Medical Complexity, Language Use, and Outcomes in the Pediatric ICU.

OBJECTIVES: To determine whether use of a language other than English (LOE) would be associated with medical complexity, and whether medical complexity and LOE together would be associated with worse clinical outcomes. METHODS: The primary outcome of this single-site retrospective cohort study of PICU encounters from September 1, 2017, through August 31, 2022 was an association between LOE and medical complexity. Univariable and multivariable analyses were performed between demographic factors and medical complexity, both for unique patients and for all encounters. We investigated outcomes of initial illness severity (using Pediatric Logistic Organ Dysfunction-2), length of stay (LOS), days without mechanical ventilation or organ dysfunction using a mixed effects regression model, controlling for age, sex, race and ethnicity, and insurance status. RESULTS: There were 6802 patients and 10 011 encounters. In multivariable analysis for all encounters, Spanish use (adjusted odds ratio [aOR], 1.29; 95% confidence interval [CI], 1.11-1.49) and language other than English or Spanish (LOES) (aOR, 1.36; 95% CI, 1.02-1.80) were associated with medical complexity. Among unique patients, there remained an association between use of Spanish and medical complexity in multivariable analysis (aOR, 1.26; 95% CI, 1.05-1.52) but not between LOES and medical complexity (aOR, 1.30; 95% CI, 0.92-1.83). Children with medical complexity (CMC) who used an LOES had fewer organ dysfunction-free days (P = .003), PICU LOS was 1.53 times longer (P = .01), and hospital LOS was 1.45 times longer (P = .01) compared with CMC who used English. CONCLUSIONS: Use of an LOE was independently associated with medical complexity. CMC who used an LOES had a longer LOS.

Racialization processes and depressive symptoms among pregnant Mexican-origin immigrant women.

This study examines how racialization processes (conceptualized as multilevel and dynamic processes) shape prenatal mental health by testing the association of discrimination and the John Henryism hypothesis on depressive symptoms for pregnant Mexican-origin immigrant women. We analyzed baseline data (n = 218) from a healthy lifestyle intervention for pregnant Latinas in Detroit, Michigan. Using separate multiple linear regression models, we examined the independent and joint associations of discrimination and John Henryism with depressive symptoms and effect modification by socioeconomic position. Discrimination was positively associated with depressive symptoms (ß = 2.84; p < .001) when adjusting for covariates. This association did not vary by socioeconomic position. Women primarily attributed discrimination to language use, racial background, and nativity. We did not find support for the John Henryism hypothesis, meaning that the hypothesized association between John Henryism and depressive symptoms did not vary by socioeconomic position. Examinations of joint associations of discrimination and John Henryism on depressive symptoms indicate a positive association between discrimination and depressive symptoms (ß = 2.81; p < .001) and no association of John Henryism and depressive symptoms (ß = -0.83; p > .05). Results suggest complex pathways by which racialization processes affect health and highlight the importance of considering experiences of race, class, and gender within racialization processes.

Análisis de las interrupciones generadas por el uso de los smartphones entre los profesionales sanitarios de Atención Primaria / Analysis of the interruptions generated by the use of smartphones among Primary Care Health professionals

