Exploring a cardio-thoracic hospital ward soundscape in relation to restoration

Hospitals can provide stressful experiences for both patients and medical staff. A well-designed hospital soundscape should avoid adding to negative emotional states (e.g. stress), limit any detrimental cognitive effects (e.g. attentional fatigue), and enable restoration. Experiences of the cardio-thoracic ward soundscape, in a UK public University hospital, were explored via semi-structured interviews with 11 patients and 16 nurses. Thematic coding analysis resulted in 11 key themes including notions of restoration and emotional responses. The themes were used to develop a conceptual model to describe the processes involved in the perception and evaluation of the soundscape. The language used by patients and nurses indicated the emotional response to the soundscape was at times stressful and at others potentially restorative. Coping methods of accepting and habituating to individual sounds were noted. The impact of the patients' and nurses' ability to maintain these coping strategies are discussed in relation to restoration and the temporal variation of the soundscape. A period of 'quiet time' was in operation at the hospital and the importance of this was noted through various responses relating to emotion and restoration. The results suggest the soundscape has potentially, a beneficial role in facilitating restoration thus helping patients' recovery and medical staff's ability to remain productive. This research supports the need to study hospital soundscapes further so that design implications can be considered for the production of a more restorative environment, possibly through the masking/removal of unwanted sounds and optimising positive sounds

T cell immune memory after covid-19 and vaccination

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. T cell memory after infection with the SARS-CoV-2 virus or vaccination is broad, and spans multiple viral proteins and epitopes, about 20 in each individual. So far the T cell memory response is long lasting and provides a high level of cross reactivity and hence resistance to viral escape by variants of the SARS-CoV-2 virus, such as the omicron variant. All current vaccine regimens tested produce robust T cell memory responses, and heterologous regimens will probably enhance protective responses through increased breadth. T cell memory could have a major role in protecting against severe covid-19 disease through rapid viral clearance and early presentation of epitopes, and the presence of cross reactive T cells might enhance this protection. T cell memory is likely to provide ongoing protection against admission to hospital and death, and the development of a pan-coronovirus vaccine might future proof against new pandemic strains

Sterol Carrier Protein-2 Directly Interacts with Caveolin-1 in Vitro and in Vivo

HDL-mediated reverse-cholesterol transport as well as phosphoinositide signaling are mediated through plasma membrane microdomains termed caveolae/lipid rafts. However, relatively little is known regarding mechanism(s) whereby these lipids traffic to or are targeted to caveolae/lipid rafts. Since sterol carrier protein-2 (SCP-2) binds both cholesterol and phosphatidylinositol, the possibility that SCP-2 might interact with caveolin-1 and caveolae was examined. Double immunolabeling and laser scanning fluorescence microscopy showed that a small but significant portion of SCP-2 colocalized with caveolin-1 primarily at the plasma membrane of L-cells and more so within intracellular punctuate structures in hepatoma cells. In SCP-2 overexpressing L-cells, SCP-2 was detected in close proximity to caveolin, 48 ± 4 Å, as determined by fluorescence resonance energy transfer (FRET) and immunogold electron microscopy. Cell fractionation of SCP-2 overexpressing L-cells and Western blotting detected SCP-2 in purified plasma membranes, especially in caveolae/ lipid rafts as compared to the nonraft fraction. SCP-2 and caveolin-1 were coimmunoprecipitated from cell lysates by anti-caveolin-1 and anti-SCP-2. Finally, a yeast two-hybrid assay demonstrated that SCP-2 directly interacts with caveolin-1 in vivo. These interactions of SCP-2 with caveolin-1 were specific since a functionally related protein, phosphatidyinositol transfer protein (PITP), colocalized much less well with caveolin-1, was not in close proximity to caveolin-1 (i.e., \u3e120 Å), and was not coimmunoprecipitated by anti-caveolin-1 from cell lysates. In summary, it was shown for the first time that SCP-2 (but not PITP) selectively interacted with caveolin-1, both within the cytoplasm and at the plasma membrane. These data contribute significantly to our understanding of the role of SCP-2 in cholesterol and phosphatidylinositol targeted from intracellular sites of synthesis in the endoplasmic reticulum to caveolae/lipid rafts at the cell surface plasma membrane

Reliability and validity of cutaneous sarcoidosis outcome instruments among dermatologists, pulmonologists, and rheumatologists

IMPORTANCE: Dermatologists, pulmonologists, and rheumatologists study and treat patients with sarcoidosis with cutaneous manifestations. The validity of cutaneous sarcoidosis outcome instruments for use across medical specialties remains unknown. OBJECTIVE: To assess the reliability and validity of cutaneous sarcoidosis outcome instruments for use by dermatologists and nondermatologists treating sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study evaluating the use of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) to assess cutaneous sarcoidosis disease severity and the Physician's Global Assessment (PGA) as a reference instrument. Four dermatologists, 3 pulmonologists, and 4 rheumatologists evaluated facial cutaneous sarcoidosis in 13 patients treated at a cutaneous sarcoidosis clinic in a 1-day study on October 24, 2014; data analysis was performed from November through December 2014. MAIN OUTCOMES AND MEASURES: Interrater and intrarater reliability and convergent validity, with correlation with quality-of-life measures as the secondary outcome. RESULTS: All instruments demonstrated excellent intrarater reliability. Interrater reliability (reported as intraclass correlation coefficient [95% CI]) was good for the CSAMI Activity scale (0.69 [0.51-0.87]) and PGA (0.66 [0.47-0.85]), weak for the CSAMI Damage scale (0.26 [0.11-0.52]), and excellent for the modified Facial SASI (0.78 [0.63-0.91]). The CSAMI Activity scale and modified Facial SASI showed moderate correlations (95% CI) with the PGA (0.67 [0.57-0.75] and 0.57 [0.45-0.66], respectively). The CSAMI Activity scale but not the modified Facial SASI showed significant correlations (95% CI) with quality-of-life instruments, such as the Dermatology Life Quality Index (Spearman rank correlation, 0.70 [0.25-0.90]) and the Skin Stigma raw score of the Sarcoidosis Assessment Tool (Pearson product moment correlation, 0.56 [0.01-0.85]). CONCLUSIONS AND RELEVANCE: The CSAMI and SASI were reliable and valid in assessing cutaneous sarcoidosis among our diverse group of specialists. The CSAMI Activity score also correlated with quality-of-life measures and suggested construct validity. These results lend credibility to expand the use of the CSAMI and SASI by dermatologists and nondermatologists in assessing cutaneous sarcoidosis disease activity

Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.

