X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease.

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

[Surveillance of rare diseases in Spain: Spanish Registry of Rare Diseases (ReeR).] / Vigilancia de las enfermedades raras en España: el Registro Estatal de Enfermedades Raras (ReeR).

Traditionally, epidemiological surveillance has focused on infectious diseases, but the concept of Public Health surveillance, introduced in Spain with the Law 33/2011, is broader and includes chronic diseases. Health strategies for these diseases need epidemiological information to improve understanding of socio-health needs and to facilitate the efficient management of resources. The European Union defines rare diseases (RD) as those that, being life-threatening or chronically debilitating, have a prevalence of less than 5 cases per 10,000 inhabitants. The RD Strategy of the National Health System, approved in 2009 and updated in 2014, recommends the development of regional registries of rare diseases (RAER), in addition to a national registry. The REpIER and Spain-RDR projects of the Institute of Health Carlos III (ISCIII) promoted the creation and regulation of 94% of the RAER. After more than 10 years of initiatives and work to improve the knowledge of RD's epidemiology in Spain, it was possible to implement the Spanish Registry of Rare Diseases (ReeR) in 2015, becoming one of the first population surveillance systems for chronic diseases of state scope. The ReeR procedures manual is the result of consensus between the RAER, the Ministry of Health, the ISCIII and the patient associations. The participatory methodology used for the implementation and launching of ReeR is considered an added value. The information system implemented will allow improving knowledge about the prevalence and distribution of RD in Spain.

Tradicionalmente la vigilancia epidemiológica se ha centrado en enfermedades transmisibles, pero el concepto de vigilancia en Salud Pública, incorporado en España con la Ley 33/2011, es más amplio e incluye las enfermedades crónicas. Las estrategias de salud para estas enfermedades necesitan disponer de información epidemiológica para mejorar el conocimiento de las necesidades sociosanitarias y facilitar la gestión eficiente de recursos. La Unión Europea define las enfermedades raras (ER) como aquellas que, con peligro de muerte o invalidez crónica, presentan una prevalencia inferior a 5 casos por cada 10.000 habitantes. La Estrategia en ER del Sistema Nacional de Salud, aprobada en 2009 y actualizada en 2014, recomienda desarrollar registros autonómicos de enfermedades raras (RAER) y uno estatal. Los proyectos REpIER y Spain-RDR del Instituto de Salud Carlos III (ISCIII) impulsaron la creación y regulación del 94% de los RAER; y tras más de 10 años de iniciativas y trabajos para mejorar el conocimiento de la epidemiología de las ER en España, se logró implementar el Registro Estatal de Enfermedades Raras (ReeR) en 2015, convirtiéndose en uno de los primeros sistemas de vigilancia poblacional de enfermedades crónicas de ámbito estatal. El manual de procedimientos del ReeR es el resultado del consenso entre los RAER, Ministerio de Sanidad, ISCIII y asociaciones de pacientes. La metodología participativa empleada para la implementación y puesta en funcionamiento del ReeR es considerada un valor añadido. El sistema de información implementado va a permitir mejorar el conocimiento sobre la prevalencia y distribución de las ER en España.

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Arteria trigeminal persistente: reporte de tres casos / Persistent trigeminal artery: three case reports

La persistencia de la arteria trigeminal es una alteración vascular infrecuente y representa la permanencia, después del nacimiento, de la comunicación entre el sistema carotideo y el sistema vertebro-basilar. Esta persistencia se ha asociado a la existencia de otras alteraciones de la morfología vascular cerebral y a condiciones clínicas variadas. Reportamos tres casos de persistencia de la arteria trigeminal, dos como hallazgo incidental en pacientes con sintomatología transitoria y uno en un cuadro de hemorragia subaracnoidea, identificados mediante reconstrucción tridimensional de imágenes obtenidas por angiotomografía.

Persistent trigeminal artery is a rare vascular disorder and represents the permanence of the communication between the carotid system and vertebrobasilar system after birth. This persistence has been associated with the existence of other alterations of brain vascular morphology and different clinical conditions. We report three cases of persistent trigeminal artery, two incidental findings in patients with transient symptoms and one in a patient with subarachnoid hemorrhage, identified by three-dimensional reconstruction of images obtained by angiotomography.

Ataxia espinocerebelosa tipo 3 (enfermedad de Machado Joseph). A propósito de un caso / Spinocerebellar ataxia type 3 (Machado-Joseph disease). Report of a case

Introducción: La enfermedad de Machado Joseph (MJD), o ataxia espinocerebelosa tipo 3 es un trastorno hereditario autosómico dominante ligado al gen de la ataxina 3 y se manifiesta en forma de ataxia progresiva, piramidalismo, oftalmoplejia, neuropatía, distonía y síndrome de piernas inquietas. Caso clínico: Varón de 34 años con ataxia progresiva, oftalmoplejia, y neuropatía periférica. Presenta antecedentes familiares con patrón autosómico dominante de trastorno similar en padre, abuelo paterno, tío, primos, sobrina y hermano. El estudio genético evidenció un alelo expandido de 67 repeticiones en heterocigosis en el gen de la SCA3. Conclusión: Presentamos el primer caso en Perú de un paciente con las características hereditarias, clínicas, neurofisiológicas y moleculares correspondientes a la enfermedad de Machado Joseph.

Introduction: Spinocerebellar ataxia type 3 (Machado Joseph disease) is an inherited autosomal dominant disorder related to the ataxina gene. Progressive ataxia, pyramidal signsm ophthalmoplegia, peripheral neuropathy, dystonia and restless legs syndrome are main clinical features. Case report: A 34 year-old man with progressive ataxia, ophthalmoplegia and oeripheral neuropathy. Positive familial antecedents with autosomal dominant pattern and included the father, grandfather, uncle, cousins and a sibling. Genetic study showed and expanded allele with 67 repeats in the SCA3 gene. Conclusion: We present the first peruvian patient with clinical, inheritance, neurophisiology and molecular features of Machado Joseph Disease.

Estudio de seroprevalencia de hepatitis B en deportistas de orientación / Seroprevalence study of hepatitis B among orienteers

Fundamento y objetivo: Detectar casos asintomáticos relacionados con un brote, valorar la seroprevalencia de hepatitis B (HB) en deportistas de orientación y establecer recomendaciones. Pacientes y método: Se realizó un estudio transversal de seroprevalencia entre 116 deportistas de orientación que habían competido en las categorías implicadas en un brote previo y una muestra estratificada de 166 corredores del resto de otras categorías de competición. Se analizaron marcadores de HB: antígeno de superficie del virus de la HB (VHB) (HBsAg), anticuerpo contra el antígeno core del VHB (anti-HBc), anticuerpos contra el HBsAg, anti-HBc tipo inmunoglobina M y antecedentes de vacunación. Los resultados se expresan utilizando pesos ponderados. Resultados: La seroprevalencia de HB (anti-HBc positivos) fue del 6,7% (n=12; intervalo de confianza [IC] del 95%: 0,6 a 12,9). No se observó ningún caso de HB aguda o crónica. Todos los marcadores fueron negativos para el 61,1% (n=64; IC del 95%: 46,3 a 75,6), y el 32,3% (n=29; IC del 95%: 18,2 a 46,4) tenía marcadores de inmunidad por vacunación. Entre los sujetos menores de 25 años, el 28,4% estaba sin vacunar a pesar de que entraban en el calendario vacunal. Conclusiones: Los resultados muestran que la seroprevalencia de HB entre deportistas de orientación no difiere de la población general. Sin embargo, es necesario reforzar la vacunación entre adolescentes y adultos jóvenes. Se dan recomendaciones generales para la prevención de HB a las federaciones de orientación (AU)

