The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

Background. One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results. The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions. We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used. © 2011 Tanzer et al; licensee BioMed Central Ltd

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Increases in Ambulance Call Volume Are an Early Warning Sign of Major COVID-19 Surges in Children

Background: Infectious diseases, including COVID-19, have a severe impact on child health globally. We investigated whether emergency medical service (EMS) calls are a bellwether for future COVID-19 caseloads. We elaborated on geographical hotspots and socioeconomic risk factors. Methods: All EMS calls for suspected infectious disease in the pediatric population (under 18 years of age) in Rhode Island between 1 March 2018 and 28 February 2022 were included in this quasi-experimental ecological study. The first of March 2020 was the beginning of the COVID-19 pandemic. We used the 2020 census tract and the most recent COVID-19 data. We investigated associations between pediatric EMS calls and positive COVID-19 tests with time series analysis and identified geographical clusters using local indicators of spatial association. Economic risk factors were examined using Poisson regression. Results: We included 980 pediatric ambulance calls. Calls during the omicron wave were significantly associated with increases in positive COVID-19 tests one week later (p < 0.001). Lower median household income (IRR 0.99, 95% CI [0.99, 0.99]; p < 0.001) and a higher child poverty rate (IRR 1.02, 95% CI [1.02, 1.02]; p < 0.001) were associated with increased EMS calls. Neighborhood hotspots changed over time. Conclusion: Ambulance calls might be a predictor for major surges of COVID-19 in children

Health Care and Public Service Use and Costs Before and After Provision of Housing for Chronically Homeless Persons With Severe Alcohol Problems

Context: Chronically homeless individuals with severe alcohol problems often have multiple medical and psychiatric problems and use costly health and criminal justice services at high rates.Objective: To evaluate association of a ?Housing First? intervention for chronically homeless individuals with severe alcohol problems with health care use and costs.Design, Setting, and Participants: Quasi-experimental design comparing 95 housed participants (with drinking permitted) with 39 wait-list control participants enrolled between November 2005 and March 2007 in Seattle, Washington.Main Outcome Measures: Use and cost of services (jail bookings, days incarcerated, shelter and sobering center use, hospital-based medical services, publicly funded alcohol and drug detoxification and treatment, emergency medical services, and Medicaid-funded services) for Housing First participants relative to wait-list controls.Results: Housing First participants had total costs of $8 175 922 in the year prior to the study, or median costs of$4066 per person per month (interquartile range [IQR], $2067-$8264). Median monthly costs decreased to $1492 (IQR,$337-$5709) and$958 (IQR, $98-$3200) after 6 and 12 months in housing, respectively. Poisson generalized estimating equation regressions using propensity score adjustments showed total cost rate reduction of 53% for housed participants relative to wait-list controls (rate ratio, 0.47; 95% confidence interval, 0.25-0.88) over the first 6 months. Total cost offsets for Housing First participants relative to controls averaged $2449 per person per month after accounting for housing program costs.Conclusions: In this population of chronically homeless individuals with high service use and costs, a Housing First program was associated with a relative decrease in costs after 6 months. These benefits increased to the extent that participants were retained in housing longer.Concerns about high public system costs incurred by chronically homeless individuals have inspired nationwide efforts to eliminate chronic homelessness. Homeless people have high barriers to health care access generally but use acute care services at high rates. Mortality rates among homeless adults are 3 or more times that of the general population.Chronically homeless people with severe alcohol problems, sometimes referred to as chronic public inebriates, are highly visible on the streets and are costly to the public through high use of publicly funded health and criminal justice systems resources. Typical interventions such as shelters, abstinence-based housing, and treatment programs fail to reverse these patterns for this population. Health conditions and mortality rates within this population are similar to those found in developing countries. Average age at death is estimated to be 42 to 52 years, with 30% to 70% of deaths related to alcohol.The provision of housing reduces hospital visits, admissions, and duration of hospital stays among homeless individuals, and overall public system spending is reduced by nearly as much as is spent on housing. One type of supportive housing, called Housing First, removes the requirements for sobriety, treatment attendance, and other barriers to housing entrance. Thus far, Housing First (HF) approaches have primarily targeted homeless people with serious mental illnesses and co-occurring substance use disorders.An HF program in Seattle?known as 1811 Eastlake?targets homeless adults with severe alcohol problems who use local crisis services at the highest levels. The project has been controversial because residents are allowed to drink in their rooms. The current study evaluated outcomes of the project on public use and costs for housed participants compared with wait-list controls and secondarily evaluated changes in reported alcohol use for housed participants and the effects of housing duration on service use