Search

BackgroundInflammation is implicated in depression, but the issue of causality remains unclear.ObjectivesTo investigate potential causality and direction of effect between inflammation and depression.MethodsUsing data from the ALSPAC birth cohort (n=4021), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression symptoms score and diagnosis, assessed at ages 18y and 24y.We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKBB) (N=115,078); for depression from the Psychiatric Genomics Consortium and UKBB (N=500,199); and for depressive symptoms (N=161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted (IVW) method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI.ResultsAfter adjusting for potential confounders we found no association between GlycA and depression symptoms score orvice versa. We observed an association between GlycA and depression diagnosis (OR=1.18, 95% CI: 1.03-1.36).MR suggested no causal effect of GlycA on depression, but there was evidence of a causal effect of depression on GlycA (mean difference in GlycA = 0.09; 95% CI: 0.03-0.16), which was maintained in some, but not all, sensitivity analyses.ConclusionWe found no consistent evidence for an effect of the inflammatory marker GlycA on depression. There was some evidence that depression may increase GlycA, but this may be confounded/mediated by BMI.

Responses of three tomato (Lycopersicon esculentum Mill.) hybrids viz. 'Luanova', 'Savarona' and 'Tessera' to various doses (0, 0.5, 1.0, 1.5 and 2.0 g L-1) of soil application of humic acid (HA) were evaluated in terms of plant growth, productivity and quality of fruits, under greenhouse conditions, during 2011-12 and 2012-13. In addition to improved quality characteristics, higher values for yield and yield components were recorded for tomato fruits harvested from plants of 'Tessera' cultivar compared to those harvested from other hybrids tested, regardless of growing seasons. Plants from 'Luanova' cultivar were, however, earlier in fruiting with higher number of fruits per plant. Soil application of HA presented positive effects on yield and physicochemical quality of tomato fruits irrespective of the dose of HA and the cultivar investigated, in both seasons. Soil application of HA at higher dose 1.5 g L-1 exhibited better results in all the three tomato cultivars tested, in terms of their vegetative and reproductive growth, and significantly improved the physicochemical quality of their fruits. Conclusively, the tomato hybrid 'Tessera' was found suitable for cultivation under greenhouse conditions while soil application of aqueous solution of HA @ 1.5 g L-1 substantially resulted in higher production of quality tomato fruits.

Funder: MQ: Transforming Mental Health; Grant(s): MQDS17/40, Around a quarter of people who experience a first episode of psychosis (FEP) will develop treatment-resistant schizophrenia (TRS), but there are currently no established clinically useful methods to predict this from baseline. We aimed to explore the predictive potential for clozapine use as a proxy for TRS of routinely collected, objective biomedical predictors at FEP onset, and to externally validate the model in a separate clinical sample of people with FEP. We developed and externally validated a forced-entry logistic regression risk prediction Model fOr cloZApine tReaTment, or MOZART, to predict up to 8-year risk of clozapine use from FEP using routinely recorded information including age, sex, ethnicity, triglycerides, alkaline phosphatase levels, and lymphocyte counts. We also produced a least-absolute shrinkage and selection operator (LASSO) based model, additionally including neutrophil count, smoking status, body mass index, and random glucose levels. The models were developed using data from two UK psychosis early intervention services (EIS) and externally validated in another UK EIS. Model performance was assessed via discrimination and calibration. We developed the models in 785 patients, and validated externally in 1,110 patients. Both models predicted clozapine use well at internal validation (MOZART: C 0.70; 95%CI 0.63,0.76; LASSO: 0.69; 95%CI 0.63,0.77). At external validation, discrimination performance reduced (MOZART: 0.63; 0.58,0.69; LASSO: 0.64; 0.58,0.69) but recovered after re-estimation of the lymphocyte predictor (C: 0.67; 0.62,0.73). Calibration plots showed good agreement between observed and predicted risk in the forced-entry model. We also present a decision-curve analysis and an online data visualisation tool. The use of routinely collected clinical information including blood-based biomarkers taken at FEP onset can help to predict the individual risk of clozapine use, and should be considered equally alongside other potentially useful information such as symptom scores in large-scale efforts to predict psychiatric outcomes.

