Molecular markers of dihydroartemisinin-piperaquine resistance in northwestern Thailand.

BACKGROUND: Dihydroartemisinin-piperaquine (DHA-PPQ) combination therapy is the current first-line treatment for Plasmodium falciparum malaria in Thailand. Since its introduction in 2015, resistance to this drug combination has emerged in the eastern part of the Greater Mekong Subregion including the eastern part of Thailand near Cambodia. This study aimed to assess whether the resistance genotypes have arisen the western part of country. METHODS: Fifty-seven P. falciparum-infected blood samples were collected in Tak province of northwestern Thailand between 2013 and 2019. Resistance to DHA was examined through the single nucleotide polymorphisms (SNPs) of kelch13. PPQ resistance was examined through the copy number plasmepsin-2 and the SNPs of Pfcrt. RESULTS: Among the samples whose kelch13 were successfully sequenced, approximately half (31/55; 56%) had mutation associated with artemisinin resistance, including G533S (23/55; 42%), C580Y (6/55; 11%), and G538V (2/55; 4%). During the study period, G533S mutation appeared and increased from 20% (4/20) in 2014 to 100% (9/9) in 2019. No plasmepsin-2 gene amplification was observed, but one sample (1/54) had the Pfcrt F145I mutation previously implicated in PPQ resistance. CONCLUSIONS: Kelch13 mutation was common in Tak Province in 2013-2019. A new mutation G533S emerged in 2014 and rose to dominance in 2019. PPQ resistance marker Pfcrt F145I was also detected in 2019. Continued surveillance of treatment efficacy and drug resistance markers is warranted.

Concurrent development of encapsulating peritoneal sclerosis and calciphylaxis in a patient with peritoneal dialysis for end-stage renal disease.

Both encapsulating peritoneal sclerosis (EPS) and calciphylaxis are rare but severe complications involving patients with end-stage renal disease. In this report, we discuss a unique case of a 73-year-old female patient who had undergone 8 years of peritoneal dialysis for IgA nephropathy and concurrently developed these two synchronous complications within 3 months of each other. Diagnosis and management of both conditions were discussed in detail as well as the possible association between the two. With surgical treatment for EPS and measures to minimise bone mineral disorder abnormalities, both complications have been successfully managed to date.

Celiac artery aneurysm causing an acute abdomen.

Abdominal pain is a very common presentation in the accident and emergency department. However, vasculitis is not the usual first differential diagnosis. This paper discusses a case of polyarteritis nodosa presenting with acute abdominal pain alone. Common surgical conditions were obviously considered, but they were not found to cause the patient's problems. We describe how investigations led to this diagnosis discussed in detail in this paper. It is important to remember that prompt recognition of unusual life-threatening conditions can lead to timely intervention.

Why behaviours do not change: structural constraints that influence household decisions to control pig diseases in Myanmar.

This article problematises the ways in which behavioural change by poor individuals dominates the global discussions on means to tackle issues caused by systemic problems. We do so by focusing on the case of animal diseases, a symptom of many systematic failures. While livestock farming has long been praised as a mitigating factor against poverty, livestock diseases threaten the lives and livelihoods of poor and marginalised people who depend on animals. Aiming at controlling animal diseases, policy makers tend to focus on behavioural change by individual farmers by enhancing their knowledge. We conducted an in-depth qualitative research among pig farmers in Myanmar, a country that is rapidly increasing livestock production, to document contextual and systematic constraints that influence farmers' understandings and perceptions of disease-related risks and household-level decisions to invest in animal disease control. We conducted in-depth interviews, focus group discussions and participant observation in three townships in the Yangon region. Structural constraints such as weak veterinary health system and limited access to low-interest credit prevent farmers from gaining necessary knowledge about disease prevention and make them economically vulnerable. These systematic constraints drive behaviours considered 'risky' for disease emergence and spread. As a result, many small- and medium-scale farmers in low- and middle-income countries remain trapped in a vicious cycle of poverty and ill health for both animals and humans. We conclude that, instead of focusing on individual behavioural change, interventions need to combine enhancing knowledge by individual farmers and tackling economic and structural constraints that limit their agency and ability to address practices that are considered risky.

Spontaneous resolution of untreated diffuse large B-cell lymphoma of maxillary bone after incisional biopsy.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphomas which require multiagent therapy for remission induction and are associated with relapse in more than 40% of patients. Spontaneous remission of diffuse large B-cell lymphoma (DLBCL) is a rare occurrence.

Factor structure and diagnostic efficiency of the Myanmar version BDI-II among substance users.

BACKGROUND: The Beck Depression Inventory II (BDI-II) has been accepted as one of the most commonly used self-report measures for depression. However, there is no study examining the psychometric properties of the BDI-II among substance users in low- and middle-income countries such as Myanmar. Therefore, this study aimed to evaluate the suitability of using this instrument in substance users and to examine the reliability and diagnostic efficiency to be compared with the International Classification of Diseases (ICD-10) among substance users in Northern Shan State of Myanmar. METHODS: A respondent-driven sampling (RDS) method was applied for recruiting the participants in this study, and total 230 substance users were recruited. On the other hand, 50 participants who visited the drop-in center (DIC) were screened for depressive symptoms using ICD-10 during the days when one consultant psychiatrist doctor was presented. These participants were interviewed face-to-face by the consultant psychiatrist using a semi-structured questionnaire including the Myanmar version of the BDI-II (mBDI-II). RESULTS: The mBDI-II showed moderate accuracy with an area under the curve of 0.68. The optimal cutoff score was 10 with the highest Youden index (0.48), and it had high sensitivity and specificity (0.78 and 0.70). The Cronbach's alpha coefficients for clinically depressed and non-clinically depressed substance users were 0.91 and 0.93, respectively. Confirmatory factor analysis of the mBDI-II indicated that a three-factor solution (cognitive, affective, and somatic) was the best fit for substance users. CONCLUSIONS: The mBDI-II has sound psychometric properties among substance users with moderate accuracy and range of possible cutoff scores together with sensitivity and specificity.

Cost-effectiveness of a community-based physical activity programme for adults (Be Active) in the UK: an economic analysis within a natural experiment.

OBJECTIVE: To determine the cost-effectiveness of a physical activity programme (Be Active) aimed at city-dwelling adults living in Birmingham, UK. METHODS: Very little is known about the cost-effectiveness of public health programmes to improve city-wide physical activity rates. This paper presents a cost-effectiveness analysis that compares a physical activity intervention (Be Active) with no intervention (usual care) using an economic model to quantify the reduction in disease risk over a lifetime. Metabolic equivalent minutes achieved per week, quality-adjusted life years (QALYs) gained and healthcare costs were all included as the main outcome measures in the model. A cost-benefit analysis was also conducted using 'willingness-to-pay' as a measure of value. RESULTS: Under base-case assumptions-that is, assuming that the benefits of increased physical activity are sustained over 5 years, participation in the Be Active programme increased quality-adjusted life expectancy by 0.06 years, at an expected discounted cost of £3552, and thus the cost-effectiveness of Be Active is £400 per QALY. When the start-up costs of the programme are removed from the economic model, the cost-effectiveness is further improved to £16 per QALY. The societal value placed on the Be Active programme was greater than the operation cost therefore the Be Active physical activity intervention results in a net benefit to society. CONCLUSIONS: Participation in Be Active appeared to be cost-effective and cost-beneficial. These results support the use of Be Active as part of a public health programme to improve physical activity levels within the Birmingham-wide population.

Taking stock of Myanmar's progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead.

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar's progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar's government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar's government should invest greater efforts into health system strengthening to pave the road to universal health coverage.

Chronic hepatitis B prognostic markers other than pre-treatment viral load predicted composite treatment outcome.

INTRODUCTION: Chronic hepatitis B (CHB) is a globally common infectious disease. Its clinical course is complicated. In Southeast Asia, nucleos(t)ide analogues (NA) are commonly used drugs for CHB treatment. Composite treatment outcome has often been used in CHB clinical practice, but rarely predicted epidemiologically. This study aimed to compare the composite treatment outcome between CHB patients with low and high treatment-naïve viral load, and to identify its predictors METHODOLOGY: This retrospective cohort study followed up 95 CHB patients on NA treatment for a year. Composite treatment outcome was defined as undetectable HBV DNA level, ALT normalization and, HBeAg clearance in the case of HBeAg-positive patients. Multinomial logistic regression analysis was applied to analyze the significant treatment response predictors. RESULTS: Complete composite treatment outcome was achieved by 52% of CHB patients with an initial viral load < 6.5 log 10 copies /ml, but 31% of those had an initial viral load ≥ log 6.5 log 10 copies /ml. Outcome was predicted by HBeAg negativity (adjusted relative risk ratio, aRRR = 11.1, 95 % confidence interval, CI 3-41.3) and ALT normalization within the sixth month of therapy (aRRR = 6.7, CI 1.8-24.9). An elevation of ALT to more than 1.5 times the normal value (40 IU/ml) can lead to an incomplete response on NA therapy (aRRR = 6.2, CI 1.5-26.6.) CONCLUSION: Routine clinical markers other than pre-treatment viral load predicted composite CHB outcome on NA Therapy.

Domain structure and protein interactions of the silent information regulator Sir3 revealed by screening a nested deletion library of protein fragments.

Transcriptional silencing in yeast is mediated by the interactions of silent information regulator (Sir) proteins with chromatin and with one another. The stable association of Sir3 with Sir4 is mediated by a C-terminal region of Sir3 that has additional functions including the dimerization of Sir3. We have developed a simple, robust expression screening methodology that allows for the unbiased identification of functional protein domains expressed from nested-deletion libraries of full-length genes. Using these methodologies, Sir3 dimerization was shown to be mediated by two separate domains. One of these domains also binds cooperatively to the C-terminal coiled-coil motif of Sir4 and dimerization further increases the affinity of Sir3 for Sir4. The resulting Sir3-Sir4 complexes form progressively higher order assemblies with increasing protein concentration, with implications for the mechanism of gene silencing.