Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

[Chemical composition and pharmacological effects of Cinnamomum camphora chvar. borneol essential oil: a review].

Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.

Prefrontal GABAA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABAARs [GABAA(δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(δ)R expression and function in their mPFC. Second, knockdown of GABAA(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.SIGNIFICANCE STATEMENT The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABAA receptor (GABAAR) family in this region act to suppress fear extinction. However, the roles of specific GABAAR subtypes in mPFC are largely unknown. We observed that the GABAAR-containing δ-subunit [GABAA(δ)R], a subtype of GABAARs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABAAR family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABAARs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABAA(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABAA(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.

Ambient air pollution and homocysteine: Current epidemiological evidence and a call for further research.

Elevated blood homocysteine (Hcy) is an independent risk factor for cardiovascular disease. A growing number of studies have evaluated the link between air pollution and blood Hcy levels, but the results are inconsistent. To date, no systematic review of the published studies has been conducted yet. We aimed to provide a comprehensive overview of these studies. We systematically searched three international databases (PubMed, Web of Science, and Embase) and four Chinese databases (Wanfang, CNKI, CBM, and VIP) for peer-reviewed epidemiological studies investigating associations between ambient air pollutants and Hcy levels published before December 2019. We screened literature, extracted data, assessed methodological quality, and evaluated the risk of bias of the included studies. Of 1157 identified articles, 10 were finally included in this systematic review. Most were cross-sectional studies and were performed in developed countries. Particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) and/or 10 µm (PM10) were investigated in all of the included studies. Overall, the evidence generally supports a positive association between higher PM concentrations and elevated Hcy levels. However, high heterogeneity in terms of study participants, study design, exposure duration, and particle components and sources, low methodological quality and probable high risk of bias in some studies, and limited literature number precluded us from drawing a robust conclusion. Associations between Hcy and gaseous pollutants were explored in only one or two studies, and the results were inconclusive. Additional, well-designed studies remain required to validate the association between air pollution and Hcy.

Exposure to ambient air pollution and chronic bronchitis: Findings from over 6.6 million adults in northwestern China.

BACKGROUND: Ambient air pollution increases the risk of respiratory mortality and morbidity, but evidence concerning effects of air pollution on chronic bronchitis (CB) is scarce. This study aimed to evaluate the associations of a set of air pollutants with the burden of CB, and to explore potential modifiers on the associations. METHODS: In 2020, a total of 6,556,440 adults living in the Northwestern region of China were recruited. The Space-Time Extra-Trees model was employed to assess the annual average concentrations of six air pollutants for the three years (2017-2019) before 2020 , and subsequently allocated to the participants based on the latitude and longitude of their home addresses. We investigated the associations between the levels of various air pollutants and the odds of CB using generalized linear mixed models, and conducted multiple sensitivity analyses and subgroup analyses. RESULTS: The odds of CB displays an approximately linear association with particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), particulate matter with aerodynamic diameter ≤10 µm (PM10), while it shows a non-linear relationship with gaseous pollutants. In the adjusted model, the odds ratios and 95% confidence intervals for CB per 10 µg/m3 increase in PM2.5, PM10, and sulfur dioxide (SO2) were 1.297 (1.262-1.332), 1.072 (1.064-1.080), and 2.587 (2.186-3.063), respectively. Furthermore, several additional sensitivity analyses demonstrated the stability of these associations. Subgroup analyses found that the aforementioned associations were greater among participants aged below 50 years old and those who smoked and had no leisure time exercise. CONCLUSION: Long-term exposure to ambient air pollutants may increase the odds of CB, especially among younger people and those with unhealthy lifestyles.

Global, regional, and national burden of preterm birth attributable to ambient and household PM2.5 from 1990 to 2019: Worsening or improving?

BACKGROUND: Maternal exposure to fine particular matter (PM2.5) during pregnancy, including ambient and household PM2.5, has been linked with increased risk of preterm birth (PTB). However, the global spatio-temporal distribution of PTB-related deaths and disability-adjusted life years (DALYs) attributable to PM2.5 is not well documented. We estimated the global, regional, and national patterns and trends of PTB burden attributable to both ambient and household PM2.5 from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study (GBD) 2019 database, we obtained the numbers of deaths and DALYs as well as age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) of PTB attributable to total, ambient, and household PM2.5 by socio-demographic index (SDI) and sex during 1990-2019. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of attributable burdens. RESULTS: In 2019, 126,752 deaths and 11.3 million DALYs related to PTB worldwide (two-thirds in Western Sub-Saharan Africa and South Asia) could be caused by excess PM2.5 above the theoretical minimum-risk exposure level (TMREL), of which 39 % and 61 % were attributable to ambient PM2.5 and household PM2.5, respectively. From 1990 to 2019, the global ASMR due to ambient PM2.5 increased slightly by 7.08 % whereas that due to household PM2.5 decreased substantially by 58.81 %, although the latter still dominated the attributable PTB burden, especially in low and low-middle SDI regions. Similar results were also observed for ASDRs. In addition, PTB burden due to PM2.5 was higher in male infants and in lower SDI regions. CONCLUSIONS: Globally in 2019, PM2.5 remains a great concern on the PTB burden, especially in Western Sub-Saharan Africa and South Asia. Between 1990 and 2019, age-standardized burden of PTB due to ambient PM2.5 increased globally, while that due to household PM2.5 decreased markedly but still dominated in low and low-middle SDI regions.

Association between Residential Greenness and Human Microbiota: Evidence from Multiple Countries.

BACKGROUND: Greenness, referring to a measurement of the density of vegetated land (e.g., gardens, parks, grasslands), has been linked with many human health outcomes. However, the evidence on greenness exposure and human microbiota remains limited, inconclusive, drawn from specific regions, and based on only modest sample size. OBJECTIVES: We aimed to study the association between greenness exposure and human microbial diversity and composition in a large sample across 34 countries and regions. METHODS: We explored associations between residential greenness and human microbial alpha-diversity, composition, and genus abundance using data from 34 countries. Greenness exposure was assessed using the normalized difference vegetation index and the enhanced vegetation index mean values in the month before sampling. We used linear regression models to estimate the association between greenness and microbial alpha-diversity and tested the effect modification of age, sex, climate zone, and pet ownership of participants. Differences in microbial composition were tested by permutational multivariate analysis of variance based on Bray-Curtis distance and differential taxa were detected using the DESeq2 R package between two greenness exposure groups split by median values of greenness. RESULTS: We found that higher greenness was significantly associated with greater richness levels in the palm and gut microbiota but decreased evenness in the gut microbiota. Pet ownership and climate zone modified some associations between greenness and alpha-diversity. Palm and gut microbial composition at the genus level also varied by greenness. Higher abundances of the genera Lactobacillus and Bifidobacterium, and lower abundances of the genera Anaerotruncus and Streptococcus, were observed in people with higher greenness levels. DISCUSSION: These findings suggest that residential greenness was associated with microbial richness and composition in the human skin and gut samples, collected across different geographic contexts. Future studies may validate the observed associations and determine whether they correspond to improvements in human health. https://doi.org/10.1289/EHP12186.

Associations between greenspace surrounding schools and lipid levels in Chinese children and teenagers.

Little evidence exists concerning the associations of greenspace with childhood lipid profiles and dyslipidemias, especially in developing countries and regions. We aimed to investigate the associations of greenspace surrounding schools with lipid levels and dyslipidemia prevalence among Chinese children and teenagers. We obtained baseline information and health data of 10,408 children and teenagers (aged 6-18 years) who studied from 94 schools in China. We measured levels of four blood lipids: triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dyslipidemias were defined using standard recommendations. Greenness surrounding schools were assessed using two satellite-based greenness indices, Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) at 300-, 500-, and 1000-m circular buffers based on each school's latitude and longitude. We used random forest model combined with meteorological and remote sensing data to estimate air pollution levels surrounding each school. We used generalized linear mixed models to estimate the associations of greenness with lipid levels and dyslipidemias prevalence. We also performed sub-group and mediation analyses. An interquartile range (IQR) increase in NDVI500m was significantly associated with a 0.064 mmol/L (95% confidence interval [CI]: 0.083, -0.045) and 0.049 mmol/L (95% CI: 0.065, -0.033) decreased TC and LDL-C levels, respectively, as well as a 0.13-fold (95% CI: 0.01, 0.23) and 0.17-fold (95% CI: 0.01, 0.30) decreased odds of hypercholesterolemia and hyperbetalipoproteinemia, respectively. Associations were stronger in students aged ≤12 years and born to parents having lower education levels compared to their counterparts. Particle with aerodynamic diameter ≤2.5 µm (PM2.5) mediated 61.5% and 16.7% of the association of greenness with TG and LDL-C levels, respectively. In summary, higher school-based greenness exposure was beneficially associated with lipid levels among Chinese children and adolescents, and part of the association can be explained by lowed PM2.5 levels.

Global burden and drivers of hyperglycemia: Estimates and predictions from 1990 to 2050.

Hyperglycemia is a key risk factor for death and disability worldwide. To better inform prevention strategies, we aimed to delineate and predict the temporal, spatial, and demographic patterns in mean fasting plasma glucose (FPG) levels and their related disease burden globally. Based on the Global Burden of Disease Study 2019, we estimated the distributions of mean FPG levels and high FPG-related disease burden by age, sex, year, socioeconomic status (SES), and geographical region from 1990 to 2050. We also investigated the possible associations of demographic, behavioral, dietary, metabolic, and environmental factors with FPG levels and high FPG-related disease burden. In 2019, the global mean FPG level was 5.40 mmol/L (95% uncertainty interval [UI]: 4.86-6.00), and high FPG contributed to 83.0 deaths (95% UI, 64.5-107.1) and 2,104.3 DALYs (95% UI: 1,740.7-2,520.7) per 100,000 people. For both historical (1990-2019) and future (2020-2050) periods, the mean FPG levels and the high FPG-related disease burden increased globally, with greater increases among the middle-aged and elderly, and people in low-to-middle SES countries, relative to their counterparts. Aging, unhealthy lifestyles, elevated body mass index, and lower air temperatures were potential risk factors for high FPG levels and the high FPG-related disease burden. This study demonstrates that high FPG continues to contribute to the global disease burden and is expected to do so for at least the next 30 years. Older people and those living in low-to-middle SES countries should receive more attention in glycemic management health interventions. In addition, effective interventions that target identified risk factors should be adopted to handle the increasingly large disease burden of high FPG.

Outdoor environmental exposome and the burden of tuberculosis: Findings from nearly two million adults in northwestern China.

We simultaneously assessed the associations for a range of outdoor environmental exposures with prevalent tuberculosis (TB) cases in a population-based health program with 1940,622 participants ≥ 15 years of age. TB status was confirmed through bacteriological and clinical assessment. We measured 14 outdoor environmental exposures at residential addresses. An exposome-wide association study (ExWAS) approach was used to estimate cross-sectional associations between environmental exposures and prevalent TB, an adaptive elastic net model (AENET) was implemented to select important exposure(s), and the Extreme Gradient Boosting algorithm was subsequently applied to assess their relative importance. In ExWAS analysis, 12 exposures were significantly associated with prevalent TB. Eight of the exposures were selected as predictors by the AENET model: particulate matter ≤ 2.5 µm (odds ratio [OR]=1.01, p = 0.3295), nitrogen dioxide (OR=1.09, p < 0.0001), carbon monoxide (OR=1.19, p < 0.0001), and wind speed (OR=1.08, p < 0.0001) were positively associated with the odds of prevalent TB while sulfur dioxide (OR=0.95, p = 0.0017), altitude (OR=0.97, p < 0.0001), artificial light at night (OR=0.98, p = 0.0001), and proportion of forests, shrublands, and grasslands (OR=0.95, p < 0.0001) were negatively associated with the odds of prevalent TB. Air pollutants had higher relative importance than meteorological and geographical factors, and the outdoor environment collectively explained 11% of TB prevalence.

Association between long-term green space exposure and mortality in China: A difference-in-differences analysis of national data in 2000, 2010 and 2019.

BACKGROUND: Effects of green space on human health have been well-documented in western, high-income countries. Evidence for similar effects in China is limited. Moreover, the underlying mechanisms linking green space and mortality are yet to be established. We therefore conducted a nation-wide study to assess the association between green space and mortality in China using a difference-in-difference approach, which applied a causal framework and well controlled unmeasured confounding. In addition, we explored whether air pollution and air temperature could mediate the association. METHODS: In this analysis, we collected data on all-cause mortality and sociodemographic characteristics for each county in China from the 2000 and 2010 censuses and the 2020 Statistical Yearbook. Green space exposure was assessed using county-level normalized difference vegetation index (NDVI) and the percentage of green space (forest, grasslands, shrub land and wetland). We applied a difference-in-differences approach to evaluate the association between green space and mortality. We also performed mediation analysis (by air pollution and air temperature). RESULTS: Our sample consisted of 2726 counties in 2000 and 2010 as well as 1432 counties in 2019. In the 2000 versus 2019 comparison, a 0.1 unit increase in NDVI was associated with a 2.4 % reduction in mortality [95 % confidence interval (CI) 0.4-4.3 %], and a 10 % increase in percentage of green space was associated with a 4.7 % reduction (95 % CI 0-9.2 %) in mortality. PM2.5 and air temperature mediated 0.3 % to 12.3 % of the associations. CONCLUSIONS: Living in greener counties may be associated with lower risk of mortality in China. These findings could indicate the potential of a population-level intervention to reduce mortality in China, which has important public health implications at the county level.

The value of fecal calprotectin in Clostridioides difficile infection: A systematic review.

As a marker of inflammation, calprotectin has potential application value in a variety of inflammatory diseases, such as arthritis and bacterial infections. Clostridioides difficile infection (CDI) is an infectious disease that causes intestinal damage and inflammation. This systematic review aims to determine whether fecal calprotectin has application value in CDI. Nine databases were searched from inception to 6 June 2022, and 17 studies were included. These studies were divided into four groups according to their content. Generally speaking, fecal calprotectin is not an ideal indicator for the diagnosis and prognosis prediction of CDI but may serve as a potential indicator for assessing disease severity and as a readily detectable marker for CDI screening. In addition, patients in need of treatment or with detectable toxins in stool may tend to have higher levels of fecal calprotectin. In summary, fecal calprotectin has some potential application value in CDI. However, further studies are needed to verify these findings and determine the reliability of calprotectin as a biomarker for CDI.

GABAA(δ) receptor hypofunction in the amygdala-hippocampal circuit underlies stress-induced anxiety.

Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders. However, the molecular and circuit mechanisms underlying the dysregulation remain elusive. Here, by using a mouse model of chronic social defeat stress (CSDS), we observed that the dysregulation varied drastically across individual projection neurons (PNs) in the basolateral amygdala (BLA), one of the kernel amygdala subregions critical for stress coping. While persistently reducing the extrasynaptic GABAA receptor (GABAAR)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus (BLA â†’ vHPC PNs), CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis (BLA â†’ adBNST PNs), suggesting projection-based dysregulation of tonic inhibition in BLA PNs by CSDS. Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss- and gain-of-function of δ-containing GABAARs (GABAA(δ)Rs) in BLA â†’ vHPC and BLA â†’ adBNST PNs, respectively. Importantly, it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice. Virally mediated maintenance of GABAA(δ)R currents in BLA â†’ vHPC PNs occluded CSDS-induced anxiety-like behavior. These findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.

Green space and cardiovascular disease: A systematic review with meta-analysis.

