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Stress has repeatedly been implicated in the onset and exacerbation of positive symptoms of psychosis. Increasing interest is growing for the role of psychosocial stress in the development of psychosis symptoms in individuals at Clinical High Risk (CHR) for psychosis. A systematic review was therefore conducted to summarize the existing evidence base regarding psychosocial stress, interpersonal sensitivity, and social withdrawal in individuals at CHR for psychosis. An electronic search of Ovid (PsychINFO, EMBASE, MEDLINE, and GLOBAL HEALTH) was conducted until February 2022. Studies that examined psychosocial stress in CHR were included. Twenty-nine studies were eligible for inclusion. Psychosocial stress, interpersonal sensitivity, and social withdrawal were higher in CHR individuals compared to healthy controls and there was some evidence of their association with positive symptoms of psychosis. Two types of psychosocial stressors were found to occur more frequently with CHR status, namely daily stressors, and early and recent trauma, while significant life events did not appear to be significant. Greater exposure to psychosocial stress, emotional abuse, and perceived discrimination significantly increased risk of transition to psychosis in CHR. No studies examined the role of interpersonal sensitivity on transition to psychosis in CHR. This systematic review provides evidence for the association of trauma, daily stressors, social withdrawal, and interpersonal sensitivity with CHR status. Further studies investigating the impact of psychosocial stress on psychosis symptom expression in individuals at CHR and its effects on transition to psychosis are therefore warranted.

The integration between Enterprise Risk Management (ERM) and Performance Management System (PMS) has become a crucial process for managing environmental complexity in companies. In this context, in order to contribute to the research field, this paper follows two purposes: (1) to identify the most relevant risk dimensions, and connected risk drivers, perceived in managerial practices; and (2) to provide a suitable way to integrate ERM and PMS in supporting the strategic decision-making process. Based on semi-structured interviews with a total of 75 senior and middle managers from 25 different Italian companies, the authors developed a conceptual model to support the corporate transition to integrate ERM and PMS processes, built on a specific set of Key Risk Indicators (KRIs) that can enable them to achieve economically and environmentally sound performance.

Resumo Objetivo Analisar a tendência da mortalidade por suicídio no estado do Espírito Santo e em sua Região Serrana no período de 1996 a 2020. Métodos Estudo descritivo e analítico de série temporal com dados consolidados dos óbitos por suicídio na população acima de 15 anos de idade obtidos no Sistema de Informações sobre Mortalidade. As unidades de análise foram o estado do Espírito Santo e sua Região Serrana. A análise da tendência foi verificada pela regressão de Prais-Winsten e pelo cálculo da variação percentual anual. Resultados Foram notificados 3.922 óbitos por suicídio no Espírito Santo e, destes, 525 na Região Serrana. A tendência da mortalidade por suicídio no estado foi crescente na população geral acima de 15 anos (APC= 5,1; IC95%= 0,28-9,92; p=0,039). A tendência da mortalidade se manteve crescente entre a população feminina, tanto em relação ao estado (APC= 6;5; IC95%= 1,55-14,46; p=0,012) como na região serrana (APC= 15,2; IC95%= 1,21-29,20; p=0,035). A mortalidade foi crescente na faixa etária de 30 a 59 anos no estado (APC= 3,4; IC95%= 0,62-6,10; p=0,018) e na Região Serrana (APC= 2,9; IC95%= 2,02-3,86; p

Background and HypothesisSchizophrenia is increasingly understood as a disorder of brain dysconnectivity. Recently, graph-based approaches such as graph convolutional network (GCN) have been leveraged to explore complex pairwise similarities in imaging features among brain regions, which can reveal abstract and complex relationships within brain networks.Study DesignWe used GCN to investigate topological abnormalities of functional brain networks in schizophrenia. Resting-state functional magnetic resonance imaging data were acquired from 505 individuals with schizophrenia and 907 controls across 6 sites. Whole-brain functional connectivity matrix was extracted for each individual. We examined the performance of GCN relative to support vector machine (SVM), extracted the most salient regions contributing to both classification models, investigated the topological profiles of identified salient regions, and explored correlation between nodal topological properties of each salient region and severity of symptom.Study ResultsGCN enabled nominally higher classification accuracy (85.8%) compared with SVM (80.9%). Based on the saliency map, the most discriminative brain regions were located in a distributed network including striatal areas (ie, putamen, pallidum, and caudate) and the amygdala. Significant differences in the nodal efficiency of bilateral putamen and pallidum between patients and controls and its correlations with negative symptoms were detected in post hoc analysis.ConclusionsThe present study demonstrates that GCN allows classification of schizophrenia at the individual level with high accuracy, indicating a promising direction for detection of individual patients with schizophrenia. Functional topological deficits of striatal areas may represent a focal neural deficit of negative symptomatology in schizophrenia.

