Upper respiratory symptoms worsen over time and relate to clinical phenotype in COPD.

Copyright © 2015 by the American Thoracic Society.Rationale: How nasal symptoms in patients with chronic obstructive pulmonary disease (COPD) change over time and resolve during naturally occurring exacerbations has not been described previously. Objectives: To evaluate the evolution and impact of upper airway symptoms in a well-defined COPD cohort when stable and at exacerbation. Methods: Patients in the LondonCOPDcohortwere asked about the presence of nasal symptoms (nasal discharge, sneezing, postnasal drip, blocked nose, and anosmia) over an 8-year period (2005-2013) every 3 months at routine clinic visits while in a stable state and daily during exacerbations with the use of diary cards. Data were prospectively collected, and, in a subgroup of patients,COPDAssessment Test scores and human rhinovirus identification by polymerase chain reaction were available. Patients were also defined as having infrequent or frequent exacerbations (<2 or ≥2 exacerbations/yr, respectively). Measurements and Main Results: At an aggregate of 4,368 visits, 209 patients with COPD were asked about their nasal symptoms. At 2,033 visits when the patients were stable, the odds ratio (OR) for nasal discharge increased by 1.32% per year (95% confidence interval [CI], 1.19-1.45; P<0.001); the OR for sneezing increased by 1.16%(95%CI, 1.05-1.29;P = 0.005); theORfor postnasal drip increased by 1.18% (95% CI, 1.03-1.36; P=0.016); and theOR for anosmia increased by 1.19% (95% CI, 1.03-1.37; P = 0.015). At visits when the patients were having exacerbations, nasal discharge was present for 7 days and blocked nose, sneezing, and postnasal drip increased for just 3 days. Anosmia did not change. Nasal dischargewasmore likely inpatientswith frequent exacerbations (OR, 1.96; 95% CI, 1.17-3.28; P= 0.011), and COPD Assessment Test scores were higher by 1.06 units (95% CI, 0.32-1.80; P=0.005) when patients were stable and higher by 1.30 units (95% CI, 0.05-2.57; P= 0.042) during exacerbations. Conclusions: Upper airway symptoms increase over time in patients with COPD and are related to the frequent exacerbation phenotype. These longitudinal changes may be due to increasing airway inflammation or to progression of COPD

Predicting Distribution of Aedes Aegypti and Culex Pipiens Complex, Potential Vectors of Rift Valley Fever Virus in Relation to Disease Epidemics in East Africa.

The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods

Tearing Out the Income Tax by the (Grass)Roots

Landscapes are increasingly fragmented, and conservation programs have started to look at network approaches for maintaining populations at a larger scale. We present an agent-based model of predator–prey dynamics where the agents (i.e. the individuals of either the predator or prey population) are able to move between different patches in a landscaped network. We then analyze population level and coexistence probability given node-centrality measures that characterize specific patches. We show that both predator and prey species benefit from living in globally well-connected patches (i.e. with high closeness centrality). However, the maximum number of prey species is reached, on average, at lower closeness centrality levels than for predator species. Hence, prey species benefit from constraints imposed on species movement in fragmented landscapes since they can reproduce with a lesser risk of predation, and their need for using anti-predatory strategies decreases.authorCount :

Rhabdomyolysis and Acute Renal Failure After Fire Ant Bites

We describe a 59-year-old patient who developed acute renal failure because of rhabdomyolysis after extensive red fire ant bites. This case illustrates a serious systemic reaction that may occur from fire ant bites. Consistent with the clinical presentation in rhabdomyolysis associated with non-traumatic causes, hyperkalemia, hypophosphatemia, hypocalcemia, and high anion gap acidosis were not observed in this patient. While local allergic reactions to fire ant bites are described in the literature, serious systemic complications with rhabdomyolysis and renal failure have not been previously reported. It is our effort to alert the medical community of the possibility of such a complication that can occur in the victims of fire ant bites

Cardiovascular risk estimated after 13 years of follow-up in a low-incidence Mediterranean region with high-prevalence of cardiovascular risk factors

