Thet Aung - Academia.edu (original) (raw)

Papers by Thet Aung

International Dental Journal

PLOS ONE

Background Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) ... more Background Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting. Methodology and principal findings To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not di...

Advances in Computer and Communication

Tropical Medicine and Infectious Disease

Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) startin... more Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) starting first-line antiretroviral therapy (ART). The first VL test was initially scheduled at 12-months and one year later this changed to 6-months. Using routinely collected secondary data, we assessed program performance of routine VL testing at 12-months and 6-months in PLHIV starting ART in the Integrated HIV-Care Program, Myanmar, from January 2016 to December 2017. There were 7153 PLHIV scheduled for VL testing at 12-months and 1976 scheduled for VL testing at 6-months. Among those eligible for testing, the first VL test was performed in 3476 (51%) of the 12-month cohort and 952 (50%) of the 6-month cohort. In the 12-month cohort, 10% had VL > 1000 copies/mL, 79% had repeat VL tests, 42% had repeat VL > 1000 copies/mL (virologic failure) and 85% were switched to second-line ART. In the 6-month cohort, 11% had VL > 1000 copies/mL, 83% had repeat VL tests, 26% had repeat VL > 1...

Emerging Infectious Diseases

International Journal of Machine Learning and Computing

Network structure is a representation of interactions among actors. Transportation network, biolo... more Network structure is a representation of interactions among actors. Transportation network, biological network and social networks have complex networks structure. Detecting community in complex networks is an important research to gain insight information. Effective optimization algorithms are needed in network community detection. Modularity based artificial bee colony (MABC) algorithm is proposed to uncover community in complex network. The proposed MABC algorithm is evaluated by Modularity and Normalize Mutual Information (NMI) metrics. Three real world datasets are used in the experiment. The proposed approach effectively detects community structure and produces noticeable good result than other previous algorithms in sample complex networks.

Journal of Aquaculture & Marine Biology

Applied Sciences

Cervical cancer can be prevented by having regular screenings to find any precancers and treat th... more Cervical cancer can be prevented by having regular screenings to find any precancers and treat them. The Pap test looks for any abnormal or precancerous changes in the cells on the cervix. However, the manual screening of Pap smear in the microscope is subjective with poorly reproducible criteria. Therefore, the aim of this study was to develop a computer-assisted screening system for cervical cancer using digital image processing of Pap smear images. The analysis of Pap smear image is important in the cervical cancer screening system. There were four basic steps in our cervical cancer screening system. In cell segmentation, nuclei were detected using a shape-based iterative method, and the overlapping cytoplasm was separated using a marker-control watershed approach. In the features extraction step, three important features were extracted from the regions of segmented nuclei and cytoplasm. RF (random forest) algorithm was used as a feature selection method. In the classification st...

BMC Pregnancy and Childbirth

Background A series of interventions are required to prevent mother to child transmission (PMTCT)... more Background A series of interventions are required to prevent mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) starting from HIV testing of pregnant women, initiating antiretroviral therapy (ART) or antiretroviral prophylaxis to HIV-positive pregnant women to providing HIV prophylaxis to newborn babies. Gaps in each step can significantly affect the effectiveness of PMTCT interventions. We aimed to determine the gap in initiation of ART/antiretroviral prophylaxis for pregnant women living with HIV, delay in initiation of ART/antiretroviral prophylaxis and factors associated with the delay. Methods This is a cross sectional study using routinely collected programme data from five health facilities providing PMTCT services located at Township Health Departments (THD) of Mandalay, Myanmar. Results There were 363 pregnant women living with HIV enrolled between January 2012 and December 2017. Sixty (16%) women were excluded from the study due to missing data on d...

International Marine Science Journal

The samples of flatfishes were collected along the Mon State from July to December 2017 including... more The samples of flatfishes were collected along the Mon State from July to December 2017 including Mawlamyine, Kyaikkhami, Setse, Zee-Phyu-Thaung Belugyun island, Paung and Thaton. The total 21 species of flatfishes were recorded in Mon State. Moreover, the relative abundance, diversity and similarity were conducted using Simpson Index, Shannon index and Jacquard’s index etc. According to the present study, the Cynoglossidae was the most dominant family and the most dominant species was Cynoglossusarelfor the present study. The relative abundance of Mawlamyine and November was relatively the highest. Furthermore, Mawlamyine was the highest diversity and Thaton was the lowest diversity. The JI value between Mawlamyine and Paung is the highest while it is the lowest between Setse and Thaton. Likewise, the JI value between August and September and the value between September and November are the same as well as the highest while it is the lowest for the comparison between July and Augus...

Open Forum Infectious Diseases

BMC Pregnancy and Childbirth

Background: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis... more Background: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis (pARV) or lifelong treatment (ART) in HIV-positive pregnant women prior to delivery has a huge impact in reducing mother to child transmission (MTCT) of HIV, maternal morbidity, mortality and increasing retention in care. In this study, we aimed to determine the following in a 'prevention of mother-to-child transmission' (PMTCT) programme in Central Women Hospital, Mandalay, Myanmar: i) uptake of ART and factors associated with the uptake ii) duration of ART/ pARV received by HIV-positive pregnant women prior to delivery, iii) factors associated with ART/ pARV initiation after delivery and iv) factors associated with shorter duration of ART/ pARV (≤ 8 weeks prior to delivery). Method: This was a retrospective cohort study using routinely collected data from PMTCT programme. We used multivariable Cox proportional Hazard model or log binomial models to assess the association between sociodemographic and clinical factors with a) uptake of ART/pARV, b) initiation of ART/pARV after delivery, c) shorter (≤8 weeks) duration of ART/PARV prior to delivery. Results: Of the 670 ART naïve HIV-positive women enrolled to PMTCT programme between March 2011 and December 2016, 588 (88%) were initiated on ART/pARV. In adjusted analysis, only pregnancy stage at enrolment was significantly associated with initiation of ART/pARV. Of 585 who had delivered babies on or before the censor date, 522 (89%) were on ART/pARV. Women who lived outside Mandalay were more likely to be initiated on ART after delivery (i.e., delayed ART initiation in those on ART). Among women who were initiated on ART/pARV before delivery (n = 468), only 59% got ART/pARV for > 8 weeks before delivery. Women whose spouses' HIV status was not recorded had 40% higher risk of short duration of ART/pARV.

Global health action, 2018

In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program ... more In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program for HIV treatment and care since 2005. To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged ≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors associated with attrition during these two periods. Children enrolled in IHC Programme and their status (death, lost to follow-up, regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 person-years) at pre - ART and ART periods were calculated and the association between demographic and clinical characteristics with attrition was assessed using Cox proportional hazards model. Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of follow-up (95% CI: 17-21) and ART attrition rate was 4 per 100 person-years of follow-u...

Biochimica et biophysica acta, Jan 18, 2018

Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiot... more Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria. First, oligomer formation by an amphiphilic xanthone, compound 2 (also coded as AM052), was investigated via solution-state nuclear magnetic resonance (NMR) spectroscopy. Then, the effects of oligomerization on membrane disruption were further studied via biophysical approaches. The results showed that the antimicrobial activities of SAPs develop in several stages: oligomer formation in aqueous solution, initial binding of oligomers to the membrane-water interface followed by insertion into the membrane bilayer,...

PloS one, 2017

Loss-to-follow-up (LTFU) throughout the Prevention of Mother-To-Child Transmission (PMTCT) cascad... more Loss-to-follow-up (LTFU) throughout the Prevention of Mother-To-Child Transmission (PMTCT) cascade remains one of the major threats to the success of PMTCT programs. In this study, we aimed to determine the mother-to-child transmission rate in a programmatic setting and to determine factors associated with LTFU among enrolled mothers and unfavorable outcomes among HIV-exposed babies which includes being HIV positive, death and LTFU. A retrospective cohort study reviewing routinely collected data in an Integrated HIV care program, Mandalay, Myanmar in June 2016.LTFU means mother/infant missing appointed visit for more than three months. Of 678 pregnant women enrolled in PMTCT program between March 2011 and June 2014, one stillbirth and 607 live births were recorded in this cohort. Of 457 HIV-exposed babies with HIV-test recorded at the end of the intervention, nine (2%) were HIV-positive. Pregnant women's and exposed-babies' LTFU rate was 7 per 1000 person-years, and 10 per 1...

The ocular surface, Jan 26, 2017

The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the p... more The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel m...

Antimicrobial agents and chemotherapy, Oct 7, 2017

The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has ... more The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ϵ-polylysine (ϵPL) is non-cytotoxic to primary human dermal fibroblasts at concentrations up to 2000 μg/ml, suggesting that the presence of isopeptide backbone has greater cell selectivity than α-peptide backbones. Both ϵPL and and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt the preformed biofilms. ϵPL displays broad spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungii. ϵPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria and its biocompatibility index i...

Journal of medicinal chemistry, Jan 27, 2017

A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has ... more A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity of more than 511, comparable to that of several membrane-active antibiotics in clinical trials. Our data show for the first time that icaritin derivatives effectively kill bacteria. Meanwhile, this is the first study deploying a biomimicking strategy to design potent flavone-based membrane targeting antimicrobials. 6 showed rapid bactericidal activity by disrupting the bacterial membrane and can circumvent the development of bacterial resistance. Importantly, 6 was highly efficacious in a mouse model of corneal infection caused by MRSA and Staphylococcus aureus.

Global health action, 2017

In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by I... more In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by Integrated HIV Care (IHC) program through its anti-retroviral therapy (ART) centers across 10 cities in five states and regions of Myanmar. Blood samples from the ART centers are sent using public transport to a centralized PCR facility. Among HIV-exposed babies <9 months at enrolment into IHC program (2013-15), to describe the EID cascade (enrolment, sample collection for PCR, result receipt by mother, HIV diagnosis and ART initiation) and factors associated with delayed (>8 weeks of age) or no blood sample collection for EID. Retrospective cohort study involving record review. A predictive poisson regression model with robust variance estimates was fitted for risk factors of delayed or no sample collection. Of 1349 babies, 523 (39%) of the babies' mothers were on ART before pregnancy. Timely uptake of EID (<8 weeks of age) was 47% (633/1349); sample collection was delayed i...

International Dental Journal

PLOS ONE

Background Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) ... more Background Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting. Methodology and principal findings To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not di...

Advances in Computer and Communication

Tropical Medicine and Infectious Disease

Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) startin... more Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) starting first-line antiretroviral therapy (ART). The first VL test was initially scheduled at 12-months and one year later this changed to 6-months. Using routinely collected secondary data, we assessed program performance of routine VL testing at 12-months and 6-months in PLHIV starting ART in the Integrated HIV-Care Program, Myanmar, from January 2016 to December 2017. There were 7153 PLHIV scheduled for VL testing at 12-months and 1976 scheduled for VL testing at 6-months. Among those eligible for testing, the first VL test was performed in 3476 (51%) of the 12-month cohort and 952 (50%) of the 6-month cohort. In the 12-month cohort, 10% had VL > 1000 copies/mL, 79% had repeat VL tests, 42% had repeat VL > 1000 copies/mL (virologic failure) and 85% were switched to second-line ART. In the 6-month cohort, 11% had VL > 1000 copies/mL, 83% had repeat VL tests, 26% had repeat VL > 1...

Emerging Infectious Diseases

International Journal of Machine Learning and Computing

Network structure is a representation of interactions among actors. Transportation network, biolo... more Network structure is a representation of interactions among actors. Transportation network, biological network and social networks have complex networks structure. Detecting community in complex networks is an important research to gain insight information. Effective optimization algorithms are needed in network community detection. Modularity based artificial bee colony (MABC) algorithm is proposed to uncover community in complex network. The proposed MABC algorithm is evaluated by Modularity and Normalize Mutual Information (NMI) metrics. Three real world datasets are used in the experiment. The proposed approach effectively detects community structure and produces noticeable good result than other previous algorithms in sample complex networks.

Journal of Aquaculture & Marine Biology

Applied Sciences

Cervical cancer can be prevented by having regular screenings to find any precancers and treat th... more Cervical cancer can be prevented by having regular screenings to find any precancers and treat them. The Pap test looks for any abnormal or precancerous changes in the cells on the cervix. However, the manual screening of Pap smear in the microscope is subjective with poorly reproducible criteria. Therefore, the aim of this study was to develop a computer-assisted screening system for cervical cancer using digital image processing of Pap smear images. The analysis of Pap smear image is important in the cervical cancer screening system. There were four basic steps in our cervical cancer screening system. In cell segmentation, nuclei were detected using a shape-based iterative method, and the overlapping cytoplasm was separated using a marker-control watershed approach. In the features extraction step, three important features were extracted from the regions of segmented nuclei and cytoplasm. RF (random forest) algorithm was used as a feature selection method. In the classification st...

BMC Pregnancy and Childbirth

Background A series of interventions are required to prevent mother to child transmission (PMTCT)... more Background A series of interventions are required to prevent mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) starting from HIV testing of pregnant women, initiating antiretroviral therapy (ART) or antiretroviral prophylaxis to HIV-positive pregnant women to providing HIV prophylaxis to newborn babies. Gaps in each step can significantly affect the effectiveness of PMTCT interventions. We aimed to determine the gap in initiation of ART/antiretroviral prophylaxis for pregnant women living with HIV, delay in initiation of ART/antiretroviral prophylaxis and factors associated with the delay. Methods This is a cross sectional study using routinely collected programme data from five health facilities providing PMTCT services located at Township Health Departments (THD) of Mandalay, Myanmar. Results There were 363 pregnant women living with HIV enrolled between January 2012 and December 2017. Sixty (16%) women were excluded from the study due to missing data on d...

International Marine Science Journal

The samples of flatfishes were collected along the Mon State from July to December 2017 including... more The samples of flatfishes were collected along the Mon State from July to December 2017 including Mawlamyine, Kyaikkhami, Setse, Zee-Phyu-Thaung Belugyun island, Paung and Thaton. The total 21 species of flatfishes were recorded in Mon State. Moreover, the relative abundance, diversity and similarity were conducted using Simpson Index, Shannon index and Jacquard’s index etc. According to the present study, the Cynoglossidae was the most dominant family and the most dominant species was Cynoglossusarelfor the present study. The relative abundance of Mawlamyine and November was relatively the highest. Furthermore, Mawlamyine was the highest diversity and Thaton was the lowest diversity. The JI value between Mawlamyine and Paung is the highest while it is the lowest between Setse and Thaton. Likewise, the JI value between August and September and the value between September and November are the same as well as the highest while it is the lowest for the comparison between July and Augus...

Open Forum Infectious Diseases

BMC Pregnancy and Childbirth

Background: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis... more Background: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis (pARV) or lifelong treatment (ART) in HIV-positive pregnant women prior to delivery has a huge impact in reducing mother to child transmission (MTCT) of HIV, maternal morbidity, mortality and increasing retention in care. In this study, we aimed to determine the following in a 'prevention of mother-to-child transmission' (PMTCT) programme in Central Women Hospital, Mandalay, Myanmar: i) uptake of ART and factors associated with the uptake ii) duration of ART/ pARV received by HIV-positive pregnant women prior to delivery, iii) factors associated with ART/ pARV initiation after delivery and iv) factors associated with shorter duration of ART/ pARV (≤ 8 weeks prior to delivery). Method: This was a retrospective cohort study using routinely collected data from PMTCT programme. We used multivariable Cox proportional Hazard model or log binomial models to assess the association between sociodemographic and clinical factors with a) uptake of ART/pARV, b) initiation of ART/pARV after delivery, c) shorter (≤8 weeks) duration of ART/PARV prior to delivery. Results: Of the 670 ART naïve HIV-positive women enrolled to PMTCT programme between March 2011 and December 2016, 588 (88%) were initiated on ART/pARV. In adjusted analysis, only pregnancy stage at enrolment was significantly associated with initiation of ART/pARV. Of 585 who had delivered babies on or before the censor date, 522 (89%) were on ART/pARV. Women who lived outside Mandalay were more likely to be initiated on ART after delivery (i.e., delayed ART initiation in those on ART). Among women who were initiated on ART/pARV before delivery (n = 468), only 59% got ART/pARV for > 8 weeks before delivery. Women whose spouses' HIV status was not recorded had 40% higher risk of short duration of ART/pARV.

Global health action, 2018

In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program ... more In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program for HIV treatment and care since 2005. To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged ≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors associated with attrition during these two periods. Children enrolled in IHC Programme and their status (death, lost to follow-up, regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 person-years) at pre - ART and ART periods were calculated and the association between demographic and clinical characteristics with attrition was assessed using Cox proportional hazards model. Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of follow-up (95% CI: 17-21) and ART attrition rate was 4 per 100 person-years of follow-u...

Biochimica et biophysica acta, Jan 18, 2018

Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiot... more Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria. First, oligomer formation by an amphiphilic xanthone, compound 2 (also coded as AM052), was investigated via solution-state nuclear magnetic resonance (NMR) spectroscopy. Then, the effects of oligomerization on membrane disruption were further studied via biophysical approaches. The results showed that the antimicrobial activities of SAPs develop in several stages: oligomer formation in aqueous solution, initial binding of oligomers to the membrane-water interface followed by insertion into the membrane bilayer,...

PloS one, 2017

Loss-to-follow-up (LTFU) throughout the Prevention of Mother-To-Child Transmission (PMTCT) cascad... more Loss-to-follow-up (LTFU) throughout the Prevention of Mother-To-Child Transmission (PMTCT) cascade remains one of the major threats to the success of PMTCT programs. In this study, we aimed to determine the mother-to-child transmission rate in a programmatic setting and to determine factors associated with LTFU among enrolled mothers and unfavorable outcomes among HIV-exposed babies which includes being HIV positive, death and LTFU. A retrospective cohort study reviewing routinely collected data in an Integrated HIV care program, Mandalay, Myanmar in June 2016.LTFU means mother/infant missing appointed visit for more than three months. Of 678 pregnant women enrolled in PMTCT program between March 2011 and June 2014, one stillbirth and 607 live births were recorded in this cohort. Of 457 HIV-exposed babies with HIV-test recorded at the end of the intervention, nine (2%) were HIV-positive. Pregnant women's and exposed-babies' LTFU rate was 7 per 1000 person-years, and 10 per 1...

The ocular surface, Jan 26, 2017

The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the p... more The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel m...

Antimicrobial agents and chemotherapy, Oct 7, 2017

The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has ... more The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ϵ-polylysine (ϵPL) is non-cytotoxic to primary human dermal fibroblasts at concentrations up to 2000 μg/ml, suggesting that the presence of isopeptide backbone has greater cell selectivity than α-peptide backbones. Both ϵPL and and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt the preformed biofilms. ϵPL displays broad spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungii. ϵPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria and its biocompatibility index i...

Journal of medicinal chemistry, Jan 27, 2017

A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has ... more A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity of more than 511, comparable to that of several membrane-active antibiotics in clinical trials. Our data show for the first time that icaritin derivatives effectively kill bacteria. Meanwhile, this is the first study deploying a biomimicking strategy to design potent flavone-based membrane targeting antimicrobials. 6 showed rapid bactericidal activity by disrupting the bacterial membrane and can circumvent the development of bacterial resistance. Importantly, 6 was highly efficacious in a mouse model of corneal infection caused by MRSA and Staphylococcus aureus.

Global health action, 2017

In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by I... more In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by Integrated HIV Care (IHC) program through its anti-retroviral therapy (ART) centers across 10 cities in five states and regions of Myanmar. Blood samples from the ART centers are sent using public transport to a centralized PCR facility. Among HIV-exposed babies <9 months at enrolment into IHC program (2013-15), to describe the EID cascade (enrolment, sample collection for PCR, result receipt by mother, HIV diagnosis and ART initiation) and factors associated with delayed (>8 weeks of age) or no blood sample collection for EID. Retrospective cohort study involving record review. A predictive poisson regression model with robust variance estimates was fitted for risk factors of delayed or no sample collection. Of 1349 babies, 523 (39%) of the babies' mothers were on ART before pregnancy. Timely uptake of EID (<8 weeks of age) was 47% (633/1349); sample collection was delayed i...