Biochemical and biological characterization of the venoms of Naja kaouthia and Naja mandalayensis from Myanmar and neutralization effects of BPI cobra antivenom.

Snakebite is a neglected public health issue, with many scientific and medical issues to be solved. Cobras are among the most common venomous snakes in Myanmar and are responsible for a considerable number of severe snakebite envenoming. There are three species of cobra (Naja kaouthia, Naja mandalayensis and Ophiophagus hannah) in Myanmar. The study aims to characterize the N. kaouthia and N. mandalayensis venoms and to investigate the efficacy of anti-cobra antivenom (BPI) against the two venoms. Protein components and fibrinogenolytic activity were determined by SDS-PAGE. Enzymatic activities for PLA2, protease and acetylcholinesterase were determined by spectrophotometric method. Anticoagulant activity was determined by recalcification time of citrated human plasma. Myotoxicity, necrotizing activity, median lethal dose (LD50) and median effective dose (ED50) were determined by WHO recommended methods. The SDS-PAGE displayed the proteins and enzymes containing in two venoms were different. N. kaouthia venom exhibited more in PLA2, acetylcholinesterase, anticoagulant, fibrinogenolytic and necrotizing activities than N. mandalayensis venom. N. mandalayensis venom had more protease activity and myotoxicity than N. kaouthia venom. The median lethal dose (LD50) of N. kaouthia and N. mandalayensis venom was 4.33 µg/mouse and 5.04 µg/mouse respectively. Both venoms induced fibrinogen Aα chain degradation in 30 min (N. kaouthia) and in 6 h (N. mandalayensis). The same median effective dose (ED50) (19.56 µg/mouse) showed that anti-NK antivenom can neutralize against lethal effect of N. mandalayensis venom. It can also neutralize the protease activity, anticoagulant activity and fibrinogenolytic activity of both venoms. Immunodiffusion and immunoblotting studies showed that the antivenom recognized its homologous venom (N. kaouthia) and cross-reacted against the heterologous venom (N. mandalayensis). The anti-NK antivenom is suitable to use for N. mandalayensis bite if monospecific antivenom is not available.

Refining the evolutionary tree of the horse Y chromosome.

The Y chromosome carries information about the demography of paternal lineages, and thus, can prove invaluable for retracing both the evolutionary trajectory of wild animals and the breeding history of domesticates. In horses, the Y chromosome shows a limited, but highly informative, sequence diversity, supporting the increasing breeding influence of Oriental lineages during the last 1500 years. Here, we augment the primary horse Y-phylogeny, which is currently mainly based on modern horse breeds of economic interest, with haplotypes (HT) segregating in remote horse populations around the world. We analyze target enriched sequencing data of 5 Mb of the Y chromosome from 76 domestic males, together with 89 whole genome sequenced domestic males and five Przewalski's horses from previous studies. The resulting phylogeny comprises 153 HTs defined by 2966 variants and offers unprecedented resolution into the history of horse paternal lineages. It reveals the presence of a remarkable number of previously unknown haplogroups in Mongolian horses and insular populations. Phylogenetic placement of HTs retrieved from 163 archaeological specimens further indicates that most of the present-day Y-chromosomal variation evolved after the domestication process that started around 4200 years ago in the Western Eurasian steppes. Our comprehensive phylogeny significantly reduces ascertainment bias and constitutes a robust evolutionary framework for analyzing horse population dynamics and diversity.

Bifid Mandibular Canal: A Proportional Meta-Analysis of Computed Tomography Studies.

