Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Pericardial Effusion with Cardiac Tamponade as a Form of Presentation of Primary Hypothyroidism

The authors describe a case of pericardial effusion accompanied by cardiac tamponade caused by primary hypothyroidism. Diagnosis was made by exclusion, because other causes of cardiac tamponade are more frequent. Emergency treatment of cardiac tamponade is pericardiocentesis (with possible pericardial window), and, after stabilization, performance of hormonal reposition therapy with L-thyroxin

Seeding density in wheat: the more, the merrier?

Adjustment of seeding schemes is one of the crop management techniques that most influences grain yield components. This work aimed to characterize the potential grain yield and its components in wheat (Triticum aestivum L.) genotypes with contrasting tillering ability under different seeding densities and environments. Five experiments were conducted in split-plot design, each with ten cultivars (main plot), sown in five distinct seeding densities (subplots). Experiments were sown in three locations in southern Brazil in the years 2005, 2006 and 2007. The grain yield per plot and its yield components: number of fertile tillers, weight of 1,000 grains, ear weight and number of grains per ear were evaluated. Genotypes with reduced tillering ability expressed an increase in grain yield with an increase in seeding densities, however showing a reduction in ear weight. The number of grains per ear did not affect grain yield but was highly influenced by seeding densities. The compensatory effect was expressed by the weight of a thousand grains as a function of the experimental conditions in which the genotypes were evaluated, regardless of seeding densities used. Results pointed to differences among cultivars tested in specific locations and years

Macrophage migration inhibitory factor:a therapeutic target in gallbladder cancer

BACKGROUND: Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer. METHODS: Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA. RESULTS: The quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells. CONCLUSIONS: Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1855-z) contains supplementary material, which is available to authorized users

The endocannabinoid system in guarding against fear, anxiety and stress

The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment. eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism's long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders. An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.B.L. was supported by the German Research Foundation (SFB TRR 58, CRC 1080 and FOR 926); G.M. by the Institut national de la santé et de la recherche médicale (INSERM), the European Commission Seventh Framework Programme (REPROBESITY, HEALTH-F2-2008-223713, PAINCAGE and HEALTH-2014-603191), the European Research Council (Endofood, ERC-2010-StG−260515, CannaPreg and ERC-2014-PoC-640923), the Fondation pour la Recherche Medicale (DRM20101220445), the Human Frontiers Science Program, Region Aquitaine, Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens ANR-13-BSV4-0006 and BRAIN ANR-10-LABX-0043); R.M. by the grants SAF2014-59648P, RETICS-RTA#RD12/0028/0023, AGAUR#2014-SGR-1547 and Health-F2-2013-602891; and C.J.H. by the US National Institutes of Health grants DA038663, DA026996 and MH102838

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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