Associations between differential aging and lifestyle, environment, current, and future health conditions : Findings from Canadian Longitudinal Study on Aging

Acknowledgement This research was made possible using the data/biospecimens collected by the Canadian Longitudinal Study on Aging (CLSA). Funding for the Canadian Longitudinal Study on Aging (CLSA) is provided by the Government of Canada through the Canadian Institutes of Health Research (CIHR) under grant reference: LSA 94473 and the Canada Foundation for Innovation, as well as the following provinces, Newfoundland, Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia. This research has been conducted using the CLSA dataset (Comprehensive Cohort), under Application Number 1906013. The CLSA is led by Drs. Parminder Raina, Christina Wolfson and Susan Kirkland.Peer reviewedPostprin

Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study.

Abstract Recent findings have disclosed the role of UDP-glucuronosyltransferase (UGT) 1A1*28 on the haematological toxicity induced by irinotecan (CPT-11), a drug commonly used in the treatment of metastatic colorectal cancer (mCRC). We investigated the pharmacogenomic profile of irinotecan-induced gastrointestinal (GI) toxicity by the novel drug-metabolizing enzyme and transporter (DMET) microarray genotyping platform. Twenty-six mCRC patients who had undergone to irinotecan-based chemotherapy were enrolled in a case (patients experiencing > grade 3 gastrointestinal, (GI) toxicity) - control (matched patients without GI toxicity) study. A statistically significant difference of SNP genotype distribution was found in the case versus control group. The homozygous genotype C/C in the (rs562) ABCC5 gene occurred in 6/9 patients with GI toxicity versus 1/17 patients without GI toxicity (P=0.0022). The homozygous genotype G/G in the (rs425215) ABCG1 was found in 7/9 patients with GI toxicity versus 4/17 patients without GI toxicity (P=0.0135). The heterozygous genotype G/A in the 388G>A (rs2306283) OATP1B1/SLCO1B1 was found in 3/9 patients with grade > 3 GI toxicity versus 14/17 patients without GI toxicity (P=0.0277). DNA extracted from peripheral blood cells was genotyped by DMET Plus chip on Affymetrix array system. Genotype association was calculated by Fisher's exact test (two tailed) and relevant SNPs were further analyzed by direct sequencing. We have identified 3 SNPs mapping in ABCG1, ABCC5 and OATP1B1/SLCO1B1 transporter genes associated with GI toxicity induced by irinotecan in mCRC patients expanding the available knowledge of irinogenomics. The DMET microarray platform is an emerging technology for easy identification of new genetic variants for personalized medicine

Troponina no Infarto Agudo do Miocárdio sem Supradesnivelamento do Segmento ST: Uma Revisão Sistemática

This work presents a systematic review on the role of troponin in Non-ST Elevation Myocardial Infarction (NSTEMI). The introduction underscores the significance of troponin as a sensitive biomarker for myocardial injury, particularly in the context of NSTEMI. The methodology outlines a rigorous approach following PRISMA guidelines, including inclusion and exclusion criteria, database searches, and study quality assessment. The development section covers the analysis of results, highlighting diagnostic sensitivity, long-term prognostic value, and challenges in interpreting troponin levels. The conclusion underscores the clinical relevance of troponin, emphasizing its role in rapidly identifying patients, risk stratification, and prognosis in NSTEMI. The evolving diagnostic methodology and challenges to be addressed are also discussed, pointing towards future directions in research.Este trabalho apresenta uma revisão sistemática sobre o papel da troponina no Infarto Agudo do Miocárdio (IAM) sem Supradesnivelamento do Segmento ST. A introdução destaca a importância da troponina como biomarcador sensível de lesão miocárdica, especialmente em contextos de IAM sem supra de ST. A metodologia descreve a abordagem rigorosa seguindo as diretrizes do PRISMA, incluindo critérios de inclusão e exclusão, busca em bases de dados e avaliação da qualidade dos estudos. O desenvolvimento abrange a análise dos resultados, destacando a sensibilidade diagnóstica, prognóstico a longo prazo e desafios na interpretação dos níveis de troponina. A conclusão ressalta a relevância clínica da troponina, enfatizando seu papel na rápida identificação de pacientes, estratificação de risco e prognóstico em IAM sem supra de ST. Discute-se também a evolução da metodologia diagnóstica e desafios a serem abordados, apontando para direções futuras na pesquisa

