Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults.

OBJECTIVE: To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years. METHODS: Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n = 156) and 10-13 year follow-up at CDAH-3 (n = 167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n = 313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML. RESULTS: In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (ß:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (ß:-141.548; 95%CI:-254.917,-28.179) and total bone area (ß:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (ß:-0.001; 95%CI:-0.002,-0.00004), and total bone area (ß:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (ß:-0.001; 95%CI:-0.001,-0.0001) and total bone area (ß:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA. CONCLUSION: COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.

Incentivising public transport use for physical activity gain: process evaluation of the COVID-19 disrupted trips4health randomised controlled trial.

BACKGROUND: Partnering with a public transport (PT) provider, state government, and local government, the single-blinded randomised controlled trial, trips4health, investigated the impact of PT use incentives on transport-related physical activity (PA) in Tasmania, Australia. The intervention involved 16-weeks of incentives (bus trip credits) for achieving weekly PT use targets, supported by weekly text messages. This study objective was to conduct a process evaluation of the COVID-19 disrupted trips4health study. METHODS: The Medical Research Council UK's framework for complex public health interventions guided the process evaluation. Participant reach, acceptability, fidelity and feasibility were evaluated. Administrative and post-intervention survey data were analysed descriptively. Semi-structured interviews with intervention participants (n = 7) and PT provider staff (n = 4) were analysed thematically. RESULTS: Due to COVID-19, trips4health was placed on hold (March 2020) then stopped (May 2020) as social restrictions impacted PT use. At study cessation, 116 participants (approximately one third of target sample) had completed baseline measures, 110 were randomised, and 64 (n = 29 in the intervention group; n = 35 in the control group) completed post-intervention measures. Participants were 18 - 80 years (average 44.5 years) with females (69%) and those with tertiary education (55%) over-represented. The intervention was delivered with high fidelity with 96% of bus trip credits and 99% of behavioural text messages sent as intended. Interviewed PT staff said implementation was highly feasible. Intervention participant acceptability was high with 90% reporting bus trip incentives were helpful and 59% reporting the incentives motivated them to use PT more. From a total of 666 possible bus trip targets, 56% were met with 38% of intervention participants agreeing and 41% disagreeing that 'Meeting the bus trip targets was easy'. Interviews and open-ended survey responses from intervention participants revealed incentives motivated bus use but social (e.g., household member commitments) and systemic (e.g., bus availability) factors made meeting bus trip targets challenging. CONCLUSIONS: trips4health demonstrated good acceptability and strong fidelity and feasibility. Future intervention studies incentivising PT use will need to ensure a broader demographic is reached and include more supports to meet PT targets. TRIAL REGISTRATION: ACTRN12619001136190 .

Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study.

STUDY QUESTION: Is high adiposity in childhood associated with menstrual irregularity and polycystic ovary syndrome (PCOS) in later life? SUMMARY ANSWER: Overall, greater childhood BMI was associated with menstrual irregularity, and greater childhood BMI and waist/height ratio (WHtR) in white but not black participants were associated with PCOS in adulthood. WHAT IS KNOWN ALREADY: Increased childhood BMI has been associated with irregular menstrual cycles and PCOS symptoms in adulthood in two longitudinal population-based studies, but no study has reported on associations with childhood abdominal obesity. Few studies have investigated whether there are racial differences in the associations of adiposity with PCOS though there has been some suggestion that associations with high BMI may be stronger in white girls than in black girls. STUDY DESIGN, SIZE, DURATION: The study included 1516 participants (aged 26-41 years) from the Australian Childhood Determinants of Adult Health study (CDAH) and 1247 participants (aged 26-57 years) from the biracial USA Babies substudy of the Bogalusa Heart Study (BBS) who were aged 7-15 years at baseline. At follow-up, questions were asked about menstruation (current for CDAH or before age 40 years for BBS), ever having had a diagnosis of PCOS and symptoms of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: In CDAH, a single childhood visit was conducted in 1985. In BBS, multiple childhood visits occurred from 1973 to 2000 and race was reported (59% white; 41% black). In childhood, overweight and obesity were defined by international age-sex-specific standards for BMI and WHtR was considered as an indicator of abdominal obesity. Multilevel mixed-effects Poisson regression estimated relative risks (RRs) adjusting for childhood age, highest parental and own education and age at menarche. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of childhood obesity was 1.1% in CDAH and 7.5% in BBS. At follow-up, menstrual irregularity was reported by 16.7% of CDAH and 24.5% of BBS participants. The prevalence of PCOS was 7.4% in CDAH and 8.0% in BBS participants. In CDAH, childhood obesity was associated with menstrual irregularity (RR = 2.84, 95% CI: 1.63-4.96) and PCOS (RR = 4.05, 95% CI: 1.10-14.83) in adulthood. With each 0.01 unit increase in childhood WHtR there was a 6% (95% CI: 1-11%) greater likelihood of PCOS. Overall, in BBS, childhood obesity was associated with increased risk of menstrual irregularity (RR = 1.44, 95% CI: 1.08-1.92) in adulthood. Significant interaction effects between race and childhood adiposity were detected in associations with PCOS. In BBS white participants, childhood obesity was associated with PCOS (RR = 2.93, 95% CI: 1.65-5.22) and a 0.01 unit increase in childhood WHtR was associated with an 11% (95% CI: 5-17%) greater likelihood of PCOS in adulthood. In BBS black participants, no statistically significant associations of childhood adiposity measures with PCOS were observed. LIMITATIONS, REASONS FOR CAUTION: The classification of menstrual irregularity and PCOS was based on self-report by questionnaire, which may have led to misclassification of these outcomes. However, despite the limitations of the study, the prevalence of menstrual irregularity and PCOS in the two cohorts was consistent with the literature. While the study samples at baseline were population-based, loss to follow-up means the generalizability of the findings is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Greater childhood adiposity indicates a higher risk of menstrual irregularity and PCOS in adulthood. Whether this is causal or an early indicator of underlying hormonal or metabolic disorders needs clarification. The stronger associations of adiposity with PCOS in white than black participants suggest that there are racial differences in childhood adiposity predisposing to the development of PCOS and other environmental or genetic factors are also important. STUDY FUNDING/COMPETING INTEREST(S): The CDAH study was supported by grants from the Australian National Health and Medical Research Council (grants 211316, 544923 and 1128373). The Bogalusa Heart Study is supported by US National Institutes of Health grants R01HD069587, AG16592, HL121230, HD032194 and P50HL015103. No competing interests existed.

An eating pattern characterised by skipped or delayed breakfast is associated with mood disorders among an Australian adult cohort.

BACKGROUND: Meal timing may influence food choices, neurobiology and psychological states. Our exploratory study examined if time-of-day eating patterns were associated with mood disorders among adults. METHODS: During 2004-2006 (age 26-36 years) and 2009-2011 (follow-up, age 31-41 years), N = 1304 participants reported 24-h food and beverage intake. Time-of-day eating patterns were derived by principal components analysis. At follow-up, the Composite International Diagnostic Interview measured lifetime mood disorder. Log binomial and adjacent categories log-link regression were used to examine bidirectional associations between eating patterns and mood disorder. Covariates included sex, age, marital status, social support, education, work schedule, body mass index and smoking. RESULTS: Three patterns were derived at each time-point: Grazing (intake spread across the day), Traditional (highest intakes reflected breakfast, lunch and dinner), and Late (skipped/delayed breakfast with higher evening intakes). Compared to those in the lowest third of the respective pattern at baseline and follow-up, during the 5-year follow-up, those in the highest third of the Late pattern at both time-points had a higher prevalence of mood disorder [prevalence ratio (PR) = 2.04; 95% confidence interval (CI) 1.20-3.48], and those in the highest third of the Traditional pattern at both time-points had a lower prevalence of first onset mood disorder (PR = 0.31; 95% CI 0.11-0.87). Participants who experienced a mood disorder during follow-up had a 1.07 higher relative risk of being in a higher Late pattern score category at follow-up than those without mood disorder (95% CI 1.00-1.14). CONCLUSIONS: Non-traditional eating patterns, particularly skipped or delayed breakfast, may be associated with mood disorders.

Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

OBJECTIVE: To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. METHODS: 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. RESULTS: Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m2, 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. CONCLUSION: Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults.

Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH.

Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pHCF) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pHCF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (AT). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pHCF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [AT], revealing that seawater pH is not the sole driver of pHCF Notably, when we synthesize our results with published data, we identify linear relationships of pHCF with the seawater [DIC]/[H+] ratio, [AT]/ [H+] ratio and [[Formula: see text]]. Our findings contribute new insights into the mechanisms determining the sensitivity of coral calcification to changes in seawater carbonate chemistry, which are needed for predicting effects of environmental change on coral reefs and for robust interpretations of isotopic palaeoenvironmental records in coral skeletons.

Associations of childhood and adult obesity with left ventricular structure and function.

BACKGROUND: Overweight and obesity are associated with left ventricular (LV) dysfunction. We sought whether echocardiographic evidence of abnormal adult cardiac structure and function was related to childhood or adult adiposity. METHODS: This study included 159 healthy individuals aged 7-15 years and followed until age 36-45 years. Anthropometric measurements were performed both at baseline and follow-up. Cardiac structure (indexed left atrial volume (LAVi), left ventricular mass (LVMi)) and LV function (global longitudinal strain (GLS), mitral e') were assessed using standard echocardiography at follow-up. Conventional cutoffs were used to define abnormal LAVi, LVMi, GLS and mitral annular e'. RESULTS: Childhood body mass index (BMI) was correlated with LVMi (r=0.25, P=0.002), and child waist circumference was correlated with LVMi (r=0.18, P=0.03) and LAVi (r=0.20, P=0.01), but neither were correlated with GLS. One s.d. (by age and sex) increase in childhood BMI was associated with LV hypertrophy (relative risk: 2.04 (95% confidence interval (CI): 1.09, 3.78)) and LA enlargement (relative risk: 1.81 (95% CI: 1.02, 3.21)) independent of adult BMI, but the association was not observed with impaired GLS or mitral e'. Cardiac functional measures were more impaired in those who had normal BMI as child, but had high BMI in adulthood (P<0.03), and not different in those who were overweight or obese as a child and remained so in adulthood (P>0.33). CONCLUSIONS: Childhood adiposity is independently associated with structural cardiac disturbances (LVMi and LAVi). However, functional alterations (GLS and mitral e') were more frequently associated with adult overweight or obesity, independent of childhood adiposity.

Childhood fitness reduces the long-term cardiometabolic risks associated with childhood obesity.

OBJECTIVE: The objective of this study was to examine whether childhood cardiorespiratory fitness attenuates or modifies the long-term cardiometabolic risks associated with childhood obesity. DESIGN AND METHODS: The study consisted of a 20-year follow-up of 1792 adults who participated in the 1985 Australian Schools Health and Fitness Survey when they were 7-15 years of age. Baseline measures included a 1.6-km run to assess cardiorespiratory fitness and waist circumference to assess abdominal adiposity. At follow-up, participants attended study clinics where indicators of Metabolic Syndrome (MetS) (waist circumference, blood pressure, fasting blood glucose and lipids) were measured and cardiorespiratory fitness was reassessed using a submaximal graded exercise test. RESULTS: Both high waist circumference and low cardiorespiratory fitness in childhood were significant independent predictors of MetS in early adulthood. The mutually adjusted relative risk of adult MetS was 3.00 (95% confidence interval: 1.85-4.89) for children in the highest (vs lowest) third of waist circumference and 0.64 (95% confidence interval: 0.43-0.96) for children with high (vs low) cardiorespiratory fitness. No significant interaction between waist circumference and fitness was observed, with higher levels of childhood fitness associated with lower risks of adult MetS among those with either low or high childhood waist circumference values. Participants who had both high waist circumference and low cardiorespiratory fitness in childhood were 8.5 times more likely to have MetS in adulthood than those who had low waist circumference and high cardiorespiratory fitness in childhood. Regardless of childhood obesity status, participants with low childhood fitness who increased their relative fitness by adulthood had a substantially lower prevalence of MetS than those who remained low fit. CONCLUSIONS: Childhood waist circumference and cardiorespiratory fitness are both strongly associated with cardiometabolic health in later life. Higher levels of cardiorespiratory fitness substantially reduce the risk of adult MetS, even among those with abdominal obesity in childhood.

Bi-directional associations between healthy lifestyles and mood disorders in young adults: The Childhood Determinants of Adult Health Study.

BACKGROUND: Healthy lifestyles prevent cardiovascular disease and are increasingly recognized in relation to mental health but longitudinal studies are limited. We examined bi-directional associations between mood disorders and healthy lifestyles in a cohort followed for 5 years. METHOD: Participants were aged 26-36 years at baseline (2004-2006) and 31-41 years at follow-up (2009-2011). At follow-up, lifetime mood disorders (depression or dysthymia) were retrospectively diagnosed with the Composite International Diagnostic Interview. A five-item lifestyle score (comprising body mass index, non-smoking, alcohol consumption, leisure time physical activity and healthy diet) was measured at both time points. Linear and log multinomial regression determined if mood disorder before baseline predicted changes in lifestyle (n = 1041). Log binomial regression estimated whether lifestyle at baseline predicted new episodes of mood disorder (n = 1233). Covariates included age, sex, socio-economic position, parental and marital status, social support, major life events, cardiovascular disease history, and self-rated physical and mental health. RESULTS: A history of mood disorder before baseline predicted unfavourable trajectories of lifestyle over follow-up, including somewhat lower risk of improvement [relative risk (RR) 0.76, 95% confidence interval (CI) 0.56-1.03] and greater risk of worsening (RR 1.46, 95% CI 0.99-2.15) of lifestyle independent of confounding factors. Higher lifestyle scores at baseline were associated with a 22% (RR 0.76, 95% CI 0.61-0.95) reduced risk of first episodes of mood disorder, independent of confounding factors. CONCLUSIONS: Healthy lifestyles and mood disorders are closely related. Our results suggest that healthy lifestyles may not only reduce cardiovascular disease but also promote mental health.

Is Helicobacter Pylori infection inversely associated with atopy? A systematic review and meta-analysis.

BACKGROUND: The role Helicobacter Pylori (H. pylori) infection plays in the aetiology of atopy remains unclear, although a possible protective role has been hypothesized. OBJECTIVE: The aim of this study was to undertake a systematic review and meta-analysis of epidemiological studies to quantify the association between H. pylori infection and atopy. METHODS: A comprehensive literature search in MEDLINE/PUBMED and EMBASE (up to August 2013) was carried out to identify all observational epidemiological studies (cross-sectional, cohort and case-control) published in English that evaluated the association between H. pylori infection and objectively measured atopy (measured by allergen skin tests or specific IgE). The quality of included studies was assessed by the Newcastle-Ottawa scale. Random-effects meta-analyses were performed to obtain pooled estimates of effect. RESULTS: Twenty-two observational studies involving 21 348 participants were identified as eligible for inclusion in the review, of which 16 were included in the meta-analysis. H. pylori infection was associated with a significantly reduced odds of atopy (pooled odds ratio (OR) 0.82; 95% confidence interval (CI) 0.73 - 0.91; P < 0.01). Subgroup analysis according to atopy definition revealed a slightly greater protective effect for atopy defined as raised allergen-specific IgE (OR 0.75; 95% CI 0.62 - 0.92; P < 0.01; seven studies). Findings did not differ according to the population age (adult or children), methodological quality or study design. CONCLUSION AND CLINICAL RELEVANCE: Evidence from epidemiological studies suggests that H. pylori infection is associated with an estimated 18% reduction in odds of atopy. If the observed association is causal, more insights into the underlying mechanisms could provide clues to possible therapeutic opportunities in allergic disease.

Exposure to Helicobacter pylori infection in early childhood and the risk of allergic disease and atopic sensitization: a longitudinal birth cohort study.

BACKGROUND: An inverse relation between Helicobacter pylori infection and allergic disease has been reported by a range of independent epidemiological studies, but evidence from longitudinal studies is scarce. OBJECTIVE: We have investigated the effects of H. pylori infection on the incidence and prevalence of allergic diseases and sensitization in a low-income birth cohort. METHODS: In 2005/2006, a population-based birth cohort was established in Butajira, Ethiopia, and the 1006 singleton babies born were followed up at ages 1, 3, and 5. Symptoms of allergic disease were collected using the ISAAC questionnaire, allergen skin tests performed, and stool samples analysed for H. pylori antigen and geohelminths. Multiple logistic regression was used to determine the independent effects of H. pylori measured at age 3 on the incidence of each outcome between ages 3 and 5 years (in those without the outcome at age 3), controlling for potential confounders, and to additionally assess cross-sectional associations. RESULTS: A total of 863 children were followed up to age 5. H. pylori infection was found in 25% of the children at both ages 3 and 5, in 21% at age 5 but not 3, and in 17% at age 3 but not at age 5. H. pylori infection at age 3 was significantly associated with a decreased risk of incident eczema between ages 3 and 5 (adjusted OR, 95% CI, 0.31; 0.10-0.94, P = 0.02). Cross-sectionally at age 5, H. pylori infection was inversely associated with skin sensitization (adjusted OR, 95% CI, 0.26; 0.07-0.92, P = 0.02). CONCLUSION AND CLINICAL RELEVANCE: These findings provide further evidence to suggest that early-life exposure to H. pylori may play a protective role in the development of allergy.

Chemotherapy-related cardiomyopathy: a neglected aspect of cancer survivorship.

Improvements in survival from cancer have led to a large population who are at risk of late complications of chemotherapy. One of the most serious cardiovascular complications is chemotherapy-related cardiomyopathy (CRC), which may become clinically overt years or even decades after treatment and has over threefold higher mortality rate compared with idiopathic dilated cardiomyopathy. The early stages of this condition appear to respond well to cardioprotective medications (i.e. angiotensin-converting enzyme inhibitors, ß-blockers). Periodic cardiac monitoring is necessary in this population to identify patients who would benefit from treatment. Cardio-oncology clinics have been established in recognition of this hazard in survivorship. This review summarises the epidemiology and pathophysiology of CRC, the evidence base for different non-invasive imaging modalities for screening and diagnosis and the rationale for treatment.

Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods.

BACKGROUND: The Patient-Oriented Eczema Measure (POEM) is a validated, patient-derived assessment measure for monitoring atopic eczema severity, although further information on how different POEM scores translate into disease severity categories is needed for clinical trials, epidemiological research and audit. OBJECTIVES: We sought to determine the relationship between Patient-Oriented Eczema Measure (POEM) scores (range 0-28) and two Global Questions (GQ1 and 2) concerning patients'/parents' views of the overall severity of their/their child's atopic eczema, in order to stratify POEM scores into five severity bands. METHODS: POEM scores and GQs were completed by 300 patients from general practice and 700 patients from dermatology outpatient clinics, including 300 adults aged ≥ 16 years and 700 children. RESULTS: The mean POEM score was 13·6 (range 0-28), and standard deviation (SD) was 7·2. Mean GQ1/GQ2 scores were 2·1/2·1, respectively (range 0-4 and SD 1·1 for both). The mean, mode and median of the GQ scores for each POEM score were used to devise possible POEM bandings. The proposed banding for POEM scores are: 0-2 (clear/almost clear); 3-7 (mild); 8-16 (moderate); 17-24 (severe); 25-28 (very severe), kappa coefficient 0·46. CONCLUSIONS: Severity banding of the POEM will allow more clinically meaningful use in everyday clinical practice and as a core outcome measure in future atopic eczema research.

Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Imaging intracellular pH in a reef coral and symbiotic anemone.

The challenges corals and symbiotic cnidarians face from global environmental change brings new urgency to understanding fundamental elements of their physiology. Intracellular pH (pHi) influences almost all aspects of cellular physiology but has never been described in anthozoans or symbiotic cnidarians, despite its pivotal role in carbon concentration for photosynthesis and calcification. Using confocal microscopy and the pH sensitive probe carboxy SNARF-1, we mapped pHi in short-term light and dark-incubated cells of the reef coral Stylophora pistillata and the symbiotic anemone Anemonia viridis. In all cells isolated from both species, pHi was markedly lower than the surrounding seawater pH of 8.1. In cells that contained symbiotic algae, mean values of pHi were significantly higher in light treated cells than dark treated cells (7.41 +/- 0.22 versus 7.13 +/- 0.24 for S. pistillata; and 7.29 +/- 0.15 versus 7.01 +/- 0.27 for A. viridis). In contrast, there was no significant difference in pHi in light and dark treated cells without algal symbionts. Close inspection of the interface between host cytoplasm and algal symbionts revealed a distinct area of lower pH adjacent to the symbionts in both light and dark treated cells, possibly associated with the symbiosome membrane complex. These findings are significant developments for the elucidation of models of inorganic carbon transport for photosynthesis and calcification and also provide a cell imaging procedure for future investigations into how pHi and other fundamental intracellular parameters in corals respond to changes in the external environment such as reductions in seawater pH.

Predictive associations between alternative measures of childhood adiposity and adult cardio-metabolic health.

OBJECTIVE: To estimate associations between alternative measures of childhood adiposity and indicators of cardio-metabolic health in adulthood, both unadjusted and adjusted for changes in adiposity from childhood to adulthood. DESIGN AND METHODS: The study consisted of a 20-year follow-up of 2188 adults who had participated in the 1985 Australian Schools Health and Fitness Survey when they were between 7 and 15 years of age. Baseline and follow-up measures of body composition included height and weight, waist and hip circumferences and skinfold thicknesses at four sites. At follow-up, participants attended study clinics where component indicators of the metabolic syndrome (MetS) (waist circumference, blood pressure, fasting blood glucose and lipids) were measured. RESULTS: Waist circumference and skinfold measures were the strongest predictors of subsequent MetS (2009 Joint Scientific Statement definition) in early adulthood. For example, relative risks (RRs) for children in the highest (vs lowest) quarter of waist circumference were 4.8 (95% confidence interval (CI): 2.5-9.2) for males and 5.8 (95% CI: 2.4-14.2) for females. After adjusting for change in waist circumference from childhood to adulthood, each 10 cm increase in childhood waist circumference was associated with an approximate twofold increase in risk for adult MetS (RR = 2.1 (95% CI: 1.7-2.7) among males and RR = 2.3 (95% CI: 1.6-3.4) among females). CONCLUSION: Elevated waist circumference and skinfold thickness measures in childhood appear to be the strongest predictors of subsequent MetS in early adulthood. The increased risk associated with higher waist circumference in childhood appears to be independent of changes in waist circumference from childhood to adulthood.

Effects of Helicobacter pylori, geohelminth infection and selected commensal bacteria on the risk of allergic disease and sensitization in 3-year-old Ethiopian children.

BACKGROUND: Epidemiological studies have suggested that gastro-intestinal infections including Helicobacter pylori, intestinal microflora (commensal bacteria) and geohelminths may influence the risk of asthma and allergy but data from early life are lacking. OBJECTIVE: We aimed to determine the independent effects of these infections on allergic disease symptoms and sensitization in an Ethiopian birth cohort. METHODS: In 2008/09, 878 children (87% of the 1006 original singletons in a population-based birth cohort) were followed up at age 3 and interview data obtained on allergic symptoms and potential confounders. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were performed, levels of Der p 1 and Bla g 1 in the child's bedding measured and stool samples analysed for geohelminths and, in a random subsample, enterococci, lactobacilli, bifidobacteria and H. pylori antigen. The independent effects of each exposure on wheeze, eczema, hayfever and sensitization were determined using multiple logistic regression. RESULTS: Children were commonly infected with H. pylori (41%; 253/616), enterococci (38.1%; 207/544), lactobacilli (31.1%; 169/544) and bifidobacteria (18.9%; 103/544) whereas geohelminths were only found in 8.5% (75/866). H. pylori infection was associated with a borderline significant reduced risk of eczema (adjusted OR 0.49, 95% CI 0.24-1.01, P=0.05) and D. pteronyssinus sensitization (adjusted OR 0.42, 95% CI 0.17-1.08, P=0.07). Geohelminths and intestinal microflora were not significantly associated with any of the outcomes measured. CONCLUSION AND CLINICAL RELEVANCE: Among young children in a developing country, we found evidence to support the hypothesis of a protective effect of H. pylori infection on the risk of allergic disease. Further investigation of the mechanism of this effect is therefore of potential therapeutic and preventive value.

The associations between parity, other reproductive factors and cartilage in women aged 50-80 years.

OBJECTIVE: Sex hormones and reproductive factors may be important for osteoarthritis (OA). The aim of this study was to describe the associations of parity, use of hormone replacement therapy (HRT) and oral contraceptives (OCs) with cartilage volume, cartilage defects and radiographic OA in a population-based sample of older women. DESIGN: Cross-sectional study of 489 women aged 50-80 years. Parity, use of HRT and OC was assessed by questionnaire; knee cartilage volume and defects by magnetic resonance imaging and knee joint space narrowing (JSN) and osteophytes by X-ray. RESULTS: Parity was associated with a deficit in total knee cartilage volume [adjusted ß=-0.69 ml, 95% confidence interval (CI) -1.34, -0.04]. Increasing parity was associated with decreasing cartilage volume in both the tibial compartment and total knee (both P trend <0.05). Parity was also associated with greater cartilage defects in the patella compartment [adjusted odds ratio (OR)=2.87, 95% CI=1.39, 5.93] but not other sites. There was a consistent but non-significant increase in knee JSN (OR=2.78, 95% CI=0.75, 10.31) and osteophytes (OR=1.69, 95% CI=0.59, 4.82) for parous women. Use of HRT and/or OC was not associated with cartilage volume, cartilage defects or radiographic change. CONCLUSIONS: Parity (but not use of HRT or OC) is independently associated with lower cartilage volume primarily in the tibial compartment and higher cartilage defects in the patella compartment in this population-based sample of older women.

Oral contraceptive use and bone mass in women aged 26-36 years.

INTRODUCTION: The association between hormonal contraceptive use and bone mineral density remains controversial. HYPOTHESIS: Hormonal contraceptive use is positively associated with bone mass in young premenopausal women. METHODS: Cross-sectional analysis of data collected from women aged 26-36 years (n = 687) in the Childhood Determinants of Adult Health study-a longitudinal study investigating childhood determinants of cardiovascular disease, diabetes, and other chronic diseases in adulthood. Participants were not currently pregnant or breast-feeding. Contraceptive use was obtained by self-administered questionnaire. Women were categorized as combined oral contraceptive users (n = 219), progestogen-only contraceptive users (n = 43), and non-users of hormonal contraceptives (n = 425). Bone mass was measured by quantitative ultrasound. RESULTS: Compared with women who were not using any hormonal contraceptives, women using combined oral contraceptives had significantly higher values of broadband ultrasound attenuation (BUA), speed of sound, and quantitative ultrasound index. These associations remained after adjustment for confounders. Progestogen-only contraceptive users had higher BUA than non-users, but the differences were not statistically significant in this small group. CONCLUSION: Combined oral contraceptive use was associated with higher bone mass measured by quantitative ultrasound in this population-based sample of premenopausal women aged 26-36 while progestogen-only contraceptives appeared to have no deleterious effect on bone mass.