Tackling discrimination in medicine head on: The impact of bystander intervention training.

PURPOSE: A mixed-methods study to evaluate Bystander Intervention Training (BiT), a simulation-based small-group training programme designed to teach skills to tackle discrimination. MATERIALS AND METHODS: Norwich Medical School delivered the intervention online between January 2020 and June 2023 to medical students, physician associate trainees, and qualified doctors. A sample of 569 participants was used in the main analysis. Participants completed pre- and post-training and follow-up evaluations. RESULTS: Paired post-training scores were significantly different (all p < 0.001) from the pre-training scores for all 12 questions, in favour of the post-training scores. Of the 159 participants who completed follow-up questionnaires, 27 (17.9%) reported having the opportunity to be an active bystander; of those, 23 (85%) intervened. Scores in the follow-up questionnaire were significantly higher than those in the pre-training survey and significantly lower than those in the post-training questionnaire (p < 0.001). Participants had an increased sense of responsibility to be an active bystander and were empowered to challenge discrimination. Participants from marginalised groups expressed positive views about the training. CONCLUSIONS: Interventions that allow open discussion and carefully supported personal disclosure in safe spaces, where difficult and uncomfortable discussions can occur, with an opportunity to change behaviour, must be developed to tackle discrimination.

Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study.

Alcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome measures for the latter repeated after around four years. For the cross-sectional analysis fractional polynomial curves were fitted in models of measures of skeletal muscle mass, appendicular lean mass/body mass index (ALM/BMI), fat-free mass as a percentage of body weight (FFM%) and grip strength, all predicted from alcohol consumption with models fitted for men and women separately. Alcohol consumption at baseline was based on the mean of up to five dietary recalls, typically over 16 months. Linear regression was used for longitudinal analyses to model the effects of alcohol consumption groups on these measures. All models were adjusted for covariates. In the cross-sectional analysis, modelled values of the muscle mass measures all showed a peak at medium levels of alcohol consumption and a steep decline with increasing alcohol consumption. Modelled differences in muscle mass from zero consumption of alcohol to 160 g/d ranged from 3.6 to 4.9% for ALM/BMI for men and women, respectively, and 3.6 to 6.1% for FFM%. Grip strength consistently increased with alcohol consumption. No association between alcohol consumption and muscle measures were seen in the longitudinal results. Our results suggest that higher levels of alcohol consumption could have detrimental effects on muscle mass in middle- and older-aged men and women.

Nonsense-mediated mRNA decay efficiency varies in choroideremia providing a target to boost small molecule therapeutics.

Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is the cell's natural surveillance mechanism that detects and destroys PTC-containing transcripts, with UPF1 being the central NMD modulator. NMD efficiency can be variable amongst individuals with some transcripts escaping destruction, leading to the production of a truncated non-functional or partially functional protein. Nonsense suppression drugs, such as ataluren, target these transcripts and read-through the PTC, leading to the production of a full length functional protein. Patients with higher transcript levels are considered to respond better to these drugs, as more substrate is available for read-through. Using Quantitative reverse transcription PCR (RT-qPCR), we show that CHM mRNA expression in blood from nonsense mutation CHM patients is 2.8-fold lower than controls, and varies widely amongst patients, with 40% variation between those carrying the same UGA mutation [c.715 C>T; p.(R239*)]. These results indicate that although NMD machinery is at work, efficiency is highly variable and not wholly dependent on mutation position. No significant difference in CHM mRNA levels was seen between two patients' fibroblasts and their induced pluripotent stem cell-derived retinal pigment epithelium. There was no correlation between CHM mRNA expression and genotype, phenotype or UPF1 transcript levels. NMD inhibition with caffeine was shown to restore CHM mRNA transcripts to near wild-type levels. Baseline mRNA levels may provide a prognostic indicator for response to nonsense suppression therapy, and caffeine may be a useful adjunct to enhance treatment efficacy where indicated.

Fracture Incidence and the Relevance of Dietary and Lifestyle Factors Differ in the United Kingdom and Hong Kong: An International Comparison of Longitudinal Cohort Study Data.

Geographic variation in fracture risk may be due to divergent profiles of dietary, lifestyle, and other risk factors between populations. We investigated differences in fracture rates between two older-population cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort (n = 7732) in the United Kingdom (UK), and the Mr and Ms Os cohort (n = 3956) in Hong Kong (HK). Data were collected by questionnaires, laboratory assessments, and hospital records. Incidence of hip, spine, and wrist fractures in the two cohorts was calculated and multivariable regression was used to explore variables important to fracture risk. Total hip, spine, and wrist fracture incidence was higher in the UK vs HK for women (13.70 vs 8.76 per 1000 person-years; p < 0.001), but not men (5.95 vs 5.37 per 1000 person-years; p = 0.337), and the proportions of different fractures also varied between cohorts (p < 0.001). Hip fracture was the most common UK fracture (accounting for 56.8% fractures in men and 52.6% in women), while wrist fracture was most common in HK (42.9% in men and 57.9% in women). The major contributor to total fracture risk in multivariable regression models of both cohorts and sexes, was age; with BMI also an important contributor to fracture risk HK men and UK women. The distribution of factors relevant to fracture risk, and the rates of different fractures, varied significantly between UK and HK cohorts. However, the importance of each factor in contributing to fracture risk was similar between the cohorts. The differences in fracture rates suggest targeted approaches may be required when developing interventions and public health recommendations to reduce the burden of osteoporosis in these two countries.

Association between heart rate variability and haemodynamic response to exercise in chronic heart failure.

OBJECTIVES: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output. DESIGN: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure. RESULTS: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043). CONCLUSIONS: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure.

Effectiveness of virtual reality in the treatment of hand function in children with cerebral palsy: A systematic review.

STUDY DESIGN: Systematic review. INTRODUCTION: Children with cerebral palsy (CP) may have limited use of their hands for functional activities and for fine motor skills. Virtual reality (VR) is a relatively new and innovative approach to facilitate hand function in children with CP. PURPOSE OF THE STUDY: The primary purpose of this study was to determine the effectiveness of VR as an intervention to improve hand function in children with CP compared to either conventional physiotherapy or other therapeutic interventions. The secondary purpose was to classify the outcomes evaluated according to the International Classification of Functioning, Disability and Health (ICF) dimensions. METHODS: A International prospective register of systematic reviews (PROSPERO)-registered literature search was carried out in August 2015 in MEDLINE, CINAHL, ERIC, HealthSTAR, AMED, BNI, Embase, PsycINFO, PEDro, Cochrane Central Register, DARE, OTSeeker, REHABDATA, HaPI, CIRRIE, and Scopus. PRISMA guidelines were followed. Only randomized controlled trials (RCTs) were included, and their methodological qualities were examined using the Cochrane collaboration's risk of bias (RoB) tool. A narrative synthesis was performed. RESULTS: The 6 RCTs published on this topic provide conflicting results. Four studies reported improved hand function (2 low RoB, 1 high RoB, and 1 unclear RoB), whereas 2 studies reported no improvement. All of the RCTs reported the activity element of ICF, but no study explicitly described the effect of VR intervention based on the ICF model. CONCLUSION: The role of VR ti imrpove hand fucntion in children with CP is unclear due to limited evidence; use as an adjunct has some support.

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.

Dietary fat and fatty acid profile are associated with indices of skeletal muscle mass in women aged 18-79 years.

Age-related loss of skeletal muscle mass results in a reduction in metabolically active tissue and has been related to the onset of obesity and sarcopenia. Although the causes of muscle loss are poorly understood, dietary fat has been postulated to have a role in determining protein turnover through an influence on both inflammation and insulin resistance. This study was designed to investigate the cross-sectional relation between dietary fat intake, as dietary percentage of fat energy (PFE) and fatty acid profile, with indices of skeletal muscle mass in the population setting. Body composition [fat-free mass (FFM; in kg)] and the fat-free mass index (FFMI; kg FFM/m(2)) was measured by using dual-energy X-ray absorptiometry in 2689 women aged 18-79 y from the TwinsUK Study and calculated according to quintile of dietary fat (by food-frequency questionnaire) after multivariate adjustment. Positive associations were found between the polyunsaturated-to-saturated fatty acid (SFA) ratio and indices of FFM, and inverse associations were found with PFE, SFAs, monounsaturated fatty acids (MUFAs), and trans fatty acids (TFAs) (all as % of energy). Extreme quintile dietary differences for PFE were -0.6 kg for FFM and -0.28 kg/m(2) for FFMI; for SFAs, MUFAs, and TFAs, these were -0.5 to -0.8 kg for FFM and -0.26 to -0.38 kg/m(2) for FFMI. These associations were of a similar magnitude to the expected decline in muscle mass that occurs over 10 y. To our knowledge, this is the first population-based study to demonstrate an association between a comprehensive range of dietary fat intake and FFM. These findings indicate that a dietary fat profile already associated with cardiovascular disease protection may also be beneficial for conservation of skeletal muscle mass.

A simple 5-point scoring system, NaURSE (Na+, urea, respiratory rate and shock index in the elderly), predicts in-hospital mortality in oldest old.

BACKGROUND: the mortality is high in acutely ill oldest old patients. Understanding the prognostic factors which influence mortality will help clinicians make appropriate management decisions. METHODS: we analysed prospective mortality audit data (November 2008 to January 2009) to identify variables associated with in-patient mortality in oldest old. We selected those with P < 0.10 from univariate analysis and determined at which cut-point they served as the strongest predictor of mortality. Using these cut-off points, we constructed multivariate logistic regression models. A 5-point score was derived from cut-off points which were significantly associated with mortality tested in a smaller independent re-audit sample conducted in October 2011. RESULTS: a total of 405 patients (mean 93.5 ± 2.7 years) were included in the study. The mean length of stay was 18.5 ± 42.4 days and 13.8% died as in-patients. Variables (cut-off values) found to be significantly associated with in-patient mortality were admission sodium (>145 mmol/l), urea (≥14 mmol/l), respiratory rate (>20/min) and shock index (>1.0): creating a 5-point score (NaURSE: NaURS in the Elderly). The crude mortality rates were 9.5, 19.9, 34.4, 66.7, and 100% for scores 0, 1, 2, 3 and 4, respectively. Using the cut-off point of ≥2, the NaURSE score has a specificity of 87% (83.1-90.3) and sensitivity of 39% (28.5-50.0), with an AUC value of 0.69 (0.63-0.76). An external independent validation study (n = 121) showed similar results. CONCLUSIONS: the NaURSE score may be particularly useful in identifying oldest old who are likely to die in that admission to guide appropriate care.

The Association Between Atypical Speech Development and Adolescent Self-Harm.

BACKGROUND: Adolescent self-harm is a major public health issue internationally. Various factors associated with adolescent self-harm have been identified, including being bullied and experiencing mental health problems. Stuttering and speech sound disorder are associated with both of these factors. It was hypothesized that both stuttering and speech sound disorder would be associated with self-harm. This is the first study to explore the relationship between communication disorders and adolescent self-harm. METHOD: Secondary analysis of a large, longitudinal, prospective, community sample, the Avon Longitudinal Study of Parents and Children, was carried out. Clinicians identified children who stuttered or exhibited speech sound disorder at the age of 8 years. When the cohort members were 16 years old, they were asked to complete a questionnaire about self-harm. Multinomial logistic regression was used to examine the associations between stuttering and speech sound disorder and the self-harm outcomes, adjusting for other relevant factors. RESULTS: Of 3,824 participants with data for both speech status and self-harm, 94 (2.5%; 95% confidence interval [CI; 2.0, 3.0]) stuttered at 8 years of age and 127 (3.3%; 95% CI [2.8, 3.9]) displayed speech sound disorder. Speech sound disorder at the age of 8 years was associated with self-harm with suicidal intent in both unadjusted and adjusted models. Differences between the adjusted and unadjusted models were small, suggesting that speech sound disorder is largely an independent risk factor for self-harm with suicidal intent. Stuttering at the age of 8 years was not associated with adolescent self-harm, and there was no association between speech sound disorder and self-harm without suicidal intent. CONCLUSION: Compared with individuals without speech sound disorder, adolescents with speech sound disorder at the age of 8 years have twice the risk of reporting self-harm with suicidal intent, even when other important predictors are taken into account. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22573030.

The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are uncommon and have unknown aetiology. The aim of the study was to investigate the epidemiology of GPA and MPA in a stable, well-defined population looking for differences in the pattern of occurrence, which might suggest a different aetiology. METHODS: Since 1988, we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset GPA and MPA as defined by the European Medicines Agency algorithm and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2010 were identified. The population in 2008 was estimated to be 459 000 (221 000 males). RESULTS: One hundred and eleven GPA and 58 MPA incident cases were identified during 1988-2010. The overall annual incidence of GPA and MPA was 11.3/million and 5.9/million, respectively. There was evidence of a cyclical pattern of occurrence with a periodicity of 7.6 years for GPA with a peak incidence of 28.3/million in 2005 and the lowest in 2002 (2.2/million). Other lesser peaks occurred in 1990 and 1996. While the peak incidence of MPA was in 2008 (15.2/million), there was no convincing evidence of periodicity. The incidence of cANCA/PR3- or pANCA/MPO-positive vasculitis showed a similar pattern to GPA and MPA, respectively. CONCLUSION: This study lends support to the notion that the aetiology of GPA and MPA may be distinct conditions with different aetiologies. The cyclical incidence of GPA is possibly an indication for the influence of infection.

Mental health, well-being and support interventions for UK ambulance services staff: an evidence map, 2000 to 2020.

BACKGROUND: Prior to COVID-19 there had been a renewed policy focus in the National Health Service on the health and well-being of the healthcare workforce, with the ambulance sector identified as a priority area. This focus is more important than ever as the sector deals with the acute and longer-term consequences of a pandemic. AIM: To systematically identify, summarise and map the evidence regarding mental health, well-being and support interventions for United Kingdom ambulance services staff and to identify evidence gaps. METHOD: Evidence mapping methodology of published and grey original research published in English from 1 January 2000 to 23 May 2020 describing the health risk, mental health and/or well-being of UK ambulance services staff including retired staff, volunteers and students. MEDLINE, EMBASE, PsychINFO, CINAHL and AMED databases, plus EThOS, Zetoc, OpenGrey and Google, were searched, alongside hand-searching of grey literature and bibliographies. Information was extracted on study aims, sample, design and methodology, funding source, country and key findings. Included studies were categorised into seven a priori theme areas. RESULTS: Of 1862 identified articles, 45 peer-reviewed studies are included as well as 24 grey literature documents. Peer-reviewed research was largely observational and focused on prevalence studies, post-traumatic stress disorder or organisational and individual social factors related to health and well-being. Most grey literature reported the development and testing of interventions. Across all study types, underpinning theory was often not cited. CONCLUSION: To date, intervention research has largely been funded by charities and published in the grey literature. Few studies were identified on self-harm, bullying, sleep and fatigue or alcohol and substance use. Theoretically informed intervention development and testing, including adaptation of innovations from other countries and 24-hour workforces, is needed. This evidence map provides important context for planning of staff well-being provision and research as the sector responds to and recovers from the pandemic. PROSPERO REGISTRATION NUMBER: CRD42018104659.

REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.

Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.

Genetic selection? A study of individual variation in the enzymes of folate metabolism.

BACKGROUND: Genetic variation in folate metabolism has been associated with survival in utero, the success of in vitro fertilisation, multiple pathologies and longevity. METHODS: We have looked at the prevalence of genetic variants of the enzymes MTHFR and TYMS in 2,898 DNA samples derived from five cohorts collected in the United Kingdom. The simultaneous analysis of genetic variants of the MTHFR and TYMS loci was carried out to investigate a putative gene-gene interaction that was first observed in an elderly male population from Norfolk. RESULTS: We have made a consistent observation in five population cohorts; the proportion of individuals who are homozygous for the 2R allele of the 5'UTR TYMS polymorphism is less in individuals who are homozygous for the T allele of MTHFR 677 than in individuals homozygous for the C allele of MTHFR 677 (p = 0.02). CONCLUSIONS: These data may suggest a gene-gene interaction and could be evidence of genetic selection, with some pregnancies more or less viable as a consequence of genetic variation. If these genetic phenomena affect the way folate is handled at the cellular level in utero it is possible that maternal folic acid intake may over-ride such genetic selection.