Background and objective: Our objectives were to detect asymptomatic cases involved in an outbreak of hepatitis B, to assess the seroprevalence of hepatitis B (HB) in orienteers and to establish recommendations. Patients and method: One hundred sixteen orienteers who had competed in the categories involved in the previous outbreak as well as a stratified random sample of 166 of the remaining orienteers in other competition categories were included in a cross-sectional serological prevalence study. HB surface antigen (anti-HBs); total antibody to HB core antigen (total anti-HBc); HB surface antigen (Ag HBs); and antibody IgM to HB core antigen (anti-HBcIgM) along with the history of vaccination for hepatitis B were analyzed. The results were weighted. Results: The seroprevalence of HB (total anti-HBc positive) was 6.7% (n=12, 95%CI 0.6-12.9). No case of acute HB or chronic infection was observed. All the serological markers were negative for 61.1% (n=64, 95%CI 46.3-75.6), and 31.5% (n=29, 95%CI 18.2-46.4) had markers of immunity due to vaccination. Among individuals under 25 years of age, 28.4% were unvaccinated, although they were covered by vaccination programs. Conclusion: Our results suggest that the seroprevalence of HB among orienteers is not different from the general population in Spain. However, it is necessary to reinforce the vaccination among adolescents and young adults. General recommendations for the prevention of HB were made to orienteering federations (AU)

[Seroprevalence study of hepatitis B among orienteers]. / Estudio de seroprevalencia de hepatitis B en deportistas de orientación.

BACKGROUND AND OBJECTIVE: Our objectives were to detect asymptomatic cases involved in an outbreak of hepatitis B, to assess the seroprevalence of hepatitis B (HB) in orienteers and to establish recommendations. PATIENTS AND METHOD: One hundred sixteen orienteers who had competed in the categories involved in the previous outbreak as well as a stratified random sample of 166 of the remaining orienteers in other competition categories were included in a cross-sectional serological prevalence study. HB surface antigen (anti-HBs); total antibody to HB core antigen (total anti-HBc); HB surface antigen (Ag HBs); and antibody IgM to HB core antigen (anti-HBcIgM) along with the history of vaccination for hepatitis B were analyzed. The results were weighted. RESULTS: The seroprevalence of HB (total anti-HBc positive) was 6.7% (n=12, 95% CI 0.6-12.9). No case of acute HB or chronic infection was observed. All the serological markers were negative for 61.1% (n=64, 95% CI 46.3-75.6), and 31.5% (n=29, 95% CI 18.2-46.4) had markers of immunity due to vaccination. Among individuals under 25 years of age, 28.4% were unvaccinated, although they were covered by vaccination programs. CONCLUSION: Our results suggest that the seroprevalence of HB among orienteers is not different from the general population in Spain. However, it is necessary to reinforce the vaccination among adolescents and young adults. General recommendations for the prevention of HB were made to orienteering federations.

Rates of Clostridium difficile infection in patients discharged from Spanish hospitals, 1997-2005.

We analyzed the Spanish hospital discharges registered from 1997 to 2005 with patient diagnoses of "intestinal infection due to Clostridium difficile." The mean annual incidence rate was 41.2 diagnoses per 100,000 discharges. A significant increase was found from 1997 to 2005 (slope of the regression line [b], 5.12; P < .001). Overall rates were 2.5 times as high in the group of patients aged at least 65 years as in the group aged 45-64 years.

Estudio clínico molecular de la enfermedad de Huntington en pacientes del Valle de Cañete - Perú / Clinical molecular study of Huntington's disease in patients of Cañete's Valley - Peru

