Synthesis and Evaluation of the Fungal Activity of New Pyrazole-Carboxamides against Colletotrichum gloeosporioides

The pyrazole core has been recognized by their biological properties and included in the synthesis of modern agrochemicals. Part of these studies consists of making structural modifications to pesticides for commercial purposes to increase efficacy. In this article, we present the synthesis of four new pyrazol-4-carboxamide 8a-8d derivatives (PCD), through a four-step synthetic protocol, starting with edaravone 1 and primary amines like benzo-fused, aliphatic, and hydrazines, through a process of low environmental impact. Synthesized derivatives were evaluated against one fungal strain of Colletotrichum gloeosporioides BA3, fungus that causes several losses to farmers around the world, through in vitro sensitivity tests. The compound 8c showed better inhibiting behavior against Colletotrichum gloeosporioides BA3, inducing a lag phase of almost 2.77 days. These results were obtained via Gompertz modeling, for the first time reported for biological evaluation of pyrazole-carboxamide derivatives against Colletotrichum gloeosporioides.Fil: Gonzalez Lopez, Edwin Javier. Universidad del Atlántico; Colombia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: León Jaramillo, Jhair Carlhino. Universidad del Atlántico; ColombiaFil: Trilleras Vásquez, Jorge Enrique. Universidad del Atlántico; ColombiaFil: Grande Tovar, Carlos D.. Universidad del Atlántico; ColombiaFil: Peralta Ruiz, Yeimmy. Universidad del Atlántico; Colombia. University Of Teramo. Faculty Of Bioscience And Technology For Food, Agriculture And Environment.; ItaliaFil: Quiroga, Jairo. Universidad del Valle; Colombi

A propósito del consenso para el manejo de las disfunciones tiroideas mínimas

Resumen El hipotiroidismo subclínico y sus consecuencias clínicas ha sido objeto de debate científico por espacio de varias décadas. A raíz de la publicación de la declaración de consenso acerca de la disfunción tiroidea sub- clínica en el año 2005, realizada por la Sociedad Americana de Endocrinologìa (The Endocrine Society), la Asociación Americana de Endocrinólogos Clínicos (AACE) y la Asociación Americana de la Tiroides (ATA) se abrió un nuevo espacio para los endocrinólogos en el manejo de algunas disfunciones tiroideas que no habían sido tenidas en cuenta dentro del campo de accion terapéutico. Los autores hacen un recuento de cómo se produce el cambio en los paradigmas y en el enfoque diagnostico y terapéutico. Luego hacen un recuento de algunas de las experiencias desarrolladas en Colombia. Finalmente sugieren algunos derroteros a partir de su propia experiencia y también basa- dos en logros científicos de otras fuentes obtenidos en otros campos de la Endocrinologìa moderna. Palabras claves: Hipotiroidismo. Abstract Subclinical hypothyroidism and its clinical consequences have been debated during several decades. With the publication of the Consensus Declaration about subclinical thyroid dysfunction by the Endocrine Society, the American Association of Clinical Endocrinologists (AACE), and the American Thyroid Association (ATA), a new field was open for endocrinologist in the management of some long ignored thyroid dysfunctions that did not have any thera- peutic solution. The authors describe the paradigm shift and the changes in the diagnostic and therapeutic approaches. Later they recount some experiences developed in Colombia, S.A. Finally, they suggest some guidelines from their own experience and from other sources obtained in different fields of modern endocrinology. Key words: Hypothyroidism

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants

Hepatitis B and Hepatitis C Infection Biomarkers and TP53 Mutations in Hepatocellular Carcinomas from Colombia

Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV), chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection

Machine learning and big data analytics in bipolar disorder:A position paper from the International Society for Bipolar Disorders Big Data Task Force

Objectives The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. Method A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. Results The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. Conclusion Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.Peer reviewe

Rostral Middle Frontal Volumetric Differences in Bipolar Offspring versus Community Controls Offspring

Neuroanatomical findings in the anterior limbic network in bipolar disorder (BD) adults have not been replicated in other populations such as bipolar offspring (BO). The aim of this study was to compare some brain areas volumes between BO with and without a lifetime affective disorder (AD) to a group of community control offspring (CCO). Methods: A descriptive observational cross-sectional study was carried out, with multiple comparison groups. Seven subjects (11-17 years old) from the BO with AD group were compared to seven subjects from the BO without AD group and seven subjects from the CCO group (match by age, gender and Tanner stage). Magnetic resonance imaging was performed with a Philips 3 Teslas device and volumetric segmentation was performed with the Freesurfer image analysis suite. Results: A larger size was found in the right middle frontal rostral region in the BO with AD group compared to the other two groups (p = 0.041). A higher volume was also found in BO with AD group in the left pars opercularis (Cohen d = 0.63) and in the right cingulate isthmus (d = 0.53) when compared with BO without AD group, and in the right hippocampus (d = 0.53) when compared to CCO group. A smaller volume was found in the BO without AD group versus CCO group in the left anterior caudate (d = 0.6). The BO groups (with and without AD) compared to CCO have a higher volume in the right frontal pole (d = 0.52). These volumetric differences can be attributed to the condition of BO with AD

Smartphone-based interventions in bipolar disorder : Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force

Background: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. Objectives: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. Methods: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). Results: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. Conclusion: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.Peer reviewe