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Propelled by global climate changes, the shrimp industry has been facing tremendous losses in production due to various disease outbreaks, particularly early mortality syndrome (EMS), a disease caused by Vibrio parahaemolyticus AHPND. Not only is the use of antibiotics as EMS control agents not yet been proven successful, but the overuse and misuse of antibiotics could also worsen one of the most challenging global health issues-antimicrobial resistance. To circumvent antibiotic usage, anti-lipopolysaccharide factor isoform 3 (ALFPm3), an antimicrobial peptide (AMP) derived from the shrimp innate immune system, was proposed as an antibiotic alternative for EMS control. However, prolonged use of AMPs could also lead to bacterial cross resistance with life-saving antibiotics used in human diseases. Here, we showed that ALFPm3-resistant strains of E. coli could be induced in vitro. Genome analysis of the resistant mutants revealed multiple mutations, with the most interesting being a qseC(L299R). A study of antibiotic susceptibility profile showed that the resistant strains harboring the qseC(L299R) not only exhibited higher degree of resistance towards polymyxin antibiotics, but also produced higher biofilm under ALFPm3 stress. Lastly, a single cell death analysis revealed that, at early-log phase when biofilm is scarce, the resistant strains were less affected by ALFPm3 treatment, suggesting additional mechanisms by which qseC orchestrates to protect the bacteria from ALFPm3. Altogether, this study uncovers involvement of qseC mutation in mechanism of resistance of the bacteria against ALFPm3 paving a way for future studies on sustainable use of ALFPm3 as an EMS control agent.

In this paper, the authors have designed and implemented the prototype for a near real-time wireless image sequence streaming cloud with two-layered restoration for a road traffic monitoring application of a small-scale network. Since the proposed design is targeted to implement outdoors where the link or node failure could occur, the fault-tolerant capability must be considered. Having only one layer restoration may not provide a good quality of service. Therefore, a two-layer restoration framework is designed in the proposed system by restoring the network layer with the underlying software-defined wireless mesh network capability and at the local broker selection over the Apache Kafka framework. The monitoring application performance has been investigated for the end-to-end average latency and image loss percentage by outdoor testing for 13 hours from 5:40 P.M. 17th November 2020 to 6:40 A.M. 18th November 2020. The end-to-end average latency and image loss percentage have been found to be within the acceptable condition i.e. less than 5 seconds on average with approximated 10% image losses. The proposed system has also been compared with the traditional ad-hoc network, running the OLSR-based network layer, in terms of the rerouting time, restoration time and end-to-end average latency. Based on the emulated wireless network in controllable laboratory environments, the proposed SDWMN-based system outperforms the conventional OLSR-based system with potentially faster rerouting/restoration time due to SDN central controllability and with only marginally increased end-to-end average latency after re-routing/restoration completion. Algorithm complexity analysis has also been given for both the systems. Both the experimental and complexity analysis results thus suggest the practical applicability of the proposed system. Given this promising result, it is therefore recommended as the future research in further developing from the prototype design into the actual deployment for daily traffic monitoring operations.

In an era where the rate of bacteria evolving to be resistant to clinically-used antibiotics far exceeds that of antibiotic discovery, the search for new sources of antibacterial agents has expanded tremendously. In recent years, interest in plant-based natural products as promising sources of antibacterial agents has taken an upward trend. Mansonones, botanically-derived naphthoqionones, having many uses in Asian traditional medicine-including anti-infective roles-have sparked interest as a possible source of antibacterial agents. Here, we show that mansonone G, extracted from Mansonia gagei Drumm. heartwoods, possessed antibacterial activities towards Bacillus subtilis, Staphylococcus aureus and Escherichia coli lptD4213, inhibiting the growth of the bacteria at 15.6 μM, 62.5 μM and 125 μM, respectively. Fourteen derivatives of mansonone G were synthesized successfully and were found to have a similar antibacterial spectrum to that of the parent compound, with some derivatives possessing improved antibacterial activities. Bacterial cytological profiling analysis showed that mansonone G harbors membrane permeabilizing activities against B. subtilis and E. coli lptD4213. Temporal analysis of SYTOX Green staining among individual cells showed that mansonone G rapidly permeabilized bacterial membrane within 10 min, with SYTOX Green intensity reaching 13-fold above that of the control. Collectively, these findings highlight the importance of mansonone G and its derivatives as potential antibacterial agents, paving the way for further modifications in order to improve their antibacterial spectrum.

