Project description:BackgroundTuberculosis (TB) is a poverty-related disease that is associated with poor living conditions. We studied TB mortality and living conditions in Bern between 1856 and 1950.MethodsWe analysed cause-specific mortality based on mortality registers certified by autopsies, and public health reports 1856 to 1950 from the city council of Bern.ResultsTB mortality was higher in the Black Quarter (550 per 100,000) and in the city centre (327 per 100,000), compared to the outskirts (209 per 100,000 in 1911-1915). TB mortality correlated positively with the number of persons per room (r = 0.69, p = 0.026), the percentage of rooms without sunlight (r = 0.72, p = 0.020), and negatively with the number of windows per apartment (r = -0.79, p = 0.007). TB mortality decreased 10-fold from 330 per 100,000 in 1856 to 33 per 100,000 in 1950, as housing conditions improved, indoor crowding decreased, and open-air schools, sanatoria, systematic tuberculin skin testing of school children and chest radiography screening were introduced.ConclusionsImproved living conditions and public health measures may have contributed to the massive decline of the TB epidemic in the city of Bern even before effective antibiotic treatment became finally available in the 1950s.
Project description:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
Project description:We used stable isotope labelling of amino acids in cell culture coupled with high throughput quantitative mass spectrometry to analyse the protein composition of highly purified wild type adenoviruses, mutant adenoviruses lacking an internal protein component (protein V) and recombinant adenoviruses of the type commonly used in gene therapy including one virus which had been used in a clinical trail. We found that the viral protein abundance and composition was consistent across all types of virus examined except for the virus lacking protein V which also had reduced amounts of another viral core protein, protein VII. In all the samples analysed we found no evidence of consistent packaging or contamination with cellular proteins. We believe this technique makes a powerful method to analyse the protein composition of this important gene therapy vector and genetically engineered or synthetic virus like particles.
Project description:BACKGROUND: Conditionally replicative adenoviruses (CRAds) preferentially infect and lyse tumor cells. While CRAds have been clinically applied, their potential for neurofibromatosis type-1 associated malignant peripheral nerve sheath tumors (MPNSTs) remains unexplored. This study evaluates Cyclooxygenase 2 (COX2)-driven CRAds as a therapy for MPNST. METHODS: Viruses with wild type (WT) and modified fiber-knob domains were assessed for binding efficiency to the MPNST models. Viral infectivity, spread, and susceptibility of MPNST cells to oncolytic adenoviruses were assessed using both WT viruses or engineered CRAd constructs, with cell viability quantification. Tumor growth rates and survival probability of mice bearing human tumor xenografts or syngeneic allografts were assessed using intratumoral injections of CRAds. RESULTS: RGD-modified fibers exhibited improved binding to MPNST cells compared to non-cancer Schwann cells. vectors effectively replicated and lysed MPNST cells, displaying enhanced selectivity towards transformed cells. Tumor-bearing immunodeficient mice survived significantly longer when injected with CRAds compared to PBS controls, and immunocompetent models demonstrate robust infiltration of CD8+ T-cells. CONCLUSIONS: CRAds demonstrate selective binding and efficient replication in MPNST cells, leading to tumor cell lysis while sparing non-cancerous cells. These results suggest that oncolytic adenoviruses may have the potential as novel agents for MPNST therapy and thus warrant further investigation.