Objetivo: Analizar el uso particular de los smartphones entre los profesionales sanitarios de Atención Primaria durante el acto asistencial y sus consecuencias. Diseño: Estudio multicéntrico, transversal en un entorno de atención primaria, realizado en 3 fases: encuesta a profesionales, checklist de profesionales y encuesta a pacientes. Participantes: Profesionales sanitarios de atención primaria de la Gerencia Territorial de Atención Primaria de Barcelona (encuesta online) y profesionales sanitarios (checklist) y pacientes (encuesta a los pacientes) de 2equipos de Atención Primaria de Barcelona ciudad. Mediciones principales: Análisis descriptivo bivariado de las variables de las distintas encuestas. Utilización del teléfono móvil en la consulta, tiempo, motivo, tipo de uso y percepción de adecuación. Características de las interrupciones. Resultados: En relación con los pacientes, un 31% considera que el profesional sanitario solo debe consultar el teléfono móvil si es para resolver algún aspecto de su motivo de consulta y un 10% lo considera una falta de respeto. El 18% de los pacientes describen interrupciones, siendo la mayoría de entre 10 y 30 s de duración y considerándolas en su mayoría evitables. En relación con los profesionales, la mayoría (96%) afirma tener el teléfono móvil en la consulta y de manera silenciada (77%), y reconociendo solo el 2% su uso en presencia del paciente, lo que contrasta con lo descrito por los pacientes. Además, el 80% de los profesionales afirman pedir permiso para utilizarlo, contrastando con lo que refieren los pacientes (50%). El 85% de los profesionales consideran su uso como adecuado...(AU)

Objective: To analyze the particular use of smartphones among Primary Care Health professionals during the care act and its consequences. Design: Multicenter, cross-sectional study in a primary care setting, carried out in 3phases: survey of professionals, checklist of professionals and survey of patients. Participants: Primary Care Health professionals from the Territorial Primary Care Management of Barcelona (online survey) and health professionals (checklist) and patients (patient survey) from 2primary care teams in Barcelona city. Main measurements: Bivariate descriptive analysis of the variables from the different surveys. Use of the mobile phone in the consultation, time, reason, type of use and perception of appropriateness. Characteristics of interruptions. Results: In relation to patients, 31% consider that the health professional should only consult the mobile phone if it is to resolve some aspect of their reason for consultation and 10% consider it a lack of respect. Eighteen percent of patients describe interruptions, the majority lasting between 10 and 30s and considering them mostly avoidable. In relation to professionals, the majority (96%) claim to have their mobile phone in the consultation and on mute (77%), with only 2% recognizing its use in the presence of the patient, which is in line with what the patients describe. Furthermore, 80% of professionals say they ask permission to use it, contrasting with what patients report (50%). Eighty-five percent of professionals consider its use appropriate. Conclusions: The use of mobile phones is perceived by patients as an interruption that can affect the care act, generating dissatisfaction, which must be taken into account by health professionals. Healthcare organizations should establish recommendations regarding the use of mobile phones in consultations.

Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we generated oligodendroglia-specific AnkG conditional knockout mice and observed the destabilization of axoglial interactions in aged but not young adult mice. In addition, these mice exhibited profound histological, electrophysiological, and behavioral pathophysiologies. Unbiased translatomic profiling revealed potential compensatory machineries. These results highlight the critical functions of glial AnkG in maintaining proper axoglial interactions throughout aging and suggests a previously unrecognized contribution of oligodendroglial AnkG to neuropsychiatric disorders.

Dietary restriction modulates ultradian rhythms and autocorrelation properties in mice behavior.

Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology.

Sustained and Localized Drug Depot Release Using Radiation-Activated Scintillating Nanoparticles.

Clinical treatment of cancer commonly incorporates X-ray radiation therapy (XRT), and developing spatially precise radiation-activatable drug delivery strategies may improve XRT efficacy while limiting off-target toxicities associated with systemically administered drugs. Nevertheless, achieving this has been challenging thus far because strategies typically rely on radical species with short lifespans, and the inherent nature of hypoxic and acidic tumor microenvironments may encourage spatially heterogeneous effects. It is hypothesized that the challenge could be bypassed by using scintillating nanoparticles that emit light upon X-ray absorption, locally forming therapeutic drug depots in tumor tissues. Thus a nanoparticle platform (Scintillating nanoparticle Drug Depot; SciDD) that enables the local release of cytotoxic payloads only after activation by XRT is developed, thereby limiting off-target toxicity. As a proof-of-principle, SciDD is used to deliver a microtubule-destabilizing payload MMAE (monomethyl auristatin E). With as little as a 2 Gy local irradiation to tumors, MMAE payloads are released effectively to kill tumor cells. XRT-mediated drug release is demonstrated in multiple mouse cancer models and showed efficacy over XRT alone (p < 0.0001). This work shows that SciDD can act as a local drug depot with spatiotemporally controlled release of cancer therapeutics.

Microbial impact on initial soil formation in arid and semiarid environments under simulated climate change.

The microbiota is attributed to be important for initial soil formation under extreme climate conditions, but experimental evidence for its relevance is scarce. To fill this gap, we investigated the impact of in situ microbial communities and their interrelationship with biocrust and plants compared to abiotic controls on soil formation in initial arid and semiarid soils. Additionally, we assessed the response of bacterial communities to climate change. Topsoil and subsoil samples from arid and semiarid sites in the Chilean Coastal Cordillera were incubated for 16 weeks under diurnal temperature and moisture variations to simulate humid climate conditions as part of a climate change scenario. Our findings indicate that microorganism-plant interaction intensified aggregate formation and stabilized soil structure, facilitating initial soil formation. Interestingly, microorganisms alone or in conjunction with biocrust showed no discernible patterns compared to abiotic controls, potentially due to water-masking effects. Arid soils displayed reduced bacterial diversity and developed a new community structure dominated by Proteobacteria, Actinobacteriota, and Planctomycetota, while semiarid soils maintained a consistently dominant community of Acidobacteriota and Proteobacteria. This highlighted a sensitive and specialized bacterial community in arid soils, while semiarid soils exhibited a more complex and stable community. We conclude that microorganism-plant interaction has measurable impacts on initial soil formation in arid and semiarid regions on short time scales under climate change. Additionally, we propose that soil and climate legacies are decisive for the present soil microbial community structure and interactions, future soil development, and microbial responses.

Enhancing Structural Diversity of Lathyrane Derivatives through Biotransformation by the Marine-Derived Actinomycete Streptomyces puniceus BC-5GB.11.

Lathyrane-type diterpenes have a wide range of biological activities. Among them, euphoboetirane A (1) exerts neurogenesis-promoting activity. In order to increase the structural diversity of this type of lathyrane and explore its potential use in neurodegenerative disorders, the biotransformation of 1 by Streptomyces puniceus BC-5GB.11 has been investigated. The strain BC-5GB.11, isolated from surface sediments collected from the intertidal zone of the inner Bay of Cadiz, was identified as Streptomyces puniceus, as determined by phylogenetic analysis using 16S rRNA gene sequence. Biotransformation of 1 by BC-5GB.11 afforded five products (3-7), all of which were reported here for the first time. The main biotransformation pathways involved regioselective oxidation at non-activated carbons (3-5) and isomerization of the ∆12,13 double bond (6). In addition, a cyclopropane-rearranged compound was found (7). The structures of all compounds were elucidated on the basis of extensive NMR and HRESIMS spectroscopic studies.

Umbrella Review: Atlas of the Meta-Analytical Evidence of Early-Onset Psychosis.

OBJECTIVE: Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in the field of this vulnerable population and to provide evidence-based recommendations. METHOD: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant, pre-registered (PROSPERO: CRD42022350868) systematic review of several databases and registers to identify meta-analyses of studies conducted in EOP individuals to conduct an umbrella review. Literature search, screening, data extraction, and quality assessment were carried out independently. Results were narratively reported, clustered across core domains. Quality assessment was performed with the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. RESULTS: A total of 30 meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% female). Individuals with EOP showed more cognitive impairments compared with controls and individuals with adult/late-onset psychosis. Abnormalities were observed meta-analytically in neuroimaging markers but not in oxidative stress and inflammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest efficacy for overall, positive, and negative symptoms. Tolerance to medication varied among the evaluated antipsychotics. The risk of discontinuation of antipsychotics for any reason or side effects was low or equal compared to placebo. CONCLUSION: EOP is associated with cognitive impairment, involuntary admissions, and poor prognosis. Antipsychotics can be efficacious in EOP, but tolerability and safety need to be taken into consideration. Clozapine should be considered in EOP individuals who are resistant to 2 non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors. STUDY PREREGISTRATION INFORMATION: Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.

[Analysis of the interruptions generated by the use of smartphones among Primary Care Health professionals]. / Análisis de las interrupciones generadas por el uso de los smartphones entre los profesionales sanitarios de Atención Primaria.

OBJECTIVE: To analyze the particular use of smartphones among Primary Care Health professionals during the care act and its consequences. DESIGN: Multicenter, cross-sectional study in a primary care setting, carried out in 3phases: survey of professionals, checklist of professionals and survey of patients. PARTICIPANTS: Primary Care Health professionals from the Territorial Primary Care Management of Barcelona (online survey) and health professionals (checklist) and patients (patient survey) from 2primary care teams in Barcelona city. MAIN MEASUREMENTS: Bivariate descriptive analysis of the variables from the different surveys. Use of the mobile phone in the consultation, time, reason, type of use and perception of appropriateness. Characteristics of interruptions. RESULTS: In relation to patients, 31% consider that the health professional should only consult the mobile phone if it is to resolve some aspect of their reason for consultation and 10% consider it a lack of respect. Eighteen percent of patients describe interruptions, the majority lasting between 10 and 30s and considering them mostly avoidable. In relation to professionals, the majority (96%) claim to have their mobile phone in the consultation and on mute (77%), with only 2% recognizing its use in the presence of the patient, which is in line with what the patients describe. Furthermore, 80% of professionals say they ask permission to use it, contrasting with what patients report (50%). Eighty-five percent of professionals consider its use appropriate. CONCLUSIONS: The use of mobile phones is perceived by patients as an interruption that can affect the care act, generating dissatisfaction, which must be taken into account by health professionals. Healthcare organizations should establish recommendations regarding the use of mobile phones in consultations.

The magnitude and variability of neurocognitive performance in first-episode psychosis: a systematic review and meta-analysis of longitudinal studies.

Neurocognitive deficits are a core feature of psychotic disorders, but it is unclear whether they affect all individuals uniformly. The aim of this systematic review and meta-analysis was to synthesize the evidence on the magnitude, progression, and variability of neurocognitive functioning in individuals with first-episode psychosis (FEP). A multistep literature search was conducted in several databases up to November 1, 2022. Original studies reporting on neurocognitive functioning in FEP were included. The researchers extracted the data and clustered the neurocognitive tasks according to the seven Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and six additional domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. The primary effect size reported was Hedges g of (1) neurocognitive functioning in individuals at FEP measuring differences with healthy control (HC) individuals or (2) evolution of neurocognitive impairment across study follow-up intervals. Of 30,384 studies screened, 54 were included, comprising 3,925 FEP individuals and 1,285 HC individuals. Variability analyses indicated greater variability in FEP compared to HC at baseline and follow-up. We found better neurocognitive performance in the HC group at baseline and follow-up but no differences in longitudinal neurocognitive changes between groups. Across the 13 domains, individuals with FEP showed improvement from baseline in all studied domains, except for visual memory. Metaregressions showed some differences in several of the studied domains. The findings suggest that individuals with FEP have marked cognitive impairment, but there is greater variability in cognitive functioning in patients than in HC. This suggests that subgroups of individuals suffer severe disease-related cognitive impairments, whereas others may be much less affected. While these impairments seem stable in the medium term, certain indicators may suggest potential further decline in the long term for a specific subgroup of individuals, although more research is needed to clarify this. Overall, this study highlights the need for tailored neurocognitive interventions for individuals with FEP based on their specific deficits and progression.

In Vitro Analysis of the Antagonistic Biological and Chemical Interactions between the Endophyte Sordaria tomento-alba and the Phytopathogen Botrytis cinerea.

Plant pathogenic infections causing substantial global food losses are a persistent challenge. This study investigates a potential biocontrol strategy against the necrotrophic fungus Botrytis cinerea using the endophytic fungus Sordaria tomento-alba isolated from Gliricidia sepium in Colombia. Today, synthetic fungicides dominate B. cinerea control, raising environmental and health concerns. S. tomento-alba exhibits notable in vitro effects, inhibiting B. cinerea growth by approximately 60% during co-culture and 50% in double disc co-culture. Additionally, it suppresses botryanes production and produces the compound heptacyclosordariolone, which has proven effective in inhibiting B. cinerea mycelial growth and spore germination in vitro. This biocontrol agent could be a potential eco-friendly alternative to replace synthetic fungicides. Our study provides insights into the chemical and biological mechanisms underpinning the antagonistic activity of S. tomento-alba, emphasizing the need for further research to understand its biosynthesis pathways and optimize its biocontrol potential. It also contributes molecular evidence of fungal interactions with implications for advanced forums in molecular studies in biology and chemistry, particularly in addressing plant pathogenic infections and promoting sustainable agriculture.

Factors related to the development of high antibody titres against SARS-CoV-2 in convalescent plasma donors from the ConPlas-19 trial.

BACKGROUND AND OBJECTIVES: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. MATERIALS AND METHODS: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. RESULTS: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). CONCLUSION: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.

In Vitro Studies of Endophytic Bacteria Isolated from Ginger (Zingiber officinale) as Potential Plant-Growth-Promoting and Biocontrol Agents against Botrytis cinerea and Colletotrichum acutatum.

Agriculture currently confronts a multitude of challenges arising from the excessive utilization of chemical pesticides and the proliferation of phytopathogenic fungi strains that exhibit resistance to commonly employed active compounds in the field. Botrytis cinerea and Colletotrichum acutatum are phytopathogenic fungi that inflict substantial economic losses within agriculture and food due to their high impacts on crops both pre- and post-harvest. Furthermore, the emergence of fungal strains that are resistant to commercial fungicides has exacerbated this problem. To explore more environmentally sustainable alternatives for the control of these pathogens, an investigation into the endophytic bacteria associated with ginger (Zingiber officinale Rosc.) was conducted. The primary focus of this study involved evaluating their inhibitory efficacy against the fungi and assessing their potential for promoting plant growth. The endophytic bacteria genera Lelliottia, Lysinibacillus, Kocuria, Agrococcus, Acinetobacter, Agrobacterium, Zymobacter, and Mycolicibacterium were identified. All isolates showed remarkable in vitro antagonistic ability against B. cinerea (>94%) and C. acutatum (>74%). Notably, the Lelliottia amnigena J29 strain exhibited a notable proficiency in producing extracellular enzymes and indole compounds (IAA), solubilizing phosphate and potassium, and forming biofilm. Furthermore, the Lysinibacillus capsici J26, Agrococcus citreus J28, and Mycolicibacterium sp. J5 strains displayed the capacity for atmospheric nitrogen fixation and siderophore production. These findings underscore the agricultural and biotechnological potential of endophytic bacteria derived from ginger plants and suggest the feasibility of developing alternative approaches to manage these two phytopathogenic fungi.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

New Eremophilane-Type Sesquiterpenes from the Marine Sediment-Derived Fungus Emericellopsis maritima BC17 and Their Cytotoxic and Antimicrobial Activities.

The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima. On the basis of the one strain-many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (1-4), together with thirteen known derivatives (5-17) and two reported diketopiperazines (18, 19), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation. Thirteen of the isolated eremophilanes were examined for cytotoxic and antimicrobial activities. PR toxin (16) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058, and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 3.75 to 33.44 µM. (+)-Aristolochene (10) exhibited selective activity against the fungal strains Aspergillus fumigatus ATCC46645 and Candida albicans ATCC64124 at 471 µM.

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis.

BACKGROUND: Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited. AIMS: To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P. METHOD: PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle-Ottawa Scale. RESULTS: Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%-75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3-92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication. CONCLUSIONS: Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.