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Aim: To examine the relationship between indices of undiagnosed OSA and the development of abnormal glycaemic control in community-dwelling men free of diabetes., Methods: The Men, Androgens, Inflammation, Lifestyle, Environment, and Stress (MAILES) Study is a population-based cohort study in Adelaide, South Australia. Clinic visits at baseline (2002-06) and follow-up (2007-10) identified abnormal glycaemic metabolism [HbA1c 6.0 to <6.5% (42 to <48mmol/mol)] in men without diabetes. At follow-up (2010-11), n=837 underwent assessment of OSA by full in-home unattended polysomnography (Embletta X100)., Results: Development of abnormal glycaemic metabolism over 4-6 years (n=103 "incident" cases, 17.0%) showed adjusted associations [odds ratio (95% CI)] with the 1st [1.7 (0.8-3.8)], 2nd [2.4 (1.1-4.9)], and 3rd [2.3 (1.1-4.8)] quartiles of mean oxygen saturation (SaO2) compared to the highest quartile. Prevalent abnormal glycaemic metabolism (n=140, 20.8%) was independently associated with the third and fourth quartiles of percentage of sleep time with oxygen saturation <90% and lowest quartile of mean SaO2. Linear regression analysis showed a significant reduction in HbA1c [unstandardized B, 95% CI: -0.02 (-0.04, -0.002), p=0.034] per percentage point increase in mean SaO2. OSA as measured by the apnea-hypopnea index showed no adjusted relationship with abnormal glycaemic metabolism., Conclusions: Development of abnormal glycaemic metabolism was associated with nocturnal hypoxemia. Improved management of OSA and glycaemic control may occur if patients presenting with one abnormality are assessed for the other., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi., Methods: The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status., Results: Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality., Conclusions: HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.

Mobile telephone numbers are increasingly being included in household surveys samples. As approach letters cannot be sent because many do not have address details, alternatives approaches have been considered. This study assesses the effectiveness of sending a short message service (SMS) to a random sample of mobile telephone numbers to increase response rates. A simple random sample of 9000 Australian mobile telephone numbers: 4500 were randomly assigned to be sent a pre-notification SMS, and the remaining 4500 did not have a SMS sent. Adults aged 18 years and over, and currently in paid employment, were eligible to participate. American Association for Public Opinion Research formulas were used to calculated response cooperation and refusal rates. Response and cooperation rate were higher for the SMS groups (12.4% and 28.6% respectively) than the group with no SMS (7.7% and 16.0%). Refusal rates were lower for the SMS group (27.3%) than the group with no SMS (35.9%). When asked, 85.8% of the pre-notification group indicated they remembered receiving a SMS about the study. Sending a pre-notification SMS is effective in improving participation in population-based surveys. Response rates were increased by 60% and cooperation rates by 79%.

Background: Case definition has long been an issue for comparability of results obtained for musculoskeletal pain prevalence, however the test-retest reliability of questions used to determine joint pain prevalence has not been examined. The objective of this study was to determine question reliability and the impact of question wording, ordering and the time between questions on responses., Methods: A Computer Assisted Telephone Interviewing (CATI) survey was used to re-administer questions collected as part of a population-based longitudinal cohort study. On two different occasions questions were asked of the same sample of 203 community dwelling respondents (which were initially randomly selected) aged 18 years and over at two time points 14 to 27 days apart (average 15 days). Reliability of the questions was assessed using Cohen's kappa (κ) and intraclass correlation coefficient (ICC) and whether question wording and period effects existed was assessed using a crossover design., Results: The self-reported prevalence of doctor diagnosed arthritis demonstrated excellent reliability (κ = 0.84 and κ = 0.79 for questionnaires 1 and 2 respectively). The reliability of questions relating to musculoskeletal pain and/or stiffness ranged from moderate to excellent for both types of questions, that is, those related to ever having joint pain on most days for at least a month (κ = 0.52 to κ = 0.95) and having pain and/or stiffness on most days for the last month (κ = 0.52 to κ = 0.90). However there was an effect of question wording on the results obtained for hand, foot and back pain and/or stiffness indicating that the area of pain may influence prevalence estimates., Conclusions: Joint pain and stiffness questions are reliable and can be used to determine prevalence. However, question wording and pain area may impact on estimates with issues such as pain perception and effect on activities playing a possible role in the recall of musculoskeletal pain.

Allografts are afforded a level of protection from rejection within immune-privileged tissues. Immune-privileged tissues involve mechanisms that suppress inflammation and promote immune tolerance. There are anatomical features, soluble factors, membrane-associated proteins, and alternative antigen-presenting cells (APC) that contribute to allograft survival in the immune-privileged tissue. This review presents the current understanding of how the mechanism of ocular immune privilege promotes tolerogenic activity by APC, and T cells in response to the placement of foreign antigen within the ocular microenvironment. Discussed will be the unique anatomical, cellular, and molecular mechanisms that lessen the chance for graft destroying immune responses within the eye. As more is understood about the molecular mechanisms of ocular immune privilege greater is the potential for using these molecular mechanisms in therapies to prevent allograft rejection.

The effects of 2 different weight training programs incorporating bench press (BP) and pullover (PO) exercises on swimming performance, power, enzyme activity, and fiber type distribution were studied on 16 men (age = 23 ± 4 years). A 30-second group (n = 6) performed up to 20 repetitions of BP and PO in 30 seconds. The 2-minute group (n = 6) performed a maximum of 80 repetitions of BP and PO in 2 minutes. As participants reached the prescribed 20 or 80 repetitions, the weight was increased 4.5 kg. A third group (n = 4) served as nontraining controls. Exercise groups trained 3 times per week for 6 weeks. Maximal effort swims of 50 and 200 yd were performed before and after training. Training resulted in increases in work on both exercises in both groups pre- to post-training (BP 30 seconds, 722 ± 236-895 ± 250 kg; PO 30 seconds, 586 ± 252-1,090 ± 677 kg; and BP 2 minutes, 1,530 ± 414-1,940 ± 296; PO 2 minutes, 1,212 ± 406-2,348 ± 194, p ≤ 0.05). Swim performances of the 30-second group improved for both the 50-yd (32.0 ± 6.9 seconds, 30.0 ± 5.9 seconds, p ≤ 0.05) and 200-yd swims 200.0 ± 54 seconds, 182 ± 45.1 seconds (p ≤ 0.05), whereas 2-minute training improved only the 200-yd swim (198.3 ± 32.3 seconds, 186.2 ± 32.2 seconds). No changes in swim performance were observed for the control group. Triceps muscle succinate dehydrogenase activities increased (pre 3.48 ± 1.1 μmol · g(-1) wet weight per minute, post 6.25 ± 1.5 μmoles · g(-1) wet weight per minute, p ≤ 0.05) in only the 30-second training group, whereas phosphofructokinase activities and fiber type distribution did not change in either training group. This study has demonstrated that a 30-second 20-repetition weight training program, specific to the swimming musculature without concurrent swim training, improves swimming performances at both 50- and 200-yd distances.

Background: Observational studies examining associations between hypertension and cancer are inconsistent. We explored the association of hypertension, graded hypertension and antihypertensive treatment with cancer incidence and mortality., Method: Eighty-six thousand five hundred and ninety-three participants from the Australian and New Zealand Diabetes and Cancer Collaboration were linked to the National Death Index and Australian Cancer Database. Cox proportional hazards models estimated hazard ratios and 95% confidence intervals (95% CI) for the association of treated and untreated hypertension with cancer incidence and mortality., Results: Over a median follow-up of 15.1 years, 12 070 incident and 4350 fatal cancers were identified. Untreated and treated hypertension, compared with normotension, were associated with an increased risk for cancer incidence [hazard ratio 1.06, 95% CI (1.00-1.11) and 1.09 (1.02-1.16) respectively], and cancer mortality (1.07, 0.98-1.18) and (1.15, 1.03-1.28), respectively. When compared with untreated hypertension, treated hypertension did not have a significantly greater risk for cancer incidence (1.03, 0.97-1.10) or mortality (1.07, 0.97-1.19). A significant dose-response relationship was observed between graded hypertension and cancer incidence and mortality; Ptrend = 0.053 and Ptrend = 0.001, respectively. When stratified by treatment status, these relationships remained significant in untreated, but not in treated, hypertension., Conclusion: Hypertension, both treated and untreated, is associated with a modest increased risk for cancer incidence and mortality. Similar risks in treated and untreated hypertension suggest that the increased cancer risk is not explained by the use of antihypertensive treatment.

Purpose: Obstructive sleep apnea (OSA) is now highly prevalent but largely undiagnosed. Quality of life is an indicator of both the impact of undiagnosed OSA and the need for strategies to increase OSA diagnosis. We determined age-related impacts of undiagnosed OSA on health-related quality of life (HRQL) and whether this was independent of sleepiness and comorbidities., Methods: In 2010-2012, 837 participants from the Men Androgen Inflammation Lifestyle Environment and Stress Study (population cohort n = 1869, ≥40 years, Adelaide, Australia), without a prior OSA diagnosis underwent full in-home polysomnography (Embletta X100) and completed the Epworth Sleepiness Scale and SF-36 questionnaire. The effects of the apnea-hypopnea index (AHI) on SF-36 physical (PCS) and mental (MCS) component summary scores and standardized SF-36 scale z-scores were estimated using multiple linear regression adjusted for major comorbidities and sleepiness, stratified by age., Results: Men ≤69 years demonstrated significant (p < 0.05) decrements/event increase in AHI in PCS score [unstandardized B coefficient (SE) = -0.068 (0.023)], physical functioning, role physical, general health, and vitality z-scores in fully adjusted models. Severe OSA (AHI ≥30) was associated with significant reductions in PCS [B = -4.1 (1.1)] and MCS score [B = -3.6 (1.2)] independent of sleepiness and comorbidities which were attenuated but persisted in men <69 years without depression. In men aged ≥70 years, statistically significant AHI-associated impairments were generally not seen., Conclusions: Undiagnosed OSA was a major independent contributor to HRQL impairments in men <69 years. Improved strategies to identify undiagnosed OSA are indicated that may require a reduced focus on daytime sleepiness.

Background: The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression. This study aimed to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders., Methods: Participants were randomly-selected from urban, community-dwelling males aged 35-80 years at recruitment (n = 1195; sample response rate:67.8%). Of these, 730 men who attended baseline (2002-5) and follow-up clinic visits (2007-10), with complete outcome measures, and without prostate or bladder cancer and/or surgery, neurodegenerative conditions, or antipsychotic medications use, were selected for the present study. Unadjusted and multi-adjusted regression models of incident storage and voiding LUTS and incident depression and anxiety were combined with serum inflammatory markers (high-sensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), soluble e-selectin (e-Sel)) and socio-demographic, lifestyle, and health-related factors. Hierarchical multiple regression was used to assessed the moderating effect of inflammatory markers., Results: The incidence of storage, voiding LUTS, depression and anxiety was 16.3% (n = 108), 12.1% (n = 88), 14.5% (n = 108), and 12.2% (n = 107). Regression models demonstrated that men with depression and anxiety at baseline were more likely to have incident storage, but not voiding LUTS (OR: 1.26, 99%CI: 1.01-4.02; and OR:1.74; 99%CI:1.05-2.21, respectively). Men with anxiety and storage LUTS at baseline were more likely to have incident depression (OR: 2.77, 99%CI: 1.65-7.89; and OR:1.45; 99%CI:1.05-2.36, respectively), while men with depression and voiding LUTS were more likely to have anxiety at follow-up (OR: 5.06, 99%CI: 2.81-9.11; and OR:2.40; 99%CI:1.16-4.98, respectively). CRP, TNF-α, and e-Sel were found to have significant moderating effects on the development of storage LUTS (1.06, 0.91-1.96, R2 change: 12.7%), depression (1.17, 1.01-1.54, R2 change: 9.8%), and anxiety (1.35, 1.03-1.76, R2 change: 10.6%), respectively., Conclusions: There is a bidirectional relationship between storage, but not voiding, LUTS and both depression and anxiety. We observed variable moderation effects for selected inflammatory markers on the development of depression, anxiety and storage LUTS.

A challenge for population health surveillance systems using telephone methodologies is to maintain representative estimates as response rates decrease. Raked weighting, rather than conventional poststratification methodologies, has been developed to improve representativeness of estimates produced from telephone-based surveillance systems by incorporating a wider range of sociodemographic variables using an iterative proportional fitting process. This study examines this alternative weighting methodology with the monthly South Australian population health surveillance system report of randomly selected people of all ages in 2013 (n = 7,193) using computer-assisted telephone interviewing. Poststratification weighting used age groups, sex, and area of residence. Raked weights included an additional 6 variables: dwelling status, number of people in household, country of birth, marital status, educational level, and highest employment status. Most prevalence estimates (e.g., diabetes and asthma) did not change when raked weights were applied. Estimates that changed by at least 2 percentage points (e.g., tobacco smoking and mental health conditions) were associated with socioeconomic circumstances, such as dwelling status, which were included in the raked-weighting methodology. Raking methodology has overcome, to some extent, nonresponse bias associated with the sampling methodology by incorporating lower socioeconomic groups and those who are routinely not participating in population surveys into the weighting formula., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128) from Stage 3 (2008-10) of the North West Adelaide Health Study (1999-2003, baseline n = 4056) to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI), waist circumference (WC), waist hip ratio (WHR) and waist height ratio (WHtR) of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67-2.76) and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14-1.98). There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08-1.93). The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14), followed by WC (OR 1.78), WHtR (OR 1.71) and WHR (OR 1.45). WHtR (42-45%) and BMI (35-36%) provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults.

There are few studies reporting the association between lifestyle and mortality among the oldest old in developing countries. We examined the association between food habits, lifestyle factors and all-cause mortality in the oldest old (≥80 years) using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). In 1998/99, 8959 participants aged 80 years and older took part in the baseline survey. Follow-up surveys were conducted every two to three years until 2011. Food habits were assessed using an in-person interview. Deaths were ascertained from family members during follow-up. Cox and Laplace regression were used to assess the association between food habits, lifestyle factors and mortality risk. There were 6626 deaths during 31,926 person-years of follow-up. Type of staple food (rice or wheat) was not associated with mortality. Daily fruit and vegetable intake was inversely associated with a higher mortality risk (hazard ratios (HRs): 0.85 (95% CI (confidence interval) 0.77-0.92), and 0.74 (0.66-0.83) for daily intake of fruit and vegetables, respectively). There was a positive association between intake of salt-preserved vegetables and mortality risk (consumers had about 10% increase of HR for mortality). Fruit and vegetable consumption were inversely, while intake of salt-preserved vegetables positively, associated with mortality risk among the oldest old. Undertaking physical activity is beneficial for the prevention of premature death.

Background: To assess the association of socioeconomic position (SEP), measured by family financial situation and housing tenure in childhood and adulthood, with mental health conditions in adulthood., Methods: Representative cross-sectional population data were collected using a risk factor surveillance system in South Australia, Australia. Each month, a random sample were selected from the Electronic White Pages. Participants aged 25 years and above (n = 10429) were asked about doctor diagnosed anxiety, stress or depression, suicidal ideation, psychological distress, demographic and socioeconomic factors using Computer Assisted Telephone Interviewing (CATI). Social mobility measures were derived from housing status and perceived financial situation during adulthood and at 10 years of age., Results: The prevalence of psychological distress was 8.1 %, current diagnosed mental health condition was 14.8 % and suicidal ideation was 4.3 %. Upward mobility in family financial situation and housing tenure was experienced by 28.6 % and 19.3 %, of respondents respectively. Downward mobility was experienced by 9.4 % for housing tenure and 11.3 % for family financial situation. In the multivariable analysis, after adjusting for age, sex, childhood family structure and adult education, downward social mobility and stable low SEP (both childhood and adulthood), in terms of both housing tenure and financial situation, were positively associated with all three mental health conditions., Conclusion: People with low SEP in adulthood had poor mental health outcomes regardless of their socioeconomic circumstances in childhood. Policies to improve SEP have the potential to reduce mental health conditions in the population.

Aging results in significant loss of mass and function of the skeletal muscle, which negatively impacts the quality of life. In this study we investigated whether aerobic exercise training has the potential to alter anabolic and catabolic pathways in the skeletal muscle. Five and twenty eight month old rats were used in the study. Aging resulted in decreased levels of follistatin/mTOR/Akt/Erk activation and increased myostatin/Murf1/2, proteasome subunits, and protein ubiquitination levels. In addition, TNF-α, reactive oxygen species (ROS), p53, and Bax levels were increased while Bcl-2 levels were decreased in the skeletal muscle of aged rats. Six weeks of exercise training at 60% of VO2max reversed the age-associated activation of catabolic and apoptotic pathways and increased anabolic signaling. The results suggest that the age-associated loss of muscle mass and cachexia could be due to the orchestrated down-regulation of anabolic and up-regulation of catabolic and pro-apoptotic processes. These metabolic changes can be attenuated by exercise training., (Copyright © 2015. Published by Elsevier Inc.)

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Study Objectives: Studies examining the longitudinal association of untreated obstructive sleep apnea (OSA) with diabetes in population samples are limited. This study therefore examined the relationship between previously undiagnosed OSA with incident type 2 diabetes in community-dwelling men aged ≥ 40 y., Methods: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study is a longitudinal population-based cohort in Adelaide, South Australia. Clinic assessments at baseline and follow-up identified diabetes (self-reported doctor diagnosed, fasting plasma glucose ≥ 7.0 mmol/L, glycated hemoglobin ≥ 6.5% or diabetes medication use) and included anthropometry. At cohort follow-up (2010-2012), n = 837 underwent full in-home unattended polysomnography (PSG, Embletta X100, Broomfield, CO)., Results: Of 736 men free of diabetes at baseline, incident diabetes occurred in 66 (9.0%) over a mean follow-up time of 56 mo (standard deviation = 5, range: 48-74 mo). Incident diabetes was associated with current oxygen desaturation index (3%) ≥ 16 events/h (odds ratio [OR]: 1.85 [1.06-3.21]), and severe OSA [OR: 2.6 (1.1-6.1)], in adjusted models including age, percentage total body fat, and weight gain (> 5 cm waist circumference). An age-adjusted association of incident diabetes with percentage of total sleep time with oxygen saturation < 90% did not persist after adjustment for percentage of body fat. No modification of these relationships by excessive daytime sleepiness was observed., Conclusions: Severe undiagnosed OSA and nocturnal hypoxemia were independently associated with the development of diabetes. A reduction in the burden of undiagnosed OSA and undiagnosed diabetes is likely to occur if patients presenting with one disorder are assessed for the other., (© 2015 American Academy of Sleep Medicine.)

The recovery of EAU, a mouse model of endogenous human autoimmune uveitis, is marked with the emergence of autoantigen-specific regulatory immunity in the spleen that protects the mice from recurrence of EAU. This regulatory immunity is mediated by a melanocortin-driven suppressor APC that presents autoantigen and uses adenosine to activate an antigen-specific CD4(+) Tregs through the A2Ar. These cells are highly effective in suppressing uveitis, and they appear to be inducible Tregs. In this study, we determined whether they are inducible or natural Tregs and identified the dependent mechanism for the function of these post-EAU Tregs. The post-EAU spleen CD25(+)CD4(+) T cells were sorted for NRP-1 expression and transferred to recipient mice immunized for EAU. The sorted NRP-1(-), but not the NRP-1(+), Tregs suppressed EAU. These NRP-1(-) Tregs coexpress PD-1 and PD-L1. Treatment of naive APCs with α-MSH promoted a regulatory APC that induced CD25(+) CD4(+) Tregs in a CD73-dependent manner. These Tregs were PD-L1(+) PD-1(+) NRP-1(-) FOXP3(+) HELIOS(-) and suppressed EAU when transferred to recipient mice. In contrast, PD-1(-) T cells did not suppress EAU, indicating that PD-1 is necessary for the suppressive activity of iTregs. Moreover, these Tregs did not suppress effector T cells when the PD/-1/PD-L1 pathway was blocked. These results demonstrate that post-EAU Tregs are inducible Tregs, which use a PD-1/PD-L1 mechanism to suppress disease., (© Society for Leukocyte Biology.)

Background: The considerably lower average life expectancy of Aboriginal and Torres Strait Islander Australians, compared with non-Aboriginal and non-Torres Strait Islander Australians, has been widely reported. Prevalence data for chronic disease and health risk factors are needed to provide evidence based estimates for Australian Aboriginal and Torres Strait Islanders population health planning. Representative surveys for these populations are difficult due to complex methodology. The focus of this paper is to describe in detail the methodological challenges and resolutions of a representative South Australian Aboriginal population-based health survey., Methods: Using a stratified multi-stage sampling methodology based on the Australian Bureau of Statistics 2006 Census with culturally appropriate and epidemiological rigorous methods, 11,428 randomly selected dwellings were approached from a total of 209 census collection districts. All persons eligible for the survey identified as Aboriginal and/or Torres Strait Islander and were selected from dwellings identified as having one or more Aboriginal person(s) living there at the time of the survey., Results: Overall, the 399 interviews from an eligible sample of 691 SA Aboriginal adults yielded a response rate of 57.7%. These face-to-face interviews were conducted by ten interviewers retained from a total of 27 trained Aboriginal interviewers. Challenges were found in three main areas: identification and recruitment of participants; interviewer recruitment and retainment; and using appropriate engagement with communities. These challenges were resolved, or at least mainly overcome, by following local protocols with communities and their representatives, and reaching agreement on the process of research for Aboriginal people., Conclusions: Obtaining a representative sample of Aboriginal participants in a culturally appropriate way was methodologically challenging and required high levels of commitment and resources. Adhering to these principles has resulted in a rich and unique data set that provides an overview of the self-reported health status for Aboriginal people living in South Australia. This process provides some important principles to be followed when engaging with Aboriginal people and their communities for the purpose of health research.

Background: Age, period and cohort (APC) analyses, using representative, population-based descriptive data, provide additional understanding behind increased prevalence rates., Methods: Data on obesity and diabetes from the South Australian (SA) monthly chronic disease and risk factor surveillance system from July 2002 to December 2013 (n = 59,025) were used. Age was the self-reported age of the respondent at the time of the interview. Period was the year of the interview and cohort was age subtracted from the survey year. Cohort years were 1905 to 1995. All variables were treated as continuous. The age-sex standardised prevalence for obesity and diabetes was calculated using the Australia 2011 census. The APC models were constructed with ''apcfit'' in Stata., Results: The age-sex standardised prevalence of obesity and diabetes increased in 2002-2013 from 18.6% to 24.1% and from 6.2% to 7.9%. The peak age for obesity was approximately 70 years with a steady increasing rate from 20 to 70 years of age. The peak age for diabetes was approximately 80 years. There were strong cohort effects and no period effects for both obesity and diabetes. The magnitude of the cohort effect is much more pronounced for obesity than for diabetes., Conclusion: The APC analyses showed a higher than expected peak age for both obesity and diabetes, strong cohort effects with an acceleration of risk after 1960s for obesity and after 1940s for diabetes, and no period effects. By simultaneously considering the effects of age, period and cohort we have provided additional evidence for effective public health interventions.

Objective: To investigate the associations between socio-demographic status, lifestyle factors, dietary patterns and urinary total phthalate concentration in a cohort of South Australian men., Method: We randomly selected 1527 males aged 39 to 84 from wave two of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. Total phthalate concentration was examined in fasting morning urine samples. Socio-demographic and lifestyle factors were assessed by questionnaire. Food intake was assessed by food frequency questionnaire (FFQ). Dietary patterns were constructed using factor analysis., Results: Total phthalates were detected in 99.6% of the urine samples. The overall geometric mean (95% CI) of total phthalate concentration was 112.4 (107.5-117.5) ng/mL. The least square geometric means (LSGMs) of total phthalate concentration were significantly higher among people who were obese (127.8 ng/mL), consuming less than two serves fruit per day (125.7 ng/mL) and drinking more than one can (375mL) of carbonated soft drink per day (131.9 ng/mL). Two dietary patterns were identified: a prudent dietary pattern and a western dietary pattern. Both the western dietary pattern (p = 0.002) and multiple lifestyle risk factors including smoking, obesity, insufficient physical activity and the highest quartile of the western dietary pattern (p<0.001), were positively associated with total phthalate levels. There was no significant relationship between total phthalate concentration and socio-demographic status., Conclusion: Phthalate exposure is ubiquitous and positively associated with lifestyle risk factors in urban dwelling Australian men.

Background and Aims: We aimed to examine the association between soft drink consumption and multimorbidity among adults in South Australia., Methods: Data were collected using a risk factor surveillance system between 2008 and 2013. Each month a representative random sample of South Australians are selected from the Electronic White Pages with interviews conducted using Computer Assisted Telephone Interviewing (CATI). We define multimorbidity as currently having two or more of nine chronic conditions: asthma, diabetes, hypertension, high cholesterol, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), mental health problems, osteoporosis, and arthritis., Results: Among 36,663 participants aged over 16 years old, 10.5% reported daily soft drink consumption of more than half a litre and 28.5% had multimorbidity. Soft drink consumption was positively associated with all nine chronic diseases except osteoporosis. High levels of soft drink consumption were positively associated with multimorbidity and increased with the number of chronic diseases. In the multivariable analysis, after adjusting for socio-demographic and lifestyle factors, comparing those who consumed more than half a litre of soft drink per day with those not consuming soft drink, the relative risk ratios (RRRs) for multimorbidity were 1.87 (95% CI 1.61-2.17) and higher for women 2.18 (95% CI 1.78-2.66). Multimorbidity prevalence increased with age but its association with soft drink consumption was stronger in those under 60 years old. In 2008, close to one out of three participants with multimorbidity had a high level of soft drink consumption. The prevalence of high levels of soft drink consumption decreased over the five years., Conclusion: There is a positive association between consumption of soft drink and multimorbidity among adults in South Australia and this relationship is stronger in younger people. This has implications for population level strategies to reduce the risk of developing chronic diseases and multimorbidity., (Copyright © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Residents of areas with lower socioeconomic status (SES) are known to be less physically active during leisure time. Neighborhood walkability has been shown to be related to recreational walking equally in low and high SES areas. This cross-sectional study tested whether associations of specific environmental attributes, measured objectively and subjectively, with walking for recreation were moderated by area-level SES. The data of the North West Adelaide Health Study collected in 2007 (n = 1500, mean age 57) were used. Self-reported walking frequency was the outcome of the study. Environmental exposure measures included objectively measured walkability components (residential density, intersection density, land use mix, and net retail area ratio) and perceived attributes (access to destinations, neighborhood esthetics, walking infrastructure, traffic/barriers, and crime safety). Participants' suburbs were categorized into low and high SES areas using an indicator of socioeconomic disadvantage. Low SES areas had lower scores in residential density, neighborhood esthetics, walking infrastructure, traffic/barriers, and crime safety. Recreational walking was associated with residential density, access to destinations, esthetics, traffic/barriers, and crime safety. Effect modification was observed for two attributes (out of nine): residential density was associated with walking only in low SES areas, while walking infrastructure was associated with walking only in high SES areas. The associations of neighborhood environmental attributes with recreational walking were largely consistent across SES groups. However, low SES areas were disadvantaged in most perceived environmental attributes related to recreational walking. Improving such attributes in low SES neighborhoods may help close socioeconomic disparities in leisure time physical activity.

Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = -0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence., (© 2014 by the Society for Experimental Biology and Medicine.)

The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In addition, the results further demonstrate the importance of an intact monolayer of RPE cells to modulate immune cell activity within the eye.

The aim of this paper is to examine the association of physical inactivity with incidence of obesity in the South Australian adult population. Two representative data sources were used - the South Australian Monitoring and Surveillance System (SAMSS), a monthly surveillance system, and the North West Adelaide Health Study (NWAHS), a biomedical cohort study. There were 75.3% (n = 12873) SAMSS participants and 72.8% (n = 1521) of NWAHS participants that were not obese at baseline. The cumulative incidence of obesity for SAMSS participants from the previous year to the current year was 2.7%. The cumulative incidence of obesity for NWAHS participants between baseline and stage 3 was 14.4%. Physical inactivity was associated with incident obesity (RR 1.48, 95% CI 1.14-1.90 [SAMSS] and RR 1.41, 95% CI 1.03-1.93 [NWAHS]). This association remained, but was attenuated after adjustment for chronic conditions, risk factors and socio-demographic factors. However, physical activity should be continued to be encouraged in the population for its known additional health benefits.

Background: Understanding how risk factors (tobacco, alcohol, physical inactivity, unhealthy diet, high blood pressure, and high cholesterol) change over time is a critical aim of public health. The associations across the social gradient over time are important considerations. Risk factor surveillance systems have a part to play in understanding the epidemiological distribution of the risk factors so as to improve preventive measures and design public health interventions for reducing the burden of disease., Methods: Representative, cross-sectional data were collected in South Australia using telephone interviews, conducted on a minimum of 600 randomly selected people (of all ages) each month. Data were collected from January 2004 to December 2013. Unadjusted prevalence over time, the relative percentage change over the 10 years, and the absolute change of the risk factors with sex, age group, and socio-economic status (SES) estimates are presented., Results: In total 55,548 adults (≥18 years) were interviewed (mean age = 47.8 years, 48.8% male). Decreases were apparent for insufficient physical activity, inadequate fruit and vegetables, smoking, and soft drink consumption of ≥500 ml/day. Increases were found over the 10 years for obesity, high cholesterol, diabetes, and for those with no risk factors. Apparent differences were noticeable by different sex, age, and SES categories. While increases in physical activity and fruit and vegetable consumption and decreases in smoking prevalence and multiple risk factors are to be expected in 2020-2021, the prevalence of obesity, high blood pressure, high cholesterol, and diabetes are expected to increase., Conclusions: Public health efforts in increasing the proportion of the population undertaking appropriate risk factor behavior are showing signs of success, with data from 2004 to 2013 showing encouraging trends. Deriving comparable trends over time by key demographics and SES variables provides evidence for policymakers and health planners to encourage interventions aimed at preventing chronic disease.

Background: Data relating to the association between tea consumption and blood pressure change are inconsistent. The aim of this analysis was to investigate the association between tea consumption and the change in blood pressure (BP) in Chinese adults over a 5-year period., Methods: Data from 1109 Chinese men (N= 472) and women (N= 637) who participated in the Jiangsu Nutrition Study (JIN) were analysed. BP was measured in 2002 and 2007. Tea (green, black and total tea) consumption was quantitatively assessed at the follow-up survey in 2007., Results: Total tea and green tea consumption were inversely associated with 5-year diastolic BP (DBP) but not systolic BP (SBP) change. In the multivariable analysis, compared with no consumption of tea, those with daily total tea/green tea consumption of at least10 g had 2.41 mmHg and 3.68 mmHg smaller increase of DBP respectively. There was a significant interaction between smoking and total tea/green tea consumption and DBP change. The inverse association between total tea/green tea consumption and DBP change was significant only in non-smokers. Green tea consumption was inversely associated with SBP change only in non-smokers and those without central obesity., Conclusion: The consumption of green tea is inversely associated with 5-year BP change among Chinese adults, an effect abrogated by smoking.

Background & Aims: In animal studies, monosodium glutamate (MSG) intake at a particular age has been found to increase the risk of insulin resistance and obesity. Inconsistent associations between MSG intake and overweight have been reported in humans. No population study has assessed the association between MSG intake and diabetes risk. This study aims to prospectively examine the association between MSG intake and hyperglycemia in a Chinese population., Methods: We followed 1056 healthy adults aged 20 years and older from 2002 to 2007. Dietary data were collected during home visits using a 3-day food record and a food frequency questionnaire. Fasting blood samples were collected at baseline and follow up. Hyperglycemia was defined as fasting plasma glucose >5.6 mmol/l., Results: During the follow-up we identified 125 cases of hyperglycemia. The highest quartile of MSG intake was associated with a lower risk of incident hyperglycemia, even after adjustment for a number of covariates, including dietary patterns. Comparing the highest with the lowest quartiles of MSG intake, the odds ratio (OR) for hyperglycemia was 0.30 (95% CI 0.13-0.66). There was a linear inverse association between MSG intake and change in blood glucose., Conclusion: This cohort study suggests that high MSG intake is associated with a decreased risk of hyperglycemia in Chinese adults., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Levels of vitamin D in the population have come under increasing scrutiny, however there are only a few studies in Australia which measure levels in the general population. The aim of this study was to measure the levels of vitamin D within a large population cohort and examine the association with seasons and selected demographic and health risk factors., Methods: A longitudinal cohort study of 2413 participants in the northwest suburbs of Adelaide, South Australia conducted between 2008 and 2010 was used to examine serum levels of 25-hydroxy vitamin D (25(OH)D) in relation to demographic characteristics (age, sex, income, education and country of birth), seasons, the use of vitamin D supplements and selected health risk factors (physical activity, body mass index and smoking). Both unadjusted and adjusted mean levels of serum 25(OH)D were examined, as were the factors associated with the unadjusted and adjusted prevalence of serum 25(OH)D levels below 50 and 75 nmol/L., Results: Overall, the mean level of serum 25(OH)D was 69.2 nmol/L with 22.7% of the population having a serum 25(OH)D level below 50 nmol/L, the level which is generally recognised as vitamin D deficiency. There were significantly higher levels of 25(OH)D among males compared to females (t = 4.65, p < 0.001). Higher levels of 25(OH)D were also measured in summer and autumn compared with winter and spring. Generally, mean levels of 25(OH)D were lower in those classified as obese. Smokers and those undertaking no or less than 150 minutes/week of physical activity also had lower levels of serum vitamin D. Obesity (as classified by body mass index), season and undertaking an insufficient level of physical activity to obtain a health benefit were significantly associated with the prevalence of vitamin D deficiency., Conclusions: Vitamin D deficiency is prevalent in South Australia, affecting almost one quarter of the population and levels are related to activity, obesity and season even when adjusted for confounding factors. Improved methods of addressing vitamin D levels in population are required.

The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study was established in 2009 to investigate the associations of sex steroids, inflammation, environmental and psychosocial factors with cardio-metabolic disease risk in men. The study population consists of 2569 men from the harmonisation of two studies: all participants of the Florey Adelaide Male Ageing Study (FAMAS) and eligible male participants of the North West Adelaide Health Study (NWAHS). The cohort has so far participated in three stages of the MAILES Study: MAILES1 (FAMAS Wave 1, from 2002-2005, and NWAHS Wave 2, from 2004-2006); MAILES2 (FAMAS Wave 2, from 2007-2010, and NWAHS Wave 3, from 2008-2010); and MAILES3 (a computer-assisted telephone interview (CATI) survey of all participants in the study, conducted in 2010). Data have been collected on a comprehensive range of physical, psychosocial and demographic issues relating to a number of chronic conditions (including cardiovascular disease, diabetes, arthritis and mental health) and health-related risk factors (including obesity, blood pressure, smoking, diet, alcohol intake and inflammatory markers), as well as on current and past health status and medication., (Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2013; all rights reserved.)

We investigated whether residential environment characteristics related to food (unhealthful/healthful food sources ratio), walkability and public open spaces (POS; number, median size, greenness and type) were associated with incidence of four cardio-metabolic risk factors (pre-diabetes/diabetes, hypertension, dyslipidaemia, abdominal obesity) in a biomedical cohort (n=3205). Results revealed that the risk of developing pre-diabetes/diabetes was lower for participants in areas with larger POS and greater walkability. Incident abdominal obesity was positively associated with the unhealthful food environment index. No associations were found with hypertension or dyslipidaemia. Results provide new evidence for specific, prospective associations between the built environment and cardio-metabolic risk factors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The clinical phenotype of advanced stage retinopathy of prematurity (ROP, stages 4 and 5) cannot be replicated in an animal model. To dissect the molecular events that can lead up to advanced ROP, we examined subretinal fluid (SRF) and surgically dissected retrolental membranes from patients with advanced ROP to evaluate its influences on cell proliferation, angiogenic properties, and macrophage polarity., Methods: We compared our findings to SRF collected from patients with uncomplicated rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy and surgically dissected epiretinal membrane from eyes with macular pucker. All subretinal fluid samples were equalized for protein. The angiogenic potential of SRF from ROP eyes was measured using a combination of capillary cord formation in a fibrin clot assay, and its proliferative effect was tested with a DNA synthesis of human retinal microvascular endothelial cells. Findings were compared with SRF collected from participants with uncomplicated rhegmatogenous RD without proliferative vitreoretinopathy. The ability of SRF to induce nitric oxide production was measured in vitro using murine J774A.1 macrophages. Cytokine profiles of SRF from ROP and RD eyes were measured using a multienzyme-linked immunosorbent assay (ELISA). Fluorescent immunohistochemistry of retrolental membranes from ROP was performed to detect the presence of leukocytes and the composition of tissue macrophages using markers for M1 and M2 differentiation., Results: The cytokine composition in SRF revealed that in ROP, not only were several proangiogenic factors were preferentially elevated but also the profile of proinflammatory factors was also increased compared to the RD eyes. SRF from ROP eyes supported cell proliferation and endothelial cord formation while SRF from RD eyes had inhibitory effects. SRF from eyes with ROP but not RD robustly induced nitric oxide production in macrophages. Furthermore, fluorescent immunostaining revealed a preponderance of M1 over M2 macrophages in retrolental fibrous membranes from ROP eyes. The cytokine profile and biologic properties of SRF in ROP promote a proangiogenic environment, which supports the maintenance and proliferation of fibrous membranes associated with advanced stages of ROP. In contrast, SRF from RD eyes exhibits a suppressive environment for endothelial cell proliferation and angiogenesis., Conclusions: Our investigation demonstrates that the microenvironment in advanced ROP eyes is proangiogenic and proinflammatory. These findings suggest that management of advanced ROP should not be limited to the surgical removal of the fibrovascular membranes and antiangiogenic therapy but also directed to anti-inflammatory therapy and to promote M2 activation over M1 activity.

We hypothesized that high altitude exposure and physical activity associated with the attack to Mt Everest could alter mRNA levels of DNA repair and metabolic enzymes and cause oxidative stress-related challenges in human skeletal muscle. Therefore, we have tested eight male mountaineers (25-40 years old) before and after five weeks of exposure to high altitude, which included attacks to peaks above 8000m. Data gained from biopsy samples from vastus lateralis revealed increased mRNA levels of both cytosolic and mitochondrial superoxide dismutase. On the other hand 8-oxoguanine DNA glycosylase (OGG1) mRNA levels tended to decrease while Ku70 mRNA levels and SIRT6 decreased with altitude exposure. The levels of SIRT1 and SIRT3 mRNA did not change significantly. However, SIRT4 mRNA level increased significantly, which could indicate decreases in fatty acid metabolism, since SIRT4 is one of the important regulators of this process. Within the limitations of this human study, data suggest that combined effects of high altitude exposure and physical activity climbing to Mt. Everest, could jeopardize the integrity of the particular chromosome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background & Aims: Multimorbidity is a common health status. The impact of nutrition on the development of multimorbidity remains to be determined. The aim of this study is to determine the association between foods, macronutrients and micronutrients and the evolution of multimorbidity., Methods: Data from 1020 Chinese who participated in the Jiangsu longitudinal Nutrition Study (JIN) were collected in 2002 (baseline) and 2007 (follow-up). Three-day weighted food records and status for 11 chronic diseases was determined using biomedical measures (hypertension, diabetes, hypercholesterolemia and anemia) or self-reports (coronary heart disease, asthma, stroke, cancer, fracture, arthritis and hepatitis). Participants were divided in six categories of stage of evolution of multimorbidity. Association of foods, macronutrients and micronutrients at baseline with stages in the evolution of multimorbidity were determined. Data were adjusted for age, sex, BMI, marital status, sedentary lifestyle, smoking status, annual income, education and energy intake., Results: The prevalence of multimorbidity increased from 14% to 34%. A high consumption of fruit and vegetables (p < 0.05) and grain products other than rice and wheat (p < 0.001) were associated with healthier stages in the evolution of multimorbidity. The consumption of grain products other than rice and wheat was highly correlated with dietary fibers (r = 0.77, p < 0.0001), iron (r = 0.46, p < 0.0001), magnesium (r = 0.49, p < 0.0001) and phosphorus (r = 0.57, p < 0.0001) intake which were also associated with healthier stages., Conclusion: This study provides the first evidence of an association between nutrition and evolution towards multimorbidity. More precisely, greater consumption of fruits and vegetable and whole grain products consumption appear to lower the risk of multimorbidity., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: The aim of this study is to describe the evolution of multimorbidity., Study Design and Setting: Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study (NWAHS) was collected between baseline (2000-2002) and follow-up (2008-2010). Status for eight chronic diseases (CDs) was determined by biomedical measurement or self-report. Chronic disease (CD) mean age of occurrence and order of appearance was investigated., Results: The prevalence of multimorbidity increased from 32% to 64% during the 7.8±1.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p<0.0001) while CVD (1%vs.5%, p<0.0001), diabetes (5%vs.11%, p<0.001) and COPD (6%vs.16%, p<0.0001) were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p<0.0001), diabetes (18%vs.9%, p<0.01) and asthma (30%vs.21%, p<0.05)., Conclusion: Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs.

Introduction: The progress and determinants of sexual dysfunction in middle-aged and elderly men remain unclear., Aim: To describe the incidence or remission and biopsychosocial predictors of erectile dysfunction (ED) and low sexual desire (SD)., Main Outcome Measures: Erectile function (International Index of Erectile Function) and sexual desire (Sexual Desire Inventory 2) were assessed at follow-up. Sociodemographic, lifestyle, and health-related factors were examined in multivariate models of ED and low SD., Methods: Data were collected from 810 randomly selected men residing in northern and western Adelaide, Australia, and aged 35-80 years at baseline, who made clinic visits 5 years apart., Results: At baseline, 23.2% (n = 123) of men had ED. ED incidence and remission were observed in 31.7% (n = 179) and 29.0% (n = 71) of eligible men, respectively. At baseline, 19.2% (n = 165) had low solitary sexual desire, and 6.0% (n = 50) had low dyadic sexual desire; incidence of low sexual desire occurred in 17.6% (n = 83) (solitary) and 8.3% (n = 51) (dyadic), while remission occurred in 15.4% (n = 68) (solitary) and 22.6% (n = 40) (dyadic) of men. In the final regression models, predictors of incident ED were higher age, lower income, higher abdominal fat mass, low alcohol intake, higher risk of obstructive sleep apnea (OSA) risk, voiding lower urinary tract symptoms (LUTS), depression, and diabetes. Predictors of ED remission were lower age, current employment, and absence of voiding LUTS, angina, diabetes, and dyslipidemia. Predictors of low dyadic SD incidence included higher age, never having been married, widowhood, being unemployed, being retired, insufficient physical activity, and low alcohol intake. Predictors of low dyadic SD remission were being married, not being widowed, higher income, lower abdominal fat mass, lower OSA risk, and higher plasma testosterone. Predictors of low solitary SD included never having been married, being unemployed, low alcohol intake, lower testosterone, storage LUTS, and hypertension. Predictors of low solitary SD remission were being married, being employed, higher income, higher physical activity, moderate alcohol intake, and depression., Conclusions: Sexual dysfunction in aging men is a dynamic disorder whose incidence and remission are predicted by a range of modifiable risk factors., (© 2014 International Society for Sexual Medicine.)

Objective: This study examined whether attributes of pedestrian environments moderate the relationships between access to public open spaces (POS) and adults' recreational walking., Methods: Data were collected from participants of the North West Adelaide Health Study in 2007. Recreational walking was determined using self-reported walking frequency. Measures of POS access (presence, count, and distance to the nearest POS) were assessed using a Geographic Information System. Pedestrian environmental attributes included aesthetics, walking infrastructure, barrier/traffic, crime concern, intersection density, and access to walking trails. Regression analyses examined whether associations between POS access and recreational walking were moderated by pedestrian environmental attributes., Results: The sample included 1574 participants (45% men, mean age: 55). POS access measures were not associated with recreational walking. However, aesthetics, walking infrastructure, and access to walking trail were found to moderate the POS-walking relationships. The presence of POS was associated with walking among participants with aesthetically pleasing pedestrian environments. Counter-intuitively, better access to POS was associated with recreational walking for those with poorer walking infrastructure or no access to walking trails., Conclusion: Local pedestrian environments moderate the relationships between access to POS and recreational walking. Our findings suggest the presence of complex relationships between POS availability and pedestrian environments., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum., Methods and Findings: The Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing., Conclusions: Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.

Background: Governments have been implementing policies aimed at halting the trend towards early retirement for Baby Boomers. Public policies can have a strong effect on when a person retires and this analysis contributes to an improved understanding of retirement aspirations in regards to health, social, workplace and economic determinants., Methods: In October 2011 a telephone survey was undertaken with participants aged 50 to 65 years who were in paid employment and who had been in the workforce for the previous three years. Participants were obtained from two identical South Australian cohort studies - the North West Adelaide Health Study and the Florey Adelaide Male Ageing Study. The results of the telephone survey were linked to the original cohort data. Data were weighted by sex, age, postcode and probability of selection in the household. Work related questions included how much they thought about their retirement, current occupation, employment status, type of workplace and hours worked per week. Health related questions included current smoking status, physical activity, body mass index, self-reported health status and overall life satisfaction. Uni-variable and multi-variable analyses were undertaken to compare the different associations between people who were and were not intending to retire., Results: In total, 25.9% (n = 210) of people who were currently in paid employment indicated that they intend to retire completely from the workforce. The remainder indicated that they will continue to work (41.8% retire from full-time work but work part-time, 25.7% continue working part-time but reduce their current hours, and 6.7% never retire). The multi-variable results indicate that those with lower education, having a savings habit, and sales workers more likely to anticipate complete retirement. The self-employed, and those thinking only moderately about retirement, were more likely to extend their working life beyond age 65., Conclusion: An important finding of this study is the large number of Baby Boomers who indicated that they would be happy to work part-time or never retire. Policies and continued dialogue aimed at making the workplace a safe, flexible and welcoming environment to accommodate this wish, and to entice others to take up this option over complete withdrawal from the labour force, is required.

The purpose of this study was to estimate prenatal human immunodeficiency virus (HIV) screening rates prior to and on admission to labor and delivery (L&D) and to examine factors associated with HIV screening, including hospital policies, with a comparison of HIV and hepatitis B prenatal screening practices and hospital policies. In March 2006, a survey of hospitals (n = 190) and review of paired maternal and infant medical records (n = 4,762) were conducted in 50 US states, DC, and Puerto Rico. Data from the survey and medical record review were analyzed using SAS software v9.2 (SAS Institute, Cary, NC). HIV testing before delivery occurred among 3,438 women (73.9%); African American and Hispanic women were more likely to be tested than white women [aOR 2.22, 95% CI (1.6-3.1) and aOR 1.55, 95% CI (1.1-2.2), respectively]. Among women without previous HIV testing, 138 (16.6%) were tested after admission to labor and delivery. Policies to test women with undocumented HIV status in at delivery were present in 65 (36.3%) hospitals. HIV testing after admission to L&D was more likely in hospitals with policies to test women with undocumented HIV status [aOR 5.91, 95% CI (2.0-17.8)]. Overall, policies and screening practices for HIV were consistently less prevalent than those for hepatitis B. Many women are not being routinely screened for HIV before or at delivery. Women with unknown HIV status were more likely to be tested in L&D in hospitals with testing policies.

It is known that inoculation of antigen into the anterior chamber (a.c.) of a mouse eye induces a.c.-associated immune deviation (ACAID), which is mediated in part by antigen-specific local and peripheral tolerance to the inciting antigen. ACAID can also be induced in vivo by intravenous (i.v.) inoculation of ex-vivo-generated tolerogenic antigen-presenting cells (TolAPC). The purpose of this study was to test if in-vitro-generated retinal antigen-pulsed TolAPC suppressed established experimental autoimmune uveitis (EAU). Retinal antigen-pulsed TolAPC were injected i.v. into mice 7 days post-induction of EAU. We observed that retinal antigen-pulsed TolAPC suppressed the incidence and severity of the clinical expression of EAU and reduced the expression of associated inflammatory cytokines. Moreover, extract of whole retina efficiently replaced interphotoreceptor retinoid-binding protein (IRBP) in the preparation of TolAPC used to induce tolerance in EAU mice. Finally, the suppression of EAU could be transferred to a new set of EAU mice with CD8⁺ but not with CD4⁺ regulatory T cells (T(reg)). Retinal antigen-pulsed TolAPC suppressed ongoing EAU by inducing CD8⁺ T(reg) cells that, in turn, suppressed the effector activity of the IRBP-specific T cells and altered the clinical symptoms of autoimmune inflammation in the eye. The ability to use retinal extract for the antigen raises the possibility that retinal extract could be used to produce autologous TolAPC and then used as therapy in human uveitis., (© 2013 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society. for Immunology.)

Background: To determine differences in sociodemographic and health related characteristics of Australian Baby Boomers and Generation X at the same relative age., Methods: The 1989/90 National Health Survey (NHS) for Boomers (1946-1965) and the 2007/08 NHS for Generation Xers (1966-1980) was used to compare the cohorts at the same age of 25-44 years. Generational differences for males and females in education, employment, smoking, physical activity, Body Mass Index (BMI), self-rated health, and diabetes were determined using Z tests. Prevalence estimates and p-values are reported. Logistic regression models examining overweight/obesity (BMI≥25) and diabetes prevalence as the dependent variables, with generation as the independent variable were adjusted for sex, age, education, physical activity, smoking and BMI(diabetes model only). Adjusted odds ratios (OR) and 95% confidence intervals are reported., Results: At the same age, tertiary educational attainment was higher among Generation X males (27.6% vs. 15.2% p<0.001) and females (30.0% vs. 10.6% p<0.001). Boomer females had a higher rate of unemployment (5.6% vs. 2.5% p<0.001). Boomer males and females had a higher prevalence of "excellent" self-reported health (35.9% vs. 21.8% p<0.001; 36.3% vs. 25.1% p<0.001) and smoking (36.3% vs. 30.4% p<0.001; 28.3% vs. 22.3% p<0.001). Generation X males (18.3% vs. 9.4% p<0.001) and females (12.7% vs. 10.4% p = 0.015) demonstrated a higher prevalence of obesity (BMI>30). There were no differences in physical activity. Modelling indicated that Generation X were more likely than Boomers to be overweight/obese (OR:2.09, 1.77-2.46) and have diabetes (OR:1.79, 1.47-2.18)., Conclusion: Self-rated health has deteriorated while obesity and diabetes prevalence has increased. This may impact workforce participation and health care utilization in the future.

Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk., Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR., Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 ± 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D., Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers., (Copyright © 2013. Published by Elsevier Ltd.)

Background: One previous large cross-sectional study across four countries suggests that riboflavin intake may be inversely associated with blood pressure., Objective: The aim of this analysis was to investigate a possible association between riboflavin intake and change in blood pressure over 5 years., Methods: The study population comprised Chinese men and women who participated in the Jiangsu Nutrition Study. Quantitative data relating to riboflavin intake at baseline in 2002 and measurements of blood pressure at baseline and follow-up in 2007 were available for 1,227 individuals., Results: Overall, 97.2% of the participants had inadequate riboflavin intake (below the Estimated Average Requirement). In multivariable analysis adjusted for sociodemographic and lifestyle factors and dietary patterns, a higher riboflavin intake was inversely associated with change in systolic blood pressure (p = .036). In participants taking antihypertensive medication at baseline, the relationship between riboflavin intake and systolic blood pressure persisted; whereas, in those not taking antihypertensive medication, the diastolic blood pressure was less likely to increase with the increasing intake of riboflavin (p = .031). There was a three-way interaction between antihypertensive medications, body mass index, and riboflavin intake. Among those who were obese and taking antihypertensive medication, a higher riboflavin intake was associated with a smaller increment in systolic blood pressure and pulse pressure., Conclusions: There are complex interactions between riboflavin intake and blood pressure change that depend on prior antihypertensive use and the presence or absence of obesity.

Background: Indicators of cardiometabolic risk typically include non-clinical factors (e.g., smoking). While the incorporation of non-clinical factors can improve absolute risk prediction, it is impossible to study the contribution of non-clinical factors when they are both predictors and part of the outcome measure. Metabolic syndrome, incorporating only clinical measures, seems a solution yet provides no information on risk severity. The aims of this study were: 1) to construct two continuous clinical indices of cardiometabolic risk (cCICRs), and assess their accuracy in predicting 10-year incident cardiovascular disease and/or type 2 diabetes; and 2) to compare the predictive accuracies of these cCICRs with existing risk indicators that incorporate non-clinical factors (Framingham Risk Scores)., Methods: Data from a population-based biomedical cohort (n = 4056) were used to construct two cCICRs from waist circumference, mean arteriole pressure, fasting glucose, triglycerides and high density lipoprotein: 1) the mean of standardised risk factors (cCICR-Z); and 2) the weighted mean of the two first principal components from principal component analysis (cCICR-PCA). The predictive accuracies of the two cCICRs and the Framingham Risk Scores were assessed and compared using ROC curves., Results: Both cCICRs demonstrated moderate accuracy (AUCs 0.72 - 0.76) in predicting incident cardiovascular disease and/or type 2 diabetes, among men and women. There were no significant differences between the predictive accuracies of the cCICRs and the Framingham Risk Scores., Conclusions: cCICRs may be useful in research investigating associations between non-clinical factors and health by providing suitable alternatives to current risk indicators which include non-clinical factors.

Objectives: Riboflavin (vitamin B2) has been shown in animal studies to affect the absorption and metabolism of iron. Cross-sectional population studies show a relationship between riboflavin intake and anemia but prospective population studies are limited. The aim of the study was to determine the relationship between riboflavin intake and the risk of anemia in a Chinese cohort., Method: The study used data from 1253 Chinese men and women who participated in two waves of the Jiangsu Nutrition Study (JIN), five years apart, in 2002 and 2007. Riboflavin intake and hemoglobin (Hb) were quantitatively assessed together with dietary patterns, lifestyle, socio-demographic and health-related factors., Results: At baseline, 97.2% of participants had inadequate riboflavin intake (below the estimate average requirement). Riboflavin intake was positively associated with anemia at baseline, but low riboflavin intake was associated with an increased risk of anemia at follow-up among those anemic at baseline. In the multivariate model, adjusting for demographic and lifestyle factors and dietary patterns, the relative risk and 95% confidence interval for anemia at follow-up, across quartiles of riboflavin intake were: 1, 0.82(0.54-1.23), 0.56(0.34-0.93), 0.52(0.28-0.98) (p for trend 0.021). There was a significant interaction between riboflavin and iron intake; when riboflavin intake was low, a high iron intake was associated with a lower probability of anemia at follow-up. This association disappeared when riboflavin intake was high., Conclusion: Inadequate riboflavin intake is common and increases the risk of anemia in Chinese adults. Given the interaction with iron intake correcting inadequate riboflavin intake may be a priority in the prevention of anemia, and population based measurement and intervention trials are required.

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [β = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081.

This study examines the relationships between area-level socioeconomic position (SEP) and the prevalence and trajectories of metabolic syndrome (MetS) and the count of its constituents (i.e., disturbed glucose and insulin metabolism, abdominal obesity, dyslipidemia, and hypertension). A cohort of 4,056 men and women aged 18+ living in Adelaide, Australia was established in 2000-2003. MetS was ascertained at baseline, four and eight years via clinical examinations. Baseline area-level median household income, percentage of residents with a high school education, and unemployment rate were derived from the 2001 population Census. Three-level random-intercepts logistic and Poisson regression models were performed to estimate the standardized odds ratio (SOR), prevalence risk ratio (SRR), ratio of SORs/SRRs, and (95% confidence interval (CI)). Interaction between area- and individual-level SEP variables was also tested. The odds of having MetS and the count of its constituents increased over time. This increase did not vary according to baseline area-level SEP (ratios of SORs/SRRs ≈ 1; p ≥ 0.42). However, at baseline, after adjustment for individual SEP and health behaviours, median household income (inversely) and unemployment rate (positively) were significantly associated with MetS prevalence (SOR (95%CI) = 0.76 (0.63-0.90), and 1.48 (1.26-1.74), respectively), and the count of its constituents (SRR (95%CI) = 0.96 (0.93-0.99), and 1.06 (1.04-1.09), respectively). The inverse association with area-level education was statistically significant only in participants with less than post high school education (SOR (95%CI) = 0.58 (0.45-0.73), and SRR (95%CI) = 0.91 (0.88-0.94)). Area-level SEP does not predict an elevated trajectory to developing MetS or an elevated count of its constituents. However, at baseline, area-level SEP was inversely associated with prevalence of MetS and the count of its constituents, with the association of area-level education being modified by individual-level education. Population-level interventions for communities defined by area-level socioeconomic disadvantage are needed to reduce cardiometabolic risks.

Purpose: We determined the metabolic, lifestyle and physical factors associated with progression or improvement of storage and voiding lower urinary tract symptoms in a population based cohort of men., Materials and Methods: After the exclusion of men with prostate or bladder cancer and/or surgery from the study, progression and improvement of storage and voiding lower urinary tract symptoms was assessed using the AUA-SI (American Urological Association symptom index) in 780 men, age 35 to 80 years at baseline, who attended 5-year followup clinics., Results: Storage and voiding lower urinary tract symptoms progressed in 39.8% (308) and 32.3% (250) of men, and improved in 33.1% (256) and 23.4% (181), respectively. In final adjusted regression models greater bother and physical activity at baseline predicted improvement in storage and voiding lower urinary tract symptoms, while greater income, high-density lipoprotein cholesterol and lower triglycerides predicted improvement of storage lower urinary tract symptoms only. Being widowed, higher plasma estradiol and depression at baseline predicted the progression of storage and voiding lower urinary tract symptoms, while greater abdominal fat mass and obstructive sleep apnea risk predicted the progression of storage lower urinary tract symptoms only. Older age, lower high-density lipoprotein cholesterol, testosterone, income, previous benign prostatic hyperplasia and erectile dysfunction at baseline predicted the progression of voiding lower urinary tract symptoms only. The initiation or continued use of α-blockers or anticholinergics (storage lower urinary tract symptoms), and 5α-reductase inhibitors (voiding lower urinary tract symptoms), were associated with symptom improvement., Conclusions: Lower urinary tract symptoms may progress or remit. Even accounting for medication use, progression may be associated with modifiable disease, or metabolic or behavioral factors, which are also risk factors for type 2 diabetes and cardiovascular disease. These factors should be looked for and managed., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)