The COVID-19 pandemic brought about a major public health concern worldwide. It forced many countries to enforce lockdowns, leading to the closure of higher learning institutions. The abrupt shift in the lifestyle of students had a profound impact on their mental health. This study aims to determine the prevalence and factors associated with mental health conditions among university students in Tanzania during the COVID-19 pandemic. A sample of 425 students from six medical universities and colleges in Tanzania completed an online survey and was included in the analysis. The questionnaire consisted of validated Depression, Anxiety and Stress Scale-21 Items (DASS-21) questions (Cronbach's alpha = 0.92) assessing the presence of mental health symptoms: depression, anxiety, and stress. Multivariable logistic regression models were fitted to explain the factors associated with mental health conditions. A P-value < 0.05 was considered statistically significant in all inferential analyses. The median age (interquartile range) of the participants was 24 (22-26). The prevalence of mental health conditions was 28.94%, 54.12%, and 15.06% for depression, anxiety, and stress, respectively, while the prevalence of having any mental health condition was 58.59%. In an adjusted regression model, being in the fourth and fifth years of study and living with a spouse were significantly associated with increased odds of depression: AOR = 5.99 (1.31-27.47), AOR = 5.52 (1.18-25.81), and AOR = 1.84 (1.08-3.15), respectively. Moreover, studying in private universities and living with a spouse were significantly associated with an increased likelihood of anxiety: AOR = 2.35 (1.72-2.76), and AOR = 2.32 (1.20-4.50), respectively. The likelihood of stress was only among participants studying in private universities; AOR = 2.90 (1.60-5.27). The study revealed alarmingly high rates of mental health conditions among medical students in Tanzania during the COVID-19 pandemic. The findings suggest the need for regular checkups for medical students regarding their mental health status. Additionally, it recommends that the government and other stakeholders establish mental health services within the universities for the effective prevention of the rising burden of mental health problems among universities in Tanzania and other countries with similar settings.

To provide a contemporary global prevalence of mental health issues among the general population amid the coronavirus disease-2019 (COVID-19) pandemic. We searched electronic databases, preprint databases, grey literature, and unpublished studies from January 1, 2020, to June 16, 2020 (updated on July 11, 2020), with no language restrictions. Observational studies using validated measurement tools and reporting data on mental health issues among the general population were screened to identify all relevant studies. We have included information from 32 different countries and 398,771 participants. The pooled prevalence of mental health issues amid the COVID-19 pandemic varied widely across countries and regions and was higher than previous reports before the COVID-19 outbreak began. The global prevalence estimate was 28.0% for depression; 26.9% for anxiety; 24.1% for post-traumatic stress symptoms; 36.5% for stress; 50.0% for psychological distress; and 27.6% for sleep problems. Data are limited for other aspects of mental health issues. Our findings highlight the disparities between countries in terms of the poverty impacts of COVID-19, preparedness of countries to respond, and economic vulnerabilities that impact the prevalence of mental health problems. Research on the social and economic burden is needed to better manage mental health problems during and after epidemics or pandemics. Systematic review registration: PROSPERO CRD 42020177120.

The prevalence of depression may be affected by changes in psychiatric practices and the availability of online mental health information in the past two decades. This study aimed to evaluate the aggregate prevalence of depression in communities from different countries between 1994 and 2014 and to explore the variations in prevalence stratified by geographical, methodological and socio-economic factors. A total of 90 studies were identified and met the inclusion criteria (n = 1,112,573 adults) with 68 studies on single point prevalence, 9 studies on one-year prevalence, and 13 studies on lifetime prevalence of depression. A random-effects model meta-analysis that was performed to calculate the aggregate point, one-year and lifetime prevalence of depression calculated prevalences of 12.9%, 7.2% and 10.8% respectively. Point prevalence of depression was significantly higher in women (14.4%), countries with a medium human development index (HDI) (29.2%), studies published from 2004 to 2014 (15.4%) and when using self-reporting instruments (17.3%) to assess depression. Heterogeneity was identified by meta-regression and subgroup analysis, and response rate, percentage of women and year of publication, respectively, were determined contribute to depression prevalence. This meta-analysis allows benchmarking of the prevalence of depression during the era when online health information emerged, facilitating future comparisons.

Depression and antidepressant medications increase risk for type 2 diabetes. Cambodian-Americans have exceedingly high rates of both depression and diabetes. This paper reports outcomes of a diabetes prevention trial for Cambodian-Americans with depression. Primary outcomes were HbA1c, insulin resistance and depressive symptoms. Participants were aged 35-75, Khmer speaking, at risk for diabetes, and met study criteria for likely depression by either (a) antidepressant medication and/or (b) prolonged elevated depressive symptoms. Participants were randomized to one of three community health worker (CHW) interventions: (1) lifestyle intervention called Eat, Walk, Sleep (EWS), (2) EWS plus medication therapy management sessions with a pharmacist/CHW team to resolve drug therapy problems (EWS + MTM), or, (3) social services (SS; control). Assessments were at baseline, post-treatment (12 months), and follow-up (15 months). The n = 188 participants were 78% female, average age of 55 years, half had a household income < $20,000, and modal educational attainment was 7.0 years. Compared to the other arms, EWS + MTM showed a significant decrease in HbA1c and a trend for reduced inflammation and stress hormones. Depressive symptoms improved for EWS and EWS + MTM relative to SS. There was no change in insulin resistance. Cardiometabolic and mental health can be improved in tandem among immigrant and refugee groups.

Antibiotic resistance is a global health crisis that requires urgent action to stop its spread. To counteract the spread of antibiotic resistance, we must improve our understanding of the origin and spread of resistant bacteria in both community and healthcare settings. Unfortunately, little attention is being given to contain the spread of antibiotic resistance in community settings (i.e., locations outside of a hospital inpatient, acute care setting, or a hospital clinic setting), despite some studies have consistently reported a high prevalence of antibiotic resistance in the community settings. This study aimed to investigate the prevalence of antibiotic resistance in commensal Escherichia coli isolates from healthy humans in community settings in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we synthesized studies conducted from 1989 to May 2020. A total of 9363 articles were obtained from the search and prevalence data were extracted from 33 articles and pooled together. This gave a pooled prevalence of antibiotic resistance (top ten antibiotics commonly prescribed in LMICs) in commensal E. coli isolates from human sources in community settings in LMICs of: ampicillin (72% of 13,531 isolates, 95% CI: 65-79), cefotaxime (27% of 6700 isolates, 95% CI: 12-44), chloramphenicol (45% of 7012 isolates, 95% CI: 35-53), ciprofloxacin (17% of 10,618 isolates, 95% CI: 11-25), co-trimoxazole (63% of 10,561 isolates, 95% CI: 52-73), nalidixic acid (30% of 9819 isolates, 95% CI: 21-40), oxytetracycline (78% of 1451 isolates, 95% CI: 65-88), streptomycin (58% of 3831 isolates, 95% CI: 44-72), tetracycline (67% of 11,847 isolates, 95% CI: 59-74), and trimethoprim (67% of 3265 isolates, 95% CI: 59-75). Here, we provided an appraisal of the evidence of the high prevalence of antibiotic resistance by commensal E. coli in community settings in LMICs. Our findings will have important ramifications for public health policy design to contain the spread of antibiotic resistance in community settings. Indeed, commensal E. coli is the main reservoir for spreading antibiotic resistance to other pathogenic enteric bacteria via mobile genetic elements.

Bystander cardiopulmonary resuscitation (BCPR), early defibrillation and timely treatment by emergency medical services (EMS) can double the chance of survival from out-of-hospital sudden cardiac arrest (OHCA). We investigated the effect of the COVID-19 pandemic on the pre-hospital chain of survival. We searched five bibliographical databases for articles that compared prehospital OHCA care processes during and before the COVID-19 pandemic. Random effects meta-analyses were conducted, and meta-regression with mixed-effect models and subgroup analyses were conducted where appropriate. The search yielded 966 articles; 20 articles were included in our analysis. OHCA at home was more common during the pandemic (OR 1.38, 95% CI 1.11-1.71, p = 0.0069). BCPR did not differ during and before the COVID-19 pandemic (OR 0.94, 95% CI 0.80-1.11, p = 0.4631), although bystander defibrillation was significantly lower during the COVID-19 pandemic (OR 0.65, 95% CI 0.48-0.88, p = 0.0107). EMS call-to-arrival time was significantly higher during the COVID-19 pandemic (SMD 0.27, 95% CI 0.13-0.40, p = 0.0006). Resuscitation duration did not differ significantly between pandemic and pre-pandemic timeframes. The COVID-19 pandemic significantly affected prehospital processes for OHCA. These findings may inform future interventions, particularly to consider interventions to increase BCPR and improve the pre-hospital chain of survival.

Access to healthcare services is a fundamental human right for every citizen, and it is the responsibility of the nation to guarantee that these services are acceptable, easily accessible, and timely. Barriers to accessing health services may have a detrimental effect on an individual's physical, and mental health, and overall quality of life. However, access to health care services is a common problem in developing countries. Therefore, this study aimed to investigate spatial distribution and determinants of barriers to healthcare access among female youths in Ethiopia. Secondary data analysis was conducted based on the Demographic and Health Surveys data conducted in Ethiopia. A total weighted sample of 6143 female youths aged 15-24 years old was included in this study. A mixed-effect analysis was employed to identify factors contributing to barriers to healthcare access among youths in Ethiopia. Adjusted Odds Ratio with 95% CI was used to declare the strength and significance of the association. The concentration index was used to assess wealth-related inequalities, while spatial analysis was used to explore the spatial distribution and significant windows of barriers to healthcare access. This study revealed that the magnitude of barriers to healthcare access among female youth was 61.3% with 95%CI (60.1 to 62.5) to at least one or more of the four reasons. Age 15-19 years old (AOR = 0.80, 95%CI 0.68 to 0.95), no formal education (AOR = 2.26, CI 1.61, 3.18), primary education (AOR = 2.21, CI 1.66, 2.95), marital status (AOR = 1.43, 95% CI 1.21, 1.70), poor household wealth (AOR = 1.63, 95% CI 1.31, 2.05), no Media exposure (AOR = 1.67, 95%CI 1.41-1.98), reside in rural areas (AOR = 1.63, 95%CI 1.05 to 2.54), and low community media exposure (AOR = 1.45, 95%CI 1.01-2.08) were significantly associated with barriers of health care service. Barriers to healthcare access were significantly and disproportionately concentrated in poor households. A non-random Barrier to healthcare access was observed in Ethiopia. Among the 9 regions, primary clusters were identified in only 4 regions (North Ormiya, Benishangul Gumuz, Gambella, and South Nation Nationality and Peoples regions. A significant proportion of female youths faced barriers to health care access Age, educational status, marital status, rural residency, low economic status, and media exposure were factors associated with barriers to health care access. Therefore, program planners and decision-makers should work on improving the country's economy to a higher economic level to improve the wealth status of the population, promote media exposure, and increase access to education.

Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta = 0.04, P = 2 × 10-10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta = 0.05, P = 6 × 10-12; rs2911280, beta = 0.09, P = 6 × 10-10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta = -0.03, P = 4 × 10-9; rs761772, beta = 0.05, P = 5 × 10-9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers.

