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

The economic well-being of nations is associated with positive daily situational experiences

People in economically advantaged nations tend to evaluate their life as more positive overall and report greater well-being than people in less advantaged nations. But how does positivity manifest in the daily life experiences of individuals around the world? The present study asked 15,244 college students from 62 nations, in 42 languages, to describe a situation they experienced the previous day using the Riverside Situational Q-sort (RSQ). Using expert ratings, the overall positivity of each situation was calculated for both nations and individuals. The positivity of the average situation in each nation was strongly related to the economic development of the nation as measured by the Human Development Index (HDI). For individuals’ daily experiences, the economic status of their nation also predicted the positivity of their experience, even more than their family socioeconomic status. Further analyses revealed the specific characteristics of the average situations for higher HDI nations that make their experiences more positive. Higher HDI was associated with situational experiences involving humor, socializing with others, and the potential to express emotions and fantasies. Lower HDI was associated with an increase in the presence of threats, blame, and hostility, as well as situational experiences consisting of family, religion, and money. Despite the increase in a few negative situational characteristics in lower HDI countries, the overall average experience still ranged from neutral to slightly positive, rather than negative, suggesting that greater HDI may not necessarily increase positive experiences but rather decrease negative experiences. The results illustrate how national economic status influences the lives of individuals even within a single instance of daily life, with large and powerful consequences when accumulated across individuals within each nation

Balanço eletrolítico da dieta e desempenho de frangos em condições naturais de estresse calórico

Avaliou-se o efeito da suplementação de eletrólitos sobre o desempenho de frangos, utilizando bicarbonato de sódio (NaHCO3) e cloreto de potássio (KCl) para ajuste do balanço eletrolítico da dieta (BED) com duas porcentagens de proteína bruta (PB). Utilizaram-se 800 frangos machos, alojados em 20 boxes, distribuídos em delineamento inteiramente ao acaso, com quatro tratamentos, cinco repetições e 40 aves por unidade experimental. Os tratamentos foram: dieta basal; dieta sem redução de PB suplementada com eletrólitos para ajuste do BED para 250mEq/kg; dieta com redução de PB, sem suplementação de eletrólitos; e dieta com redução de PB, com eletrólitos para ajuste do BED para 250mEq/kg. Foram avaliados: consumo da dieta, peso final, ganho de peso, ganho de peso médio diário, conversão alimentar e calórica e eficiência de utilização de nitrogênio e lisina nas fases de sete a 21 e de sete a 42 dias. Não se observaram diferenças (P>0,05) no consumo da dieta. A correção do BED com menor teor de PB melhorou (P<0,05) o peso final, na fase inicial. Houve piora (P<0,05) no ganho de peso e na conversão alimentar nas duas fases. A redução de três pontos percentuais na PB da dieta piorou o desempenho dos frangos