Public Health and Air Pollution in Asia (PAPA): A Multicity Study of Short-Term Effects of Air Pollution on Mortality

Background and Objectives: Although the deleterious effects of air pollution from fossil fuel combustion have been demonstrated in many Western nations, fewer studies have been conducted in Asia. The Public Health and Air Pollution in Asia (PAPA) project assessed the effects of short-term exposure to air pollution on daily mortality in Bangkok, Thailand, and in three cities in China: Hong Kong, Shanghai, and Wuhan. Methods: Poisson regression models incorporating natural spline smoothing functions were used to adjust for seasonality and other time-varying covariates that might confound the association between air pollution and mortality. Effect estimates were determined for each city and then for the cities combined using a random effects method. Results: In individual cities, associations were detected between most of the pollutants [nitrogen dioxide, sulfur dioxide, particulate matter ≤ 10 μm in aerodynamic diameter (PM 10), and ozone] and most health outcomes under study (i.e., all natural-cause, cardiovascular, and respiratory mortality). The city-combined effects of the four pollutants tended to be equal or greater than those identified in studies conducted in Western industrial nations. In addition, residents of Asian cities are likely to have higher exposures to air pollution than those in Western industrial nations because they spend more time outdoors and less time in air conditioning. Conclusions: Although the social and environmental conditions may be quite different, it is reasonable apply estimates derived from previous health effect of air pollution studies in the West to Asia.published_or_final_versio

Identification of Genes Directly Involved in Shell Formation and Their Functions in Pearl Oyster, Pinctada fucata

Mollusk shell formation is a fascinating aspect of biomineralization research. Shell matrix proteins play crucial roles in the control of calcium carbonate crystallization during shell formation in the pearl oyster, Pinctada fucata. Characterization of biomineralization-related genes during larval development could enhance our understanding of shell formation. Genes involved in shell biomineralization were isolated by constructing three suppression subtractive hybridization (SSH) libraries that represented genes expressed at key points during larval shell formation. A total of 2,923 ESTs from these libraries were sequenced and gave 990 unigenes. Unigenes coding for secreted proteins and proteins with tandem-arranged repeat units were screened in the three SSH libraries. A set of sequences coding for genes involved in shell formation was obtained. RT-PCR and in situ hybridization assays were carried out on five genes to investigate their spatial expression in several tissues, especially the mantle tissue. They all showed a different expression pattern from known biomineralization-related genes. Inhibition of the five genes by RNA interference resulted in different defects of the nacreous layer, indicating that they all were involved in aragonite crystallization. Intriguingly, one gene (UD_Cluster94.seq.Singlet1) was restricted to the ‘aragonitic line’. The current data has yielded for the first time, to our knowledge, a suite of biomineralization-related genes active during the developmental stages of P.fucata, five of which were responsible for nacreous layer formation. This provides a useful starting point for isolating new genes involved in shell formation. The effects of genes on the formation of the ‘aragonitic line’, and other areas of the nacreous layer, suggests a different control mechanism for aragonite crystallization initiation from that of mature aragonite growth

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Amelioration of hyperglycemia-induced mitochondrial ROS generation of single pancreatic islet β-cells of obese/diabetic mice by chronic N-Acetyl-L-Cysteine

This journal issue contain abstracts of the 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine 2009Abstracts for Posters: no. P12BACKGROUND: Mitochondria are the principal source of reactive oxygen species (ROS) in pancreatic islets β-cells and impairment of mitochondrial functions is intrinsically related with diabetes mellitus. Hyperglycemiainduced ROS production by mitochondria is an important aspect in β-cell glucose toxicity. However, most previous studies were performed in either normal islets/single β-cells or insulinoma cells which were bathed in high glucose medium which could not mimic the pathophysiological conditions. OBJECTIVES: To compare and measure hyperglycemia-induced mitochondria ROS generation of primary pancreatic islet β-cells of obese/diabetic (+db/+db) and lean/control (+db/+m) mice, and the effects (acute and chronic) of N-acetyl-L-cysteine (NAC) on ROS generation. METHODS: Collagenase-dissociated single pancreatic islet β-cells of C57BL/KsJ obese/diabetic (+db/+db) mice which exhibit phenotypes of the human T2DM were harvested, and the effects (acute, 10 min; chronic, 24 h) of NAC (20 mM) on high glucose-induced mitochondrial ROS generation were evaluated. Mitochondrial ROS levels were estimated by MitoTracker Red (reduced form) (a selective fluorescence probe for mitochondrial ROS measurement) using con-focal microscope. RESULTS: A trend of, but a non-significant, higher resting/basal ROS level was observed in single pancreatic β-cells of +db/+db mice compared to +db/+m mice. High glucose (15 mM) application gradually caused an increase in ROS levels in single pancreatic β-cells of +db/+db mice whereas no apparent change was observed in +db/+m mice. Chronic (24 h), but not acute (10 min), treatments with NAC (20 mM) ameliorated high-glucose induced ROS generation in single pancreatic β-cells of +db/+db mice. CONCLUSIONS: Hyperglycemia elicited mitochondrial ROS generation only in single pancreatic β-cells of +db/+db mice. Chronic NAC (a well known anti-oxidant) pre-treatment eradicated high glucose-induced ROS generation. Current study is underway to elucidate the underlying mechanism(s) involved in the differential effects of high glucose on ROS generation as well as the identification of the particular mitochondrial ROS generating system.link_to_OA_fulltex

Distinct effects of simvastatin on cytosolic Ca2+ changes and Ca2+: sensing receptor expression of isolated pancreatic islets ß cells of obese/diabetic mice

Abstracts for Posters: no. P30link_to_OA_fulltex