Strengthening Health Research and Ethics Systems in Timor-Leste.

Introduction: Meaningful health research should lead to evidence-based decision-making that can be translated into policy and practice. Every country needs to have a well-functioning and resourced ethics review and clearance system to ensure health and medical research is conducted in line with ethical standards, preventing harm to research participants, and contributing to better health outcomes and national priorities. The purpose of this study is to describe the origins of the system for managing health research and ethics in Timor-Leste and how it has evolved over time; to identify the strengths and limitations of the current system; and to recommend areas for improvement. Materials and Methods: A narrative review of the literature (published papers, gray literature, and unpublished data) was conducted alongside key informant interviews with 15 Ministry of Health (MOH) policymakers and National Institute of Health staff between October 2020 and March 2021. Results: The system for managing health research and ethics in Timor-Leste has remained largely the same since it was first established in 2009, with some adaptations to cope with a progressively increasing workload. Main findings include: the Department of Research and Studies (DRS) oversees complex ethics approval process in addition to other responsibilities; the DRS lacks the legal authority, policies, and procedures to help implement its full range of functions and responsibilities; national research priorities should be identified; MOH experiences difficulties in securing funding to support health research; training in health research, ethics and governance is an important priority for DRS. Conclusion: It is timely and important to invest in strengthening key components of health research and ethics systems in Timor-Leste. Despite limited resources, improvements can be achieved in key areas with focused assistance and collaboration with local, national, and international partners.

Sex-specific epigenetic gene activation profiles are differentially modulated in human placentas affected by intrauterine growth restriction.

BACKGROUND: The purpose of this study was to investigate the sex specific expression of histone protein modifications responsible for rapid gene expression in IUGR placentas. PATIENTS AND METHODS: We screened for fetal sex-specific expression of the histone proteins H3K4me3 and H3K9ac in 23 IUGR and 40 control placentas via immunohistochemistry. The trophoblast-like cell line BeWo was used in order to analyze a potential effect of stimulation with prednisolone on H3K4me3 and H3K9ac in vitro. Calculating regression models with additional adjustment for potential confounders were used. RESULTS: A significantly decreased level of H3K4me3 was detectable in female syncytiotrophoblasts, whereas H3K9ac was reduced predominantly in male extravillous throphoblast (EVT). No association to the gestational age existed. CONCLUSION: Our data showed a reduced expression of the histone proteins H3K4me3 (female) and H3K9ac (male) in IUGR, furthermore elevated cortisol levels may lead to a sex-specific down-regulation of histone proteins in IUGR placentas.

Glucocorticoid receptors α and ß are modulated sex specifically in human placentas of intrauterine growth restriction (IUGR).

PURPOSE: The objective of this study was to analyze the expression of the glucocorticoid receptor (GR) subtypes GRα and GRß in placentas affected by intrauterine growth restriction (IUGR). METHODS: We analyzed the sex-specific placental expression of GRα and GRß in 23 IUGR and 40 control placentas using immunohistochemistry and immunofluorescence. The GR gene, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1), mRNA production in trophoblast-like cell line BeWo after stimulation with prednisolone was analyzed using quantitative polymerase chain reaction (qPCR) and on the protein level using western blot analysis. RESULTS: GR subtypes showed a sex-specific upregulation in placentas from IUGR compared to control placentas. An increased expression of GRα was detectable in female placental tissue, whereas GRß was increased in males. CONCLUSION: Our data support previous findings suggesting that the glucocorticoid metabolism plays a role in the pathophysiology of IUGR. Furthermore, the data suggest that the underlying molecular mechanisms differ between male and female cases.

Thermodynamic Analysis of Isomerization Equilibria of Chlorotoluenes and Dichlorobenzenes in a Biphasic Reaction Systems Containing Highly Acidic Chloroaluminate Melts.

Thermodynamics and kinetics of the isomerization of chlorotoluenes and dichlorobenzene to the technically desired meta-isomers have been studied in the presence of highly acidic chloroaluminate melts with alkali metal and organic imidazolium cations. Enthalpies of four isomerization processes in reacting systems of chlorotoluenes and dichlorobenzene were obtained from temperature dependencies of the corresponding equilibrium constants in the liquid phase. Experimental reaction enthalpies, enthalpies of vaporization, and absolute vapor pressures of chlorotoluenes and dichlorobenzene have been used for the validation of quantum-chemical methods to predict thermodynamic functions of the four reactions under study successfully. Values of the standard Gibbs energies of formation, standard enthalpies and entropies of formation of chlorotoluenes and dichlorobenzenes in the liquid and in the gas phase have been derived. These values allow optimization of liquid-liquid biphasic manufacturing technologies for halogen-substituted benzenes.