Background: Individuals with a diagnosis of schizophrenia are known to be at high risk of premature mortality due to poor physical health, especially cardiovascular disease, diabetes, and obesity. The reasons for these physical health outcomes within this patient population are complex. Despite well-documented cardiometabolic adverse effects of certain antipsychotic drugs and lifestyle factors, schizophrenia may have an independent effect.Aims: To investigate if there is evidence that schizophrenia is causally related to cardiometabolic traits (blood lipids, anthropometric traits, glycaemic traits, blood pressure) and vice versa using bi-directional two-sample Mendelian randomization (MR) analysis.Methods: We used 185 genetic variants associated with schizophrenia from the latest Psychiatric Genomics Consortium GWAS (n = 130,644) in the forward analysis (schizophrenia to cardiometabolic traits) and genetic variants associated with the cardiometabolic traits from various consortia in the reverse analysis (cardiometabolic traits to schizophrenia), both at genome-wide significance (5 × 10−8). The primary method was inverse-variance weighted MR, supported by supplementary methods such as MR-Egger, as well as median and mode-based methods.Results: In the forward analysis, schizophrenia was associated with slightly higher low-density lipoprotein (LDL) cholesterol levels (0.013 SD change in LDL per log odds increase in schizophrenia risk, 95% CI, 0.001–0.024 SD; p = 0.027) and total cholesterol levels (0.013 SD change in total cholesterol per log odds increase in schizophrenia risk, 95% CI, 0.002–0.025 SD; p = 0.023). However, these associations did not survive multiple testing corrections. There was no evidence of a causal effect of cardiometabolic traits on schizophrenia in the reverse analysis.Discussion: Dyslipidemia and obesity in schizophrenia patients are unlikely to be driven primarily by schizophrenia itself. Therefore, lifestyle, diet, antipsychotic drugs side effects, as well as shared mechanisms for metabolic dysfunction and schizophrenia such as low-grade systemic inflammation could be possible reasons for the apparent increased risk of metabolic disease in people with schizophrenia. Further research is needed to examine the shared immune mechanism hypothesis.

Background: It has been suggested that glycoprotein acetyls (GlycA) better reflects chronic inflammation than high sensitivity C-reactive protein (hsCRP), but paediatric/life-course data are sparse. Method: Using data from the Avon Longitudinal Study of Parents and Children and UK Biobank, we compared short- (over weeks) and long-term (over years) correlations of GlycA and hsCRP, cross-sectional correlations between GlycA and hsCRP, and associations of pro-inflammatory risk factors with GlycA and hsCRP across the life-course. Results: GlycA showed high short-term (weeks) stability at 15y (r=0.75; 95% CI=0.56, 0.94), 18y (r=0.74; 0.64, 0.85), 24y (r=0.74; 0.51, 0.98) and 48y (r=0.82 0.76, 0.86) and this was comparable to the short-term stability of hsCRP at 24y. GlycA stability was moderate over the long-term, for example between 15y and 18y r=0.52; 0.47, 0.56 and between 15y and 24y r=0.37; 0.31, 0.44. These were larger than equivalent correlations of hsCRP. GlycA and concurrently measured hsCRP were moderately correlated at all ages, for example at 15y (r=0.44; 0.40, 0.48) and at 18y (r=0.55; 0.51, 0.59). We found similar associations of known proinflammatory factors and inflammatory diseases with GlycA and hsCRP. For example, BMI was positively associated with GlycA (mean difference in GlycA per standard deviation change in BMI=0.08; 95% CI=0.07, 0.10) and hsCRP (0.10; 0.08, 0.11). Conclusion: This study showed that GlycA has greater long-term stability than hsCRP, however associations of proinflammatory factors with GlycA and hsCRP were broadly similar.

