The Current State of Climate Change Perceptions and Policies in Myanmar: 2014 Report

This report was constructed to assess the current perceptions and policies regarding climate change in Myanmar. It is comprised of a country report outlining current policies relating to climate change, as well as results from two stakeholder perception surveys conducted at the local and national level in Myanmar. The stakeholder perception survey was administered to 33 local stakeholders and 12 national stakeholders from government organizations, farmers’ groups, universities, and research institutes. Results indicate that the primary concern regarding climate change is mostly concentrated on rainfall trends, such as drought and flooding. In addition, local stakeholders have concerns over heat stress, whereas national stakeholders are less concerned with the issue. Only 11 local stakeholders report that their institution currently has a division or staff member working on climate change issues. Seven of 12 national stakeholders reported that their institutions did have a division or staff member working on climate change issues

Single stranded fully Modified-Phosphorothioate oligonucleotides can induce structured nuclear inclusions, alter nuclear protein localization and disturb the transcriptome In Vitro

Oligonucleotides and nucleic acid analogues that alter gene expression are now showing therapeutic promise in human disease. Whilst the modification of synthetic nucleic acids to protect against nuclease degradation and to influence drug function is common practice, such modifications may also confer unexpected physicochemical and biological properties. Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence. Recently, the non-antisense or other off-target effects of 2′ O- fully modified phosphorothioate linkage oligonucleotides are becoming better understood. Here, we report chemistry-specific effects of oligonucleotides composed of modified or unmodified bases, with phosphorothioate linkages, on subnuclear organelles and show altered distribution of nuclear proteins, the appearance of highly stable and strikingly structured nuclear inclusions, and disturbed RNA processing in primary human fibroblasts and other cultured cells. Phosphodiester, phosphorodiamidate morpholino oligomers, and annealed complimentary phosphorothioate oligomer duplexes elicited no such consequences. Disruption of subnuclear structures and proteins elicit severe phenotypic disturbances, revealed by transcriptomic analysis of transfected fibroblasts exhibiting such disruption. Our data add to the growing body of evidence of off-target effects of some phosphorothioate nucleic acid drugs in primary cells and suggest alternative approaches to mitigate these effects

Matching action to need: an analysis of Global Burden of Disease 2017 and population health data to focus adolescent health policy and actions in Myanmar

Background: Myanmar is a country undergoing rapid transitions in health. Its national strategic policy for young people's health is being revised but there is a paucity of population data to inform local priorities and needs. Objective: In this paper we describe a comprehensive profile of adolescent health in Myanmar to focus policy and health actions. Methods: We used available primary data, and modelled estimates from the GBD 2017, to describe health outcomes (mortality and morbidity), health risks and determinants for adolescents in Myanmar between 1990-2017. A governance group of key stakeholders guided the framing of the study, interpretation of findings, and recommendations. Results: Overall health has improved for adolescents in Myanmar since 1990, however adolescent mortality remains high, particularly so for older adolescent males; all-cause mortality rate for 10-24 years was 70 per 100,000 for females and 149 per 100,000 for males (16,095 adolescent deaths in 2017). Overall, the dominant health problems were injuries for males and non-communicable disease for females in a context of ongoing burden of communicable and nutritional diseases for both sexes, and reproductive health needs for females. Health risks relating to undernutrition (thinness and anaemia) remain prevalent, with other health risks (overweight, binge alcohol use, and substance use) relatively low by global and regional standards but increasing. Gains have been made in social determinants such as adolescent fertility and modern contraception use; however, advances have been more limited in secondary education completion and engagement in employment and post education training. Conclusions: These results highlight the need to focus current efforts on addressing disease and mortality experienced by adolescents in Myanmar, with a specific focus on injury, mental health and non-communicable disease.Karly I. Cini, Phone Myint Win, Zay Yar Swe, Kyu Kyu Than, Thin Mar Win ... Peter S. Azzopardi ... et al

Biomarkers of Multiple Sclerosis

The search for an ideal multiple sclerosis biomarker with good diagnostic value, prognostic reference and an impact on clinical outcome has yet to be realized and is still ongoing. The aim of this review is to establish an overview of the frequent biomarkers for multiple sclerosis that exist to date. The review summarizes the results obtained from electronic databases, as well as thorough manual searches. In this review the sources and methods of biomarkers extraction are described; in addition to the description of each biomarker, determination of the prognostic, diagnostic, disease monitoring and treatment response values besides clinical impact they might possess. We divided the biomarkers into three categories according to the achievement method: laboratory markers, genetic-immunogenetic markers and imaging markers. We have found two biomarkers at the time being considered the gold standard for MS diagnostics. Unfortunately, there does not exist a single solitary marker being able to present reliable diagnostic value, prognostic value, high sensitivity and specificity as well as clinical impact. We need more studies to find the best biomarker for MS.publishersversionPeer reviewe

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe