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1.
Am J Epidemiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960701

RESUMO

Endometrial cancer is one of few cancers that has continued to rise in incidence over the past decade with disproportionate increases in adults younger than 50 years old. We used data from the Surveillance, Epidemiology, and End Results Registry (2000-2019) to examine endometrial cancer incidence trends by race/ethnicity and age of onset among women in the United States. Case counts and proportions, age-adjusted incidence rates (per 100,000), and average annual percent changes were calculated by race/ethnicity, overall and stratified by age of onset (early vs late). We found a disproportionate increase in endometrial cancer incidence among women of color, for both early and late onset endometrial cancer. The highest increases in early onset endometrial cancer (<50 years old) were observed among American Indian/Alaska Native women (4.8), followed by Black (3.3), Hispanic/Latina (3.1), and Asian and Pacific Islander women (2.4), whereas white women (0.9) had the lowest increase. Late onset (>50 years old) endometrial cancer incidence followed a similar pattern, with the greatest increases for women of color. The increasing burden of endometrial cancer among women of color, particularly those younger than 50 years old, is a major public health problem necessitating further research and clinical efforts focused on health equity.

2.
Front Mol Neurosci ; 17: 1394058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828282

RESUMO

During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38713848

RESUMO

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.

4.
Pediatrics ; 153(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747049

RESUMO

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.


Assuntos
Unidades de Terapia Intensiva Pediátrica , Idioma , Tempo de Internação , Humanos , Masculino , Feminino , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Estudos Retrospectivos , Criança , Tempo de Internação/estatística & dados numéricos , Pré-Escolar , Lactente , Adolescente , Índice de Gravidade de Doença , Respiração Artificial/estatística & dados numéricos
5.
Res Sq ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38798510

RESUMO

Gut educated IgA secreting plasma cells that disseminate beyond the mucosa and into systemic tissues have been described as providing beneficial effects from disease in several contexts. Several bacteria have been implicated in the induction of systemic IgA, however the mechanisms that result in differential levels of induction by each bacterial species are still unknown. Here we show, the commensal bacteria, Bacteroides fragilis (Bf), is an efficient inducer of systemic IgA responses. The ability of Bf to induce the production of bone marrow IgA plasma cells and high levels of serum IgA relied on high levels of gut colonization in a dose-dependent manner. Colonization induced Bf-specific IgA responses were severely diminished in the absence of Peyer's patches, but not the murine cecal patch. Colonization of mice with Bf, a natural human commensal, resulted in few changes within the microbiome and the host transcriptional profile in the gut, suggesting a commensal relationship with the host. Bf colonization did benefit the mice by inducing systemic IgA that led to increased protection in a bowel perforation model resulting in lower peritoneal abscess formation. These findings demonstrate a critical role for bacterial colonization and Peyer's patches in the induction of robust systemic IgA responses that confer protection from bacterial dissemination outside of the gut.

6.
bioRxiv ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38617359

RESUMO

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.

7.
Commun Biol ; 7(1): 303, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461321

RESUMO

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.


Assuntos
Ritmo Ultradiano , Camundongos , Animais , Atividade Motora/fisiologia , Comportamento Animal/fisiologia , Ingestão de Alimentos , Agricultura
8.
Adv Mater ; 36(23): e2312326, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38389502

RESUMO

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.


Assuntos
Nanopartículas , Animais , Nanopartículas/química , Camundongos , Humanos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Preparações de Ação Retardada/química , Oligopeptídeos/química , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Portadores de Fármacos/química
9.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396965

RESUMO

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.


Assuntos
Diterpenos , Streptomyces , RNA Ribossômico 16S/genética , Filogenia , Diterpenos/química , Biotransformação
10.
Front Microbiol ; 15: 1319997, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298893

RESUMO

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.

11.
J Am Acad Child Adolesc Psychiatry ; 63(7): 684-697, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38280414

RESUMO

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. PLAIN LANGUAGE SUMMARY: This umbrella review summarized the meta-analytical knowledge from 30 meta-analyses on early-onset psychosis. Early-onset psychosis refers to the development of psychosis before the age of 18 years and is associated with cognitive impairment, hospitalization, and poor prognosis. Individuals with early-onset psychosis show more cognitive impairments and abnormalities compared with controls. Clozapine was the antipsychotic with the highest efficacy for positive, negative, and overall symptoms and should be considered in individuals with early-onset psychosis. STUDY PREREGISTRATION INFORMATION: Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.


Assuntos
Transtornos Psicóticos , Humanos , Transtornos Psicóticos/tratamento farmacológico , Adolescente , Idade de Início , Antipsicóticos/uso terapêutico , Antipsicóticos/farmacologia , Metanálise como Assunto , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico
12.
Aten Primaria ; 56(4): 102855, 2024 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-38232681

RESUMO

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.


Assuntos
Telefone Celular , Smartphone , Humanos , Estudos Transversais , Inquéritos e Questionários , Atenção Primária à Saúde
13.
Transl Psychiatry ; 14(1): 15, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191534

RESUMO

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.


Assuntos
Disfunção Cognitiva , Transtornos Psicóticos , Humanos , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Bases de Dados Factuais , Estudos Longitudinais , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico
14.
Int J Mol Sci ; 25(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38256097

RESUMO

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.


Assuntos
Fungicidas Industriais , Sordariales , Endófitos , Fungicidas Industriais/farmacologia , Agricultura , Botrytis
15.
Vox Sang ; 119(1): 27-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986640

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Humanos , Masculino , Anticorpos Neutralizantes , Anticorpos Antivirais , Doadores de Sangue , COVID-19/terapia , Soroterapia para COVID-19 , Imunização Passiva/métodos , Imunoglobulina G , Ensaios Clínicos como Assunto
16.
Psychol Med ; 53(15): 7375-7384, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38078747

RESUMO

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.


Assuntos
Experiências Adversas da Infância , Cannabis , Transtornos Psicóticos , Esquizofrenia , Humanos , Criança , Cannabis/efeitos adversos , Estudos de Casos e Controles , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/psicologia , Esquizofrenia/epidemiologia , Esquizofrenia/complicações
17.
Plants (Basel) ; 12(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068667

RESUMO

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.

18.
Mar Drugs ; 21(12)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38132955

RESUMO

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.


Assuntos
Anti-Infecciosos , Antineoplásicos , Hypocreales , Sesquiterpenos , Humanos , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Antineoplásicos/química , Sedimentos Geológicos/microbiologia , Anti-Infecciosos/química , Estrutura Molecular
19.
Mol Psychiatry ; 28(9): 3671-3687, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37957292

RESUMO

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.


Assuntos
Transtornos Mentais , Esquizofrenia , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Qualidade de Vida , Recidiva , Esquizofrenia/terapia
20.
Science ; 381(6658): eabq5693, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37561875

RESUMO

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.


Assuntos
Metilação de DNA , Epigênese Genética , Mamíferos , Adulto , Animais , Humanos , Epigenoma , Genoma , Mamíferos/genética , Filogenia
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