Exposure to green space has been proposed to be beneficially associated with cardiovascular morbidity and mortality. Many studies have explored this topic, but the results remain conflicting. We aimed to evaluate the epidemiological evidence on this topic by performing a systematic review with meta-analysis. We searched PubMed, Web of Science and Embase for studies on the association between green space and cardiovascular disease (CVD) that were published till January 2022. Two authors independently performed study selection, data extraction, quality assessment, and risk of bias assessment. For studies providing detailed numeric data, we also conducted quantitative meta-analyses and calculated the pooled odd ratios (ORs) for associations between the most commonly used exposure estimate (normalized difference vegetative index [NDVI]) and five CVD events: CVD mortality, ischemic heart disease (IHD) mortality, cerebrovascular disease (CBVD) mortality, and stroke incidence/prevalence. Additional analyses were conducted to explore the geographical scale effects of NDVI. Publication bias tests were also conducted. Of the 6787 records identified, 53 studies were eligible for inclusion. These studies covered 18 countries and included data from more than 100 million persons. Meta-analyses showed that a 0.1 increase in NDVI was significantly associated with 2-3% lower odds of CVD mortality (OR: 0.97, 95% CI: 0.96-0.99), IHD mortality (OR: 0.98, 95% CI: 0.96-1.00), CBVD mortality (OR: 0.98, 95% CI: 0.97-1.00), and stroke incidence/prevalence (OR: 0.98, 95% CI: 0.96-0.99). There was no significant difference between the pooled estimates for different buffer sizes. No evidence of publication bias was detected. We provide strong and robust evidence for the beneficial effects of green space exposure on cardiovascular health. More prospective studies and mechanistic studies, especially that conducted in low- and middle-income countries, are merited to strengthen our conclusions.

Machine learning identifies prominent factors associated with cardiovascular disease: findings from two million adults in the Kashgar Prospective Cohort Study (KPCS).

BACKGROUND: Identifying factors associated with cardiovascular disease (CVD) is critical for its prevention, but this topic is scarcely investigated in Kashgar prefecture, Xinjiang, northwestern China. We thus explored the CVD epidemiology and identified prominent factors associated with CVD in this region. METHODS: A total of 1,887,710 adults at baseline (in 2017) of the Kashgar Prospective Cohort Study were included in the analysis. Sixteen candidate factors, including seven demographic factors, 4 lifestyle factors, and 5 clinical factors, were collected from a questionnaire and health examination records. CVD was defined according to International Clinical Diagnosis (ICD-10) codes. We first used logistic regression models to investigate the association between each of the candidate factors and CVD. Then, we employed 3 machine learning methods-Random Forest, Random Ferns, and Extreme Gradient Boosting-to rank and identify prominent factors associated with CVD. Stratification analyses by sex, ethnicity, education level, economic status, and residential setting were also performed to test the consistency of the ranking. RESULTS: The prevalence of CVD in Kashgar prefecture was 8.1%. All the 16 candidate factors were confirmed to be significantly associated with CVD (odds ratios ranged from 1.03 to 2.99, all p values < 0.05) in logistic regression models. Further machine learning-based analysis suggested that age, occupation, hypertension, exercise frequency, and dietary pattern were the five most prominent factors associated with CVD. The ranking of relative importance for prominent factors in stratification analyses showed that the factor importance generally followed the same pattern as that in the overall sample. CONCLUSIONS: CVD is a major public health concern in Kashgar prefecture. Age, occupation, hypertension, exercise frequency, and dietary pattern might be the prominent factors associated with CVD in this region.In the future, these factors should be given priority in preventing CVD in future.

Epidemiology and pain in elementary school-aged players: a survey of Japanese badminton players participating in the national tournament.

Pain is common in athletes which should be well managed. To identify risk factors for shoulder pain, and the association between shoulder pain, lower back pain and knee pain among elementary school-aged badminton players, we conducted a cross-sectional study to collect data of the past year among 611 elementary school age (7-12 years old) badminton players belonging to the Japan Schoolchildren Badminton Federation using a questionnaire. Odds ratio (OR) and 95% confidence interval (CI) were estimated by multivariate logistic regression analysis. The overall incidence rate of shoulder injuries, lower back injuries and knee injuries was 0.38 injuries per 1000 h of badminton training. Players with training time per day > 2.5 h were 2.64 times (95% CI 1.03-6.78, p = 0.043) more likely to sustain shoulder pain than those with training time per day ≤ 2.5 h. A significant association was revealed between shoulder pain and knee pain as well as between lower back pain and knee pain as training hours per day > 2.5 h. Moreover, lower back pain was significantly associated with shoulder pain independent of training hours per day (≤ 2.5 h: p = 0.001; > 2.5 h: p < 0.001). These findings indicate that training time per day is risk factor, and shoulder pain, lower back pain and knee pain were associated with each other in elementary school-aged badminton players.

Early life stress induces anxiety-like behavior during adulthood through dysregulation of neuronal plasticity in the basolateral amygdala.

AIMS: Early life stress (ELS) increases the risk of psychiatric diseases such as anxiety disorders and depression in later life. Hyperactivation of the basolateral amygdala (BLA) neurons plays a pivotal role in the pathogenesis of stress-related diseases. However, the functional roles of BLA neurons in ELS-induced anxiety disorders are not completely understood. MAIN METHODS: Mice were subjected to maternal separation (MS) during postnatal days 3 to 21 to mimic ELS. Anxiety-like behavior was tested by open field test (OFT), elevated plus maze (EPM), and novelty suppressed feeding (NSF). Then, c-fos expression, a proxy for neuronal activity, was evaluated by immunofluorescence. Finally, synaptic transmission and intrinsic excitability were measured by whole-cell patch-clamp recordings. KEY FINDINGS: MS significantly increased anxiety-like behavior in adulthood, as indicated by less time spent in the center area of the OFT, less time spent in and fewer entries to the open arms of the EPM, and increased latency to feed in NSF. Mechanistically, MS increased the expression of c-fos in BLA. MS enhanced the excitatory, but not inhibitory, synaptic transmission onto BLA projection neurons (PNs), which was caused by enhanced presynaptic glutamate release. Moreover, MS also markedly increased the intrinsic neuronal excitability of BLA PNs, probably due to the reduced medium afterhyperpolarization (mAHP) in BLA PNs. SIGNIFICANCE: Our results suggest that the changes of neuronal activity and synaptic transmission in the BLA PNs may play a crucial role in ELS-induced anxiety-like behavior, and these findings provide new insights into the pathological mechanisms of stress-related anxiety disorders.

Greenspace and human health: An umbrella review.

Multiple systematic reviews on greenspace and health outcomes exist, but the overall evidence base remains unclear. Therefore, we performed an umbrella review to collect and appraise all relevant systematic reviews of epidemiological studies on greenness exposure and health. We searched PubMed, Embase, and Web of Science from inception to June 28, 2021, and screened references of relevant articles. Systematic reviews with or without meta-analyses of epidemiological studies that examined the associations of greenness with any health outcome were included. Two independent investigators performed study selection and data extraction. We also evaluated the methodological quality of the included systematic reviews using the "Assessing the Methodological Quality of Systematic Reviews 2" checklist. A total of 40 systematic reviews and meta-analyses were included, of which most were cross-sectional studies conducted in high-income countries. Greenspace exposure was estimated with various objective and subjective parameters. Beneficial associations of greenspace with all-cause and stroke-specific mortality, CVD morbidity, cardiometabolic factors, mental health, low birth weight, physical activity, sleep quality, and urban crime were observed. No consistent associations between greenspace and other health outcomes (e.g., cancers) were observed. Most of the included systematic reviews and meta-analyses had one or more limitations in methodology. Our findings provide supportive evidence regarding the beneficial effects of greenspace exposure on some aspects of human health. However, the credibility of such evidence was compromised by methodological limitations. Better performed systematic reviews and meta-analyses as well as longitudinal designed primary studies are needed to validate this conclusion.