Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs.

BACKGROUND: Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses. METHODS: At 119-120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3-4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit. RESULTS: LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte "end feet" vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS. CONCLUSION: LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

Laser therapy for retinopathy in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with SCD develop ocular manifestations. Vision-threatening complications are mainly due to proliferative sickle retinopathy, which is characterised by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy (PSR) to prevent sight-threatening complications. OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in SCD-related proliferative retinopathy. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched the following resources (26 June 2022): Latin American and Caribbean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults with SCD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and risk of bias of the included trials; we extracted and analysed data, contacting trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS: We included three trials (414 eyes of 339 children and adults) comparing the efficacy and safety of laser photocoagulation to no therapy in people with PSR. There were 160 males and 179 females ranging in age from 13 to 67 years. The trials used different laser photocoagulation techniques; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; a two-centre trial employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre; while a third trial employed focal scatter laser photocoagulation using argon laser. The mean follow-up periods were 21 to 32 months in one trial, 42 to 47 months in a second, and 48 months in the third. Two trials had a high risk of allocation bias due to the randomisation method for participants with bilateral disease; the third trial had an unclear risk of selection bias. One trial was at risk of reporting bias. Given the unit of analysis is the eye rather than the individual, we chose to report the data narratively. Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported no difference between groups for complete regression of PSR: 30.2% in the laser group and 22.4% in the control group. The same trial also reported no difference between groups in the development of new PSR: 34.3% of lasered eyes and 41.3% of control eyes (very low-certainty evidence). The two-centre trial using feeder vessel coagulation, only presented data at follow-up for one centre (mean period of nine years) and reported the development of new sea fan in 48.0% in the treated and 45.0% in the control group; no statistical significance (P = 0.64). A third trial reported regression in 55% of the laser group versus 28.6% of controls and progression of PSR in 10.5% of treated versus 25.7% of control eyes. We graded the evidence for these two primary outcomes as very low-certainty evidence. The sectoral scatter laser photocoagulation trial reported visual loss in 3.0% of treated eyes (mean follow-up 47 months) versus 12.0% of controlled eyes (mean follow-up 42 months) (P = 0.019). The feeder vessel coagulation trial reported visual loss in 1.14% of the laser group and 7.5% of the control group (mean follow-up 26 months at one site and 32 months in another) (P = 0.07). The focal scatter laser photocoagulation trial (mean follow-up of four years) reported that 72/73 eyes had the same visual acuity, while visual loss was seen in only one eye from the control group. We graded the certainty of the evidence as very low. The sectoral scatter laser trial detected vitreous haemorrhage in 12.0% of the laser group and 25.3% of control with a mean follow-up of 42 (control) to 47 months (treated) (P ≤ 0.5). The two-centre feeder vessel coagulation trial observed vitreous haemorrhage in 3.4% treated eyes (mean follow-up 26 months) versus 27.5% control eyes (mean follow-up 32 months); one centre (mean follow-up nine years) reported vitreous haemorrhage in 1/25 eyes (4.0%) in the treatment group and 9/20 eyes (45.0%) in the control group (P = 0.002). The scatter laser photocoagulation trial reported that vitreous haemorrhage was not seen in the treated group compared to 6/35 (17.1%) eyes in the control group and appeared only in the grades B and (PSR) stage III) (P < 0.05). We graded evidence for this outcome as low-certainty. Regarding adverse effects, only one occurrence of retinal tear was reported. All three trials reported on retinal detachment, with no significance across the treatment and control groups (low-certainty evidence). One trial reported on choroidal neovascularization, with treatment with xenon arc found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow-up of three years or more. The included trials did not report on other adverse effects or quality of life. AUTHORS' CONCLUSIONS: Our conclusions are based on the data from three trials (two of which were conducted over 30 years ago). Given the limited evidence available, which we assessed to be of low- or very low-certainty, we are uncertain whether laser therapy for sickle cell retinopathy improves the outcomes measured in this review. This treatment does not appear to have an effect on clinical outcomes such as regression of PSR and development of new incidences. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence).  Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors (VEGFs) . Patient-important outcomes as well as cost-effectiveness should be addressed.

Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among Malaria Patients in Southern Thailand: 8 Years Retrospective Study.

Erythrocytes deficient in glucose-6-phosphate dehydrogenase (G6PD) is more susceptible to oxidative damage from free radical derived compounds. The hemolysis triggered by oxidative agents such as primaquine (PQ) is used for the radical treatment of hypnozoites of P. vivax. Testing of G6PD screening before malaria treatment is not a common practice in Thailand, which poses patients at risk of hemolysis. This retrospective study aimed to investigate the prevalence of G6PD in malaria patients who live in Southern Thailand. Eight hundred eighty-one malaria patients were collected for 8-year from 2012 to 2019, including 785 (89.1%) of P. vivax, 61 (6.9%) of P. falciparum, 27 (3.1%) of P. knowlesi, and 8 (0.9%) of mixed infections. The DiaPlexC genotyping kit (Asian type) and PCR-RFLP were employed to determine the G6PD variants. The result showed that 5 different types of G6PD variants were identified in 26 cases (2.9%); 12/26 (46.2%) had Mahidol (487G>A) and 11/26 (42.3%) had Viangchan (871G>A) variants, while the rest had Kaiping (1388G>A), Union (1360C>T), and Mediterranean (563C>T) variants. G6PD Songklanagarind (196T>A) variant was not found in the study. Our result did not show a significant difference in the malaria parasite densities in patients between G6PD-deficient and G6PD-normal groups. According to our findings, testing G6PD deficiency and monitoring the potential PQ toxicity in patients who receive PQ are highly recommended.

Outcomes of the CT2 study: A 'one-stop-shop' for community-based hepatitis C testing and treatment in Yangon, Myanmar.

BACKGROUND: With the advent of low-cost generic direct-acting antivirals (DAA), hepatitis C (HCV) elimination is now achievable even in low-/middle-income settings. We assessed the feasibility and effectiveness of a simplified clinical pathway using point-of-care diagnostic testing and non-specialist-led care in a decentralized, community-based setting. METHODS: This feasibility study was conducted at two sites in Yangon, Myanmar: one for people who inject drugs (PWID), and the other for people with liver disease. Participants underwent on-site rapid anti-HCV testing and HCV RNA testing using GeneXpert(R) . General practitioners determined whether participants started DAA therapy immediately or required specialist evaluation. Primary outcome measures were progression through the HCV care cascade, including uptake of RNA testing and treatment, and treatment outcomes. FINDINGS: All 633 participants underwent anti-HCV testing; 606 (96%) were anti-HCV positive and had HCV RNA testing. Of 606 tested, 535 (88%) were RNA positive and had pre-treatment assessments; 30 (6%) completed specialist evaluation. Of 535 RNA positive participants, 489 (91%) were eligible to initiate DAAs, 477 (98%) completed DAA therapy and 421 achieved SVR12 (92%; 421/456). Outcomes were similar by site: PWID site: 91% [146/161], and liver disease site: 93% [275/295]). Compensated cirrhotic patients were treated in the community; they achieved an SVR12 of 83% (19/23). Median time from RNA test to DAA initiation was 3 days (IQR 2-5). CONCLUSIONS: Delivering a simplified, non-specialist-led HCV treatment pathway in a decentralized community setting was feasible in Yangon, Myanmar; retention in care and treatment success rates were very high. This care model could be integral in scaling up HCV services in Myanmar and other low- and middle-income settings.

A LAMP-SNP Assay Detecting C580Y Mutation in Pfkelch13 Gene from Clinically Dried Blood Spot Samples.

Artemisinin resistance (ART) has been confirmed in Greater Mekong Sub-region countries. Currently, C580Y mutation on Pfkelch13 gene is known as the molecular marker for the detection of ART. Rapid and accurate detection of ART in field study is essential to guide malaria containment and elimination interventions. A simple method for collection of malaria-infected blood is to spot the blood on filter paper and is fast and easy for transportation and storage in the field study. This study aims to evaluate LAMP-SNP assay for C580Y mutation detection by introducing an extra mismatched nucleotide at the 3' end of the FIP primer. The LAMP-SNP assay was performed in a water bath held at a temperature of 56°C for 45 min. LAMP-SNP products were interpreted by both gel-electrophoresis and HNB-visualized changes in color. The method was then tested with 120 P. falciparum DNA from dried blood spot samples. In comparing the LAMP-SNP assay results with those from DNA sequencing of the clinical samples, the 2 results fully agreed to detect C580Y. The sensitivity and specificity of the LAMP-SNP assay showed 100%. There were no cross-reactions with other Plasmodium species and other Pfkelch13 mutations. The LAMP-SNP assay performed in this study was rapid, reliable, and useful in detecting artemisinin resistance in the field study.

Effect of COVID-19-restrictive measures on ambient particulate matter pollution in Yangon, Myanmar.

BACKGROUND: Particulate matter (PM) is recognized as the most harmful air pollutant to the human health. The Yangon city indeed suffers much from PM-related air pollution. Recent research has interestingly been focused on the novel subject of changes in the air quality associated with the restrictive measures in place during the current coronavirus disease-2019 (COVID-19) pandemic. The first case of COVID-19 in Myanmar was diagnosed on March 23, 2020. In this article, we report on our attempt to evaluate any effects of the COVID-19-restrictive measures on the ambient PM pollution in Yangon. METHODS: We measured the PM concentrations every second for 1 week on four occasions at three study sites with different characteristics; the first occasion was before the start of the COVID-19 pandemic and the remaining three occasions were while the COVID-19-restrictive measures were in place, including Stay-At-Home and Work-From-Home orders. The Pocket PM2.5 Sensor [PRO] designed by the National Institute for Environmental Studies (NIES), Japan, in cooperation with Yaguchi Electric Co., Ltd., (Miyagi, Japan) was used for the measurement of the ambient PM2.5 and PM10 concentrations. RESULTS: The results showed that there was a significant reduction (P < 0.001) in both the PM2.5 and PM10 concentrations while the COVID-19-restrictive measures were in place as compared to the measured values prior to the pandemic. The city experienced a profound improvement in the PM-related air quality from the "unhealthy" category prior to the onset of the COVID-19 pandemic to the "good" category during the pandemic, when the restrictive measures were in place. The percent changes in the PM concentrations varied among the three study sites, with the highest percent reduction noted in a semi-commercial crowded area (84.8% for PM2.5; 88.6% for PM10) and the lowest percent reduction noted in a residential quiet area (15.6% for PM2.5; 12.0% for PM10); the percent reductions also varied among the different occasions during the COVID-19 pandemic that the measurements were made. CONCLUSIONS: We concluded that the restrictive measures which were in effect to combat the COVID-19 pandemic had a positive impact on the ambient PM concentrations. The changes in the PM concentrations are considered to be largely attributable to reduction in anthropogenic emissions as a result of the restrictive measures, although seasonal influences could also have contributed in part. Thus, frequent, once- or twice-weekly Stay-At-Home or Telework campaigns, may be feasible measures to reduce PM-related air pollution. When devising such an action plan, it would be essential to raise the awareness of public about the health risks associated with air pollution and create a social environment in which Telework can be carried out, in order to ensure active compliance by the citizens.

Interventions for preventing and managing advanced liver disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. This is an updated version of a previously published review. OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020. SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both). DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review. MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials. AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.

Improvement of GPS-attached Pocket PM2.5 Measuring Device for Personal Exposure Assessment.

Assessment of personal exposure to particulate matter with an aerodynamic diameter less than or 2.5 µm (PM2.5) is necessary to study the association between PM exposure and health risk. Development of a personal PM2.5 sensor or device is required for the evaluation of individual exposure level. In this study, we aimed to develop a small-sized, lightweight sensor with a global positioning system (GPS) attached that can measure PM2.5 and PM10 every second to assess continuous personal exposure levels. The participants in this study were apparently healthy housewives (n = 15) and university female teaching staff (n = 15) who live in a high PM2.5 area, Yangon, Myanmar. The average PM2.5 exposure levels during 24 h were 16.1 ± 10.0 µg/m3 in the housewives and 15.8 ± 4.0 µg/m3 in the university female teaching staff. The university female teaching staff showed high exposure concentrations during commuting hours, and had stable, relatively low concentrations at work, whereas the housewives showed short-term high exposure peaks due to differences in their lifestyles. This is the first study to show that a GPS-attached standalone PM2.5 and PM10 Sensor [PRO] can be successfully used for mobile sensing, easy use, continuous measurement, and rapid data analysis.

Molecular identification and genetic diversity of Gnathostoma spinigerum larvae in freshwater fishes in southern Lao PDR, Cambodia, and Myanmar.

Gnathostomiasis, an emerging food-borne parasitic zoonosis in Asia, is mainly caused by Gnathostoma spinigerum (Nematoda: Gnathostomatidae). Consumption of raw meat or freshwater fishes in endemic areas is the major risk factor. Throughout Southeast Asia, including Thailand, Lao PDR, Cambodia, and Myanmar, freshwater fish are often consumed raw or undercooked. The risk of this practice for gnathostomiasis infection in Lao PDR, Cambodia, and Myanmar has never been evaluated. Here, we identified larvae of Gnathostoma species contaminating freshwater fishes sold at local markets in these three countries. Public health authorities should advise people living in, or travelling to, these areas to avoid eating raw or undercooked freshwater fishes. Identification of larvae was done using molecular methods: DNA was sequenced from Gnathostoma advanced third-stage larvae recovered from snakehead fishes (Channa striata) and freshwater swamp eels (Monopterus albus). Phylogenetic analysis of a portion of the mitochondrial cytochrome c oxidase subunit I gene showed that the G. spinigerum sequences recovered from southern Lao PDR, Cambodia, and Myanmar samples had high similarity to those of G. spinigerum from China. Sequences of the nuclear ribosomal DNA internal transcribed spacer 2 region closely resembled sequences of G. spinigerum from Thailand, Indonesia, the USA, and central Lao PDR. This is the first molecular evidence of G. spinigerum from freshwater fishes in southern Lao PDR, Cambodia, and Myanmar.

Genetic Diversity of Plasmodium vivax in Clinical Isolates from Southern Thailand using PvMSP1, PvMSP3 (PvMSP3α, PvMSP3ß) Genes and Eight Microsatellite Markers.

Plasmodium vivax is usually considered morbidity in endemic areas of Asia, Central and South America, and some part of Africa. In Thailand, previous studies indicated the genetic diversity of P. vivax in malaria-endemic regions such as the western part of Thailand bordering with Myanmar. The objective of the study is to investigate the genetic diversity of P. vivax circulating in Southern Thailand by using 3 antigenic markers and 8 microsatellite markers. Dried blood spots were collected from Chumphon, Phang Nga, Ranong and, Surat Thani provinces of Thailand. By PCR, 3 distinct sizes of PvMSP3α, 2 sizes of PvMSP3ß and 2 sizes of PvMSP1 F2 were detected based on the length of PCR products, respectively. PCR/RFLP analyses of these antigen genes revealed high levels of genetic diversity. The genotyping of 8 microsatellite loci showed high genetic diversity as indicated by high alleles per locus and high expected heterozygosity (HE). The genotyping markers also showed multiple-clones of infection. Mixed genotypes were detected in 4.8% of PvMSP3α, 29.1% in PvMSP3ß and 55.3% of microsatellite markers. These results showed that there was high genetic diversity of P. vivax isolated from Southern Thailand, indicating that the genetic diversity of P. vivax in this region was comparable to those observed other areas of Thailand.

Molecular Surveillance of Pfkelch13 and Pfmdr1 Mutations in Plasmodium falciparum Isolates from Southern Thailand.

Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.

Indole and Derivatives Modulate Biofilm Formation and Antibiotic Tolerance of Klebsiella pneumoniae.

Intercellular communication is a crucial process for the multicellular community in both prokaryotes and eukaryotes. Indole has been recognized as a new member of the signal molecules which enables the regulated control of various bacterial phenotypes. To elucidate the inter-species relationship among enteric microorganisms via indole signaling, Klebsiella pneumoniae (KP) culture was treated with indole solution and examined for the pathogenicity by using various phenotypic tests. Both synthetic and naturally-produced indole preparations had no deteriorating effect on growth and autoaggregative capacity of KP. The results showed that biofilm formation of carbapenem-susceptible K. pneumoniae (KP-S) was clearly induced by indole exposure (≈ 2-10 folds), whereas no significant difference was observed in the resistant counterpart. In addition, the tolerance to ß-lactam antibiotics of KP was altered upon exposure to indole and/or derivatives assessed by Kirby-Bauer disk diffusion test. Taken together, our finding indicates the functional role of indole in changing or modulating pathogenic behaviors of other bacteria.

O-GlcNAcylation in oral squamous cell carcinoma.

BACKGROUND: Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked ß-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading. METHODS: Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody. RESULTS: The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading. CONCLUSION: Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.

Molecular identification of Ascaris lumbricoides and Ascaris suum recovered from humans and pigs in Thailand, Lao PDR, and Myanmar.

Ascaris lumbricoides is the largest roundworm known from the human intestine while Ascaris suum is an internal parasite of pigs. Ascariasis, caused by Ascaris lumbricoides, has a worldwide distribution. Here, we have provided the first molecular identification of Ascaris eggs and adults recovered from humans and pigs in Thailand, Lao PDR, and Myanmar. We amplified and sequenced nuclear ribosomal DNA (ITS1 and ITS2 regions) and mitochondrial DNA (cox1 gene). Sequence chromatograms of PCR-amplified ITS1 region revealed a probable hybrid genotype from two human ascariasis cases from Chiang Mai Province, northern Thailand. All complete ITS2 sequences were identical and did not differ between the species. Phylogenetic trees and haplotype analysis of cox1 sequences showed three clusters with 99 haplotypes. Forty-seven samples from the present study represented 14 haplotypes, including 7 new haplotypes. To our knowledge, this is the first molecular confirmation of Ascaris species in Thailand, Lao PDR, and Myanmar. Zoonotic cross-transmission of Ascaris roundworm between pigs and humans probably occurs in these countries.

Preliminary monitoring of concentration of particulate matter (PM2.5) in seven townships of Yangon City, Myanmar.

BACKGROUND: Airborne particulate pollution is more critical in the developing world than in the developed countries in which industrialization and urbanization are rapidly increased. Yangon, a second capital of Myanmar, is a highly congested and densely populated city. Yet, there is limited study which assesses particulate matter (PM2.5) in Yangon currently. Few previous local studies were performed to assess particulate air pollution but most results were concerned PM10 alone using fixed monitoring. Therefore, the present study aimed to assess distribution of PM2.5 in different townships of Yangon, Myanmar. This is the first study to quantify the regional distribution of PM2.5 in Yangon City. METHODS: The concentration of PM2.5 was measured using Pocket PM2.5 Sensor (Yaguchi Electric Co., Ltd., Miyagi, Japan) three times (7:00 h, 13:00 h, 19:00 h) for 15 min per day for 5 days from January 25th to 29th in seven townships. Detailed information of eight tracks for PM2.5 pollution status in different areas with different conditions within Kamayut Township were also collected. RESULTS: The results showed that in all townships, the highest PM2.5 concentrations in the morning followed by the evening and the lowest concentrations in the afternoon were observed. Among the seven townships, Hlaingtharyar Township had the highest concentrations (164 ± 52 µg/m3) in the morning and (100 ± 35 µg/m3) in the evening. Data from eight tracks in Kamayut Township also indicated that PM2.5 concentrations varied between different areas and conditions of the same township at the same time. CONCLUSION: Myanmar is one of the few countries that still have to establish national air quality standards. The results obtained from this study are useful for the better understanding of the nature of air pollution linked to PM2.5. Moreover, the sensor which was used in this study can provide real-time exposure, and this could give more accurate exposure data of the population especially those subpopulations that are highly exposed than fixed station monitoring.

Interventions for preventing and managing advanced liver disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 06 April 2017.We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 04 January 2017. SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both). DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review. MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials. AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.

Laser therapy for retinopathy in sickle cell disease.

BACKGROUND: Sickle cell disease includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with the disease develop ocular manifestations due to vaso-occlusion. Vision-threatening complications of sickle cell disease are mainly due to proliferative sickle retinopathy which is characterized by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies such as proliferative sickle retinopathy and proliferative diabetic retinopathy. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy to prevent sight-threatening complications. OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 21 September 2015.We also searched the following resources (24 March 2015): Latin American and Carribean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, the risk of bias of the included trials and extracted and analysed data. We contacted the trial authors for additional information. MAIN RESULTS: Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias.Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes.There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation.Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more.Data regarding quality of life and other adverse effects were not reported in the included trials. AUTHORS' CONCLUSIONS: Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.

Stimuli Responsive Molecular Exchange of Structure Directing Agents on Gold Nanobipyramids: Cancer Cell Detection and Synergistic Therapeutics.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

Identification of the variants in PARL, the nuclear modifier gene, responsible for the expression of LHON patients in Thailand.

The present study explored variation in the PARL gene as one of the potential nuclear modifiers in the pathogenesis of Leber hereditary optic neuropathy (LHON). Ten exons, their franking introns and 3' UTR of the PARL gene were analysed. Seventeen SNPs detected were investigated in 83 affected and 53 unaffected individuals from 47 independent Thai LHON pedigrees using MQLS statistics in order to minimize the influence of the family background. Three intronic SNPs (rs953419, rs3749446 and rs1402000) showed statistically significant results. Joint haplotypes were constructed based on the genotypes at 3 SNPs and 7 possible haplotypes were observed in the 136 subjects. Our findings that the frequency of the haplotype AAC, and AAT were significantly higher in the unaffected cases and the frequencies of haplotype GGT were significantly higher in LHON cases, indicate that it might have a role in the penetrance of this mitochondrial disease.