Factores preditivos da formação de aderências pleurais e sucesso da pleurodese nos doentes com derrame pleural

RESUMO: As aderências pleurais podem complicar a realização da pleurodese por toracoscopia. Os autores decidiram realizar este estudo para determinar os factores preditivos da formação e extensão das aderências pleurais e do sucesso da pleurodese em doentes submetidos a toracoscopia e talcagem.Os doentes submetidos a toracoscopia no Georgetown University Medical Center entre Agosto de 1995 e Março de 2002 foram estudados retrospectivamente. Os autores registaram o n.° de toracenteses, a duração do derrame, a malignidade, a origem doença subjacente, a existência de irradiação torácica, a presença e extensão das aderências pleurais e o sucesso da pleurodese. Foram estudados 89 doentes que tinham todos estes dados registados.Numa análise global, só os derrames pleurais que tinham uma duração superior a 5 meses têm um valor preditivo na formação das aderências (p=0,037) e extensão das mesmas (p=0,038). No grupo dos derrames pleurais malignos com uma duração superior a 5 meses este aspecto também tem um valor preditivo na formação (p=0,020) e extensão (p=0,037) das aderências. No grupo particular dos derrames pleurais secundários ao cancro da mama, a duração superior a 5 meses também tem um valor preditivo na formação (p=0,008) e extensão (p=0,011) das aderências pleurais.A regressão estatística determinou que a duração dos derrames superior a 5 meses é neste estudo o único factor preditivo na formação das aderências pleurais e que não existem factores preditivos do sucesso da pleurodese. A duração do derrame pleural, independentemente da sua etiologia, está associada à formação de espessas aderências pleurais, particularmente naqueles que tem uma duração superior a 5 meses. COMENTÁRIO: Nos EUA, 1,5 a 2 milhões de doentes por ano tem um derrame pleural. Cerca de 1/3 são secundários a insuficiência cardíaca e 20% estão relacionados com pneumonias bacterianas. Quinze a 40% são derrames pleurais malignos e, destes, cerca de 30% a 40% são secundários ao cancro do pulmão e 25% ao cancro da mama.A rentabilidade da citologia do líquido pleural (50% a70%) e das biópsias pleurais (39% a 75%) não é satisfatória. Estes factos levam a considerar a toracoscopia o exame indicado nos derrames pleurais sem diagnóstico, pois permite a visualização directa das superfícies pleurais e a realização das biópsias directamente. A toracoscopia permite também realizar a insuflação de talco e a pleurodese.A presença de aderências pleurais dificulta a realização da toracoscopia. A efectividade da pleurodese é diminuída porque as aderências cobrem parcialmente a pleura visceral e a pleura parietal, dificultando a sua aderência.A referência na literatura que a produção de citocinas inflamatórias, a subsequente formação de fibrina e a eventual formação de aderências pleurais, estão relacionadas com o número de toracenteses realizadas previamente à toracoscopia e que poderão afectar o êxito da pleurodese, é um dos aspectos que levou os autores a realizarem este estudo.Os resultados contrariaram em parte estes conceitos. Os autores constataram que a formação das aderências e a sua extensão estavam em parte relacionadas com a gravidade da doença subjacente e com a duração do derrame pleural. Não conseguiram estabelecer relação entre número de toracenteses e a formação de aderências assim como com o êxito ou não da pleurodese.Estatiscamente, só conseguiram estabelecer como factor preditivo da formação e da extensão de aderências a duração do derrame pleural quando superior a 5meses. Em relação aos factores preditivos do sucesso da pleurodese, neste estudo os autores não conseguiram estabelecer; contudo, não foram analisados os valores do pH do líquido pleural que é considerado em algumas séries como factor preditivo (pH <7,20 é um sinal de insucesso da pleurodese).A existência de aderências pleurais não é um factor directo de insucesso da pleurodese, mas como dificulta a realização da toracoscopia e da eventual talcagem é sempre um aspecto a considerar no êxito da toracoscopia/talcagem. Palavras-chave: Derrame pleural, aderências pleurais, toracoscopia, talcage

