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Alzheimer's disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16(th), 2021. Fixed- and random-effects meta-analyses were complemented with the I(2) statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs' expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

BACKGROUND: Physical multimorbidity (i.e., =2 chronic conditions) may induce feelings of wish to die (WTD), but there is limited literature on this topic, while the mediators in this association are largely unknown. Thus, the aim of the present study was to investigate this association and its mediators among older Irish adults.; METHODS: Cross-sectional, nationally representative data from Wave 1 of the Irish Longitudinal Study on Ageing 2009-2011 were analyzed. Information on self-reported lifetime diagnosis of 14 chronic physical conditions were obtained. WTD was defined as answering affirmatively to the question "In the last month, have you felt that you would rather be dead?" Multivariable logistic regression and mediation analyses were conducted.; RESULTS: Data on 2941 adults aged =65years [mean (SD) age 73.2 (5.2) years; 45.0% males] were analyzed. Physical multimorbidity was associated with 3.39 (95%CI 1.58, 7.28) times higher odds for WTD. This association was largely explained by pain (% mediated 28.1%), followed by depression (19.4%), sleep problems (18.4%), perceived stress (13.0%), loneliness (10.4%), anxiety (8.1%), and disability (7.2%).; CONCLUSIONS: Multimorbidity was associated with increased odds for WTD among Irish older adults. Addressing the identified mediators may contribute to reducing feelings of WTD among older adults with multimorbidity. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide.\ud \ud MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients.\ud \ud RESULTS: Patients infected with COVID-19 have high amounts of IL-1β, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed.\ud \ud CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Objective The period immediately after the onset of first-episode psychosis (FEP) may present with high risk for suicidal ideation (SI) and attempts, although this risk may differ among patients. Thus, we aimed to identify trajectories of SI in a 2-years follow-up FEP cohort and to assess baseline predictors and clinical/functional evolution for each trajectory of SI. Methods We included 334 FEP participants with data on SI. Growth mixture modeling was used to identify trajectories of SI. Putative sociodemographic, clinical, and cognitive predictors of the distinct trajectories were examined using multinomial logistic regression. Results We identified three distinct trajectories: Non-SI trajectory (85.53% sample), Improving SI trajectory (9.58%), and Worsening SI trajectory (6.89%). Multinomial logistic regression model revealed that greater baseline pessimistic thoughts, anhedonia, and worse perceived family environment were associated with higher baseline SI followed by an Improving trajectory. Older age, longer duration of untreated psychosis, and reduced sleep predicted Worsening SI trajectory. Regarding clinical/functional evolution, individuals within the Improving SI trajectory displayed moderate depression at baseline which ameliorated during the study period, while the Worsening SI subgroup exhibited persistent mild depressive symptoms and greater functional impairment at follow-up assessments. Conclusion Our findings delineated three distinct trajectories of SI among participants with FEP, one experiencing no SI, another in which SI might depend on acute depressive symptomatology, and a last subset where SI might be associated with mild but persistent clinical and functional impairments. These data provide insights for the early identification and tailored treatment of suicide in this at-risk population.

INTRODUCTION: In 2015, the elimination of hunger worldwide by 2030 was declared by the United Nations as a Sustainable Development Goal. However, food insecurity remains pervasive, contributing to socioeconomic health inequalities. The overall objective was to investigate the relationship between food insecurity and intentional injuries among adolescents. METHODS: Individual-level data from the Global School-based Student Health Survey from 89 countries were used (370 719 adolescents, aged 12-17 years). Multilevel logistic regressions were used to examine the sex-specific association between the level of food insecurity (none, medium and high) and intentional injuries (interpersonal violence and suicide attempts), accounting for the clustering of observations within surveys. Random-effects meta-analyses were used to analyse dose-response relationships. RESULTS: Medium and high food insecurity were associated with increased odds of reporting an injury from interpersonal violence among both sexes. A positive dose-response relationship was found, where each level increase in food insecurity was associated with a 30% increase in the odds of an injury due to interpersonal violence among boys (1.30; 95% CI 1.26 to 1.34) and a 50% increase among girls (1.53; 95% CI 1.46-1.62). The odds for suicide attempts increased by 30% for both sexes with each level increase in food insecurity (boys: 1.29; 95% CI 1.25-1.32; girls: 1.29; 95% CI 1.25-1.32). DISCUSSION: The findings indicate that socioeconomic inequalities exist in the risk of intentional injuries among adolescents. Although additional studies are needed to establish causality, the present study suggests that the amelioration of food insecurity could have implications beyond the prevention of its direct consequences.