Psychosis is associated with a high risk of relapse, with 67% of clients relapsing within one year following a first episode. In light of the high personal, social, and healthcare costs of the illness, it is paramount to understand the risk factors associated with psychosis relapse. The current systematic review aims to critically review the role of psychosocial stress in psychosis relapse in individuals with an established psychotic disorder. This review systematically searched Ovid (PsycINFO, EMBASE, MEDLINE) literature databases from inception until 28th February 2022. Sixteen studies were eligible for inclusion. Most studies found that individuals with psychosis demonstrate high levels of psychosocial stress and are more likely to be socially withdrawn compared to healthy controls or other clinical presentations. Most studies reported a statistically significant association between psychosocial stress and psychosis relapse, as well as between social withdrawal and psychosis relapse. However, no studies examined the association between high levels of interpersonal sensitivity and psychosis relapse. Individuals with psychosis tend to experience high levels of psychosocial stress and social withdrawal, and these appear to increase the risk of psychosis relapse. Due to high levels of heterogeneity within the literature, we could only conduct a narrative synthesis of the findings. Future studies would benefit from employing a meta-analytic approach.

Although the discovery of the critical role of α-synuclein (α-syn) in the pathogenesis of Parkinson’s disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.

O alcoolismo produz alterações na saúde individual e coletiva, podendo resultar em manifestações físicas, psíquicas e sociais muito importantes, requerendo uma intervenção integral e em rede. O objetivo desse estudo é descrever o processo de trabalho da equipe de enfermagem no Programa de Atenção ao Alcoolista (PAA) do Hospital Universitário Cassiano Antônio Moraes (HUCAM) da Universidade Federal do Espírito Santo (UFES). Utilizou-se a técnica da observação direta geral (profissionais) e específica (equipe de enfermagem) e pesquisa documental (relatórios, artigos e livros), para captar a realidade assistencial do Programa. O PAA-HUCAM-UFES é um serviço ambulatorial para o tratamento do alcoolismo, com abordagem interprofissional composta por Enfermeiro, Médico e Assistente Social. No Programa é realizada a Consulta de Enfermagem (CE) com atividades educação em saúde para suprir as Necessidades Humanas Básicas (NHB) e promover o autocuidado do alcoolista, com base na Teoria de Horta e Orem. E, ao longo de mais de 30 anos de experiência, a equipe de enfermagem vem desenvolvendo o cuidado do alcoolista, buscando sua autonomia, seu protagonismo ativo e o respeito aos seus direitos de cidadão.

Purpose The purpose of this paper is twofold: to provide a clear picture on the cognitive biases affecting managers’ decision-making process of implementing a performance management system (PMS), and to identify managerial practices, measures and the key challenges to manage the cognitive biases in the corporate strategy. Design/methodology/approach Semi-structured interviews, based on theoretical milestones of performance management and cognitive psychology, gathered from 104 experienced professionals’ evaluations on the likelihood and impact of managers’ cognitive biases in PMS implementation, potential solutions as well as drivers and connected criticalities. Findings Recurring cognitive biases, together with considerable impacts, emerged in the first, and most strategic, phases of the PMS implementation. The authors developed a roadmap to support corporate transition to integrate behavioral strategy into the PMS implementation aiming to achieve economically and efficiently sound performance. Research limitations/implications From the view of proper behavioral strategy affirmation in performance management literature, in a small way, the authors contribute to a desirable taxonomy of cognitive biases so differentiated decision-making scenarios may be built to compare results and draw new observations. Behavioral studies could transversally connect the cognitive biases of performance management to actors’ sociodemographic features and personality types. Practitioners may check biases affecting their organizations by means of the questionnaire and, consequently, adopt the framework illustrated to reduce them. Originality/value Performance management literature has constantly investigated positive and negative behavioral factors related to the PMS. This study, instead, makes a theoretical and methodological contribution to the PMS implementation as a decision-making process. The authors propose a theoretical framework that integrates cognitive psychology insights and applies measures to reduce biases.

Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas, genital papillomatosis, and carcinomas. During a survey on the fertility status of a mare, a novel Equus caballus PV (EcPV) has been identified using Next Generation Sequencing, and it was further confirmed with genome-walking PCR and Sanger sequencing. The complete circular genome 7607 bp long shares 67% average percentage of identity with EcPV9, EcPV2, EcPV1, and EcPV6, justifying a new classification as Equus caballus PV 10 (EcPV10). All EcPV genes are conserved in EcPV10, and phylogenetic analysis indicates that EcPV10 is closely related to EcPV9 and EcPV2, genus Dyoiota 1. A preliminary EcPV10 genoprevalence study, carried out on 216 horses using Real Time PCRs, suggested a low incidence of this isolate (3.7%) compared to EcPVs of the same genus such as EcPV2 and EcPV9 in the same horse population. We hypothesize a transmission mechanism different from the one observed in the closely related EcPV9 and EcPV2 that particularly infect Thoroughbreds. This horse breed is usually submitted to natural mating, thus indicating a possible sexual diffusion. No differences were detected for breeds in terms of susceptibility to EcPV10. Further studies are needed to investigate the molecular mechanisms behind the host and EcPV10 infection to explain the reduced viral spread.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.

Loneliness is a major public health concern with links to social and environmental factors. Previous studies have typically investigated loneliness as a stable emotional state using retrospective cross-sectional designs. Yet people experience different levels of loneliness throughout the day depending on their surrounding environment. In the present study, we investigated the associations between loneliness and social and environmental factors (i.e. overcrowding, population density, social inclusivity and contact with nature) in real-time. Ecological momentary assessment data was collected from participants using the Urban Mind smartphone application. Data from 756 participants who completed 16,602 assessments between April 2018 and March 2020 were used in order to investigate associations between momentary feeling of loneliness, the social environment (i.e. overcrowding, social inclusivity, population density) and the built environment (i.e. contact with nature) using multilevel modelling. Increased overcrowding and population density were associated with higher levels of loneliness; in contrast, social inclusivity and contact with nature were associated with lower levels of loneliness. These associations remained significant after adjusting for age, gender, ethnicity, education and occupation. The positive association between social inclusivity and lower levels of loneliness was more pronounced when participants were in contact with nature, indicating an interaction between the social and built environment on loneliness. The feeling of loneliness changes in relation to both social and environmental factors. Our findings have potential implications for public health strategies and interventions aimed at reducing the burden of loneliness on society. Specific measures, which would increase social inclusion and contact with nature while reducing overcrowding, should be implemented, especially in densely populated cities.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Schizophrenia is a complex and heterogeneous syndrome. Whether quantitative imaging biomarkers can identify discrete subgroups of patients as might be used to foster personalized medicine approaches for patient care remains unclear. Cross-sectional structural MR images of 163 never-treated first-episode schizophrenia patients (FES) and 133 chronically ill patients with midcourse schizophrenia from the Bipolar and Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium and a total of 403 healthy controls were recruited. Morphometric measures (cortical thickness, surface area, and subcortical structures) were extracted for each subject and then the optimized subtyping results were obtained with nonsupervised cluster analysis. Three subgroups of patients defined by distinct patterns of regional cortical and subcortical morphometric features were identified in FES. A similar three subgroup pattern was identified in the independent dataset of patients from the multi-site B-SNIP consortium. Similarities of classification patterns across these two patient cohorts suggest that the 3-group typology is relatively stable over the course of illness. Cognitive functions were worse in subgroup 1 with midcourse schizophrenia than those in subgroup 3. These findings provide novel insight into distinct subgroups of patients with schizophrenia based on structural brain features. Findings of different cognitive functions among the subgroups support clinical differences in the MRI-defined illness subtypes. Regardless of clinical presentation and stage of illness, anatomic MR subgrouping biomarkers can separate neurobiologically distinct subgroups of schizophrenia patients, which represent an important and meaningful step forward in differentiating subtypes of patients for studies of illness neurobiology and potentially for clinical trials.

Idiopathic normal pressure hydrocephalus (iNPH) shares clinical and radiological features with progressive supranuclear palsy (PSP) and Alzheimer’s disease (AD). Corpus callosum (CC) involvement in these disorders is well established on structural MRI and diffusion tensor imaging (DTI), but alterations overlap and lack specificity to underlying tissue changes. We propose a semi-automated approach to assess CC integrity in iNPH based on the spatial distribution of DTI-derived principal diffusion direction orientation (V1). We processed DTI data from 121 subjects (Site1: iNPH = 23, PSP = 27, controls = 14; ADNI: AD = 35, controls = 22) to obtain V1, fractional anisotropy (FA) and mean diffusivity (MD) maps. To increase the estimation accuracy of DTI metrics, analyses were restricted to the midsagittal CC portion (± 6 slices from midsagittal plane). Group-wise comparison of normalized altered voxel count in midsagittal CC was performed using Kruskal–Wallis tests, followed by post hoc comparisons (Bonferroni-corrected p

Objetivo: analisar o consumo de álcool e tabaco entre os estudantes do curso de Fonoaudiologia de uma universidade pública. Método: trata-se de um estudo transversal; a investigação foi fundamentada no preenchimento do instrumento proposto pela Secretaria Nacional de Políticas sobre Drogas. O estudo possui uma amostra de 130 estudantes matriculados no curso de Fonoaudiologia, o que corresponde a 79,06% dos alunos matriculados em 2018. Resultados: o álcool apresenta-se como uma das substâncias lícitas mais consumidas entre os universitários, o uso na vida, no ano e nos últimos 30 dias foram de 79,2%, 56,2% e 45,4%, respectivamente. Quanto ao tabaco, 21,5% relataram que realizaram o consumo de tabaco em algum momento da vida; no ano, 8,5% e, nos últimos 30 dias, 7,7%. Na análise multivariada, as variáveis preditoras significativas para o uso de álcool foram idade (no mês) e prática religiosa (no ano e no mês). Já para o uso do tabaco foram: sexo (ao longo da vida), prática religiosa (ao longo da vida e no ano) e grupo étnico (no ano). Conclusão: os achados deste estudo apontam que prevalece o consumo das substâncias lícitas entre os universitários, tornando-se importante maior abordagem do tema e ações de prevenção ao uso ...

Here we host extended data of a bionformatical analysis of SARS-CoV-2 and other virus-host interaction networks suggesting autoimmune and comorbidity-dependent mechanisms implicated in severe COVID-19, and a network-based drug repuroposing screening.

The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae. We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood–brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases.

Existing evidence shows positive effects of being in nature on wellbeing, but we know little about the mental health benefits of spending time near canals and rivers specifically. This study investigates the association between visits to canals and rivers and mental wellbeing. We addressed the following questions: Are visits to canals and rivers associated with higher levels of mental wellbeing? Does this association depend on age and gender? Does this association vary between people with and without a diagnosis on mental illness?We used Urban Mind, a flexible smartphone application for examining the impact of different aspects of the built and social environment on mental wellbeing, a strong predictor of mental health. Participants were invited to complete an ecological momentary assessment three times a day for fourteen days. Each assessment included questions about their surrounding environment and mental wellbeing. A total of 7,975 assessments were completed by 299 participants including 87 with a diagnosis of mental illness. Multilevel regression models were used to analyse the data.We found positive associations between visits to canals and rivers and mental wellbeing (pSpending time near canals and rivers is associated with better mental wellbeing. These findings have potential implications for mental health as well as urban planning and policy. Visits to canals and rivers could become part of social prescribing schemes, playing a role in preventing mental health difficulties and complementing more traditional interventions.

Il tema centrale del capitolo è la valutazione delle aziende sequestrate e confiscate alla criminalità organizzata. Tale valutazione si rende necessaria nelle varie fasi delle misure di prevenzione patrimoniale, anche perché prescritta da specifiche norme (il D.Lgs. n. 159/2011). Il contesto valutativo è tuttavia caratterizzato da numerosi ostacoli sia di natura aziendale (organizzativi, gestionali, di difficoltà al reperimento di dati e informazioni) che ambientale. I proficui contributi di dottrina e, di recente, la predisposizione di apposite linee guida, hanno offerto la definizione di un primo framework valutativo nell’ambito delle distinte fasi del sequestro e della confisca, ciascuna delle quali contraddistinta da autonome peculiarità normative e gestionali, criticità valutative, basi informative, soggetti valutatori, presupposti di continuità, metodiche estimative, ottiche da adottare e relazioni di stima.

In this contribution we propose and rigorously analyze new variants of adaptive Trust-Region methods for parameter optimization with PDE constraints and bilateral parameter constraints. The approach employs successively enriched Reduced Basis surrogate models that are constructed during the outer optimization loop and used as model function for the Trust-Region method. Each Trust-Region sub-problem is solved with the projected BFGS method. Moreover, we propose a non-conforming dual (NCD) approach to improve the standard RB approximation of the optimality system. Rigorous improved a posteriori error bounds are derived and used to prove convergence of the resulting NCD-corrected adaptive Trust-Region Reduced Basis algorithm. Numerical experiments demonstrate that this approach enables to reduce the computational demand for large scale or multi-scale PDE constrained optimization problems significantly.

Deep grey nuclei of the human brain accumulate minerals both in aging and in several neurodegenerative diseases. Mineral deposition produces a shortening of the transverse relaxation time which causes hypointensity on magnetic resonance (MR) imaging. The physician often has difficulties in determining whether the incidental hypointensity of grey nuclei seen on MR images is related to aging or neurodegenerative pathology. We investigated the hypointensity patterns in globus pallidus, putamen, caudate nucleus, thalamus and dentate nucleus of 217 healthy subjects (ages, 20-79 years; men/women, 104/113) using 3T MR imaging. Hypointensity was detected more frequently in globus pallidus (35.5%) than in dentate nucleus (32.7%) and putamen (7.8%). A consistent effect of aging on hypointensity (p < 0.001) of these grey nuclei was evident. Putaminal hypointensity appeared only in elderly subjects whereas we did not find hypointensity in the caudate nucleus and thalamus of any subject. In conclusion, the evidence of hypointensity in the caudate nucleus and thalamus at any age or hypointensity in the putamen seen in young subjects should prompt the clinician to consider a neurodegenerative disease.

Introdução: O alcoolismo é um problema de saúde pública e também um dos principais fatores de risco à saúde. O alcoolismo feminino possui peculiaridades, uma vez que as repercussões são intensas, precoces e potencializam a vulnerabilidade social feminina. Objetivo: Identificar as evidências científicas acerca do alcoolismo feminino no Brasil. Métodos: Foi realizada uma revisão integrativa da literatura. Os critérios de inclusão foram artigos publicados entre 2006 e 2016, nos idiomas português, inglês ou espanhol e relativos a estudos primários. O levantamento dos artigos científicos foi realizado em novembro de 2018, nas bibliotecas digitais Scielo, Lilacs e Medline. Foram utilizados os seguintes descritores: Álcool, Alcoolismo, Abstinência de Álcool, Abstinência Alcoólica, Síndrome da Dependência Alcoólica e Transtornos Relacionados ao Uso de Álcool e Mulheres. A partir da seleção da amostra, foi estruturado um banco de dados com as seguintes informações: ano de publicação, autores, título do artigo, delineamento do estudo, objetivos, resultados e nível de evidência. Resultados: Foram selecionados 31 artigos e identificados os seguintes temas: fatores de proteção; fatores de risco; uso de álcool na gravidez; tratamento; papel social e sua relação com o alcoolismo e vulnerabilidades. Conclusão: A análise da literatura revelou o álcool como fator de risco para diversos agravos, como: violência doméstica, abandono familiar, conflitos familiares e comorbidades psicossociais. A produção científica brasileira sobre o impacto do alcoolismo na saúde feminina é essencial para estruturar as abordagens sobre o alcoolismo feminino, serviços de saúde, enfrentamento às vulnerabilidades sociais e promoção dos fatores de proteção.

Background and ObjectivesFluid biomarkers are a recent field of interest in Huntington disease (HD). We focused on small circulating RNAs from plasma of subjects with prodromal (pre-HD) and overt disease by a two-stage approach: an unbiased investigation by an array method and a validation study to quantify a significant small nucleolar RNA.MethodsThrough Affymetrix Gene-Chip-miRNA-Array we performed an exploratory study on 9 HD patients, 8 healthy subjects (HS) and 5 psychiatric patients (PP; who share drugs with HD patients, to control for iatrogenic effects). Through real time PCR we validated the results in an independent population of 24 HD patients, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (added to control the disease-specificity of our finding) and 23 HS. A bioinformatic analysis was also performed to interpret our finding.ResultsThe microarray results showed a significant signal for U13 small nucleolar RNA (SNORD13) that was increased in plasma of HD patients compared to controls (fold change, 1.54, p =0.003 HD vs. HS, and fold change 1.44 p = 0.0026 HD vs. PP). In the validation population the significant increase in HD patients was evident compared to both pre-HD and the three control groups (pDiscussionWe report the unprecedented finding of a potential role of small nucleolar RNAs in HD. Circulating SNORD13 seems a good biomarker for clinical purposes. It seems to be specific for HD and to peripherally report a plausible ‘tipping point’ in the pathogenic cascade at neuronal level, possibly paving the way for new therapeutic targets.

BackgroundIdentification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.MethodsA total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine (n= 71) or lithium (n= 50). Participants completed structural magnetic resonance imaging (MRI) at baseline before treatment and 1 week after treatment initiation, and brain morphometric features were extracted for each individual based on MRI scans. Positive antimanic treatment response at week 6 was defined as an over 50% reduction of Young Mania Rating Scale scores from baseline. Two-stage deep learning prediction model was established to distinguish responders and non-responders based on different feature sets.ResultsPre-treatment morphometry and morphometric changes occurring during the first week can both independently predict treatment outcome of quetiapine and lithium with balanced accuracy over 75% (allp< 0.05). Combining brain morphometry at baseline and week 1 allows prediction with the highest balanced accuracy (quetiapine: 83.2% and lithium: 83.5%). Predictions in the quetiapine and lithium group were found to be driven by different morphometric patterns.ConclusionsThese findings demonstrate that pre-treatment morphometric measures and acute brain morphometric changes can serve as medication response predictors in pediatric BD. Brain morphometric features may provide promising biomarkers for developing biologically-informed treatment outcome prediction and patient stratification tools for BD treatment development.

PurposeThe purpose of this paper is to estimate foreign direct investment (FDI) premia in the former Soviet states.Design/methodology/approachThe authors follow an empirical approach. Using Orbis data for a sample of more than 3,000 companies, the authors characterize FDI involvement and FDI premia of firms from three distinctive groups of former Soviet states, designated “upper-middle”-income, “lower-middle”-income and “high”-income countries. This yields interesting within-group and between-group results on the effects of outward FDI (OFDI) and inward FDI (IFDI) on firm-level innovation.FindingsThe authors unveil new facts about innovation and FDI in the former Soviet states. FDI firms innovate more than non-FDI firms and OFDI firms innovate more than IFDI firms. The innovation effect of OFDI is the largest for firms from the “lower-middle” countries, followed by the “high” and “upper-middle” countries. The innovation effect of IFDI is the largest for firms from the “lower-middle” countries, followed by the “upper-middle” and “high” countries. FDI to and from Europe has the largest impact on innovation; this holds across country groups.Research limitations/implicationsThe estimates of this paper document robust FDI premia, i.e., a positive and significant correlation between firm-level innovation and FDI. However, the cross-sectional nature of the data does not permit a proper causality analysis.Originality/valueThe paper contributes to the literature on FDI premia by: considering IFDI and OFDI in a unified empirical framework; dissecting IFDI and OFDI by location; measuring firm-level productivity in terms of innovation; and providing cross-country comparable evidence on both emerging and advanced economies. At the same time, the paper contributes to the literature on FDI from emerging economies by: taking a firm-level quantitative approach; focusing on a relatively unexplored set of countries; and providing comparable cross-country evidence on both emerging and advanced economies.