Acknowledgements: We would like to thank Dr Mary-Ellen Lynall (University of Cambridge) for providing additional information regarding their study for our systematic review and meta-analysis., Funder: Medical Research Council Epidemiology Unit PhD Studentship, Funder: Versus Arthritis Award (Grant No. 22453), Funder: Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1), Funder: NIHR Cambridge BioResource, Funder: The MQ: Transforming Mental Health (Grant No. MQDS17/40); BMA Foundation (J. Moulton Grant 2019), INTRODUCTION: Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to controls. White blood cells (WBC) both produce and are influenced by cytokines, and play key roles in orchestrating innate and adaptive immune responses, but their role in depression remains unclear. Therefore, a systematic review of studies of various WBC subsets in depression is required for a greater understanding of the nature of immune dysfunction in this illness. METHODS: We searched PubMed and PsycINFO databases (inception to 5th April 2022) and conducted a systematic review and meta-analysis of identified studies comparing absolute count and/or relative percentage of flow cytometry-derived WBC subsets between depression cases and controls. Selected studies were quality assessed. Random-effect meta-analysis was performed. RESULTS: Thirty-three studies were included and 27 studies (n = 2277) were meta-analysed. We report an increase in mean absolute counts of WBC (seven studies; standardised mean difference [SMD] = 1.07; 95% CI, 0.61-1.53; P < 0.01; I2 = 64%), granulocytes (two studies; SMD = 2.07; 95% CI, 1.45-2.68; P < 0.01; I2 = 0%), neutrophils (four studies; SMD = 0.91; 95% CI, 0.23-1.58; P < 0.01; I2 = 82%), monocytes (seven studies; SMD = 0.60; 95% CI, 0.19-1.01; P < 0.01; I2 = 66%), CD4+ helper T cells (11 studies; SMD = 0.30; 95% CI, 0.15-0.45; P < 0.01; I2 = 0%), natural killer cells (11 studies; SMD = 1.23; 95% CI, 0.38-2.08; P < 0.01; I2 = 95%), B cells (10 studies; SMD = 0.30; 95% CI, 0.03-0.57; P = 0.03; I2 = 56%), and activated T cells (eight studies; SMD = 0.45; 95% CI, 0.24-0.66; P < 0.01; I2 = 0%) in depression, compared to controls. Fewer studies reported relative percentage, indicating increased neutrophils and decreased total lymphocytes, Th1, and Th2 cells in depression. CONCLUSIONS: Depression is characterised by widespread alterations in circulating myeloid and lymphoid cells, consistent with dysfunction in both innate and adaptive immunity. Immune cells could be useful biomarkers for illness subtyping and patient stratification in future immunotherapy trials of depression, along with cytokines, other biomarkers, and clinical measures.

Moringa oleifera seed solution was used in this study to treat municipal wastewater that were used as the treatment in this study. There were 3 treatments used; treated wastewater, normal tape water and untreated wastewater. The wastewater were collected at main drainage at Batu 7 (5o52’57.2’’N 118o02’39.7”E) and diagnosed based on the pH and EC. Data on plant height (cm), number of leaves, leaves length (cm), chlorophyll, and number of primary branches were taken every week until week 4. For root length (cm), fresh weight (g), dry weight (g) and moisture were taken after the harvesting. The data collected were analyzed by using Statistical Analysis Software (SAS) version 9.4 computer program with experimental design was Randomized Complete Block Design (RCBD). The means were separated and compared using Duncan’s Multiple Range Test (DMRT) at 0.05 significant level. M. oleifera seeds solution treated irrigation exhibited positive outcomes for most of the parameters recorded, but response of different vegetables were also different on varied parameters. The increase of pH from untreated waste water (6.40) to sanitized/treated waste water (6.73) and reduction of EC from untreated waste water (367.9) to sanitized/treated waste water (359.1) is the proof of making nutrients more available for plants uptake. From the overall study it is proved that M. oleifera seeds are suitable as the replacement and an alternative besides chemical coagulant to treat wastewater which is cheaper, eco-friendly and sustainable to be used in agricultural irrigation based on all the parameters evaluated in this study.

Funder: Oxford Biomedical Research Centre, Funder: EU-ERDF, Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100010269, Funder: GlaxoSmithKline; funder-id: http://dx.doi.org/10.13039/100004330, Funder: Sepsis Research, Funder: Intensive Care Society; funder-id: http://dx.doi.org/10.13039/501100000846, BACKGROUND: Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin 6 (IL-6). Genetic variants in IL6R known to down-regulate IL-6 signalling are associated with improved Coronavirus Disease 2019 (COVID-19) outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RAs). We hypothesised that blockade of IL6R could also improve outcomes in sepsis. METHODS AND FINDINGS: We performed a Mendelian randomisation (MR) analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis (primary outcome), sepsis severity, other infections, and COVID-19 (secondary outcomes). We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP and gp130 in a similar analysis. In the UK Biobank cohort (N = 486,484, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of our primary outcome, sepsis (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.66 to 0.96, per unit of natural log-transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR = 0.74; 95% CI 0.47 to 1.15); critical care admission with sepsis (OR = 0.48, 95% CI 0.30 to 0.78) and critical care death with sepsis (OR = 0.37, 95% CI 0.14 to 0.98). Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 to 0.97) and for sepsis survival in critical care (OR = 0.22; 95% CI 0.04 to 1.31) in the GainS and GenOSept consortium, although this result had a large degree of imprecision. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR = 0.69, 95% CI 0.57 to 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results. These results are subject to the limitations and assumptions of MR, which in this case reflects interpretation of these SNP effects as causally acting through blockade of IL6R, and reflect lifetime exposure to IL6R blockade, rather than the effect of therapeutic IL6R blockade. CONCLUSIONS: IL6R blockade is causally associated with reduced incidence of sepsis. Similar but imprecisely estimated results supported a causal effect also on sepsis related mortality and critical care admission with sepsis. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. These data suggest that a randomised trial of IL-6 receptor antagonists in sepsis should be considered.

[Background]: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors., [Methods]: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16–35y without MetS at baseline who had 1–6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered., [Findings]: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68–0.79, partial-model C=0.68, 95% C.I., 0.62–0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66–0.78; partial-model C=0.66, 95% C.I., 0.60–0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration., [Interpretation]: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality., NIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).

Inflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood. Using the prospective Avon Longitudinal Study of Children and Parents birth cohort (N = up-to 6401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10-28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors. Serum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10 and 28y in the base model (n = 4835; β = 0.066; 95%CI:0.020-0.113; pFDR = 0.041) which was weaker when adjusting for metabolic and sociodemographic factors. Weak associations were observed between inflammatory markers (serum IL-6 and CRP DNAm scores) and total number of PEs. Other inflammatory markers were not associated with depression or PEs. Early-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention.

Funder: NIHR Imperial Biomedical Research Centre, The antipsychotic clozapine is known to have immune-modulating effects. Clozapine treatment has been reported to be associated with increased risk of COVID-19 infection. However, it remains unclear whether this is because of increased testing of this patient group, who are closely monitored. We linked anonymised health records from mental health services in Cambridgeshire (UK), for patients taking antipsychotic medication, with data from the local COVID-19 testing hub. Patients receiving clozapine were more likely to be tested for COVID-19, but not to test positive. Increased testing in patients receiving clozapine suggests prudent judgement by clinicians, considering the overall health vulnerabilities of this group.

BackgroundInflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood.MethodsUsing the prospective Avon Longitudinal Study of Children and Parents birth cohort (N=up-to 6,401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10-28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors.ResultsSerum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10-28y (n=4,262; β=0.086; 95%CI:0.036-0.137; pFDR=0.009). CRP DNAm score at birth was associated with total number of PEs, size but this association did not survive correction for multiple testing (n=822; β=0.204; 95%CI:0.024-0.388; puncorrected=0.027; pFDR=0.252). Other immune measures were not associated with depression or PEs.ConclusionsEarly-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention.

IntroductionEvidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. However, no interventional studies in patients with psychosis, stratified using inflammatory markers, have been conducted to assess the therapeutic potential of targeting IL-6 in psychosis and to elucidate potential mechanism of effect. Tocilizumab is a humanised monoclonal antibody targeting the IL-6 receptor to inhibit IL-6 signalling, licensed in the UK for treatment of rheumatoid arthritis. The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. A secondary objective is to examine characteristics of inflammation-associated psychosis.Methods and analysisA proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of IL-6 inhibition on anhedonia in patients with psychosis. Approximately 60 participants with a diagnosis of schizophrenia and related psychotic disorders (ICD-10 codes F20, F22, F25, F28, F29) with evidence of low-grade inflammation (IL-6≥0.7 pg/mL) will receive either one intravenous infusion of tocilizumab (4.0 mg/kg; max 800 mg) or normal saline. Psychiatric measures and blood samples will be collected at baseline, 7, 14 and 28 days post infusion. Cognitive and neuroimaging data will be collected at baseline and 14 days post infusion. In addition, approximately 30 patients with psychosis without evidence of inflammation (IL-6Ethics and disseminationThe study is sponsored by the University of Bristol and has been approved by the Cambridge East Research Ethics Committee (reference: 22/EE/0010; IRAS project ID: 301682). Study findings will be published in peer-review journals. Findings will also be disseminated by scientific presentation and other means.Trial registration numberISRCTN23256704.

BackgroundMetabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology are limited.MethodsUsing data from 3,258 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers (leptin, adiponectin, insulin, interleukin-6, C-Reactive protein, low density lipoprotein, high density lipoprotein, triglycerides, and BMI), we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures.ResultsChildhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.31; 95% CI, 1.02-1.71) and negative symptoms (aOR=1.15; 95% CI, 1.07-1.24), but not positive psychotic symptoms. The general immuno-metabolic factor was associated with atypical depressive symptoms (aOR=1.07; 95% CI, 1.01-1.14) and psychotic experiences (aOR=1.21; 95% CI, 1.02-1.44). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). Point estimates tended to be larger in women, though 95% credible intervals overlapped with those for men. In women, the inflammatory factor was associated with depressive episodes (aOR=1.27; 95% CI, 1.03-1.57).ConclusionsWhile general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation appear to be particularly linked to affective (depressive and negative), but not positive psychotic symptoms.

Cadmium (Cd) is one of non-essential heavy metals which is released into environment naturally or anthropogenically. It is highly persistent toxic metals that are exceptionally distressing industrial and agriculture activities by contaminating soil, water and food. Its long-duration endurance in soil and water results in accumulation and uptake into plants, leading to the food chain. This becomes a serious global problem threatening humans and animals as food chain components. Living organisms, especially humans, are exposed to Cd through plants as one of the main vegetative food sources. This review paper is concentrated on the symptoms of the plants affected by Cd toxicity. The absorption of Cd triggers several seen and unseen symptoms by polluted plants such as stunted growth, chlorosis, necrosis and wilting. Apart from that, factors that affect the uptake and translocation of Cd in plants are elaborated to understand the mechanism that contributes to its accumulation. By insight of Cd accumulation, this review also discussed the phytoremediation techniques-phytoextraction, phytostimulation, phytostabilization, phytovolatization and rhizofiltration in bioremediating the Cd. Resumo O cádmio (Cd) é um dos metais pesados não essenciais que é liberado no meio ambiente de forma natural ou antropogênica. São metais tóxicos altamente persistentes que prejudicam excepcionalmente as atividades industriais e agrícolas, contaminando o solo, a água e os alimentos. Sua resistência de longa duração no solo e na água resulta em acúmulo e absorção pelas plantas, levando à cadeia alimentar. Isso se torna um sério problema global que ameaça humanos e animais como componentes da cadeia alimentar. Os organismos vivos, principalmente os humanos, são expostos ao Cd através das plantas como uma das principais fontes de alimento vegetativo. Este artigo de revisão concentra-se nos sintomas das plantas afetadas pela toxicidade do Cd. A absorção de Cd desencadeia vários sintomas visíveis e invisíveis por plantas poluídas, como crescimento atrofiado, clorose, necrose e murcha. Além disso, são elaborados fatores que afetam a absorção e translocação de Cd nas plantas para entender o mecanismo que contribui para o seu acúmulo. A partir do conhecimento do acúmulo de Cd, esta revisão também discutiu as técnicas de fitorremediação - fitoextração, fitoestimulação, fitoestabilização, fitovolatização e rizofiltração na biorremediação do Cd.

Continuous use of chemical fertilizers gradually shrinks the crop yield and quality, and these adverse effects can be reduced by adopting new sustainable practices such as the use of manure, biofertilizers, and nano fertilizers. Limited information is existed on the application of Trichoderma harzianum and Bacillus thuringiensis microbes to improve lemon seedlings growth, physiology, and fruit formation. Therefore, the current study is aimed to evaluate the effects of T. harzianum and B. thuringiensis microbes mixing with low levels of inorganic fertilizer (NPK) on the plant growth, development, and quality of limau nipis (key lemon) fruits. The lemon seedlings growing media were inoculated during transplanting with T. harzianum and B. thuringiensis at various NPK fertilizers under polybagged conditions. The seedlings were grown around eighteen (18) months after inoculation with biofertilizers followed by Randomized Complete Block Design (RCBD) with five (5) replications. The results showed that T. harzianum with 50 g of NPK treatment (T2) increased the seedling's height, branch number, leaf height, ground area, and absolute growth rate (AGR) plant height by 50.12%, 107.84%, 17.91%, 17.91%, 116.93%, and 56.02%, respectively, over the control treatment. The number of leaves (60.82%), leaf area (42.75%), stem diameter (27.34%), specific leaf area (SLA) (39.07%), leaf area index (LAI) (54.40%), and absolute growth rate for leaf number (73.86%), leaf area (306.85%) and stem diameter (46.8%) of lemon seedlings increased significantly with B. thuringiensis plus 50 g NPK treatment (T3). The applications of B. thuringiensis with 25 g NPK fertilizer treatment (T5) increased leaf fresh weight (LFW), leaf dry weight (LDW), leaf moisture content (LMC), specific leaf weight (SLW), leaf relative growth rate (RGR), and chlorophyll content by 96.45%, 56.78%, 13.60%, 24.76%, 45.45%, and 16.22%, respectively, over the control group. In addition, T5 treatment increased the fruits number, individual fruit weight, fruit diameter, fruit dimension, leaf total soluble solids (TSS), and fruit TSS content of lemon tress by 81.81%, 55.52%, 43.54%, 25.69%, 89.47%, and 70.78% compared to the control treatment. Furthermore, soil inoculation of B. thuringiensis significantly increased the pulp to peel ratio and juice content of lemon fruits. From this study, it can be concluded that soil inoculation of both T. harzianum and B. thuringiensis with 25-50% NPK during transplanting improved plant growth, physiology, and fruit quality of limau nipis trees.

