Hypoxia and dehydroepiandrosterone in old age: a mouse survival study

BACKGROUND: Survival remains an issue in pulmonary hypertension, a chronic disorder that often affects aged human adults. In young adult mice and rats, chronic 50% hypoxia (11% FIO2 or 0.5 atm) induces pulmonary hypertension without threatening life. In this framework, oral dehydroepiandrosterone was recently shown to prevent and reverse pulmonary hypertension in rats within a few weeks. To evaluate dehydroepiandrosterone therapy more globally, in the long term and in old age, we investigated whether hypoxia decreases lifespan and whether dehydroepiandrosterone improves survival under hypoxia. METHODS: 240 C57BL/6 mice were treated, from the age of 21 months until death, by normobaric hypoxia (11% FIO2) or normoxia, both with and without dehydroepiandrosterone sulfate (25 mg/kg in drinking water) (4 groups, N = 60). Survival, pulmonary artery and heart remodeling, weight and blood patterns were assessed. RESULTS: In normoxia, control mice reached the median age of 27 months (median survival: 184 days). Hypoxia not only induced cardiopulmonary remodeling and polycythemia in old animals but also induced severe weight loss, trembling behavior and high mortality (p < 0.001, median survival: 38 days). Under hypoxia however, dehydroepiandrosterone not only significantly reduced cardiopulmonary remodeling but also remarkably extended survival (p < 0.01, median survival: 126 days). Weight loss and trembling behavior at least partially remained, and polycythemia completely, the latter possibly favorably participating in blood oxygenation. Interestingly, at the dose used, dehydroepiandrosterone sulfate was detrimental to long-term survival in normoxia (p < 0.05, median survival: 147 days). CONCLUSION: Dehydroepiandrosterone globally reduced what may be called an age-related frailty induced by hypoxic pulmonary hypertension. This interestingly recalls an inverse correlation found in the prospective PAQUID epidemiological study, between dehydroepiandrosterone blood levels and mortality in aged human smokers and former smokers

Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients

© 2008 Drummond et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

How safe are the biologicals in treating asthma and rhinitis?

A number of biological agents are available or being investigated for the treatment of asthma and rhinitis. The safety profiles of these biologic agents, which may modify allergic and immunological diseases, are still being elucidated. Subcutaneous allergen immunotherapy, the oldest biologic agent in current use, has the highest of frequency of the most serious and life-threatening reaction, anaphylaxis. It is also one of the only disease modifying interventions for allergic rhinitis and asthma. Efforts to seek safer and more effective allergen immunotherapy treatment have led to investigations of alternate routes of delivery and modified immunotherapy formulations. Sublingual immunotherapy appears to be associated with a lower, but not zero, risk of anaphylaxis. No fatalities have been reported to date with sublingual immunotherapy. Immunotherapy with modified formulations containing Th1 adjuvants, DNA sequences containing a CpG motif (CpG) and 3-deacylated monophospholipid A, appears to provide the benefits of subcutaneous immunotherapy with a single course of 4 to 6 preseasonal injections. There were no serious treatment-related adverse events or anaphylaxis in the clinical trials of these two immunotherapy adjuvants. Omalizumab, a monoclonal antibody against IgE, has been associated with a small risk of anaphylaxis, affecting 0.09% to 0.2% of patients. It may also be associated with a higher risk of geohelminth infection in patients at high risk for parasitic infections but it does not appear to affect the response to treatment or severity of the infection

A multi-scale modelling framework to guide management of plant invasions in a transboundary context

Background Attention has recently been drawn to the issue of transboundary invasions, where species introduced and naturalized in one country cross international borders and become problematic in neighbouring countries. Robust modelling frameworks, able to identify the environmental drivers of invasion and forecast the current and future potential distribution of invasive species, are needed to study and manage invasions. Limitations due to the lack of species distribution and environmental data, or assumptions of modelling tools, often constrain the reliability of model predictions. Methods We present a multiscale spatial modelling framework for transboundary invasions, incorporating robust modelling frameworks (Multimodel Inference and Ensemble Modelling) to overcome some of the limitations. The framework is illustrated using Hakea sericea Schrad. (Proteaceae), a shrub or small tree native to Australia and invasive in several regions of the world, including the Iberian Peninsula. Two study scales were considered: regional scale (western Iberia, including mainland Portugal and Galicia) and local scale (northwest Portugal). At the regional scale, the relative importance of environmental predictors sets was evaluated and ranked to determine the main general drivers for the species distribution, while the importance of each environmental predictor was assessed at the local scale. The potential distribution of H. sericea was spatially projected for both scale areas. Results Model projections for western Iberia suggest that a large area is environmentally suitable in both Portugal and Spain. Climate and landscape composition sets were the most important determinants of this regional distribution of the species. Conversely, a geological predictor (schist lithology) was more important in explaining its local-scale distribution. Conclusions After being introduced to Portugal, H. sericea has become a transboundary invader by expanding in parts of Galicia (Spain). The fact that a larger area is predicted as environmentally suitable in Spain raises concerns regarding its potential continued expansion. This highlights the importance of transboundary cooperation in the early management of invasions. By reliably identifying drivers and providing spatial projections of invasion at multiple scales, this framework provides insights for the study and management of biological invasions, including the assessment of transboundary invasion risk.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and by National Funds through FCT - Foundation for Science and Technology under the project PTDC/AAGMAA/4539/2012 / FCOMP-01-0124-FEDER-027863 (IND_CHANGE). J. Vicente is supported by POPH/FSE funds and by National Funds through FCT - Foundation for Science and Technology through Post-doctoral grant SFRH/BPD/84044/2012. D.M. Richardson acknowledges support from the DST-NRF Centre of Excellence for Invasion Biology and the National Research Foundation (grant 85417).info:eu-repo/semantics/publishedVersio

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

Robust image analysis with sparse representation on quantized visual features

10.1109/TIP.2012.2219543IEEE Transactions on Image Processing223860-871IIPR

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