<p>Abstract</p> <p>Background</p> <p>Murcia (south-east Spain) shows increased cardiovascular (CV) morbimortality as compared to other Spanish regions. Our objective was to assess the CV risk associated with major risk factors (RF) among adult population of Murcia.</p> <p>Methods</p> <p>A cohort of 2314 subjects (18-70 years) with full biochemical and questionnaire data was followed-up for 13 years. Incident cases of ischemic heart disease and stroke were identified by record linkage, individual questionnaires and revision of medical records. Relative risks were obtained by multivariate Cox regression stratified by age and sex, and ischemic risk attributable to CVRF was calculated.</p> <p>Results</p> <p>After more than 26276 person-years of follow-up, 57 incident ischemic events (77% men) and 37 stroke cases (62% men) were identified. Independent risk factors of ischemic heart disease (IHD) and all CV events combined, with RR ranging from 1.6 to 2.6, were total serum cholesterol ≥ 240 mg/dl (HR = 2.6, 95%CI:1.3-5.1), blood pressure levels ≥ 140/90 mmHg (HR = 2.6, 95%CI:1.4-4.8), ever tobacco smoking (HR = 2.2; 95%CI:1.1-4.5), and diabetes (HR = 2.0; 95%CI: 1.0-3.8). No increased CV risk was detected for known participants under treatment who showed cholesterol and blood pressure values below the clinical risk threshold. Smoking was significantly associated with stroke. For all events combined, the major risk factors were hypercholesterolemia, hypertension and ever use of tobacco. Despite its high prevalence, obesity was not associated to CV risk. Most of the IHD cases were attributable to smoking (44%), hypertension (38%) and hypercholesterolemia (26%).</p> <p>Conclusions</p> <p>In the Region of Murcia, smoking accounted for the largest proportion of cardiovascular risk, whereas hypertension displaced hypercholesterolemia as the second leading cause of CV disease. Our study deepens in our understanding of the cardiovascular epidemiology in Spanish areas of Mediterranean Europe with relatively high cardiovascular morbimortality, that are poorly represented by the available risk equations.</p

Genome-Wide Identification of Transcription Start Sites, Promoters and Transcription Factor Binding Sites in E. coli

Despite almost 40 years of molecular genetics research in Escherichia coli a major fraction of its Transcription Start Sites (TSSs) are still unknown, limiting therefore our understanding of the regulatory circuits that control gene expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is aimed at integrating the genetic regulatory network of E. coli K12 as an entirely bioinformatic project up till now. In this work, we extended its aims by generating experimental data at a genome scale on TSSs, promoters and regulatory regions. We implemented a modified 5′ RACE protocol and an unbiased High Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700 TSSs with high precision. From this collection, about 230 corresponded to previously reported TSSs, which helped us to benchmark both our methodologies and the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped belong to about 1000 different genes, many of them with no assigned function. We identified promoter sequences and type of σ factors that control the expression of about 80% of these genes. As expected, the housekeeping σ70 was the most common type of promoter, followed by σ38. The majority of the putative TSSs were located between 20 to 40 nucleotides from the translational start site. Putative regulatory binding sites for transcription factors were detected upstream of many TSSs. For a few transcripts, riboswitches and small RNAs were found. Several genes also had additional TSSs within the coding region. Unexpectedly, the HTPS experiments revealed extensive antisense transcription, probably for regulatory functions. The new information in RegulonDB, now with more than 2400 experimentally determined TSSs, strengthens the accuracy of promoter prediction, operon structure, and regulatory networks and provides valuable new information that will facilitate the understanding from a global perspective the complex and intricate regulatory network that operates in E. coli

“Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction”