O Uso Do Escore Poligênico Como Uma Ferramenta De Determinação De Risco De Esquizofrenia

Schizophrenia (Scz) Is A Severe And Debilitating Psychiatric Disorder. Its Main Characteristics Are The Positive, Negative And Cognitive Deficits Symptoms. It Is A Multifactorial Disease; Thus, Environmental (Such As Use Of Substances) And Genetic Factors (Single Nucleotide Polymorphisms - Snps, With Low Effect Size, As Well As Copy Number Variations - Cnvs, With Lower Effect Size) Interact Together To Its Development. From Genome-Wide Association Studies (Gwas), An Instrument Called Polygenic Risk Score (Prs) Is Used To Estimate The Individual Genetic Risk To Scz Development (From Low Size Effect Variants). Objectives: To Verify How An Interracial Admixture May Interfere To Prs Results. Additionally, To Verify The Effects Of Environmental And Genetic Factors On Scz Patients, In Order To Improve A Tool For Risk Measurement. Methodology: We Used The Summary Statistics From Pgc (Psychiatric Genomics Consortium) Scz-Gwas (36,989 Patients And 113,075 Controls) To Calculate Prs In Our Sample (309 Patients And 445A Esquizofrenia (Scz) É Um Transtorno Mental Grave E Incapacitante Que Engloba Quadros De Sintomas Negativos, Positivos E Déficits Cognitivos. É Uma Doença Multifatorial, Na Qual Fatores Genéticos (Tanto De Baixo Efeito, Como Os Polimorfismos De Nucleotídeo Único - Snps, Quanto Os De Alto Efeito, Como As Copy Number Variations " Cnvs) E Ambientais Interagem Para O Seu Desenvolvimento. A Partir De Estudos Genômicos De Associação Em Larga Escala (Gwas), É Possível Calcular E Aplicar Uma Ferramenta, O Escore Poligênico De Risco (Polygenic Risk Score " Prs), Com O Intuito De Estimar O Risco Genético Poligênico (A Partir Das Variantes De Baixo Efeito) De Cada Indivíduo Em Desenvolver Scz. Objetivo: Os Objetivos Do Trabalho Foram: 1) Compreender Como A Miscigenação Da População Pode Interferir Na Eficácia Do Prs, A Fim De Aprimorar Essa Ferramenta De Determinação De Risco Para A Esquizofrenia; 2) Investigar Os Efeitos Da Combinação De Fatores Ambientais E Genéticos De Risco (Prs E Cnv) Sobre A Doença, Na TentativaDados abertos - Sucupira - Teses e dissertações (2018

Rivastigmine in the treatment of hypersexuality in alzheimer disease

Inappropriate sexual behaviors (ISB) represent uncommon and often misdiagnosed clinical disorders among patients with Alzheimer disease. So far, no randomized clinical trials regarding the treatment of ISB in demented people have been conducted, but available data from case series and isolated case reports suggest the efficacy of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, antiandrogens, and H2-receptor antagonists. Controversial data exist on the therapeutic influence of cholinesterase inhibitors on sexual disorders. In the present article, we describe the case of an Alzheimer disease patient presenting hypersexuality, successfully treated with rivastigmine. Thus, we perform a revision of the existing literature regarding the therapeutical effect of cholinesterase inhibitors in the treatment of ISB. © 2013 by Lippincott Williams & Wilkins

Familial Alzheimer's disease sustained by presenilin 2 mutations: Systematic review of literature and genotype-phenotype correlation

Familial Alzheimer's disease (FAD), despite representing a rare condition, is attracting a growing interest in the scientific community. Improved phenotyping of FAD cases may have a relevant impact both in clinical and research contexts. We performed a systematic review of studies describing the phenotypic features of FAD cases sustained by PSEN2 mutations, the less common cause of monogenic AD. Special attention was given to the clinical manifestations as well as to the main findings coming from the most commonly and widely adopted diagnostic procedures. Basing on the collected data, we also attempted to conduct a genotype phenotype correlation analysis. Overall, the mutations involving the PSEN2 gene represent an extremely rare cause of FAD, having been reported to date in less than 200 cases. They are mainly associated, despite some peculiar and heterogeneous features, to a typical AD phenotype. Nevertheless, the frequent occurrence of psychotic symptoms may represent a potential distinctive element. The scarcity of available phenotypic descriptions strongly limits the implementation of genotype phenotype correlations. (c) 2014 Elsevier Ltd. All rights reserved

Risk factors for developmental vulnerability: Insight from population-level surveillance using the Early Development Instrument

Objectives Population-level studies may elucidate the most promising intervention targets to prevent negative outcomes of developmental vulnerability in children. This study aims to bridge the current literature gap on identifying population-level developmental vulnerability risk factors using combined social and biological/health information. Methods This study assessed developmental vulnerability among kindergarten children using the 2016 Early Development Instrument (EDI) and identified risk factors of developmental vulnerability using EDI data cross-linked to a population-wide administrative health dataset. A total number of 23,494 children aged 5–6 were included (48% female). Prenatal, neonatal, and early childhood risk factors for developmental vulnerability were investigated, highlighting the most important ones contributing to early development. Results The main risk factors for developmental vulnerability were children with a history of mental health diagnosis (risk ratio  = 1.46), biological sex–male (risk ratio =  1.51), and poor socioeconomic status (risk ratio =  1.58). Conclusion Our study encompasses both social and health information in a populational-level representative sample of Alberta, Canada. The results confirm evidence established in other geographic regions and jurisdictions and demonstrate the association between perinatal risk factors and developmental vulnerability. Based on these results, we argue that the health system should adopt a multilevel prevention and intervention strategy, targeting individual, family, and community together

The Mu.Ta.Lig. Chemotheca: A Community-Populated Molecular Database for Multi-Target Ligands Identification and Compound-Repurposing

For every lead compound developed in medicinal chemistry research, numerous other inactive or less active candidates are synthetized/isolated and tested. The majority of these compounds will not be selected for further development due to a sub-optimal pharmacological profile. However, some poorly active or even inactive compounds could live a second life if tested against other targets. Thus, new therapeutic opportunities could emerge and synergistic activities could be identified and exploited for existing compounds by sharing information between researchers who are working on different targets. The Mu.Ta.Lig (Multi-Target Ligand) Chemotheca database aims to offer such opportunities by facilitating information exchange among researchers worldwide. After a preliminary registration, users can (a) virtually upload structures and activity data for their compounds with corresponding, and eventually known activity data, and (b) search for other available compounds uploaded by the users community. Each piece of information about given compounds is owned by the user who initially uploaded it and multiple ownership is possible (this occurs if different users uploaded the same compounds or information pertaining to the same compounds). A web-based graphical user interface has been developed to assist compound uploading, compounds searching and data retrieval. Physico-chemical and ADME properties as well as substructure-based PAINS evaluations are computed on the fly for each uploaded compound. Samples of compounds that match a set of search criteria and additional data on these compounds could be requested directly from their owners with no mediation by the Mu.Ta.Lig Chemotheca team. Guest access provides a simplified search interface to retrieve only basic information such as compound IDs and related 2D or 3D chemical structures. Moreover, some compounds can be hidden to Guest users according to an owner's decision. In contrast, registered users have full access to all of the Chemotheca data including the permission to upload new compounds and/or update experimental/theoretical data (e.g., activities against new targets tested) related to already stored compounds. In order to facilitate scientific collaborations, all available data are connected to the corresponding owner's email address (available for registered users only). The Chemotheca web site is accessible at http://chemotheca.unicz.it