Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability

Vitamin D (VitD) may modulate anti-HIV-1 responses modifying the risk to acquire the HIV-1-infection. We performed a nested case-control exploratory study involving 413 individuals; HIV-1-exposed seropositives (cases) and seronegatives (HESN) (controls) from three cohorts: sexually-exposed from Colombia and Italy and parenterally-exposed from Spain. The association and interactions of 139 variants in 9 VitD pathway genes, and in 14 antiviral genes with resistance/susceptibility (R/S) to HIV-1 infection was evaluated. Associations between variants and mRNA levels were also analyzed in the Colombian samples. Variants and haplotypes in genes of VitD and antiviral pathways were associated with R/S, but specific associations were not reproduced in all cohorts. Allelic heterogeneity could explain such inconsistency since the associations found in all cohorts were consistently in the same genes: VDR and RXRA of the VitD pathway genes and in TLR2 and RNASE4. Remarkably, the multi-locus genotypes (interacting variants) observed in genes of VitD and antiviral pathways were present in most HESNs of all cohorts. Finally, HESNs carrying resistance-associated variants had higher levels of VitD in plasma, of VDR mRNA in blood cells, and of ELAFIN and defensins mRNA in the oral mucosa. In conclusion, despite allelic heterogeneity, most likely due to differences in the genetic history of the populations, the associations were locus dependent suggesting that genes of the VitD pathway might act in concert with antiviral genes modulating the resistance phenotype of the HESNs. Although these associations were significant after permutation test, only haplotype results remained statistically significant after Bonferroni test, requiring further replications in larger cohorts and functional analyzes to validate these conclusions.This work was supported by Departamento administrativo de ciencia, tecnología e innovación de Colombia, COLCIENCIAS (grant no. 111549326091); Universidad de Antioquia UdeA, Colombia (sostenibilidad); Universidad Cooperativa de Colombia (code INV1900); Consejería de Salud de la Junta de Andalucía (PI-0335/2009, PI-0118-2013, PI-0481-2012, and AC-0095-2013), Gilead (GLDL13-00145), the Ministerio de Sanidad (EC11-2086, PI021476, and PI10/01232), the Red de Investigación en SIDA (ISCIII-RETIC RD06/006 and RD12/0017), the Fundación Maratón TV3 (020730 and 020732) and the Universidad de Jaén (UJA2013/10/03 and UJA2013/08/12)

A genome-wide association study on liver stiffness changes during hepatitis c virus infection cure

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP 011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes

Association of complement receptor 2 polymorphisms withinnate resistance to HIV-1 infection

HIV-1 induces activation of complement through the classical and lectin pathways. However, the virus incorporates several membrane-bound or soluble regulators of complement activation (RCA) that inactivate complement. HIV-1 can also use the complement receptors (CRs) for complement-mediated antibody-dependent enhancement of infection (Ć-ADE). We hypothesize that hypofunctional polymorphisms in RCA or CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19 RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR)=2.27, P=1 × 10-4) and rs2842704 in C4BPA (OR=2.11, P=2 × 10-4). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Although not significant (P=0.25, OR=1.57), similar genotypic proportions were obtained for the CR2 marker rs1567190. The results of the two association analyses were combined through a random effect meta-analysis, with a significant P-value of 2.6x10-5 (OR=2.07). Furthermore, we found that the protective CR2 genotype is correlated with lower levels CR2 mRNA as well as differences in the ratio of the long and short CR2 isoforms.Genes and Immunity advance online publication, 8 January 2015; doi:10.1038/gene.2014.71.This work was supported by Spanish Health Ministry [PI021476, PI051778 and PI10/01232 to JF, JAP and ACar]; Instituto de Salud Carlos III-RETIC [RD06/006 to JAP]; Fundació Marató TV3 [020730 and 020732 to JF and ACar]; Junta de Andalucía [PI-0335/2009 to ACar]; Fundación Progreso y Salud of the Consejería de Salud de la Junta de Andalucía [AI-0021 to JAP]; and Universidad de Jaen [UJA2013/10/03 to ACar]

Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

Objectives: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV.Methods: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected.Results: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. Conclusions: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.This study was partly supported by grants from the Ministerio de Economía, Industria y competitividad, Instituto de Salud Carlos III (grant no. PI15/01124) and from Grupo de Estudio de Hepatitis Vírica-SEIMC (grant no. GEHEP-001). AG-S and AR-J are recipients of Miguel Servet Research Contracts by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00146; CP18/00111). JM is the recipient of a grant from the Servicio Andaluz de Salud de la Junta de Andalucía (grant no. B-0037). JAP is recipient of an intensification grant from the Instituto de Salud Carlos III (grant no. Programa-I3SNS)

The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study)

© 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background & aims] It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV).[Objective] To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype.[Patients and methods] In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0.[Results] It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition.[Conclusions] Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.This work was supported by grants from the Grupo de Estudio de Hepatitis Víricas from the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEHEP-012) and Consejería de Salud de la Junta de Andalucía (PI-0001/2017). CMS is supported by CIBERINFEC -Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas- (grant number CB21/13/00118), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea (Spain) (NextGeneration EU). ACG has received a research extension grant from “Acciones para el refuerzo con recursos humanos de la actividad investigadora en las Unidades Clínicas del Servicio Andaluz de Salud 2021, acción B (Clínico-Investigadores)” (grant number B-0061-2021). MS has received a Río Hortega grant from the Instituto de Salud Carlos III (grant number CM21/00263).Peer reviewe

Cognitive factors predicting therapeutic adherence in people with overweight and obesity / Factores cognitivos predictivos de adherencia terapéutica en personas con sobrepeso y obesidad

AbstractThe lack of adherence to treatment (ADT) in people with chronic diseases range from 40 to 75%. Two thirds of the patients with obesity under treatment recover the weight lost after one year, and almost all of them after five years, which is associated with the lack of ADT. Adherence refers to a multidimensional phenomenon that involves the reciprocal action of several factors, including those related to the patient. Assumption that triggered the first socio-cognitive models of ADT. The aim of the present work was to identify which factors of three different models (Theory of the planned behavior [TPB], Beliefs in health, and the one of Wallston) can predict the ADT of patients with overweight or obesity. A total of 118 adults participated, with an average age of 52.0 years (SD = 19.0), who were under pharmacological treatment and completed three questionnaires, each one related to the models evaluated, and another one related to ADT. Of the 13 factors, only one (attitudes, from the TPB model) showed ability to predict ADT (t = 2.75, ß = .26, p < .01). Therefore, for overweight and obesity it is necessary to propose models that can reflect better the differences that underlie the ADT.  Resumen La falta de adherencia al tratamiento (ADT) en personas con enfermedades crónicas puede fluctuar entre 40 y 75%. Dos tercios de los pacientes con obesidad bajo tratamiento recuperan el peso perdido tras un año, y casi todos a los cinco años, lo que se asocia con la falta de ADT. Esta refiere a un fenómeno multidimensional que supone la acción recíproca de diversos factores, y entre ellos los relativos al paciente. Supuesto que dio paso al surgimiento de los modelos socio-cognitivos de la ADT. El objetivo del presente trabajo fue identificar qué factores de tres diferentes modelos (Teoría de la conducta planeada [TCP], Creencias en salud y el de Wallston) pueden predecir la ADT de pacientes con sobrepeso u obesidad. Participaron 118 adultos, con edad promedio de 52.0 años (DE = 19.0), quienes estaban bajo tratamiento farmacológico y completaron tres cuestionarios, cada uno relativo a los modelos evaluados, y otro más referente a ADT. De los 13 factores, solo uno (Actitudes, del modelo de TCP) mostró capacidad para predecir la ADT (t = 2.75, ß = .26, p < .01). Por tanto, en el caso del sobrepeso u obesidad resulta necesario proponer modelos que reflejen mejor los aspectos que subyacen a la ADT

Temporal changes in the genotypes of Paslahepevirus balayani in southern Spain and their possible link with changes in pig trade imports

[Introduction] Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022.[Methods] Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period.[Results] A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022.[Conclusions] HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.This work was supported by Secretaría General de Investigación, Desarrollo e Innovación en Salud (PI-0287-2019) for grants for the financing of Investigación, Desarrollo e Innovación Biomédica y en Ciencias de la Salud en Andalucía; the Ministerio de Sanidad (RD12/0017/0012) integrated into the Plan Nacional de I + D + I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (Research Project grant numbers: PI19/00864, PI21/00793 and PI22/01098). Antonio Rivero-Juarez is the recipient of a Miguel Servet Research Contract by the Ministerio de Ciencia, Promoción y Universidades of Spain (CP18/00111). Mario Frias is the recipient of a Sara Borrell Research Contract program by the Ministerio de Ciencia, Promoción y Universidades of Spain (CD18/00091). Antonio Rivero is the beneficiary of Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud by the Ministerio de Ciencia, Promoción y Universidades of Spain (INT20–00028). Javier Caballero Gómez is supported by the CIBER -Consorcio Centro de Investigación Biomédica en Red-(CB21/13/00083), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.Peer reviewe

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells

Lo glocal y el turismo. Nuevos paradigmas de interpretación.

El estudio del turismo se realiza desde múltiples escalas y enfoques, este libro aborda muchos temas que es necesario discutir desde diversas perspectivas; es el caso de la reflexión sobre la propia disciplina y sus conceptos, así como los asuntos específicos referidos al impacto territorial, los tipos de turismo, las cuestiones ambientales, el tema de la pobreza, la competitividad, las políticas públicas, el papel de las universidades, las áreas naturales protegidas, la sustentabilidad, la cultura, el desarrollo, la seguridad, todos temas centrales documentados y expuestos con originalidad y dominio del asunto. Lo multiescalar es básico para la comprensión del sistema turístico, sistema formado de procesos globales, regionales y locales. El eje de discusión del libro es lo glocal, esa interacción entre lo nacional y local con lo global

PENSAMIENTO CRÍTICO EN LA INVESTIGACIÓN CIENTÍFICA Y ACADÉMICA COLECCIÓN CIENTÍFICA EDUCACIÓN, EMPRESA Y SOCIEDAD

PENSAMIENTO CRÍTICO EN LA INVESTIGACIÓN CIENTÍFICA Y ACADÉMICA COLECCIÓN CIENTÍFICA EDUCACIÓN, EMPRESA Y SOCIEDAD Primera Edición 2023 Vol. 21 Editorial EIDEC Sello Editorial EIDEC (978-958-53018) NIT 900583173-1 ISBN: 978-628-95884-1-5 Formato: Digital PDF (Portable Document Format) DOI: https://doi.org/10.34893/e1150-3660-8721-s Publicación: Colombia Fecha Publicación: 13/09/2023 Coordinación Editorial Escuela Internacional de Negocios y Desarrollo Empresarial de Colombia – EIDEC Centro de Investigación Científica, Empresarial y Tecnológica de Colombia – CEINCET Red de Investigación en Educación, Empresa y Sociedad – REDIEES Revisión y pares evaluadores Centro de Investigación Científica, Empresarial y Tecnológica de Colombia – CEINCET Red de Investigación en Educación, Empresa y Sociedad – REDIEE