Comparison of skin cancer risk between renal transplant recipients and patients with glomerular diseases in rural Queensland.

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Effect of Sevoflurane on the Proliferation of A549 Lung Cancer Cells.

Background and Objectives: Sevoflurane has opposing effects on cancer progression, depending on its concentration and the cancer type. This study investigated the effects of sevoflurane on the proliferation of A549 lung cancer cells. Materials and Methods: In vitro, the number of A549 cells exposed to different concentrations of sevoflurane was counted. The size and weight of tumors from a xenograft mouse model exposed to air or sevoflurane were measured in vivo experiments. Additionally, hematoxylin and eosin staining and immunohistochemical detection of Ki-67 in the harvested tumor tissues were performed. Results: A total of 72 culture dishes were used and 24 dishes were assigned to each group: Air group; 2% Sevo group (air + 2% sevoflurane); and 4% Sevo group (air + 4% sevoflurane). The number of A549 cells in the 2% Sevo group was less than that in the Air and 4% Sevo groups (Air: 7.9 ± 0.5; 0.5, 2% Sevo: 6.8 ± 0.4, 4% Sevo: 8.1 ± 0.3; p = 0.000). The tumor size was not significantly different between the two groups (Air: 1.5 ± 0.7, 2% Sevo: 2.4 ± 1.9; p = 0.380). Conclusions: The in vitro data showed that sevoflurane inhibited the proliferation of A549 lung cancer cells in a concentration-specific manner. However, the in vivo data showed no correlation between sevoflurane exposure and A549 cell proliferation. Thus, further research is required to understand fully the effects of sevoflurane on cancer progression and to reconcile differences between the in vitro and in vivo experimental results.

Positive Selection of Mutations in the Helicobacter pylori katA 5' Untranslated Region in a Mongolian Gerbil Model of Gastric Disease.

To evaluate potential effects of gastric inflammation on Helicobacter pylori diversification and evolution within the stomach, we experimentally infected Mongolian gerbils with an H. pylori strain in which Cag type IV secretion system (T4SS) activity is controlled by a TetR/tetO system. Gerbils infected with H. pylori under conditions in which Cag T4SS activity was derepressed had significantly higher levels of gastric inflammation than gerbils infected under conditions with repressed Cag T4SS activity. Mutations in the 5' untranslated region (UTR) of katA (encoding catalase) were detected in strains cultured from 8 of the 17 gerbils infected with Cag T4SS-active H. pylori and none of the strains from 17 gerbils infected with Cag T4SS-inactive H. pylori. Catalase enzymatic activity, steady-state katA transcript levels, and katA transcript stability were increased in strains with these single nucleotide polymorphisms (SNPs) compared to strains in which these SNPs were absent. Moreover, strains harboring these SNPs exhibited increased resistance to bactericidal effects of hydrogen peroxide, compared to control strains. Experimental introduction of the SNPs into the wild-type katA 5' UTR resulted in increased katA transcript stability, increased katA steady-state levels, and increased catalase enzymatic activity. Based on site-directed mutagenesis and modeling of RNA structure, increased katA transcript levels were correlated with higher predicted thermal stability of the katA 5' UTR secondary structure. These data suggest that high levels of gastric inflammation positively select for H. pylori strains producing increased levels of catalase, which may confer survival advantages to the bacteria in an inflammatory gastric environment.

Serum anion gap revisited: a verified reference interval for contemporary use.

BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. AIMS: To determine the reference interval for AG based on current laboratory techniques. METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+ ] - [Cl- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. RESULTS: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L. CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders.

An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease.

Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.

Enhanced Fitness of a Helicobacter pylori babA Mutant in a Murine Model.

Helicobacter pylori genomes encode over 60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains exhibiting differential fitness in vivo compared to in vitro, we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro. The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a nonselective bottleneck in vivo. We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro. Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro. These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

Reducing non-melanoma skin cancer risk in renal transplant recipients.

With an increasing number of renal transplant recipients (RTRs) and improving patient survival, a higher incidence of non-melanoma skin cancer (NMSC) has been observed. NMSC in RTRs are often more numerous and biologically more aggressive than the general population, thus contributing towards an increase in morbidity and to a lesser degree, mortality. The resultant cumulative health and financial burden is a recognized concern. Proposed strategies in mitigating risks of developing NMSC and early therapeutic options thereof include tailored modification of immunosuppressants in conjunction with sun protection in all transplant patients. This review highlights the clinical and financial burden of transplant-associated skin cancers, carcinogenic mechanisms in association with immunosuppression, importance of skin cancer awareness campaign and integrated transplant skin clinic, and the potential role of chemoprotective agents. A scheme is proposed for primary and secondary prevention of NMSC based on the available evidence.

Comparison of skin cancer awareness and sun protection behaviours between renal transplant recipients and patients with glomerular disease treated with immunosuppressants.

BACKGROUND: There is no previous study that compare skin cancer awareness and photoprotective behaviours between renal transplant recipients (RTR) and patients with glomerular disease (GD). OBJECTIVES/METHODS: Sixty-one RTR and 51 patients with GD were given a self-reported questionnaire to evaluate skin cancer awareness and photoprotective behaviours in this cross-sectional study. The former group received a formal education on skin cancer and the latter an informal session prior to immunosuppressant use. RESULTS: Ninety-three percent (n = 57) of RTRs and 88% (n = 45) of patients with GD responded to the survey. Majority of participants from both groups were aware that ultraviolet radiation could play a role in the occurrence of skin cancers and the awareness increased in participants with higher education (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.15-1.95, P = .003). Ninety-eight percent vs 71% were aware that immunosuppressants can increase the risk of developing cancer (P < .001) and higher awareness was noted in younger participants (OR = 0.92, 95% CI = 0.87-0.97, P = .003). Suboptimal photoprotective behaviours (sun avoidance, sunscreen usage and sun-protective clothing) were noted in both cohorts and slightly lower sun protection rates were reported in RTR when compared with patients having GD. The level of sun protective measures in RTR based on high, moderate and minimal use of photoprotective measures were 21%, 46% and 33%, respectively. In terms of patients with GD, the latter practices were 13%, 50% and 37%, respectively (P = .560). Higher educational status was significantly associated with better sunscreen usage in RTR (P = .017) whereas this finding was not observed in patients with GD. CONCLUSION: Patients with GD and RTR should have formal education on the risks of skin cancers before starting immunosuppressants. Follow-up education and surveillance is required to improve skin protective practices in these patients.

Bacterial Energetic Requirements for Helicobacter pylori Cag Type IV Secretion System-Dependent Alterations in Gastric Epithelial Cells.

Helicobacter pylori colonizes the stomach in about half of the world's population. H. pylori strains containing the cag pathogenicity island (cag PAI) are associated with a higher risk of gastric adenocarcinoma or peptic ulcer disease than cag PAI-negative strains. The cag PAI encodes a type IV secretion system (T4SS) that mediates delivery of the CagA effector protein as well as nonprotein bacterial constituents into gastric epithelial cells. H. pylori-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interleukin-8 (IL-8) secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. In this study, we analyzed the bacterial energetic requirements associated with these cellular alterations. Mutant strains lacking Cagα, Cagß, or CagE (putative ATPases corresponding to VirB11, VirD4, and VirB4 in prototypical T4SSs) were capable of T4SS core complex assembly but defective in CagA translocation into host cells. Thus, the three Cag ATPases are not functionally redundant. Cagα and CagE were required for H. pylori-induced NF-κB activation, IL-8 secretion, and TLR9 activation, but Cagß was dispensable for these responses. We identified putative ATP-binding motifs (Walker-A and Walker-B) in each of the ATPases and generated mutant strains in which these motifs were altered. Each of the Walker box mutant strains exhibited properties identical to those of the corresponding deletion mutant strains. These data suggest that Cag T4SS-dependent delivery of nonprotein bacterial constituents into host cells occurs through mechanisms different from those used for recruitment and delivery of CagA into host cells.

Health system strengthening: Integration of breast cancer care for improved outcomes.

The adoption of the goal of universal health coverage and the growing burden of cancer in low- and middle-income countries makes it important to consider how to provide cancer care. Specific interventions can strengthen health systems while providing cancer care within a resource-stratified perspective (similar to the World Health Organization-tiered approach). Four specific topics are discussed: essential medicines/essential diagnostics lists; national cancer plans; provision of affordable essential public services (either at no cost to users or through national health insurance); and finally, how a nascent breast cancer program can build on existing programs. A case study of Zambia (a country with a core level of resources for cancer care, using the Breast Health Global Initiative typology) shows how a breast cancer program was built on a cervical cancer program, which in turn had evolved from the HIV/AIDS program. A case study of Brazil (which has enhanced resources for cancer care) describes how access to breast cancer care evolved as universal health coverage expanded. A case study of Uruguay shows how breast cancer outcomes improved as the country shifted from a largely private system to a single-payer national health insurance system in the transition to becoming a country with maximal resources for cancer care. The final case study describes an exciting initiative, the City Cancer Challenge, and how that may lead to improved cancer services.

Role of a Stem-Loop Structure in Helicobacter pylori cagA Transcript Stability.

Helicobacter pylori CagA is a secreted effector protein that contributes to gastric carcinogenesis. Previous studies showed that there is variation among H. pylori strains in the steady-state levels of CagA and that a strain-specific motif downstream of the cagA transcriptional start site (the +59 motif) is associated with both high levels of CagA and premalignant gastric histology. The cagA 5' untranslated region contains a predicted stem-loop-forming structure adjacent to the +59 motif. In the current study, we investigated the effect of the +59 motif and the adjacent stem-loop on cagA transcript levels and cagA mRNA stability. Using site-directed mutagenesis, we found that mutations predicted to disrupt the stem-loop structure resulted in decreased steady-state levels of both the cagA transcript and the CagA protein. Additionally, these mutations resulted in a decreased cagA mRNA half-life. Mutagenesis of the +59 motif without altering the stem-loop structure resulted in reduced steady-state cagA transcript and CagA protein levels but did not affect cagA transcript stability. cagA transcript stability was not affected by increased sodium chloride concentrations, an environmental factor known to augment cagA transcript levels and CagA protein levels. These results indicate that both a predicted stem-loop structure and a strain-specific +59 motif in the cagA 5' untranslated region influence the levels of cagA expression.

The prevalence of selected risk factors for non-communicable diseases in Hargeisa, Somaliland: a cross-sectional study.

BACKGROUND: Non-communicable diseases (NCDs), particularly cardiovascular diseases, diabetes, respiratory conditions and cancers, are the most common causes of morbidity and mortality globally. Information on the prevalence estimates of NCD risk factors such as smoking, low fruit & vegetable intake, physical inactivity, raised blood pressure, overweight, obesity and abnormal blood lipid are scarce in Somaliland. The aim of this study was to determine the prevalence of these selected risk factors for NCDs among 20-69 year old women and men in Hargeisa, Somaliland. METHODS: A cross-sectional study was conducted in five districts of Hargeisa (Somaliland), using the STEPwise approach to noncommunicable disease risk factor surveillance (STEPS) to collect data on demographic and behavioral characteristics and physical measurements (n = 1100). The STEPS approach is a standardized method for collecting, analysing and disseminating data on NCD risk factor burden. Fasting blood sugar, serum lipids (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides) were collected in half of the participants. RESULTS: The vast majority of participants had ≤1 serving of fruits daily (97.7%) and ≤ 1 serving of vegetables daily (98.2%). The proportion of participants with low physical activity levels was 78.4%. The overall prevalence of high salt intake was 18.5%. The prevalence of smoking and khat chewing among men was 27 and 37% respectively, and negligible among women. In women, the prevalence of hypertension increased from 15% in the age group 20-34 years to 67% in the age group 50-69 years, the prevalence of overweight and obesity (BMI ≥ 25 kg/m2) from 51 to 73%, and the prevalence of diabetes from 3 to 22%. Similar age-trends were seen in men. CONCLUSION: Most of the selected risk factors for noncommunicable diseases were high and increased by age in both women and men. Overweight and obesity and low physical activity needs intervention in women, while hypertension and low fruit and vegetable consumption needs intervention in both men and women. Somaliland health authorities should develop and/or strengthen health services that can help in treating persons with hypertension and hyperlipidaemia, and prevent a future burden of NCDs resulting from a high prevalence of NCD risk factors.

Indigenous and tribal peoples' health (The Lancet-Lowitja Institute Global Collaboration): a population study.

BACKGROUND: International studies of the health of Indigenous and tribal peoples provide important public health insights. Reliable data are required for the development of policy and health services. Previous studies document poorer outcomes for Indigenous peoples compared with benchmark populations, but have been restricted in their coverage of countries or the range of health indicators. Our objective is to describe the health and social status of Indigenous and tribal peoples relative to benchmark populations from a sample of countries. METHODS: Collaborators with expertise in Indigenous health data systems were identified for each country. Data were obtained for population, life expectancy at birth, infant mortality, low and high birthweight, maternal mortality, nutritional status, educational attainment, and economic status. Data sources consisted of governmental data, data from non-governmental organisations such as UNICEF, and other research. Absolute and relative differences were calculated. FINDINGS: Our data (23 countries, 28 populations) provide evidence of poorer health and social outcomes for Indigenous peoples than for non-Indigenous populations. However, this is not uniformly the case, and the size of the rate difference varies. We document poorer outcomes for Indigenous populations for: life expectancy at birth for 16 of 18 populations with a difference greater than 1 year in 15 populations; infant mortality rate for 18 of 19 populations with a rate difference greater than one per 1000 livebirths in 16 populations; maternal mortality in ten populations; low birthweight with the rate difference greater than 2% in three populations; high birthweight with the rate difference greater than 2% in one population; child malnutrition for ten of 16 populations with a difference greater than 10% in five populations; child obesity for eight of 12 populations with a difference greater than 5% in four populations; adult obesity for seven of 13 populations with a difference greater than 10% in four populations; educational attainment for 26 of 27 populations with a difference greater than 1% in 24 populations; and economic status for 15 of 18 populations with a difference greater than 1% in 14 populations. INTERPRETATION: We systematically collated data across a broader sample of countries and indicators than done in previous studies. Taking into account the UN Sustainable Development Goals, we recommend that national governments develop targeted policy responses to Indigenous health, improving access to health services, and Indigenous data within national surveillance systems. FUNDING: The Lowitja Institute.

Changes in prevalence, awareness, treatment and control of hypertension from 2004 to 2014 among 25-74-year-old citizens in the Yangon Region, Myanmar.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases, and little is known about trends in prevalence, awareness, treatment and the control of hypertension in Myanmar. This study aims at evaluating changes from 2004 to 2014 in the prevalence, awareness, treatment and control of hypertension in the Yangon Region, Myanmar, and to compare associations between hypertension and selected socio-demographic, behavioural- and metabolic risk factors in 2004 and 2014. METHODS: In 2004 and 2014, household-based cross-sectional studies were conducted in urban and rural areas of Yangon Region using the WHO STEPS protocol. Through a multi-stage cluster sampling method, a total of 4448 and 1486 participated in 2004 and 2014, respectively, with the response rates above 89%. RESULTS: From 2004 to 2014, there was a significant increase in the age-standardized prevalence of hypertension from 26.7% (95% CI:24.4-29.1) - 34.6% (32.2-37.1), as well as an awareness from 19.4% (17.2-21.9) to 27.8% (24.9-31.0), while treatment and control rates did not change. The age-standardized mean systolic blood pressure increased from 122.8 (SE) ± 0.82 mmHg in 2004 to 128.1 ± 0.53 mmHg in 2014, whereas diastolic blood pressure increased from 76.2 ± 0.35 mmHg to 80.9 ± 0.53 mmHg. In multivariate analyses, hypertension was significantly associated with age, alcohol consumption, overweight and diabetes in both 2004 and 2014, and additionally associated with low physical activity and hypercholesterolemia in 2004. Combining all data, a significant association between study-year and hypertension persisted in different models with an adjustment for socio-demographic variables and behavioural variables, but not when adjusting for a combination of socio-demographic variables, the metabolic variables, BMI and hypercholesterolemia. CONCLUSION: The prevalence of hypertension has risen from 2004 to 2014 in both urban and rural areas of the Yangon Region, while, the awareness, treatment and control rate of hypertension remains low in urban and rural areas among both males and females. It is likely that changes in the metabolic variables, BMI and hypercholesterolemia have contributed to an increase in the prevalence of hypertension from 2004 to 2014. Factors associated with hypertension in both study years were age, alcohol consumption, overweight and diabetes. A national hypertension control programme should be implemented in order to reduce premature deaths in Myanmar.

