Searching for Synthetic Opioid Rescue Agents: Identification of a Potent Opioid Agonist with Reduced Respiratory Depression.

While in the process of designing more effective synthetic opioid rescue agents, we serendipitously identified a new chemotype of potent synthetic opioid. Here, we report that conformational constraint of a piperazine ring converts a mu opioid receptor (MOR) antagonist into a potent MOR agonist. The prototype of the series, which we have termed atoxifent (), possesses potent in vitro agonist activity.

Chemical constituents from the heterotrophic marine microalgae sp. SC145 and their antimicrobial activities.

One new indol, -methoxymethyltryptophol (), one new phenolic, (2 )-2-(4-hydroxyphenyl)ethyl 2-hydroxy-3-phenylpropanoate () and fifteen known compounds () were isolated from the methanol extract of the fermentation of marine microalgae sp. SC145. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, quantum chemical calculation methods and by comparing their NMR data with those reported in the literature.

Aromatic hydrazides: A potential solution for Acinetobacter baumannii infections.

The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics against these infections have led to the urgent need for novel antibiotics. Acinetobacter baumannii is one of high-priority pathogens due to its ability to mount resistance to different classes of antibiotics. In an effort to provide novel agents in the fight against infections caused by A.

Stepwise Reduction of Mycophenolate Mofetil with Conversion to Everolimus for the Treatment of Active BKV in Kidney Transplant Recipients: A Single-Center Experience in Vietnam.

Background: No specific antiviral drug can effectively treat BKV reactivation after kidney transplantation. Thus, we evaluated stepwise-reduced immunosuppression to treat BKV reactivation. Methods: 341 kidney-transplant recipients were monitored for BKV infection (BKV-viremia, BKV-viruria).

Characterization and Optimization of Culture Conditions for sp. SC145 Isolated from Sand Cay (Son Ca) Island, Vietnam, and Antioxidative and Neuroprotective Activities of Its Polyunsaturated Fatty Acid Mixture.

is a heterotrophic marine microalga that has potential industrial applications. The main objectives of this study were to isolate an strain from Sand Cay (Son Ca) Island, Vietnam, optimize its culture conditions, determine its nutritional composition, extract polyunsaturated fatty acids (PUFAs) in the free (FFA) and the alkyl ester (FAAE) forms, and evaluate the antioxidation and neuroprotection properties of the PUFAs. sp.

Undergraduate Medical Education Reform in Viet Nam for a Primary Health Care Workforce.

Strong primary health care (PHC) systems require a robust PHC workforce. Traditionally, medical education takes place in academic medical centres that favour subspecialty care rather than PHC settings. This may undervalue primary care as a career and contribute to a shortage of PHC workers.

Exposure to conflict and child health outcomes: evidence from a large multi-country study.

Background: Previous research has consistently found evidence of poor health outcomes among children living in conflict areas. However, the methodological focus of these studies has largely been on case studies, chart or registry reviews, qualitative studies, and single country studies. This reflects the need for a comprehensive multi-country analysis of the associations between conflicts and child health over a longer period.

Conflicts and son preference: Micro-level evidence from 58 countries.

Research on the association between armed conflict and son preference has largely been based on single-country studies, often presenting descriptive patterns. This paper empirically analyzes the association between conflict and son preference using a sample of more than 1.1 million individuals from 58 countries over the period 2003-2018.

Is There an Informal Employment Penalty in Food Security? Evidence from Rural Vietnam.

In this paper, we investigate the association between informal non-farm wage employment and household food security in rural Vietnam. The data for our analyses come from a nationally representative panel dataset of 1390 rural households from Vietnam Household Living Standards Survey. We conduct multivariate regression analysis using robust quantitative tools to show that informal employment is associated with a reduction in the consumption of nutritious foods.

Exposure to conflicts and the continuum of maternal healthcare: Analyses of pooled cross-sectional data for 452,192 women across 49 countries and 82 surveys.

Background: Violent conflicts are observed in many parts of the world and have profound impacts on the lives of exposed individuals. The limited evidence available from specific country or region contexts suggest that conflict exposure may reduce health service utilization and have adverse affects on health. This study focused on identifying the association between conflict exposure and continuum of care (CoC) services that are crucial for achieving improvements in reproductive, maternal, newborn, and child health and nutrition (RMNCHN).

Salience and Impact of Health Warning Label on Cigarette Packs in Vietnam: Findings From the Global Adult Tobacco Survey 2015.

Viet Nam is among the countries having highest rate of male smokers in the world. The country has joined the Global Tobacco Surveillance System since 2010. Under this system, two rounds of Global Adult Tobacco Survey (GATS) were conducted in 2010 and 2015.

The Internalized Homophobia Scale for Vietnamese Sexual Minority Women: Conceptualization, Factor Structure, Reliability, and Associations With Hypothesized Correlates.

We developed the first Vietnamese Internalized Homophobia (IH) scale for use with Vietnamese sexual minority women (SMW). Drawing from existing IH scales in the international literature and based on prior qualitative research about SMW in the Viet Nam context, the scale covers two domains: self-stigma (negative attitudes toward oneself as a sexual minority person) and sexual prejudice (negative attitudes toward homosexuality/same-sex relations in general). Scale items, including items borrowed from existing scales and items based on local expressions, were reviewed and confirmed by members of the target population.

Delays in the diagnosis and treatment of tuberculosis patients in Vietnam: a cross-sectional study.

Background: Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e.

Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly.

The synthesis of ribosomes in eukaryotic cells is a complex process involving many nonribosomal protein factors and snoRNAs. In general, the processes of rRNA transcription and ribosome assembly are treated as temporally or spatially distinct. Here, we describe the identification of a point mutation in the second largest subunit of RNA polymerase I near the active center of the enzyme that results in an elongation-defective enzyme in the yeast Saccharomyces cerevisiae.

Expression of rRNA genes and nucleolus formation at ectopic chromosomal sites in the yeast Saccharomyces cerevisiae.

We constructed yeast strains in which rRNA gene repeats are integrated at ectopic sites in the presence or absence of the native nucleolus. At all three ectopic sites analyzed, near centromere CEN5, near the telomere of chromosome VI-R, and in middle of chromosome V-R (mid-V-R), a functional nucleolus was formed, and no difference in the expression of rRNA genes was observed. When two ribosomal DNA (rDNA) arrays are present, one native and the other ectopic, there is codominance in polymerase I (Pol I) transcription.

Role of histone deacetylase Rpd3 in regulating rRNA gene transcription and nucleolar structure in yeast.

The 35S rRNA genes at the RDN1 locus in Saccharomyces cerevisiae can be transcribed by RNA polymerase (Pol) II in addition to Pol I, but Pol II transcription is usually silenced. The deletion of RRN9 encoding an essential subunit of the Pol I transcription factor, upstream activation factor, is known to abolish Pol I transcription and derepress Pol II transcription of rRNA genes, giving rise to polymerase switched (PSW) variants. We found that deletion of histone deacetylase gene RPD3 inhibits the appearance of PSW variants in rrn9 deletion mutants.

Histones are required for transcription of yeast rRNA genes by RNA polymerase I.

Nucleosomes and their histone components have generally been recognized to act negatively on transcription. However, purified upstream activating factor (UAF), a transcription initiation factor required for RNA polymerase (Pol) I transcription in Saccharomyces cerevisiae, contains histones H3 and H4 and four nonhistone protein subunits. Other studies have shown that histones H3 and H4 are associated with actively transcribed rRNA genes.

SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast.

It is known that mutations in gene SIR2 increase and those in FOB1 decrease recombination within rDNA repeats as assayed by marker loss or extrachromosomal rDNA circle formation. SIR2-dependent chromatin structures have been thought to inhibit access and/or function of recombination machinery in rDNA. We measured the frequency of FOB1-dependent arrest of replication forks, consequent DNA double-strand breaks, and formation of DNA molecules with Holliday junction structures, and found no significant difference between sir2Delta and SIR2 strains.

Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to the promoter but does not participate in alteration of the number of active genes.

Yeast cells entering into stationary phase decrease rRNA synthesis rate by decreasing both the number of active genes and the transcription rate of individual active genes. Using chromatin immunoprecipitation assays, we found that the association of RNA polymerase I with the promoter and the coding region of rDNA is decreased in stationary phase, but association of transcription factor UAF with the promoter is unchanged. Similar changes were also observed when growing cells were treated with rapamycin, which is known to inhibit the Tor signaling system.

Silencing in yeast rDNA chromatin: reciprocal relationship in gene expression between RNA polymerase I and II.

About half of approximately 150 rRNA genes are transcriptionally active in Saccharomyces cerevisiae. Chromatin structures in the inactive, and not the active, copies were previously thought to silence both rRNA genes and reporter Pol II genes. Contrary to this belief, we found that silencing of reporters is much stronger in a mutant with approximately 25 rDNA copies, all of which are transcriptionally active.