Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules.

BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-ß)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (ß2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test). RESULTS: An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-ß. In the correlation analysis, ß2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine. CONCLUSIONS: This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.

Effects of antipsychotics on the gastrointestinal microbiota: A systematic review.

Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment.

Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) has a multifactorial etiology involving an interaction of genetic and environmental factors. The Apolipoprotein E ε4 (ApoE ε4) is the single most important genetic risk factor for sporadic AD. Our aim was to study the association between sociodemographic, clinical data and gene polymorphisms in patients with sporadic AD in a heterogeneous genomic Brazilian population with low educational levels. METHODS: We selected 169 sporadic AD patients and 97 controls older than 65 years and compared co-variables between them: age, years of education, vascular risk factors, genomic ancestry, and functional polymorphisms of ApoE, BDNF, COMT, and 5-HTTLPR. We also determined the genomic ancestry of all individuals. RESULTS: The average years of education was significantly smaller in the patient's group (p = 0.003), and they had a history of depression when compared with controls (p < 0.001). The carriers of ApoE ε4 have an earlier onset of the disease (76.9 years) (p = 0.001) than ApoE ε3 (79.5 years) (p = 0.024). Patients with Met allele of Val66Met have a tendency to later onset of disease (p = 0.056). There were no differences in the genomic ancestry between groups. CONCLUSION: Low level of education and history of depression were associated with AD. Public policies and intensive observation of old-age patients with lifetime history of depression, especially APOE ε4 carriers, could improve the well-being of our population.

Use of biomarkers for predicting a malignant course in acute ischemic stroke: an observational case-control study.

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers-S100B protein, MMP-9, and IL-10-were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke.

Impacts of mental health in the sleep pattern of healthcare professionals during the COVID-19 pandemic in Brazil.

BACKGROUND: After >2 years of the Coronavirus Disease-19 (COVID-19) pandemic, it is well established how sleep symptoms are rising, especially among healthcare workers (HCW). The aim of this study is to evaluate what features are associated with sleep disturbances in the HCW population. METHODS: Cross-sectional and longitudinal analysis of social and clinical variables associated with sleep problems and insomnia incidence in HCW in a large, national-level cohort. The measurement of sleep problems was assessed by self-report using Jenkins Sleep Scale (JSS). A multivariate analysis was used in the cross-sectional design and generalized linear models were used in the longitudinal design. RESULTS: 10,467 HCW were analyzed in the cross-sectional analysis, 3313 participants were analyzed in the three timepoints of the study. Sex, previously diagnosed mental illness and frontline work with COVID-19 were associated with higher scores in JSS in the univariate analysis. In the multivariate analysis, only previous diagnosis of mental illness was related with sleep difficulties, especially previously diagnosed insomnia. The longitudinal analysis concluded that previous diagnosis of mental illnesses was associated with higher levels of insomnia development (OR = 11.62). The self-reported disorders found to be major risk factors were addiction (OR = 7.69), generalized anxiety disorder (OR = 3.67), social anxiety (OR = 2.21) and bipolar disorder (OR = 2.21). LIMITATIONS: Attrition bias. CONCLUSIONS: Previous diagnosis of mental illness was strongly related to insomnia development in HCW during the COVID-19 pandemic. Strategies that focus on this population are advised.

Online parent training platform for complementary treatment of disruptive behavior disorders in attention deficit hyperactivity disorder: A randomized controlled trial protocol.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a diversity of impairments and Oppositional Defiant Disorder (ODD) is a very frequent comorbidity. Parent Training, as an evidence-based intervention, seems effective in reducing externalizing/disruptive behaviors, possibly leading to a better prognosis. This clinical trial aims to evaluate the effectiveness of an online parent training model as a complementary treatment for ADHD and ODD. METHODS: Patients and their families will be screened upon their entry into the Research Center of Impulsivity and Attention (NITIDA) at UFMG-Brazil. Ninety families whose children are male, between 6-12 years old, and have significant externalizing symptoms and whose primary caregiver have complete high school education will be invited to participate. Families will be randomized (1:1) into 03 groups: 1) standard care; 2) standard care + face-to-face parent training; 3) standard care + online parent training. Interventions are analogous, differing only in delivery format. In the face-to-face format, the intervention will be conducted by a specialized therapist and the online format will be carried out through a platform. There will be six sessions/modules, arranged on a weekly basis. Measures of externalizing symptoms, parental and children quality of life, parental stress and parenting style will be collected at baseline and after the intervention. DISCUSSION: This clinical trial intends to verify the effects of a new, online, model of an evidence-based intervention, which would allow a wider access in the Brazilian context. TRIAL REGISTRATION: Registered on Brazilian Registry of Clinical Trials (ReBEC). Number: RBR-6cvc85. July 24th (2020) 05:35 pm.

How is COVID-19 pandemic impacting mental health of children and adolescents?

The coronavirus disease (COVID-19) affected virtually all countries. Uncertain about the health risk and an increasing financial loss will contribute to widespread emotional distress and an increased risk of psychiatric disorders shortly. Posttraumatic, anxiety, and depression disorders are expected during and aftermath of the pandemic. Some groups, like children, have more susceptibility to having long term consequences in mental health. Herein, we made a comprehensive and non-systematic search in four databases (PubMed, Scopus, SciELO, and Google Scholars) to answer the question: What are children's and adolescents' mental health effects of the pandemic? Furthermore, which features are essential for mental health in a pandemic? Results: Seventy-seven articles were selected for full text read, and 51 were included. Children answer stress differently, depending on the development stage. High rates of anxiety, depression, and post-traumatic symptoms were identified among children. Discussion: Symptoms were as expected. New supportive strategies have appeared during this pandemic, but there is no measure of its effectiveness. Some groups seem to be more vulnerable to the mental health burden of the COVID-19 pandemic, and the mitigation actions should prioritize them. The school's role appears to be revalued by society. This review seems to pick good targets to prioritize mitigation actions aiming to spare children not only from the severe cases of COVID-19 but also to help them to deal with the mental health burden of the pandemics.

Temporal Reward Discounting in Children with Attention Deficit/Hyperactivity Disorder (ADHD), and Children with Autism Spectrum Disorder (ASD): A Systematic Review.

Children with ADHD and ASD may present differences in the affective-motivational processes. We systematically review the literature regarding temporal discounting in children up to 12 years with ADHD and ASD. Six articles were included, five studies with ADHD children (n = 231), one with ASD children (n = 21), all including typically developing children as controls (n = 210). Five studies (four with ADHD and one with ASD) found greater temporal reward discounting for clinical groups. Occurrence of ADHD appears to rush even more the decision-making process at this stage of development, but there is still a lack in the literature, especially evaluating individuals with ASD.

The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood.

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.