Depression and psychosis have a developmental component to their origin. Epidemiologic evidence, which we synthesize in this nonsystematic review, suggests that early-life infection, inflammation, and metabolic alterations could play a role in the etiology of these psychiatric disorders. The risk of depression and psychosis is associated with prenatal maternal and childhood infections, which could be mediated by impaired neurodevelopment. Evidence suggests linear dose-response associations between elevated concentrations of circulating inflammatory markers in childhood, particularly the inflammatory cytokine interleukin 6, and the risk for depression and psychosis subsequently in early adulthood. Childhood inflammatory markers are also associated with persistence of depressive symptoms subsequently in adolescence and early adulthood. Developmental trajectories reflecting persistently high insulin levels during childhood and adolescence are associated with a higher risk of psychosis in adulthood, whereas increased adiposity during and after puberty is associated with the risk of depression. Together, these findings suggest that higher levels of infection, inflammation, and metabolic alterations commonly seen in people with depression and psychosis could be a cause for, rather than simply a consequence of, these disorders. Therefore, early-life immuno-metabolic alterations, as well as factors influencing these alterations such as adversity or maltreatment, could represent targets for prevention of these psychiatric disorders. Inflammation could also be an important treatment target for depression and psychosis. The field requires further research to examine sensitive periods when exposure to such immuno-metabolic alterations is most harmful. Interventional studies are also needed to test the potential usefulness of targeting early-life immuno-metabolic alterations for preventing adult depression and psychosis.

Positive maternal mental health can improve perceptions of stressful situations and promote the use of adaptive coping strategies. However, few studies have examined how positive maternal mental health affects children's development. The aims of this study were to examine the associations between positive maternal mental health and children's internalizing and externalizing symptoms, and to ascertain whether positive maternal mental health moderated the associations between prenatal stress and children's internalizing and externalizing symptoms. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa), and comprised 36,584 mother-child dyads. Prenatal stress was assessed using 41 self-reported items measured during pregnancy. Positive maternal mental health (self-efficacy, self-esteem, and enjoyment) was assessed by maternal report during pregnancy and postpartum. Child internalizing and externalizing symptoms were assessed by maternal report at age 5. Structural equation modeling was used for analysis. Maternal self-efficacy, self-esteem, and enjoyment were negatively associated with internalizing and externalizing symptoms in males and females. The association between prenatal stress and internalizing symptoms in males was stronger at low than at high levels of maternal self-esteem and enjoyment, whereas for females, the association was stronger at low than at high levels of maternal self-esteem and self-efficacy. This study provides evidence of associations between positive maternal mental health and children's mental health, and suggests that higher positive maternal mental health may buffer against the impacts of prenatal stress. Positive maternal mental health may represent an important intervention target to improve maternal-child well-being and foster intergenerational resilience.

We present the first measurement of di-hadron angular correlations in electron-nucleus scattering. The data were taken with the CLAS detector and a 5.0 GeV electron beam incident on deuterium, carbon, iron, and lead targets. Relative to deuterium, the nuclear yields of charged-pion pairs show a strong suppression for azimuthally opposite pairs, no suppression for azimuthally nearby pairs, and an enhancement of pairs with large invariant mass. These effects grow with increased nuclear size. The data are qualitatively described by the GiBUU model, which suggests that hadrons form near the nuclear surface and undergo multiple-scattering in nuclei. These results show that angular correlation studies can open a new way to elucidate how hadrons form and interact inside nuclei, Comment: 6 pages, 4 figures

Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, (an archetypal generalized inflammatory marker) and/or IL-6 activity, as a potential explanation for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated reciprocal relationships of lifetime smoking with depression (ORSmk–Dep = 2.01, 95% CI 1.71–2.37, p Dep–Smk = 1.09, 95% CI 1.06–1.13, p Smk–CRP = 1.40, 95% CI 1.21–1.55, p CRP–Smk = 1.03, 95% CI 1.02–1.05, p IL-6/CRP–Smk = 1.06 (1.03–1.09), p 500 genetic instruments for CRP) and depression (ORCRP–Dep = 1.01, 95% CI 0.99–1.04; ORDep–CRP = 1.03, 95% CI 0.99–1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. Our study supports potential bidirectional causal associations between lifetime smoking and depression which may be at least in part explained by the IL-6 signalling pathway. The IL-6 pathway may represent a putative therapeutic target for smoking and to mitigate the effects of smoking on depression.