Introduction: Growing body of evidences showed different grades in prevalence of bifid mandibular canals. Because the previous reviews focused solely on patient-level occurrence, hemi-mandible-level prevalence, bilateral symmetry, length, and diameter of bifid mandibular canals were required to be estimated collectively. The research question of this meta-analysis was "What is the prevalence of bifid mandibular canal among patients seeking computed tomography examinations"? Materials and Methods: In vivo, computed tomography, and cross-sectional studies were eligible. Studies, with less than 100 subjects or anatomic site restriction or controlled class of bifid mandibular canal, were excluded. Joanna Briggs Institute (JBI) critical appraisal tool for prevalence studies was used to assess methodological quality of all included studies. Random effect meta-analyses for proportion of bifid mandibular canal were done. Results: 40 studies met the inclusion criteria. All studies were selected for both systematic review and meta-analyses. Totally, 17714 patients and 31973 hemi-mandibles were included. All eligible studies showed moderate risk of bias on average. Resulting from the random effect model, more than 20% of patients seeking computed tomographic examinations had bifid mandibular canals (BMCs) which penetrated into slightly more than 14% of hemi-mandibles. Of the patients having bifid mandibular canals (BMCs), nearly 23% exhibited such anatomy on both sides of their mandibles. Estimated mean length and diameter of the accessory canals of bifid mandibular canals were 12.17 mm and 1.54 mm, respectively. Conclusion: The geographical locations, classifications, reliability test, and voxel size of computed tomography were all implicated in the prevalence of bifid mandibular canals along with gender and laterality, although considerable heterogeneity and bias were detected.

Spatiotemporal dynamics of malaria in Banmauk Township, Sagaing region of Northern Myanmar: characteristics, trends, and risk factors.

BACKGROUND: While national malaria incidence has been declining in Myanmar, some subregions within the nation continue to have high burdens of malaria morbidity and mortality. This study assessed the malaria situation in one of these regions, Banmauk Township, located near the Myanmar-India border. Our goal was to provide a detailed description of the malaria epidemiology in this township and to provide some evidence-based recommendations to formulate a strategy for reaching the national malaria elimination plan. Banmauk consistently has one of the highest malaria burdens in Myanmar. METHODS: With the implementation of strengthened malaria control and surveillance activities after the endorsement of a national malaria elimination plan in 2015, detailed incidence data were obtained for 2016-2018 for Banmauk Township. The data include patient demographics, parasite species, disease severity, and disease outcome. Data were analyzed to identify characteristics, trends, distribution, and risk factors. RESULTS: During 2016-2018, 2,402 malaria cases were reported, with Plasmodium falciparum accounting for 83.4% of infections. Both P. falciparum and P. vivax were transmitted more frequently during the rainy season (May-October). Despite intensified control, the annual parasite incidence rate (API) in 2017 (11.0) almost doubled that in 2016 (6.5). In total, 2.5% (59/2042) of the cases, of which 54 P. falciparum and 5 P. vivax, were complicated cases, resulting in 5 deaths. Malaria morbidity was high in children < 15 years and accounted for 33.4% of all cases and about 47% of the complicated cases. Older age groups and males living with poor transportation conditions were more likely to test positive especially in rainy and cold seasons. Despite the clear seasonality of malaria, severe cases were found among young children even more common in the dry season, when malaria incidence was low. CONCLUSIONS: Despite the declining trend, the malaria burden remained high in Banmauk Township. Our study also documented severe cases and deaths from both falciparum and vivax malaria. P. falciparum remained the predominant parasite species, demanding increased efforts to achieve the goal of elimination of P. falciparum by 2025. As P. falciparum cases decreased, the proportion of cases attributable to P. vivax increased. In order to eliminate malaria, it will likely be important to increasingly target this species as well.

Clinical Features and Outcomes of COVID-19 at a Teaching Hospital in Kingston, Jamaica

ObjectiveWe examined the demographic, clinical characteristics and indicators of poor outcomes among hospitalized adults with COVID-19 at the University Hospital of the West Indies, Jamaica. MethodsA retrospective medical record review between March 10 and December 31, 2020 analyzed data for 362 participants. ResultsThere were 218 males (mean age 59.5 years) and 144 females (mean age 55.7 years). Hypertension, diabetes mellitus, cardiovascular disease, obesity and chronic kidney disease were the most common comorbidities. Cough, shortness of breath, fever and malaise were the most common presenting complaints. Fifty-one percent of patients were moderately to severely ill on admission; 11% were critically ill; 18% were admitted to the Intensive Care Unit (ICU). Death occurred in 62 (17%) patients (95% CI 13.6-21.4%). Among obese participants, there were increased odds of developing respiratory failure (OR 5.2, p < 0.001), acute kidney injury (OR 4.7, p < 0.001), sepsis (OR 2.9, p =0.013) and the need for ICU care (OR 3.7, p < 0.001). Factors independently associated with increased odds of death were age (OR 1.03 per year, p = 0.013) and obesity (OR 2.26, p = 0.017). Mortality also correlated significantly with D-dimer > 1000 ng/ml (OR 2.78; p = 0.03), serum albumin < 40 g/L (OR 3.54; p = 0.03) and serum LDH > 485 U/L OR 1.92, p = 0.11). ConclusionsTargeted interventions among these high-risk patient subgroups may reduce in-patient morbidity and mortality.

Correction: Influence of rice varieties, organic manure and water management on greenhouse gas emissions from paddy rice soils.

[This corrects the article DOI: 10.1371/journal.pone.0253755.].

Elevated lipoprotein A in acute on chronic CTEPH with cardiogenic shock: a case report.

The natural history of most thrombi undergoes total or near total resolution, but the thrombi in chronic thromboembolic pulmonary hypertension (CTEPH) do not resolve completely and subsequently increase the pulmonary vascular resistance. We hypothesised that the elevated lipoprotein A in acute pulmonary embolism could lessen the autoresorption of the emboli and ultimately lead to CTEPH.

Influence of rice varieties, organic manure and water management on greenhouse gas emissions from paddy rice soils.

The study is focused on impact of manure application, rice varieties and water management on greenhouse gas (GHG) emissions from paddy rice soil in pot experiment. The objectives of this study were a) to assess the effect of different types of manure amendments and rice varieties on greenhouse gas emissions and b) to determine the optimum manure application rate to increase rice yield while mitigating GHG emissions under alternate wetting and drying irrigation in paddy rice production. The first pot experiment was conducted at the Department of Agronomy, Yezin Agricultural University, Myanmar, in the wet season from June to October 2016. Two different organic manures (compost and cow dung) and control (no manure), and two rice varieties; Manawthukha (135 days) and IR-50 (115 days), were tested. The results showed that cumulative CH4 emission from Manawthukha (1.084 g CH4 kg-1 soil) was significantly higher than that from IR-50 (0.683 g CH4 kg-1 soil) (P<0.0046) with yield increase (P<0.0164) because of the longer growth duration of the former. In contrast, higher cumulative nitrous oxide emissions were found for IR-50 (2.644 mg N2O kg-1 soil) than for Manawthukha (2.585 mg N2O kg-1 soil). However, IR-50 showed less global warming potential (GWP) than Manawthukha (P<0.0050). Although not significant, the numerically lowest CH4 and N2O emissions were observed in the cow dung manure treatment (0.808 g CH4 kg-1 soil, 2.135 mg N2O kg-1 soil) compared to those of the control and compost. To determine the effect of water management and organic manures on greenhouse gas emissions, second pot experiments were conducted in Madaya township during the dry and wet seasons from February to October 2017. Two water management practices {continuous flooding (CF) and alternate wetting and drying (AWD)} and four cow dung manure rates {(1) 0 (2) 2.5 t ha-1 (3) 5 t ha-1 (4) 7.5 t ha-1} were tested. The different cow dung manure rates did not significantly affect grain yield or greenhouse gas emissions in this experiment. Across the manure treatments, AWD irrigation significantly reduced CH4 emissions by 70% during the dry season and 66% during the wet season. Although a relative increase in N2O emissions under AWD was observed in both rice seasons, the global warming potential was significantly reduced in AWD compared to CF in both seasons (P<0.0002, P<0.0000) according to reduced emission in CH4. Therefore, AWD is the effective mitigation practice for reducing GWP without compromising rice yield while manure amendment had no significant effect on GHG emission from paddy rice field. Besides, AWD saved water about 10% in dry season and 19% in wet season.

BoLA-DRB3 genetic diversity in Highland Creole cattle from Bolivia.

The genetic diversity of the BoLA-DRB3 gene has been reported in different cattle breeds owing to its central role in the immune response. However, it is still unknown in hundreds of cattle breeds, especially native populations. Here, we studied BoLA-DRB3 genetic diversity in Highland Creole cattle (CrAl) from Western Bolivia, raised at altitudes between 3800 and 4200 m. DNAs from 48 CrAl cattle were genotyped for BoLA-DRB3 exon 2 alleles using polymerase chain reaction-sequence-based typing (PCR-SBT). The results were compared with 1341 previously reported data from Tropical Creole cattle and other breeds raised in the region. Twenty-three BoLA-DRB3 alleles were identified in CrAl, including the BoLA-DRB3*029:02 variant previously detected in other Creole cattle. Observed and expected heterozygosity were 0.87 and 0.93, respectively. Nucleotide diversity and the number of pairwise difference values were 0.078 and 19.46, respectively. The average number of nonsynonymous and synonymous substitutions were 0.037 and 0.097 for the entire BoLA-DRB3 exon 2, and 0.129 and 0.388 for the antigen-binding site, respectively. Venn analysis and the review of the IPD-MHC database and the literature showed that 2 of 64 alleles were only detected in CrAl, including BoLA-DRB3*029:01 previously reported in African cattle and *048:01 detected in Philippine cattle. Two additional alleles, BoLA-DRB3*007:02 and *029:02, were only present in CrAl and Lowland Creole cattle. Principal Component Analysis (PCA) showed that Bolivian Creole cattle breeds were closely located but they were distant from the Colombian Hartón del Valle Creole. FST analysis showed a low degree of genetic differentiation between Highland and Lowland Bolivian Creole cattle (FST = 0.015). The present results contribute to increasing our knowledge of BoLA-DRB3 genetic diversity in cattle breeds.

Characterization of bovine MHC DRB3 diversity in global cattle breeds, with a focus on cattle in Myanmar.

BACKGROUND: Myanmar cattle populations predominantly consist of native cattle breeds (Pyer Sein and Shwe), characterized by their geographical location and coat color, and the Holstein-Friesian crossbreed, which is highly adapted to the harsh tropical climates of this region. Here, we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus that has been linked to the immune response, in Myanmar cattle populations. METHODS: Blood samples (n = 294) were taken from two native breeds (Pyer Sein, n = 163 and Shwe Ni, n = 69) and a cattle crossbreed (Holstein-Friesian, n = 62) distributed across six regions of Myanmar (Bago, n = 38; Sagaing, n = 77; Mandalay, n = 46; Magway, n = 46; Kayin, n = 43; Yangon, n = 44). In addition, a database that included 2428 BoLA-DRB3 genotypes from European (Angus, Hereford, Holstein, Shorthorn, Overo Negro, Overo Colorado, and Jersey), Zebuine (Nellore, Brahman and Gir), Asian Native from Japan and Philippine and Latin-American Creole breeds was also included. Furthermore, the information from the IPD-MHC database was also used in the present analysis. DNA was genotyped using the sequence-based typing method. DNA electropherograms were analyzed using the Assign 400ATF software. RESULTS: We detected 71 distinct alleles, including three new variants for the BoLA-DRB3 gene. Venn analysis showed that 11 of these alleles were only detected in Myanmar native breeds and 26 were only shared with Asian native and/or Zebu groups. The number of alleles ranged from 33 in Holstein-Friesians to 58 in Pyer Seins, and the observed versus unbiased expected heterozygosity were higher than 0.84 in all the three the populations analyzed. The FST analysis showed a low level of genetic differentiation between the two Myanmar native breeds (FST = 0.003), and between these native breeds and the Holstein-Friesians (FST <  0.021). The average FST value for all the Myanmar Holstein-Friesian crossbred and Myanmar native populations was 0.0136 and 0.0121, respectively. Principal component analysis (PCA) and tree analysis showed that Myanmar native populations grouped in a narrow cluster that diverged clearly from the Holstein-Friesian populations. Furthermore, the BoLA-DRB3 allele frequencies suggested that while some Myanmar native populations from Bago, Mandalay and Yangon regions were more closely related to Zebu breeds (Gir and Brahman), populations from Kayin, Magway and Sagaing regions were more related to the Philippines native breeds. On the contrary, PCA showed that the Holstein-Friesian populations demonstrated a high degree of dispersion, which is likely the result of the different degrees of native admixture in these populations. CONCLUSION: This study is the first to report the genetic diversity of the BoLA-DRB3 gene in two native breeds and one exotic cattle crossbreed from Myanmar. The results obtained contribute to our understanding of the genetic diversity and distribution of BoLA-DRB3 gene alleles in Myanmar, and increases our knowledge of the worldwide variability of cattle BoLA-DRB3 genes, an important locus for immune response and protection against pathogens.

A case of ventricular standstill in a patient with acute gastrointestinal bleeding.

Ventricular stand still is an electrophysiologic phenomenon characterized by the absence of ventricular activity or contraction. It is the result of the lack of impulse formation in ventricles (absence of idioventricular automaticity) or the failure of impulse transmission to ventricles (conduction disturbance) [1]. It is an uncommon condition that can affect a wide range of age groups with life threatening consequences. There are no set guidelines on the treatment of ventricular standstill - swift and sound clinical judgment is required. The condition should be treated as a cardiac arrest, with resolution of precipitating factors. Here we present a case of a 59-year-old man with multiple comorbidities, who presented with massive gastrointestinal hemorrhage and recurrent episodes of ventricular standstill during hospitalization, with his immediate treatment and stabilization.

Comparison of the Osteoporosis Self-Assessment Tool for Asians and the fracture risk assessment tool - FRAX to identify densitometric defined osteoporosis: A discriminatory value analysis in a multi-ethnic female population in Southeast Asia.

OBJECTIVES: The accuracy of FRAX® as a screening tool to identify osteoporosis and how it compares with tools such as Osteoporosis Self-Assessment Tool for Asians (OSTA), in Southeast Asian women has so far been unexplored. We aimed to determine the FRAX® thresholds that accurately identify densitometric osteoporosis and to compare its performance with that of OSTA for this purpose. METHODS: Singaporean postmenopausal women (n = 1056) were evaluated. FRAX® Major Osteoporotic Fracture Probability (MOFP), Hip Fracture Probability (HFP) scores, and OSTA indices were calculated. Receiver operating characteristic (ROC) curves were constructed and via the Youden index, the optimal cut-off points of balanced sensitivity and specificity for dual energy X-ray absorptiometry (DXA)-defined osteoporosis were identified and the performance characteristics were compared. RESULTS: A FRAX® MOFP threshold of ≥3.7% had sensitivity, specificity, positive predictive value and negative predictive value of 0.78 (0.73-0.83), 0.63 (0.59-0.66), 0.4 (0.36-0.44), and 0.9 (0.87-0.92), respectively in identifying osteoporosis. The corresponding values for a HFP threshold of ≥0.6% were 0.85 (0.80-0.89), 0.58 (0.55-0.62), 0.39 (0.35-0.43), and 0.92 (0.9-0.94) and that for an OSTA index cut-off of ≤ -1.2 were 0.76 (0.70-0.81), 0.74 (0.71-0.77), 0.48 (0.43-0.54), and 0.91 (0.88-0.93). The area under the ROC curves were 82.8% (79.9%-85.6%), 77.6% (74.2%-81%), and 79.6% (76.5%-82.8%) for OSTA, MOFP, and HFP thresholds respectively. CONCLUSIONS: FRAX® and OSTA perform comparably in identifying osteoporosis in our population. OSTA has only 2 parameters and may be simpler to use. However, FRAX® may also have a role in primary screening to identify the postmenopausal woman to be referred for DXA scanning and may help facilitate fracture risk reduction discussions with the patient.

New evidence of bovine leukemia virus circulating in Myanmar cattle through epidemiological and molecular characterization.

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. BLV infects cattle worldwide and causes serious problems for the cattle industry. In this study, we examined the prevalence of BLV infection and the distribution of BLV genotypes in cattle in the northern, central, and southern parts of Myanmar. The prevalence of BLV infection among Myanmar cattle (37.04%) in this study was markedly higher than the prevalence (9.1%) observed in our earlier study in which BLV was detected from the limited number of cattle only from a small area of Myanmar. Phylogenetic analysis of partial env-gp51 sequence of the isolated BLV strains revealed that there are at least three BLV genotypes (genotype-1, genotype-6, and genotype-10) in Myanmar, which have also been detected in the neighboring countries. We performed this study to estimate the BLV proviral load, which is a major diagnosis index for determining the virus transmission risk. The cattle of the three test regions with warm, wet, and humid climatic conditions (upper Sagaing, Yangon, and Kayin) exhibited a high mean proviral load, while cattle of three other regions with low annual rainfall and very high temperature (Mandalay, Magway, and upper Bago) exhibited a low mean proviral load. Further, the level of proviral load and the prevalence of BLV infection in Myanmar native cattle (N = 235) were lower than that in the hybrid cattle (Holstein Friesian × Myanmar native) (N = 62). We also observed that the cattle with high risk for BLV transmission, which have high proviral load, may enhance the BLV infection rate. Hence, to control BLV transmission, it is necessary to eliminate these cattle with high-risk for BLV transmission and to diagnose BLV provirus in cattle in the remaining regions/states of Myanmar sharing a boundary with neighboring countries.

Pathogenetic Potential Relating to Metabolic Activity in a Mouse Model of Infection with the Chikungunya Virus East/Central/South African Genotype.

Epidemics of the Chikungunya virus (CHIKV) from 2004 onwards were caused by the East/Central/South African (ECSA) genotype. However, the pathogenesis of the genotype infection has not been fully explained. In this study, we examined the pathogenic potential of CHIKV ECSA genotype M-30 (M-30) by comparing it with that of African genotype S-27 (S-27) in mice. Following low titer infections in type-I IFN receptor KO (A129) mice, we found that the M-30 infection caused high and acute fatality compared with the S-27 infection. M-30-infected A129 mice showed higher viral loads in their central nervous systems and peripheral organs, and increased levels of IFN-γ responses in their brains. Interestingly, M-30-infected mice did not show the hypophagia and reductions in weight which were observed in S-27-infected mice. Our observations provide a novel explanation of the pathogenic mechanisms attributed to virus proliferation, anti-type-II IFN response and metabolic activity in the CHIKV ECSA virus in mice.

Takayasu Arteritis: What Can Go Wrong in The Glomeruli for Large Vessel Vasculitis? A Case Report of an Unusual Cause of Persistent Microscopic Hematuria in a Patient with Takayasu Arteritis.

We describe a case of persistent microscopic hematuria in a patient with Takayasu arteritis (TA). Urological cause has been excluded. Classically, TA is found to only involve large arteries like the aorta and its branches. There is some evidence that showed the association of small vessel vasculitis like glomerulonephritis with TA. Histopathological studies showed similar features of vasculitis between the small and large vessel involvement in TA. This may explain the similar disease process that has not been well understood in TA. We believe that the persistent microscopic haematuria in the patient described is caused by TA associated glomerulonephritis. A series of investigations ruled out other causes of glomerular microscopic haematuria like autoimmune or infection related glomerulonephritis.

A Study of Burkholderia pseudomallei in the Environment of Farms in Thanlyin and Hmawbi Townships, Myanmar.

Melioidosis is a tropical infection, first described in Myanmar but now rarely diagnosed there, which is widespread in Southeast Asia. The infection is predominantly acquired by people and animals through contact with soil or water. This study aimed to detect the causative organism, Burkholderia pseudomallei, in environmental samples from farms in Thanlyin and Hmawbi townships near Yangon, Myanmar. One hundred and twenty soil samples and 12 water samples were collected and processed using standard microbiological methods. Burkholderia species were isolated from 50 of the 120 (42%) soil samples but none of the water samples. Arabinose assimilation was tested to differentiate between B. pseudomallei and the nonpathogenic Burkholderia thailandensis, and seven of 50 isolates (14%) were negative. These were all confirmed as B. pseudomallei by a species-specific multiplex polymerase chain reaction (PCR). This is the first study to detect environmental B. pseudomallei in Myanmar and confirms that melioidosis is still endemic in the Yangon area.

An Interesting Case and Literature Review of a Coronary Stent Fracture in a Current Generation Platinum Chromium Everolimus-Eluting Stent.

Coronary interventions are the mainstay of treatment for stenotic coronary vascular lesions. New stent designs are constantly being evaluated to improve stent performances and clinical outcomes. Coronary stent fracture is uncommon; however, it is associated with potential major consequences including acute coronary syndrome and the need for repeated target vessel revascularization due to in-stent restenosis or stent thrombosis. We report a case of a 66-year-old man with an extensive cardiac disease history, who presented with intractable angina and was found to have a fracture of a current generation, platinum chromium everolimus-eluting stent (Synergy, Boston Scientific Inc.).