Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in <i>Caenorhabditis elegans</i>

The nematode cuticle is a protective collagenous extracellular matrix that is modified, cross-linked, and processed by a number of key enzymes. This Ecdysozoan-specific structure is synthesized repeatedly and allows growth and development in a linked degradative and biosynthetic process known as molting. A targeted RNA interference screen using a cuticle collagen marker has been employed to identify components of the cuticle biosynthetic pathway. We have characterized an essential peroxidase, MoLT-7 (MLT-7), that is responsible for proper cuticle molting and re-synthesis. MLT-7 is an active, inhibitable peroxidase that is expressed in the cuticle-synthesizing hypodermis coincident with each larval molt. mlt-7 mutants show a range of body morphology defects, most notably molt, dumpy, and early larval stage arrest phenotypes that can all be complemented with a wild type copy of mlt-7. The cuticles of these mutants lacks di-tyrosine cross-links, becomes permeable to dye and accessible to tyrosine iodination, and have aberrant collagen protein expression patterns. Overexpression of MLT-7 causes mutant phenotypes further supporting its proposed enzymatic role. In combination with BLI-3, an H2O2-generating NADPH dual oxidase, MLT-7 is essential for post-embryonic development. Disruption of mlt-7, and particularly bli-3, via RNA interference also causes dramatic changes to the in vivo cross-linking patterns of the cuticle collagens DPY-13 and COL-12. This points toward a functionally cooperative relationship for these two hypodermally expressed proteins that is essential for collagen cross-linking and proper extracellular matrix formation

The Political Economy of Myanmar's Transition

This is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the JOURNAL OF CONTEMPORARY ASIA, 07 Feb 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/00472336.2013.764143.Since holding elections in 2010, Myanmar has transitioned from a direct military dictatorship to a formally democratic system and has embarked on a period of rapid economic reform. After two decades of military rule, the pace of change has startled almost everyone and led to a great deal of cautious optimism. To make sense of the transition and assess the case for optimism, this article explores the political economy of Myanmar's dual transition from state socialism to capitalism and from dictatorship to democracy. It analyses changes within Myanmar society from a critical political economy perspective in order to both situate these developments within broader regional trends and to evaluate the country's current trajectory. In particular, the emergence of state-mediated capitalism and politico-business complexes in Myanmar's borderlands are emphasised. These dynamics, which have empowered a narrow oligarchy, are less likely to be undone by the reform process than to fundamentally shape the contours of reform. Consequently, Myanmar's future may not be unlike those of other Southeast Asian states that have experienced similar developmental trajectories

Health-state utilities in a prisoner population : a cross-sectional survey

Background: Health-state utilities for prisoners have not been described. Methods: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. Results: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. Conclusion: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs

Qualitative methods: are you enchanted or are you alienated?

Copyright © 2007 SAGE Publications. Author's draft version; post-print. Final version published by Sage available on Sage Journals Online http://online.sagepub.com/Since the last report on qualitative methods (Crang, 2005), many of the practical procedures of doing qualitative research remain the same. Human geographers continue to study texts, to conduct interviews, to convene focus groups and to engage in ethnography. Indeed, it is hard, though perhaps not impossible, to imagine what a radically new form of qualitative research practice might look like. So, for the time being, this suite of methods remains the backbone of qualitative research in human geography. Yet we would like to contend that, while these activities continue as before, there are changes in the way they are being conceived and carried out, and related to this there are transformations in the way these methods are being used to make claims to understanding and intervening in the world. In the first of our three reports, it is this link between qualitative methodologies and interpretative strategies we would like to reflect on

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

Explore Transplant at Home: A randomized control trial of an educational intervention to increase transplant knowledge for Black and White socioeconomically disadvantaged dialysis patients

BackgroundCompared to others, dialysis patients who are socioeconomically disadvantaged or Black are less likely to receive education about deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) before they reach transplant centers, often due to limited availability of transplant education within dialysis centers. Since these patients are often less knowledgeable or ready to pursue transplant, educational content must be simplified, made culturally sensitive, and presented gradually across multiple sessions to increase learning and honor where they are in their decision-making about transplant. The Explore Transplant at Home (ETH) program was developed to help patients learn more about DDKT and LDKT at home, with and without telephone conversations with an educator.Methods and study designIn this randomized controlled trial (RCT), 540 low-income Black and White dialysis patients with household incomes at or below 250&nbsp;% of the federal poverty line, some of whom receive financial assistance from the Missouri Kidney Program, will be randomly assigned to one of three education conditions: (1) standard-of-care transplant education provided by the dialysis center, (2) patient-guided ETH (ETH-PG), and (3) health educator-guided ETH (ETH-EG). Patients in the standard-of-care condition will only receive education provided in their dialysis centers. Those in the two ETH conditions will receive four video and print modules delivered over an 8 month period by mail, with the option of receiving supplementary text messages weekly. In addition, patients in the ETH-EG condition will participate in multiple telephonic educational sessions with a health educator. Changes in transplant knowledge, decisional balance, self-efficacy, and informed decision making will be captured with surveys administered before and after the ETH education.DiscussionAt the conclusion of this RCT, we will have determined whether an education program administered to socioeconomically disadvantaged dialysis patients, over several months directly in their homes, can help more individuals learn about the options of DDKT and LDKT. We also will be able to examine the efficacy of different educational delivery approaches to further understand whether the addition of a telephone educator is necessary for increasing transplant knowledge.Trial registrationClinicalTrials.gov, NCT02268682

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

Your Path to Transplant: A randomized controlled trial of a tailored computer education intervention to increase living donor kidney transplant

Background: Because of the deceased donor organ shortage, more kidney patients are considering whether to receive kidneys from family and friends, a process called living donor kidney transplantation (LDKT). Although Blacks and Hispanics are 3.4 and 1.5 times more likely, respectively, to develop end stage renal disease (ESRD) than Whites, they are less likely to receive LDKTs. To address this disparity, a new randomized controlled trial (RCT) will assess whether Black, Hispanic, and White transplant patients’ knowledge, readiness to pursue LDKT, and receipt of LDKTs can be increased when they participate in the Your Path to Transplant (YPT) computer-tailored intervention. Methods/Design: Nine hundred Black, Hispanic, and White ESRD patients presenting for transplant evaluation at University of California, Los Angeles Kidney and Pancreas Transplant Program (UCLA-KPTP) will be randomly assigned to one of two education conditions, YPT or Usual Care Control Education (UC). As they undergo transplant evaluation, patients in the YPT condition will receive individually-tailored telephonic coaching sessions, feedback reports, video and print transplant education resources, and assistance with reducing any known socioeconomic barriers to LDKT. Patients receiving UC will only receive transplant education provided by UCLA-KPTP. Changes in transplant knowledge, readiness, pros and cons, and self-efficacy to pursue LDKT will be assessed prior to presenting at the transplant center (baseline), during transplant evaluation, and 4- and 8-months post-baseline, while completion of transplant evaluation and receipt of LDKTs will be assessed at 18-months post-baseline. The RCT will determine, compared to UC, whether Black, Hispanic, and White patients receiving YPT increase in their readiness to pursue LDKT and transplant knowledge, and become more likely to complete transplant medical evaluation and pursue LDKT. It will also examine how known patient, family, and healthcare system barriers to LDKT act alone and in combination with YPT to affect patients’ transplant decision-making and behavior. Statistical analyses will be performed under an intent-to-treat approach. Discussion: At the conclusion of the study, we will have assessed the effectiveness of an innovative and cost-effective YPT intervention that could be utilized to tailor LDKT discussion and education based on the needs of individual patients of different races in many healthcare settings. Trial Registration: ClinicalTrials.gov, number NCT02181114

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho