IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

Integrating rehabilitation into health systems: A comparative study of nine middle-income countries using WHO's Systematic Assessment of Rehabilitation Situation (STARS).

BACKGROUND AND OBJECTIVE: The need for rehabilitation is growing due to health and demographic trends, especially the rise of non-communicable diseases and the rapid ageing of the global population. However, the extent to which rehabilitation is integrated into health systems is mostly unclear. Our objective is to describe and compare the nature and extent of integration of rehabilitation within health systems across nine middle-income countries using available Systematic Assessment of Rehabilitation Situation (STARS) reports. METHODS: Cross-country comparative study with variable-oriented design using available rehabilitation health system assessment reports from nine middle income countries. FINDINGS: The integration of rehabilitation into health systems is limited across countries. Governance and financing for rehabilitation are mostly established within health ministries but weakly so, while health information systems are characterized by no available data or data that is insufficient or not routinely generated. The overall numbers of rehabilitation workforce per capita are low, with frequent reports of workforce challenges. In most countries the availability of longer-stay, high-intensity rehabilitation is extremely low, the availability of rehabilitation in tertiary hospitals is modest and in government supported primary care its almost non-existent. Multiple concerns about rehabilitation quality arose but the lack of empirical data hinders formal appraisal. CONCLUSION: The study sheds light on the limited integration of rehabilitation in health systems and common areas of difficulty and challenge across nine middle income countries. All countries were found to have a basis on which to strengthen rehabilitation and there were often multiple areas within each health system building block that required action in order to improve the situation. Findings can inform governments, regional and global agencies to support future efforts to strengthen rehabilitation. Additionally, our study demonstrates the value of STARS reports for health policy and systems research and can serve as a model for further comparative studies.

Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities.

The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.

Fundamental motor skill proficiency among 7- to 10-year-old children with Down syndrome.

[Purpose] The purposes of this study were to assess the fundamental motor skill (FMS) of children with Down syndrome (DS) and to compare their FMS proficiencies to those of chronological age-matched and gender-matched typically developing children (TDC). [Participants and Methods] This cross-sectional study involved a total of 60 participants (30 children with DS and 30 TDC). The FMS proficiency of participants was assessed by using the test of gross motor development, second edition (TGMD-2). The data were analyzed using independent samples t-tests to verify the differences between the two groups and gender. The effect size of Cohen's d was also determined for comparing the two groups. [Results] The results showed that there were significant differences between children with DS and the TDC on locomotor and object control standard scores, and the gross motor quotient (GMQ). However, there were no significant gender-based differences in the locomotor and object control standard scores and the GMQ in both groups. [Conclusion] Based on the current results, the FMS proficiency of children with DS is lower than the TDC. Therefore, a therapeutic intervention program is necessary for children with DS to improve their FMS proficiency.

Loneliness in Myanmar's older population: A mixed-methods investigation.

OBJECTIVES: Little is known about loneliness in lower- and middle-income countries. This study investigates loneliness in the older population of Myanmar using a mixed-methods approach. METHODS: To identify predictors of loneliness, hierarchical regression models were used to analyze data from the Myanmar Aging Survey 2012 (N = 3,618, 57% women). In a mixed-methods sequential explanatory design, quantitative data were integrated with qualitative data from semi-structured interviews with older adults in Myanmar in 2019. RESULTS: The prevalence of loneliness varied by between-person characteristics. Health impairments, lower income, being widowed, not having children, and living with fewer household members were each associated with loneliness. Qualitative findings suggested that the physical presence of family members was especially protective against loneliness. Religion had mixed associations with loneliness, depending on the type of religious practice, demographic characteristics, health status, and community engagement. DISCUSSION: The findings contribute to a better understanding of individuals' experiences of loneliness and may inform the design of interventions to prevent loneliness in Myanmar and globally.

Epidemiology and outcome of septic arthritis in childhood: a 16-year experience and review of literature.

