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Rare diseases are defined by a limited prevalence of ≤5 cases per 10 000 individuals in Europe [1]. This definition includes around 8000 diseases, many of which are unknown not only to the public but also to the vast majority of healthcare professionals and text books. It is estimated that, as a whole, rare diseases affect around 25 to 30 million people in Europe. Most rare diseases are chronic and debilitating and appear in early childhood or young adulthood, accounting for a significant proportion of infant mortality and childhood/life-long disability. Rare diseases have a number of problems in common: 1) being “invisible” to the healthcare systems; 2) the paucity of experts; 3) the lack of appropriate treatments; and 4) the social exclusion faced by patients and their families [1]. Specific coordinated initiatives in the field of rare diseases are required so as to assure equity in the provision of care, development of best practice, and adequate information for the healthcare professionals and society at large., General Practitioners need support to recognise rare lung disorders and advise patients on the best available care http://ow.ly/kDgy304rX94

The purpose of this study is to propose a User Experience (UX) model to support the design of a wearable Augmented Reality (AR) application for Opera. To this end, it implements the UX approach by Hassenzahl and Tractinsky [17] and User-Centered Design methods within a People Action Context Technologies (PACT) analysis. The preliminary results identify users' requirements relating to People, Actions and Contexts for a visual AR interface at Opera. The study contributes to generate useful knowledge to support the design of visual AR interfaces for predominantly hedonic contexts, such as performative arts. Further, being among the first to investigate UX for wearable AR at Opera, this study provides a foundation for the implementation of wearable digital applications in this context.

The discussion within the round table dealt with the objectives, methods and findings of the OpeRA project.

BACKGROUND: The expression and localization of transforming growth factor-beta (TGF-β) pathway proteins in different compartments of the lower airways of stable COPD patients is unclear. OBJECTIVE: To determine TGF-β pathway protein expression in patients with stable COPD. METHODS: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lung of patients with stable COPD (n=44), control smokers with normal lung function (n=24) and control non-smoking subjects (n=11) using immunohistochemistry. RESULTS: TGF-β1, TGF-β3 and CCN2 expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, of stable COPD patients compared to control smokers with normal lung function. TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and mild/moderate stable COPD compared to control non-smokers and correlated significantly with pack-years. However, TGF-β3+ cells decreased in severe/very severe COPD compared to control smokers. LTBP-1 expression was increased in the bronchial lamina propria in stable COPD of all severities compared with control smokers with normal lung function. BAMBI expression in the bronchial mucosa was significantly increased in stable COPD of all severities compared to control subjects. No other significant differences were observed between groups for all the other molecules studied either in the bronchial mucosa and peripheral lung. CONCLUSION: Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD. Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD.

Background In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. Objectives To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Methods Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. Results In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups. Conclusions Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.

Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality worldwide. Through shared risk factors and pathophysiological mechanisms, CHF and COPD frequently coexist. The concurrent disease has important therapeutic implications and independently predicts worsened mortality, impaired functional status, and health service use. However, assessment of the comorbidity varies widely according to the population studied, diagnostic criteria and measurement tools applied. Both syndromes have been studied extensively but largely separately, mostly in the domain of the pulmonologist for COPD and in the domain of the cardiologist for CHF.

Cigarette smoke is a potent stressor for the respiratory system, contributing to pathogenesis, for instance in chronic obstructive pulmonary disease (COPD), but its effects on the expression, function, and cellular localization of mitochondrial chaperonins are still largely unknown. We studied in vivo (airways biopsies) the localization of Hsp10 and Hsp60 in patients (smokers and non-smokers) affected by mild-moderate COPD, and characterized the effects of non-lethal doses of cigarette smoke extract (CSE) on the expression of these molecules in two human cell lines: lung fibroblasts (HFL-1) and bronchial epithelial (16HBE). We applied various in vitro methods: immunohistochemistry (IHC), subcellular fractionation analyses (SFA), Western blotting (WB), immunocytochemistry (ICC), and transmission electron microscopy (TEM) immunogold, and used bioinformatics and databases searches to gather structural in silico data for interpreting and complementing the in vitro results. IHC showed that in smokers and non-smokers COPD patients Hsp10 was localized in both, the cytoplasm and the nucleus of epithelial and lamina propria cells, while Hsp60 was present only in the cytosol. ICC, SFA, and WB on both CSE-exposed cell lines confirmed the presence of nuclear Hsp10, with an increasing trend in parallel to CSE concentration. TEM immunogold further confirmed Hsp10 in the nucleus, in addition to its presence in the cytoplasm and mitochondria, on both cell lines. Bioinformatics and in silico structural analyses indicated that Hsp10 can localize in extramitochondrial sites, such as the nucleus, even if Hsp10 lacks known DNA-binding motifs or nuclear import signals in its primary sequence. Our data suggest a link between exposure to exogenous oxidative stress and cell response, involving Hsp10, which would play roles different from its canonical functions. It is known that Hsp10 can display an array of functions depending on its location: cytoplasm, mitochondria, or extracellular. Here, we show for the first time the presence of Hsp10 in the nucleus of epithelial and stromal human-lung cell lines, paralleling the observations in vivo in COPD patients, and indicating that intranuclear Hsp10 levels are affected by oxidative stress due to an exogenous stressor like cigarette-smoke. The questions now are by what mechanism Hsp10 becomes a resident of the nucleus and what are its functions there.

Inflammation is a major component of chronic obstructive pulmonary disease (COPD) and its cause and mechanisms are still incompletely understood. For example, the role of heat shock proteins (Hsps), many of which are molecular chaperones, has not been explored in detail in COPD, despite the fact that these molecules are known to participate in inflammation in other diseases. It has been shown that extracellular Hsps can signal certain types of T cells, macrophages, dendritic cells, and neutrophils and, thereby, elicit inflammation and immunity. However, these phenomena have not been investigated in COPD despite: a) the increasing awareness of Hsp participation in inflammation and immunity; and b) the fact that this disease is waiting for new knowledge to benefit from effective treatment and continues to be one of the commonest and most serious illnesses in the Western countries. We developed a strategy to study Hsps in COPD involving a multipronged approach, using in vivo and in vitro methods, which would, at least in part, compensate for the limitations inherent to the analysis of human diseases. We determined the levels of six Hsps in bronchial mucosa biopsies, as well as several inflammatory markers, from patients at various stages compared to smoker and non-smoker controls by immunohistochemistry, and found significant increase of Hsp60, Hsp10, and Hsp40 in COPD but no changes for Hsp27, Hsp70 and Hsp90. We also found that the increase in Hsp60 positively correlated with number of neutrophils, and it localized in them. Hsp60 has been implicated in human inflammatory pathology; hence it was pertinent to investigate whether the chaperonin originated only in the neutrophils or also in other cells. In vitro experiments showed that in bronchial epithelial cells submitted to oxidative stress, a characteristic of COPD mucosa, Hsp60 was overexpressed and was released into the extracellular medium. Other measurements indicated that NFkB-p65 was involved in the hsp60-gene upregulation whereas HSF-1 apparently was not. All the data we obtained using a battery of complementary in vivo and in vitro methods coincided to indicate that Hsp60 plays an active role in inflammation in COPD. Hence, one can infer that the chaperonin does contribute to the etiology and/or pathogenesis of COPD and that it is pertinent to investigate this aspect of Hsp60 biology-COPD pathology with renewed intensity. The results could have a significant impact on the developing of strategies for diagnosis, determining prognosis, and treatment that should be centered on Hsp60., Italian Journal of Anatomy and Embryology, Vol 116, No 1 (Supplement) 2011

BACKGROUND: The literature shows conflicting results when high-resolution computed tomography (HRCT) scores of emphysema were correlated with different indices of airflow obstruction. OBJECTIVES: We correlated HRCT scores of emphysema with different indices of airflow obstruction. METHODS: We performed HRCT of the chest in 59 patients, all smokers or ex-smokers, with stable chronic obstructive pulmonary disease of different severity [GOLD stages I-IV; mean age ± SD 67.8 ± 7.3 years; pack/years 51.0 ± 34.6; percent predicted forced expiratory volume in 1 s (FEV(1)% predicted) 52.3 ± 17.6; post-bronchodilator FEV(1)% predicted 56.5 ± 19.1; FEV(1)/forced vital capacity (FVC) ratio 50.8 ± 10.2; post-bronchodilator FEV(1)/FVC ratio 51.6 ± 11.0; percent diffusion lung capacity for carbon monoxide (DLCO%) 59.2 ± 21.1; DLCO/percent alveolar volume (VA%) 54.5 ± 18.2; percent residual volume 163.0 ± 35.6; percent total lung capacity (TLC%) 113.2 ± 15; residual volume/TLC 1.44 ± 0.2]. All patients were in stable phase. RESULTS: The mean ± SD visual emphysema score in all patients was 25.6 ± 25.4%. There was a weak but significant correlation between the percentage of pulmonary emphysema and numbers of pack/years (R = +0.31, p = 0.024). The percentage of emphysema was inversely correlated with the FEV(1)/FVC ratio before and after bronchodilator use (R = -0.44, p = 0.002, and R = -0.39, p = 0.005), DLCO% (R = -0.64, p = 0.0003) and DLCO/VA% (R = -0.68, p < 0.0001). A weak positive correlation was also found with TLC% (R = +0.28, p = 0.048). When patients with documented emphysema were considered separately, the best significant correlation observed was between DLCO/VA% and HRCT scan score (p = 0.007). CONCLUSIONS: These data suggest that in patients with stable chronic obstructive pulmonary disease of varying severity, the presence of pulmonary emphysema is best represented by the impaired gas exchange capability of the respiratory system.

Airway epithelial cells modulate bronchial remodelling in COPD and asthma. TGF-β1 up-regulation was observed in the bronchial epithelial cells of asthmatics and COPD patients. TGF-β is involved in airways remodelling mainly acting via the Smad pathway. Increased CCL5 was also observed in bronchi of patients with severe COPD. We investigated the effects of TGF-β1 on collagen type I, Smad 3-4 and 7 expression and the effects of CCL5 on TGF-β1-induced collagen production in human bronchial epithelial cells (16HBE).Cells were treated with 10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5 for 0,3 and 24 hours.TGF-b1 increased Smad3,Smad4 and collagen type I(p=0.0472, p=0.0433 and p

Cigarette smoke is a potent stressor for the respiratory system, contributing to pathogenesis, for instance in chronic obstructive pulmonary disease (COPD), but its effects on the expression, function, and cellular localization of mitochondrial chaperonins are still largely unknown. We studied in vivo (airways biopsies) the localization of Hsp10 and Hsp60 in patients (smokers and non-smokers) affected by mild-moderate COPD, and characterized the effects of non-lethal doses of cigarette smoke extract (CSE) on the expression of these molecules in two human cell lines: lung fibroblasts (HFL-1) and bronchial epithelial (16HBE). We applied various in vitro methods: immunohistochemistry (IHC), subcellular fractionation analyses (SFA), Western blotting (WB), immunocytochemistry (ICC), and transmission electron microscopy (TEM) immunogold, and used bioinformatics and databases searches to gather structural in silico data for interpreting and complementing the in vitro results. IHC showed that in smokers and non-smokers COPD patients Hsp10 was localized in both, the cytoplasm and the nucleus of epithelial and lamina propria cells, while Hsp60 was present only in the cytosol. ICC, SFA, and WB on both CSE-exposed cell lines confirmed the presence of nuclear Hsp10, with an increasing trend in parallel to CSE concentration. TEM immunogold further confirmed Hsp10 in the nucleus, in addition to its presence in the cytoplasm and mitochondria, on both cell lines. Bioinformatics and in silico structural analyses indicated that Hsp10 can localize in extramitochondrial sites, such as the nucleus, even if Hsp10 lacks known DNA-binding motifs or nuclear import signals in its primary sequence. Our data suggest a link between exposure to exogenous oxidative stress and cell response, involving Hsp10, which would play roles different from its canonical functions. It is known that Hsp10 can display an array of functions depending on its location: cytoplasm, mitochondria, or extracellular. Here, we show for the first time the presence of Hsp10 in the nucleus of epithelial and stromal human-lung cell lines, paralleling the observations in vivo in COPD patients, and indicating that intranuclear Hsp10 levels are affected by oxidative stress due to an exogenous stressor like cigarette-smoke. The questions now are by what mechanism Hsp10 becomes a resident of the nucleus and what are its functions there., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

Airway epithelial cells play an important role in inflammatory, apoptotic and remodelling process associate with fibrosis and COPD. Transforming growth factor 1 (TGF-b1) is involved in airways remodelling by Smads signalling pathway. We investigated the role of TGF-b1 on type I collagen production and Smads (Smad 2-3-4-and 7) expression in bronchial epithelial cells (16HBE). Cells were treated with 1ng/ml and 10ng/ml of TGF-b1 for 0, 3 and 24 hours. With low dose of TGF-b1 we observed no significant variation on Smad2 mRNA expression for both times but a significant increased of Smad7 mRNA expression at 3h (p=0.0043) and a significant reduction of Smad3, Smad4 and Smad7 mRNA expression at 24h of treatment (p=0.0207, p=0.0381 and p=0.0087, respectively); TGF-b1 increases type I collagen mRNA expression (p=0.0190), but no significantly Smad3 activation after just 3 hours of treatment (p=0.0571). High dose of TGF-b1 increases Smad2 mRNA expression at 3h (p=0.0190), Smad3 and Smad4 mRNA (p=0.0081, p=0.0087, respectively) and type I collagen mRNA at 24h (p=0.00022); no change were observed on Smad7 mRNA level. Than we observed a time dependent phospho-Smad3 significant increase (p= 0.0286 for 3 and 24h) but a phospho-Smad2 expression reduction. These results let think that TGF-b1 is involved on type I collagen production in 16HBE in a time and dose-dependent manner and this effect is mediated more by phosphor-Smad3 than phosphor-Smad2. These data shows that low doses of TGF-b1 had not effect on inhibitor Smad7 mechanism whom balances and reduces Smad3 activation and type I collagen production, while high doses seems act on inhibitor Smad7 mRNA expression with increase on phospho-Smad3 and type I collagen expression in 16HBE.

En este artículo se presenta una semblanza de la vida y obra del Dr. Federico Milá de la Roca, médico venezolano, quien fue uno de los fundadores del Instituto Nacional de Higiene, resaltando diferentes rasgos de su personalidad y sus destacadas actuaciones en el campo profesional y personal. This paper presents a brief biography of Federico Milá de la Roca, Venezuelan medical doctor, who was one of the founders of the Instituto Nacional de Higiene, highlighting various features of his personality and outstanding performances related with his personal and profesional life.

La Gerencia Sectorial de Producción elabora vacunas bacterianas y virales de uso humano y veterinario, para satisfacer necesidades específicas de nuestra población. Igualmente responde a los requerimientos del resto de las áreas técnicas de la institución, a las que provee de insumos, reactivos químicos y biológicos como cultivos celulares y animales de experimentación, entre otros. También presta servicios con fines diagnósticos, productivos, de control e investigación. Un ejemplo relevante de proyección de la Gerencia Sectorial de Producción, y del Instituto, lo constituye la nueva Planta de Vacunas, instalación de alta tecnología que representa un contundente aporte para consolidar la autosuficiencia nacional en la producción de tan importantes rubros para la salud. The Sectorial Productión Management produces bacterial and viral vaccines for human and veterinary use to satisfy specific needs of our population. It also responds, to the requirements of the rest of the technical units of the Institute, to whom it provides with chemical and biological reagents like cellular cultures and laboratory animals, among others. It also carry out activities for diag nostic purposes, production, control and research. An excellent example of projection of The Sectorial Productión Management and the Institute constitutes the new Vaccine Plant, installation of high technology that will allow to consolidate the national self-sufficiency in the production of such important headings for the health.