A scoping review of behavioural science approaches and frameworks for health protection and emergency response.

AIMS: Rapid intervention development, implementation, and evaluation are required for emergency public health contexts, such as the recent COVID-19 pandemic. A novel Agile Co-production and Evaluation (ACE) framework has been developed to assist this endeavour in future public health emergencies. This scoping review aimed to map available behavioural science resources that can be used to develop and evaluate public health guidance, messaging, and interventions in emergency contexts onto components of ACE: rapid development and implementation, co-production with patients or the public including seldom heard voices from diverse communities, and inclusion of evaluation. METHODS: A scoping review methodology was used. Searches were run on MEDLINE, EMBASE, PsycINFO, and Google, with search terms covering emergency response and behavioural science. Articles published since 2014 and which discussed a framework or guidance for using behavioural science in response to a public health emergency were included. A narrative synthesis was conducted. RESULTS: Seventeen records were included in the synthesis. The records covered a range of emergency contexts, the most frequent of which were COVID-19 (n = 7) and non-specific emergencies (n = 4). One record evaluated existing approaches, 6 proposed new approaches, and 10 described existing approaches. Commonly used approaches included the Behavioural Change Wheel; Capability, Opportunity, and Motivation Behaviour model; and social identity theory. Three records discuss co-production with the target audience and consideration of diverse populations. Four records incorporate rapid testing, evaluation, or validation methods. Six records state that their approaches are designed to be implemented rapidly. No records cover all components of ACE. CONCLUSION: We recommend that future research explores how to create guidance involving rapid implementation, co-production with patients or the public including seldom heard voices from diverse communities, and evaluation.

Quantum limits of position-sensitive photodiodes.

The split photodiode and the lateral effect photodiode are two popular detectors for measuring beam displacement. For small displacements of a Gaussian beam, which is the case of interest here, they are often seen as equivalent and used interchangeably, giving a signal proportional to the displacement. We show theoretically and experimentally that in the limit of low technical noise, where the signal to noise ratio is dominated by the shot noise of the light, the lateral effect photodiode produces a better signal to noise ratio than the split photodiode, owing to its optimum spatial detector response. This quantum advantage can be practically exploited in spite of the intrinsic thermal noise of the lateral effect photodiode.

Low uptake of COVID-19 lateral flow testing among university students: a mixed methods evaluation.

OBJECTIVE: This study aimed to evaluate COVID-19 lateral flow testing (LFT) among asymptomatic university students. STUDY DESIGN: This study was a mixed methods evaluation of LFT among University of Bristol students. METHODS: We conducted (1) an analysis of testing uptake and exploration of demographic variations in uptake using logistic regression; (2) an online student survey about views on university testing; and (3) qualitative interviews to explore participants' experiences of testing and subsequent behaviour, analysed using a thematic approach. RESULTS: A total of 12,391 LFTs were conducted on 8025 of 36,054 (22.3%) students. Only one in 10 students had the recommended two tests. There were striking demographic disparities in uptake with those from ethnic minority groups having lower uptake (e.g. 3% of Chinese students were tested vs 30.7% of White students) and variations by level and year of study (ranging from 5.3% to 33.7%), place of residence (29.0%-35.6%) and faculty (15.2%-32.8%). Differences persisted in multivariable analyses. A total of 436 students completed the online survey, and 20 in-depth interviews were conducted. Barriers to engagement with testing included a lack of awareness, knowledge and understanding, and concerns about the accuracy and safety. Students understood the limitations of LFTs but requested further information about test accuracy. Tests were used to inform behavioural decisions, often in combination with other information, such as the potential for exposure to the virus and perceptions of vulnerability. CONCLUSIONS: The low uptake of testing brings into question the role of mass LFT in university settings. Innovative strategies may be needed to increase LFT uptake among students.

Astrocyte inflammatory signaling mediates α-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis.

Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein following infection with western equine encephalitis virus (WEEV). Infections were conducted in both wildtype mice and in transgenic mice lacking NFκB inflammatory signaling in astrocytes. For 2 months following WEEV infection, we analyzed glial activation, neuronal loss and protein aggregation across multiple brain regions, including the substantia nigra pars compacta (SNpc). These data revealed that WEEV induces loss of SNpc dopaminergic neurons, persistent activation of microglia and astrocytes that precipitates widespread aggregation of α-synuclein in the brain of C57BL/6 mice. Microgliosis and macrophage infiltration occurred prior to activation of astrocytes and was followed by opsonization of ⍺-synuclein protein aggregates in the cortex, hippocampus and midbrain by the complement protein, C3. Astrocyte-specific NFκB knockout mice had reduced gliosis, α-synuclein aggregate formation and neuronal loss. These data suggest that astrocytes play a critical role in initiating PD-like pathology following encephalitic infection with WEEV through innate immune inflammatory pathways that damage dopaminergic neurons, possibly by hindering clearance of ⍺-synuclein aggregates. Inhibiting glial inflammatory responses could therefore represent a potential therapy strategy for viral parkinsonism.

Manganese exposure in juvenile C57BL/6 mice increases glial inflammatory responses in the substantia nigra following infection with H1N1 influenza virus.

Infection with Influenza A virus can lead to the development of encephalitis and subsequent neurological deficits ranging from headaches to neurodegeneration. Post-encephalitic parkinsonism has been reported in surviving patients of H1N1 infections, but not all cases of encephalitic H1N1 infection present with these neurological symptoms, suggesting that interactions with an environmental neurotoxin could promote more severe neurological damage. The heavy metal, manganese (Mn), is a potential interacting factor with H1N1 because excessive exposure early in life can induce long-lasting effects on neurological function through inflammatory activation of glial cells. In the current study, we used a two-hit model of neurotoxin-pathogen exposure to examine whether exposure to Mn during juvenile development would induce a more severe neuropathological response following infection with H1N1 in adulthood. To test this hypothesis, C57BL/6 mice were exposed to MnCl2 in drinking water (50 mg/kg/day) for 30 days from days 21-51 postnatal, then infected intranasally with H1N1 three weeks later. Analyses of dopaminergic neurons, microglia and astrocytes in basal ganglia indicated that although there was no significant loss of dopaminergic neurons within the substantia nigra pars compacta, there was more pronounced activation of microglia and astrocytes in animals sequentially exposed to Mn and H1N1, as well as altered patterns of histone acetylation. Whole transcriptome Next Generation Sequencing (RNASeq) analysis was performed on the substantia nigra and revealed unique patterns of gene expression in the dual-exposed group, including genes involved in antioxidant activation, mitophagy and neurodegeneration. Taken together, these results suggest that exposure to elevated levels of Mn during juvenile development could sensitize glial cells to more severe neuro-immune responses to influenza infection later in life through persistent epigenetic changes.

The Balance Hypothesis for the Avian Lumbosacral Organ and an Exploration of Its Morphological Variation.

Birds (Aves) exhibit exceptional and diverse locomotor behaviors, including the exquisite ability to balance on two feet. How birds so precisely control their movements may be partly explained by a set of intriguing modifications in their lower spine. These modifications are collectively known as the lumbosacral organ (LSO) and are found in the fused lumbosacral vertebrae called the synsacrum. They include a set of transverse canal-like recesses in the synsacrum that align with lateral lobes of the spinal cord, as well as a dorsal groove in the spinal cord that houses an egg-shaped glycogen body. Based on compelling but primarily observational data, the most recent functional hypotheses for the LSO consider it to be a secondary balance organ, in which the transverse canals are analogous to the semicircular canals of the inner ear. If correct, this hypothesis would reshape our understanding of avian locomotion, yet the LSO has been largely overlooked in the recent literature. Here, we review the current evidence for this hypothesis and then explore a possible relationship between the LSO and balance-intensive locomotor ecologies. Our comparative morphological dataset consists of micro-computed tomography (µ-CT) scans of synsacra from ecologically diverse species. We find that birds that perch tend to have more prominent transverse canals, suggesting that the LSO is useful for balance-intensive behaviors. We then identify the crucial outstanding questions about LSO structure and function. The LSO may be a key innovation that allows independent but coordinated motion of the head and the body, and a full understanding of its function and evolution will require multiple interdisciplinary research efforts.

Pilot multi-centre randomised trial of the impact of pre-operative focused cardiac ultrasound on mortality and morbidity in patients having surgery for femoral neck fractures (ECHONOF-2 pilot).

Hip fracture surgery is common, usually occurs in elderly patients who have multiple comorbidities, and is associated with high morbidity and mortality. Pre-operative focused cardiac ultrasound can alter diagnosis and management, but its impact on outcome remains uncertain. This pilot study assessed feasibility and group separation for a proposed large randomised clinical trial of the impact of pre-operative focused cardiac ultrasound on patient outcome after hip fracture surgery. Adult patients requiring hip fracture surgery in four teaching hospitals in Australia were randomly allocated to receive focused cardiac ultrasound before surgery or not. The primary composite outcome was any death, acute kidney injury, non-fatal myocardial infarction, cerebrovascular accident, pulmonary embolism or cardiopulmonary arrest within 30 days of surgery. Of the 175 patients screened, 100 were included as trial participants (screening:recruitment ratio 1.7:1), 49 in the ultrasound group and 51 as controls. There was one protocol failure among those recruited. The primary composite outcome occurred in seven of the ultrasound group patients and 12 of the control group patients (relative group separation 39%). Death, acute kidney injury and cerebrovascular accident were recorded, but no cases of myocardial infarction, pulmonary embolism or cardiopulmonary arrest ocurred. Focused cardiac ultrasound altered the management of 17 participants, suggesting an effect mechanism. This pilot study demonstrated that enrolment and the protocol are feasible, that the primary composite outcome is appropriate, and that there is a treatment effect favouring focused cardiac ultrasound - and therefore supports a large randomised clinical trial.

The effect of intensive care unit admission on smokers' attitudes and their likelihood of quitting smoking.

We sought to estimate the proportion of patients admitted to a metropolitan intensive care unit (ICU) who were current smokers, and the relationships between ICU survivors who smoked and smoking cessation and/or reduction six months post-ICU discharge. We conducted a prospective cohort study at a metropolitan level III ICU in Melbourne, Victoria. One hundred consecutive patients who met the inclusion criteria were included in the study. Inclusion criteria consisted of patients who were smokers at time of ICU admission, had an ICU length of stay greater than one day, survived to ICU discharge, and provided written informed consent. A purpose-designed questionnaire which included the Fagerstrom test for nicotine dependence and evaluation of patients' attitude towards smoking cessation was completed by participants following ICU discharge and prior to hospital discharge. Participants were re-interviewed over the phone at six months post-ICU discharge. Of the 1,062 patients admitted to ICU, 253 (23%) were current smokers and 100 were enrolled. Six months post-ICU discharge, 28 (33%) of the 86 participants who were alive and contactable had quit smoking and 35 (41%) had reduced smoking. The median number of reported cigarettes smoked per day reduced by 40%. Participants who initially believed their ICU admission was smoking-related were more likely to have quit six months post-ICU discharge (odds ratio 2.98; 95% confidence interval 1.07 to 8.26; P=0.036). Six months post-ICU discharge, 63/86 (74%) of participants had quit or reduced their smoking. Further research into targeted smoking cessation counselling for ICU survivors is indicated.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review.

BACKGROUND: In recent years, infections with carbapenemase-producing Enterobacteriaceae (CPE) have been increasing globally and present a major public health challenge. AIM: To review the international literature: (i) to describe CPE outbreaks in acute hospital settings globally; and (ii) to identify the control measures used during these outbreaks and report on their effectiveness. METHODS: A systematic search of MEDLINE and EMBASE databases, abstract lists for key conferences and reference lists of key reviews was undertaken, and information on unpublished outbreaks was sought for 2000-2015. Where relevant, risk of bias was assessed using the Newcastle-Ottawa scale. A narrative synthesis of the evidence was conducted. FINDINGS: Ninety-eight outbreaks were eligible. These occurred worldwide, with 53 reports from Europe. The number of cases (CPE infection or colonization) involved in outbreaks varied widely, from two to 803. In the vast majority of outbreaks, multi-component infection control measures were used, commonly including: patient screening; contact precautions (e.g. gowns, gloves); handwashing interventions; staff education or monitoring; enhanced environmental cleaning/decontamination; cohorting of patients and/or staff; and patient isolation. Seven studies were identified as providing the best-available evidence on the effectiveness of control measures. These demonstrated that CPE outbreaks can be controlled successfully using a range of appropriate, commonly used, infection control measures. However, risk of bias was considered relatively high for these studies. CONCLUSION: The findings indicate that CPE outbreaks can be controlled using combinations of existing measures. However, the quality of the evidence base is weak and further high-quality research is needed, particularly on the effectiveness of individual infection control measures.

Citrobacter freundii as a test platform for recombinant cellulose degradation systems.

Cellulosic biomass represents a huge reservoir of renewable carbon, but converting it into useful products is challenging. Attempts to transfer cellulose degradation capability to industrially useful micro-organisms have met with limited success, possibly due to poorly understood synergy between multiple cellulases. This is best studied by co-expression of many combinations of cellulases and associated proteins. Here, we describe the development of a test platform based on Citrobacter freundii, a cellobiose-assimilating organism closely related to Escherichia coli. Standard E. coli cloning vectors worked well in Cit. freundii. Expression of cellulases CenA and Cex of Cellulomonas fimi in Cit. freundii gave recombinant strains which were able to grow at the expense of cellulosic filter paper or microcrystalline cellulose (Avicel) in a mineral medium supplemented with a small amount of yeast extract. Periodic physical agitation of the cultures was highly beneficial for growth at the expense of filter paper. This provides a test platform for the expression of combinations of genes encoding biomass-degrading enzymes to develop effective genetic cassettes for degradation of different biomass streams. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofuels have been shown to be the best sustainable and alternative source of fuel to replace fossil fuels. Of the different types of feedstocks used for producing biofuels, lignocellulosic biomass is the most abundant. Converting this biomass to useful products has met with little success. Different approaches are being used and microbial platforms are the most promising and sustainable method. This study shows that Citrobacter freundii is a better test platform than Escherichia coli for testing various combinations of cellulases for the development of microbial systems for biomass conversion.

Presentation for care and antenatal management of HIV in the UK, 2009-2014.

OBJECTIVES: Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV-positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care. METHODS: We used the UK's National Study of HIV in Pregnancy and Childhood for 2009-2014. Data were analysed by fitting logistic regression and Cox proportional hazards models. RESULTS: A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0-15.6 weeks] and booking was significantly earlier during 2012-2014 vs. 2009-2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1-24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later. CONCLUSIONS: Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART.

Small-Molecule Targeting of BET Proteins in Cancer.

BET proteins have recently become recognized for their role in a broad range of cancers and are defined by the presence of two acetyl-histone reading bromodomains and an ET domain. This family of proteins includes BRD2, BRD3, BRD4, and BRDT. BRD4 is the most-studied BET protein in cancer, and normally serves as an epigenetic reader that links active chromatin marks to transcriptional elongation through activation of RNA polymerase II. The role of BRD3 and BRD4 first became known in cancer as mutant oncoproteins fused to the p300-recruiting NUT protein in a rare aggressive subtype of squamous cell cancer known as NUT midline carcinoma (NMC). BET inhibitors are acetyl-histone mimetics that specifically bind BET bromodomains, competitively inhibiting its engagement with chromatin. The antineoplastic effects of BET inhibitors were first demonstrated in NMC and have since been shown to be effective at inhibiting the growth of many different cancers, particularly acute leukemia. BET inhibitors have also been instrumental as tool compounds that have demonstrated the key role of BRD4 in driving NMC and non-NMC cancer growth. Many clinical trials enrolling patients with hematologic and solid tumors are ongoing, with encouraging preliminary findings. BET proteins BRD2, BRD3, and BRD4 are expressed in nearly all cells of the body, so there are concerns of toxicity with BET inhibitors, as well as the development of resistance. Toxicity and resistance may be overcome by combining BET inhibitors with other targeted inhibitors, or through the use of novel BET inhibitor derivatives.

Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates.

BACKGROUND: Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D-1,25(OH)2D takes place at 40 ng/mL in pregnant women. OBJECTIVE: Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community. METHODS: Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20 ng/mL, >20 to <40 ng/mL, and ≥40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth. RESULTS: Women with serum 25(OH)D concentrations ≥40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ∼40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40 ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations ≥40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04). CONCLUSIONS: In this post-hoc analysis, achieving a 25(OH)D serum concentration ≥40 ng/mL significantly decreased the risk of preterm birth compared to ≤20 ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20 ng/mL; reaching 40 ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone.

NUT Carcinoma of the Sublingual Gland.

NUT carcinoma (NC) is a recently described, rare and extremely aggressive cancer primarily located to supradiaphragmatic structures and affecting young individuals. NC is characterized by translocations involving the NUT gene on 15q14 with the most common translocation partner gene being BRD4 on 19p13, resulting in the t(15;19)(q14;p13) karyotype. NC is poorly differentiated and is likely to be overlooked and misdiagnosed as poorly differentiated squamous cell carcinoma (SCC) when immunohistochemical evaluation of NUT protein expression is omitted. Previously, NC has been found in the parotid and submandibular glands and we present the first case in the sublingual gland arising in a 40-year-old woman. We discuss the diagnostic considerations for poorly differentiated carcinomas of the salivary glands and advocate the inclusion of NUT immunohistochemistry in this setting. Not only does the NC diagnosis confer a grave prognosis when treated as SCC as illustrated by the present case, but is important for the inclusion of patients in ongoing clinical trials.

Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml.

Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.

Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients.

BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are uremic toxins derived solely from colonic bacterial fermentation of protein. Dietary fiber may counteract this by limiting proteolytic bacterial fermentation. However, the influence of dietary intake on the generation of IS and PCS has not been adequately explored in chronic kidney disease (CKD). METHODS AND RESULTS: This cross-sectional study included 40 CKD participants (60% male; age 69 ± 10 years; 45% diabetic) with a mean estimated glomerular filtration rate (eGFR) of 24 ± 8 mL/min/1.73 m(2), who enrolled in a randomized controlled trial of synbiotic therapy. Total and free serum IS and PCS were measured at baseline by ultra-performance liquid chromatography. Dietary intake was measured using in-depth diet histories collected by a dietitian. Associations between each toxin, dietary fiber (total, soluble and insoluble), dietary protein (total, and amino acids: tryptophan, tyrosine and phenylalanine), and the protein-fiber index (ratio of protein to fiber) were assessed using linear regression. Dietary fiber was associated with free and total serum PCS (r = -0.42 and r = -0.44, both p < 0.01), but not IS. No significant association was observed between dietary protein and either toxin. The protein-fiber index was associated with total serum IS (r = 0.40, p = 0.012) and PCS (r = 0.43, p = 0.005), independent of eGFR, sex and diabetes. CONCLUSION: Dietary protein-fiber index is associated with serum IS and PCS levels. Such association, beyond fiber and protein alone, highlights the importance of the interplay between these nutrients. We speculate that dietary modification towards a lower protein-fiber index may contribute to lowering IS and PCS.

Effects of an in-house coordinator and practitioner referral rather than proxy referral on tissue donation rates.

INTRODUCTION: Timely referral of patients following asystolic death to an organ procurement organization (OPO) may increase tissue donation rates. Lack of education of health care providers and nonphysicians (admitting department) about timely referral to the OPO following asystolic death may adversely affect tissue donation rates. We hypothesized that using an in-house donation coordinator for provider education and changing the responsibility for calling the OPO from the admitting department to the licensed independent practitioner (LIP) declaring death would increase timely referral and tissue donation rates. METHODS: An education program was developed in 2005 by a newly hired in-house coordinator to highlight the importance of tissue donation. In addition, to improve timely referrals to the OPO after death, the instructions accompanying the working copy of the death certificate were altered to require the patient's LIP to call the OPO within 1 hour of death (early 2007). Rates for both timely referrals and tissue donors were modeled by a Poisson regression model with a log link function. RESULTS: Timely referral rates rose from 48% before the interventions to 72% after the intervention (P < .0001). The number of tissue donors per number of referrals also increased significantly (P = .025) over that period. CONCLUSIONS: An in-house donation coordinator initiated education program and LIP referral rather than referral by other parties following asystolic death results in higher tissue donation rates.