Four-month incidence of suicidal thoughts and behaviors among healthcare workers after the first wave of the Spain COVID-19 pandemic

[EN] Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May–September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October–December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0–4; odds ratio [OR] range = 1.23–1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0–4; OR range 1.30–1.32), and the perceived lack of healthcare center preparedness (scaled 0–4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3–57.6%. Other significant risk factors were financial stressors (OR range 1.26–1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies.S

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Qualidade da silagem de resíduo de manga com diferentes aditivos Quality of mango residue silage with different additives

Com o objetivo de avaliar a qualidade da silagem de resíduo de manga (Mangifera indica L.) em mistura com diferentes aditivos, em níveis crescentes de adição, foi conduzido este estudo. O delineamento experimental utilizado foi o inteiramente casualizado, com três repetições, sendo os tratamentos dispostos em um esquema fatorial do tipo (4 x 3) + 1, sendo quatro aditivos (milho desintegrado com palha e sabugo (MDPS), palha de feijão (PF), sabugo de milho (SM) e casca de café (CC)) em três níveis de adição (10, 20 e 30%) e um tratamento testemunha (resíduo de manga puro ensilado). O material experimental foi ensilado em silos de PVC adaptados com válvula tipo "Bunsen" com capacidade para aproximadamente 3 kg cada. Todos os aditivos utilizados elevaram os teores de MS. À medida que se aumentou os níveis de adição dos aditivos, houve uma redução nos valores de poder tampão (PT). Os valores de pH e nitrogênio amoniacal (N-NH3 /%N total) mantiveram-se dentro dos padrões indicativos de um bom processo fermentativo. O padrão de fermentação das silagens aditivadas foi satisfatório, sem haver comprometimento na qualidade destas. Os aditivos milho desintegrado com palha e sabugo, palha de feijão ou casca de café podem ser adicionados ao processo de ensilagem do resíduo de manga nos níveis de adição de 20 ou 30%, melhorando seu padrão fermentativo.<br>With the objective to evaluate the quality of mango (Mangifera indica L.) residue silage in mixture with different additives at growing levels of addition, this study was undertaken. The experimental design utilized was the completely randomized, with three replicates. The treatments were arranged in a factorial scheme (4 x 3) + 1 type and the additives being four (ground ears with husks (GEWH), bean straw (BS), corn cob (CC) and coffee hull (CH)) at three levels of addition (10, 20 and 30%) and a control treatment (ensiled unmixed mango residue). The experimental material was ensiled in PVC silos, fitted with a "Bunsen" type valve, with a capacity of about 3 kg each. All the additives utilized raised the DM contents of the silages. As the levels of addition of the additives were increased, there was a reduction in the values of buffering power (PT). The values of pH and ammoniac nitrogen (N-NH3 /%total N) were maintained within the indicative standard of a goof fermentative process. The fermentation standard of silages with additives was satisfactory with no damage in their quality. The additives GEWH, BS or CH may be added to the process of ensiling the mango residue at the levels of addition of 20 or 30%, to improve its fermentative standard for silages of good quality

Qualidade de manga 'tommy atkins' pós-colheita com uso de cloreto de cálcio na pré-colheita Quality of 'tommy atkins' mangoes in post-harvest with calcium choride spray use in the pre-harvest period

Mangas da cultivar Tommy Atkins produzidas em Livramento de Nossa Senhora, Bahia, foram analisadas com o objetivo de verificar a influência da aplicação pré-colheita de cloreto de cálcio na vida útil pós-colheita e em relação ao distúrbio fisiológico. As pulverizações de CaC1(2) foram realizadas em três épocas: 35; 65 e 95 dias após o florescimento. Os tratamentos foram concentrações de cloreto de cálcio: 0,0%; 2,0%; 3,5%; 5,0% e 6,5%. Frutos foram colhidos, transportados para o Laboratório de Biotecnologia da UESB, armazenados em câmara fria a 10ºC e 90% UR e avaliados por período de 35 dias. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial 5 x 6 (concentração x tempo de armazenamento), com 3 repetições e 2 frutos por parcela. Os parâmetros analisados foram: perda de massa, firmeza, acidez titulável, pH, sólidos solúveis, relação sólidos solúveis/acidez, incidência e severidade de colapso interno. Durante o período de armazenamento, observou-se que, a partir do 28º dia de armazenamento, a perda de massa dos frutos foi menor em doses maiores de cloreto de cálcio. A firmeza e o teor de sólidos solúveis foram influenciados em maiores concentrações de CaC1(2), enquanto as demais características não foram influenciadas significativamente. A incidência e a severidade do colapso interno dos frutos não foram afetadas com uso de cloreto de cálcio. Verificou-se que a aplicação pré-colheita de cloreto de cálcio, em doses maiores (> 3,5%), aumenta a vida útil pós-colheita da manga, contudo não reduz a incidência do colapso interno.<br>The fruits produced in Livramento de Nossa Senhora, Bahia, had been analyzed with the objective to verify the influence of spraying application of calcium chloride in pre-harvest period on shelf life of 'Tommy Atkins' mangoes. The sprayings of CaC1(2) were made three times: 35, 65 and 95 days after mango flowering. The used treatments were composed of the following concentrations of calcium chloride: 0.0%; 2.0%; 3.5%; 5.0% and 6.5%. The fruits were harvested, transported to the Laboratory of Biotechnology of Bahia Southwest State University, stored at 10ºC and 90% RH and evaluated during 35 days. The statistical design was an entirely randomized, using a factorial scheme 5 x 6, with 3 repetitions and 2 fruits/plot. The analyzed parameters were: loss of mass, firmness, titratable acidity, pH, soluble solids, soluble solids and titratable acidity ratio, incidence and severity of internal breakdown. During the period of fruit storage it was observed that in relation to the loss of mass, the fruits presented inferior loss when higher concentration of calcium chloride were used, from the 28th day of storage. For soluble solids and firmness they were also influenced in higher concentrations. For the other characteristics no differences were observed among them. No effects were verified in incidence and severity of internal breakdown in mangoes. From the results it can be concluded that the application of high concentrations of calcium chloride (>3,5%) in mango tree in pre-harvest period, increase shelf-life after 28 days of fruit storage, however it does not reduce the incidence of internal breakdown

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

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

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