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action.

BACKGROUND: Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. METHODS: Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. RESULTS: Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. CONCLUSIONS: Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action.

Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins.

Circulating adiponectin is emerging as an important link between obesity, type 2 diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle factors that modulate the adiponectin concentration remains to be elucidated, particularly among women. We conducted a cross-sectional study of 877 female twin pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined dietary and body composition influences on adiponectin by conducting matched, within-pair analyses to eliminate confounding. Following multivariable adjustment within-twin pairs, significant influences on adiponectin (log-transformed, percent change per SD of the dietary/body composition variable) were observed for nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08). These modest positive associations cannot be explained by confounding through other lifestyle factors shared by the twins. A significant relationship between adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English), carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: -13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were significant both when twins were analyzed as individuals and when characteristics were contrasted within-twin pairs, suggesting a direct effect. We observed modest associations between dietary factors and adiponectin in female twins, independent of adiposity, and report strong inverse associations with body composition. These data reinforce the importance of weight maintenance and increasing consumption of diets rich in plant-based foods to prevent CVD and type 2 diabetes.

Use of dietary indices to control for diet in human gut microbiota studies.

BACKGROUND: Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. RESULTS: All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. CONCLUSIONS: We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.

A novel cardiac output response to stress test developed to improve diagnosis and monitoring of heart failure in primary care.

AIMS: Primary care physicians lack access to an objective cardiac function test. This study for the first time describes a novel cardiac output response to stress (CORS) test developed to improve diagnosis and monitoring of heart failure in primary care and investigates its reproducibility. METHODS AND RESULTS: Prospective observational study recruited 32 consecutive primary care patients (age, 63 ± 9 years; female, n = 18). Cardiac output was measured continuously using the bioreactance method in supine and standing positions and during two 3 min stages of a step-exercise protocol (10 and 15 steps per minute) using a 15 cm height bench. The CORS test was performed on two occasions, i.e. Test 1 and Test 2. There was no significant difference between repeated measures of cardiac output and stroke volume at supine standing and Stage 1 and Stage 2 step exercises (all P > 0.3). There was a significant positive relationship between Test 1 and Test 2 cardiac outputs (r = 0.92, P = 0.01 with coefficient of variation of 7.1%). The mean difference in cardiac output (with upper and lower limits of agreement) between Test 1 and Test 2 was 0.1 (-1.9 to 2.1) L/min, combining supine, standing, and step-exercise data. CONCLUSIONS: The CORS, as a novel test for objective evaluation of cardiac function, demonstrates acceptable reproducibility and can potentially be implemented in primary care.

Dietary patterns and heritability of food choice in a UK female twin cohort.

To examine the contribution of genetic factors to food choice, we determined dietary patterns from food frequency questionnaires in 3262 UK female twins aged 18 to 79 years. Five distinct dietary patterns were identified (fruit and vegetable, high alcohol, traditional English, dieting, low meat) that accounted for 22% of the total variance. These patterns are similar to those found in other singleton Western populations, and were related to body mass index, smoking status, physical activity and deprivation scores. Older subjects had higher scores on the fruit and vegetable and traditional English patterns, while lower social deprivation was associated with higher scores for fruit and vegetable, and lower scores for traditional English patterns. All 5 patterns were heritable, with estimates ranging from 41% to 48%. Among individual dietary components, a strongly heritable component was identified for garlic (46%), coffee (41%), fruit and vegetable sources (49%), and red meat (39%). Our results indicate that genetic factors have an important influence in determining food choice and dietary habits in Western populations. The relatively high heritability of specific dietary components implicates taste perception as a possible target for future genetic studies.