Prevalence and determinants of hypertension in Myanmar - a nationwide cross-sectional study.

BACKGROUND: Non-communicable diseases (NCDs), malaria and tuberculosis dominate the disease pattern in Myanmar. Due to urbanization, westernized lifestyle and economic development, it is likely that NCDs such as cerebrovascular disease and ischemic heart disease are on a rise. The leading behavioral- and metabolic NCDs risk factors are tobacco smoke, dietary risks and alcohol use, and high blood pressure and body mass index, respectively. The study aimed at estimating the prevalence and determinants of hypertension, including metabolic-, behavioral- and socio-demographic risk factors. METHODS: A nationwide, cross-sectional study of 7429 citizens of Myanmar aged 15-64 years were examined in 2009, using the WHO STEPS methodology. In separate analyses by gender, odds radios (ORs) and 95 % confidence intervals (CIs) for determinants of hypertension were estimated using logistic regression analyses. Confounders included in analyses were chosen based on Directed acyclic graphs (DAGs). RESULTS: The prevalence of hypertension was 30.1 % (95 % CI: 28.4-31.8) in males and 29.8 % (28.5-31.1) in females. The mean BMI was 21.7 (SD 4.3) kg/m(2) for males and 23.0 (5.1) kg/m(2) for females. In fully adjusted analyses, we found in both genders increased OR for hypertension if the participants had high BMI (males: OR = 2.6; 95 % CI 2.1-3.3, females: OR = 2.3; 2.0-2.7) and high waist circumference (males: OR = 3.4; 1.8-6.8, females: OR = 2.7; 2.2-3.3). In both sexes, associations were also found between hypertension and low physical activity at work, or living in urban areas or the delta region. Being underweight and use of sesame oil in cooking was associated with lower odds for hypertension. CONCLUSIONS: The prevalence of hypertension was high and associated with metabolic-, behavioral- and socio-demographic factors. Due to expected rapid economic growth in Myanmar we recommend similar studies in the future to follow up and describe trends in the risk factors, especially modifiable factors, which will most likely be on rise. Studies on effectiveness on interventions are needed, and policies to reduce the burden of NCD risk factors should be implemented if proven effective in similar settings.

Urban-rural differences in the prevalence of non-communicable diseases risk factors among 25-74 years old citizens in Yangon Region, Myanmar: a cross sectional study.

BACKGROUND: Recent societal and political reforms in Myanmar may upturn the socio-economy and, thus, contribute to the country's health transition. Baseline data on urban-rural disparities in non-communicable disease (NCD) risk factors are not thoroughly described in this country which has been relatively closed for more than five decades. We aim to investigate urban-rural differences in mean values and the prevalence of selected behavioral and metabolic risk factors for non-communicable diseases and 10-years risk in development of coronary heart diseases (CHD). METHODS: Two cross-sectional studies were conducted in urban and rural areas of Yangon Region in 2013 and 2014 respectively, using the WHO STEPwise approach to surveillance of risk factors of NCDs. Through a multi-stage cluster sampling method, 1486 participants were recruited. RESULTS: Age-standardized prevalence of the behavioral risk factors tended to be higher in the rural than urban areas for all included factors and significantly higher for alcohol drinking (19.9% vs. 13.9%; p = 0.040) and low fruit & vegetable consumption (96.7% vs. 85.1%; p = 0.001). For the metabolic risk factors, the tendency was opposite, with higher age-standardized prevalence estimates in urban than rural areas, significantly for overweight and obesity combined (40.9% vs. 31.2%; p = 0.023), obesity (12.3% vs.7.7%; p = 0.019) and diabetes (17.2% vs. 9.2%; p = 0.024). In sub-group analysis by gender, the prevalence of hypercholesterolemia and hypertriglyceridemia were significantly higher in urban than rural areas among males, 61.8% vs. 40.4%; p = 0.002 and 31.4% vs. 20.7%; p = 0.009, respectively. Mean values of age-standardized metabolic parameters showed higher values in urban than rural areas for both male and female. Based on WHO age-standardized Framingham risk scores, 33.0% (95% CI = 31.7-34.4) of urban dwellers and 27.0% (95% CI = 23.5-30.8) of rural dwellers had a moderate to high risk of developing CHD in the next 10 years. CONCLUSION: The metabolic risk factors, as well as a moderate or high ten-year risk of CHD were more common among urban residents whereas behavioral risk factors levels were higher in among the rural people of Yangon Region. The high prevalences of NCD risk factors in both urban and rural areas call for preventive measures to reduce the future risk of NCDs in Myanmar.

Is Low Serum Klotho Level Associated with Alterations in Coronary Flow Reserve?

BACKGROUND: The Klotho gene, described as an "aging suppressor" gene, encodes a single-pass transmembrane protein. The extracellular part of Klotho is cleaved and released into the circulation where it may function as a vasculoprotective hormone. Coronary flow reserve (CFR) is accepted as a marker of coronary microvascular dysfunction when epicardial coronary stenosis is absent. There are no data regarding the relationship between serum Klotho levels and disorders in coronary microcirculation in healthy adults. We aimed to investigate the association between serum Klotho levels and alterations in coronary microcirculation in healthy adults using echocardiographic measurements of CFR. METHODS: Thirty-four healthy volunteers (median age: 34 [27-39], 14 males) were enrolled in this study. The study population was divided into two subgroups according to the median value of serum Klotho levels: a high Klotho (HK) group (n = 17, median age: 34 [30-38]; 6 males) and a low Klotho (LK) group (n = 17, median age: 32 [26-39]; 8 males). The analysis of coronary flow velocities was performed by transthoracic Doppler echocardiography. RESULTS: Hyperemic diastolic peak flow velocities and CFR were significantly higher in the HK group than in the LK group (70 [66-92] versus 61 [47-66], P = 0.003 and 3.0 [2.6-3.8] versus 2.2 [1.7-2.8], respectively, P = 0.001). Serum Klotho levels were positively correlated with CFR (P < 0.001). CONCLUSION: Serum Klotho levels correlate with CFR in a healthy population. Low serum Klotho levels may potentially identify patients with impaired CFR.

Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis.

The Klotho gene, identified as an 'aging suppressor' gene, encodes a single-pass transmembrane protein. The extracellular domain of Klotho is cleaved and released in the blood stream, where it may function as a vasculoprotective hormone. Carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery and epicardial fat thickness (EFT) have been reported as early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and early atherosclerotic predictors, including EFT, FMD and CIMT in healthy adults. Fifty healthy volunteers were enrolled in this study, consisting of 21 males and 29 females with median age of 32 years. They were free of known risk factors for cardiovascular diseases. Serum Klotho levels were determined by the ELISA method. The study population was divided into two groups (n = 25 for each) according to the median serum Klotho level (459.4 pg/mL): higher Klotho (HK) group (613.6 pg/mL; ranges of 501.2-772.6 pg/mL) and lower Klotho (LK) group (338.7 pg/mL; ranges of 278.8-430.3 pg/mL). EFT was measured by transthoracic echocardiography, and CIMT and FMD were measured with standard procedures. The LK group showed lower values of FMD (p = 0.012) and larger values of EFT (p = 0.01) and CIMT (p < 0.001), compared to the HK group. Thus, the low serum Klotho levels were associated with increased EFT and CIMT and with the decreased FMD in the study population. We propose that the lower serum Klotho level is a newly identified predictor of atherosclerosis.