Objetivos: Estudiar las características clínicas y moleculares de 30 pacientes con Enfermedad de Huntington (EH) provenientes del Valle de Cañete. Población y métodos: Estudio analítico, transversal. Se estudió el ADN de 30 pacientes para determinar el número de tripletes CAG. Resultados: De 30 pacientes, 17 (56.7 por ciento) fueron varones, 13 (43.3 por ciento) mujeres, con edades entre 23 y 71 años y una media de 43.2 años. La manifestación clínica de inicio de la enfermedad más frecuente fue la corea. La expansión dentro del límite patológico del triplete CAG de 20 pacientes osciló entre 40 y 56 repeticiones mientras que en los alelos normales estuvo comprendido entre 14 y 33. Diez pacientes presentaron rangos entre 36 y 39 tripletes. Un paciente con 43 repeticiones inició la enfermedad antes de los 20 años. Se halló correlación inversa entre el número de tripletes CAG y la edad de inicio de la enfermedad (r= -0.718; p menor igual 0.001) y entre el Minimental Test de Folstein y el UHDRS (r=-0.678, p menor 0.01) mientras que se halló correlación directa entre el UHDRS y el tiempo de enfermedad (r=0.773, p menor 0.001). Conclusiones: Aunque el número de repeticiones esta fuertemente correlacionado con la edad de inicio, estos datos no serán particularmente útiles en el diagnóstico presintomático excepto en aquellos pacientes con un alto número de repeticiones.

Antimicrobial resistance in non-typhoidal Salmonella from human sources, Spain, 2001-2003.

OBJECTIVES: To determine the current state of antimicrobial resistance among non-typhoidal Salmonella strains isolated from humans in Spain. METHODS: All strains of Salmonella from human sources received in the reference laboratory from 2001 to 2003 were serotyped and phage types were determined in the most common serovars. A systematic sampling procedure was carried out in order to obtain a random sample for susceptibility testing. The selected strains were tested for susceptibility to 12 different antimicrobial agents by a disc diffusion method using Mueller-Hinton agar. Results were scored as susceptible, moderately susceptible or resistant, according to CLSI criteria. RESULTS: From 2001 to 2003, 5777 strains of Salmonella were tested for susceptibility. Fifty per cent of strains of Salmonella Enteritidis were resistant to nalidixic acid. This was the most frequent resistance pattern of this serovar and it was characteristic of PT1, the most frequent phage type of Salmonella Enteritidis in Spain. Seventy-four per cent of Salmonella Typhimurium strains were resistant to four antibiotics or more. Resistance to ampicillin, chloramphenicol, streptomycin, sulphonamide and tetracycline was the most frequent resistance pattern of Salmonella Typhimurium and it was characteristic of DT104, the most frequent phage type in Spain. Sixty-nine per cent of Salmonella Hadar strains were resistant to at least four antibiotics. CONCLUSIONS: The results of our study showed both a worrying percentage of strains of Salmonella Enteritidis resistant to nalidixic acid and of strains of Salmonella Typhimurium with a pattern of resistance to four antibiotics or more. Surveillance of antimicrobial resistance should carry on and improve in order to be able to evaluate the control measures carried out for decreasing resistance in Salmonella, specifically that addressed to the prudent use of antimicrobial agents by farmers and veterinarians.

Relación de instrumentos internacionales multilaterales en materia de salud / Relationship multilateral instruments international health

El presente documento detalla los resultados de protocolos, convenios, enmiendas, y acuerdos realizados con diversas instituciones cooperantes de salud durante el período 2004(AU)

Relación de instrumentos internacionales bilaterales en materia de salud / Relationship bilateral international health

El presente documento detalla los resultados de los acuerdos, protocolos y convenios realizados entre el gobierno del Perú con Alemania, Brasil, reino de los Países Bajos, Ecuador y Bolivia durante la gestión del Ministerio de Salud 2004(AU)

Relación de instrumentos internacionales bilaterales en materia de salud / Relationship bilateral international health

El presente documento destalla los resultados de tres acuerdos de proyectos pactados entre el gobierno del Perú y el Fondo de Población de las Naciones Unidas para el apoyo al programa Nacional de atención a la Salud Reproductiva (FNUAP), en la región Nor-Oriental de Marañón (Jaén, Bagua, Chachapoyas y Cajamarca(AU)

Relación de instrumentos internacionales bilaterales en materia de salud / Relationship bilateral international health

El documento detalla los resultados de los acuerdos, protocolos y convenios realizados entre el gobierno del Perú con Alemania, Brasil, reino de los Países Bajos, Ecuador y Bolivia durante la gestión del Ministerio de Salud 2004