Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15)

Respiratory syncytial virus (RSV) is a major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. Factors attributing to this problem are associated with an incomplete understanding of the mechanisms by which RSV modulates the host cell response to infection. In the present study, we investigate suppressor of cytokine signaling (SOCS)-1 and SOCS3 expression associated with the type I IFN and IFN-stimulated gene (ISG)-15 response following infection of mouse lung epithelial (MLE-15) cells with RSV or RSV mutant viruses lacking the G gene, or NS1 and NS2 gene deletions. Studies in MLE-15 cells are important as this cell line represents the distal bronchiolar and alveolar epithelium of mice, the most common animal model used to evaluate the host cell response to RSV infection, and exhibit morphologic characteristics of alveolar type II cells, a primary cell type targeted during RSV infection. These results show an important role for SOCS1 regulation of the antiviral host response to RSV infection, and demonstrate a novel role for RSV G protein manipulation of SOCS3 and modulation of ISG15 and IFNβ mRNA expression

Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15)

Respiratory syncytial virus (RSV) is a major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. Factors attributing to this problem are associated with an incomplete understanding of the mechanisms by which RSV modulates the host cell response to infection. In the present study, we investigate suppressor of cytokine signaling (SOCS)-1 and SOCS3 expression associated with the type I IFN and IFN-stimulated gene (ISG)-15 response following infection of mouse lung epithelial (MLE-15) cells with RSV or RSV mutant viruses lacking the G gene, or NS1 and NS2 gene deletions. Studies in MLE-15 cells are important as this cell line represents the distal bronchiolar and alveolar epithelium of mice, the most common animal model used to evaluate the host cell response to RSV infection, and exhibit morphologic characteristics of alveolar type II cells, a primary cell type targeted during RSV infection. These results show an important role for SOCS1 regulation of the antiviral host response to RSV infection, and demonstrate a novel role for RSV G protein manipulation of SOCS3 and modulation of ISG15 and IFNβ mRNA expression

Impact of obesity on acyclovir-induced nephrotoxicity

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Triamcinolone acetonide (TA), an intermediate acting corticosteroid, is used in the treatment of posterior ocular diseases, such as inflammation, posterior uveitis, and diabetic macular edema. The objective of this investigation was to prepare TA-loaded solid lipid nanoparticles (TA-SLNs) and in situ gel (TA-SLN-IG) formulations for delivery into the deeper ocular tissues through the topical route. TA-SLNs were prepared by hot homogenization and ultrasonication method using glyceryl monostearate and Compritol® 888ATO as solid lipids and Tween®80 and Pluronic® F-68 as surfactants. TA-SLNs were optimized and converted to TA-SLN-IG by the inclusion of gellan gum and evaluated for their rheological properties.In vitro transcorneal permeability and in vivo ocular distribution of the TA-SLNs and TA-SLN-IG were studied using isolated rabbit corneas and New Zealand albino rabbits, respectively, and compared with TA suspension, used as control (TA-C). Particle size, PDI, zeta potential, assay, and entrapment efficiency of TA-SLNs were in the range of 200–350 nm, 0.3–0.45, −52.31 to −64.35 mV, 70–98%, and 97–99%, respectively. TA-SLN-IG with 0.3% gellan gum exhibited better rheological properties. The transcorneal permeability of TA-SLN and TA-SLN-IG was 10.2 and 9.3-folds higher compared to TA-C. TA-SLN-IG showed maximum tear concentration at 2 h, indicating an improved pre-corneal residence time, as well as higher concentrations in aqueous humor, vitreous humor and cornea at 6 h, suggesting sustained delivery of the drug into the anterior and posterior segment ocular tissues, when compared to TA-SLN and TA-C. The results, therefore, demonstrate that the lipid based nanoparticulate system combined with the in situ gelling agents can be a promising drug delivery platform for the deeper ocular tissues

Fluoroquinolone versus nonfluoroquinolone treatment of bloodstream infections caused by chromosomally mediated ampc‐producing enterobacteriaceae

Objectives: Chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) display high susceptibility to fluoroquinolones; minimal clinical data exist supporting comparative clinical outcomes. The objective of this study was to compare treatment outcomes between fluoroquinolone and nonfluoroquinolone definitive therapy of bloodstream infections caused by CAE. Methods: This retrospective cohort assessed adult patients with positive blood cultures for CAE that received inpatient treatment for 48 hours. The primary outcome was difference in clinical failure between patients who received fluoroquinolone (FQ) versus non‐FQ treatment. Secondary endpoints included microbiological cure, infection‐related length of stay, 90‐day readmission, and all‐cause inpatient mortality. Results: 56 patients were included in the study (31 (55%) received a FQ as definitive therapy; 25 (45%) received non‐FQ). All non‐FQ patients received a beta‐lactam (BL). Clinical failure occurred in 10 (18%) patients, with 4 (13%) in the FQ group and 6 (24%) in the BL group (p = 0.315). Microbiological cure occurred in 55 (98%) patients. Median infection‐related length of stay was 10 (6–20) days, with a significantly longer stay occurring in the BL group (p = 0.002). There was no statistical difference in 90‐day readmissions between groups (7% FQ vs. 17% BL; p = 0.387); one patient expired. Conclusion: These results suggest that fluoroquinolones do not adversely impact clinical outcomes in patients with CAE. When alternatives to beta‐lactam therapy are needed, fluoroquinolones may provide an effective option

Does What Goes up Also Come Down? Using a Recruitment Model to Balance Alewife Nutrient Import and Export

Migrating adult Alewives Alosa pseudoharengus are a source of marine-derived nutrients on the East Coast of North America, importing nitrogen and phosphorus into freshwater habitats. Juvenile migrants subsequently transport freshwater-derived nutrients into the ocean. We developed a deterministic model to explore the theoretical nutrient dynamics of Alewife migrations at differing spawner abundances. Net nutrient balance was calculated relative to these abundances along the spawner–recruit curve. The ecological consequences of these subsidies in a particular watershed depend on the magnitude of adult escapement relative to the habitat\u27s carrying capacity for juveniles. At low escapement levels and assuming complete habitat access, the number of recruits produced per spawner was high and juvenile nutrient export dominated. At high escapement levels, fewer recruits were produced per spawner because recruitment is density dependent. As a result, adult nutrient import dominated. At varying levels of freshwater productivity and fisheries mortality for upstream spawners, this trend remained the same while the magnitude of the endpoints changed. Productivity level was the major determinant of export, while fisheries mortality had the strongest effect on adult import. The dynamics of this nutrient trade-off are important for managers to consider as a recovering population will likely shift from net export to net import as escapement increases. This transition will be sensitive to both harvest rates and to fish passage efficacy at dams and other barriers

Black-White Differences in Pregnancy Desire During the Transition to Adulthood

This article explores race differences in the desire to avoid pregnancy or become pregnant using survey data from a random sample of 914 young women (ages 18-22) living in a Michigan county and semi-structured interviews with a subsample of 60 of the women. In the survey data, desire for pregnancy, indifference, and ambivalence are very rare but are more prevalent among Black women than White women. In the semi-structured interviews, although few women described fatalistic beliefs or lack of planning for future pregnancies, Black and White women did so equally often. Women more often described fatalistic beliefs and lack of planning when retrospectively describing their past than when prospectively describing their future. Using the survey data to compare prospective desires for a future pregnancy with women\u27s recollections of those desires after they conceived, more Black women shifted positive than shifted negative, and Black women were more likely to shift positive than White women-that is, Black women do not differentially retrospectively overreport prospectively desired pregnancies as having been undesired before conception. Young women\u27s consistent (over repeated interviews) prospective expression of strong desire to avoid pregnancy and correspondingly weak desire for pregnancy, along with the similarity of Black and White women\u27s pregnancy plans, lead us to conclude that a planning paradigm -in which young women are encouraged and supported in implementing their pregnancy desires-is probably appropriate for the vast majority of young women and, most importantly, is similarly appropriate for Black and White young women

Impact of Obesity in Patients with Candida Bloodstream Infections: A Retrospective Cohort Study

© 2020, The Author(s). Background: Candida species are responsible for 15% of bloodstream infections, leading to prolonged hospitalizations and increased mortality. With the rise in obesity, antifungal dosing is unclear. The purpose of this study was to determine differences in clinical outcomes between obese versus non-obese patients with Candida bloodstream infections. Methods: This retrospective cohort included adult patient’s first episode of Candida bloodstream infection treated with ≥ 48 h of antifungal therapy between 1 June 2013 and 31 August 2019. Patients were excluded for: dual systemic antifungal therapy, polymicrobial infections, or chronic candidiasis. The primary outcome was infection-related length of stay. Secondary outcomes included: time to candidemia resolution, 30-day readmission rates, and in-hospital mortality. Results: Eighty patients were included (28 obese; 52 non-obese). Most were male (55%); median age was 54 years. Median BMI and weight were 36.3 kg/m2 and 103 kg versus 20.4 kg/m2 and 61 kg, respectively (p \u3c 0.01). Baseline characteristics were comparable. C. albicans was isolated in 37.5% of cultures and C. glabrata in 30%. Micafungin was utilized empirically in 72.5% of patients; obese patients received definitive micafungin more frequently (57.1% vs. 21.2%; p \u3c 0.01) and were treated longer (13 versus 10 days; p = 0.04). Infection-related length of stay was 19 days in the obese patients and 13 days in the non-obese patients (p = 0.05). Non-obese patients had a shorter duration of candidemia (5 versus 6 days; p = 0.02). In-hospital mortality was numerically higher in obese patients (21.4% versus 13.5%; p = 0.36). There were no differences in 30-day readmissions between groups. Conclusions: Worse clinical outcomes were observed for obese versus non-obese patients. Further clinical research is warranted

Perinatal Bisphenol A Exposure in C57B6/129svj Male Mice: Potential Altered Cytokine/Chemokine Production in Adulthood

Pregnant mice (n = 3) were exposed to BPA by intraperitoneal injection, from gestation day 9.5 until end of lactation. Male offspring were evaluated for cytokine production at 20 wk-of-age. One pregnant control mouse produced no males, precluding statistical analysis. However, recurring shifts in cytokines were suggested in the adult BPA offspring. Serum showed a numeric increase in 16 of 21 basal cytokine levels. ConA-stimulated splenocytes showed a numeric increase in 17 of 21 cytokines, and LPS-stimulated splenocytes an increase in 18 of 21 cytokines. The cytokine profile was one of TH1 up-regulation more than TH2, and with skewing toward TH17 responses

Pastoral power in the community pharmacy: a Foucauldian analysis of services to promote patient adherence to new medicine use

Community pharmacists play a growing role in the delivery of primary healthcare. This has led manyto consider the changing power of the pharmacy profession in relation to other professions and patient groups. This paper contributes to these debates through developing a Foucauldian analysis of the changing dynamics of power brought about by extended roles in medicines management and patient education. Examining the New Medicine Service, the study considers how both patient and pharmacist subjectivities are transformed as pharmacists seek to survey patient’s medicine use, diagnose non-adherence to prescribed medicines, and provide education to promote behaviour change. These extended roles in medicines management and patient education expand the ‘pharmacy gaze’ to further aspects of patient health and lifestyle, and more significantly, established a form of ‘pastoral power’ as pharmacists become responsible for shaping patients’ self-regulating subjectivities. In concert, pharmacists are themselves enrolled within a new governing regime where their identities are conditioned by corporate and policy rationalities for the modernisation of primary care

New ways for our families : Designing an Aboriginal and Torres Strait Islander cultural practice framework and system responses to address the impacts of domestic and family violence on children and young people

Little has been done to understand what works to support First Nations children and young people to heal from their experiences of violence. This research project explores how services and systems can better respond to the needs of Aboriginal and Torres Strait Islander children and young people exposed to DFV who come to the attention of child protection systems. Led by the Queensland Aboriginal and Torres Strait Islander Child Protection Peak (QATSICPP), a team of First Nations researchers, supported by non-Indigenous researchers, utilised a participatory action research methodology – ensuring cultural safety and adherence to cultural values and protocols, including co-creation of knowledge. This report, the first in a series for this project, presents the results of a literature review and the findings from the initial cycles of action research conducted with Aboriginal and Torres Strait Islander chief investigators, community researchers and practitioners working in eight community-controlled child and family services across Queensland. The literature review and the outcomes of the initial action research cycle confirmed that the experience of DFV in childhood is resulting in negative lifelong outcomes for First Nations children, including increased interactions with the child protection and justice systems. The researchers also found that these responses (child protection and justice) are not adequate or culturally safe. To support healing for these children and young people, the report recommends: • holistic healing opportunities • culturally strong and community-led whole-of-family support • therapeutic healing circles and camps • connection to and knowledge about traditional cultural values, systems and traditions • a framework of perpetrator accountability • system changes include procuring place-based and healing responses for Aboriginal and Torres Strait Islander community-controlled services that support self-determination, and working collectively with the whole family. Additionally, cultural capability across the service system needs to be enhanced, and structural racism needs to be eliminated in order to reduce the load on existing Aboriginal and Torres Strait Islander services. Future publications from this research project, due in 2022, will consist of a research report on the remaining action research cycles and a framework for working with Aboriginal and Torres Strait Islander children and young people who have experienced DFV and have also come in contact with the child protection system