BACKGROUND: One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18). RESULTS: Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. CONCLUSION: None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Effectiveness of a training program for police officers who come into contact with people with mental health problems : A pragmatic randomised controlled trial

INTRODUCTION: Police officers frequently come into contact with individuals with mental health problems. Specialist training in this area for police officers may improve how they respond to individuals with mental health problems; however, evidence to support this is sparse. This study evaluated the effectiveness of one bespoke mental health training package for frontline police officers relative to routine training. DESIGN: Pragmatic, two-armed cluster randomised controlled trial in one police force in England. Police stations in North Yorkshire were randomised with frontline police officers receiving either a bespoke mental health training package or routine training. The primary outcome was the number of incidents which resulted in a police response reported to the North Yorkshire Police control room up to six months after delivery of training. Secondary outcomes included: likelihood of incidents using Section 136 of the Mental Health Act; likelihood of incidents having a mental health tag applied; and number of individuals with a mental health warning marker involved in incidents. The appropriateness of mental health tags applied to a random sample of incidents was checked by an independent mental health professional. Routinely collected data were used. RESULTS: Twelve police stations were recruited and randomised (Intervention group n = 6; Control group n = 6), and 249 officers received the bespoke mental health training intervention. At follow-up, a median of 397 incidents were assigned to trial stations in the intervention group, and 498 in the control group. There was no evidence of a difference in the number of incidents with a police response (adjusted incidence rate ratio (IRR) 0.92, 95% CI 0.61 to 1.38, p = 0.69), or in the number of people with mental health warning markers involved in incidents (adjusted IRR 1.39, 95% CI 0.91 to 2.10, p = 0.13) between the intervention and control groups up to six months following the intervention; however, incidents assigned to stations in the intervention group were more likely to have a mental health tag applied to them than incidents assigned to control stations (adjusted odds ratio 1.41, 95% CI 1.16 to 1.71, p = 0.001). The review of 100 incidents suggests that there may be incidents involving individuals with mental health issues that are not being recorded as such (Kappa coefficient 0.65). There was no statistically significant difference in the likelihood of Section 136 of the Mental Health Act being applied to an incident. CONCLUSIONS: The bespoke one day mental health training delivered to frontline officers by mental health professionals did not reduce the number of incidents reported to the police control room up to six months after its delivery; however training may have a positive effect on how the police record incidents involving individuals with mental health problems. Our trial has shown that conducting pragmatic trials within the police setting is feasible and acceptable. There is a wealth of routinely collected police data that can be utilised for research and further collaboration between police forces and academia is encouraged. TRIAL REGISTRATION: ISRCTN (ISRCTN11685602). The authors confirm that all ongoing and related trials for this drug/intervention are registered

Pacific Ocean–wide profile of CYP1A1 expression, stable carbon and nitrogen isotope ratios, and organic contaminant burden in sperm whale skin biopsies

This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 119 (2011): 337-343, doi:10.1289/ehp.0901809.Background: Ocean pollution affects marine organisms and ecosystems as well as humans. The International Oceanographic Commission recommends ocean health monitoring programs to investigate the presence of marine contaminants and the health of threatened species and the use of multiple and early-warning biomarker approaches. Objective: We explored the hypothesis that biomarker and contaminant analyses in skin biopsies of the threatened sperm whale (Physeter macrocephalus) could reveal geographical trends in exposure on an oceanwide scale. Methods: We analyzed cytochrome P450 1A1 (CYP1A1) expression (by immunohistochemistry), stable nitrogen and carbon isotope ratios (as general indicators of trophic position and latitude, respectively), and contaminant burdens in skin biopsies to explore regional trends in the Pacific Ocean. Results: Biomarker analyses revealed significant regional differences within the Pacific Ocean. CYP1A1 expression was highest in whales from the Galapagos, a United Nations Educational, Scientific, and Cultural Organization World Heritage marine reserve, and was lowest in the sampling sites farthest away from continents. We examined the possible influence of the whales’ sex, diet, or range and other parameters on regional variation in CYP1A1 expression, but data were inconclusive. In general, CYP1A1 expression was not significantly correlated with contaminant burdens in blubber. However, small sample sizes precluded detailed chemical analyses, and power to detect significant associations was limited. Conclusions: Our large-scale monitoring study was successful at identifying regional differences in CYP1A1 expression, providing a baseline for this known biomarker of exposure to aryl hydrocarbon receptor agonists. However, we could not identify factors that explained this variation. Future oceanwide CYP1A1 expression profiles in cetacean skin biopsies are warranted and could reveal whether globally distributed chemicals occur at biochemically relevant concentrations on a global basis, which may provide a measure of ocean integrity.Funding was provided by National Institute of Environmental Health Sciences grant P42-ES-0469, Superfund Basic Research Program grant P42ES007381, NOAA Sea Grant NA86RG0075 R/B-162, and the Ocean Alliance

CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination ("vaccine breakthrough") have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough