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Purpose: The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoimmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of phagolysosome-activation in macrophages following α-MSH-treatment of EAU., Methods: The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(-/-) mice were used to treat macrophages to assay for phagolysosome activation., Results: MC5r(-/-) mice treated with α-MSH recovered from EAU, but with greater retinal damage, and the RPE suppressed phagolysosome activation in wild type but not in MC5r(-/-) macrophages. In addition, α-MSH did not suppress phagolysosome activation in MC5r(-/-) macrophages, and resting-MC5r(-/-) macrophages had augmented phagocytic activity., Conclusion: α-MSH treatment of EAU mediates a MC5r-dependent recovery of RPE suppression of phagolysosome activation in macrophages possibly altering antigen processing and presentation. Also, MC5r-expression helps protect the retina from inflammatory damage. In addition, MC5r-expression is important in the homeostatic maintenance of phagosome-maturation within macrophages.

Almost one-third of Australians report having made errors at work that are related to sleep issues. While there is significant literature investigating the role of sleep in workplace health and safety in shiftworking and nightwork operations, long working hours, work-family conflict, and commute times getting longer also impact day workers' sleep behaviors and opportunities. The aim of this study was to examine the relationship between sleep duration and disorders, sleep health and hygiene factors, work-related factors and errors at work in Australian workers. From a sample of 1011 Australian adults, age-adjusted binary logistic regression analyses were conducted in 512 workers who provided responses to the question "Thinking about the past three months, how many days did you make errors at work because you were too sleepy or you had a sleep problem?" A number of sleep behaviors and poor sleep hygiene factors were linked with work errors related to sleepiness or sleep problems, with age-adjusted odds of errors (confidence intervals) up to 11.6 times higher (5.4-25.1, p < 0.001) in those that snored, 7.7 (4.6-12.9) times higher in those reporting more than three sleep issues (p < 0.001), 7.0 times higher (3.4-14.8) in short (≤5 hours/night) sleepers (p < 0.021), 6.1 times higher (2.9-12.7) in those staying up later than planned most nights of the week (p< 0.001) and 2.4 times higher (1.6-3.7) in those drinking alcohol ≥3 nights/week before bed (p < 0.001). More than 40% of participants working non-standard hours reported making errors at work, and they were more likely to be young (compared to the main sample of workers) and more likely to engage in work activities in the hour before bed. Sleep factors (other than clinical sleep disorders) were associated with an increased likelihood of sleep-related work errors. Both day workers and those working non-standard hours engage in work, sleep and health behaviors that do not support good sleep health, which may be impacting safety and productivity in the workplace through increased sleepiness-related errors.

Melanocortins are a highly conserved family of peptides and receptors that includes multiple proopiomelanocortin-derived peptides and five defined melanocortin receptors. The melanocortins have an important role in maintaining immune homeostasis and in suppressing inflammation. Within the healthy eye, the melanocortins have a central role in preventing inflammation and maintaining immune privilege. A central mediator of the anti-inflammatory activity is the non-steroidogenic melanocortin peptide alpha-melanocyte stimulating hormone. In this review we summarize the major findings of melanocortin regulation of ocular immunobiology with particular interest in the ability of melanocortin to induce immune tolerance and cytoprotection. The melanocortins have therapeutic potential because their mechanisms of action in regulating immunity are distinctly different from the actions of steroids.

Reactive oxygen species (ROS) are continuously generated during metabolism. ROS are involved in redox signaling, but in significant concentrations they can greatly elevate oxidative damage leading to neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain a normal redox state in brain and spinal cord cell types. The complex effects of exercise benefit brain function, including functional enhancement as well as its preventive and therapeutic roles. Exercise can induce neurogenesis via neurotrophic factors, increase capillarization, decrease oxidative damage, and enhance repair of oxidative damage. Exercise is also effective in attenuating age-associated loss in brain function, which suggests that physical activity-related complex metabolic and redox changes are important for a healthy neural system.

Objectives: To assess the prevalence and associations of hand symptoms in a community setting., Methods: The North West Adelaide Health Study (NWAHS) is a longitudinal cohort study of people aged ≥ 18 years. Analysis was performed in participants who completed a telephone interview, a quality of life questionnaire [the 36-item short-form health survey, (SF-36)], and the Australian/Canadian (AUSCAN) Osteoarthritis (OA) Hand Index, and underwent grip strength measurement., Results: Overall, 477 (13.7%) reported hand pain, aching, or stiffness. Of these, 169 (35.8%) had been diagnosed with hand arthritis. Women were more likely to have hand symptoms than men, as were those aged ≥ 50 years (p < 0.001). Hand symptoms were associated with lower quality of life scores (p < 0.05). Participants with hand arthritis had more severe pain, stiffness, and poorer physical functioning as reflected by higher AUSCAN scores. Grip strength was reduced in those with hand symptoms and hand arthritis (p < 0.05) and inversely associated with mean AUSCAN subscores and SF-36 physical functioning scores (p < 0.001)., Conclusions: Hand symptoms were present in 14% of the population and were more common in women and those aged ≥ 50 years. Hand symptoms were associated with reduced grip strength and reduced quality of life. Hand arthritis was associated with higher AUSCAN scores. Hand symptoms and hand arthritis have a significant impact on physical functioning and quality of life.

The phrase "immune privilege" was coined by Peter Medawar to describe the absence of an immune response to allografts placed into the anterior chamber of the eye or brain. We now understand that immune privilege is more than a passive microenvironment with a distinctive anatomical structure that holds back immunity. The ocular microenvironment actively engages the immune system with immunosuppressive biochemical mechanisms. The unique characteristics of ocular immune privilege appear designed to protect the eye from damage while preserving foveal vision, thus providing the host with a definite survival advantage. However, the protection is not always sufficient and the eye becomes susceptible to uveitis. Uveitis is an intraocular inflammatory disorder that encompasses a wide range of underlying etiologies. It may be idiopathic or associated with systemic disease or infection. Understanding the biochemistry of immune privilege has the potential to identify its weaknesses that allow for immunity to break through.

Purpose: We have previously found that retinal pigment epithelial (RPE) cells suppressed endotoxin-stimulated macrophages; moreover, it induced expression of anti-inflammatory cytokines. We further assessed the possibility that the RPE is alternatively activating macrophages., Methods: J774A.1 cells were stimulated with endotoxin and treated with the conditioned media (CM) of RPE, or neuroretinal eyecups from healthy mouse eyes. The supernatant was assayed for IL-1 beta, TNF-alpha, IL-6, IL-12(p70), and IL-10, and for nitric-oxide generation. The RPE conditioned media (RPE CM) was absorbed of known soluble factors to identify the factor that augments nitric-oxide generation., Results: We found the RPE CM suppressed all cytokine production except IL-10, and augmented nitric-oxide generation. The augmented nitric-oxide levels were mediated by RPE derived alpha-melanocyte stimulating hormone (alpha-MSH)., Conclusions: Healthy RPE not only suppresses inflammatory activity, it promotes an alternative activation of macrophages that can further promote immune privilege.

Objective: To describe the prevalence of menopausal hormone therapy (HT) in 2008 and trends over the last 17 years in an Australian population., Methods: Data were obtained from nine representative population face-to-face interview surveys of the South Australian population from 1991 to 2008. The surveys used consistent method and quality control procedures. In 2008, demographic data, HT use and eight dimensions of health, using the SF-36 health survey questionnaire, were measured. Participants Over 3000 South Australian adults were interviewed in their own home by trained health interviewers in each of the surveys; in the 2008 survey, 1555 women participated, of whom 953 were over age 40., Results: After a peak in use in the 2000 survey, HT use fell from 2003 and has continued to decline in 2008. In 2008, current use over age 50 of registered conventional HT products is now 11.8%, with a further 4.0% using non-registered alternative 'hormonal' products. Current HT use is highest between the ages of 50 and 59 years, where 13.4% use conventional HT and 7.7% use unconventional alternative hormones. Use of these unregistered hormonal products was rare in previous surveys. Median and mean length of conventional HT use were 10.0 and 10.5 years, respectively. HT users continued to have a demographic profile similar to those in previous surveys, i.e. they were better educated, employed, partnered, had a higher income and were less inclined to use complementary and alternative medicines., Conclusions: There has been a continuing decline in both the overall prevalence and length of use of conventional HT from 2003, probably in association with negative media about HT. Of medical concern is that about one-quarter of women using HT around menopause now chooses unregistered hormonal mixtures that are untested for long-term safety and efficacy.

Objectives: To use representative population chronic disease and risk factor data to investigate the relationship between asthma and social factors in school-age children., Methods: Representative cross-sectional data for children 5 to 15 years of age were collected from 2002 to June 2007 (n = 4,611) in the South Australian Monitoring and Surveillance System (SAMSS) using Computer-Assisted Telephone Interviews (CATI). Univariate and multivariate analyses were conducted to investigate the variables that were associated with asthma among children., Results: The overall prevalence of self-reported asthma among children 5 to 15 years of age was 18.6% (95% CI = 17.5-19.8). Children with asthma were more likely to have been treated for a mental health problem, have been unhappy at school, have been absent from school in the last month, have fair or poor overall health and well-being, have ongoing pain or chronic illness, and less likely to have a group of friends to play with. Asthma was also more prevalent among males and less likely to occur in children from households where the gross annual income was greater than $AU80,000., Conclusions: Children with asthma were more likely to be treated for a mental health problem and demonstrate more negative social outcomes as well as poorer overall health and well-being. Asthma management plans need to be sensitive to these psychosocial factors for adequate care of these vulnerable young patients.

Objective: To continue surveillance of hormone therapy (HT) use in an Australian population and to assess the impact of the Women's Health Initiative (WHI) and associated reports on HT use 16 months after the results of the WHI were first reported., Methods: Data were obtained from the 2003 South Australian Health Omnibus Survey, which involves a representative, population face-to-face interview survey. Data were compared to five surveys undertaken between 1991 and 2000, which had consistent methods and quality-control procedures. A total of 907 interviews were conducted with women over 40 years in their own homes by trained health interviewers., Results: In association with the timing of media reporting of the WHI, current HT use rates dropped from 28% in women over 50 years in 2000 to an estimated 10.2% in 2002. By October 2003, current use rates had returned to 18.8% in this age group. The media had been the main influence in the women's decision-making. Half of those who restarted therapy changed to another type of HT. Only 2.8% changed to an alternative/complementary therapy., Conclusions: Nearly two-thirds (64%) of those currently using HT in 2002 stopped therapy, mostly in response to the media reporting of the WHI. Nearly half of those who stopped HT in 2002 have since restarted. Media reporting greatly influences the use of hormonal therapies.

Objectives: To describe the prevalence of hormone replacement therapy (HRT) during the 1990s in an Australian population and the length of time this therapy has been used. Design Data were obtained from five biennial representative population face-to-face interview surveys of the South Australian population from 1991 to 2000, and an additional telephone survey in 2001. The main surveys used consistent methods and quality control procedures., Participants: Over 3000 South Australian adults were interviewed in their own homes by trained health interviewers in each of the biennial surveys., Results: In 2000, 28% of women aged over 50 were currently using HRT, and ever-use of HRT was 43%. Highest use of HRT was in the 55-59-year age group, where current use was 47% and ever-use was 70%. Among women 55 years and older there was a statistically significant increase in the prevalence of HRT use between 1991 and 2000. Mean length of use in women aged over 55 years increased from 5.4 years in 1991 to 9.6 years in 2000., Conclusions: Consistent surveillance of the population has shown that HRT use has not increased before age 55, but has greatly increased thereafter. Long-term effects may now be occurring, and further results of current long-term randomized trials are awaited to confirm the overall risk/benefit ratio suggested by observational studies and early results from long-term trials.

Background: The objective of this study was to assess the current trends of hormone replacement therapy (HRT) use, including rates of use, length of use, continuation rates and characteristics of users and non-users and to examine the hypothesis that 'healthy women' are more likely to be users of HRT., Methods: Analysis was carried out of three representative South Australian population studies in 1991, 1993 and 1995 comprising 3019, 3004 and 3016 personal interviews, respectively., Results: Current use (and ever-use) of HRT in all women aged 50 years and over rose from 13.2% (26.7%) in 1991, to 21.2% (31.9%) in 1993 and 26.0% (40.5%) in 1995. Highest use is now in the 55-59-year age group where, in 1995, current use was 50.9% and ever use was 69.0%. Median compliance rates with HRT rose from 24 months in 1991 to 60 months in 1995 for current users aged 50 years of age or above. The pattern of increasing use of HRT is not consistent across age groups. Analyses of the 1995 data show that, in contrast with increasing rates of current use in women over 55 years, there was no overall change in rates for women below this age. There were no statistically significant differences in health indicators, e.g. blood pressure, smoking, cholesterol levels or body mass index between users and non-users of HRT. However, users reported significantly higher rates of previous osteoporosis and hysterectomy., Conclusions: Prevalence rates of HRT use are increasing together with compliance rates and this may reflect increased confidence with HRT therapy. Users of HRT have an increased rate of mammography compared to non-users and this may contribute to earlier detection and, therefore, increased estimates of breast cancer in HRT users. There was no support from the 1995 data for a 'healthy women' hypothesis among HRT users.

Background: The objective of this study was to compare the health status of women who use and do not use hormone replacement therapy (HRT)., Method: The 1994 South Australian Health Omnibus Survey (a population health interview survey) was used to administer the short form-36 health survey questionnaire (SF-36) to users and non-users of HRT. A representative sample of 813 women aged 40 years and older were interviewed. The response rate of the survey was 72.4%. Eight health dimensions of the SF-36 were measured: physical functioning, social functioning, role limitations owing to emotional problems, role limitations owing to physical problems, mental health, vitality, pain and general health., Results: The mean score for all eight health dimensions was in the bottom 50% of the population for HRT users while non-users were in the upper 50%. Users of HRT had significantly poorer scores for physical limitations, body pain, general health, vitality, social functioning and mental health., Conclusion: Women who use HRT are less healthy than non-users when measured by a generic health status measure.

Purpose: The intraocular microenvironment is an immune-privileged site where immunogenic inflammation is suppressed. Suppression of immunogenic inflammation has been associated with immunosuppressive factors found in aqueous humor produced by ocular tissues. To further understand the mechanisms suppressing immunogenic inflammation in the eye, we have examined the production of lymphokines by primed T-cells activated in the presence of aqueous humor., Methods: Enriched in vivo primed T-cells were T-cell receptor-stimulated in the presence of fresh aqueous humor. The culture supernatant was assayed for IFN-gamma and IL-4 by sandwich ELISA. TGF-beta production by T-cells stimulated in the presence of aqueous humor was assayed by a TGF-beta bioassay of the culture supernatant and by quantitative RT-PCR for TGF-beta 1 mRNA expression. Aqueous humor-treated T-cells were assayed for their capacity to suppress IFN-gamma production by stimulated, primed T-cells., Results: Aqueous humor-enhanced proliferation but irreversibly suppressed production of both IFN-gamma and IL-4 by in vitro-activated, in vivo-primed T-cells. Aqueous humor induced in vivo primed T-cells to produce TGF-beta in vitro, and these TGF-beta-producing T-cells suppressed IFN-gamma production by other T-cells activated in co-cultures., Conclusions: Aqueous humor alters the functional program of TCR-ligand-activated, primed T-cells, converting the cells to TGF-beta-producing regulatory cells.

The aqueous humor of the eye contains factors that regulate immunological responses within the immunosuppressive ocular microenvironment. Besides TGF-beta, the proteins in the low molecular weight (< 3500 Da) fraction of normal aqueous humor are also immunosuppressive. The low molecular weight fraction of aqueous humor inhibits IFN-gamma production and proliferation of antigen-stimulated lymph node cells. Neuropeptides are one possible family of low molecular weight factors in aqueous humor. Through the utilization of an antigen capturing enzyme-assay, the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) was detected in normal aqueous humor of humans, rabbits, and mice. The mean concentration of alpha-MSH in normal aqueous humor of humans was 20 +/- 3 pM, of rabbits 11 +/- 1 pM, of BALB/c mice 16 +/- 3 pM, and of C57BL/6 mice 14 +/- 3 pM. These physiological concentrations of alpha-MSH inhibited the production of IFN-gamma by antigen-stimulated lymph node cells. In contrast to the low molecular weight fraction, alpha-MSH did not inhibit proliferation. There was a 26% recovery of IFN-gamma production when alpha-MSH was absorbed from the low molecular weight fraction. The results demonstrate neuropeptides to be constitutive components of normal aqueous humor and that factors with the capability of differential regulation of effector T-cell activity may be present within the immunosuppressive ocular microenvironment.