Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

<p>Abstract</p> <p>Background</p> <p>Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. <it>In vitro </it>and <it>ex vivo </it>cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.</p> <p>Results</p> <p>Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition.</p> <p>Conclusion</p> <p>The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells.</p

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

<p>Abstract</p> <p>Background</p> <p>There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.</p> <p>Methods</p> <p>Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total <it>n </it>= 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total <it>n </it>= 220).</p> <p>Results</p> <p>Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04).</p> <p>Conclusions</p> <p>A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.</p

Geo-textual Index Structure for Spatial Keyword Query with Myanmar Language

Geographic query is composed of querykeywords and a location. Spatial keywordqueries which are queries on spatial objectsassociated with textual attributes have receivedsignificant attention in geographic informationsystem (GIS) recently. A spatial keyword querytakes a user location and user-supplied keywordsas arguments and returns objects that arespatially and textually relevant to thesearguments. Geo-textual index play an importantrole in spatial keyword querying. There are anumber of geo-textual indices have beenproposed in recent years. Mostly, the R-tree andits variants and the inverted file are combined.Most of the keywords are considered for Englishlanguage and keyword with Myanmar nativelanguage is also necessary for the users who arenot familiar with the English language. Thispaper proposes an index structure that combinesK-d tree and inverted file which is considered onthe Myanmar keywords queries to find thedesired location with Myanmar languageefficiently. Myanmar 3 Unicode is used forkeyword search

Detection of Class 1 Integron Among Klebsiella Species Isolated from Clinical Samples at No (1) Defence Services General Hospital (1000 Bedded)

Klebsiella species is commonly associated with serious nosocomial infections. Multi-drug resistant Klebsiella species isolates are becoming increasingly prevalent in the clinical and nosocomial environments. The high prevalence of Klebsiella infections is related to the ability of Klebsiella species to acquire and disseminate exogenous genes associated with mobile elements, such as plasmids, transposons and integrons. This study was conducted to find out the presence of class 1 integron and antibiotic susceptibility patterns of Klebsiella species from clinical specimens at No (1) Defence Services General Hospital (1000-Bedded). A laboratory based cross-sectional descriptive study was carried out from January to september, 2020. Identification and antimicrobial susceptibility testing of Klebsiella species was performed by VITEK 2 Compact Analyzer. Class 1 integrons were detected by conventional PCR. In this study, 110 Klebsiella species were isolated from various clinical specimens and most of the isolates were from medical ward (52.3%, 63 isolates). The highest rate of resistance was observed for ampicillin (100%) and Cefotaxime (97.3 %) whereas the lowest antibiotic resistance was to Amikacin (15.5%). Out of 110 Klebsiella isolates, 107 (97.3%) were multidrug resistant (MDR). Forty-four (40%) out of 110 Klebsiella isolates carried int1 gene and all these isolates were MDR. However, there was no association between multidrug resistance and integron positivity (p value = 0.273). The presence of class I integron genes among Klebsiella species highlights the continued monitoring is necessary for prevention of wide dissemination of integrons and infections by MDR pathogens

Gender difference in early initiation of methamphetamine use among current methamphetamine users in Muse, Northern Shan State, Myanmar

Abstract Background Globally, methamphetamine (MA) use is a significant public health concern due to unprecedented health effects of its use. However, gender similarities and differences in early age of MA initiation and its risk factors among current MA users have been understudied in a developing country setting. Methods A community-based, cross-sectional study was conducted using a computer assisted self-interviewing program from January to March 2013 in Muse, Northern Shan State, Myanmar. A total of 1362 (775 male and 587 female) self-reported current MA users aged between 18 and 35 years were recruited using respondent-driven sampling. Two gender-stratified multiple logistic regression models (models I and II) were done for analysis. Results For similarities, 73.0% of males and 60.5% of females initiated MA before their 18th birthday. The early age of MA initiation was positively associated with the reasons and places of the first time MA use among both genders. For differences, males [hazard ratio 1.35; 95% confidence interval, 1.18–1.54] had a significantly higher risk than females to initiate MA at earlier age. Among male users, participants who had bisexual/homosexual preferences were more likely to initiate MA use earlier. In contrast, female users who exchanged sex for money and/or drugs were more likely to initiate MA in earlier age. Conclusions More than 60.0% of male and female participants initiated MA use early; however, males initiated use earlier than females. Although similarities were found among both genders, differences found in key risk factors for early age MA initiation suggest that gender-specific, MA prevention programs are urgently needed in Myanmar

Burden of Chikungunya Virus Infection during an Outbreak in Myanmar

Chikungunya virus (CHIKV) infection is a re-emerging arboviral disease with no approved vaccine, although numerous options are in development. Before vaccine implementation, disease burden, affected age group, and hospitalization rate information should be documented. In 2019, a sizeable outbreak of the East Central South African genotype of CHIKV occurred in Myanmar, and during this period, a cross-sectional study was conducted in two regions, Mandalay and Yangon, to examine the molecular and seropositivity rate of the CHIKV infection. The participants (1124) included dengue-suspected pediatric patients, blood donors, and healthy volunteers, who were assessed using molecular assays (quantitative real-time RT-PCR), serological tests (anti-CHIKV IgM capture and IgG indirect enzyme-linked immunosorbent assays), and neutralization tests. The tests confirmed the following positivity rates: 11.3% (127/1124) for the molecular assay, 12.4% (139/1124) for the anti-CHIKV IgM Ab, 44.5% (500/1124) for the anti-CHIKV IgG Ab, and 46.3% (520/1124) for the CHIKV neutralizing Ab. The highest rate for the molecular test occurred with the dengue-suspected pediatric patients. The seroprevalence rate through natural infection was higher in the healthy volunteers and blood donors than that in the pediatric patients. The results of this study will help stakeholders determine the criteria for choosing appropriate recipients when a CHIKV vaccine is introduced in Myanmar

Seroprevalence and associated risk factors of Toxoplasma gondii infection among slaughterhouse workers in Yangon Region, Myanmar: A cross-sectional study

Background Toxoplasmosis, having the significant consequences affecting mortality and quality of life, is still prevalent in various places throughout the world. The major gap in surveillance for Toxoplasma gondii infection among high-risk population, slaughterhouse workers, is an obstacle for the effective policies formulation to reduce the burden of toxoplasmosis in Myanmar. Therefore, this study aimed to assess the seroprevalence of toxoplasmosis and associated factors of seropositivity among slaughterhouse workers in Yangon Region, Myanmar. Methods A cross-sectional study that was conducted from June to November 2020 included 139 slaughterhouse workers involving at five main slaughterhouses under Yangon City Development Committee, Myanmar. The presence of IgG and IgM anti-T. gondii antibodies in serum was detected using the OnSite Toxo IgG/IgM Combo Rapid Test. A face-to-face interview was also performed using pretested structured questionnaires to obtain the detail histories: sociodemographic characteristics, level of knowledge, occupational factors, and environmental factors related to T. gondii infection. Bivariate logistic regression was used to determine the factors associated with T. gondii infection. Results Of all participants, the overall seroprevalence of anti-T. gondii was 43.9% (95% CI: 35.5–52.5%), of whom 98.4% (95% CI: 91.2–100.0%) were reactive only for IgG antibody and 1.6% (95% CI: 0.0–8.8%) were reactive for IgG and IgM antibodies. The significant factors associated with the seropositivity of T. gondii antibodies were blood transfusion history (OR: 5.74, 95% CI: 1.17–28.09), low level of knowledge (OR: 2.91, 95% CI: 1.46–5.83), contact with animal organs, muscles or blood (OR: 14.29, 95% CI: 1.83–111.51), and animals most frequently slaughtered (cattle) (OR: 3.22, 95% CI: 1.16–8.93). Conclusions A high seroprevalence of toxoplasmosis was detected among slaughterhouse workers in Yangon Region and it raises a significant public health concern. Therefore, providing health education regarding toxoplasmosis, enforcement of personal hygiene practices in workplaces, the establishment of training for occupational hygiene, and commencement of the risk assessment and serological screening for toxoplasmosis are crucial to curtail the prevalence of T. gondii infection among slaughterhouse workers

Prevalence of alcohol consumption and its risk factors among university students: A cross-sectional study across six universities in Myanmar.

BACKGROUND:Globally, alcohol consumption is a significant public health concern and it is one of the most important risk behaviours among university students. Alcohol consumption can lead to poor academic performance, injuries, fights, use of other substances, and risky sexual behaviours among students. However, the study explored the prevalence of alcohol consumption and the associated risk factors among university students since these have not been fully examined in previous research. Therefore, the aim of this study was to explore the prevalence of alcohol consumption and the associated risk factors among university students in Myanmar. METHODS:The present cross-sectional study was conducted using a sample of 15-24-year-old university students who were selected from six universities in Mandalay, Myanmar, in August 2018. In total, 3,456 students (males: 1,301 and females: 2,155) were recruited and asked to respond to a self-administered questionnaire. Multiple logistic regression analysis was used to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for alcohol consumption among university students. RESULTS:The prevalence of alcohol consumption in the previous 30 days was 20.3% (males: 36.0%, females: 10.8%). The alcohol consumption was significantly higher among males (AOR = 2.3, 95% CI; 1.9-2.9), truant students (AOR = 2.1, 95% CI; 1.3-3.3), smokers (AOR = 7.0, 95% CI; 5.1-9.7), students who reported feeling of hopelessness or sadness (AOR = 1.4, 95% CI; 1.2-1.8), peers' alcohol consumption (AOR = 7.5, 95% CI; 4.8-11.7). CONCLUSION:The present study revealed that males, smokers, peer alcohol consumption, and truant students had higher odds of alcohol consumption among the students. Therefore, effective campus-based counselling, peer education, and national surveillance systems that can monitor risky drinking behaviours among university students should be implemented. Further, government regulations that control the production, sale, promotion, advertising, and restriction of alcohol should be well developed and strengthened, as in the case of other Southeast Asian countries

A Framework for New National Forest Inventory in Myanmar: Improving National Measuring and Reporting Capacities for REDD+ and Beyond

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