Vascular surveillance by haptotactic blood platelets in inflammation and infection

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets

Effect of Operating and Sampling Conditions on the Exhaust Gas Composition of Small-Scale Power Generators

Small stationary diesel engines, like in generator sets, have limited emission control measures and are therefore responsible for 44% of the particulate matter (PM) emissions in the United States. The diesel exhaust composition depends on operating conditions of the combustion engine. Furthermore, the measurements are influenced by the used sampling method. This study examines the effect of engine loading and exhaust gas dilution on the composition of small-scale power generators. These generators are used in different operating conditions than road-transport vehicles, resulting in different emission characteristics. Experimental data were obtained for gaseous volatile organic compounds (VOC) and PM mass concentration, elemental composition and nitrate content. The exhaust composition depends on load condition because of its effect on fuel consumption, engine wear and combustion temperature. Higher load conditions result in lower PM concentration and sharper edged particles with larger aerodynamic diameters. A positive correlation with load condition was found for K, Ca, Sr, Mn, Cu, Zn and Pb adsorbed on PM, elements that originate from lubricating oil or engine corrosion. The nitrate concentration decreases at higher load conditions, due to enhanced nitrate dissociation to gaseous NO at higher engine temperatures. Dilution on the other hand decreases PM and nitrate concentration and increases gaseous VOC and adsorbed metal content. In conclusion, these data show that operating and sampling conditions have a major effect on the exhaust gas composition of small-scale diesel generators. Therefore, care must be taken when designing new experiments or comparing literature results

Variation in the Gene Encoding the Serotonin 2A Receptor Is Associated with Outcome of Antidepressant Treatment

Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide–polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1×10(-6) to 3.7×10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action

Implementação da reforma sanitária: a formação de uma política Health reform implementation and policy formation

Este artigo procura interpretar o processo de implementação da reforma do sistema de saúde ocorrida na década de 1990. A implantação de uma política é dotada de autonomia e envolve decisões, além de ser um processo de adaptação em função das mudanças do contexto, portanto, sua implementação exige decisão e iniciativa governamental, e instrumentos para efetivá-la, entre os quais a disponibilidade de recursos financeiros e o suporte político organizado, particularmente, por parte dos grupos sociais afetados positivamente. O processo de implementação da reforma da política de saúde não é simplesmente a tradução concreta de decisões, mas um processo ainda de formulação da política de saúde. Durante esse processo, tiveram grande importância não apenas os efeitos do contexto político-econômico de ajustes e a reconfiguração da agenda pública, mas principalmente os efeitos de feedback das políticas de saúde anteriores, que se traduziram na ausência de suporte político, no subfinanciamento e na incapacidade de publicização da rede de serviços, os quais funcionaram como constrangimentos à implementação completa da reforma nos termos de seus formuladores. Dentro desses limites, foram tomadas decisões cruciais que redefiniram a reforma, sendo as mais significativas o estabelecimento do marco regulatório da assistência privada, que explicita a segmentação e derruba formalmente as pretensões universalistas, e as relacionada ao financiamento, que ainda configurava objeto de disputa. O resultado foi a consolidação de um sistema de saúde dual - público e privado.<br>This paper analyses the process of implementation of the health system reform in the 1990s. The starting point is the proposition that policy implementation is endowed with autonomy and involves decisions, apart from being a process of adaptation to changes in context; implementation requires governmental decision and initiative and tools to make it effective, among them the availability of financial resources and organized political support, especially from those groups that benefit more directly. The process of implementation of the health system reform was not simply a concrete translation of decisions, but also a process of health policy design. In it, the effects not only of adjustments in the political and economic contexts and of the reconfiguration of the public agenda, but mainly the feedback effects of previous health policies could be felt. The latter translated themselves into the absence of political support, underfinancing and the incapacity to create a public network of services. They acted as constraints to the full implementation of the reform, as it was conceived by its formulators. Within these limits, crucial decisions were made, which redefined the reform, the most important being, on the one hand, the creation of a regulatory framework for private assistance that made the segmentation explicit, formally abandoning any universalistic intent, and, on the other hand, those related to financing, which still are an object of dispute. The result is the consolidation of a dualistic health system - public and private

Effect of low-dose gaseous ozone on pathogenic bacteria

<p>Abstract</p> <p>Background</p> <p>Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes.</p> <p>Methods</p> <p>A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2^nd phase, eight bacterial strains with well characterized resistance patterns were evaluated <it>in vitro</it> using agar-blood in adapted Petri dishes (10⁵ bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O₃/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used.</p> <p>Results</p> <p>The selected ozone dose was applied to the following eight strains: <it>Escherichia coli</it>, oxacillin-resistant <it>Staphylococcus aureus</it>, oxacillin-susceptible <it>Staphylococcus aureus</it>, vancomycin-resistant <it>Enterococcus faecalis</it>, extended-spectrum beta-lactamase-producing <it>Klebsiella pneumoniae</it>, carbapenem-resistant <it>Acinetobacter baumannii</it>, <it>Acinetobacter baumannii</it> susceptible only to carbapenems, and <it>Pseudomonas aeruginosa</it> susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups.</p> <p>Conclusion</p> <p>A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents.</p