There is evidence to suggest that tobacco use is associated with suicide attempts. However, it is unclear whether such an association can be extended to include second-hand smoke exposure. Using nationally representative data of school-attending adolescents from 33 countries, we examined the association of tobacco use and exposure to second-hand smoke with suicide attempts.

The objective was to identify immune alterations in patients with fibromyalgia syndrome (FMS) compared to healthy controls (HC) using meta-analysis and meta-regression. Six electronic databases were searched for suitable original articles investigating immune biomarkers in FMS in comparison to HC. We extracted outcomes and variables of interest, such as mean and SD of peripheral blood immune biomarkers, age or sex. A random-effects model with restricted maximum-likelihood estimator was used to compute effect sizes (standardized mean difference and 95% CI, Hedges' g) and meta-analysis, group meta-analysis and meta-regressions were conducted. Forty-three papers were included in this systematic review, of which 29 were suitable for meta-analysis. Interleukin (IL)-6 (g = 0.36 (0.09-0.63); I(2) = 85.94; p = 0.01), IL-4 (g = 0.50 (0.03-0.98); I(2) = 81.87; p = 0.04), and IL-17A (g = 0.53 (0.00-1.06); I(2) = 87.15; p = 0.05), were significantly higher in FMS compared to HC while also combinations of cytokines into relevant phenotypes were significantly upregulated including M1 macrophage (g = 0.23 (0.03-0.43); I(2) = 77.62; p = 0.02), and immune-regulatory (g = 0.40 (0.09-0.72); I(2) = 84.81; p = 0.01) phenotypes. Heterogeneity levels were very high and subgroup and meta-regression analyses showed that many covariates explained part of the heterogeneity including medication washout, sex, time of blood sampling and exclusion of patients with major depressive disorder. In conclusion, FMS is accompanied by a disbalance between upregulated pro-inflammatory (M1 and Th-17) and immune-regulatory cytokines although effect sizes are small-to-moderate. Based on our results we provide specific methodological suggestions for future research, which should assess Th-1, Th-17, chemokines, and Th-2 phenotypes while controlling for possible confounding variables specified in this study.

Second-hand smoking (SHS) may be a risk factor for obesity in adolescence but data on the association between SHS and obesity are scarce, especially from low- and middle-income countries (LMICs). Therefore, the aim of this study was to assess the association between SHS and obesity among adolescents aged 12-15 years from 38 LMICs.

PURPOSE: To update the prevalence of depression in the US and identify whether misperception exists in depression assessed by self-report versus validated tools administered by trained professionals. METHODS: We extracted data on sociodemographic characteristics, lifestyle factors, medical conditions, depressive symptoms, and self-reported depressive feeling from National Health and Nutrition Examination Survey (NHANES) study 2015-2018. We calculated the weighted prevalence and 95% CI of depressive symptoms assessed by a validated tool PHQ-9 (score=10) and self-reported depression respectively. Then, we performed multivariable logistic regressions to identify their sociodemographic and lifestyle correlates. Finally, we calculated the agreement between PHQ-9 assessed depressive symptoms and self-reported depressive feeling to examine possible misperception. RESULTS: The present analysis included a total of 10,257 adults (Weighted N?=?215,964,374) aged 20 years and older. Prevalence of depressive symptoms (PHQ-9 score =10) were 8.0% from 2015 to 2018 in the US. 19.7% and 11.3% adults reported feeling depressed at least once a month and at least once a week, respectively. Depressive experience was largely misperceived in the US (Kappa agreement = 50.98%, Cohen's Kappa = 0.16, p

Although low-grade inflammation is associated with onset and persistence of depression, most biomarkers display modest predictive effects. GlycA (glycoprotein acetylation) is a unique metabolomic composite of pro-inflammatory acute-phase glycoproteins. We hypothesized that GlycA levels would predict depression incidence, remission and persistence, with higher accuracy than high-sensitivity c-reactive protein (hsCRP). We also explored the additive predictive value of GlycA above and beyond hsCRP.