Felidae as definitive hosts for Toxoplasma gondii play a major role in transmission to all warm-blooded animals trough oocysts dissemination. Therefore the current comprehensive study was performed to determine the global status of T. gondii infection in domestic and wild felids aiming to provide comprehensive data of interest for further intervention approaching the One Health perspective. Different databases were searched by utilizing particular key words for publications related to T. gondii infecting domestic and wild feline host species, worldwide, from 1970 to 2020. The review of 337 reports showed that the seroprevalence of T. gondii in domestic cats and wild felids was estimated in 37.5% (95% CI 34.7-40.3) (I2 = 98.3%, P < 0.001) and 64% (95% CI 60-67.9) (I2 = 88%, P < 0.0001), respectively. The global pooled prevalence of oocysts in the fecal examined specimens from domestic cats was estimated in 2.6% (95% CI 1.9-3.3) (I2 = 96.1%, P < 0.0001), and that in fecal samples from wild felids was estimated in 2.4% (95% CI 1.1-4.2) (I2 = 86.4%, P < 0.0001). In addition, from 13,252 examined soil samples in 14 reviewed studies, the pooled occurrence of T. gondii oocysts was determined in 16.2% (95% CI 7.66-27.03%). The observed high rates of anti-T. gondii antibodies seroprevalence levels and oocyst excretion frequency in the felids, along with soil (environmental) contamination with oocysts may constitute a potential threat to animal and public health, and data will result of interest in further prophylaxis programs.

The α7 subtype of nicotinic acetylcholine receptor (nAChR) plays a role in the inflammation which is implicated in depression. This study was undertaken to examine the role of α7 nAChR in depression using α7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-α and interlukin-1β in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. α7 nAChR KO mice showed depression-like phenotype. Furthermore, KO mice showed increased brain-derived neurotrophic factor (BDNF) and its receptor TrkB signaling, as well as increased synaptogenesis and spine density in the nucleus accumbens (NAc), although BDNF-TrkB signaling and synaptogenesis were not altered in the prefrontal cortex and hippocampus. Systemic administration of the TrkB antagonist ANA-12, but not the TrkB agonist 7,8-dihydroxyflavone and the selective serotonin reuptake inhibitor fluoxetine, showed a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. In addition, bilateral infusion of ANA-12 into NAc promoted a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. These findings suggest that increased BDNF-TrkB signaling and synaptogenesis in the NAc by deletion of α7 nAChR plays a key role in depression.

Schizophrenia is a chronic mental condition presenting a wide range of symptoms. Although it has a low prevalence compared to other mental conditions, it has a negative impact on social and occupational functions. This study aimed to assess the appropriateness of antipsychotic medications administered to schizophrenic patients and describe current treatment patterns for schizophrenia. A retrospective cohort study was conducted in all patients over the age of 15 with an active diagnosis of schizophrenia and treated with antipsychotics between 2008 and 2013 in the Valencia region. A total of 19,718 patients were eligible for inclusion. The main outcome assessed was inappropriateness of the pharmacotherapeutic management, including polypharmacy use. Altogether, 30.4% of patients received antipsychotic polypharmacy, and 6.8% were prescribed three or more antipsychotics. Overdosage affected 318 individuals (1.6%), and 21.5% used concomitant psychotropics without an associated psychiatric diagnosis. Women and people with a comorbid condition like anxiety or depression were less likely to receive antipsychotic polypharmacy. In contrast, increased polypharmacy was associated with concomitant treatment with other psychoactive drugs, and only in user on maintenance therapy, with more visits to the mental health hospital. Overall, we observed a high level of inappropriateness in antipsychotic prescriptions. Greater adherence to guidelines could maximize the benefits of antipsychotic medications while minimizing risk of adverse effects.

Structural and functional plasticity of dendritic spines is the basis of animal learning. The rapid remodeling of actin cytoskeleton is associated with spine enlargement and shrinkage, which are essential for structural plasticity. The calcium-dependent protein kinase C isoform, PKCα, has been suggested to be critical for this actin-dependent plasticity. However, mechanisms linking PKCα and structural plasticity of spines are unknown. Here, we examine the spatiotemporal activation of actin regulators, including small GTPases Rac1, Cdc42 and Ras, in the presence or absence of PKCα during single-spine structural plasticity. Removal of PKCα expression in the postsynapse attenuated Rac1 activation during structural plasticity without affecting Ras or Cdc42 activity. Moreover, disruption of a PDZ binding domain within PKCα led to impaired Rac1 activation and deficits in structural spine remodeling. These results demonstrate that PKCα positively regulates the activation of Rac1 during structural plasticity.

This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

This study aimed to develop a Self-Active Aging Index (S-AAI) for the rural community of Thailand using the World Health Organization (WHO) framework, and score it according to age and gender. Overall, 1,098 elderly people were randomly selected. The self-reported questionnaires were categorized into three segments: health, participation, and security according to the WHO framework. An exploratory factor analysis was used to determine appropriate components. The S-AAI comprised 28 indicators and 9 factors: (1) mental/subjective health; (2) physical health; (3) health behavior and chronic disease; (4) vision and hearing; (5) oral health; (6) social participation; (7) stability in life; (8) financial stability; and (9) secure living. The overall S-AAI for all components was 0.65, with the index inversely proportional to age, but with no gender differences. The S-AAI is potentially Thailand's first multi-dimensional interactive aging assessment tool with a unique cultural context for rural areas. Although this tool is valid, it requires reliability testing.

Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6-12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases.

Patched domain-containing 1 (PTCHD1) is a well-established susceptibility gene for autism spectrum disorder (ASD) and intellectual disability (ID). Previous studies have suggested that alterations in the dosage of PTCHD1 may contribute to the etiology of both ASD and ID. However, there has not yet been a thorough investigation regarding mechanisms that regulate PTCHD1 expression. We sought to characterize the Ptchd1 promoter in a mouse neuronal model, as well as to identify and validate cis regulatory elements. We defined specific regions of the Ptchd1 promoter essential for robust expression in P19-induced neurons. Evolutionarily-conserved putative transcription factor binding sites within these regions were subsequently identified. Using a pairwise comparison of chromatin accessibility between mouse forebrain and liver tissues, a candidate regulatory region, ~ 9.1 kbp downstream of the Ptchd1 stop codon was defined. This region harbours two ENCODE-predicted enhancer cis-regulatory elements. Further, using DNase footprint analysis, a putative YY1-binding motif was also identified. Genomic deletion of the entire 8 kbp downstream open chromatin region attenuated Ptchd1 transcription by over 60% in our neuronal model, corroborating its predicted regulatory function. This study provides mechanistic insights related to the expression of PTCHD1, and provides important context to interpret genetic and genomic variation at this locus which may influence neurodevelopment.

Cortical and subcortical structural alteration has been extensively reported in schizophrenia, including the unusual expansion of gray matter volumes (GMVs) of basal ganglia (BG), especially putamen. Previous genome-wide association studies pinpointed kinectin 1 gene (KTN1) as the most significant gene regulating the GMV of putamen. In this study, the role of KTN1 variants in risk and pathogenesis of schizophrenia was explored. A dense set of SNPs (n = 849) covering entire KTN1 was analyzed in three independent European- or African-American samples (n = 6704) and one mixed European and Asian Psychiatric Genomics Consortium sample (n = 56,418 cases vs. 78,818 controls), to identify replicable SNP-schizophrenia associations. The regulatory effects of schizophrenia-associated variants on the KTN1 mRNA expression in 16 cortical or subcortical regions in two European cohorts (n = 138 and 210, respectively), the total intracranial volume (ICV) in 46 European cohorts (n = 18,713), the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258), and the surface areas (SA) and thickness (TH) of whole cortex and 34 cortical regions in 50 European cohorts (n = 33,992) and eight non-European cohorts (n = 2944) were carefully explored. We found that across entire KTN1, only 26 SNPs within the same block (r2 > 0.85) were associated with schizophrenia across ≥ 2 independent samples (7.5 × 10-5 ≤ p ≤ 0.048). The schizophrenia-risk alleles, which increased significantly risk for schizophrenia in Europeans (q < 0.05), were all minor alleles (f < 0.5), consistently increased (1) the KTN1 mRNA expression in 12 brain regions significantly (5.9 × 10-12 ≤ p ≤ 0.050; q < 0.05), (2) the ICV significantly (6.1 × 10-4 ≤ p ≤ 0.008; q < 0.05), (3) the SA of whole (9.6 × 10-3 ≤ p ≤ 0.047) and two regional cortices potentially (2.5 × 10-3 ≤ p ≤ 0.042; q > 0.05), and (4) the TH of eight regional cortices potentially (0.006 ≤ p ≤ 0.050; q > 0.05), and consistently decreased (1) the BG GMVs significantly (1.8 × 10-19 ≤ p ≤ 0.050; q < 0.05), especially putamen GMV (1.8 × 10-19 ≤ p ≤ 1.0 × 10-4; q < 0.05, (2) the SA of four regional cortices potentially (0.010 ≤ p ≤ 0.048), and (3) the TH of four regional cortices potentially (0.015 ≤ p ≤ 0.049) in Europeans. We concluded that we identified a significant, functional, and robust risk variant block covering entire KTN1 that might play a critical role in the risk and pathogenesis of schizophrenia.

Treatment-resistant depression (TRD) is a severe form of major depressive disorder (MDD) with substantial public health impact and poor treatment outcome. Treatment outcome in MDD is significantly heritable, but genome-wide association studies have failed to identify replicable common marker alleles, suggesting a potential role for uncommon variants. Here we investigated the hypothesis that uncommon, putatively functional genetic variants are associated with TRD. Whole-exome sequencing data was obtained from 182 TRD cases and 2021 psychiatrically healthy controls. After quality control, the remaining 149 TRD cases and 1976 controls were analyzed with tests designed to detect excess burdens of uncommon variants. At the gene level, 5 genes, ZNF248, PRKRA, PYHIN1, SLC7A8, and STK19 each carried exome-wide significant excess burdens of variants in TRD cases (q < 0.05). Analysis of 41 pre-selected gene sets suggested an excess of uncommon, functional variants among genes involved in lithium response. Among the genes identified in previous TRD studies, ZDHHC3 was also significant in this sample after multiple test correction. ZNF248 and STK19 are involved in transcriptional regulation, PHYIN1 and PRKRA are involved in immune response, SLC7A8 is associated with thyroid hormone transporter activity, and ZDHHC3 regulates synaptic clustering of GABA and glutamate receptors. These results implicate uncommon, functional alleles in TRD and suggest promising novel targets for future research.

The scientific community widely acknowledges that the gut microbiota plays a critical role in maintaining host health and can be altered by a range of factors, such as antibiotic use, diet, stress, and infections. Therefore, this study utilized bibliometric analysis to thoroughly investigate research trends in the microbiota and antibiotics. Scopus was used to extract papers linked to microbiota and antibiotics published between 2002 and 2021, and both Microsoft Excel and VOSviewer were used to conduct the analysis of the data. A total of 2,816 publications discussed the connection between the microbiota and antibiotics. Growth occurred in two stages: the first (2002-2015) was characterized by fairly slow publication production, while the second (2016-2021) saw a rapid increase in publishing progress. The United States has the most publications, 654, representing 23.22% of the total. China came second with 372 publications (13.21%), followed by the United Kingdom with 161 publications (5.72%) and India with 157 publications (5.58%). In addition, publications on 'altered intestinal microbiota composition with antibiotic treatment' were introduced after 2017, while 'gut microbiota and antimicrobial resistance' and 'probiotics as an alternative antimicrobial therapy' were introduced before 2017. Based on these results, this study provides an in-depth look at key moments in the history of microbiota and antibiotic research, as well as possible directions for future research in different areas of microbiota and antibiotic research. Therefore, it is suggested that more attention should be given to the latest promising hotspots, such as how antibiotic treatment changes the composition of the gut microbiota.