INTRODUCTION: Septic arthritis (SA) is a devastating infection with a high rate of sequelae. The aim of this retrospective study was to determine the epidemiology, clinically significant sequelae and risk factors for developing these sequelae in children admitted to our hospital with SA. METHODS: Patients with bacteriologically and/or radiologically confirmed SA from January 1999 to December 2014 were identified from discharge and laboratory records. Data was collected through a retrospective review of the case notes. RESULTS: A total of 75 patients (62.7% male) met the inclusion criteria. The median age at presentation was six years (range two weeks to 15 years), and six patients were neonates. Microbiologic aetiology was determined in 40 (53.3%) patients, with Staphylococcus aureus being the most common organism. 68.0% of the patients underwent arthrotomy, and the average hospital stay was 15.3 days. Sequelae of SA were observed in nine patients on follow-up. Univariate and multivariate statistical analyses showed that young age, pyogenic bacterial isolation and concomitant osteomyelitis were significant risk factors for developing sequelae. CONCLUSION: Our study demonstrated that young age, pyogenic bacterial isolation and concomitant osteomyelitis are associated with a high risk of sequelae. Timely microbiologic diagnosis by novel polymerase chain reaction methods and the use of magnetic resonance imaging in high-risk children to identify adjacent infection could possibly prevent lifelong disabling sequelae in SA.

Diagnostic value of recombinant nanoluciferase fused Toxoplasma gondii antigens in Luciferase-linked Antibody Capture Assay (LACA) for Toxoplasma infection in pigs.

Toxoplasmosis is a widespread protozoan zoonosis. Since ingesting undercooked meat harboring Toxoplasma gondii cyst is considered one of the major transmission routes to humans, the screening of T. gondii in meat-producing animals can reduce the risk of food-borne toxoplasmosis in humans. Among serological diagnostic methods, Luciferase-linked Antibody Capture Assay (LACA) has been found to be a promising platform with high sensitivity and specificity. In this study, we aimed to evaluate recombinant nanoluciferase fused-T. gondii antigens (rNluc-GRA6, rNluc-GRA7, rNluc-GRA8 and rNluc-BAG1) for their potential use in LACA for pigs. As a result, the sensitivity of GRA6-, GRA7-, GRA8- and BAG1-LACA were 70.0%, 80.0%, 80.0% and 30.0% with specificity 87.0%, 81.5%, 74.1% and 50.0%, respectively. The cocktail LACA using a mixture of rNluc-GRA6, rNluc-GRA7 and rNluc-GRA8 indicated higher sensitivity (90.0%) and a similar specificity (96.3%) in comparison with the commercial ELISA kit. Compared to the Dye-Test as a reference test, cocktail LACA showed strong agreement (kappa value=0.811) when we assessed pig sera collected at the slaughterhouse. In addition, we also successfully established the rapid LACA format for the detection of Toxoplasma infection in pigs (called Rapid-LACA) in which the test could be performed within 30 min. In Rapid-LACA, the protein A pre-coated/blocked plates could be preserved at -30°C, 4°C or room temperature conditions for at least two months without compromising on the quality of assay.

Southeast Asia must narrow down the yield gap to continue to be a major rice bowl.

Southeast Asia is a major rice-producing region with a high level of internal consumption and accounting for 40% of global rice exports. Limited land resources, climate change and yield stagnation during recent years have once again raised concerns about the capacity of the region to remain as a large net exporter. Here we use a modelling approach to map rice yield gaps and assess production potential and net exports by 2040. We find that the average yield gap represents 48% of the yield potential estimate for the region, but there are substantial differences among countries. Exploitable yield gaps are relatively large in Cambodia, Myanmar, Philippines and Thailand but comparably smaller in Indonesia and Vietnam. Continuation of current yield trends will not allow Indonesia and Philippines to meet their domestic rice demand. In contrast, closing the exploitable yield gap by half would drastically reduce the need for rice imports with an aggregated annual rice surplus of 54 million tons available for export. Our study provides insights for increasing regional production on existing cropland by narrowing existing yield gaps.

Residual malaria among migrant workers in Myanmar: why still persistent and how to eliminate it?

BACKGROUND: Residual malaria is probably an important source for the re-emergence of malaria infection in the elimination era. Assessment to identify the factors influencing residual malaria in high-risk groups is needed to develop evidence-based decisions by stakeholders and policymakers. METHODS: This study was conducted to explore the factors influencing the residual malaria infection among migrant workers in two sentinel sites (endemic vs. pre-elimination areas) in Myanmar using the mixed-model method. RESULTS: A total of 102 migrant respondents (65 in Bamauk and 37 in Shwegyin) were included for the quantitative assessment using pretested questionnaires during household visits. Although 87.3% of them had insecticidal bed nets (ITNs/LLINs), only 68.3% of the migrants in Bamauk and 57.9% in Shwegyin used it regularly. The use of any bed net was high (79.9% in Bamauk vs. 91.0% in Shwegyin). The mean LLINs in their families were 1.64 (95%CI: 1.48-1.81) in Bamauk and 2.89 (95%CI: 2.67-3.11) in Shwegyin. Most of them received no health information for malaria prevention within the last year and their knowledge about malaria was low. Their working nature was a challenge for control measures against malaria in migrants. CONCLUSION: The strategy for distributing LLINs and health promotion activities for mobile/migrant populations should be reviewed, and an appropriate action plan should be developed for the specific migrant group. Moreover, health promotion activities for behavior change communication should be strengthened in the migrant population in Myanmar.

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Seroprevalence of toxoplasmosis among reproductive-aged women in Myanmar and evaluation of luciferase immunoprecipitation system assay.

BACKGROUNDS: Primary infection with Toxoplasma gondii during pregnancy can pose serious health problems for the fetus. However, the epidemiological status of toxoplasmosis among reproductive-aged population in Myanmar is largely unknown. Although luciferase immunoprecipitation system (LIPS) assays for serodiagnosis of toxoplasmosis was developed mostly using mouse infection model, had not been tested by using field-derived human samples. METHODS: A total of 251 serum samples were collected from reproductive-aged women, residing in Shwegyin township, Bago region, Myanmar and analyzed with a commercial ELISA kit, as well as in-house LIPS assays. RESULTS: The overall seroprevalence for Toxoplasma gondii infection by the commercial ELISA was 11.5%. No clear risk factor was identified except for being in the younger age group (15-30 years old). Overall, LIPS assays showed low sensitivity when the commercial ELSA was used as a reference test. CONCLUSION: We identified the epidemiological situation of toxoplasmosis in some rural communities in Myanmar. The data obtained here will serve as a primary information for the effort to reduce toxoplasmosis in this region. Although looked promising in the previous experiments with mouse infection model, we found that the reported LIPS procedures need further improvements to increase the sensitivities.

A novel luciferase-linked antibody capture assay (LACA) for the diagnosis of Toxoplasma gondii infection in chickens.

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes the most common parasitic zoonosis worldwide in multiples species of mammals and birds. Although free-range chickens may play a role as an important reservoir for T. gondii, there is no reliable and commercially available diagnostic test for this disease in chickens. In this study, we aimed to develop a novel Luciferase-linked Antibody Capture Assay (LACA) for the serodiagnosis of Toxoplasma infection in chickens. Recombinant nanoluciferase fused-T. gondii dense granule antigen 8 (rNluc-GRA8) was produced and applied to LACA assay as a diagnostic antigen. GRA8-LACA was tested with the sera from uninfected and experimentally infected chickens with T. gondii and other parasitic pathogens and showed unexpectedly high sensitivity (90.5%) and specificity (95.4%). Interestingly, E. coli lysate expressing rNluc-GRA8 could be applied in GRA8-LACA with 85.7% sensitivity and an increased specificity (96.9%) that gave better diagnostic performance compared to conventional ELISA. We applied our diagnostic system to examine 267 free-range chicken sera collected from 12 farms and 100 closed-house broiler chicken sera from local poultry abattoirs. The overall seroprevalence of toxoplasmosis in free-range chickens was 10.9% (95% CI: 10.6%-11.1%), while no positive case was found in broiler chickens. GRA8-LACA could be a useful diagnostic technique for T. gondii infection in chickens. The detection of T. gondii seropositive chickens in this study warns a potential risk of Toxoplasma transmission by the consumption of raw or undercooked chicken meat.

Prevalence of Dental Caries in 5- and 6-Year-Old Myanmar Children.

There are no national data available of the oral health in Myanmar. In this study, we examined dental caries status of 187 school children located in the suburban area of Naypyidaw, capital of Myanmar, at the age of five and six and analyzed by the individual level and tooth level. Maxillary D and B were sensitive for dental caries almost at the same level. They were less sensitive than maxillary A. Mandibular A and B were tolerant for dental caries. Prevalence of dental caries in Myanmar children was still high. By applying item response theory and multilevel modeling, tooth level analysis can be implemented to confirm the tendency for sensitivity or tolerance for dental caries by the tooth level.

Effects of task-oriented training on upper extremity functional performance in patients with sub-acute stroke: a randomized controlled trial.

[Purpose] The present study aimed to determine the effects of a task-oriented training on paretic upper extremity functional performance in patients with subacute stroke. [Participants and Methods] Twenty-eight subacute stroke sufferers (mean age: 50.07, standard deviation 9.31 years; mean time since stroke 11.11, standard deviation 6.73 weeks) were randomly allocated to task-oriented training (n=14) or conventional exercise program (n=14) group. They were trained as a hospital-based, individualized training 1 hour a session, 5 sessions a week for 4 weeks. Wolf Motor Function Test (primary outcome), motor portion of Fugl-Meyer assessment upper extremity, and hand function domain of Stroke Impact Scale were assessed at baseline, after 2 and 4 weeks of training. [Results] All participants completed their training programs. At all post-training assessments, the task-oriented training group showed significantly more improvements in all outcomes than the conventional exercise program group. No serious adverse effects were observed during or after the training. [Conclusion] Task-oriented training produced statistically significant and clinically meaningful improvements of paretic upper extremity functional performance in patients with subacute stroke. These beneficial effects were observed after 2 weeks (10 hours) of training. Future investigation is warranted to confirm and expand these findings.

Tramadol: a valuable treatment for pain in Southeast Asian countries.

BACKGROUND: The supply of controlled drugs is limited in the Far East, despite the prevalence of health disorders that warrant their prescription. Reasons for this include strict regulatory frameworks, limited financial resources, lack of appropriate training amongst the medical profession and fear of addiction in both general practitioners and the wider population. Consequently, the weak opioid tramadol has become the analgesic most frequently used in the region to treat moderate to severe pain. METHODS: To obtain a clearer picture of the current role and clinical use of tramadol in Southeast Asia, pain specialists from 7 countries in the region were invited to participate in a survey, using a questionnaire to gather information about their individual use and experience of this analgesic. RESULTS: Fifteen completed questionnaires were returned and the responses analyzed. Tramadol is used to manage acute and chronic pain caused by a wide range of conditions. Almost all the specialists treat moderate cancer pain with tramadol, and every one considers it to be significant or highly significant in the treatment of moderate to severe non-cancer pain. The reasons for choosing tramadol include efficacy, safety and tolerability, ready availability, reasonable cost, multiple formulations and patient compliance. Its safety profile makes tramadol particularly appropriate for use in elderly patients, outpatients, and for long-term treatment. The respondents strongly agreed that tighter regulation of tramadol would reduce its medical availability and adversely affect the quality of pain management. In some countries, there would no longer be any appropriate medication for cancer pain or the long-term treatment of chronic pain. CONCLUSIONS: In Southeast Asia, tramadol plays an important part in the pharmacological management of moderate to severe pain, and may be the only available treatment option. If it were to become a controlled substance, the standard of pain management in the region would decline.

Evaluation of LIPS (luciferase immunoprecipitation system) for serodiagnosis of Toxoplasmosis.

Development of reliable, quantitative technologies for serodiagnosis of Toxoplasma gondii infection remains desirable. The luciferase immunoprecipitation system (LIPS) is a relatively simple, highly sensitive, and rapid quantitative immunoassay. The major advantages of this assay over ELISA are a wider dynamic range, shorter overall assay time, and less sample volume. In this study, we aimed to use this method for the serodiagnosis of toxoplasmosis. Recombinant Toxoplasma antigens (dense granule antigens GRA6, GRA7, and GRA8 and bradyzoite antigen BAG1) fused with nanoluciferase (Nluc, a small luciferase enzyme) were expressed in Escherichia coli, purified, and tested in LIPS assays with sera from experimental mice infected with T. gondii and a WHO standard anti-Toxoplasma human immunoglobulin (TOXM). In the experimentally infected mice, LIPS assays detected antibodies against Nluc-GRA6, Nluc-GRA7, and Nluc-GRA8 as early as day 14, whereas antibodies against Nluc-BAG1 remained undetected until day 21 and then showed significant elevation on day 60. In TOXM sera, LIPS assays with each Nluc recombinant protein produced reliable standard curves with a coefficient of determination (R2) of 0.980-0.989 for GRA6, 0.986-0.990 for GRA7, 0.998-0.999 for GRA8, and 0.942-0.987 for BAG1. The detection limits were estimated to be 3.9, 2, 1, and 1 IU/ml for rGRA6, rGRA7, rGRA8, and rBAG1, respectively. The LIPS assay for toxoplasmosis could detect antibodies against T. gondii in the mouse and human sera with a reasonably high sensitivity. We consider the LIPS assay to be a promising alternative tool for screening, diagnosing, and monitoring toxoplasmosis. In particular, detection of antibodies against BAG1 may be useful for a longitudinal seroprevalence study in suspected high-risk areas on the basis of its elevated serum concentration in the chronic phase.

Effectiveness of a novel long-lasting pyriproxyfen larvicide (SumiLarv®2MR) against Aedes mosquitoes in schools in Yangon, Myanmar.

BACKGROUND: Mosquito-borne diseases are prevalent in Myanmar, with the number of dengue cases showing a significant increase in recent years. Dengue vectors have developed resistance to insecticides and currently used larvicides show only short-term effectiveness. As a result, an alternative larvicide is urgently needed. The present study evaluated the larvicidal effectiveness of long-lasting pyriproxyfen resin discs (SumiLarv®2MR) against dengue virus vectors in schools in Hlaing Thar Yar Township, Yangon. RESULTS: The proportion of Aedes mosquito-infested containers was significantly reduced in the schools applied with the larvicide (OR: 0.24, 95% CI: 0.12-0.48) while there was little reduction noted in the control schools (OR: 0.97, 95% CI: 0.55-1.72). The density of infested containers was also significantly reduced in the intervention schools (Beta: -1.50, 95% CI: -1.98- -1.04), but there was no significant reduction in density in the control schools (Beta: -0.19, 95% CI: -0.53-0.14). The proportion of adult emergence was less than 20% in the treated water collected from the intervention schools for six months, while the proportion was over 90% in the untreated water. In addition, eight-month-old SumiLarv®2MR resin discs were still 100% effective when tested in the laboratory. More than 50% of the discs disappeared from treated containers within two months of intervention. CONCLUSIONS: SumiLarv®2MR was effective in reducing Aedes-infested containers at least six months after its application in schools. This new pyriproxyfen formulation has great potential for improving the current dengue vector control program in Myanmar.

Reliability of the test of gross motor development second edition (TGMD-2) for Kindergarten children in Myanmar.

[Purpose] The purpose of this study was to investigate reliability of the test of gross motor development second edition (TGMD-2) for Kindergarten children in Myanmar. [Subjects and Methods] Fifty healthy Kindergarten children (23 males, 27 females) whose parents/guardians had given written consent were participated. The subjects were explained and demonstrated all 12 gross motor skills of TGMD-2 before the assessment. Each subject individually performed two trials for each gross motor skill and the performance was video recorded. Three raters separately watched the video recordings and rated for inter-rater reliability. The second assessment was done one month later with 25 out of 50 subjects for test-rest reliability. The video recordings of 12 subjects were randomly selected from the first 50 recordings for intra-rater reliability six weeks after the first assessment. The agreement on the locomotor and object control raw scores and the gross motor quotient (GMQ) were calculated. [Results] The findings of all the reliability coefficients for the locomotor and object control raw scores and the GMQ were interpreted as good and excellent reliability. [Conclusion] The results represented that TGMD-2 is a highly reliable and appropriate assessment tool for assessing gross motor skill development of Kindergarten children in Myanmar.

Gross motor skill development of 5-year-old Kindergarten children in Myanmar.

[Purpose] The purpose of this study was to examine the gross motor skill development of 5-year-old Kindergarten children in Myanmar. [Subjects and Methods] Total 472 healthy Kindergarten children (237 males, 235 females) of 2016-2017 academic year from four schools in urban area and four schools in rural area of Myanmar were recruited. The gross motor skill development of all subjects was assessed with the test of gross motor development second edition (TGMD-2). All subjects performed two trials for each gross motor skill and the performance was video recorded and scored. The assessment procedures were done according to the standardized guidelines of TGMD-2. [Results] The majority of subjects had average level of gross motor skill rank. The significant differences were found on the run and gallop of locomotor skills and the most of object control skills except the catch between males and females. The significant differences were also found between subjects from urban and rural areas. [Conclusion] Gross motor skill development of 5-year-old Kindergarten children in Myanmar had gender-based and region-based differences on both locomotor and object control skills. This study added a valuable information to the establishment of a normative reference of Kindergarten aged children for future studies.