In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation

Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.

The long and winding road : health services for clients with chronic leg ulcers in the community

The prevalence of leg ulcers of is 0.12%–1.1% and >3,000 lower limb amputations are performed yearly in Australia due to non-healing leg or foot ulcers. Although evidence on leg ulcer management is available, a significant evidence-practice gap exists. To identify current leg ulcer management, a cross-sectional retrospective study was undertaken in Brisbane, Australia. A sample of 104 clients was recruited from a community specialist wound clinic and a tertiary hospital outpatient’s specialist wound clinic. All clients had an ulcer below their knee or on their foot for ≥4 weeks. Data were collected on ulcer care, health service usage and clinical history for the year prior to admission. On admission, participants reported having their ulcer for a median of 25 weeks (range 2-728 weeks); with 51% (53/104) reporting an ulcer duration of ≥24 weeks. Including the wound clinic, participants sought ulcer care from a median of 3 health care providers (range 2-7). General Practitioners provided ulcer care to 82% of participants. Nearly half (42%) had self-cared for their ulcer; 29% (30/104) received treatment by a community nurse. A gap was found between the community-based ulcer care experienced by this population and evidence-based guidelines in regards to assessment, management, advice, and referrals.

'Women on a Wiki’ : the role of interactive websites in reflective learning practices for undergraduate women’s health students

Aim Our pedagogical research addressed the following research questions: 1) Can shared ‘cyber spaces’, such as a ‘wiki’, be occupied by undergraduate women’s health students to improve their critical thinking skills? 2) What are the learning processes via which this occurs? 3) What are the implications of this assessment trial for achieving learning objectives and outcomes in future public health undergraduate courses? Methods The students contributed written, critical reflections (approximately 250 words) to the Wiki each week following the lecture. Students reflected on a range of topics including the portrayal of women in the media, femininity, gender inequality, child bearing and rearing, domestic violence, mental health, Indigenous women, older women, and LGBTIQ communities. Their entries were anonymous, but visible to their peers. Each wiki entry contained a ‘discussion tab’ wherein online conversations were initiated. We used a social constructivist approach to grounded theory to analyse the 480 entries posted over the semester. (http://pub336womenshealth.wikispaces.com/) Results The social constructivist approach initiated by Vygotsky (1978) and further developed by Jonasson (1994) was used to analyse the students’ contributions in relation to four key thematic outcomes including: 1) Complexities in representations across contexts; 2) Critical evaluation in real world scenarios; 3) Reflective practice based on experience, and; 4) Collaborative co-construction of knowledge. Both text and image/visual contributions are provided as examples within each of these learning processes. A theoretical model depicting the interactive learning processes that occurred via discussion of the textual and visual stimulus is presented.

Comparative genomics of koala, cattle and sheep strains of Chlamydia pecorum

Background Chlamydia pecorum is an important pathogen of domesticated livestock including sheep, cattle and pigs. This pathogen is also a key factor in the decline of the koala in Australia. We sequenced the genomes of three koala C. pecorum strains, isolated from the urogenital tracts and conjunctiva of diseased koalas. The genome of the C. pecorum VR629 (IPA) strain, isolated from a sheep with polyarthritis, was also sequenced. Results Comparisons of the draft C. pecorum genomes against the complete genomes of livestock C. pecorum isolates revealed that these strains have a conserved gene content and order, sharing a nucleotide sequence similarity > 98%. Single nucleotide polymorphisms (SNPs) appear to be key factors in understanding the adaptive process. Two regions of the chromosome were found to be accumulating a large number of SNPs within the koala strains. These regions include the Chlamydia plasticity zone, which contains two cytotoxin genes (toxA and toxB), and a 77 kbp region that codes for putative type III effector proteins. In one koala strain (MC/MarsBar), the toxB gene was truncated by a premature stop codon but is full-length in IPTaLE and DBDeUG. Another five pseudogenes were also identified, two unique to the urogenital strains C. pecorum MC/MarsBar and C. pecorum DBDeUG, respectively, while three were unique to the koala C. pecorum conjunctival isolate IPTaLE. An examination of the distribution of these pseudogenes in C. pecorum strains from a variety of koala populations, alongside a number of sheep and cattle C. pecorum positive samples from Australian livestock, confirmed the presence of four predicted pseudogenes in koala C. pecorum clinical samples. Consistent with our genomics analyses, none of these pseudogenes were observed in the livestock C. pecorum samples examined. Interestingly, three SNPs resulting in pseudogenes identified in the IPTaLE isolate were not found in any other C. pecorum strain analysed, raising questions over the origin of these point mutations. Conclusions The genomic data revealed that variation between C. pecorum strains were mainly due to the accumulation of SNPs, some of which cause gene inactivation. The identification of these genetic differences will provide the basis for further studies to understand the biology and evolution of this important animal pathogen. Keywords: Chlamydia pecorum; Single nucleotide polymorphism; Pseudogene; Cytotoxin

Health states for schizophrenia and bipolar disorder within the Global Burden of Disease 2010 Study

A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

Adolescent peer aggression and its association with mental health and substance use in an Australian cohort

Prospective longitudinal birth cohort data was used to examine the association between peer aggression at 14 years and mental health and substance use at 17 years. A sample of 1590 participants from the Western Australian Pregnancy Cohort (Raine) study were divided into mutually exclusive categories (victims, perpetrators, victim-perpetrators and uninvolved). Involvement in any type of peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim-perpetrator (8.7%) was reported by 40.2% of participants. After adjusting for confounding factors, those who were a victim of peer aggression had increased odds of later depression and internalising symptoms whilst perpetrators of peer aggression were found to be at increased risk of depression and harmful alcohol use. Victim-perpetrators of peer aggression were more likely to have externalising behaviours at 17 years. These results show an independent temporal relationship between peer aggression and later mental health and substance use problems in adolescence.

The long-term health consequences of child physical abuse, emotional abuse, and neglect : a systematic review and meta-analysis

Background Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes. Methods and Findings A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships. Conclusions This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence.

Alcohol use in South Africa : findings from the first demographic and health survey (1998)

Objective This study formed part of the 1998 South African Demographic and Health Survey, which included questions assessing the extent of alcohol use, risky drinking and alcohol problems among South Africans to obtain up-to-date baseline estimates of consumption and risky drinking and to inform intervention efforts. Method A two-stage random sample of 13,826 persons ages 15 or older (59% women) was included in the survey. Alcohol use was assessed through eight questions, including the CAGE questionnaire. Frequency analyses for different age groups, geographic setting, education level, population group and gender were calculated, as were odds ratios for these variables in relation to symptoms of alcohol problems. Results Current alcohol consumption was reported by 45% of the men and 17% of the women. White men (71%) were most likely and Asian women (9%) least likely to be current drinkers. Urban residents were more likely than nonurban dwellers to report current drinking. One third of the current drinkers reported risky drinking over weekends, and 28% of the men and 10% of the women scored above the cutoff level on the CAGE questionnaire. Symptoms of alcohol problems were significantly associated with lower socioeconomic status, no school education in women and being older than 25 years of age. Conclusions A comprehensive strategy is required to address the high levels of risky drinking and reported symptoms of alcohol problems.

Common values in assessing health outcomes from disease and injury: Disability weights measurement study for the Global Burden of Disease Study 2010

BACKGROUND Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.

Determinants and treatment of hypertension in South Africans: The first demographic and health survey

Objectives: To identify the groups of patients with high prevalence and poor control of hypertension in South Africa. Methods: In the first national Demographic and Health Survey, 12 952 randomly selected South Africans, aged 15 years and older were surveyed. Trained interviewers completed questionnaires on socio-demographic characteristics, lifestyle and the management of hypertension. This cross-sectional survey also included blood pressure, height and weight measurements. Logistic regression analyses identified the determinants of hypertension and the treatment status in this dataset. Results: A high risk of hypertension was associated with less than tertiary education, older age groups, overweight and obese people, using alcohol in excess, and a family history of stroke and hypertension. Rural Africans had the lowest risk of hypertension, which was significantly higher in obese African women than in women with normal body mass index. Improved hypertension control was found in the wealthy, women, older persons, being Asian, and having medical insurance. Conclusions: Rural African people had lower hypertension prevalence rates than the other groups. The poorer, younger men, without health insurance had the worst level of hypertension control.

Tobacco use in South Africans during 1998: The first demographic and health survey

Objective To determine smoking patterns in South Africa, and to identify groups requiring culturally appropriate smoking cessation programmes. Methods A random sample of 13 826 people (415 years), was interviewed to identify tobacco use patterns and respiratory symptoms. Peak expiratory flow rates were measured. Multinomial regression analyses identified sociodemographic factors related to tobacco use, and the latter’s association with respiratory conditions. Results In 1998, 24.6% adults (44.2% of males and 11.0% of females) smoked regularly. Coloured women had a higher rate (39%) than African women (5.4%). About 24% of the regular smokers had attempted to quit, with only 9.9% succeeding. African women (13.2%) used smokeless tobacco more frequently than others. Of the nonsmokers 28% and 19% were exposed to environmental tobacco smoke in their homes and workplaces, respectively. The regression analysis showed that the demographic characteristics of light smokers (1–14 tobacco equivalents per day) and heavy smokers (>=15 tobacco equivalents per day) differed. Light smoking occurred significantly more frequently in the poorest, least educated and urban people. The relative risk for light smoking was 18 in Coloured women compared with African women. Heavy smoking occurred most frequently in the highest educated group. A dose–response was observed between the amount smoked and the presence of respiratory diseases. Conclusions Smoking in South Africa is decreasing and should continue with the recently passed tobacco control legislation. Culturally appropriate tobacco cessation programmes for the identified target groups need to be developed.

The impact of the environment on health in Mongolia : a systematic review

Mongolia has significant exposure to environmental risk factors because of poor environmental management and behaviors, and children are increasingly vulnerable to these threats. This study aimed to assess levels of exposure and summarize the evidence for associations between exposures to environmental risk factors and adverse health outcomes in Mongolia, with a particular focus on children. A systematic review was conducted using the PubMed, EMBASE, Web of Science, Global Health Library, CINAHL, CABI, Scopus, and mongolmed.mn electronic databases up to April 2014 . A total of 59 studies meeting the predetermined criteria were included. Results indicate that the Mongolian population has significant exposure to outdoor and indoor air pollution, metals, environmental tobacco smoke, and other chemical toxins, and these risk factors have been linked to respiratory and cardiovascular diseases among adults and respiratory diseases and neurodevelopmental disorders among children. Well-designed epidemiological investigations in vulnerable populations especially in pregnant women and children are recommended.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.