The state of indoor air quality in Pakistan—a review

Background and purpose: In Pakistan, almost 70% of the population lives in rural areas. Ninety-four percent of households in rural areas and 58% in urban areas depend on biomass fuels (wood, dung, and agricultural waste). These solid fuels have poor combustion efficiency. Due to incomplete combustion of the biomass fuels, the resulting smoke contains a range of health-deteriorating substances that, at varying concentrations, can pose a serious threat to human health. Indoor air pollution accounts for 28,000 deaths a year and 40 million cases of acute respiratory illness. It places a significant economic burden on Pakistan with an annual cost of 1% of GDP. Despite the mounting evidence of an association between indoor air pollution and ill health, policy makers have paid little attention to it. This review analyzes the existing information on levels of indoor air pollution in Pakistan and suggests suitable intervention methods. Methods: This review is focused on studies of indoor air pollution, due to biomass fuels, in Pakistan published in both scientific journals and by the Government and international organizations. In addition, the importance of environmental tobacco smoke as an indoor pollutant is highlighted. Results: Unlike many other developing countries, there are no long-term studies on the levels of indoor air pollution. The limited studies that have been undertaken indicate that indoor air pollution should be a public health concern. High levels of particulate matter and carbon monoxide have been reported, and generally, women and children are subject to the maximum exposure. There have been a few interventions, with improved stoves, in some areas since 1990. However, the effectiveness of these interventions has not been fully evaluated. Conclusion: Indoor air pollution has a significant impact on the health of the population in Pakistan. The use of biomass fuel as an energy source is the biggest contributor to poor indoor air quality followed by smoking. In order to arrest the increasing levels of indoor pollution, there is a dire need to recognize it as a major health hazard and formulate a national policy to combat it. An integrated effort, with involvement of all stakeholders, could yield promising results. A countrywide public awareness campaign, on the association of indoor air pollution with ill health, followed by practical intervention would be an appropriate approach. Due to the current socioeconomic conditions in the country, development and adoption of improved cooking stoves for the population at large would be the most suitable choice. However, the potential of biogas as a fuel should be explored further, and modern fuels (natural gas and LPG) need to be accessible and economical. Smoking in closed public spaces should be banned, and knowledge of the effect of smoking on indoor air quality needs to be quantified. © 2010 Springer-Verlag

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease

Urban coral reefs: Degradation and resilience of hard coral assemblages in coastal cities of East and Southeast Asia

© 2018 The Author(s) Given predicted increases in urbanization in tropical and subtropical regions, understanding the processes shaping urban coral reefs may be essential for anticipating future conservation challenges. We used a case study approach to identify unifying patterns of urban coral reefs and clarify the effects of urbanization on hard coral assemblages. Data were compiled from 11 cities throughout East and Southeast Asia, with particular focus on Singapore, Jakarta, Hong Kong, and Naha (Okinawa). Our review highlights several key characteristics of urban coral reefs, including “reef compression” (a decline in bathymetric range with increasing turbidity and decreasing water clarity over time and relative to shore), dominance by domed coral growth forms and low reef complexity, variable city-specific inshore-offshore gradients, early declines in coral cover with recent fluctuating periods of acute impacts and rapid recovery, and colonization of urban infrastructure by hard corals. We present hypotheses for urban reef community dynamics and discuss potential of ecological engineering for corals in urban areas

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

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Reflections on the early invasive clinical cardiac electrophysiology era through fifty manuscripts: 1967-1992

In 1967, researchers in The Netherlands and France independently reported a new technique, later called programmed electrical stimulation. The ability to reproducibly initiate and terminate arrhythmias heralded the beginning of invasive clinical cardiac electrophysiology as a medical discipline. Over the next fifty years, insights into the pathophysiologic basis of arrhythmias would transform the field into an interventional specialty with a tremendous armamentarium of procedures. In 2015, the variety and complexity of these procedures were major reasons that led to the recommendation for an increase in the training period from one year to two years. The purpose of this manuscript is to present fifty manuscripts from the early invasive clinical cardiac electrophysiology era, between 1967 and 1992, to serve as an educational resource for current and future electrophysiologists. It is our hope that reflection on the transition from a predominantly noninvasive discipline to one where procedures are commonly utilized will lead to more thoughtful patient care today and to inspiration for innovation tomorrow. In the words of the late Dr. Mark E. Josephson, It is only by getting back to the basics that the field of electrophysiology will continue to grow instead of stagnate