Identification and properties of TRPV4 mutant channels present in polycystic kidney disease patients.

Polycystic kidney disease (PKD), a disease characterized by enlargement of the kidney through cystic growth is the fourth leading cause of end-stage kidney disease world-wide. TRPV4, a calcium-permeable TRP, channel participates in kidney cell physiology and since TRPV4 forms complexes with another channel whose malfunction is associated to PKD, TRPP2 (or PKD2), we sought to determine whether patients with PKD, exhibit previously unknown mutations in TRPV4. Here, we report the presence of mutations in the TRPV4 gene in patients diagnosed with PKD and determine that they produce gain-of-function (GOF). Mutations in the sequence of the TRPV4 gene have been associated to a broad spectrum of neuropathies and skeletal dysplasias but not PKD, and their biophysical effects on channel function have not been elucidated. We identified and examined the functional behavior of a novel E6K mutant and of the previously known S94L and A217S mutant TRVP4 channels. The A217S mutation has been associated to mixed neuropathy and/or skeletal dysplasia phenotypes, however, the PKD carriers of these variants had not been diagnosed with these reported clinical manifestations. The presence of certain mutations in TRPV4 may influence the progression and severity of PKD through GOF mechanisms. PKD patients carrying TRVP4 mutations are putatively more likely to require dialysis or renal transplant as compared to those without these mutations.

Reversal of high-glucose-induced transcriptional and epigenetic memories through NRF2 pathway activation.

Diabetes complications such as nephropathy, retinopathy, or cardiovascular disease arise from vascular dysfunction. In this context, it has been observed that past hyperglycemic events can induce long-lasting alterations, a phenomenon termed "metabolic memory." In this study, we evaluated the genome-wide gene expression and chromatin accessibility alterations caused by transient high-glucose exposure in human endothelial cells (ECs) in vitro. We found that cells exposed to high glucose exhibited substantial gene expression changes in pathways known to be impaired in diabetes, many of which persist after glucose normalization. Chromatin accessibility analysis also revealed that transient hyperglycemia induces persistent alterations, mainly in non-promoter regions identified as enhancers with neighboring genes showing lasting alterations. Notably, activation of the NRF2 pathway through NRF2 overexpression or supplementation with the plant-derived compound sulforaphane, effectively reverses the glucose-induced transcriptional and chromatin accessibility memories in ECs. These findings underscore the enduring impact of transient hyperglycemia on ECs' transcriptomic and chromatin accessibility profiles, emphasizing the potential utility of pharmacological NRF2 pathway activation in mitigating and reversing the high-glucose-induced transcriptional and epigenetic alterations.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Local Ancestry at the Major Histocompatibility Complex Region is Not a Major Contributor to Disease Heterogeneity in a Multiethnic Lupus Cohort.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies. METHODS: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE, and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age at onset, and autoantibody status with both global and local ancestry proportions within the Major Histocompatibility Complex region. RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo patients with SLE who presented with the clinical manifestations of interest compared with those who did not. CONCLUSION: These findings suggest that local genetic ancestry within the Major Histocompatibility Complex region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations.

ASSOCIATION BETWEEN APOE-ε4 CARRIER STATUS AND QUALITATIVE NEUROIMAGING CHARACTERISTICS IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT.

BACKGROUND: The pathogenesis of mild cognitive impairment (MCI) is multifactorial and includes the presence of genetic variants such as the ε4 allele of the apolipoprotein E gene (APOE-ε4). Association between the APOE-ε4 carrier status and deleterious structural and functional changes on magnetic resonance imaging (MRI) has been previously described in individuals with Alzheimer's disease. However, the central nervous system changes may possibly develop in earlier stages of cognitive impairment, as reflected in MCI. OBJECTIVE: The objective of the study was to determine the association between APOE-ε4 carrier status and qualitative changes on MRI (medial temporal and parietal atrophy), as well as the detection of white matter hyperintensities (WMH) in older adults with MCI, in the memory clinic of a tertiary care hospital in Mexico City. METHODS: A cross-sectional study of 72 adults aged 60 years or above who underwent an exhaustive clinical, neuroimaging, and neuropsychological evaluation. Multivariate logistic regression models were constructed to determine the association between APOE-ε4 carrier status and qualitative/quantitative changes on MRI. RESULTS: Mean age was 75.2 years (± 7.2) and 64% were female. Twenty-one participants were cognitively normal and 51 had MCI. Almost 56% were APOE-ε4 carriers and were associated with medial-temporal atrophy according to the Scheltens scale (odds ratio [OR]: 20.0, 95% confidence intervals [CI]: 3.03-131.7), parietal atrophy according to the Koedam's score (OR: 6.3; 95% CI 1.03-39.53), and WMH according to the Fazekas scale (OR: 11.7, 95% CI: 1.26-108.2), even after adjusting for age, educational level, and cardiovascular risk factors. CONCLUSION: The APOE-ε4 carrier status was associated with medial temporal and parietal atrophy, as well as WMH. Our findings support the hypothesis suggesting the contribution of this genotype to neurodegeneration and cerebral vascular pathology.

Genetic discovery and risk characterization in type 2 diabetes across diverse populations.

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the TGFB1 gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10-8), which replicated in independent studies of African ancestry (p = 6.26 × 10-23). We identified a multiethnic risk variant in the BACE2 gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10-9), which also replicated in independent studies (p = 3.45 × 10-4). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (pheterogeneity = 3.85 × 10-20). Comparing individuals in the top GRS risk category (40%-60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations.

Differences in MTHFR and LRRK2 variant's association with sporadic Parkinson's disease in Mexican Mestizos correlated to Native American ancestry.

Parkinson's disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case-control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 in LRRK2. However, when stratification by ancestry was performed, a risk effect for MTHFR rs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect for LRRK2 rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect of LRRK2 rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors' role in the pathophysiological mechanisms of this neurodegenerative disorder.

Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults.

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer's disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

The causal effect of obesity on prediabetes and insulin resistance reveals the important role of adipose tissue in insulin resistance.

Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2×10-3 and p = 3.1×10-24). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p≤0.05 for each) when adjusting for the decomposed adipose cell-type proportions. Next, we showed that these 3 factors, adipose MT gene expression, body fat percent, and adipose cell types, explain a substantial amount (44.39%) of variance in insulin resistance and can be used to predict it (p≤2.64×10-5 in 3 independent human cohorts). In summary, we demonstrated that obesity is a strong determinant of both prediabetes and insulin resistance, and discovered that individuals' adipose cell-type composition, adipose MT gene expression, and body fat percent predict their insulin resistance, emphasizing the critical role of adipose tissue in systemic insulin resistance.

Contribution of Known Genetic Risk Variants to Dyslipidemias and Type 2 Diabetes in Mexico: A Population-Based Nationwide Study.

Dyslipidemias are common risk factors for the development of chronic disorders including type 2 diabetes (T2D). Over 100 associated loci have been identified but few reports have evaluated the population attributable fraction captured by them in population-based nationwide surveys. Therefore, we determined the population contribution of a set of known genetic risk variants to the development of dyslipidemias and T2D in Mexico. This study included 1665 participants from a Mexican National Health Survey carried out in the year 2000. It is a probabilistic complex sample survey of households, which comprises representative data at a national level. 103 previously reported SNPs associated with different dyslipidemias or T2D were genotyped and used to compute polygenic risk scores. We found that the previously known variants associated with dyslipidemias explain at most 7% of the total risk variance of lipid levels. In contrast, the known genetic risk component for T2D explained a negligible amount of variance (0.1%). Notably, variants derived from the Native-American ancestry have the strongest effect and contribute with a high proportion of the variance. These results support the need for additional studies aimed to identify specific genetic risk variants for Mexican population.

A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos.

BACKGROUND: Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. RESULTS: We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r2 = 0.972. CONCLUSIONS: Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals.

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry.

BACKGROUND: FSHR SNPs may influence the ovarian sensitivity to endogenous and exogenous FSH stimulation. Given the paucity of data on the FSHR c.919A > G, c.2039A > G and - 29G > A SNPs in Hispanic population, we here analyzed their frequency distribution in Mexican mestizo women. METHODS: Samples from 224 Mexican mestizo women enrolled in an IVF program as well as a genotype database from 8182 Mexican mestizo subjects, were analyzed for FSHR SNPs at positions c.919, c.2039 and - 29G > A. Association between the genetic variants and reproductive outcomes was assessed. RESULTS: The c.919 and c.2039 SNPs were in strong linkage disequilibrium and their corresponding genotype frequencies in the IVF group were: AA 46.8%, AG 44.2%, and GG 8.9%, and AA 41.9%, AG 48.2% and GG 9.8%, respectively. For the -29G > A SNP, genotype frequencies were 27% (GG), 50% (GA) and 23% (AA). In normal oocyte donors with the c.2039 GG genotype, the number of oocytes recovered after ovarian stimulation (COS) were significantly (p < 0.01) lower than in those bearing other genotypes in this or the -29G > A SNP. Analysis of the large scale database revealed that both allelic and genotype frequencies for the three SNPs were very similar to those detected in the IVF cohort (p ≥ 0.38) and that female carriers of the c.2039 G allele tended to present lower number of pregnancies than women bearing the AA genotype; this trend was stronger when women with more Native American ancestry was separately analyzed (OR = 2.0, C.I. 95% 1.03-3.90, p = 0.04). There were no differences or trends in the number of pregnancies among the different genotypes of the -29G > A SNP. CONCLUSIONS: The frequency of the GG/GG combination genotype for the c.919 and c.2039 SNPs in Mexican hispanics is among the lowest reported. The GG genotype is associated with decreased number of oocytes recovered in response to COS as well as to lower pregnancy rates in Hispanic women from the general population. The absence of any effect of the -29AA genotype on the response to COS, indicates that there is no need to perform this particular genotype testing in Hispanic women with the purpose of providing an individually-tailored COS protocol.

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes.

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

Genetic contributions to lupus nephritis in a multi-ethnic cohort of systemic lupus erythematous patients.

OBJECTIVE: African Americans, East Asians, and Hispanics with systemic lupus erythematous (SLE) are more likely to develop lupus nephritis (LN) than are SLE patients of European descent. The etiology of this difference is not clear, and this study was undertaken to investigate how genetic variants might explain this effect. METHODS: In this cross-sectional study, 1244 SLE patients from multiethnic case collections were genotyped for 817,810 single-nucleotide polymorphisms (SNPs) across the genome. Continental genetic ancestry was estimated utilizing the program ADMIXTURE. Gene-based testing and pathway analysis was performed within each ethnic group and meta-analyzed across ethnicities. We also performed candidate SNP association tests with SNPs previously established as risk alleles for SLE, LN, and chronic kidney disease (CKD). Association testing and logistic regression models were performed with LN as the outcome, adjusted for continental ancestries, sex, disease duration, and age. RESULTS: We studied 255 North European, 263 South European, 238 Hispanic, 224 African American and 264 East Asian SLE patients, of whom 606 had LN (48.7%). In genome-wide gene-based and candidate SNP analyses, we found distinct genes, pathways and established risk SNPs associated with LN for each ethnic group. Gene-based analyses showed significant associations between variation in ZNF546 (p = 1.0E-06), TRIM15 (p = 1.0E-06), and TRIMI0 (p = 1.0E-06) and LN among South Europeans, and TTC34 (p = 8.0E-06) was significantly associated with LN among Hispanics. The SNP rs8091180 in NFATC1 was associated with LN (OR 1.43, p = 3.3E-04) in the candidate SNP meta-analysis with the highest OR among African-Americans (OR 2.17, p = 0.0035). CONCLUSION: Distinct genetic factors are associated with the risk of LN in SLE patients of different ethnicities. CKD risk alleles may play a role in the development of LN in addition to SLE-associated risk variants. These findings may further explain the clinical heterogeneity of LN risk and response to therapy observed between different ethnic groups.

Salud, enfermedad y cuidado de adultos mayores inmigrantes / Health, illness and care of immigrant older adults / Saúde, doença e cuidado de idosos imigrantes

Objetivo: describir el significado de salud, enfermedad y cuidado del adulto mayor inmigrante de la comunidad El Mezquital ubicada al nordeste de la costa mexicana del golfo de México en relación a su cosmovisión y el entorno donde viven. Método: una investigación etnográfica fue realizada con estadías largas en el sitio de estudio, observación participante y entrevista abierta a 15 participantes, durante enero de 2016 a abril de 2017. La validación de datos se realiza mediante una técnica de triangulación de la información. Resultados: patrones recurrentes de significado de salud fueron: sentirse bien, tener familia, tener dinero, el lugar donde viven; de enfermedad: conocimiento personal, alimentación, actividad física y tener fe; y en el cuidado se identificaron la medicación, estudios diagnósticos, cirugías. Conclusión: conocer el significado de salud, enfermedad y cuidado de adultos mayores permitió identificar patrones recurrentes que inciden culturalmente sobre lo que ayuda a la persona a estar bien y lo que la enferma o le hace mal, expresando el cuidado desde el entorno del hogar. La investigación desde perspectiva cultural, potencia un campo natural de cuidado basado en el entendimiento y comprensión cultural para brindar cuidado culturalmente congruente.

