Trauma craneoencefálico en motociclistas, Hospital Traumatológico Ney Arias Lora.

Introducción: El trauma craneoencefálico es un problema de salud global que limita al individuo en las esferas motora, cognitiva y del comportamiento, es el primer productor de discapacidad a nivel mundial y la primera causa de muerte en personas entre los 15 a 45 años de edad. Objetivo: Determinar la frecuencia del uso correcto de casco protector en pacientes con trauma craneoencefálico por accidente de tránsito en motocicleta en el Hospital Traumatológico Ney Arias Lora. Métodos: Se realizó un estudio observacional descriptivo, de corte transversal. El universo estuvo constituido por un total de 149 casos de trauma craneoencefálico en motociclistas. Se emplearon estadígrafos de estadística descriptiva, con uso del programa SPSS 2.0. Resultados: De 149 casos estudiados, en 128 se encontró que no utilizaron el casco protector, correspondiendo al 86%. Los pacientes con edades entre 19 y 45 años conformaron la mayoría de casos con un total de 93 pacientes para un 65%. Los pacientes del género masculino representaron la mayoría, 138 casos para un 93%. Sobre la clasificación del trauma, del grupo de pacientes que usaron correctamente el casco de seguridad no hubo casos severos y de los que no lo usaron, 20 casos fueron severos para un 15,5%. Conclusiones: El uso de casco de seguridad disminuye la gravedad del trauma craneoencefálico en motociclistas sufrieron accidente de tránsito. El trauma de forma general, se ubica entre las primeras causa de muerte en República Dominicana. Especialmente el trauma craneoencefálico afectó a personas jóvenes por lo que representó una gran cantidad de años potencialmente perdidos entre las víctimas; de manera que debe sensibilizarse a la población sobre la importancia del uso del caso de protección, toda vez que solo la quinta parte de los accidentados o usaron

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease

Abstract: Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases

Trauma craneoencefálico en motociclistas, Hospital Traumatológico Ney Arias Lora

Introduction: The traumatic brain injury is a problem of global health that limits to the people in the motor spheres, cognitive and of the behavior, is the first producer of disability to world level and the first cause of death in people between them 15 to 45 years of age. Objetive: To determine the frequency of the correct use of protective helmet in patients with traumatic brain injury by traffic accident on a motorcycle in the Ney Arias Lora Traumatology Hospital. Methods: Was carried out a observational descriptive study, of cutting cross. The universe was made up of a total of 149 cases of traumatic brain injury in motorcyclists. Statisticians of descriptive statistics, with use of the program SPSS 2.0 were used. Results: Of 149 cases studied, in 128 was found that does not used the helmet shield, corresponding to the 86%. Those patients with ages between 19 and 45 years formed the majority of cases with a total of 93 patients for a 65%. Male patients accounted for most, 138 cases to 93%. On the classification of the trauma, of the group of patients that used correctly the helmet of security not there were cases severe and of which no it used, 20 cases were severe for a 15,5%. Conclusions: Safety helmet use reduces the severity of craniocerebral trauma in motorcyclist suffered a traffic accident. The trauma of way general, is located between the first cause of death in Dominican Republic. traumatic brain injury especially affected young people so it represented a large number of years potentially lost among the victims; so every time that only the fifth part of the injured should sensitize the population about the importance of the use of the protective case, or used.Introducción: El trauma craneoencefálico es un problema de salud global que limita al individuo en las esferas motora, cognitiva y del comportamiento, es el primer productor de discapacidad a nivel mundial y la primera causa de muerte en personas entre los 15 a 45 años de edad.Objetivo: Determinar la frecuencia del uso correcto de casco protector en pacientes con trauma craneoencefálico por accidente de tránsito en motocicleta en el Hospital Traumatológico Ney Arias Lora.Métodos: Se realizó un estudio observacional descriptivo, de corte transversal. El universo estuvo constituido por un total de 149 casos de trauma craneoencefálico en motociclistas. Se emplearon estadígrafos de estadística descriptiva, con uso del programa SPSS 2.0.Resultados: De 149 casos estudiados, en 128 se encontró que no utilizaron el casco protector, correspondiendo al 86%. Los pacientes con edades entre 19 y 45 años conformaron la mayoría de casos con un total de 93 pacientes para un 65%. Los pacientes del género masculino representaron la mayoría, 138 casos para un  93%. Sobre la clasificación del trauma, del grupo de pacientes que usaron  correctamente el casco de seguridad no hubo casos severos y de los que no lo usaron, 20 casos fueron severos para un 15,5%.Conclusiones: El uso de casco de seguridad disminuye la gravedad del trauma craneoencefálico en motociclistas sufrieron accidente de tránsito. El trauma de forma general, se ubica entre las primeras causa de muerte en República Dominicana. Especialmente el trauma craneoencefálico afectó a personas jóvenes por lo que representó una gran cantidad de años potencialmente perdidos entre las víctimas; de manera que debe sensibilizarse a la población sobre la importancia del uso del caso de protección, toda vez que solo la quinta parte de los accidentados o usaron.

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments