New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Valores de referência e influência da idade no eritrograma de fêmeas bovinas da raça Aquitânica Reference values and age effect on the erythrogram of bovine females of the Aquitanian breed

Determinaram-se os valores de referência e estudou-se a influência da idade sobre o eritrograma em fêmeas bovinas da raça Aquitânica. Amostras de sangue de 80 fêmeas bovinas, acima de 12 meses de idade, e não reagentes ao antígeno do vírus da leucose dos bovinos, foram colhidas utilizando-se EDTA como anticoagulante para realização das seguintes provas: contagem global das hemácias, determinação do volume globular, concentração de hemoglobina, cálculo dos índices hematimétricos absolutos - volume corpuscular médio (VCM), hemoglobina corpuscular média (HCM) e concentração de hemoglobina corpuscular média (CHCM). A idade exerceu influência significativa (P<0,05) sobre a maioria dos parâmetros hematológicos estudados, com diminuição da quantidade de hemácias e aumento do volume globular, quantidade de hemoglobina, VCM e HCM. Os valores foram: hemácias 6,68&plusmn;0,58&times;10(6)/mm³, volume globular 41,2&plusmn;4,5%, hemoglobina 12,8&plusmn;1,31g/dl, VCM 61,83&plusmn;6,54fl, HCM 19,28&plusmn;2,25pg, CHCM 31,4&plusmn;2,3%.<br>The reference values and the influence of the age factor on the erytrogram in bovine females of the Aquitanian breed were evaluated. Blood samples of 80 healthy females, all tested negative for bovine leucose virus, were utilized for the analysis. Erythrocyte counts, determination of the packed cell volume, concentration of hemoglobin, calculation of hematimetric absolute rates of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were evaluated. Significant influence (P<0.05) of age was observed for most of the hematological characteristics, with decreased of the number of erythrocytes and increase of packed cell volume, quantity of hemoglobin, MCV, MCH. The reference values were: erythrocytes counting 6.68&plusmn;0.58&times;10(6)/mm³, packed cell volume 41.2&plusmn;4.5%, hemoglobin 12.8&plusmn;1.31g/dl, VCM 61.83&plusmn;6.54fl, HCM 19.28&plusmn;2.25pg, CHCM 31.4&plusmn;2.3%