Exposure to violence may be associated with increased risk for obesogenic behavior among adolescents but studies providing a global perspective are lacking. The aim of this work was to assess the relationship between violence and obesogenic behaviors among young adolescents from 62 countries. Cross-sectional data from the Global School-based Student Health Survey 2009-2016 were analyzed. Information on violence (intentional injury, physical attack, physical fight) and obesogenic behavior (anxiety-induced sleep problems, low physical activity, sedentary behavior, fast-food consumption, carbonated soft-drink consumption) were self-reported. Associations were analyzed using meta-analysis based on country-wise multivariable logistic regression analyses. A total of 165,380 adolescents aged 12-15?years [mean (SD) age 13.8 (1.0) years; 50.9% boys] were included in the analysis. All types of violence were positively associated with higher odds for all types of obesogenic behavior with the exception of low physical activity. Associations were particularly pronounced for anxiety-induced insomnia. In contrast, intentional injury (OR?=?0.72; 95%CI?=?0.64-0.81) and physical fight (OR?=?0.90; 95%CI?=?0.86-0.95) were associated with lower odds for low physical activity. In this large global sample of adolescents, exposure to violence was associated with all obesogenic behaviors apart from low physical activity. Multidimensional government programs and policies addressing exposure to violence among young adolescents may lead to reduction in obesogenic behavior and hence curtail the global obesity epidemic.

Obsessive-compulsive disorder (OCD) has been associated with a wide range of biological and neurocognitive findings, which could assist in the search for biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses to assess and grade the strength of the evidence of the association between OCD and several potential diagnostic biomarkers while controlling for several potential biases. Twenty-four systematic reviews and meta-analyses were included, comprising 352 individual studies, more than 10,000 individuals with OCD, and covering 73 potential biomarkers. OCD was significantly associated with several neurocognitive biomarkers, with varying degrees of evidence, ranging from weak to convincing. A number of biochemical, neurophysiological, and neuroimaging biomarkers also showed statistically significant, albeit weak, associations with OCD. Analyses in unmedicated samples (123 studies) weakened the strength of the evidence for most biomarkers or rendered them non-significant. None of the biomarkers seem to have sufficient sensitivity and specificity to become a diagnostic biomarker. A more promising avenue for future biomarker research in OCD might be the prediction of clinical outcomes rather than diagnosis.

Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in schizophrenia patients with (n=40) and without (n=40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial Least Squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.

Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder.

IMPORTANCE: Previous studies suggest that depression and anxiety are common in patients with hidradenitis suppurativa (HS), more so than other dermatological conditions. Yet, to the authors' knowledge, no previous systematic review or meta-analysis has estimated the prevalence or odds ratio (OR) for those psychiatric comorbidities in this population. OBJECTIVE: To assess the prevalence and odds for depression and anxiety in patients with HS. DATA SOURCES: From July 25 to September 30, 2018, observational studies investigating the prevalence and odds for depression and anxiety in adults with HS were systematically searched without language restriction from the inception of each database to July 25, 2018, in PubMed/MEDLINE, Embase, and PsycINFO databases. Searches used various configurations of the terms hidradenitis suppurativa; acne inversa; depressive disorder; depression; anxiety; anxiety disorders; phobia, social; suicide; and suicide, attempted. In addition, the reference lists of included references were screened manually. STUDY SELECTION: Two investigators independently screened references that measured prevalence rates and odds for depressive and anxiety symptoms in patients with HS. Of 136 unique references, 10 ultimately met inclusion criteria. DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted from eligible references. Authors were contacted to provide further information when necessary. Methodological quality of included studies was assessed through a modified version of the Newcastle-Ottawa Scale. Random-effects models were used to synthesize available evidence. MAIN OUTCOMES AND MEASURES: Prevalence rates and ORs for depression and anxiety in adults with HS were the primary outcome measures. Heterogeneity across studies was assessed with the I2 statistic. Sources of heterogeneity were explored through subgroup and meta-regression analyses. RESULTS: Ten studies comprising 40?307 participants with HS met inclusion criteria. The overall prevalence of depression was 16.9% (95% CI, 9.9%-27.2%). Heterogeneity was large. In the subgroup of studies that considered a clinical criteria-based diagnosis of depression, the prevalence of depression was 11.9% (95% CI, 4.9%-26.2%), compared with 26.8% (95% CI, 20.4%-34.5%) in studies that used a screening instrument. The methodological quality of included studies moderated those findings. The OR for depression in individuals with HS compared with individuals without HS was 1.84 (95% CI, 1.57-2.15). The prevalence of anxiety was 4.9% (95% CI, 1.7%-13.2%); there were insufficient data to determine an odds ratio for anxiety in persons with HS because 2 studies included a comparison group. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis indicates that depression and anxiety are common comorbid conditions in patients with HS. Results suggest that the development of strategies to recognize and treat those psychiatric comorbidities in patients with HS is warranted.