The wax apple or jambu madu, is a non-climacteric tropical fruit from Myrtaceae family and widely cultivated in South East Asia. The limited availability of good quality seedlings of wax apple is the main problem to development of flourish it’s market share in the current fruit industry. Therefore, in order to produce good quality planting materials, a study aimed at optimizing propagation and adventitious rooting technique and survivability of wax apple air layer was conducted. In this study, four different levels of Indole-3-Butyric Acid (IBA) concentration (0, 1000, 1500 and 2000 mg L-1) and three rooting media (sphagnum moss, vermicompost and garden soil) were applied after removal of bark (phloem) on the shoot to determine the effect on rooting and survivability of the wax apple air layer under field conditions. The results showed that the wax apple shoots treated with 2000 mg L-1 IBA produced the significantly higher number of roots, increased length of root, diameter of branch, length of branch, number of leaf and leaf area of air layers. In addition, the highest chlorophyll content and stomatal aperture were recorded in 2000 mg L-1 IBA treatment compared to other treatments including control. Vermicompost medium was better than garden soil and sphagnum moss in respect of rooting and survivability of air layers. The results showed that the combination of 2000 mg L-1 IBA and vermicompost as rooting media give the best combination to root initiation, root number, root length and survival rate (100%) of wax apple air layers. From this study, it can be concluded that 2000 mg L-1 IBA and vermicompost treatment enhance the root initiation, early establishment and survivability of wax apple air layered under field conditions. Resumo A maçã de cera, ou jambu madu, é uma fruta tropical não climatérica da família Myrtaceae e amplamente cultivada no Sudeste Asiático. A disponibilidade limitada de mudas de macieira de boa qualidade é o principal problema para o desenvolvimento de sua participação de mercado na fruticultura atual. Portanto, com o objetivo de produzir materiais de plantio de boa qualidade, foi realizado um estudo visando otimizar a técnica de propagação e enraizamento adventício e a sobrevivência da camada aérea da cera de macieira. Neste estudo, quatro diferentes níveis de concentração de ácido indol-3-butírico (AIB) (0, 1000, 1500 e 2000 mg L-1) e três meios de enraizamento (musgo esfagno, vermicomposto e solo de jardim) foram aplicados após a remoção da casca (floema) na parte aérea para determinar o efeito no enraizamento e capacidade de sobrevivência da camada de ar da macieira em condições de campo. Os resultados mostraram que os brotos de macieira tratados com 2000 mg L-1 de AIB produziram significativamente maior número de raízes, maior comprimento de raiz, diâmetro de galho, comprimento de galho, número de folhas e área foliar das camadas aéreas. Além disso, o maior teor de clorofila e abertura estomática foram registrados no tratamento 2000 mg L-1 IBA em comparação com outros tratamentos, incluindo o controle. O meio de vermicomposto foi melhor do que o solo de jardim e o musgo esfagno em relação ao enraizamento e capacidade de sobrevivência das camadas aéreas. Os resultados mostraram que a combinação de 2000 mg L-1 de AIB e vermicomposto como meio de enraizamento proporciona a melhor combinação para iniciação radicular, número de raízes, comprimento radicular e taxa de sobrevivência (100%) das camadas aéreas de macieira. A partir deste estudo, pode-se concluir que 2.000 mg L-1 de AIB e tratamento com vermicomposto melhoram a iniciação radicular, o estabelecimento precoce e a capacidade de sobrevivência de macieiras em camadas de ar em condições de campo.

Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD and autism in children. Polygenic risk score analyses of the Avon Longitudinal Study of Parents and Children suggested associations between maternal genetic liability to IBD and autistic traits in children. Two-sample Mendelian randomization analyses provided evidence of a potential causal effect of genetic liability to IBD, especially ulcerative colitis, on autism. Linkage disequilibrium score regression did not indicate a genetic correlation between IBD and autism. Triangulating evidence from these four complementary approaches, we found evidence of a potential causal link between parental, particularly maternal, IBD and autism in children. Perinatal immune dysregulation, micronutrient malabsorption and anemia may be implicated.