Cause for Concern: Nurses’ Reports of Hospital Care in Five Countries

According to most experts, the U.S. faces a growing shortage of registered nurses, threatening the quality of care hospitals can provide. In the setting of nurse shortages and simultaneous concern about patient safety, nurses’ job satisfaction and their assessment of quality of care become critical. This Issue Brief highlights a crossnational survey that describes nurses’ perceptions of their hospital work environment, and identifies core problems in work design and workforce management in five countries

Impact and amelioration of sediment pollution on coral reefs of St. Lucia, West Indies

Includes Policy and Management Brief 1: Annex A2.# Appendix 1 of the Final Technical Report of project R766

Using Mendelian randomisation to identify opportunities for type 2 diabetes prevention by repurposing medications used for lipid management

Background: Maintaining a healthy lifestyle to reduce type 2 diabetes (T2D) risk is challenging and additional strategies for T2D prevention are needed. We evaluated several lipid control medications as potential therapeutic options for T2D prevention using tissue-specific predicted gene expression summary statistics in a two-sample Mendelian randomisation (MR) design. Methods: Large-scale European genome-wide summary statistics for lipids and T2D were leveraged in our multi-stage analysis to estimate changes in either lipid levels or T2D risk driven by tissue-specific predicted gene expression. We incorporated tissue-specific predicted gene expression summary statistics to proxy therapeutic effects of three lipid control medications [i.e., statins, icosapent ethyl (IPE), and proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK-9i)] on T2D susceptibility using two-sample Mendelian randomisation (MR). Findings: IPE, as proxied via increased FADS1 expression, was predicted to lower triglycerides and was associated with a 53% reduced risk of T2D. Statins and PCSK-9i, as proxied by reduced HMGCR and PCSK9 expression, respectively, were predicted to lower LDL-C levels but were not associated with T2D susceptibility. Interpretation: Triglyceride lowering via IPE may reduce the risk of developing T2D in populations of European ancestry. However, experimental validation using animal models is needed to substantiate our results and to motivate randomized control trials (RCTs) for IPE as putative treatment for T2D prevention. Funding: Only summary statistics were used in this analysis. Funding information is detailed under Acknowledgments. © 2022Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A study protocol for a randomised controlled feasibility trial of an intervention to increase activity and reduce sedentary behaviour in people with severe mental illness: Walking fOR Health (WORtH) Study

Abstract Background People with severe mental illness (SMI) are less physically active and more sedentary than healthy controls, contributing to poorer physical health outcomes in this population. There is a need to understand the feasibility and acceptability, and explore the effective components, of health behaviour change interventions targeting physical activity and sedentary behaviour in this population in rural and semi-rural settings. Methods This 13-week randomised controlled feasibility trial compares the Walking fOR Health (WORtH) multi-component behaviour change intervention, which includes education, goal-setting and self-monitoring, with a one-off education session. It aims to recruit 60 inactive adults with SMI via three community mental health teams in Ireland and Northern Ireland. Primary outcomes are related to feasibility and acceptability, including recruitment, retention and adherence rates, adverse events and qualitative feedback from participants and clinicians. Secondary outcome measures include self-reported and accelerometer-measured physical activity and sedentary behaviour, anthropometry measures, physical function and mental wellbeing. A mixed-methods process evaluation will be undertaken. This study protocol outlines changes to the study in response to the COVID-19 pandemic. Discussion This study will address the challenges and implications of remote delivery of the WORtH intervention due to the COVID-19 pandemic and inform the design of a future definitive randomised controlled trial if it is shown to be feasible. Trial registration The trial was registered on clinicaltrials.gov ( NCT04134871 ) on 22 October 2019

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Investigation of sphingosine kinase 1 in interferon responses during dengue virus infection

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1−/− pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and −7 in SK1−/− pMEF. Direct IFN stimulation induced ISGs (viperin, IFIT1), CXCL10, IRF1 and −7 and p-STAT1. Responses, however, were significantly reduced in SK1−/− pMEF, except for IFN-stimulated CXCL10 and IRF7. Poor IFN responses in SK1−/− pMEF were associated with a small reduction in basal cell-surface IFNAR1 and IRF1 mRNA in uninfected SK1−/− compared with WT pMEF. In contrast, treatment of cells with the SK1 inhibitor, SK1-I or expression of an inhibitory SK1 short hairpin RNA (shRNA), both of which reduce DENV infection, does not alter basal IRF1 mRNA or affect type I IFN stimulation of p-STAT1. Thus, cells genetically lacking SK1 can induce many responses normally following DENV infection, but have adaptive changes in IFNAR1 and IRF1 that compromise DENV-induced type I IFN responses. This suggests a biological link between SK1 and IFN-stimulated pathways. Other approaches to reduce SK1 activity, however, do not influence these important antiviral pathways but reduce infection and may be useful antiviral strategies

Butyrylated starch is less susceptible to enzymic hydrolysis and increases large-bowel butyrate more than high-amylose maize starch in the rat

Large-bowel fermentation of resistant starch produces SCFA that are believed to be important in maintaining visceral function. High-amylose maize starch (HAMS) and acylated starches are sources of resistant starch and are an effective means of increasing colonic SCFA. Cooking increases digestibility of starches but its effects on the capacity of these starches to raise large-bowel SCFA are unknown. We have examined the effects of cooking of HAMS and butyrylated HAMS (HAMSB) on amylolysis in vitro and their capacity to raise caeco-colonic SCFA in rats. The starches were boiled in excess water and microwaved, followed by drying at 100°C. Cooking increased in vitro glucose release for both starches but significantly less from HAMSB. Rat growth rates were unaffected when fed cooked resistant starch. Digesta pH was increased in the caecum and proximal colon of rats fed cooked HAMS. Distal colonic pH was highest in rats fed cooked HAMSB. Factorial analyses (2×2) of caecal SCFA pools showed significant differences between HAMS and HAMSB, and that cooking significantly lowered caecal butyrate pools. Portal venous butyrate concentrations were higher in both HAMSB groups than those fed HAMS. The data suggest that HAMSB is less susceptible to in vitro amylolysis than HAMS following cooking and delivers more butyrate to rat caecum than HAMS. This attribute may be useful in food applications for specific delivery of SCFA to the colon. Preparation of carbohydrates to simulate human food in animal experiments may be important to assess nutritional and physiological effects accurately.Balázs H. Bajka, David L. Topping, Lynne Cobiac and Julie M. Clark

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

Sample size assessments for thermal physiology studies: An R package and R Shiny application

Required sample sizes for a study need to be carefully assessed to account for logistics, cost, ethics and statistical rigour. For example, many studies have shown that methodological variations can impact the critical thermal limits (CTLs) recorded for a species, although studies on the impact of sample size on these measures are lacking. Here, we present ThermalSampleR; an R CRAN package and Shiny application that can assist researchers in determining when adequate sample sizes have been reached for their data. The method is particularly useful because it is not taxon specific. The Shiny application offers a user‐friendly interface equivalent to the package for users not familiar with R programming. ThermalSampleR is accompanied by an in‐built example dataset, which we use to guide the user through the workflow with a fully worked tutorial.Funder: National Research Foundation; doi: http://dx.doi.org/10.13039/501100001321 Funder: South African Research Chairs Initiative of the Department of Science and Technology Funder: Working for Water (WfW) programme of the Department of Environmental Affairs: Natural Resource Management programme (DEA: NRM