Land Use Regression Models for Ultrafine Particles in Six European Areas

Long-term ultrafine particle (UFP) exposure estimates at a fine spatial scale are needed for epidemiological studies. Land use regression (LUR) models were developed and evaluated for six European areas based on repeated 30 min monitoring following standardized protocols. In each area; Basel (Switzerland), Heraklion (Greece), Amsterdam, Maastricht, and Utrecht ("The Netherlands"), Norwich (United Kingdom), Sabadell (Spain), and Turin (Italy), 160-240 sites were monitored to develop LUR models by supervised stepwise selection of GIS predictors. For each area and all areas combined, 10 models were developed in stratified random selections of 90% of sites. UFP prediction robustness was evaluated with the intraclass correlation coefficient (ICC) at 31-50 external sites per area. Models from Basel and The Netherlands were validated against repeated 24 h outdoor measurements. Structure and model R2 of local models were similar within, but varied between areas (e.g., 38-43% Turin; 25-31% Sabadell). Robustness of predictions within areas was high (ICC 0.73-0.98). External validation R2 was 53% in Basel and 50% in The Netherlands. Combined area models were robust (ICC 0.93-1.00) and explained UFP variation almost equally well as local models. In conclusion, robust UFP LUR models could be developed on short-term monitoring, explaining around 50% of spatial variance in longer-term measurements

Applications of fluorescence and bioluminescence resonance energy transfer to drug discovery at G protein coupled receptors

The role of G protein coupled receptors (GPCRs) in numerous physiological processes that may be disrupted or modified in disease makes them key targets for the development of new therapeutic medicines. A wide variety of resonance energy transfer (RET) techniques such as fluorescence RET and bioluminescence RET have been developed in recent years to detect protein–protein interactions in living cells. Furthermore, these techniques are now being exploited to screen for novel compounds that activate or block GPCRs and to search for new, previously undiscovered signaling pathways activated by well-known pharmacologically classified drugs. The high resolution that can be achieved with these RET methods means that they are well suited to study both intramolecular conformational changes in response to ligand binding at the receptor level and intermolecular interactions involving protein translocation in subcellular compartments resulting from external stimuli. In this review we highlight the latest advances in these technologies to illustrate general principles

Two-thirds lip defects. A new combined reconstructive technique for patients with epithelial cancer

BACKGROUND: The lips are a common site prone to squamous cell carcinomas, which arise in the facial region. There are different techniques to reconstruct the excised lip region, according to dimensions, area, and position of the tumor. The authors describe a new technique of lip reconstruction born from a combination between a nasolabial flap and adipose tissue transplant. METHODS: The study was lead in the Plastic and Reconstructive Surgery Department of the University of Catanzaro. It includes 10 patients with squamous and basal cell carcinomas that interested lower or upper lip. The authors used a nasolabial flap to reconstruct two-thirds of the excised lip. All patients were staged and resulted free of disease. As a result of surgery, deformities and depressions persisted in 5 patients. This induced the authors to subject them to transplantation of adipose tissue to maximize results. Aesthetic and functional evaluation was performed with the Patient and Observer Scar Assessment Scale v 2.0 and drooling rating scale questionnaires. Moreover, an anthropometric analysis was performed in patients treated with fat transplant. Data were analyzed using Wilcoxon signed-rank test. RESULTS: All patients had an acceptable aesthetic and functional outcome. Oral competence, sensation, and movements of the area were adequate and aesthetic was good. Adipose tissue transplant compared with surgery alone, determine a real modification of various parameters, that was statistically significant (P = 0.043) to our analysis. CONCLUSIONS: The inverted nasolabial flap is versatile and simple. This technique allows to repair large lip defects by maintaining the eurythmia of the face. Autologous fat transplant is a favorable filler. Our data show that surgery alone is unable to restore face eurythmia after a tumor excision. Adipose tissue transplant allows to reach this goal. These 2 techniques, together, may significantly modify the functional and aesthetic result of the lip reconstruction, ensuring an optimal long-term result

Effects of budesonide on p38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells

Background: Nontypeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is represented by bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study was to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by budesonide. Methods: p38 MAPK phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. Results: NTHi was able to markedly potentiate the stimulatory actions of TNFalpha on p38 MAPK phosphorylation, caspase-3 expression and IL-8 secretion. All these effects were significantly (P < 0.01) inhibited by budesonide. Conclusions: These results suggest that NTHi and TNF-alpha can synergistically stimulate, via activation of p38 MAPK signalling pathway, airway epithelial cell apoptosis and IL-8 release. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by NTHi and TNF-alpha

Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTHi

Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTH

Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTH

Traumatismo torácico: estudo retrospectivo de 168 casos

OBJETIVO: Avaliar o atendimento ao paciente portador de traumatismo torácico. MÉTODO: Estudo retrospectivo de 168 casos de trauma do tórax, com ênfase na abordagem inicial, conduta operatória e cuidados pós-operatórios. RESULTADOS: Dos 168 pacientes, 120 eram do sexo masculino e a média de idade encontrada foi de 35,5 anos. Dez pacientes foram toracotomizados de urgência, quatro por ferimento cardíaco, quatro devido à lesão de vasos pulmonares, um por lesão do saco pericárdico e outro do pedículo pulmonar. Os demais tiveram suas condições clínicas corrigidas através de simples drenagem torácica do hemitórax atingido. Ocorreram dois óbitos não cirúrgicos e um devido à insuficiência respiratória. CONCLUSÕES: O traumatismo torácico, além de ser muito freqüente, é na maioria das vezes, de fácil resolução. Podem ocorrer, no entanto, lesões torácicas graves envolvendo órgãos vitais que merecem intervenção mais agressiva e perícia técnica, com suporte hospitalar de alto nível

ExpoApp: an integrated system to assess multiple personal environmental exposures

To assess environmental exposures at the individual level, new assessment methods and tools are required. We developed an exposure assessment system (ExpoApp) for smartphones. ExpoApp integrates: (i) geo-location and accelerometry measurements from a waist attached smartphone, (ii) data from portable monitors, (iii) geographic information systems, and (iv) individual's information. ExpoApp calculates time spent in microenvironments, physical activity level, inhalation rate, and environmental exposures and doses (e.g., green spaces, inhaled ultrafine particles- UFP). We deployed ExpoApp in a panel study of 158 adults from five cities (Amsterdam and Utrecht- the Netherlands, Basel- Switzerland, Norwich- UK, and Torino- Italy) with an UFP monitor. To evaluate ExpoApp, participants also carried a reference accelerometer (ActiGraph) and completed a travel-activity diary (TAD). System reliability and validity of measurements were evaluated by comparing the monitoring failure rate and the agreement on time spent in microenvironments and physical activity with the reference tools. There were only significant failure rate differences between ExpoApp and ActiGraph in Norwich. Agreement on time in microenvironments and physical activity level between ExpoApp and reference tools was 86.6% (86.5-86.7) and 75.7% (71.5-79.4), respectively. ExpoApp estimated that participants inhaled 16.5 × 1010 particles/day of UFP and had almost no contact with green spaces (24% of participants spent ≥30 min/day in green spaces). Participants with more contact with green spaces had higher inhaled dose of UFP, except for the Netherlands, where the relationship was the inverse. ExpoApp is a reliable system and provides accurate individual's measurements, which may help to understand the role of environmental exposures on the origin and course of diseases.The study was funded by EC grants EXPOsOMICs (FP7-ENV-2012-308610) and HELIX (FP7-ENV-2012-308333)

The Amoebozoa

The model organism Dictyostelium discoideum is a member of the Amoebozoa, one of the six major ­divisions of eukaryotes. Amoebozoa comprise a wide variety of amoeboid and flagellate organisms with single cells measuring from 5 μm to several meters across. They have adopted many different life styles and sexual behaviors and can live in all but the most extreme environments. This chapter provides an overview of Amoebozoan diversity and compares roads towards multicellularity within the Amoebozoa with inventions of multicellularity in other protist divisions. The chapter closes with a scenario for the evolution of Dictyostelid multicellularity from an Amoebozoan stress response