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Background: Transfusion‐related acute lung injury (TRALI) is a leading cause of transfusion‐related mortality. A concern with passive surveillance to detect transfusion reactions is underreporting. Our aim was to obtain evidence‐based estimates of TRALI incidence using meta‐analysis of active surveillance studies and to compare these estimates with passive surveillance. Study Design and Methods: We performed a systematic review and meta‐analysis of studies reporting TRALI rates. A search of Medline and Embase by a research librarian identified studies published between January 1, 1991 and January 20, 2023. Prospective and retrospective observational studies reporting TRALI by blood component (red blood cells [RBCs], platelets, or plasma) were identified and all inpatient and outpatient settings were eligible. Adult and pediatric, as well as general and specific clinical populations, were included. Platelets and plasma must have used at least one modern TRALI donor risk mitigation strategy. A random effects model estimated TRALI incidence by blood component for active and passive surveillance studies and heterogeneity was examined using meta‐regression. Results: Eighty studies were included with approximately 176‐million blood components transfused. RBCs had the highest number of studies (n = 66) included, followed by platelets (n = 35) and plasma (n = 34). Pooled TRALI estimates for active surveillance studies were 0.17/10,000 (95% confidence intervals [CI]: 0.03–0.43; I2 = 79%) for RBCs, 0.31/10,000 (95% CI: 0.22–0.42; I2 = <1%) for platelets, and 3.19/10,000 (95% CI: 0.09–10.66; I2 = 86%) for plasma. Studies using passive surveillance ranged from 0.02 to 0.10/10,000 among the various blood components. Discussion: In summary, these estimates may improve a quantitative understanding of TRALI risk, which is important for clinical decision‐making weighing the risks and benefits of transfusion. [ABSTRACT FROM AUTHOR]

Background: The relative safety of bacterial risk control strategies for platelets that include culture with or without rapid testing has been compared using simulation analysis. A wide range of bacterial lag and doubling times were included. However, published data on growth rates are available and these data have not been synthesized. We conducted a systematic review and meta‐analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance Study Design and Methods: Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. Results: In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1–5 h. The revised comparative safety simulation using the narrower 1–5‐h range showed similar rankings to the prior simulation, with 48‐h large‐volume delayed sampling with 7‐day expiration (48C‐7) demonstrating the lowest‐ranking relative performance at the 103 and 105 colony forming unit (CFU)/mL exposure thresholds. Discussion: This was a two‐step study. First, meta‐analysis of published data on aerobic bacterial growth rates in stored platelets showed the vast majority of doubling times were 1–5 h. Next, an updated comparative safety simulation yielded similar results to a prior study, with 48C‐7 showing the least favorable relative safety performance. [ABSTRACT FROM AUTHOR]

Background The protective effect of community water fluoridation (CWF) against dental caries may be modified by secular changes in health behaviour. We aimed to determine the contemporary association between fluoride in public water supplies (PWS) and dental caries indicators and inequalities in England. Methods We estimated exposure to CWF and PWS fluoride concentrations from national monitoring data, using Geographic Information Systems and water supply boundaries, categorizing mean period exposure into <0.1, 0.1–<0.2, 0.2–<0.4, 0.4–<0.7 and ≥0.7 mg/l. We used area-level health outcome and confounder data in multivariable regression models to determine the association between fluoride and caries outcomes and calculated preventive fractions using these coefficients. Results The odds of caries and of severe caries in 5-year-olds fell with increasing fluoride concentration in all SES quintiles (P  < 0.001 to P  = 0.003). There was a negative trend between increasing fluoride concentration and dental extractions (P  < 0.001). Compared to PWS with <0.2 mg/l, CWF prevented 17% (95% confidence interval (CI): 5–27%) to 28% (95% CI: 24–32%) of caries (high-low SES) and 56% (95% CI: 25–74%) of dental extractions. The association between fluoride concentration and caries prevalence/severity varied by socioeconomic status (SES) (P  < 0.001). Conclusions Exposure to fluoride in PWS appears highly protective against dental caries and reduces oral health inequalities. [ABSTRACT FROM AUTHOR]

Background: The purpose of this scoping review was to identify available sources of evidence on the epidemiology of transfusion‐related acute lung injury (TRALI) and whether meta‐analysis on the incidence of TRALI is feasible. TRALI is a serious complication and the second leading cause of death related to blood transfusion. Estimates of the incidence of TRALI would provide a useful benchmark for research to reduce TRALI. Study Design and Methods: We searched the Medline, EMBASE, and PubMed databases for publications related to the incidence of TRALI and hemovigilance. We included all studies irrespective of language or country. Both full‐text articles and conference abstracts were included. Participants of the studies must all have received a blood transfusion. Reviews and case studies were excluded. Results: We identified 427 articles or abstracts to include for review. More than half were abstracts, and the majority were published after 2010. Reported TRALI definitions varied, but only 27.2% of studies reported any definition for TRALI. TRALI rates were reported using different denominators, such as per blood unit (54.1%), patient (34.4%), and transfusion episode (14.8%). Study populations and contexts were mostly general (75.6% and 80.3%, respectively). There was also variation in study design with most being observational (90.6%) and only 13.1% of all studies used modern donor restriction policies. Discussion: There was substantial variation in reporting in studies on TRALI incidence. Meta‐analysis of TRALI rates may be feasible in specific circumstances where reporting is clear. Future studies should clearly report key items, such as a TRALI definition. [ABSTRACT FROM AUTHOR]

Background: Non‐pathogen reduction platelet bacterial risk control strategies in the US FDA guidance include at least one culture. Almost all of these strategies have a culture hold time of ≥12 h. Studies have reported time to detection (TTD) of bacterial cultures inoculated with bacteria from contaminated platelets, but these data and estimates of risk associated with detection failures have not been synthesized. Methods: We performed a literature search to identify studies reporting TTD for samples obtained from spiked platelet components. Using extracted data, regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components are transfused to a patient. We then used published data on time of transfusion (ToT) to estimate the risk of detection failures in practice. Results: The search identified 1427 studies, of which 16 were included for analysis. TTD data were available for 16 different organisms, including 14 in aerobic cultures and 11 in anaerobic cultures. For inocula of 1 colony forming unit (CFU), the average TTD for aerobic organisms was 19.2 h while it was 24.9 h in anaerobic organisms, but there was substantial overall variation. A hold time of 12 versus 24 h had minimal effect for most organisms. Conclusion: TTD variation occurs between bacterial species and within a particular species. Under typical inventory management, the relative contribution of culture detection failures is much smaller than the residual risk from sampling failures. Increasing the hold period beyond 12 h has limited value. [ABSTRACT FROM AUTHOR]

Comamonas spp. are non-fermenting Gram-negative bacilli. They were first discovered in 1894, and since then, twenty-four species have been characterized. The natural habitat of these bacteria is soil, wastewater/sludge, fresh water such as ponds and rivers, and the animal intestinal microbiome. They were also isolated from industrial settings, such as activated sludge and polluted soil, and from the hospital environment and clinical samples, such as urine, pus, blood, feces, and kidney. Comamonas spp. are associated with environmental bioremediation and are considered an important environmental bacterium rather than a human pathogen. However, in the 1980s, they became a concern when several human infections associated with these species were reported. Here, the Comamonas genus was examined in terms of its members, identification techniques, and pathogenicity. Seventy-seven infection cases associated with these microorganisms that have been discussed in the literature were identified and investigated in this project. All relevant information regarding year of infection, country of origin, patient information such as age, sex, underlying medical conditions if any, type of infection caused by the Comamonas species, antibiotic susceptibility testing, treatment, and outcomes for the patient were extracted from case reports. The findings suggest that even though Comamonas spp. are thought of as being of low virulence, they have caused harmful health conditions in many healthy individuals and even death in patients with underlying conditions. Antimicrobial treatment of infections associated with these species, in general, was not very difficult; however, it can become an issue in the future because some strains are already resistant to different classes of antibiotics. Therefore, these pathogens should be considered of such importance that they should be included in the hospital screening programs. [ABSTRACT FROM AUTHOR]

Objectives: Paediatric hospital admissions for dental extractions remain a cause for concern, despite decreasing levels of dental diseases in some areas of the country. While local investigations have taken place, little is known about national patterns, and how the relationship between the number of hospital admissions and key independent variables differs across England. The aim of this study was to examine spatial differences in the number of paediatric hospital admissions for extractions in relation to four key independent variables: dental caries, deprivation, units of dental activity and child access to dentists. Methods: Hospital admissions data (for all dental‐related reasons) were taken from the Hospital Episode Statistics (HES) for England (2017/18) for children and adolescents aged up to 19 years. All data were collected at local authority level. Geographically weighted regression was used to examine associations between the number of hospital admissions and the independent variables, as well as the strength of these associations and how they differed spatially. Results: Geographically weighted regression revealed considerable differences in the associations between the number of paediatric hospital admissions and the independent variables across England, with distinct regional clusters identified in the data. Some areas exhibited positive associations between independent variables and the number of hospital admissions, such as in Yorkshire and areas of south‐west, south‐east and north‐west England, where greater mean dmft scores were associated with greater numbers of hospital admissions. Negative associations were also found, such as in south‐west, north‐west and North East England, where higher deprivation scores were associated with lower admission numbers. Despite the patterns found, a much smaller sample of the associations between the independent variables and the number of hospital admissions was statistically significant. Conclusions: This analysis allows for a better understanding of the spatial associations between the number of hospital admissions and key independent variables, as well as how changes to these independent variables may affect the number of admissions in each local authority. These findings should be considered in the context of the limitations of HES dataset. [ABSTRACT FROM AUTHOR]

Background and objectives: Septic transfusion reactions are a principal cause of transfusion‐related mortality. The frequency of detectable bacterial contamination is greater in platelets compared to other blood components because platelets are stored at room temperature. Most strategies outlined in the September 2019 FDA guidance require both aerobic culture (AC) and anaerobic culture (AnC) testing. We performed a systematic review and meta‐analysis in an effort to provide the best available estimate of the effectiveness of AnC. Materials and methods: Our analysis was performed according to published guidelines. Broad and context‐specific meta‐analyses of bacterial detection rates in platelets by AnC were performed to assess the practical effectiveness of AnC as a risk control measure. Results: Seven studies with a total of 1 767 014 tested platelet components were included for analysis. With exclusion of positives due to Cutibacterium/Propionibacterium species and redundancy due to AC results, AnC detected 0·06 contamination events per thousand (EPT) components tested, twofold lower than the AC (0·12 EPT). Conclusion: Excluding Cutibacterium/Propionibacterium species, AnC detects occasional bacterial contamination events that are not detected by AC (~1 in 17 000 platelet components). [ABSTRACT FROM AUTHOR]

Background: Primary culture alone was a bacterial risk control strategy intended to facilitate interdiction of contaminated platelets (PLTs). A September 2019 FDA guidance includes secondary testing options to enhance safety. Our objective was to use meta-analysis to determine residual contamination risk after primary culture using secondary culture and rapid testing.Study Design and Methods: A December 2019 literature search identified articles on PLT bacterial detection rates using primary culture and a secondary testing method. We used meta-analysis to estimate secondary testing detection rates after a negative primary culture. We evaluated collection method, sample volume, sample time, and study date as potential sources of heterogeneity.Results: The search identified 6102 articles; 16 were included for meta-analysis. Of these, 12 used culture and five used rapid testing as a secondary testing method. Meta-analysis was based on a total of 103 968 components tested by secondary culture and 114 697 by rapid testing. The residual detection rate using secondary culture (DRSC ) was 0.93 (95% CI, 0.24-0.6) per 1000 components, while residual detection rate using rapid testing (DRRT ) was 0.09 (95% CI, 0.01-0.25) per 1000 components. Primary culture detection rate was the only statistically significant source of heterogeneity.Conclusion: We evaluated bacterial detection rates after primary culture using rapid testing and secondary culture. These results provide a lower and upper bound on real-world residual clinical risk because these methods are designed to detect high-level exposures or any level of exposure, respectively. Rapid testing may miss some harmful exposures and secondary culture may identify some clinically insignificant exposures. [ABSTRACT FROM AUTHOR]

Background: Bacterial contamination of platelets is a problem that can lead to harmful septic transfusion reactions. The US Food and Drug Administration published a guidance in September 2019 detailing several permissible risk control strategies. Our objective was to compare the safety of each bacterial testing strategy for apheresis platelets.Study Design and Methods: We used simulation to compare safety of the nine risk control strategies involving apheresis platelet testing. The primary outcome was the risk of exposure. An exposure event occurred if a patient received platelets exceeding a specific contamination threshold (>0, 103 , and 105 colony-forming units (CFU/mL). We generated a range of bacterial contamination scenarios (inoculum size, doubling time, lag time) and compared risk of exposure for each policy in each contamination scenario. We then computed the average risk difference over all scenarios.Results: At the 0 CFU/mL exposure threshold, two-step policies that used secondary culture ranked best (all top three), while single-step 24-hour culture with 3-day expiration ranked last (ninth). This latter policy performed well (median rank of 1) at both the 103 and 105 CFU/mL thresholds, but 48-hour culture with 7-day expiration performed relatively poorly. At these higher thresholds, median ranks of two-step policies that used secondary culture were again top three. Two-step policies that used rapid testing improved at the higher (105 CFU/mL) harm threshold, with median rankings between 1 and 5.Conclusion: Two-step policies that used secondary culture were generally safer than single-step policies. Performance of two-step policies that used rapid testing depended on the CFU per milliter threshold of exposure used. [ABSTRACT FROM AUTHOR]

Background: Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide information about residual risk and inform optimal testing strategies. We performed a systematic review and meta-analysis of platelet contamination rates by primary culture.Study Design and Methods: A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta-analysis to estimate the overall rate of contamination and meta-regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods.Results: The search identified 6102 studies, and 22 were included for meta-analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38-0.67) including AP (0.23, 95% CI: 0.18-0.28), PRP, (0.38, 95% CI: 0.15-0.70), and BC (1.12, 95% CI: 0.51-1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity.Conclusion: The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between-study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time. [ABSTRACT FROM AUTHOR]

Background: Our national reference laboratory sought to improve stewardship for multiple sclerosis (MS) testing, which included orders for myelin basic protein (MBP) and oligoclonal bands (OCB). From 2011 to 2012, we performed 2 interventions for MS testing: one gentle-strength intervention of a publication designed to educate others about the lack of utility for MBP results and a second mediumstrength intervention that included removal of MBP from the panel of MS tests. The ordering trends and practice variation were examined for OCB and MBP to retrospectively observe the effect of the interventions. Methods: Data from clients within academic and community hospitals were examined (n = 1710 clients). Ordering patterns for OCB and MBP were investigated from 2008 to 2018 by calculating the %OCB: %OCB = (OCB)/(OCB + MBP). Practice variation was examined by comparing the distribution of clients with different %OCB statistics before and after the interventions in 5-year blocks (2008-2012 vs 2014-2018). Results: From 2000 to 2011, the%OCBwas approximately 50%, but gradually increased to 67% in 2018. For practice variation, analysis of the distribution of clients by %OCB also demonstrated a shift toward clients favoring OCB alone vs OCB + MBP for MS testing for the later time period of 2014-2018. Conclusion: Our 2 interventions had a measurable, beneficial effect on ordering trends for MS testing over a 10-year period at a single reference laboratory. However, given that MBP has questionable clinical utility, stronger interventions are likely needed to bring about larger changes in ordering behavior. [ABSTRACT FROM AUTHOR]

Objectives: Anti-β2 glycoprotein I domain I (anti-domain I) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are present in patients with antiphospholipid syndrome (APS); however, their use in evaluation remains unclear.Methods: Diagnostic attributes of lupus anticoagulant (LAC), anti-domain I IgG, anti-cardiolipin, anti-β2 glycoprotein I (anti-β2GPI), and aPS/PT IgG and IgM antibodies were assessed in 216 patients evaluated for APS.Results: LAC had the best odds ratio (OR, 14.2) while that for anti-domain 1 IgG was comparable to anti-β2GPI IgG (OR, 8.3 vs 9.4) but higher than all others. Significant correlations were observed for thrombosis (P = .03) and pregnancy-related morbidity (P = .001) with anti-domain IgG and for any thrombosis with aPS/PT IgG (P = .006). Use of noncriteria antiphospholipid with or without criteria markers did not significantly increase the probability to diagnose APS.Conclusions: Noncriteria tests can contribute to diagnosis and stratification of APS but do not improve diagnostic yield. Optimal strategies for implementation require prospective investigation. [ABSTRACT FROM AUTHOR]

Background Point of care (POC) testing is rapidly evolving. POC testing is often managed by POC coordinators (POCC), but this role is relatively new and has not been characterized. Objectives To characterize the background, responsibilities, and job satisfaction of POCCs. Methods Structured interviews were conducted with 15 POCCs. On the basis of these interviews, a 38-item questionnaire was developed and administered as a web-based survey. Results The respondents (N = 98) were mostly female (87%) and had a bachelor's degree (79%). About half the respondents were older than 55 years and were in supervisory positions. Overall, respondents indicated high job satisfaction, but women were significantly less satisfied than men. POCCs were infrequently involved in decisions regarding the implementation of new tests. The number of tests managed by each POCC varied widely (median, 6.0; range, 1–30). Conclusions The POCC role is in flux. There is consensus regarding some aspects of the job, but there are significant differences in the way that hospitals organize the POCC function. [ABSTRACT FROM AUTHOR]

Background: Risk-adjusted benchmarking could be useful to compare blood utilization between hospitals or individual groups, such as physicians, while accounting for differences in patient complexity. The aim of this study was to analyze the association of red blood cell (RBC) use and diagnosis-related group (DRG) weights across all inpatient hospital stays to determine the suitability of using DRGs for between-hospital risk-adjusted benchmarking. Specific hierarchical organizational units (surgical vs. nonsurgical patients, departments, and physicians) were also evaluated.Study Design and Methods: We studied blood use among all adult inpatients, and within organizational units, over 4 years (May 2014 to March 2018) at an academic center. Number of RBCs transfused, all patient refined (APR)-DRGs, and other variables were captured over entire hospital stays. We used multilevel generalized linear modeling (zero-inflated negative binomial) to study the relationship between RBC utilization and APR-DRG.Results: A total of 97,955 hospital stays were evaluated and the median APR-DRG weight was 1.2. The association of RBCs transfused and APR-DRG weight was statistically significant at all hierarchical levels (incidence rate ratio = 1.22; p < 0.001). The impact of APR-DRG on blood use, measured by the incidence rate ratio, demonstrated an association at the all-patient and surgical levels, at several department and physician levels, but not at the medical patient level. The relationship between RBCs transfused and APR-DRG varied across organizational units.Conclusion: Number of RBCs transfused was associated with APR-DRG weight at multiple hierarchical levels and could be used for risk-adjusted benchmarking in those contexts. The relationship between RBC use and APR-DRG varied across organizational units. [ABSTRACT FROM AUTHOR]

Fibroproliferative diseases affect a significant proportion of the world's population. Despite this, core mechanisms driving organ fibrosis of diverse etiologies remain ill defined. Recent studies suggest that integrin‐alpha V serves as a master driver of fibrosis in multiple organs. Although diverse mechanisms contribute to the progression of fibrosis, TGF‐β and IL‐13 have emerged as central mediators of fibrosis during type 1/type 17, and type 2 polarized inflammatory responses, respectively. To investigate if integrin‐alpha V interactions or signaling is critical to the development of type 2 fibrosis, we analyzed fibroblast‐specific integrin‐alpha V knockout mice in three type 2‐driven inflammatory disease models. While we confirmed a role for integrin‐alpha V in type 17‐associated fibrosis, integrin‐alpha V was not critical to the development of type 2‐driven fibrosis. Additionally, our studies support a novel mechanism through which fibroblasts, via integrin‐alpha V expression, are capable of regulating immune polarization. We show that when integrin‐alpha V is deleted on fibroblasts, initiation of type 17 inflammation is inhibited leading to a deregulation of type 2 inflammation. This mechanism is most evident in a model of severe asthma, which is characterized by a mixed type 2/type 17 inflammatory response. Together, these findings suggest dual targeting of integrin‐alpha V and type 2 pathways may be needed to ameliorate fibrosis and prevent rebound of opposing pro‐fibrotic and inflammatory mechanisms. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review was to identify and conceptualize the barriers and enablers to accessing dental services for people experiencing homelessness in the United Kingdom. Methods: A literature search for studies relevant to homelessness and dental care was conducted. The PRISMA and ENTREQ guidelines were followed. Electronic databases (EMBASE, MEDLINE, DOSS, CINAHL, SOCINDEX and PsycINFO) and grey literature sources (Electronic Theses Online Service – EThOS, Kings Fund, NICE Evidence, Open Grey, Google and the Health Foundation) were searched up to 28 August 2018. The critical appraisal was conducted using CASP and an adjusted version of a JBI Critical Appraisal tool. Thematic analysis was used to develop the themes and domains. Results: Twenty‐eight papers were included. Barriers to homeless people accessing dental care stemmed both from the lived experience of homelessness and the healthcare system. Within homelessness, the themes identified included complexity, emotions and knowledge. Regarding the healthcare system, identified themes included staff encounter, accessibility and organization issues. Conclusion: Homelessness can actively contribute to both an increased need for dental care and barriers to accessing that care. The arrangement of dental healthcare services can also act as barriers to care. This is the first systematic review to conceptualize the factors associated with access to dental care for people who are homeless. It provides a set of recommendations for overcoming the main barriers for homeless people to accessing dental care. It also offers directions for future research, policy and commissioning. [ABSTRACT FROM AUTHOR]

Objectives: Diacetyl, a butter flavour compound used in food and flavouring production, is a respiratory toxin. We characterised the burden of respiratory abnormalities in workers at popcorn and flavouring manufacturing facilities that used diacetyl as evaluated through US National Institute for Occupational Safety and Health (NIOSH) health hazard evaluations.Methods: We performed analyses describing the number and percentage of current and former workers from popcorn and flavouring manufacturing facilities where NIOSH administered a respiratory health questionnaire and spirometry testing who met case definitions of suspected flavouring-related lung disease. Case definitions were pathologist reported: lung biopsy pathology report stating supportive of/consistent with constrictive bronchiolitis or bronchiolitis obliterans; probable: obstructive/mixed spirometric pattern with forced expiratory volume in 1 s (FEV1) <60% predicted; possible: obstructive/mixed spirometric pattern with FEV1 ≥60% or any spirometric restriction; symptoms only: normal spirometry plus exertional dyspnoea or usual cough.Results: During 2000-2012, NIOSH collected questionnaire and spirometry data on 1407 workers (87.0% current, 13.0% former) at nine facilities in eight states. After applying case definitions, 4 (0.3%) were classified as pathologist reported, 48 (3.4%) as probable, 234 (16.6%) as possible and 404 (28.7%) as symptoms only. The remaining 717 (51.0%) workers had normal spirometry without exertional dyspnoea or usual cough. Seven of 11 workers with biopsies did not meet the pathologist-reported case definition, although four met probable and three met possible.Conclusions: This approach demonstrates the substantial burden of respiratory abnormalities in these workers. A similar approach could quantify the burden of respiratory abnormalities in other industries that use diacetyl. [ABSTRACT FROM AUTHOR]

There is limited information on the natural history of building occupants’ health in relation to attempts to remediate moisture damage. We examined changes in respiratory and non-respiratory symptoms in 1,175 office building occupants over seven years with multiple remediation attempts. During each of four surveys, we categorized participants using a severity score: 0 = asymptomatic; 1 = mild, symptomatic in the last 12 months, but not frequently in the last 4 weeks; 2 = severe, symptomatic at least once weekly in the last 4 weeks. Building-related symptoms were defined as improving away from the building. We used random intercept models adjusted for demographics, smoking, building tenure, and microbial exposures to estimate temporal changes in the odds of building-related symptoms or severity scores independent of the effect of microbial exposures. Trend analyses of combined mild/severe symptoms showed no changes in the odds of respiratory symptoms but significant improvement in non-respiratory symptoms over time. Separate analyses showed increases in the odds of severe respiratory symptoms (odds ratio/year = 1.15‒1.16, p-values<0.05) and severity scores (0.02/year, p-values<0.05) for wheezing and shortness of breath on exertion, due to worsening of participants in the mild symptom group. For non-respiratory symptoms, we found no changes in the odds of severe symptoms but improvement in severity scores (-0.04‒-0.01/year, p-values<0.05) and the odds for mild fever and chills, excessive fatigue, headache, and throat symptoms (0.65–0.79/year, p-values<0.05). Our study suggests that after the onset of respiratory and severe non-respiratory symptoms associated with dampness/mold, remediation efforts might not be effective in improving occupants’ health. [ABSTRACT FROM AUTHOR]

The article discusses the health risk of nonalcoholic fatty liver disease (NAFLD) due to obesity in developed countries. It examines the immunopathogenesis of NAFLD as well as the immune response of the individuals with NAFLD. It also cites the manifestation of metabolic syndrome that could lead to chronic liver disease.

Course-based research experiences (CREs) are powerful strategies for promoting learning and persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation. [ABSTRACT FROM AUTHOR]

Highly ordered chromophoric linkers positioned within the metal–organic frameworks (MOFs) have the potential to mimic natural light-harvesting complexes. Herein we report topological control over the photophysical properties of MOFs via modular interchromophoric electronic coupling to manifest different steady-state singlet emission spectra and their corresponding fluorescence lifetimes. [ABSTRACT FROM AUTHOR]

The article offers information on a study highlighting the importance of early combined targeting of thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33, which are important initiators of type 2–associated mucosal inflammation and immunity, to ameliorate progressive type 2–driven disease. Information related to inflammation and fibrosis is presented.

The article offers information on a cross-sectional study of asthmatics of varying severity (n = 51). Topics discussed include major patient clusters such as TH2-high, TH17-high, and TH2/17-low, which were obtained from endobronchial tissue gene expression analysis; importance of identifying the molecular mechanisms driving subtypes of asthma for drug targeting; and clinical characteristics of the patients separated by molecular phenotypes of TH2/17 inflammation.

Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαflox/deltaLysMCre mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80hiCD11bhi macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysMCre-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2loIL-4Rα+ macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM) population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2hiIL-4Rα+ macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis. [ABSTRACT FROM AUTHOR]

This article describes an innovation in baccalaureate nursing education that is intended to assist in the preparation of nursing students for careers in which evidence-informed practice is an imperative. The innovation involves the combination of central aspects of the internationally recognized Registered Nurses' Association of Ontario Best Practice Guidelines Program with existing curricular goals and themes in a baccalaureate nursing program at a small university in southern Ontario in Canada. [J Nurs Educ. 2014;53(3,Suppl.):S55-S58J [ABSTRACT FROM AUTHOR]

A reminder of the guidance for domestic abuse and safeguarding for general dental practices by Sandra White, national lead for dental public health for Public Health England [ABSTRACT FROM AUTHOR]

A diverse suite of effector immune responses provide protection against various pathogens. However, the array of effector responses must be immunologically regulated to limit pathogen- and immune-associated damage. CD4+Foxp3+ regulatory T cells (Treg) calibrate immune responses; however, how Treg cells adapt to control different effector responses is unclear. To investigate the molecular mechanism of Treg diversity we used whole genome expression profiling and next generation small RNA sequencing of Treg cells isolated from type-1 or type-2 inflamed tissue following Leishmania major or Schistosoma mansoni infection, respectively. In-silico analyses identified two miRNA “regulatory hubs” miR-10a and miR-182 as critical miRNAs in Th1- or Th2-associated Treg cells, respectively. Functionally and mechanistically, in-vitro and in-vivo systems identified that an IL-12/IFNγ axis regulated miR-10a and its putative transcription factor, Creb. Importantly, reduced miR-10a in Th1-associated Treg cells was critical for Treg function and controlled a suite of genes preventing IFNγ production. In contrast, IL-4 regulated miR-182 and cMaf in Th2-associed Treg cells, which mitigated IL-2 secretion, in part through repression of IL2-promoting genes. Together, this study indicates that CD4+Foxp3+ cells can be shaped by local environmental factors, which orchestrate distinct miRNA pathways preserving Treg stability and suppressor function. [ABSTRACT FROM AUTHOR]

Background Water damage in buildings has been associated with reports of upper airway inflammation among occupants. Methods This survey included a questionnaire, allergen skin testing, nasal nitric oxide, and nasal lavage on 153 participants. We conducted exposure assessments of 297 workstations and analyzed collected dust for fungi, endotoxin, and (1 → 3)-β- D-glucan to create floor-specific averages. Results Males had higher levels of nasal inflammatory markers, and females reported more symptoms. ECP, IL-8, and MPO were significantly associated with nasal symptoms, flu-like achiness, or chills. Fungi and glucan were positively associated with blowing out thick mucus. Endotoxin was significantly associated with ECP in overall models, and with ECP, IL-8, MPO, and neutrophils among non-atopic females. Conclusions In this study, we documented an association between endotoxin and nasal inflammatory markers among office workers. The results of our study suggest that a non-allergic response may contribute to symptoms occurring among occupants in this water-damaged building. Am. J. Ind. Med. 56:522-530, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND. Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS. Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS. HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant ( P = .002 by the Fisher exact test). CONCLUSIONS. To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia. Cancer (Cancer Cytopathol) 2013;121:37-46 © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The negative impact of sustaining an injury on a military deployment on subsequent mental health is well-documented, however, the relationship between having an illness on a military operation and subsequent mental health is unknown. Methods: Population based study, linking routinely collected data of attendances at emergency departments in military hospitals in Iraq and Afghanistan [Operational Emergency Department Attendance Register (OpEDAR)], with data on 3896 UK Army personnel who participated in a military health study between 2007 and 2009 and deployed to Iraq or Afghanistan between 2003 to 2009. Results: In total, 13.8% (531/3896) of participants had an event recorded on OpEDAR during deployment; 2.3% (89/3884) were medically evacuated. As expected, those medically evacuated for an injury were at increased risk of post deployment probable PTSD (odds ratio 4.27, 95% confidence interval 1.80-10.12). Less expected was that being medically evacuated for an illness was also associated with a similarly increased risk of probable PTSD (4.39, 1.60-12.07) and common mental disorders (2.79, 1.41-5.51). There was no association between having an OpEDAR event and alcohol misuse. Having an injury caused by hostile action was associated with increased risk of probable PTSD compared to those with a non-hostile injury (3.88, 1.15 to 13.06). Conclusions: Personnel sustaining illnesses on deployment are just as, if not more, at risk of having subsequent mental health problems as personnel who have sustained an injury. Monitoring of mental health problems should consider those with illnesses as well as physical injuries. [ABSTRACT FROM AUTHOR]

A survey was carried out to identify the type of cancer nurse-led clinics established in one region of Scotland. It also aimed to establish the scope of the clinics, with a view to making recommendations for further developments. One hundred clinics were surveyed, with data on 88 clinics returned. The results are discussed in relation to demographic and organisational factors, function of clinic, competency and training, scope of practice, governance and evaluation. Recommendations include a structured and strategic approach to developing new clinics, clear governance arrangements, development of a framework and protocol template, research to evaluate clinics, further development of advanced practice and non-medical prescribing. [ABSTRACT FROM AUTHOR]

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+ CD44+ CD25+ GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni. [ABSTRACT FROM AUTHOR]

Background Damp buildings are commonly remediated without removing employees or ongoing medical surveillance. Methods We examined paired pulmonary function and questionnaire data from 2002 and 2005 for 97 employees in a water-damaged building during ongoing but incomplete remediation. Results We observed no overall improvement in respiratory health, as reflected in symptom scores, overall medication use, spirometry abnormalities, or sick leave. Four employees went from borderline bronchial hyperresponsiveness to bronchial hyperresponsiveness; six developed abnormal spirometry; three more reported post-occupancy current asthma, and four hypersensitivity pneumonitis. The numberof participants without lower respiratory symptoms decreased from 27 in 2002 to 20 in 2005. Respiratory cases relocated in the building had a decrease in medication use and sick leave in 2005. Conclusions During dampness remediation, relocation may be health protective and prevent incident building-related respiratory cases. Without relocation of entire workforces, medical surveillance is advisable for secondary prevention of existing building-related disease. [ABSTRACT FROM AUTHOR]

The article presents a study on the breast cancer mortality difference of African-American women and white women. The study examined racial disparities in diagnoses, treatment and mortality based on data obtained from Southern U.S. health plan claims. The results revealed that more breast-conserving surgery and chemotherapy were given to white women than the other. The study showed existing disparities between African-American women and white women with breast cancer in terms of medical care.

The article discusses the item analysis regarding the area of difficulties of the students who took the National Science Education Content Standard B in Ohio. It states that an item analysis was conducted by the school district to determine the standards and concepts that find the students difficult. The principals and curriculum directors have gathered some information from the websites of the Department of Education (ODE). Suggested activities and programs have been presented to help teachers enhance the understanding of the students on physical and chemical changes.

BACKGROUND: Damp building-related respiratory illnesses are an important public health issue. OBJECTIVE: We compared three respiratory case groups defined by questionnaire responses [200 respiratory cases, 123 of the respiratory cases who met the epidemiologic asthma definition, and 49 of the epidemiologic asthma cases who had current physician-diagnosed asthma with postoccupancy onset] to a comparison group of 152 asymptomatic employees in an office building with a history of water damage. METHODS: We analyzed dust samples collected from floors and chairs of 323 cases and comparisons for culturable fungi, ergosterol, endotoxin, and cat and dog allergens. We examined associations of total fungi, hydrophilic fungi (requiring water activity ≥ 0.9), and ergosterol with the health outcomes using logistic regression models. RESULTS: In models adjusted for demographics, respiratory illnesses showed significant linear exposure-response relationships to total culturable fungi [interquartile range odds ratios (IQR-OR) = 1.37-1.72], hydrophilic fungi (IQR-OR = 1.45-2.19), and ergosterol (IQR-OR = 1.54-1.60) in floor and chair dusts. Of three outcomes analyzed, current asthma with postoccupancy physician diagnosis was most strongly associated with exposure to hydrophilic fungi in models adjusted for ergosterol, endotoxin, and demographics (IQR-OR = 2.09 for floor and 1.79 for chair dusts). Ergosterol levels in floor dust were significantly associated with epidemiologic asthma independent of culturable fungi (IQR-OR = 1.54-1.55). CONCLUSIONS: Our findings extend the 2004 conclusions of the Institute of Medicine [Human health effects associated with damp indoor environments. In: Damp Indoor Spaces and Health. Washington DC:National Academies Press, 183-269] by showing that mold levels in dust were associated with new-onset asthma in this damp indoor environment. Hydrophilic fungi and ergosterol as measures of fungal biomass may have promise as markers of risk of building-related respiratory diseases in damp indoor environments. [ABSTRACT FROM AUTHOR]

Background: Dampness and mold problems are frequently encountered in schools. Approximately one third of US public schools require extensive repairs or need at least 1 building replaced. This study illustrates how national data can be used to identify building-related health risks in school employees and students. Methods: School employees (n = 309) in 2 elementary schools (schools A and B) with dampness and mold problems completed standardized questionnaires. Responses were compared with participant responses from the 3rd National Health and Nutrition Examination Survey and were indirectly standardized for gender, age, smoking status, and (for school B) race. Uncontrolled comparisons were made to responses from a study of office workers, as well as between responses from school employees in different sections of the school buildings designated by decade of construction. Results: Employees from both schools had excess work-related throat and lower respiratory symptoms, as well as eye, nasal, sinus, and wheezing symptoms. School B employees also had excess physician-diagnosed asthma and work-related fatigue, headache, and skin irritation. Employees in sections of the school buildings that were categorized as having greater dampness and mold contamination had more frequent upper and lower respiratory symptoms than employees working in other building sections. Conclusions: This noncostly type of analysis of indoor air quality complaints can be used to motivate and prioritize building remediation in public schools where funds for building remediation are usually limited. [ABSTRACT FROM AUTHOR]

Purpose: This research provides state policy makers and others interested in developing needs-based reimbursement models for Medicaid-funded assisted living with an evaluation of different methodologies that affect the structure and outcomes of these models. Design and Methods: We used assessment data from Medicaid-enrolled assisted living residents and waiver-eligible community-dwelling individuals (N = 726) in order to evaluate five methodologies in the design of these tiered needs-based models. We used ordinary least squares regression analyses in order to evaluate each model's ability to predict the time needed to care for individuals with varying needs (e.g., activities of daily living limitations, dementia, special services.) Results: These models varied in fit from .127 to a high of .357 using the adjusted R2 statistic. Both count and weighted models adequately predicted service needs and discriminated individuals into their appropriate tiers well. Weighted models with the largest score range worked best and provided more flexibility. Implications: Policy makers can tailor the generic tiered models developed with these methods to a state's population: Any state considering adoption of a needs-based tiered model will need to refine its model-based on its assisted living population characteristics, its resources, and how the model fits its long-term care system. For the industry, these models can serve to identify levels of care needed in planning for staff time and skill mix required for assisted living as well as other long-term care populations. [ABSTRACT FROM AUTHOR]

Penicillium expansum is commonly associated with patulin production in pomaceous fruits. Both the full-length isoepoxydon dehydrogenase ( idh) gene and a 470 bp fragment of the 6-methylsalicylic acid synthase ( 6-msas) gene have been cloned from P. expansum. In addition, we cloned a 715 bp fragment of a putative ATP-binding cassette transporter gene peab1, together with part of two putative cytochrome P450 monooxygenase genes P-450 1 and P-450 2. Increased expression of all five genes was observed under patulin-permissive conditions, indicating not only their likely involvement in patulin biosynthesis but indicating for the first time that regulation of patulin biosynthesis in P. expansum is mediated at the level of gene transcription. [ABSTRACT FROM AUTHOR]

We conducted a study on building-related respiratory disease and associated social impact in an office building with water incursions in the northeastern United States. An initial questionnaire had 67% participation (888/1,327). Compared with the U.S. adult population, prevalence ratios were 2.2-2.5 for wheezing, lifetime asthma, and current asthma, 3.3 for adult-onset asthma, and 3.4 for symptoms improving away from work (p < 0.05). Two-thirds (66/103) of the adult-onset asthma arose after occupancy, with an incidence rate of 1.9/1,000 person-years before building occupancy and 14.5/1,000 person-years after building occupancy. We conducted a second survey on 140 respiratory cases, 63 subjects with fewer symptoms, and 44 comparison subjects. Health-related quality of life decreased with increasing severity of respiratory symptoms and in those with work-related symptoms. Symptom status was not associated with job satisfaction or how often jobs required hard work. Respiratory health problems accounted for one-third of sick leave, and respiratory cases with work-related symptoms had more respiratory sick days than those without work-related symptoms (9.4 vs. 2.4 days/year; p < 0.01). Abnormal lung function and/or breathing medication use was found in 67% of respiratory cases, in 38% of participants with fewer symptoms, and in 11% of the comparison group (p < 0.01), with similar results in never-smokers. Postoccupancy-onset asthma was associated with less atopy than preoccupancy-onset asthma. Occupancy of the water-damaged building was associated with onset and exacerbation of respiratory conditions, confirmed by objective medical tests. The morbidity and lost work time burdened both employees and employers. [ABSTRACT FROM AUTHOR]

We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cyclespecific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow. [J Natl Cancer Inst 83:1149–1156, 1991] [ABSTRACT FROM PUBLISHER]