OBJECTIVE: Adolescent suicide is a global public health problem. Bullying is a risk factor for suicidality in adolescence; however, global data on its association with suicide attempts are lacking, and data from low- and middle-income countries and non-Western settings are scarce. Thus, this study assessed the association between bullying victimization and suicide attempts using data from 48 countries (predominantly low- and middle-income countries) across multiple continents. METHOD: Data from the Global School-based Student Health Survey were analyzed. Data on past 12-month suicide attempts and past 30-day bullying victimization were collected. Multivariable logistic regression and meta-analysis with random effects were conducted to assess the associations. RESULTS: The final sample consisted of 134,229 adolescents 12 to 15 years of age. The overall prevalences of suicide attempts and bullying victimization were 10.7% and 30.4%, respectively. After adjustment for sex, age, and socioeconomic status, bullying victimization was significantly associated with higher odds for a suicide attempt in 47 of the 48 countries studied, with the pooled odds ratio being 3.06 (95% CI 2.73-3.43). A larger number of days bullied in the past month was dose-dependently associated with higher odds for suicide attempts. The past-year prevalence of suicide attempts ranged from 5.9% for the "no bullying" group up to 32.7% for the "being bullied for 20 to 30 days/month" group (odds ratio 5.51, 95% CI 4.56-6.65). CONCLUSION: Bullying victimization could be an important risk factor of suicide attempts among adolescents globally. Thus, there is an urgent need to implement effective and evidence-based interventions to address bullying to prevent suicides and suicide attempts among adolescents worldwide.

BACKGROUND: Evidence suggests that cannabis use may be associated with suicidality in adolescence. Nevertheless, very few studies have assessed this association in low- and middle-income countries (LMICs). In this cross-sectional survey, we investigated the association of cannabis use and suicidal attempts in adolescents from 21 LMICs, adjusting for potential confounders. METHOD: Data from the Global school-based Student Health Survey was analyzed in 86,254 adolescents from 21 countries [mean (SD) age = 13.7 (0.9) years; 49.0% girls]. Suicide attempts during past year and cannabis during past month and lifetime were assessed. Multivariable logistic regression analyses were conducted. RESULTS: The overall prevalence of past 30-day cannabis use was 2.8% and the age-sex adjusted prevalence varied from 0.5% (Laos) to 37.6% (Samoa), while the overall prevalence of lifetime cannabis use was 3.9% (range 0.5%-44.9%). The overall prevalence of suicide attempts during the past year was 10.5%. Following multivariable adjustment to potential confounding variables, past 30-day cannabis use was significantly associated with suicide attempts (OR = 2.03; 95% CI: 1.42-2.91). Lifetime cannabis use was also independently associated with suicide attempts (OR = 2.30; 95% CI: 1.74-3.04). CONCLUSION: Our data indicate that cannabis use is associated with a greater likelihood for suicide attempts in adolescents living in LMICs. The causality of this association should be confirmed/refuted in prospective studies to further inform public health policies for suicide prevention in LMICs.

Beatrice Bortolato,1 Kamilla W Miskowiak,2 Cristiano A Köhler,3 Eduard Vieta,4 André F Carvalho3 1Department of Mental Health, ULSS 10 “Veneto Orientale”, Venice, Italy; 2Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 3Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; 4Bipolar Disorders Program, Institute of Neuroscience, Hospital Clínic Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Catalonia, Spain Abstract: Cognitive impairment is a core feature of schizophrenia (SZ) and bipolar disorder (BD). A neurocognitive profile characterized by widespread cognitive deficits across multiple domains in the context of substantial intellectual impairment, which appears to antedate illness onset, is a replicated finding in SZ. There is no specific neuropsychological signature that can facilitate the diagnostic differentiation of SZ and BD, notwithstanding, neuropsychological deficits appear more severe in SZ. The literature in this field has provided contradictory results due to methodological differences across studies. Meta-analytic techniques may offer an opportunity to synthesize findings and to control for potential sources of heterogeneity. Here, we performed a systematic review of meta-analyses of neuropsychological findings in SZ and BD. While there is no conclusive evidence for progressive cognitive deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a subgroup of patients with BD may be related to a shared genetically determined influence on neurodevelopment. Keywords: schizophrenia, bipolar disorder, psychosis, neuropsychological tests, cognition, meta-analysis, psychiatry

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO2) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO2-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO2-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO2-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

BACKGROUND: The associations of different patterns of alcohol consumption and the incidence and persistence of depressive and anxiety symptoms in older age remain unclear. METHODS: Data on 6095 adults aged?=?50 years old from the Irish Longitudinal Study on Aging (TILDA) was analyzed. Participants completed the CAGE instrument to screen for problematic alcohol use at baseline between October 2009 and February 2011. Outcomes were incident (assessed by the CES-D scale) and anxiety (assessed by the Hospital Anxiety and Depressive scale) symptoms after a two-year follow-up as well as persistence of probable depression and anxiety among those with a positive screen for those disorders at baseline. Associations were adjusted for potential confounders through multivariable models. RESULTS: In the overall sample, problem drinking did not predict incident and persistent depression and anxiety in this sample. Among females, problem drinking increased the risk for incident depression (OR?=?2.11; 95%CI?=?1.12-4.00) and anxiety (OR?=?2.22; 95%CI?=?1.01-4.86). In addition, problem drinking increased the risk of persistent depressive symptoms (OR?=?2.43; 95%CI?=?1.05-5.06) among females. CONCLUSION: Problem drinking may increase the risk of incident probable depression and anxiety among older females. Furthermore, problem drinking led to a higher likelihood of persistent depressive symptoms in older female participants. Interventions targeting problem drinking among older females may prevent the onset and persistence of depression in this population, while also decreasing the incidence of anxiety symptoms.

BACKGROUND: Smoking is a leading modifiable cause of global morbidity and mortality. Research from high-income countries has found a high prevalence of smoking among people with depression and suggested that this may partially contribute to the increased premature mortality in this population. Limited research has investigated smoking behaviors across the depression spectrum and in low- and middle-income countries (LMICs). This study explored the relationship between depression and smoking across 48 LMICs. METHODS: We conducted a cross-sectional, community-based study comprising 242,952 people [mean age 38.4 (SD?=?16.1) years, 50.8% females] from the World Health Survey. Multivariable binary logistic regression analyses were performed to investigate the relationship between depression (including subsyndromal, brief depressive episode and depressive episodes) and smoking behaviours. RESULTS: Overall, the prevalence of current smoking was lowest in Africa (13.5%) and highest in Asia (32.2%). A depressive episode was present in 6.7% of the sample. Compared to people without depression, subsyndromal depression, brief depressive episode, and depressive episodes were all significantly associated with smoking with similar effect sizes (ORs: 1.36-1.49). Countrywide meta-analysis found that the pooled overall OR for smoking in depression was 1.42 (95%CI?=?1.32-1.52, I(2)?=?39.7%). Furthermore, alcohol consumption and male gender were consistently associated with smoking across all regions and smoking was consistently less common in those who were wealthier and had a higher education. CONCLUSION: These data suggest that the depression spectrum is consistently associated with high levels of smoking behaivours in LMICs. Given that most of the world's smokers reside in LMICs, future smoking cessation interventions are required to target people with depression.

Caregiving has been associated with adverse health outcomes. However, there is a paucity of multi-country, population-based studies on mental health outcomes of caregivers especially from low- and middle-income countries (LMICs). Thus, we assessed the association of caregiving with depression, sleep problems, and perceived stress in 10 high-, 27 middle-, and 21 low-income countries. Cross-sectional community-based data of the World Health Survey including 258,793 adults aged =18 years were analyzed. Multivariable logistic and linear regression analyses were conducted to explore the association of past 12-month caregiving with past 12-month DSM-IV depression, and past 30-day perceived stress [range 0 (low)-100 (high)] and severe/extreme sleep problems. Nearly 20% of the individuals were engaged in caregiving with particularly high rates observed in high-income countries (HICs) (e.g., Finland 43.3%). Across the entire sample, after adjustment for potential confounders, caregivers had a significantly higher likelihood of having depression (OR = 1.54; 95%CI = 1.37-1.73), sleep problems (OR = 1.37; 95%CI = 1.25-1.50), while their mean perceived stress score was 3.15 (95%CI = 2.46-3.84) points higher. These associations tended to be stronger in HICs. A greater number of caregiving activities was associated with a greater likelihood of depression, sleep problems, and perceived stress regardless of country income levels. In conclusion, caregiving has a negative impact on mental health worldwide with possibly greater effects in HICs. Given the growing contribution of caregivers in long-term care, interventions and policies to alleviate the mental health burden of caregivers are urgently needed to maintain sustainable and effective care practices.

Objective: Adverse life events may contribute to the emergence of suicidality. We aimed to test the relationship between the impact of the Greek recession and suicidal risk in people with long-term conditions (LTCs) and to determine whether this relationship is moderated by the presence of a mental disorder. Methods: Suicidal risk (RASS) and crisis parameters were assessed in a cross-sectional survey including 376 patients with LTCs (type-II diabetes mellitus, rheumatological disorders and chronic obstructive pulmonary disease) attending the Emergency Department or specialty clinics. A diagnosis of mental disorder was confirmed by the Mini International Neuropsychiatric Interview (MINI) interview. Hierarchical regression models were used to quantify moderator effects. Results: Suicidal risk was significantly associated with the perceived impact of the recession (p = 0.028). However, moderation analysis showed that this relationship was significant only in those diagnosed with either major depressive disorder or generalized anxiety disorder. Conclusions: These findings suggest that the perceived impact of the current Greek recession is not correlated with suicidal risk per se, but the recession may act as precipitator in combination with other risk factors, such as the presence of a mental illness, thus supporting the importance of early diagnosis and treatment of mental disorders in vulnerable groups.

BACKGROUND: Jealousy is a heterogenous emotion on a spectrum from normality to psychopathology. The relationship between different jealousy subtypes/dimensions and affective temperaments remain unknown. In addition, few large surveys have investigated the associations between jealousy subtypes and psychopathological dimensions. METHODS: A Brazilian Portuguese version of the "Questionario della Gelosia" (QUEGE) was developed. We obtained data from an anonymous web-based research platform. Socio-demographic data was obtained and participants answered the QUEGE, the TEMPS-Rio de Janeiro, and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: 2042 participants (29% men, 71% female, mean age+SD: 28.9±8.8 years), took part in this survey. Confirmatory factor analysis provided a five-factor model for the QUEGE with self-esteem, paranoia, interpersonal sensitivity, fear of being abandoned, and obsessive dimensions. The anxious, irritable, cyclothymic, and depressive temperaments were independently associated with jealousy dimensions, whereas the hyperthymic temperament was associated with lower scores on the self-esteem jealousy dimension (N=2042, P

BACKGROUND: There is a paucity of nationally representative data available on the correlates of physical activity (PA) among people with depression, especially in low- and middle-income countries (LMICs). Thus, we investigated PA correlates among community-dwelling adults with depression in this setting. METHODS: World Health Survey data included 24,230 adults (43.1 ± 16.1 years; 36.1% male) with ICD-10 diagnoses of depression including brief depressive episode and subsyndromal depression aged = 18 years from 46 LMICs. PA was assessed by the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-to-high physically active groups. Associations between PA and a range of sociodemographic, health behaviour and mental and physical health variables were examined using multivariable logistic regressions. RESULTS: 34.8% of participants with depression were physically inactive. In the multivariate analyses, inactivity was associated with male sex, older age, not being married/cohabiting, high socio-economic status, unemployment, living in an urban setting, less vegetable consumption, and poor sleep/ low energy. In addition, mobility difficulties and some somatic co-morbidity were associated with not complying with the 150min per week moderate-to-vigorous PA recommendations. CONCLUSIONS: The current data provide guidance for future population level interventions across LMICs to help people with depression engage in regular PA.

AIM: Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty. METHODS: Two authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders. RESULTS: From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07-47.10, I(2)=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I(2)=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I(2)=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I(2)=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I(2)=0%). CONCLUSION: This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.

Population-based studies investigating the relationship of arthritis with mental health outcomes are lacking, particularly among low- and middle-income countries (LMICs). We investigated the relationship between arthritis and mental health (depression spectrum, psychosis spectrum, anxiety, sleep disturbances and stress) across community-dwelling adults aged =18 years across 46 countries from the World Health Survey. Symptoms of psychosis and depression were established using questions from the Mental Health Composite International Diagnostic Interview. Severity of anxiety, sleep problems, and stress sensitivity over the preceding 30 days were self-reported. Self-report lifetime history of arthritis was collected, including presence or absence of symptoms suggestive of arthritis: pain, stiffness or swelling of joints over the preceding 12-months. Multivariable logistic regression analyses were undertaken. Overall, 245,706 individuals were included. Having arthritis increased the odds of subclinical psychosis (OR = 1.85; 95%CI = 1.72-1.99) and psychosis (OR = 2.48; 95%CI = 2.05-3.01). People with arthritis were at increased odds of subsyndromal depression (OR = 1.92; 95%CI = 1.64-2.26), a brief depressive episode (OR = 2.14; 95%CI = 1.88-2.43) or depressive episode (OR = 2.43; 95%CI = 2.21-2.67). Arthritis was also associated with increased odds for anxiety (OR = 1.75; 95%CI = 1.63-1.88), sleep problems (OR = 2.23; 95%CI = 2.05-2.43) and perceived stress (OR = 1.43; 95%CI = 1.33-1.53). Results were similar for middle-income and low-income countries. Integrated interventions addressing arthritis and mental health comorbidities are warranted to tackle this considerable burden.

Polysulfone membranes (PSF) were modified with silver nanoparticles obtained by new synthesis (nAgNS), silver nanoparticles obtained commercially (nAgC), silver sulfadiazine (SP), dodecyltrimethylammonium bromide (DOTAB), benzalkonium chloride (CB) or sodium dodecylbenzene sulfonate (DBSS) to improve the efficiency of the water filtration process by reducing biofouling. All membranes had lower hydrophobicity compared with PSF. The zeta potentials of all membranes were negative at pH 7.0, except for CB 10%. In the agar diffusion test, E. coli was considered to be sensitive to the antimicrobial effect of the nAgNS 1%, 3%, 6%, 10% and DOTAB 10%, whereas S. aureus was sensitive to the nAgNS 1%, 3%, 6%, 10%, DOTAB 10%, CB 0.22%, 2% and 10%. The lowest adhesion of E. coli was found in the nAgNS 6% and 10%. In the evaluation of the loss of flow rate during filtration of the E. coli suspension and pure water, nAgNS showed higher flow rate values when compared with PSF. The nAgNS did not release quantities of silver (0.1 mg/l) above the amount considered safe by the World Health Organization. Membranes nAgNS 6% and 10% showed the best anti-biofouling characteristic.

Notwithstanding their scarcity and uneven distribution, zooarchaeological and stable isotope data sets on the Early and Middle Neolithic (5500-3200 cal BC) in the region of Estremadura in Central Portugal strongly suggest that two succeeding stages in subsistence strategies took place: sheep and goat itinerant pastoralism (across large areas) and/or renewed focus on wild food sources (cervid hunting, harvesting marine and freshwater food) which replaced livestock farming within smaller areas and less specialised hunting practices. This economic shift seems to have coincided with two other dramatic changes: the 5.9 kyr cal BP climate event and the onset of megalithism. Possible correlations between these past cultural and palaeoenvironmental phenomena are herein preliminarily outlined. info:eu-repo/semantics/publishedVersion

Este trabalho visou caracterizar macro e microscopicamente o saco vitelino em pacas (Agouti paca) e cutias (Dasyprocta aguti) no início de gestação. Três embriões/fetos de pacas e três de cutias foram utilizados para a análise do saco vitelino, durante as fases iniciais de gestação. Fragmentos do saco vitelino foram removidos do embrião/feto e rotineiramente processados para inclusão em parafina (técnica histológica rotineira) e em resina Spurr (análise ultra-estrutural). Macroscopicamente, a placenta vitelínica em ambas as espécies inseria-se na superfície da placenta principal, com suas margens projetando-se completamente sobre o embrião/fetos. Na microscopia de luz, a placenta vitelínica apresentava-se constituída pelo epitélio endodérmico e um mesenquima com inúmeros vasos vitelínicos. Ultraestruturalmente, a placenta vitelínica visceral da paca era formada por células endodérmicas com núcleos na região mediana e da cutia por núcleos dispostos apicalmente; outra característica foi o grande número de mitocôndrias, vesículas de conteúdo eletrodenso e com microvilosidades. Com base nos resultados concluímos, que (1) a placenta vitelínica das duas espécies apresenta inserção na superfície da placenta principal; (2) a placenta vitelínica de paca se apóia na membrana de Reichert, diferentemente da cutia, que não possui tal membrana; (3) o cório e alantóide apresentam-se fusionados, formando a placenta corioalantoídea; e (4) o saco vitelino em ambas as espécies é invertido e vascularizado. The study aimed to characterize gross and microscopic features of the yolk sac in paca (Agouti paca) and agouti (Dasyprocta aguti) in early gestation. Fragments of the yolk sac of 3 paca and 3 agouti fetuses at early gestation were taken and processed for histological and ultrastructural analyses. Gross features of the vitelline placenta in both species showed its insertion over the main placenta surface and projections to the embryos/fetuses. Microscopically, the vitelline placenta was constituted by endoderm epithelium and mesenchyme, in which vitelline vessels are abundant. The ultrastructure of the samples showed that the visceral yolk sac of the paca was formed by endodermic cells with nuclei in the median region, and that the visceral yolk sac of the agouti was formed by nuclei arranged apically; other characteristic was the large number of mitochondrias, eletrodense vesicles with microvilosities We conclude that (1) the vitelline placenta of the two species presents insertion in the surface of the main placenta; (2) the vitelline placenta of paca rests on the Reichert's membrane, whereas the agouti vitelline placenta does not have this membrane; (3) the chorion and allantoic are fusioned; and (4) the chorioallantoic placenta and the yolk sac in both species are reversed and vascularized.

