National scale-up of tuberculosis-human immunodeficiency virus collaborative activities in Myanmar from 2005 to 2016 and tuberculosis treatment outcomes for patients with human immunodeficiency virus-positive tuberculosis in the Mandalay Region in 2015.

Background: HIV-associated TB is a serious public health problem in Myanmar. Study objectives were to describe national scale-up of collaborative activities to reduce the double burden of TB and HIV from 2005 to 2016 and to describe TB treatment outcomes of individuals registered with HIV-associated TB in 2015 in the Mandalay Region. Methods: Secondary analysis of national aggregate data and, for treatment outcomes, a cohort study of patients with HIV-associated TB in the Mandalay Region. Results: The number of townships implementing collaborative activities increased from 7 to 330 by 2016. The number of registered TB patients increased from 1577 to 139 625 in 2016, with the number of individuals tested for HIV increasing from 432 to 114 180 (82%) in 2016: 10 971 (10%) were diagnosed as HIV positive. Uptake of co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) nationally in 2016 was 77% and 52%, respectively. In the Mandalay Region, treatment success was 77% and mortality was 18% in 815 HIV-associated TB patients. Risk factors for unfavourable outcomes and death were older age (≥45 years) and not taking CPT and/or ART. Conclusion: Myanmar is making good progress with reducing the HIV burden in TB patients, but better implementation is needed to reach 100% HIV testing and 100% CPT and ART uptake in TB-HIV co-infected patients

Computer Simulation Study of the Phase Behavior and Structural Relaxation in a Gel-Former Modeled by Three Body Interactions

We report a computer simulation study of a model gel-former obtained by modifying the three-body interactions of the Stillinger-Weber potential for silicon. This modification reduces the average coordination number and consequently shifts the liquid-gas phase coexistence curve to low densities, thus facilitating the formation of gels without phase separation. At low temperatures and densities, the structure of the system is characterized by the presence of long linear chains interconnected by a small number of three coordinated junctions at random locations. At small wave-vectors the static structure factor shows a non-monotonic dependence on temperature, a behavior which is due to the competition between the percolation transition of the particles and the stiffening of the formed chains. We compare in detail the relaxation dynamics of the system as obtained from molecular dynamics with the one obtained from Monte Carlo dynamics. We find that the bond correlation function displays stretched exponential behavior at moderately low temperatures and densities, but exponential relaxation at low temperatures. The bond lifetime shows an Arrhenius behavior, independent of the microscopic dynamics. For the molecular dynamics at low temperatures, the mean squared displacement and the (coherent and incoherent) intermediate scattering function display at intermediate times a dynamics with ballistic character and we show that this leads to compressed exponential relaxation. For the Monte Carlo dynamics we find always an exponential or stretched exponential relaxation. Thus we conclude that the compressed exponential relaxation observed in experiments is due to the out-of-equilibrium dynamics

Assessment of skeletal maturity: a new classification scheme using distal radius and ulna radiographs

Concurrent Session 6A - Innovative & Diagnostic Methods: paper no. 97SUMMARY: Our study describes a new classification scheme to assess skeletal maturity by utilizing the distal radius and ulna radiographs. This classification demonstrates a relationship with adolescent growth spurt and cessation of growth. Introduction: The progression of the curve in adolescent idiopathic scoliosis has always been associated with pubertal growth spurt. The commonly used clinical or radiological methods are still deficient in predicting this growth peak among adolescents and bone age is too complicated to apply. To address these concerns, we ...postprin

Identification of RecQL1 as a Holliday junction processing enzyme in human cell lines

Homologous recombination provides an effective way to repair DNA double-strand breaks (DSBs) and is required for genetic recombination. During the process of homologous recombination, a heteroduplex DNA structure, or a ‘Holliday junction’ (HJ), is formed. The movement, or branch migration, of this junction is necessary for recombination to proceed correctly. In prokaryotes, the RecQ protein or the RuvA/RuvB protein complex can promote ATP-dependent branch migration of Holliday junctions. Much less is known about the processing of Holliday junctions in eukaryotes. Here, we identify RecQL1 as a predominant ATP-dependent, HJ branch migrator present in human nuclear extracts. A reduction in the level of RecQL1 induced by RNA interference in HeLa cells leads to an increase in sister chromatid exchange. We propose that RecQL1 is involved in the processing of Holliday junctions in human cells

Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort.

OBJECTIVES: To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases. SETTING: Suspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected. PARTICIPANTS: Two expert cardiologists reviewed data for 293 referred cases: 130 were included. Inclusion criteria were new onset or exacerbation of pre-existing ventricular arrhythmias, QTc >500 ms, QTc >450 ms (men) or >470 ms (women) with cardiac syncope, all secondary to drug administration. Exclusion criteria were acute ischaemia and ischaemic polymorphic ventricular tachycardia at presentation, structural heart disease, consent withdrawn or deceased prior to study. Descriptive analysis of Caucasian cases (95% of included cases, n=124) and culpable drug exposures was performed. RESULTS: Of the 124 Caucasian cases, 95 (77%) were QTc interval prolongation-related; mean age was 62 years (SD 15), and 63% were female. Cardiovascular comorbidities included hypertension (53%) and patient-reported 'heart rhythm problems' (73%). Family history of sudden death (36%) and hypokalaemia at presentation (27%) were common. 165 culpable drug exposures were reported, including antiarrhythmics (42%), of which amiodarone and flecainide were the most common. Sotalol, a beta-blocking agent with antiarrhythmic activity, was also common (15%). 26% reported multiple drugs, of which 84% reported at least one cytochrome (CYP) P450 inhibitor. Potential pharmacodynamics interactions identified were mainly QT prolongation (59%). CONCLUSIONS: Antiarrhythmics, non-cardiac drugs and drug combinations were found to be culpable in a large cohort of 124 clinically validated proarrhythmia cases. Potential clinical factors that may warn the prescriber of potential proarrhythmia include older women, underlying cardiovascular comorbidity, family history of sudden death and hypokalaemia

Prioritizing Metro Service Quality Attributes to Enhance Commuter Experience: TOPSIS Ranking and Importance Satisfaction Analysis methods

A metro infrastructure, facility and service quality investigation based on commuter perception was conducted in this study to explore and prioritize the key attributes influencing overall metro service quality in typical Indian context. Based on the critical state of the art review, 12 key attributes were identified and they were accommodated in a paper based questionnaire to elicit commuter perception of importance and satisfaction by using a five point Likert scale. Subsequently, TOPSIS, an extensively adopted Multi attribute decision making technique, was carried out to rank the attributes with respect to perceived importance and satisfaction. Then an importance satisfaction analysis (ISA) was conducted to further classify the attributes in four quadrants based on their perceived degree of importance and satisfaction using an ISA matrix. Finally, the derived results from the TOPSIS and ISA analysis were combined and compared to obtain a prioritized set of attributes requiring intervention for better metro service quality in Indian context. Results of this study clearly indicated the relative strengths and weaknesses of each metro service/infrastructure specific attribute and presented the probable role of metro authorities for each of them. Attributes such as, Metro fare, Connection to metro and Metro frequency were observed to be the most important but were not performing satisfactorily, indicating that more emphasis is required on these attributes for improving the overall quality of travel by metro rail in Indian context. Hence, this methodology would be instrumental to detect a set of priority areas of improvement in metro rail service, which could contribute to retain the existing commuters and attract new metro users

The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

All enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity

Re-evaluation of the phylogeny based on mitochondrial cytochrome b gene in the house shrew, Suncus murinus-S. montanus species complex, with special reference to Yemen and Myanmar populations

The house shrew (Suncus murinus-S. montanus species complex) is considered to have been unintentionally introduced by humans from their original range to other regions around the　Indian Ocean and neighboring seas, but this has yet not fully been investigated. A phylogenetic tree and haplotype network were reconstructed　based on the mitochondrial cytochrome b gene nucleotide sequences (1140 bp) of 179 individuals of house shrews from 46 localities in southern East Asia, Southeast Asia, West Asia, and islands in the western Indian Ocean. There was small genetic variation among shrews in Japan (Okinawa), southern China, Vietnam, and insular Southeast Asia. However, the shrew populations in Myanmar and Sri Lanka showed of a variety of different haplotypes. In the region of the western Indian Ocean, three interesting findings were obtained. First, the shrews on Zanzibar Island (Tanzania) shared same haplotype as those in southwestern Iran, and the haplotype was close to a group in Pakistan, despite these three regions being distantly located. Second, inferring from the haplotype network, it was suggests that the shrews in Yemen might have derived from Madagascar/Comoros populations. Third, the shrews on Réunion Island were genetically different from other populations around the western Indian Ocean but closer to Malaysia and Myanmar populations. Thus, the present study demonstrates that there have been dynamic immigration/emigration processes in the house shrews, especially for those around the western Indian Ocean. In addition, the house shrews in Myanmar may include several different species

A novel role for Lyl1 in primitive erythropoiesis

© 2018. Published by The Company of Biologists Ltd. Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq data of early embryos showed that primitive erythroid cells express both Scl and Lyl1. Therefore, to determine whether Lyl1 can function in primitive erythropoiesis, we crossed conditional Scl knockout mice with mice expressing a Cre recombinase under the control of the Epo receptor, active in erythroid progenitors. Embryos with 20% expression of Scl from E9.5 survived to adulthood. However, mice with reduced expression of Scl and absence of Lyl1 (double knockout; DKO) died at E10.5 because of progressive loss of erythropoiesis. Gene expression profiling of DKO yolk sacs revealed loss of Gata1 and many of the known target genes of the SCL-GATA1 complex. ChIP-seq analyses in a human erythroleukemia cell line showed that LYL1 exclusively bound a small subset of SCL targets including GATA1. Together, these data show for the first time that Lyl1 can maintain primitive erythropoiesis