The first-time adoption of IAS/IFRS accompanied by the issuance of new international accounting standards has provided mixed results regarding their ability to improve accounting quality. A possible reason is that not only the quality of the standard-setting process, but also other factors might affect accounting quality and one of its dimensions, namely, value relevance. By analysing data from a sample of 316 financial entities listed in 43 countries from all over the world and adopting IFRS 9 in place of IAS 39 as of 1st January 2018, this paper tests whether the quality of firm-level corporate governance and country-level investor protection environments affects the value relevance of equity values calculated according to the requirements of IFRS 9 and IAS 39. The results suggest that, despite both accounting standards providing investors with value relevant information, in the presence of high-quality corporate governance or a high-quality investor protection environment, IFRS 9 is more value relevant than IAS 39, whereas the opposite is true in the presence of low-quality corporate governance or a low-quality investor protection environment. The research results provide the first empirical evidence of the value relevance of the new accounting standard on financial instruments and contribute to the debate on the existence of other factors that, together with the quality of the IASB standards, affect the quality of financial reporting.

ObjectivesChildhood maltreatment is associated with altered neural reactivity during autobiographical memory (ABM) recall and a pattern of overgeneral memory (OGM). Altered ABM and OGM have been linked with psychopathology and poorer social functioning. The present study investigated the association between altered ABM and subsequent socio-emotional functioning (measured two years later) in a sample of adolescents with (N = 20; maltreatment group, MT) and without (N = 17; non-MT group) documented childhood maltreatment histories.MethodAt baseline, adolescents (aged 12.6 ± 1.45 years) were administered the Autobiographical Memory Test to measure OGM. Participants also recalled specific ABMs in response to emotionally valenced cue words during functional MRI. Adolescents in both groups underwent assessments measuring depressive symptoms and prosocial behavior at both timepoints. Regression analyses were carried out to predict outcome measures at follow-up controlling for baseline levels.ResultsIn the MT group, greater OGM at baseline significantly predicted reduced prosocial behavior at follow-up and showed a trend level association with elevated depressive symptoms. Patterns of altered ABM-related brain activity did not significantly predict future psycho-social functioning.ConclusionsThe current findings highlight the potential value of OGM as a cognitive mechanism that could be targeted to reduce risk of depression in adolescents with prior histories of maltreatment.

The first-time adoption of International Financial Reporting Standard (IFRS) 9 at the beginning of fiscal year 2018 has offered the opportunity to test whether the information provided by this new accounting standard on financial instruments is more useful for investors than International Accounting Standard (IAS) 39. This paper assesses and compares the value relevance of book value calculated ac-cording to the requirements of the two accounting standards on financial instru-ments at the beginning of the transition year for a sample of 110 financial entities listed in 20 stock markets that have recorded transition effects between retained earnings. Findings provide evidence that both IAS 39 and IFRS 9 are value rele-vant and that the second one adds more information than that previously supplied by the first one. The paper contributes to the literature by providing the first evi-dence of the usefulness of the new accounting standard on financial instruments. About its practical implications, the paper provides insights regarding the high quality of the International Accounting Standard Board (IASB)'s standard setting process.

Aims Around 15% of patients at clinical high risk for psychosis (CHR-P) experience symptomatic remission and functional recovery at follow-up, yet the definition of a good outcome (GO) in this population requires further development. Outcomes are typically designed and rated by clinicians rather than patients, to measure adverse as opposed to GOs. Here we investigate how CHR-P subjects define a GO, with the aim of developing a checklist that could be used to measure GO in this clinical group. Methods A set of GO-focused questions were designed in collaboration with a service-user. CHR-P patients (n = 48) were asked to rate the importance of items that could indicate short-term (1 year) and long-term (5 years) GO. These items were then ranked using the relative importance index (RII). Results Patients rated improvement in subjective wellbeing (RII = 0.829) and non-specific presenting symptoms (RII = 0.817) amongst the factors most important for indicating GO in the short-term, and improved resilience (RII = 0.879) and negative symptoms (RII = 0.858) as key items for indicating long-term GO. Patients regarded building resilience (RII = 0.842) and having support from mental health services (RII = 0.833) as being protective for their mental health. These measures were included in a preliminary 12-item GO checklist (GO-12) for assessing GO in CHR-P subjects. Conclusions Patient-defined measures of GO included items that are not incorporated into conventional measures of outcomes in CHR-P subjects, such as subjective wellbeing and resilience. Integrating patient-defined metrics of GO may improve the assessment of outcomes in the CHR-P population.

Background: MS is a chronic inflammatory disease of the CNS leading to demyelination and neurodegeneration, with a complex and still to be clarified aetiology. Several data, coming from patients' samples and from animal models, show that Oxidative Status (OS) plays an important role in MS pathogenesis. Overproduction of reactive oxidative species by macrophages/microglia can bring about cellular injury and ensuing cell death by oxidizing cardinal cellular components. Oxidized molecules are present in active MS lesions and are associated with neurodegeneration. Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature focusing on OS in MS. The contents of the selected papers were described in the context of a conceptual framework. A special emphasis was given to the results of our study in the field. Results: The results of our three recent studies were put in the context and discussed taking into account the literature on the topic. Oxidative damage underpinned an imbalance shared by MS and neurodegenerative diseases such as Alzheimer and Parkinson diseases. In people with clinically isolated syndrome (an early phase of MS) oxidative stress proved to contribute to disease pathophysiology and to provide biomarkers that may help predict disease evolution. A drug screening platform based on multiple assays to test the remyelinating potential of library of approved compounds showed two anti-oxidants, edaravone and 5-methyl-7- methoxyisoflavone, as active drugs. Moreover, an analysis of 'structure activity relationship' showed off-targets sites of these compounds that accounted for their remyelinating activity, irrespective of their antioxidant action. Conclusion: Overall, edaravone emerges as a candidate to treat complex disease such as MS, where inflammation, oxidative stress and neurodegeneration contribute to disease progression, together or individually, in different phases and disease types. Furthermore, approaches based on drug repositioning seem to maintain the promise of helping discover novel treatment for complex diseases, where molecular targets are largely unknown.

Resumo O objetivo deste artigo é analisar a completude dos campos de notificações de dengue registradas em um município de pequeno porte no Brasil, no período de 2007 a 2015. Estudo descritivo com abordagem quantitativa, composto pela totalidade de registros disponíveis no Sistema Nacional de Agravos de Notificação. Analisou-se o número absoluto e o percentual de não preenchimento das variáveis chave, obrigatórias e essenciais das fichas de notificação de dengue e com a finalidade de avaliar os graus de não completude, adotou-se escore proposto por Romero e Cunha. Foi calculado o coeficiente não paramétrico de correlação linear de Spearman (rs), sendo precedido pela verificação da distribuição dos dados através do teste de Kolmogorov Smirnov. A proporção de informações ignoradas foi elevada para a maioria das variáveis e para algumas, as tendências de não completude no decorrer dos anos foram decrescentes e estatisticamente significantes. A qualidade dos dados foi, em sua maioria, classificada como regular e muito ruim, tornando-se imprescindível o estabelecimento de estratégias no processo de capacitação das equipes de saúde que atuam na atenção primária, para a sensibilização e conscientização da importância da qualidade no registro das notificações compulsórias.

Objetivo: traçar o perfil do uso de álcool e tabaco e seus fatores associados entre universitários de Terapia Ocupacional. Método: estudo transversal realizado com estudantes acima de 18 anos do primeiro ao último período do curso de Terapia Ocupacional de uma universidade pública. O instrumento de pesquisa utilizado foi o questionário proposto pela Secretaria Nacional de Políticas sobre Drogas para o I Levantamento Nacional sobre o Uso de Álcool e Outras Drogas entre Universitários das 27 Capitais Brasileiras. Para a análise estatística, foi utilizado o Statistical Package for the Social Science. Resultados: a prevalência de “binge drinking no ano” foi de 61,5% e de “binge drinking no mês” foi de 46,8%. O uso na vida de tabaco foi de 36% e no ano de 25,7%. A religião mostrou-se significativamente associada ao “binge drinking no ano” e ao uso na vida e no ano de tabaco. “Pegar carona com o motorista da vez” e “Pegar carona com motorista alcoolizado” associaram-se significativamente às variáveis “binge drinking no ano” e “binge drinking no mês”. Conclusão: os resultados contribuem para criar ações de prevenção ao uso indevido de álcool e tabaco, bem como à inclusão ou ampliação da abordagem do tema no currículo do curso.

The mental health benefits of everyday encounters with birdlife for mental health are poorly understood. Previous studies have typically relied on retrospective questionnaires or artificial set-ups with little ecological validity. In the present study, we used the Urban Mind smartphone application to examine the impact of seeing or hearing birds on self-reported mental wellbeing in real-life contexts. A sample of 1292 participants completed a total of 26,856 ecological momentary assessments between April 2018 and October 2021. Everyday encounters with birdlife were associated with time-lasting improvements in mental wellbeing. These improvements were evident not only in healthy people but also in those with a diagnosis of depression, the most common mental illness across the world. These findings have potential implications for both environmental and wildlife protection and mental healthcare policies. Specific measures, aimed at preserving and increasing everyday encounters with birdlife in urban areas, should be implemented.

Patients with major depressive disorder (MDD) exhibit concurrent deficits in both sensory and higher-order cognitive processing. Connectome studies have suggested a principal primary-to-transmodal gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether this gradient structure is disrupted in patients with MDD and how this disruption associates with gene expression profiles and treatment outcome remain unknown. Using a large cohort of resting-state fMRI data from 2227 participants (1148 MDD patients and 1079 healthy controls) recruited at nine sites, we investigated MDD-related alterations in the principal connectome gradient. We further used Neurosynth, postmortem gene expression, and an 8-week antidepressant treatment (20 MDD patients) data to assess the meta-analytic cognitive functions, transcriptional profiles, and treatment outcomes related to MDD gradient alterations, respectively. Relative to the controls, MDD patients exhibited global topographic alterations in the principal primary-to-transmodal gradient, including reduced explanation ratio, gradient range, and gradient variation (Cohen's d = 0.16-0.21), and focal alterations mainly in the primary and transmodal systems (d = 0.18-0.25). These gradient alterations were significantly correlated with meta-analytic terms involving sensory processing and higher-order cognition. The transcriptional profiles explained 53.9% variance of the altered gradient pattern, with the most correlated genes enriched in transsynaptic signaling and calcium ion binding. The baseline gradient maps of patients significantly predicted symptomatic improvement after treatment. These results highlight the connectome gradient dysfunction in MDD and its linkage with gene expression profiles and clinical management, providing insight into the neurobiological underpinnings and potential biomarkers for treatment evaluation in this disorder.

Cognitive-behavioural therapy (CBT) is the first line of treatment for several mental health disorders. However, not all patients show clinical improvements after receiving CBT. Machine learning allows inferences at the individual level and therefore is a promising approach for predicting who will and will not benefit from CBT. A comprehensive literature search was conducted to identify all studies that used machine learning to predict clinical response to CBT. A random-effects meta-analysis of proportions was used to estimate an overall performance accuracy across all studies. Twenty-four studies (N = 7497) were identified, covering five diagnostic groups: Major Depressive Disorder (k = 4), Obsessive-Compulsive Disorder (OCD, k = 5), Post-Traumatic Stress Disorder (k = 2), Anxiety Disorders (AD, k = 7), Substance Use Disorders (k = 4) and two transdiagnostic models. Studies used clinical, neuroimaging, cognitive and genetic data, or a combination of these, as predictors. The overall performance accuracy across studies was 74.0% [70.0–77.8]. Accuracies differed significantly between diagnostic groups and was highest in PTSD (78.7%, 69.1–87.0), AD (77.6%, 67.5–86.4) and OCD (76.1%, 67.3–84.0). Some studies were at a high risk of bias due to how the outcome was operationalised and/or how the analyses were conducted/reported. There are many challenges to overcome before these promising results can be applied to real-world clinical practice.

This paper links the debate on the decrease in competitiveness and busi ness dynamism with that on rising inequality. We build a framework with entry, imperfect competition, heterogeneous households, and incomplete markets. Recent trends in markups, factorsíshare, and business dynamism are explained through an increase in barriers to entry for new Örms, which restrict competition. Those trends account for 11% to 22% of the increase in income inequality observed between 1989 and 2007 and for 10% of the in crease in wealth inequality. Just 16% of the population experiences a welfare gain during the transition from a high to a low competition environment. These are either the wealthy, or agents with low productivity relative to their asset holdings.

Plasma small RNAs have been recently explored as biomarkers in Huntington’s disease (HD). We performed an exploratory study on nine HD patients, eight healthy subjects (HS), and five psychiatric patients (PP; to control for iatrogenic confounder effects) through an Affymetrix-Gene-Chip-miRNA-Array. We validated the results in an independent population of 23 HD, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (to control the disease-specificity) and 22 HS through real-time PCR. The microarray results showed higher levels of U13 small nucleolar RNA (SNORD13) in HD patients than controls (fold change 1.54, p = 0.003 HD vs. HS, and 1.44, p = 0.0026 HD vs. PP). In the validation population, a significant increase emerged with respect to both pre-HD and the control groups (p < 0.0001). SNORD13 correlated with the status of the mutant huntingtin carrier (r = 0.73; p < 0.001) and the disease duration (r = 0.59; p = 0.003). The receiver operating characteristic (ROC) curve analysis showed the high accuracy of SNORD13 in discriminating HD patients from other groups (AUC = 0.963). An interactome and pathway analysis on SNORD13 revealed enrichments for factors relevant to HD pathogenesis. We report the unprecedented finding of a potential disease-specific role of SNORD13 in HD. It seems to peripherally report a ‘tipping point’ in the pathogenic cascade at the neuronal level.

The tumor microenvironment is a complex system, where neoplastic cells interact with immune and stromal cells. Tumor-associated macrophages (TAMs) are considered among the most numerically and biologically noteworthy cellular components in tumors and the attention on this cellular population has been growing during the last decade, both for its prognostic role and as a potential future therapeutic target. Melanoma, particularly the oral form, despite being one of the most immunogenic tumors, bears a poor prognosis in dogs and humans, due to its highly aggressive biological behavior and limited therapeutic options. The aims of this study are to characterize and quantify TAMs (using CD163, CD204, Iba1, and MAC387) in canine melanocytic tumors and to evaluate the association of these markers with diagnosis, histologic prognostic features, presence of metastases, and outcome, and to provide preliminary data for possible future therapies targeting TAMs. Seventy-two melanocytic tumors (27 oral melanomas, 25 cutaneous melanomas, 14 cutaneous melanocytomas, and 6 oral melanocytomas) were retrospectively selected and submitted to immunohistochemistry and double immunofluorescence. Double immunolabeling revealed that most CD163+ and CD204+cells co-expressed Iba1, which labeled also dendritic cells. Iba1 was instead rarely co-expressed with MAC387. Nevertheless, the expression of macrophagic markers showed a mild to moderate association among the four markers, except for CD204 and MAC387. The number of CD163+, CD204+, and MAC387+ cells was significantly higher in oral melanomas compared to oral melanocytomas (p < 0.001; p < 0.05 and p < 0.01, respectively), whereas Iba1 was differentially expressed in cutaneous melanomas and melanocytomas (p < 0.05). Moreover, CD163, IBA1 and MAC387 expression was associated with nuclear atypia and mitotic count. The number of CD163+cells was associated with the presence of metastases and tumor-related death in oral melanocytic tumors (p < 0.05 and p = 0.001, respectively).