Excess suicides in Japan: A three-year post-pandemic assessment of gender and age disparities.

This study offers an in-depth analysis of Japan's suicide trends three years after the COVID-19 outbreak. Using data from the National Police Agency (January 2010-May 2023), we examined suicide rates across genders and age groups. Employing the quasi-Poisson regression, we predicted monthly death counts. Findings indicate a steady rise in female suicides from April 2020 to January 2023. Notably, male cohorts aged 50-59 and over 80 in 2022 displayed heightened death rates. While these trends may reflect the impacts of the pandemic, it is essential to consider other factors, including socio-economic changes, to fully understand the context of Japan's suicide patterns.

A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress.

The gut-brain axis, which includes gut microbiota and microbiome-derived metabolites, might be implicated in depression. We reported the sustained prophylactic effects of a new antidepressant arketamine in chronic restrain stress (CRS) model of depression. In this study, we investigated the role of gut-brain axis on the prophylactic effects of arketamine in the CRS (7 days) model. Pretreatment with arketamine (10 mg/kg, 1 day prior to the CRS onset) significantly prevented CRS-induced body weight loss, increased immobility time of forced swimming test, decreased sucrose preference of sucrose preference test, and reduced expressions of synaptic proteins (GluA1 and PSD-95) in the prefrontal cortex (PFC) in the male mice. Gut microbiota analysis showed that pretreatment with arketamine might restore altered abundance of gut microbiota in CRS-exposed mice. An untargeted metabolomics analysis revealed four metabolites (e.g., L-leucine, N-acetyl-l-glutamine, 2-(2,4-dichlorophenyl)-3-[4-(dimethylamino)phenyl]acrylonitrile, L-threonine amide) that were altered between control and CRS group; however, there were found to be altered between the saline + CRS group and the arketamine + CRS group. Network analysis demonstrated correlations among synaptic proteins in the PFC and certain microbiota, and blood metabolites. These findings suggest that gut-brain axis, including its metabolites, might partially contribute to the persistent prophylactic effects of arketamine in the CRS model.

Changes in Place of Death among Patients with Dementia during the COVID-19 Pandemic in Japan: A Time Series Analysis.

BACKGROUND: A key measure of the effectiveness of end-of-life care is the place of death. The COVID-19 pandemic affected end-of-life care and the circumstances of patients with dementia. METHODS: This observational, retrospective cohort study used Japanese national data to examine the numbers and locations of reported deaths among patients with dementia older than 65 years during the COVID-19 pandemic. Locations were grouped as medical institutions, nursing facilities, homes, or all the above. The quasi-Poisson regression model known as the Farrington algorithm was employed. RESULTS: Between December 30, 2019, and January 29, 2023, 279,703 patients who died of causes related to dementia were reported in Japan. A decline was seen in early 2020, followed by increased numbers of deaths in homes, medical facilities, and nursing homes beginning in October 2020, December 2020, and March 2021, respectively. In 2021, the percentage of excess deaths at home peaked at 35.2%, while in 2022, those in medical facilities and nursing homes peaked at 18.8% and 16.6%, respectively. In 2022, the percentage of excess deaths in nursing homes exceeded that of other locations. CONCLUSIONS: The results suggest a change in the preferred place of death, along with pandemic-related visitation restrictions among healthcare facilities. Excess deaths also suggest strained medical resources and limited access to care. Methodological limitations include data from a limited period (2017 onwards) and post-2020 data used to estimate data after 2021, albeit with weighting. Considering these findings, physicians should reconfirm preferred places of death among older patients with dementia.

Depression-like phenotypes in mice following common bile duct ligation: Insights into the gut-liver-brain axis via the vagus nerve.

Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated in depression through the gut-brain axis via the vagus nerve. This study explored the potential role of the gut-liver-brain axis via the vagus nerve in depression-like phenotypes in mice with liver cirrhosis. These mice underwent common bile duct ligation (CBDL), a method used to stimulate liver cirrhosis. To assess depression-like behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The mice with CBDL displayed symptoms such as splenomegaly, elevated plasma levels of interleukin-6 and tumor necrosis factor-α, depression-like behaviors, decreased levels of synaptic proteins in the prefrontal cortex (PFC), disrupted gut microbiota balance, and changes in blood metabolites (or lipids). Additionally, there were positive or negative correlations between the relative abundance of microbiome and behavioral data or blood metabolites (or lipids). Significantly, these changes were reversed in CBDL mice by performing a subdiaphragmatic vagotomy. Intriguingly, depression-like phenotypes in mice with CBDL were improved after a single injection of arketamine, a new antidepressant. These results suggest that CBDL-induced depression-like phenotypes in mice are mediated through the gut-liver-brain axis via the subdiaphragmatic vagus nerve, and that arketamine might offer a new treatment approach for depression in liver cirrhosis patients.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Factors associated with barriers to healthcare access among ever-married women of reproductive age in Bangladesh: Analysis from the 2017-2018 Bangladesh Demographic and Health Survey.

BACKGROUND: Globally, women experience healthcare inequalities, which may contribute to excessive mortality rates at various stages of their lives. Though Bangladesh has achieved excellent progress in providing healthcare, the country still has some critical challenges that need immediate attention. The objective of this study is to examine the association between social determinants and barriers to accessing healthcare among ever-married women aged 15-49 in Bangladesh. METHODS: The study was conducted among 20,127 women aged 15-49, using data from the 2017-2018 Bangladesh Demographic and Health Survey. Four barriers to healthcare were considered: whether women face problems with permission, obtaining money, distance, and companionship. The multivariable logistic regression analysis was used, with a broad array of independent variables (such as age, and educational level) to identify the determinants of barriers to healthcare access. The associations were expressed as adjusted odds ratios (AOR) with a 95% confidence interval (CI). RESULTS: More than two-thirds (66.3%) of women reported having at least one perceived barrier to accessing healthcare. Women with a higher level of education (AOR = 0.49, 95% CI: 0.41-0.57), owning a mobile telephone (AOR = 0.78, 95% CI: 0.73-0.84), and those in the richest wealth quintile (AOR = 0.45, 95% CI: 0.38-0.52) had lower odds of having barriers to accessing healthcare. In addition, widowed (AOR = 1.53, 95% CI: 1.26-1.84), divorced (AOR = 1.91, 95% CI:1.47-2.48), or separated (AOR = 1.98, 95% CI: 1.46-2.69) women had higher odds of having a money barrier to accessing healthcare, than married women. CONCLUSIONS: This study shows that individual-, household-, and community-level factors are associated with barriers to healthcare accessibility. To improve the state of women's health in Bangladesh, it is vital to consider these socio-economic factors and implement fundamental measures, such as supporting the national health policy, empowering women's socio-economic situation, and spreading the flexible way of healthcare access.

The association between clustering based on composition of volatile organic compound in indoor air and building-related symptoms.

Volatile organic compounds (VOCs) have been suspected to cause building-related symptoms (BRSs). Although some studies investigated the association between BRSs and VOCs in indoor air, those results were inconsistent. This study investigated the contamination status of VOCs in the indoor air of 154 houses in Japan. Additionally, these samples were grouped by hierarchical clustering analysis based on the VOC composition, and the relationship between a VOC cluster and the BRSs was investigated. The median concentration of the sum of VOCs (ΣVOCs) was 140 µg m-3 (range: 18-3500 µg m-3). The levels of acetaldehyde in four samples and p-dichlorobenzene in one sample exceeded the guideline value. As a result of the hierarchical clustering analysis, the samples in this study were divided into six characteristic clusters based on the VOC composition. The ΣVOCs in cluster 1 were significantly lower than those in other clusters. In cluster 2, acyclic and aromatic hydrocarbons were dominant. Cluster 3 had a relatively high proportion of limonene. In cluster 4, the concentrations and composition ratios of α-pinene were higher than those of other clusters. In cluster 5, p-dichlorobenzene accounted for 42 %-72 % of the total VOCs. Cluster 6 had a relatively high proportion of decamethyl cyclopentasiloxane. This clustering likely depended on the construction of houses and lifestyles. As a result of logistic regression analysis, cluster 5 was associated with the cough symptoms of the BRSs. The results of the present study suggest that investigating the association between VOCs and BRSs is necessary to consider not only total concentrations such as TVOC and ΣVOCs but also VOC composition.

Toxicity Assessment of Mixed Exposure of Nine Perfluoroalkyl Substances at Concentrations Relevant to Daily Intake.

Per- and poly-fluoroalkyl substances (PFAS) exhibit high persistence in the environment and accumulate within the human body, warranting a thorough assessment of their toxicity. In this study, we exposed mice (male C57BL/6J mice aged 8 weeks) to a composite of nine PFAS, encompassing both long-chain PFAS (e.g., perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g., perfluorobutanoic acid and perfluorobutanesulfonic acid). The exposure concentrations of PFAS were equivalent to the estimated daily human intake in the composition reported (1 µg/L (sum of the nine compounds), representing the maximum reported exposure concentration). Histological examination revealed hepatocyte vacuolization and irregular hepatocyte cord arrangement, indicating that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, with the annotation of substances such as glutathione and 5-aminovaleric acid. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism- and cancer-related genes as well as phospholipid metabolism.

Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress.

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported that the gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the stress resilience effects of MDMA in mice subjected to chronic restrain stress (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like behavior and reduced expression of synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in CRS-exposed mice. Analysis of gut microbiome revealed alterations in four measures of α-diversity between the sham + MDMA + CRS group and the SDV + MDMA + CRS group. Moreover, specific microbes differed between the vehicle + CRS group and the MDMA + CRS group, and further differences in microbial composition were observed among all four groups. Untargeted metabolomics analysis showed that SDV prevented the increase in plasma levels of three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] observed in the sham + MDMA + CRS group. Interestingly, positive correlations were found between the plasma levels of two of these compounds and the abundance of several microbes across all groups. In conclusion, our data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the stress resilience of MDMA.

The Efficacy of an mHealth App in Facilitating Weight Loss Among Japanese Fitness Center Members: Regression Analysis Study.

BACKGROUND: Self-tracking smartphone apps have emerged as promising tools to encourage healthy behaviors. In this longitudinal study, we used gym use data from members of a major fitness club that operates gyms throughout Japan from January 2014 to December 2019. OBJECTIVE: Our objective was to assess the extent to which a health and fitness self-tracking mobile app introduced to gym members on January 1, 2018, contributed to their weight loss. The app allows users to input information regarding diet, sleep, weight, and gym exercise so that they can receive personalized feedback from an artificial intelligence chatbot to improve their health behaviors. METHODS: We used linear regression to quantify the association between app use and weight loss. The primary outcome of the study was the weight loss achieved by each gym user, which was calculated as the difference between their initial and final weights in kilograms, as recorded in the app. Individuals who did not attend the gym or failed to use the mobile app at least twice during the study period were excluded from the analysis. The model accounted for age, gender, distance between the gym and the member's residence, average weekly number of times a member used the gym, user's gym membership length in weeks, average weekly number of times a member input information into the app, and the number of weeks that the app was used at least once. RESULTS: Data from 26,589 participants were analyzed. Statistically significant associations were detected between weight loss and 2 metrics related to app use: the average weekly frequency of use and the total number of weeks in which the app was used at least once. One input per week was found to be associated with a loss of 62.1 (95% CI 53.8-70.5) g, and 1 week of app use was associated with 21.7 (95% CI 20.5-22.9) g of weight loss from the day of the first input to that of the final input to the app. Furthermore, the average number of times that a member used the gym weekly was also shown to be statistically significantly associated with weight loss: 1 use per week was associated with 255.5 (95% CI 228.5-282.6) g of weight loss. CONCLUSIONS: This empirical study demonstrated a significant association between weight loss among gym members and not only the frequency of weekly gym use but also the use of a health and fitness self-tracking app. However, further work is needed to examine the mechanisms through which mobile apps affect health behaviors and to identify the specific app features that are most effective in promoting weight loss.

Prediction of gestational diabetes mellitus using machine learning from birth cohort data of the Japan Environment and Children's Study.

Recently, prediction of gestational diabetes mellitus (GDM) using artificial intelligence (AI) from medical records has been reported. We aimed to evaluate GDM-predictive AI-based models using birth cohort data with a wide range of information and to explore factors contributing to GDM development. This investigation was conducted as a part of the Japan Environment and Children's Study. In total, 82,698 pregnant mothers who provided data on lifestyle, anthropometry, and socioeconomic status before pregnancy and the first trimester were included in the study. We employed machine learning methods as AI algorithms, such as random forest (RF), gradient boosting decision tree (GBDT), and support vector machine (SVM), along with logistic regression (LR) as a reference. GBDT displayed the highest accuracy, followed by LR, RF, and SVM. Exploratory analysis of the JECS data revealed that health-related quality of life in early pregnancy and maternal birthweight, which were rarely reported to be associated with GDM, were found along with variables that were reported to be associated with GDM. The results of decision tree-based algorithms, such as GBDT, have shown high accuracy, interpretability, and superiority for predicting GDM using birth cohort data.

Impact of the COVID-19 pandemic on cancer death locations in Japan: an analysis up to February 2023 on excess mortality.

IntroductionThe Covid-19 pandemic has significantly impacted end-of-life decisions for cancer patients in Japan, with disparities existing between preferred and actual care settings. Our study investigates the potential shifts in cancer death locations during the pandemic and if there were excess cancer deaths.MethodsUtilizing national mortality data from the Ministry of Health, Labour, and Welfare from January 2012 to February 2023, we identified cancer deaths using ICD-10 codes. We assessed death locations, including medical institutions, nursing facilities, and homes. The Farrington algorithm was employed to estimate expected death counts, and the differences between observed and expected counts were denoted as excess deaths.ResultsFrom January 2018 to February 2023, there was consistently increase in the weekly observed cancer deaths. The presence of a definitive excess during the pandemic period remains uncertain. The percentage of deaths in medical institutions declined from 83.3% to 70.1% , while home deaths increased from 12.1% to 22.9%. Between April 2020 and February 2023, deaths in medical institutions frequently fell below the 95% prediction lower limit. Home deaths consistently exceeded the 95% prediction upper limit, with significant excess deaths reported annually.ConclusionOur study found a shift in cancer death locations from medical institutions to homes in Japan during the COVID-19 pandemic. Our study did not confirm an overall increase in cancer deaths during this period. As with global trends, the profound shift from hospitals to homes in Japan calls for a comprehensive exploration to grasp the pandemic's multifaceted impact on end-of-life cancer care decisions.

Understanding factors related to healthcare avoidance for menstrual disorders and menopausal symptoms: A cross-sectional study among women in Japan.

This study explored the factors associated with healthcare avoidance behavior for menstrual disorders and menopausal symptoms among women in Japan. Using data from a nationally representative cross-sectional online survey conducted in September 2022, responses from 4,950 women aged 25-59 were analyzed. This study applied binomial logistic regression models specifically to participants who reported having ever felt the need to seek healthcare assistance due to health issues related to menstruation and menopause. We computed adjusted odds ratios for key sociodemographic traits, work environment factors, health literacy, menstrual and menopausal symptoms, and attitudes and understanding regarding women's health, associated with healthcare avoidance behavior in the past 12 months. As a sensitivity analysis, a regression was performed limited to those who are working. The results showed that 50.6% of respondents recognized the need for healthcare support for menstrual or menopausal health issues, but 22.8% exhibited healthcare avoidance in the past year. Younger and high-income individuals showed higher avoidance rates. Those with diagnosed gynecological conditions and those perceiving menstrual pain as something to endure also displayed increased avoidance tendencies. Women experiencing significant health effects beyond work and those lacking understanding of the purpose of health check-ups were more prone to healthcare avoidance. Our results underscore the importance of implementing strategically tailored health education initiatives, and re-examining societal attitudes concerning women's health, in order to cultivate enhanced healthcare-seeking behaviors among women.

Estimation of the time of exposure based on interval and censored data using the ε-accelerated EM algorithm.

Accurately estimating the timing of pathogen exposure plays a crucial role in outbreak control for emerging infectious diseases, including the source identification, contact tracing, and vaccine research and development. However, since surveillance activities often collect data retrospectively after symptoms have appeared, obtaining accurate data on the timing of disease onset is difficult in practice and can involve "coarse" observations, such as interval or censored data. To address this challenge, we propose a novel likelihood function, tailored to coarsely observed data in rapid outbreak surveillance, along with an optimization method based on an ε $$ \varepsilon $$ -accelerated EM algorithm for faster convergence to find maximum likelihood estimates (MLEs). The covariance matrix of MLEs is also discussed using a nonparametric bootstrap approach. In terms of bias and mean-squared error, the performance of our proposed method is evaluated through extensive numerical experiments, as well as its application to a series of epidemiological surveillance focused on cases of mass food poisoning. The experiments show that our method exhibits less bias than conventional methods, providing greater efficiency across all scenarios.

Estimating global changes in routine childhood vaccination coverage during the COVID-19 pandemic, 2020-2021.

OBJECTIVES: The COVID-19 pandemic has disrupted the distribution of routine immunizations globally. Multi-country studies assessing a wide spectrum of vaccines and their coverage rates are needed to determine global performance in achieving vaccination goals. METHODS: Global vaccine coverage data for 16 antigens were obtained from WHO/UNICEF Estimates of National Immunization Coverage. Tobit regression was performed for all country-antigen pairs for which data were continuously available between 2015-2020 or 2015-2021 to predict vaccine coverage in 2020/2021. Vaccines for which multi-dose data were available were assessed to determine whether vaccine coverage for subsequent doses were lower than that of first doses. RESULTS: Vaccine coverage was significantly lower-than-predicted for 13/16 antigens in 2020 and all assessed antigens in 2021. Lower-than-predicted vaccine coverage was typically observed in South America, Africa, Eastern Europe, and Southeast Asia. There was a statistically significant coverage drop for subsequent doses of the diphtheria-tetanus-pertussis, pneumococcus, and rotavirus vaccines compared to first doses in 2020 and 2021. CONCLUSION: The COVID-19 pandemic exerted larger disruptions to routine vaccination services in 2021 than in 2020. Global efforts will be needed to recoup vaccine coverage losses sustained during the pandemic and broaden vaccine access in areas where coverage was previously inadequate.

Abnormal compositions of gut microbiota and metabolites are associated with susceptibility versus resilience in rats to inescapable electric stress.

BACKGROUND: Increasing evidence suggests the role of gut microbiota in resilience versus vulnerability after stress. However, the role of gut microbiota and microbiome-derived metabolites in resilience versus susceptibility in rodents exposed to stress remains unclear. METHODS: Adult male rats were exposed to inescapable electric stress under the learned helplessness (LH) paradigm. The composition of gut microbiota and metabolites in the brain and blood from control (no stress) rats, LH resilient rats, and LH susceptible rats were examined. RESULTS: At the genus level, the relative abundances of Asaccharobacter, Eisenbergiella, and Klebsiella in LH susceptible rats were significantly higher than that of LH resilient rats. At the species level, the relative abundances of several microbiome were significantly altered between LH susceptible rats and LH resilient rats. Furthermore, there were several metabolites in the brain and blood altered between LH susceptible rats and LH resilient rats. A network analysis showed correlations between the abundance of several microbiome and metabolites in the brain (or blood). LIMITATIONS: Detailed roles of microbiome and metabolites are unclear. CONCLUSIONS: These findings suggest that abnormal compositions of the gut microbiota and metabolites might contribute to susceptibility versus resilience in rats subjected to inescapable electric foot shock.

Reducing salt intake with umami: A secondary analysis of data in the UK National Diet and Nutrition Survey.

Reducing sodium content in foods is an important public health measure to reduce salt intake and decrease the incidence of noncommunicable diseases, such as cardiovascular disease and chronic kidney disease. This study quantified the amount of salt intake that could potentially be reduced by using umami substances, including glutamate, inosinate, and guanylate, without compromising taste, for adults in the United Kingdom (UK). We used data comprised of 1834 adults aged 20 years and over from the National Diet and Nutrition Survey (NDNS RP) 2016/2017-2018/2019. Four hypothetical scenarios in which the market share of low-sodium foods accounts for 0%, 30%, 60%, or 90% of consumed products were considered in the analyses. Per capita daily salt intake corresponding to the NDNS RP food groups was calculated for each scenario, and the salt intake was aggregated by gender and age groups. Replacing salt with umami substances could help UK adults reduce daily salt intake by 9.09%-18.59% (9.21%-18.43% for women; 8.83%-19.43% for men), which is equivalent to 0.45-0.92 g/day of salt reduction (0.41-0.82 g/day for women; 0.50-1.10 g/day for men). The use of umami substances may serve as one method for the UK government to encourage salt intake reduction, particularly in the context of food product reformulation, as 80% of salt consumed in the country comes from processed foods. Empirical studies with sensory evaluation should be conducted to confirm consumer tolerance. The food industry should also be engaged in conversations regarding the addition of umami to food products in the United Kingdom.

Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut-microbiota-bone-brain axis.

Patients with depression exhibit reduced bone mineral density (BMD). We previously reported that the new antidepressant arketamine improved the reduced BMD seen in chronic social defeat stress (CSDS) susceptible mice and ovariectomized mice. Considering the role of the gut microbiota in maintaining bone health, the current study investigated whether the gut microbiota, along with metabolites derived from the microbiome, play a role in the beneficial actions of arketamine with respect to the anhedonia-like behavior and reduced BMD seen in CSDS susceptible mice. A single administration of arketamine (10 mg/kg) ameliorated anhedonia-like behavior and decreased femoral neck cortical (and total) BMD in CSDS susceptible mice. There was a negative correlation between anhedonia-like behavior and BMD. Furthermore, significant differences in the abundance of microbiota (and plasma metabolites) were found between the CSDS + saline and CSDS + arketamine groups. Correlations were observed between the abundance of certain microbiota (and plasma metabolites) and cortical (and total) BMD. These data suggest that, in addition to its anti-anhedonia effect, arketamine might ameliorate the reduced cortical (and total) BMD seen in CSDS susceptible mice through the gut-microbiota-bone-brain axis. Therefore, arketamine could serve as a drug therapy for depressed patients with low BMD. This article is part of the Special Issue on "Ketamine and its Metabolites".

Investigation of dichlorodiphenyltrichloroethane (DDT) on xenobiotic enzyme disruption and metabolomic bile acid biosynthesis in DDT-sprayed areas using wild rats.

Dichlorodiphenyltrichloroethane (DDT) is an organochlorine insecticide used worldwide. Several studies have reported the toxic effects of DDT and its metabolites on steroid hormone biosynthesis; however, its environmental effects are not well understood. This study examined wild rats collected in DDT-sprayed areas of South Africa and quantified plasma metabolites using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Fold change analysis of the metabolome revealed the effect of DDT on bile acid biosynthesis. Gene expression of the related enzyme in rat liver samples was also quantified. Significant association was found between DDT and gene expression levels related to constitutive androstane receptor mediated enzymes, such as Cyp2b1 in rat livers. However, our results could not fully demonstrate that enzymes related to bile acid biosynthesis were strongly affected by DDT. The correlation between DDT concentration and gene expression involved in steroid hormone synthesis in testis was also evaluated; however, no significant correlation was found. The disturbance of metabolic enzymes occurred in rat liver in the target area. Our results suggest that DDT exposure affects gene expression in wild rats living in DDT-sprayed areas. Therefore, there is a need for DDT toxicity evaluation in mammals living in DDT-sprayed areas. We could not find an effective biomarker that could reflect the mechanism of DDT exposure; however, this approach can provide new insights for future research to evaluate DDT effects in sprayed areas.