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Research reported in this publication was supported by the Bill & Melinda Gates Foundation. S Afzal acknowledges the support for intellectual contributions to this manuscript by the Department of Community Medicine and Epidemiology at King Edward Medical University, Lahore, Pakistan. T Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. L Belo acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. D Bennett is supported by the UK Medical Research Council Population Health Research Unit at the University of Oxford (Oxford, UK). M Carvalho acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. L Castro-de-Araujo was funded by the Medical Research Council (UK), Grant no. MR/T03355X/1 and by the National Institute of Mental Health Grant no. R01MH128911. FJ Elgar is supported by the Canada Research Chairs program. F Greaves acknowledges support from the NIHR Applied Research Collaboration for NW London. V K Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. VB Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. C Herteliu is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is partially supported by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported by the Operational Programme Research, Development and Education –Project, Postdoc2MUNI “(No. CZ.02.2.69/0.0/0.0/18_053/0016952). S M S Islam is funded by the National Health and Medical Research Council and received funding from the National Heart Foundation of Australia. The Serbian part of this GBD-related contribution has been co-financed through Grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. M Kivimaki was supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1), the US National Institute on Aging (R01AG056477), and the Academy of Finland (350426). K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. B Lacey acknowledges support from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome. S Lorkowski acknowledges institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (Germany; German Federal Ministry of Education and Research; grant agreement number 01EA1808A). G Lucchetti received a productivity scholarship from the Brazilian National Council for Scientific and Technological Development — CNPq (Level 1D). J McGrath was supported by the Danish National Research Foundation (Niels Bohr Professor). J McGrath is employed by the Queensland Centre for Mental Health Research (Australia), which receives support from the Queensland Health Department. C Parry acknowleges the South African Medical Research Council. A Peden is supported by a National Health and Medical Research Council Emerging Leadership Fellowship (Grant ID: APP2009306). M R Phillips was supported in part by the Global Alliance for Chronic Diseases - National Natural Science Foundation of China (NSFC. No. 81761128031). M Pinheiro acknowledges FCT for funding through program DL 57/2016 – Norma transitória. A Rahman acknowledges the support from the Data Science Research Unit in Charles Sturt University (Bathurst, NSW, Australia). U Saeed would like to acknowledge the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges support from Ain Shams University (Cairo, Egypt) and the Egyptian Fulbright Mission Program. N Senthil Kumar acknowledges the DBT, New Delhi sponsored Advanced State Level Biotech Hub (BT/NER/143/SP44475/2021), Mizoram University (Aizawl, Mizoram, India) for facilitating this work. F Sha is supported by the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662). A Shetty acknowledges Kasturba Medical College (Mangalore, India) and Manipal Academy of Higher Education (Manipal, India) for all the academic support. R Shrestha acknowledges a career development award from the National Institutes of Health (K01DA051346). D Silva was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001 and is supported in part by CNPq - Brazil (309589/2021-5). D Sleet acknowledges partial support from Veritas Management Group, Inc and The Bizzell Group, LLC. S Trias-Llimós acknowledges research funding from the Juan de la Cierva-Formación program of the Spanish Ministry of Science and Innovation (FJC-2019-039314-I). Sí