Objective: it was to describe the health, disease and care of immigrant older adults living in the Mezquital in Northeastern Mexican coast of the Gulf of Mexico. Method: an ethnographic research was conducted with long stays in the study site, participant observation and open interviews to 15 participants, during january 2016 through february 2017. Data obtained was validated through a triangulation technique. Results: recurring patterns of meaning of health were: feel good, have a family, have money, where they live; of disease were personal knowledge, physical activity, food and faith; in care were identified: medication, diagnostic tests and surgeries. Conclusions: to know the meaning of health, illness and care of major adults allowed identifying patterns appellants who affect culturally on what helps the person it is to be well and what the sick person or it harms him, reflecting the care from the environment of the hearth. The investigation from cultural perspective, promotes a natural field of care established in the understanding and cultural comprehension to offer culturally coherent care.

Objetivo: descrever o significado de saúde, doença e cuidado do idoso imigrante da comunidade El Mezquital localizada no nordeste da costa mexicana do Golfo do México em relação à sua cosmovisão e o entorno de onde vivem. Método: uma investigação etnográfica foi realizada com estadias longas no local do estudo, observação participante e entrevistas abertas a 15 participantes, durante janeiro de 2016 a fevereiro de 2017. A validação dos dados se realizou mediante uma técnica de triangulação de informações. Resultados: padrões recorrentes de significância em saúde foram: sentir-se bem, ter uma família, ter dinheiro, o lugar onde vivem; de doença: conhecimento pessoal, comida, atividade física e ter fé; e no cuidado se identificaram a medicação, estudos diagnósticos e cirurgias. Conclusão: conhecer o significado de saúde, doença e cuidado de idosos permitiu identificar padrões recorrentes que incidem culturalmente sobre o que ajuda a pessoa a estar bem e o que a torna doente ou que faz mal, expressando o cuidado desde o entorno do lar. A investigação a partir da perspectiva cultural potencializa um campo natural de cuidado baseado no entendimento e compreensão cultural para fornecer cuidado culturalmente congruente.

Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

OBJECTIVE: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. METHODS: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. RESULTS: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment. CONCLUSION: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Manifestaciones somáticas en un grupo de adolescentes con ansiedad / Somatic manifestations in a group of adolescents with anxiety disorders

INTRODUCCIÓN: la ansiedad es el síntoma psiquiátrico más prevalente en la sociedad moderna, también en la infancia y adolescencia. OBJETIVO: caracterizar un grupo de adolescentes ansiosos, la intensidad de la ansiedad, las manifestaciones clínicas y las áreas de conflictos. MÉTODOS: se realizó un estudio descriptivo con técnicas cuanti-cualitativas en 30 adolescentes entre 11 y 16 años de edad, con ansiedad de más de 6 meses de evolución, seleccionado aleatoriamente, que dieron el consentimiento para ser incluidos en el estudio. Fueron atendidos por Psiquiatría Infantil del Hospital Pediátrico Universitario Centro Habana, entre enero y junio del año 2014. Las variables estudiadas fueron: edad, sexo, intensidad de la ansiedad, manifestaciones clínicas y áreas de conflictos. Se realizó historia social psiquiátrica, examen psiquiátrico, entrevista psicológica, test IDAREN y de Frases Incompletas de Rotter. RESULTADOS: 77 % tienen entre 11 y 14 años, 73 % es del sexo femenino, con nivel medio y alto para la ansiedad-estado (97 %) y ansiedad-rasgo del 83 %; predominaron las manifestaciones somáticas, como trastornos del sueño (83 %), hiperactividad-excitación (80 %), síntomas cardíacos (77 %), salto epigástrico (70 %), dolor abdominal (63 %) y sudoración (53 %); y las psicológicas, como inseguridad (70 %), sensación de amenaza (67 %), dificultad en la concentración y la memoria (63 %), sentimientos negativos (60 %) e irritabilidad (53 %). El 83 % tenía conflictos en área familiar, 70 % en las relaciones sociales, y 50 % en área escolar. CONCLUSIONES: predominan el sexo femenino, las edades entre 11 y 14 años, con niveles medio y alto para ansiedad-estado y ansiedad-rasgo, así como los síntomas somáticos de ansiedad y conflictos en el área familiar.

INTRODUCTION: anxiety is the most prevailing psychiatric symptom in the modern society and also in childhood and adolescence. Objective: to characterize a group of anxious adolescence, the intensity of anxiety, the clinical manifestations and the areas of conflict. METHODS: a descriptive study based on quantitative and qualitative techniques was performed in 30 adolescents aged 11 to 16 years, who presented anxiety disorders for over 6 months and randomly selected after giving their consent to be included in the study. These patients had been seen at the infantile psychiatry service of the university pediatric hospital Centro Habana from January to June 2014. The studied variables were: age, sex, intensity of anxiety, clinical manifestations and areas of conflicts. A psychiatric social history, psychiatric exam, psychological interview, IDAREN test and Rotter's incomplete phrase test were all applied. RESULTS: in the study group, 77 % were 11 to 14 years, 73 % were females, with middle and high level for anxiety-state (97 %) and anxiety-trait (83 %); somatic manifestations such as sleep disorders (83 %), hyperactivity-excitement (80 %), heart symptoms (77 %), epigastric_beat (70 %), stomachache (63 %), sweating (53 %), and psychological manifestations as insecurity (70 %), feeling of being threatened (67 %), difficult concentration and memorization (63 %), negative feelings (60 %) and irritability (53 %) predominated. Eighty three percent of them faced conflicts in their family setting, 70 % with their social relationships and 50 % at the school area. CONCLUSIONS: females, 11-14 years of age, middle and high levels for anxiety-state and anxiety-trait, somatic symptoms of anxiety and conflicts in the family setting are predominant.

Manifestaciones somáticas en un grupo de adolescentes con ansiedad / Somatic manifestations in a group of adolescents with anxiety disorders

Introducción: la ansiedad es el síntoma psiquiátrico más prevalente en la sociedad moderna, también en la infancia y adolescencia.Objetivo: caracterizar un grupo de adolescentes ansiosos, la intensidad de la ansiedad, las manifestaciones clínicas y las áreas de conflictos.Métodos: se realizó un estudio descriptivo con técnicas cuanti-cualitativas en 30 adolescentes entre 11 y 16 años de edad, con ansiedad de más de 6 meses de evolución, seleccionado aleatoriamente, que dieron el consentimiento para ser incluidos en el estudio. Fueron atendidos por Psiquiatría Infantil del Hospital Pediátrico Universitario Centro Habana, entre enero y junio del año 2014. Las variables estudiadas fueron: edad, sexo, intensidad de la ansiedad, manifestaciones clínicas y áreas de conflictos. Se realizó historia social psiquiátrica, examen psiquiátrico, entrevista psicológica, test IDAREN y de Frases Incompletas de Rotter.Resultados: 77 por ciento tienen entre 11 y 14 años, 73 por ciento es del sexo femenino, con nivel medio y alto para la ansiedad-estado (97 por ciento) y ansiedad-rasgo del 83 por ciento; predominaron las manifestaciones somáticas, como trastornos del sueño (83 por ciento), hiperactividad-excitación (80 por ciento), síntomas cardíacos (77 por ciento), salto epigástrico (70 por ciento), dolor abdominal (63 por ciento) y sudoración (53 por ciento); y las psicológicas, como inseguridad (70 por ciento), sensación de amenaza (67 por ciento), dificultad en la concentración y la memoria (63 por ciento), sentimientos negativos (60 por ciento) e irritabilidad (53 por ciento). El 83 por ciento tenía conflictos en área familiar, 70 por ciento en las relaciones sociales, y 50 por ciento en área escolar.Conclusiones: predominan el sexo femenino, las edades entre 11 y 14 años, con niveles medio y alto para ansiedad-estado y ansiedad-rasgo, así como los síntomas somáticos de ansiedad y conflictos en el área familiar(AU)

Introduction: anxiety is the most prevailing psychiatric symptom in the modern society and also in childhood and adolescence.Objective: to characterize a group of anxious adolescence, the intensity of anxiety, the clinical manifestations and the areas of conflict.Methods: a descriptive study based on quantitative and qualitative techniques was performed in 30 adolescents aged 11 to 16 years, who presented anxiety disorders for over 6 months and randomly selected after giving their consent to be included in the study. These patients had been seen at the infantile psychiatry service of the university pediatric hospital Centro Habana from January to June 2014. The studied variables were: age, sex, intensity of anxiety, clinical manifestations and areas of conflicts. A psychiatric social history, psychiatric exam, psychological interview, IDAREN test and Rotter's incomplete phrase test were all applied.Results: in the study group, 77 percent were 11 to 14 years, 73 percent were females, with middle and high level for anxiety-state (97 percent) and anxiety-trait (83 percent); somatic manifestations such as sleep disorders (83 percent), hyperactivity-excitement (80 percent), heart symptoms (77 percent), epigastric_beat (70 percent), stomachache (63 percent), sweating (53 percent), and psychological manifestations as insecurity (70 percent), feeling of being threatened (67 percent), difficult concentration and memorization (63 percent), negative feelings (60 percent) and irritability (53 percent) predominated. Eighty three percent of them faced conflicts in their family setting, 70 percent with their social relationships and 50 percent at the school area.Conclusions: females, 11-14 years of age, middle and high levels for anxiety-state and anxiety-trait, somatic symptoms of anxiety and conflicts in the family setting are predominant(AU)