BackgroundHepatitis B infection is a major health concern in Myanmar. Hepatitis B birth dose vaccination to prevent mother-to-child transmission is not universal, especially in births outside of health care facilities. Little is documented about delivery of immunization programs in rural Myanmar or in conflict-affected regions. To address this gap, this study describes the implementation of a novel community delivered neonatal hepatitis B immunization program in rural Karenni State, Myanmar.MethodsA mixed-methods study assessed the effectiveness and feasibility of hepatitis B birth dose immunization program. 1000 pregnant women were screened for hepatitis B virus (HBV) infection using point of care testing. Neonates of HBV positive mothers were immunized with a three dose HBV vaccine schedule at birth, 1, and 6 months of age. HBV testing was completed for children at 9 months to assess for infection. Descriptive statistics were collected including demographic data of mothers, neonatal vaccination schedule completion, and child HBV positivity at 9 months. Qualitative data examining barriers to implementation were collected through semi-structured interviews, participant-observation, and analysis of program documents. Themes were codified and mapped onto the Consolidated Framework for Implementation Research.Results46 pregnant women tested HBV positive leading to 40 live births. 39 women-child dyads were followed until the 9-month age mark. With the exception of two neonates who received their birth dose past 24 hours, all children received their vaccines on time. None of the 39 children tested positive for HBV at nine months. Themes regarding barriers included adaptability of the program to the rural setting, friction with other stakeholders and not meeting all needs of the community. Identified strengths included good communication and leadership within the implementing ethnic health organization.ConclusionA community delivered neonatal HBV vaccination program by ethnic health organizations is feasible and effective in rural Myanmar.

BACKGROUND:Cyberbullying is a global public health concern with tremendous negative impacts, not only on the physical and mental health of students but also on their well-being and academic performance. However, there are very few studies on cyberbullying among university students, especially in Myanmar. This study aims to determine the percentage of university students who suffered cyberbullying victimization in the last 12 months, and the association between students' socio-demographic characteristics, adverse events following cyberbullying and cyberbullying victimization. METHODS:A cross-sectional study was conducted among university students aged 18 years and older at one medical university in Magway, Myanmar. A total of 412 students (277 males and 135 females) participated in the study. Data were collected from August to September, 2018 using a self-administered questionnaire. Multiple logistic regression analyses (models I and II) were performed to estimate the unadjusted (UOR) and adjusted odds ratios (AOR), and 95% confidence intervals (CI). RESULTS:In total, 40.8% of males and 51.1% of females in the study had suffered cyberbullying victimization in the past 12 months. In model I, students who had been studying at the university for 3 years or less (AOR = 1.81; 95% CI 1.14-2.85), and who had witnessed psychological, physical or sexual violence, or cyberbullying in their neighborhoods, (AOR = 2.95; 95% CI 1.48-5.91) were more likely to have suffered cyberbullying victimization in the past 12 months. In model II, being a victim of cyberbullying was associated with difficulties in concentrating and understanding lectures (AOR = 3.96; 95% CI 1.72-9.11), and substance abuse (AOR = 2.37; 95% CI 1.02-5.49). Non-resident students were at a higher risk of being cyberbullying victims than their resident peers (AOR = 1.86; 95% CI 1.04-3.34). CONCLUSION:Two out of five students had suffered cyberbullying victimization in the past 12 months, and only half of the victims discussed their experience(s) with someone else. Students who suffered cyberbullying victimization faced academic difficulties and started or increased smoking, betel chewing or alcohol drinking. Counter measures to prevent and mitigate the adverse events related to cyberbullying victimization are urgently needed among university students in Myanmar. Periodic screening for cyberbullying, counseling services, cyber-safety educational programs, and awareness raising campaigns should be implemented.

The current extinction crisis leaves us increasingly reliant on captive populations to maintain vulnerable species. Approximately one third of Asian elephants (Elephas maximus) are living in semi-captive conditions in range countries. Their relationship with humans stretches back millennia, yet elephants have never been fully domesticated. We rely on the expertise of traditional handlers (mahouts) to manage these essentially wild animals, yet this profession may be threatened in the modern day. Here, we study the handling system of semi-captive timber elephants in Myanmar; the largest global semi-captive population (~5 000). We investigate how recent changes in Myanmar may have affected the keeping system and mahout-elephant interactions. Structured interviews investigated changes to mahout attitude and experience over the last two decades, as perceived by those who had worked in the industry for at least 10 years (n = 23) and as evaluated in current mahouts (n = 210), finding mahouts today are younger (median age 22yrs), less experienced (median experience 3yrs), and change elephants frequently, threatening traditional knowledge transfer. Mahout-elephant interactions manifested as 5 components ('job appreciation'; 'experience is necessary'; 'human-elephant interaction'; 'own knowledge'; 'elephant relationship'), according to Principal Components Analysis. Experienced mahouts and mahouts of bulls and younger elephants were more likely to agree that 'experience is necessary' to be a mahout. Mahouts with difficult elephants scored lower on 'human-elephant interaction' and a mahout's perception of their 'own knowledge' increased with more experience. Our finding of change in terms of mahout experience, age and commitment in the largest semi-captive elephant population suggests need for formal training and assessment of impacts on elephant welfare; these are findings applicable to thousands of elephants under similar management.

Rheumatic heart disease (RHD) is a major cause of premature death in low and middle-income countries. The greatest barrier to RHD control is neglect of the disease in national health policies and a lack of prevalence data that might inform control efforts. Myanmar is making remarkable progress against many infectious diseases, but there are almost no data to define the clinical burden of RHD in the country. This prospective audit was performed in an adult medical ward of a tertiary-referral hospital in Yangon, to gain an insight into the prevalence of RHD in Myanmar.All patients admitted to the ward between May 1, 2016 and April 30, 2017 were eligible for enrolment. RHD was confirmed in 96 patients who were admitted on 134 occasions, representing 1.1% of the 12,172 adult medical admissions during the study period. This compared with 410 (3.4%) admissions with HIV and 14 (0.1%) with malaria. Patients with RHD had a median age of 44 years (interquartile range: 35-59); 70 (73%) were female. Only one patient had ever had surgery despite 79 (82%) meeting criteria for intervention; 54 (56%) patients were not receiving any regular clinician review. Prior to hospitalisation only 18 (19%) patients were receiving regular penicillin. Only 8 (19%) of the 42 women

Propelled by global climate changes, the shrimp industry has been facing tremendous losses in production due to various disease outbreaks, particularly early mortality syndrome (EMS), a disease caused by Vibrio parahaemolyticus AHPND. Not only is the use of antibiotics as EMS control agents not yet been proven successful, but the overuse and misuse of antibiotics could also worsen one of the most challenging global health issues—antimicrobial resistance. To circumvent antibiotic usage, anti-lipopolysaccharide factor isoform 3 (ALFPm3), an antimicrobial peptide (AMP) derived from the shrimp innate immune system, was proposed as an antibiotic alternative for EMS control. However, prolonged use of AMPs could also lead to bacterial cross resistance with life-saving antibiotics used in human diseases. Here, we showed that ALFPm3-resistant strains of E. coli could be induced in vitro. Genome analysis of the resistant mutants revealed multiple mutations, with the most interesting being a qseC(L299R). A study of antibiotic susceptibility profile showed that the resistant strains harboring the qseC(L299R) not only exhibited higher degree of resistance towards polymyxin antibiotics, but also produced higher biofilm under ALFPm3 stress. Lastly, a single cell death analysis revealed that, at early-log phase when biofilm is scarce, the resistant strains were less affected by ALFPm3 treatment, suggesting additional mechanisms by which qseC orchestrates to protect the bacteria from ALFPm3. Altogether, this study uncovers involvement of qseC mutation in mechanism of resistance of the bacteria against ALFPm3 paving a way for future studies on sustainable use of ALFPm3 as an EMS control agent. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression. This effect is blocked by specific inhibition or genetic depletion of these disintegrins and we show that WNF up-regulates ADAM10 transcription and ADAM17 maturation. In addition, WNF reduces Aβ40 and Aβ42 generation in human cell lines. Altogether, WNF presents all the characteristics of a potent preventive anti-Alzheimer formula. Importantly, this natural recipe, currently prescribed to patients for the treatment of other symptoms without any secondary effect, can be tested immediately for further clinical studies.

Rhoptry-associated membrane antigen (RAMA) is an abundant glycophosphatidylinositol (GPI)-anchored protein that is embedded within the lipid bilayer and is implicated in parasite invasion. Antibody responses against rhoptry proteins are produced by individuals living in a malaria-endemic area, suggesting the immunogenicity of Plasmodium vivax RAMA (PvRAMA) for induction of immune responses during P. vivax infection. To determine whether PvRAMA contributes to the acquisition of immunity to malaria and could be a rational candidate for a vaccine, the presence of memory T cells and the stability of the antibody response against PvRAMA were evaluated in P. vivax-exposed individuals. The immunogenicity of PvRAMA for the induction of T cell responses was evaluated by in vitro stimulation of peripheral blood mononuclear cells (PBMCs). High levels of interferon (IFN)-γ and interleukin (IL)-10 cytokines were detected in the culture supernatant of PBMCs, and the CD4+ T cells predominantly produced IL-10 cytokine. The levels of total anti-PvRAMA immunoglobulin G (IgG) antibody were significantly elevated, and these antibodies persisted over the 12 months of the study. Interestingly, IgG1, IgG2 and IgG3 were the major antibody subtypes in the response to PvRAMA. The frequency of IgG3 in specific to PvRAMA antigen maintained over 12 months. These data could explain the immunogenicity of PvRAMA antigen in induction of both cell-mediated and antibody-mediated immunity in natural P. vivax infection, in which IFN-γ helps antibody class switching toward the IgG1, IgG2 and IgG3 isotypes and IL-10 supports PvRAMA-specific antibody production.

Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct diagnosis of G6PD status in patients is crucial for safe treatment of both relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium falciparum. Lack of suitable point-of-care tests has hampered a much needed wide use of primaquine for malaria elimination. In this study we have assessed the performances of two qualitative tests, the fluorescent spot test (FST) and the G6PD CareStart test (CST), against the gold standard quantitative spectrophotometric assay in a population of 1000 random adult healthy volunteers living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and 6.8% (11.1% in males) respectively. The FST and CST showed comparable performances with sensitivity over 95% and specificity over 90%, however for cases with severe G6PD activity the FTS had improved performance. If used with a conservative interpretation of the signal, the CareStart test has the potential to be used in the field and, by allowing a wider use of primaquine, to help malaria elimination.

Information on an organism's body size is pivotal in understanding its life history and fitness, as well as helping inform conservation measures. However, for many species, particularly large-bodied wild animals, taking accurate body size measurements can be a challenge. Various means to estimate body size have been employed, from more direct methods such as using photogrammetry to obtain height or length measurements, to indirect prediction of weight using other body morphometrics or even the size of dung boli. It is often unclear how accurate these measures are because they cannot be compared to objective measures. Here, we investigate how well existing estimation equations predict the actual body weight of Asian elephants Elephas maximus, using body measurements (height, chest girth, length, foot circumference and neck circumference) taken directly from a large population of semi-captive animals in Myanmar (n = 404). We then define new and better fitting formulas to predict body weight in Myanmar elephants from these readily available measures. We also investigate whether the important parameters height and chest girth can be estimated from photographs (n = 151). Our results show considerable variation in the ability of existing estimation equations to predict weight, and that the equations proposed in this paper predict weight better in almost all circumstances. We also find that measurements from standardised photographs reflect body height and chest girth after applying minor adjustments. Our results have implications for size estimation of large wild animals in the field, as well as for management in captive settings.

Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes.

G12 rotaviruses are emerging rotavirus strains causing severe diarrhea in infants and young children worldwide. However, the whole genomes of only a few G12 strains have been fully sequenced and analyzed. In this study, we sequenced and characterized the complete genomes of six G12 strains (RVA/Human-tc/MMR/A14/2011/G12P[8], RVA/Human-tc/MMR/A23/2011/G12P[6], RVA/Human-tc/MMR/A25/2011/G12P[8], RVA/Human-tc/MMR/P02/2011/G12P[8], RVA/Human-tc/MMR/P39/2011/G12P[8], and RVA/Human-tc/MMR/P43/2011/G12P[8]) detected in six stool samples from children with acute gastroenteritis in Myanmar. On whole genomic analysis, all six Myanmarese G12 strains were found to have a Wa-like genetic backbone: G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strains A14, A25, P02, P39, and P43, and G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strain A23. Phylogenetic analysis showed that most genes of the six strains examined in this study were genetically related to globally circulating human G1, G3, G9, and G12 strains. Of note is that the NSP4 gene of strain A23 exhibited the closest relationship with the cognate genes of human-like bovine strains as well as human strains, suggesting the occurrence of reassortment between human and bovine strains. Furthermore, strains A14, A25, P02, P39, and P43 were very closely related to one another in all the 11 gene segments, indicating derivation of the five strains from a common origin. On the other hand, strain A23 consistently formed distinct clusters as to all the 11 gene segments, indicating a distinct origin of strain A23 from that of strains A14, A25, P02, P39, and P43. To our knowledge, this is the first report on whole genome-based characterization of G12 strains that have emerged in Myanmar. Our observations will provide important insights into the evolutionary dynamics of spreading G12 rotaviruses in Asia.

BACKGROUND:Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS:We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. RESULTS:If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). CONCLUSIONS:Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.