Direct application of plasmid DNA containing type I interferon transgenes to vaginal mucosa inhibits HSV-2 mediated mortality

The application of naked DNA containing type I interferon (IFN) transgenes is a promising potential therapeutic approach for controlling chronic viral infections. Herein, we detail the application of this approach that has been extensively used to restrain ocular HSV-1 infection, for antagonizing vaginal HSV-2 infection. We show that application of IFN-α1, -α5, and –β transgenes to vaginal mouse lumen 24 hours prior to HSV-2 infection reduces HSV-2 mediated mortality by 2.5 to 3-fold. However, other type I IFN transgenes (IFN- α4, -α5, -α6, and –α9) are non effectual against HSV-2. We further show that the efficacy of IFN-α1 transgene treatment is independent of CD4+ T lymphocytes. However, in mice depleted of CD8+ T lymphocytes, the ability of IFN-α1 transgene treatment to antagonize HSV-2 was lost

Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

Rift Valley fever virus is transmitted mainly by mosquitoes and causes disease in humans and animals throughout Africa and the Arabian Peninsula. The impact of disease is large in terms of human illness and mortality, and economic impact on the livestock industry. For these reasons, and because there is a risk of this virus spreading to Europe and North America, it is important to develop a vaccine that is stable, safe and effective in preventing infection. Potential vaccine viruses have been developed through deletion of two genes (NSs and NSm) affecting virus virulence. Because this virus is normally transmitted by mosquitoes we must determine the effects of the deletions in these vaccine viruses on their ability to infect and be transmitted by mosquitoes. An optimal vaccine virus would not infect or be transmitted. The viruses were tested in two mosquito species: Aedes aegypti and Culex quinquefasciatus. Deletion of the NSm gene reduced infection of Ae. aegypti mosquitoes indicating a role for the NSm protein in mosquito infection. The virus with deletion of both NSs and NSm genes was the best vaccine candidate since it did not infect Ae. aegypti and showed reduced infection and transmission rates in Cx. quinquefasciatus

Phylogeny in Aid of the Present and Novel Microbial Lineages: Diversity in Bacillus

Bacillus represents microbes of high economic, medical and biodefense importance. Bacillus strain identification based on 16S rRNA sequence analyses is invariably limited to species level. Secondly, certain discrepancies exist in the segregation of Bacillus subtilis strains. In the RDP/NCBI databases, out of a total of 2611 individual 16S rDNA sequences belonging to the 175 different species of the genus Bacillus, only 1586 have been identified up to species level. 16S rRNA sequences of Bacillus anthracis (153 strains), B. cereus (211 strains), B. thuringiensis (108 strains), B. subtilis (271 strains), B. licheniformis (131 strains), B. pumilus (83 strains), B. megaterium (47 strains), B. sphaericus (42 strains), B. clausii (39 strains) and B. halodurans (36 strains) were considered for generating species-specific framework and probes as tools for their rapid identification. Phylogenetic segregation of 1121, 16S rDNA sequences of 10 different Bacillus species in to 89 clusters enabled us to develop a phylogenetic frame work of 34 representative sequences. Using this phylogenetic framework, 305 out of 1025, 16S rDNA sequences presently classified as Bacillus sp. could be identified up to species level. This identification was supported by 20 to 30 nucleotides long signature sequences and in silico restriction enzyme analysis specific to the 10 Bacillus species. This integrated approach resulted in identifying around 30% of Bacillus sp. up to species level and revealed that B. subtilis strains can be segregated into two phylogenetically distinct groups, such that one of them may be renamed

Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology

Research question: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? Design: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. Results: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways – increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient–provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. Conclusions: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.</p

Older adults’ home- and community-based care service use and residential transitions: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>As Home-and Community-Based Services (HCBS), such as skilled nursing services or personal care services, have become increasingly available, it has become clear that older adults transit through different residential statuses over time. Older adults may transit through different residential statuses as the various services meet their needs. The purpose of this exploratory study was to better understand the interplay between community-dwelling older adults’ use of home- and community-based services and their residential transitions.</p> <p>Methods</p> <p>The study compared HCBS service-use patterns and residential transitions of 3,085 older adults from the Second Longitudinal Study of Aging. Based on older adults’ residential status at the three follow-up interviews, four residential transitions were tracked: (1) Community-Community-Community (CCC: Resided in community during the entire study period); (2) Community-Institution-Community (CIC: Resided in community at T1, had lived in an institution at some time between T1 and T2, then had returned to community by T3); (3) Community-Community-Institution (CCI: Resided in community between at T1, and betweenT1 and T2, including at T2, but had used institutional services between T2 and T3); (4) Community-Institution-Institution (CII: Resided in community at T1 but in an institution at some time between T1 and T2, and at some time between T2 and T3.).</p> <p>Results</p> <p>Older adults’ use of nondiscretionary and discretionary services differed significantly among the four groups, and the patterns of HCBS use among these groups were also different. Older adults’ use of nondiscretionary services, such as skilled nursing care, may help them to return to communities from institutions. Personal care services (PCS) and senior center services may be the key to either support elders to stay in communities longer or help elders to return to their communities from institutions. Different combinations of PCS with other services, such as senior center services or meal services, were associated with different directions in residential transition, such as CIC and CII respectively.</p> <p>Conclusions</p> <p>Older adults’ differing HCBS use patterns may be the key to explaining older adults’ transitions. Attention to older adults’ HCBS use patterns is recommended for future practice. However, this was an exploratory study and the analyses cannot establish causal relationships.</p