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

Comunicación corta. Efecto de la fuente de forraje (pasto vs. ensilado) sobre el contenido de ácido linoleico conjugado en la grasa láctea de vacas Holstein-Friesian en Galicia (NO España)

The aim of this study was to investigate the effect of different feeding proportions of forage ―grazing vs. silage― on milk fatty acids (FA) profile and conjugated linoleic acid (CLA) content of autumn calving Holstein-Friesian cows (n = 61) at CIAM (Galicia, NW Spain). Three treatments (S, 100% silage; G/S, 50% grazing + 50% silage; G, 100% grazing) were set and milk FA profile of dairy cows was determined by gas chromatography-mass spectrometry. The G group showed a decrease in short (p < 0.05) and medium chain FA (p < 0.001), with an increase in long chain FA (p < 0.001) in comparison to the G/S and S groups, which showed the lowest levels (p < 0.001) of mono- and polyunsaturated FA. The CLA content in milk fat increased (p < 0.001) linearly in relation to the increased proportion of fresh grass in the diet of dairy cows from 0.49 and 0.82 to 1.14 g/100 g FA for the treatments S, G/S and G, respectively. During spring and summer, the levels of CLA were three times higher (p < 0.001, +0.76 g/100 g FA) in milk from dairy cows at the G group than in cows at the S group and twice higher (p < 0.001, +0.40 g/100 g FA) than in cows at the G/S group. High proportion of grass in the diet of cows increased CLA content, with the highest levels of unsaturated FA and the lowest levels of saturated FA, increasing the added value of milk on grazing systems using available farm resources.El objetivo de este estudio fue investigar el efecto de utilizar diferentes proporciones de forraje, pasto vs. silo, en el perfil de ácidos grasos (AG) de la leche y en el contenido de ácido linoleico conjugado (CLA) en vacas lecheras Holstein- Friesian (n = 61) de partos de otoño. Se establecieron tres tratamientos (S, 100% ensilaje; G/S, 50% pastoreo y 50% ensilaje; G, 100% pastoreo) y se determinó el perfil de AG de la leche por cromatografía de gases-espectrometría de masas. El grupo G mostró una disminución en los AG de cadena corta (p < 0,05) y media (p < 0,001), con un aumento en los AG de cadena larga (p < 0,001) en comparación con los grupos G/S y S, que mostraron unos contenidos menores (p < 0,001) de AG mono- y poli-insaturados. El contenido de CLA en la grasa láctea aumentó linealmente con el incremento en la proporción de pasto fresco en la dieta de las vacas lecheras desde 0,49 y 0,82 a 1,14 g/100 g de AG para los tratamientos S, G/S y G, respectivamente. Durante la primavera y el verano, los niveles de CLA fueron tres veces superiores (p < 0,001, +0,76 g/100 g de AG) en la leche de las vacas del grupo G respecto a la del grupo S y dos veces superiores (p < 0,001, +0,40 g/100 g de AG) a la del grupo G/S. Una alta proporción de pasto en la dieta incrementó el contenido de CLA, con niveles superiores de AG insaturados y menores de saturados, lo que aumenta el valor añadido de la leche producida en los sistemas de pastoreo que aprovechan los recursos existentes en las explotaciones

Prevalence and Risk Factors for Colonization by Multidrug-Resistant Microorganisms among Long-Term Travelers and Recently Arrived Migrants

Multidrug-resistant (MDR) bacteria have become one of the most important health problems. We aimed to assess whether international travel may facilitate their spread through the colonization of asymptomatic travelers. A cross-sectional study was conducted (November 2018 to February 2022). Pharyngeal and rectal swabs were obtained from long-term travelers and recently arrived migrants from non-European countries, and an epidemiological survey was performed. Colonization by Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) was determined by chromogenic media and MALDI-TOF-MS. Resistance mechanisms were determined by the biochip-based molecular biology technique. Risk factors for colonization were assessed by logistic regression. In total, 122 participants were included: 59 (48.4%) recently arrived migrants and 63 (51.6%) long-term travelers. After their trip, 14 (11.5%) participants-5 (8.5%) migrants and 9 (14.3%) travelers-had rectal colonization by one MDR bacterium. Escherichia coli carrying the extended-spectrum beta-lactamase (ESBL) CTX-M-15 was the most frequent. No participants were colonized by MRSA or carbapenemase-producing Enterobacteriaceae. The only risk factor independently associated with MDR bacterial colonization was previous hospital attention [OR, 95% CI: 10.16 (2.06-50.06)]. The risk of colonization by MDR bacteria among recently arrived migrants and long-term travelers is similar in both groups and independently associated with previous hospital attention