A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene

Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer's disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer's disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer's disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer's disease and COVID-19, and development of biomarkers to track disease progression

Exploring the negotiation thesis application among ski resort tourists: a segmentation approach

The negotiation thesis offers a framework for understanding the participation decision making of tourists. Unlike previous studies that investigate the causal relationship between constraints and tourists’ revisit intention, this study identified distinct segments of ski tourist based on the relative strength of constraints experienced and then investigated their decision-making process across a sample of 1,348 tourists of ski resorts. Chi-Squared Automated Interaction Detection (CHAID) analysis revealed that the decision making process regarding intention to revisit a ski destination varies between highly versus less constrained ski tourists, indicating different relative strengths of interpersonal, intrapersonal and structural constraints and different interactions among them when predicting revisit intention. On a practical basis, albeit the vast majority of participants were willing to repeat its visit, we offer customized per segment recommendations on increasing frequency of visitation and spending levels

Exploring the constraint profile of winter sports resort tourist segments

Many studies have confirmed the importance of market segmentation both theoretically and empirically. Surprisingly though, no study has so far addressed the issue from the perspective of leisure constraints. Since different consumers face different barriers, we look at participation in leisure activities as an outcome of the negotiation process that winter sports resort tourists go through, to balance between related motives and constraints. This empirical study reports the findings on the applicability of constraining factors in segmenting the tourists who visit winter sports resorts. Utilizing data from 1,391 tourists of winter sports resorts in Greece, five segments were formed based on their constraint, demographic and behavioral profile. Our findings indicate that such segmentation sheds light on factors that could potentially limit the full utilization of the market. To maximize utilization, we suggest customizing marketing to the profile of each distinct winter sports resort tourist segment that emerge

In-hospital informal caregivers' needs as perceived by themselves and by the nursing staff in Northern Greece: A descriptive study

<p>Abstract</p> <p>Background</p> <p>Informal care is common in many countries, especially in Greece, where families provide care in hospitals. Health education and informational needs are important factors for family members which are often underestimated by nursing staff. The aim of this study was to compare the perceptions of the nurses and the in-hospital informal caregivers about the in-hospital informal caregivers' knowledge and informational needs, as well as the factors that influence these perceptions.</p> <p>Methods</p> <p>This was a non-experimental descriptive study conducted in three general hospitals in Greece. The sample consisted of 320 nurses and 370 in-hospital informal caregivers who completed questionnaires. Descriptive statistics were analyzed using t-tests; group comparisons were conducted using ANOVA.</p> <p>Results</p> <p>The score of the questionnaire for health education and informational needs was significantly greater for informal caregivers (57.1 ± 6.9 and 26.6 ± 2.8) than for nurses (53.4 ± 5.7 and 22.4 ± 3.1) (p < 0.001). For the nursing staff, the factors that influence the informational needs of patients' caregivers were <it>level of education </it>and <it>working experience</it>, while for the caregivers the <it>level of education </it>was independently associated with the score for the health education needs. Finally, <it>age, marital status</it>, and <it>level of education </it>of informal caregivers' were independently associated with informational needs.</p> <p>Conclusions</p> <p>The in-hospital informal caregivers perceived that they have more educational and informational needs than the nurses did. The findings of this study also show that the nursing staff has to identify the needs of in-hospital informal caregivers in order to be able to meet these needs.</p

Genetic variability in response to Aβ deposition influences Alzheimer's risk

Genetic analysis of late-onset Alzheimer's disease risk has previously identified a network of largely microglial genes that form a transcriptional network. In transgenic mouse models of amyloid deposition we have previously shown that the expression of many of the mouse orthologs of these genes are co-ordinately up-regulated by amyloid deposition. Here we investigate whether systematic analysis of other members of this mouse amyloid-responsive network predicts other Alzheimer's risk loci. This statistical comparison of the mouse amyloid-response network with Alzheimer's disease genome-wide association studies identifies 5 other genetic risk loci for the disease (OAS1, CXCL10, LAPTM5, ITGAM and LILRB4). This work suggests that genetic variability in the microglial response to amyloid deposition is a major determinant for Alzheimer's risk

Ideal cardiovascular health and inflammation in European adolescents: The HELENA study

Background and aims Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents. Methods and results As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls. Conclusion Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention