Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome.

The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

Environmental plastics in the context of UV radiation, climate change, and the Montreal Protocol.

There are close links between solar UV radiation, climate change, and plastic pollution. UV-driven weathering is a key process leading to the degradation of plastics in the environment but also the formation of potentially harmful plastic fragments such as micro- and nanoplastic particles. Estimates of the environmental persistence of plastic pollution, and the formation of fragments, will need to take in account plastic dispersal around the globe, as well as projected UV radiation levels and climate change factors.

Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023.

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.

Liver and cardiometabolic markers and conditions in a cross-sectional study of three Australian communities living with environmental per- and polyfluoroalkyl substances contamination.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive. OBJECTIVES: We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities. METHODS: Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression). RESULTS: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease. DISCUSSION: Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference.

Long-term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood.

Atmospheric carbon dioxide (CO2 ) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2 . Here, we assess the broader systemic physiological responses to this exposure. Mice were exposed to either 460 or 890 ppm from preconception to 3 months of age, and assessed for effects on developmental, renal and osteological parameters. Locomotor, memory, learning and anxiety-like behaviours of the mice were also assessed. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. These findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. KEY POINTS: Long-term exposure to elevated levels of atmospheric CO2 is an uncontrolled experiment already underway. This is the first known study to assess non-respiratory physiological impacts of long-term (conception to young adulthood) exposure of mice to CO2 at levels that may arise in the atmosphere due to global emissions. Exposure to elevated CO2 , in comparison to control mice, altered growth patterns in early life and resulted in hyperactive behaviours in young adulthood. Renal and bone parameters, which are important to balance acid-base levels to compensate for increased CO2 exposure, remained relatively unaffected. This work adds to the body of evidence regarding the effects of carbon emissions on mammalian health and highlights a potential future burden of disease.

Smokers Increasingly Motivated and Able to Quit as Smoking Prevalence Falls: Umbrella and Systematic Review of Evidence Relevant to the "Hardening Hypothesis," Considering Transcendence of Manufactured Doubt.

INTRODUCTION: The "hardening hypothesis" proposes that as the prevalence of smoking in a population declines, there will be a "hardening" of the remaining smoker population. This review examines the evidence regarding smokers' motivation, dependence, and quitting behavior as smoking prevalence declines, to assess whether population "hardening" (decreasing propensity to quit) or "softening" (the converse) is occurring. METHODS: MEDLINE, PsychINFO, Scopus, Web of Science, and Cochrane Library were searched to July 2019, using terms related to smoking and hardening, for reviews and large, population-based repeat cross-sectional studies. There were additional searches of reference lists and citations of key research articles. Two reviewers screened half the titles and abstracts each, and two reviewers screened full texts independently using tested criteria. Four reviewers independently and systematically extracted data from eligible publications, with one reviewer per study, checked by another reviewer. RESULTS: Of 265 titles identified, three reviews and ten repeat cross-sectional studies were included. Reviews concluded that hardening has not occurred among the general smoking population over time. Among repeated cross-sectional studies, five examined motivation, nine examined dependence, five examined hardcore smoking, and two examined quit outcomes. All but one study found a lack of hardening. Most found softening within the smoking population, consistent across hardening indicators, definitions, countries (and tobacco control environments), and time periods examined. CONCLUSIONS: Tobacco control reduces smoking prevalence and fosters a smoking population more amenable to evidence-based interventions. Based on the weight of the available evidence, the "hardening hypothesis" should be rejected and the reality of softening accepted. IMPLICATIONS: This umbrella review and systematic review provides a critical consideration of evidence from epidemiology and psychology and other fields regarding the "hardening hypothesis"-a persistent myth undermining tobacco control. It reaches the conclusion that the sum-total of the worldwide evidence indicates either "softening" of the smoking population, or a lack of hardening. Hence, tobacco control reduces smoking prevalence and fosters a smoking population more amenable to evidence-based interventions. The review indicates that the time has come to take active steps to combat the myth of hardening and to replace it with the reality of "softening."

Surveying the changing climate of Northern Territory medical workforce retention.

INTRODUCTION: Low retention is a significant contributor to medical workforce shortages in rural and remote regions of Australia, including in the Northern Territory (NT). Many of these areas are susceptible to climate change, which could exacerbate workforce retention problems. OBJECTIVE: To examine factors influencing medical workforce retention in the NT, including the potential impact of climate change. DESIGN: Cross sectional online survey of NT medical professionals, distributed via email through professional networks. Predominantly quantitative mixed methods (descriptive statistics, multivariate logistic regression, thematic analysis). Main 2 outcome measures reported were proportion of respondents intending to leave the NT, timeframe of intention to leave and motivating factors. FINDINGS: Of 1407 registered practising medical professionals in the NT, 362 responded who met inclusion criteria (26% estimated response rate) and 351 completed all questions. Of the latter, 143 (41%) intended to leave the NT, 102 (29%) were unsure, and 106 (30%) did not intend to leave. Among doctors in training (DITs) 67 (55%) intended to leave and 29 (24%) were unsure. The best multivariable predictive model included only practice type (with general practitioners/rural generalists and non-GP specialists significantly less likely to intend to leave compared to DITs), and location of primary medical degree (with non-NT training non-significantly associated with greater intention to leave). Of those intending to leave 94 (66%) reported planning to do so within two years. Training and career development opportunities, job dissatisfaction, moving to a preferred location and family-related factors were all important motivators. Of those considering leaving, 58 (24%) identified climate change as a motivating factor. CONCLUSION: Retention remains a key challenge in addressing rural workforce shortages. In addition to established factors, climate change is an important driver that has the potential to worsen workforce shortages in susceptible regions.

Metabolic dysfunction induced by a high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice.

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the 'whitening' effect of eating a high-fat diet upon interscapular (i) BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPCs and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional DCs (cDCs) increased in both of these tissues. When compared with a low-fat diet, consumption of a high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed the high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin [blocked using the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO)], but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction .

An exploratory study of diet in childhood and young adulthood and adult-onset multiple sclerosis.

There is little evidence on the role of diet in childhood/adolescence and multiple sclerosis (MS) in adulthood. The MS Sunshine Study recruited adults with recent-onset MS (n = 602) and matched controls (n = 653). Of these, 84% provided dietary recall for specific ages between childhood and young adulthood (6-10, 11-15 and 16-20 years). We used logistic regression to test associations between age-specific diet and case-control status. Consumption of fruit (all ages), yoghurt (all ages) and legumes (11-15 years) was associated with lower probability of adult-onset MS (all p < 0.05). These results suggest that healthy dietary habits between childhood and young adulthood may reduce MS risk.

High Prudent diet factor score predicts lower relapse hazard in early multiple sclerosis.

BACKGROUND: Dietary patterns and their association with subsequent clinical course have not been well studied in early multiple sclerosis (MS). OBJECTIVES: To describe dietary patterns in people in 5 years following first clinical demyelination and assess associations with MS conversion and relapse. METHODS: This study included baseline food frequency questionnaire dietary intake (entry to the Ausimmune Study) and 5-year follow-up; iterated principal factor analysis was applied. MS conversion and relapse risks were assessed by Cox proportional hazards models, adjusted for age, sex, study site, education, body mass index (BMI), smoking and omega-3 supplement use. RESULTS: In cases with a first clinical diagnosis of central nervous system (CNS) demyelination, we identified three major dietary patterns, 'Prudent', 'High-Vegetable' and 'Mixed', explaining 43%, 37% and 24% of diet variance in dietary intake, respectively. Fruits, vegetables, fish, wholegrains and nuts loaded highly on the Prudent pattern, starchy vegetables and legumes on the High-Vegetable pattern, and meats and alcohol on the Mixed pattern. Diet factor scores were not associated with MS conversion risk. Those with baseline Prudent scores above the median had significantly lower relapse risk (adjusted hazard ratio = 0.54, 95% confidence interval (CI) 0.37, 0.81) with some evidence of a plateau effect. CONCLUSION: Prudent diet factor score above the median was prospectively associated with lower relapse risk in the 5 years following the first clinical demyelinating event.

Prevalence and predictors of vitamin D deficiency in a nationally representative sample of Australian Aboriginal and Torres Strait Islander adults.

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/l) is recognised as a public health problem globally. The present study details the prevalence and predictors of vitamin D deficiency in a nationally representative sample (n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012-2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS. Survey-weighted logistic regression models were used to determine the independent predictors of vitamin D deficiency. Approximately 27 % of adult AATSIHS participants were vitamin D deficient. Vitamin D deficiency was more prevalent in remote areas (39 %) than in non-remote areas (23 %). Independent predictors of vitamin D deficiency included assessment during winter (men, adjusted OR (aOR) 5·7; 95 % CI 2·2, 14·6; women, aOR 2·2; 95 % CI 1·3, 3·8) and spring (men, aOR 3·3; 95 % CI 1·4, 7·5; women, aOR 2·6; 95 % CI 1·5, 4·5) compared with summer, and obesity (men, aOR 2·6; 95 % CI 1·2, 5·4; women, aOR 4·3; 95 % CI 2·8, 6·8) compared with healthy weight. Statistically significant associations were evident for current smokers (men only, aOR 2·0; 95 % CI 1·2, 3·4), remote-dwelling women (aOR 2·0; 95 % CI 1·4, 2·9) and university-educated women (aOR 2·4; 95 % CI 1·2, 4·8). Given the high prevalence of vitamin D deficiency in this population, strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches are needed.

Hospitalisations for falls and hip fractures attributable to vitamin D deficiency in older Australians.

Vitamin D deficiency is associated with an increased risk of falls and fractures. Assuming this association is causal, we aimed to identify the number and proportion of hospitalisations for falls and hip fractures attributable to vitamin D deficiency (25 hydroxy D (25(OH)D) <50 nmol/l) in Australians aged ≥65 years. We used 25(OH)D data from the 2011/12 Australian Health Survey and relative risks from published meta-analyses to calculate population-attributable fractions for falls and hip fracture. We applied these to data published by the Australian Institute of Health and Welfare to calculate the number of events each year attributable to vitamin D deficiency. In men and women combined, 8·3 % of hospitalisations for falls (7991 events) and almost 8 % of hospitalisations for hip fractures (1315 events) were attributable to vitamin D deficiency. These findings suggest that, even in a sunny country such as Australia, vitamin D deficiency contributes to a considerable number of hospitalisations as a consequence of falls and for treatment of hip fracture in older Australians; in countries where the prevalence of vitamin D deficiency is higher, the impact will be even greater. It is important to mitigate vitamin D deficiency, but whether this should occur through supplementation or increased sun exposure needs consideration of the benefits, harms, practicalities and costs of both approaches.

Experiences of healthcare for people living with multiple sclerosis and their healthcare professionals.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative condition of the central nervous system that commonly strikes in young adulthood and has no cure. Many people living with MS (PwMS) will have significant contact with a range of healthcare professionals (HCPs). To achieve optimal health outcomes in MS, it is important to understand factors that contribute to positive or negative healthcare experiences. Previous studies have shown that PwMS want clear communication and in-depth relationships with their HCPs. However, many studies have lacked qualitative feedback from HCPs. OBJECTIVE: This study aimed to investigate healthcare experiences of PwMS and HCPs and identify areas that are working well and areas that could be improved. METHODS: Semistructured interviews with 15 PwMS and 11 HCPs (seven neurologists, four MS nurses) from across Australia were conducted. Interviews were transcribed verbatim and analysed thematically. RESULTS: Both PwMS and HCPs valued clear communication, recognized uncertainties associated with MS and highlighted the importance of rapport. PwMS focused on decision-making, understanding roles and expectations, self-directed management and their needs for support. HCPs discussed issues related to medical management, providing hope and reassurance, barriers to healthcare and multidisciplinary care. CONCLUSION: Greater transparency and communication, particularly around the approach to care and the roles played by HCPs, is likely to enhance healthcare experiences and contribute to better health outcomes for PwMS. PUBLIC CONTRIBUTION: PwMS and HCPs volunteered to be interviewed, and PwMS assisted with the development of interview content and structure.

Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue.

AIMS/HYPOTHESIS: Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. Here, we explore further mechanistic pathways through which low-dose UVR exerts these beneficial effects. METHODS: We fed mice with a luciferase-tagged Ucp1 gene (which encodes uncoupling protein-1 [UCP-1]), referred to here as the Ucp1 luciferase transgenic mouse ('Thermomouse') a high-fat diet and examined the effects of repeated exposure to low-dose UVR on weight gain and development of metabolic dysfunction as well as UCP-1-dependent thermogenesis in interscapular brown adipose tissue (iBAT). RESULTS: Repeated exposure to low-dose UVR suppressed the development of glucose intolerance and hepatic lipid accumulation via dermal release of nitric oxide while also reducing circulating IL-6 (compared with mice fed a high-fat diet only). Dietary nitrate supplementation did not mimic the effects of low-dose UVR. A single low dose of UVR increased UCP-1 expression (by more than twofold) in iBAT of mice fed a low-fat diet, 24 h after exposure. However, in mice fed a high-fat diet, there was no effect of UVR on UCP-1 expression in iBAT (compared with mock-treated mice) when measured at regular intervals over 12 weeks. More extensive circadian studies did not identify any substantial shifts in UCP-1 expression in mice exposed to low-dose UVR, although skin temperature at the interscapular site was reduced in UVR-exposed mice. The appearance of cells with a white adipocyte phenotype ('whitening') in iBAT induced by consuming the high-fat diet was suppressed by exposure to low-dose UVR in a nitric oxide-dependent fashion. Significant shifts in the expression of important core gene regulators of BAT function (Dio2, increased more than twofold), fatty acid transport (increased Fatp2 [also known as Slc27a2]), lipolysis (decreased Atgl [also known as Pnpla2]), lipogenesis (decreased Fasn) and inflammation (decreased Tnf), and proportions of macrophages (increased twofold) were observed in iBAT of mice exposed to low-dose UVR. These effects were independent of nitric oxide released from skin. CONCLUSIONS/INTERPRETATION: Our results suggest that non-burning (low-dose) UVR suppresses the BAT 'whitening', steatotic and pro-diabetic effects of consuming a high-fat diet through skin release of nitric oxide, with some metabolic and immune pathways in iBAT regulated by UVR independently of nitric oxide.

Seafood, fatty acid biosynthesis genes, and multiple sclerosis susceptibility.

BACKGROUND: The role of omega-3 fatty acid in multiple sclerosis (MS) susceptibility is unclear. OBJECTIVE: To determine whether fish/seafood intake or genetic factors that regulate omega-3 fatty acids levels are associated with MS risk. METHODS: We examined the association of fish and shrimp consumption and 13 tag single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2 with risk of MS in 1153 individuals from the MS Sunshine Study, a case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California. RESULTS: Consuming fish/seafood at least once a week or at least once a month with regular fish oil use was associated with 44% reduced odds of MS/CIS (adjusted OR = 0.56; 95% CI = 0.41-0.76; p = 0.0002) compared with consuming fish/seafood less than once a month and no fish oil supplementation. Two FADS2 SNPs (rs174611 and rs174618) were independently associated with a lower risk of MS (adjusted ORs = 0.74, 0.79, p = 0.0056, 0.0090, respectively). Association of FADS2 SNPs with MS risk was confirmed in an independent dataset. CONCLUSION: These findings suggest that omega-3 fatty acid intake may be an important modifiable risk factor for MS. This is consistent with the other known health benefits of fish consumption and complementary genetic studies supporting a key role for omega-3 regulation.

Recalling our day in the sun: comparing long-term recall of childhood sun exposure with prospectively collected parent-reported data.

To examine the impact of sun exposure on human health, accurate measures of past sun exposure are required. We investigated how young adults' recall of childhood sun-related behaviours compares with parent-reported measures collected during childhood. The Kidskin-Young Adult Myopia Study (KYAMS) is a follow-up of the Kidskin Study, a sun-protection intervention study conducted from 1995-2001. KYAMS participants, aged 25-30 years, reported time in sun, and use of hats and sunscreen, for each year from ages 5-26 years (n = 244). Using weighted kappa, we assessed agreement between these data and corresponding variables derived from the Kidskin Study parent questionnaires completed when KYAMS participants were aged 6-12 years. Ordinal logistic regression was used to test the association between self-reported sun-behaviours and corresponding parent-reported data. We found slight agreement between self-reported and parent-reported data for all sun-behaviour measures except hat use at 12 years. KYAMS recall of time in sun at 8-12 years was not associated with Kidskin Study parent-reported responses after adjustment for current time in sun. Recall of higher hat and sunscreen use was associated with higher parent-reported hat and sunscreen use (OR[hat] = 1.37, 95% CI: 1.16, 1.62; OR[sunscreen] = 1.23, 95% CI: 1.03, 1.48). However, KYAMS self-reported data were unable to predict corresponding parent-reported responses. Group data from retrospective recall of sun-related behaviours may be of limited value in studying the relationship between sun exposure and health outcomes; however, individual data are likely of little use.

Re-engaging an inactive cohort of young adults: evaluating recruitment for the Kidskin Young Adult Myopia Study.

BACKGROUND: Recent changes in communication technologies, including increased reliance on mobile phones and the internet, may present challenges and/or opportunities to re-engaging inactive study cohorts. We evaluate our ability to recruit participants for the Kidskin Young Adult Myopia Study (KYAMS), a follow-up of the Kidskin Study. METHODS: KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5-6 year-olds running from 1995 to 1999 with most recent follow-up in 2005. From 2015 to 2019, the KYAMS used mail-outs, phone calls and social media to contact Kidskin Study participants. Multivariable logistic regression was used to identify variables associated with successful contact of a Kidskin Study participant or family member and KYAMS participation. RESULTS: Of 1695 eligible participants, 599 (35.5%) participants (or a family member) were contacted and 303 (17.9%) participated in the KYAMS. KYAMS participation was more likely in those who participated in the 2005 follow-up (odds ratio [OR] = 5.09, 95% confidence interval [CI]: 3.67-7.06) and had a mobile phone number on record (OR = 2.25, CI: 1.57-3.23). Of those contacted, participants who were the first point of contact (OR = 4.84, CI: 2.89-8.10) and who were contacted by letter in the first (OR = 6.53, CI: 3.35-12.75) or second (OR = 5.77, CI: 2.85-11.67) round were more likely to participate in the KYAMS, compared to contact by landline phone. CONCLUSIONS: We recruited approximately one-fifth of Kidskin Study participants for the KYAMS. Participants were more likely to participate in the KYAMS if they were contacted directly, rather than through a family member, and if they were contacted by invitation letter. TRIAL REGISTRATION: ACTRN12617000812392.

Poor access to kidney disease management services in susceptible patient populations in rural Australia is associated with increased aeromedical retrievals for acute renal care.

BACKGROUND: Inequalities in access to renal services and acute care for rural and remote populations in Australia have been described but not quantified. AIM: To describe: the coverage of renal disease management services in rural and remote Australia; and the characteristics of patients who had an aeromedical retrieval for renal disease by Australia's Royal Flying Doctor Service (RFDS). METHODS: Data from the RFDS, the Australian Bureau of Statistics, and Health Direct were used to estimate provision of renal disease management services by geographic area. RFDS patient diagnostic data were prospectively collected from 2014 to 2018. RESULTS: Many rural and remote areas have limited access to regular renal disease management services. Most RFDS retrievals for renal disease are from regions without such services. The RFDS conducted 1636 aeromedical retrievals for renal disease, which represented 1.6% of all retrievals. Among retrieved patients, there was a higher proportion of men than women (54.6% vs 45.4%, P < 0.01), while indigenous patients (n = 546, 33.4%) were significantly younger than non-indigenous patients (40.9 vs 58.5, P < 0.01). There were significant differences in underlying diagnoses triggering retrievals between genders, with males being more likely than females to be transferred with acute renal failure, calculus of the kidney and ureter, renal colic, obstructive uropathy, and kidney failure (all P < 0.01). Conversely, females were more likely to have chronic kidney disease, disorders of the urinary system, acute nephritic syndrome, tubulo-interstitial nephritis, and nephrotic syndrome (all P < 0.01). CONCLUSION: Aeromedical retrievals for acute care were from rural areas without regular access to renal disease prevention or management services.