BACKGROUND: Patient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics. METHODS: We generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization. We performed drug sensitivity assays with a panel of both standard and non-standard agents in five long-term cultures, and integrated drug response with a baseline proteomic and transcriptomic characterization by SWATH-MS and RNA-seq analysis, respectively. RESULTS: PDOs were successfully generated from heavily pre-treated patients, including a paired model of advanced MSI high CRC deriving from pre- and post-chemotherapy liver metastasis. Our PDOs faithfully reproduced genomic and phenotypic features of original tissue. Drug panel testing identified differential response among PDOs, particularly to oxaliplatin and palbociclib. Proteotranscriptomic analyses revealed that oxaliplatin non-responder PDOs present enrichment of the t-RNA aminoacylation process and showed a shift towards oxidative phosphorylation pathway dependence, while an exceptional response to palbociclib was detected in a PDO with activation of MYC and enrichment of chaperonin T-complex protein Ring Complex (TRiC), involved in proteome integrity. Proteotranscriptomic data fusion confirmed these results within a highly integrated network of functional processes involved in differential response to drugs. CONCLUSIONS: Our strategy of integrating PDOs drug sensitivity with SWATH-mass spectrometry and RNA-seq allowed us to identify different baseline proteins and gene expression profiles with the potential to predict treatment response/resistance and to help in the development of effective and personalized cancer therapeutics

Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma

BACKGROUND: Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA. DESIGN: Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity. RESULTS: This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (p = 0.043). CONCLUSIONS: This transcriptomic classification could improve precision immunotherapy for GEA

Prevalence of metabolic syndrome in Murcia Region, a southern European Mediterranean area with low cardiovascular risk and high obesity

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MS) is associated with subsequent appearance of diabetes and cardiovascular disease. As compared to other Spanish regions, Murcia (southern Spain) registers increased obesity as well as cardiovascular morbidity and mortality. The aim of this study was to assess the prevalence of MS and its components, awareness of obesity as a health risk and associated lifestyles.</p> <p>Methods</p> <p>A population-based, cross-sectional study was conducted in 2003, covering a sample of 1555 individuals 20 years and over. MS was defined according to the Revised National Cholesterol Education Program Adult Treatment Panel III (R-ATPIII), International Diabetes Federation (IDF) and Joint Interim Statement (JIS) criteria. Both low (94/80) and high (102/88) waist circumference (WC) thresholds were considered.</p> <p>Results</p> <p>Prevalence of MS was 27.2% (95%CI: 25.2-29.2), 32.2% (95%CI: 30.1-34.3) and 33.2% (95%CI: 31.2-35.3) according to the R-ATPIII, IDF and JIS94/80 respectively. It increased with age until reaching 52.6% (R-ATPIII) or 60.3% (JIS94/80) among persons aged 70 years and over, and was higher in persons with little or no formal education (51.7% R-ATPIII, 57.3% JIS94/80). The most common risk factors were hypertension (46.6%) and central obesity (40.7% and 66.1% according to high and low WC cut-off points respectively). Although most persons were aware that obesity increased health risks, regular exercise was very unusual (13.0% centrally obese, 27.2% non-centrally obese). Adherence to dietary recommendations was similar among centrally obese and non-centrally obese subjects.</p> <p>Conclusions</p> <p>Prevalence of MS is high in our population, is comparable to that found in northern Europe and varies with the definition used. Adherence to preventive recommendations and to adequate weight promotion is very low. In the absence of a specific treatment for MS, integrated intervention based on a sustained increase in physical activity and changes in diet should be reinforced.</p

The Tree versus the Forest: The Fungal Tree of Life and the Topological Diversity within the Yeast Phylome

A recurrent topic in phylogenomics is the combination of various sequence alignments to reconstruct a tree that describes the evolutionary relationships within a group of species. However, such approach has been criticized for not being able to properly represent the topological diversity found among gene trees. To evaluate the representativeness of species trees based on concatenated alignments, we reconstruct several fungal species trees and compare them with the complete collection of phylogenies of genes encoded in the Saccharomyces cerevisiae genome. We found that, despite high levels of among-gene topological variation, the species trees do represent widely supported phylogenetic relationships. Most topological discrepancies between gene and species trees are concentrated in certain conflicting nodes. We propose to map such information on the species tree so that it accounts for the levels of congruence across the genome. We identified the lack of sufficient accuracy of current alignment and phylogenetic methods as an important source for the topological diversity encountered among gene trees. Finally, we discuss the implications of the high levels of topological variation for phylogeny-based orthology prediction strategies