Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. We thank Drs. D. Stephen Snyder and Marilyn Miller from NIA who are ex-officio ADGC members. EADI. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease) including funding from MEL (Metropole européenne de Lille), ERDF (European Regional Development Fund) and Conseil Régional Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RS-I, RS-II, RS-III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the
Background
Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis.
Methods
The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.
Results
ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05).
Conclusions
The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics.
Nineteen pregnant women with uncomplicated pregnancies were studied during the first, second, and third trimesters. We measured the following hemostatic parameters: prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, protein S, platelet number and volume. Platelet function was examined by a cytofluorimetric method, using an anti-GPM-140 antibody which is directed against a platelet alpha granule membrane protein. Activated platelets were expressed as a percentage of the GMP-140-positive platelets over total platelets. Fibrinogen levels showed a steady increase during pregnancy; conversely prothrombin time, activated partial thromboplastin time, protein C, and antithrombin III showed no significant modifications and remained within the reference range. There was a decrease of protein S activity throughout pregnancy, although protein S antigen did not follow this trend. The decrease occurred early in pregnancy and persisted during the second and third trimesters, reaching a stable plateau. We observed no platelet volume change or activation: the percentage of activated platelets was within the normal reference range, even in late pregnancy.
Background
In March 2020 we faced a huge spread of the epidemic of SARS-CoV2 in northern Italy; the Emergency Departments (ED) and the Emergency Medical Services (EMS) were overwhelmed by patients requiring care. The hospitals were forced to reorganize their services, and the ED was the focal point of this challenge. As Emergency Department in a metropolitan area of the region most affected, we saw an increasing number of patients with COVID-19, and we made some structural and staff implementations according to the evolution of the epidemic.
Methods
We analysed in a narrative way the weaknesses and the point of strength of our response to COVID-19 first outbreak, focusing point by point on main challenges and minor details involved in our ED response to the pandemics.
Results
The main stems for our response to the pandemic were: use of clear and shared contingency plans, as long as preparedness to implement them; stockage of as much as useful material can be stocked; training of the personnel to be prepared for a fast response, trying to maintain divided pathway for COVID-19 and non-COVID-19 patients, well-done isolation is a key factor; preparedness to de-escalate as soon as needed.
Conclusions
We evaluated our experience and analysed the weakness and strength of our first response to share it with the rest of the scientific community and colleagues worldwide, hoping to facilitate others who will face the same challenge or similar challenges in the future. Shared experience is the best way to learn and to avoid making the same mistakes.
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