RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy

TDP-43 proteinopathies including frontotemporal lobar dementia (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic-acid binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed an endogenous model of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43K145Q resulted in stress-induced nuclear TDP-43 foci and loss-of-TDP-43-function in primary mouse and human induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies

Changes in Healthcare Utilization During the COVID-19 Pandemic and Potential Causes—A Cohort Study From Switzerland

Objectives: To describe the frequency of and reasons for changes in healthcare utilization in those requiring ongoing treatment, and to assess characteristics associated with change, during the second wave of the pandemic.Methods: Corona Immunitas e-cohort study (age ≥20 years) participants completed monthly questionnaires. We compared participants reporting a change in healthcare utilization with those who did not using descriptive and bivariate statistics. We explored characteristics associated with the number of changes using negative binomial regression.Results: The study included 3,190 participants from nine research sites. One-fifth reported requiring regular treatment. Among these, 14% reported a change in healthcare utilization, defined as events in which participants reported that they changed their ongoing treatment, irrespective of the reason. Reasons for change were medication changes and side-effects, specifically for hypertension, or pulmonary embolism treatment. Females were more likely to report changes [Incidence Rate Ratio (IRR) = 2.15, p = 0.002]. Those with hypertension were least likely to report changes [IRR = 0.35, p = 0.019].Conclusion: Few of those requiring regular treatment reported changes in healthcare utilization. Continuity of care for females and chronic diseases besides hypertension must be emphasized

Interplay of Digital Proximity App Use and SARS-CoV-2 Vaccine Uptake in Switzerland: Analysis of Two Population-Based Cohort Studies

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic.Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes.Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]) compared to participants who did not get vaccinated.Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions

Interplay of digital proximity app use and SARS-CoV-2 vaccine uptake in Switzerland : analysis of two population-based cohort studies

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic. Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes. Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]) compared to participants who did not get vaccinated. Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Enhancing PV Self-Consumption through Energy Communities in Heating-Dominated Climates

The European Union, in accordance with its decarbonization objectives, has enacted the Directive (EU) 2018/2001 and subsequently the Directive (EU) 2019/944 that legally recognizes and regulates the formation of citizen energy communities. These are believed to be key enablers for reducing buildings’ carbon footprint by allowing for a wider diffusion of on-site renewable energy generation and by maximizing renewable energy self-consumption. In this study, the benefits of the energy community are assessed through simulations of average Italian buildings of various sizes, different energy efficiency levels, equipped with a photovoltaic system and a heat pump-driven heating system, and located in heating-dominated climates. The work focuses on energy communities both at the apartment scale—i.e., in a multi-family building—and at the building scale—i.e., in a neighborhood. The net energy consumption, the self-consumption, and the self-sufficiency of all the possible energy communities obtainable by combining the different buildings are compared to the baseline case that is represented by the absence of energy sharing between independent building units. The energy community alone at both the building-scale and the neighborhood-scale increases self-consumption by up to 5% and reduces net energy consumption by up to 10%. However, when the energy community is combined with other maximization strategies such as demand-side management and rule-based control, self-consumption can be raised by 15%. These results quantify the lower bound of the achievable self-consumption in energy communities, which, in the rush towards climate neutrality, and in light of these results, could be considered among the solutions for rationalizing the energy consumption of buildings

On the Effect of the Time Interval Base and Home Appliance on the Renewable Quota of a Building in an Alpine Location

The European goal of decarbonization drives design toward high-performance buildings that maximize the use of renewable sources. Therefore, the European RED II Directive and Italian law raise the minimum renewable share required for new buildings and major renovations. Currently, the renewable energy ratio (RER) is used for the mandatory verification, obtained with a quasi-steady state calculation on a monthly basis, while much of the scientific literature uses self-consumption factor (SCF) and load coverage factor (LCF) often calculated through dynamic simulation. However, the use of a monthly balance implies the use of the national grid as a virtual battery through the net metering mechanism. The actual share of renewable coverage in the absence of expensive electric storage will necessarily be lower. The link between the different indices, the effect of the time base used in the calculation as well as the actual renewable share achieved by buildings, considering also plug loads not in the regulatory verification framework, are still open issues. This work analyzes the actual renewable share achievable for a new building in a heating-dominated climate, i.e., the mountainous area of the municipality of Trento. The renewable share is evaluated through a coupled dynamic simulation of the building and the energy systems. The results show that the RER decreases by 13% and 15% when switching from monthly to instantaneous balance in the case without and with additional home appliance loads, respectively. Similarly, simulations show how the time interval base affects the difference between the RER index and the LCF of PV energy

Dall'archivio : rimontaggi radicali

Il volume raccoglie una serie di rimontaggi radicali costruiti con materiali tratti dall\u2019archivio del Centre Pompidou. Progetti di monografie, mostre e riviste rimettono in valore il ruolo dell\u2019autore, racconti per immagini definiscono nuove antropometrie urbane. L\u2019oggetto di questi esercizi, costruiti con strumenti differenti, \ue8 il design radicale: le esperienze degli autori degli anni Sessanta e Settanta del Novecento sono rilette e ricomposte in discorsi sull\u2019architettura e sulla citt\ue0 del nuovo millennio

JAK inhibitors for the treatment of VEXAS syndrome

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a novel described autoinflammatory entity for which the diagnosis is defined by somatic mutations of the UBA1 X-linked gene in hematopoietic progenitor cells. The clinical manifestations are heterogeneous since they range from autoinflammatory symptoms to the presence of underlying hematologic disorders such as myelodysplastic syndromes. Response to treatment in VEXAS is very poor and to date, the therapeutic strategies adopted are only partially effective. However, recently described cohorts of subjects with VEXAS treated with Janus kinase inhibitors (JAK-I) proved that these drugs can be effective in the treatment of several manifestations related to the disease. Herein, we carried out a brief literature review that includes cohorts and single cases in which JAK-I were adopted as a promising strategy to manage VEXAS patients. Subsequently, we described our experience with JAK-I in VEXAS, illustrating the first case, to our knowledge, of a 65-year-old man who was successfully treated with the selective JAK-1 inhibitor filgotini