization may have an elevated risk of experiencing POHCA. These findings highlight the importance of addressing disparities through targeted prevention and intervention efforts.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

Long-term effects of the Hebei Spirit oil spill on the prevalence and incidence of allergic disorders.

The Hebei Spirit oil spill accident occurred in December 2007, approximately 10 km off the coast of Taean, South Korea, a location notably close to residential areas. Crude oil substances have been detected in various environmental mediums since the accident, yet previous studies have primarily focused on the acute effects of oil exposure due to the short latency period of allergic diseases. Therefore, this study evaluated the long-term effects of oil spill exposure on allergic disorders. Our study included adult residents who had participated in the Health Effects Research on Hebei Spirit Oil Spill (HEROS) study up to five years post-incident, which was a prospective cohort to monitor the health status of Taean residents. We used two indicators to assess oil spill exposure, namely the distance from the initial contaminated coastline to each participant's residence and the number of days participants had engaged in oil clean-up work. Current symptoms such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and multimorbidity were considered allergic disorders. In the baseline survey, the prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and allergic multimorbidity symptoms was associated with both exposure indicators; however, these associations were not observed in the two consecutive surveys. Significant longitudinal associations between oil spill exposure indicators and the four allergic disorders, as well as multimorbidity incidences, were observed during a five-year follow-up period. Our results suggest that oil spill exposure can affect acute and long-term allergic symptoms in residents near the accident site.

Health risks of pest control and disinfection workers after the COVID-19 outbreak in South Korea.

The exposure patterns of pest control and disinfection workers have changed after the coronavirus disease 2019 (COVID-19) outbreak, but the health risks of chemical exposure have not been assessed. We identified these workers' chemical exposure patterns and risks before and after the COVID-19 outbreak. We used data conducted between 2018 (pre-pandemic) and 2021 (post-pandemic) from three-year cross-sectional surveys on pest control and disinfection workers. Inhalation and dermal exposure concentrations were estimated using equations based on a biocidal product risk assessment model from the Korean National Institute of Environmental Research. The non-carcinogenic and carcinogenic risks of chemicals were calculated using the United States Environmental Protection Agency risk assessment model. We found that the annual work frequency (50th percentile) of foggers using disinfectants increased the most among all the work types, from 140 uses/year to 176 uses/year after the COVID-19 outbreak. Moreover, all chemicals' non-carcinogenic and carcinogenic risks increased regardless of exposure routes. In the worst scenario (95th percentile), the margin of exposure for citric acid, benzethonium chloride, benzyl-C12-16-alkyldimethyl chlorides, and sodium chlorite of inhalation exposure, and isopropyl alcohol and benzyl-C12-16-alkyldimethyl chlorides of dermal exposure were acceptable (>100) before the COVID-19 outbreak but became unacceptable (<100) after the COVID-19 outbreak. Carcinogenic risks of dichlorvos from inhalation and dermal exposure were above acceptable levels (>10-6) before and after the COVID-19 outbreak but comparatively high after the COVID-19 outbreak. Additionally, significantly more workers experienced health symptoms after the COVID-19 outbreak (p<0.05), with the most common being muscle lethargy (31%), skin/face stinging (28.7%), and breath shortness/neck pain (24.1%).

Construction and validation of the area level deprivation index for health research: A methodological study based on Nepal Demographic and Health Survey.

Area-level factors may partly explain the heterogeneity in risk factors and disease distribution. Yet, there are a limited number of studies that focus on the development and validation of the area level construct and are primarily from high-income countries. The main objective of the study is to provide a methodological approach to construct and validate the area level construct, the Area Level Deprivation Index in low resource setting. A total of 14652 individuals from 11,203 households within 383 clusters (or areas) were selected from 2016-Nepal Demographic and Health survey. The index development involved sequential steps that included identification and screening of variables, variable reduction and extraction of the factors, and assessment of reliability and validity. Variables that could explain the underlying latent structure of area-level deprivation were selected from the dataset. These variables included: housing structure, household assets, and availability and accessibility of physical infrastructures such as roads, health care facilities, nearby towns, and geographic terrain. Initially, 26-variables were selected for the index development. A unifactorial model with 15-variables had the best fit to represent the underlying structure for area-level deprivation evidencing strong internal consistency (Cronbach's alpha = 0.93). Standardized scores for index ranged from 58.0 to 140.0, with higher scores signifying greater area-level deprivation. The newly constructed index showed relatively strong criterion validity with multi-dimensional poverty index (Pearson's correlation coefficient = 0.77) and relatively strong construct validity (Comparative Fit Index = 0.96; Tucker-Lewis Index = 0.94; standardized root mean square residual = 0.05; Root mean square error of approximation = 0.079). The factor structure was relatively consistent across different administrative regions. Area level deprivation index was constructed, and its validity and reliability was assessed. The index provides an opportunity to explore the area-level influence on disease outcome and health disparity.

Astrocytic FoxO1 in the hypothalamus regulates metabolic homeostasis by coordinating neuropeptide Y neuron activity.

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis.

Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.