Human and Mouse Mast Cells Express and Secrete the GPI-Anchored Isoform of CD160

CD160 is expressed by human and mouse natural killer (NK) cells and other cytotoxic lymphocyte subpopulations. CD160 is mostly expressed as a trimeric 83kDa glycosylphosphatidylinositol (GPI)-anchored activating NK receptor, cleaved upon IL-15 stimulation in a secreted trimeric soluble form (sCD160) that binds to major histocompatibility complex (MHC) class I molecules, while a transmembrane isoform appears. sCD160 exhibits immunoregulatory function as it inhibits CD8+ T-lymphocyte cytotoxic activity. We show that human mast cells (MCs) express CD160. In human and mouse skin, resident MCs expressed CD160, whereas in C57BL/6-KitW-sh/W-sh mice, CD160+ cells were only identified at the site of reconstitution with syngeneic cultured MCs. In the human mast cell line, HMC-1, we only identified the transcripts of the GPI-anchored CD160 isoform. Furthermore, CD160 was identified in HMC-1 and mouse MC supernatants, suggesting that MCs release sCD160. Supporting this hypothesis, HMC-1 express the GPI-specific phospholipase D variant 2 involved in the NK lymphocyte membrane cleavage of CD160, and morphological studies highlighted a relative loss of CD160 expression in inflammatory skin sites, where MC degranulation is expected to occur. We also demonstrated an inhibition of T-cell cytotoxicity by HMC-1 supernatant that was partially reversed by anti-CD160 mAb. In conclusion, sCD160, produced by MCs, may have a role in T-cell–MC interactions in vivo

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment:A patient-level meta-analysis from randomized controlled trials

Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR0.05). This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates

Effect of capping groups at the N- and C-termini on the conformational preference of α,β-peptoids

invitation, special theme issue on Foldamer ChemistryInternational audienc

State of the Antarctic and Southern Ocean Climate System

This paper reviews developments in our understanding of the state of the Antarctic and Southern Ocean climate and its relation to the global climate system over the last few millennia. Climate over this and earlier periods has not been stable, as evidenced by the occurrence of abrupt changes in atmospheric circulation and temperature recorded in Antarctic ice core proxies for past climate. Two of the most prominent abrupt climate change events are characterized by intensification of the circumpolar westerlies (also known as the Southern Annular Mode) between ∼6000 and 5000 years ago and since 1200–1000 years ago. Following the last of these is a period of major trans-Antarctic reorganization of atmospheric circulation and temperature between A.D. 1700 and 1850. The two earlier Antarctic abrupt climate change events appear linked to but predate by several centuries even more abrupt climate change in the North Atlantic, and the end of the more recent event is coincident with reorganization of atmospheric circulation in the North Pacific. Improved understanding of such events and of the associations between abrupt climate change events recorded in both hemispheres is critical to predicting the impact and timing of future abrupt climate change events potentially forced by anthropogenic changes in greenhouse gases and aerosols. Special attention is given to the climate of the past 200 years, which was recorded by a network of recently available shallow firn cores, and to that of the past 50 years, which was monitored by the continuous instrumental record. Significant regional climate changes have taken place in the Antarctic during the past 50 years. Atmospheric temperatures have increased markedly over the Antarctic Peninsula, linked to nearby ocean warming and intensification of the circumpolar westerlies. Glaciers are retreating on the peninsula, in Patagonia, on the sub-Antarctic islands, and in West Antarctica adjacent to the peninsula. The penetration of marine air masses has become more pronounced over parts of West Antarctica. Above the surface, the Antarctic troposphere has warmed during winter while the stratosphere has cooled year-round. The upper kilometer of the circumpolar Southern Ocean has warmed, Antarctic Bottom Water across a wide sector off East Antarctica has freshened, and the densest bottom water in the Weddell Sea has warmed. In contrast to these regional climate changes, over most of Antarctica, near-surface temperature and snowfall have not increased significantly during at least the past 50 years, and proxy data suggest that the atmospheric circulation over the interior has remained in a similar state for at least the past 200 years. Furthermore, the total sea ice cover around Antarctica has exhibited no significant overall change since reliable satellite monitoring began in the late 1970s, despite large but compensating regional changes. The inhomogeneity of Antarctic climate in space and time implies that recent Antarctic climate changes are due on the one hand to a combination of strong multidecadal variability and anthropogenic effects and, as demonstrated by the paleoclimate record, on the other hand to multidecadal to millennial scale and longer natural variability forced through changes in orbital insolation, greenhouse gases, solar variability, ice dynamics, and aerosols. Model projections suggest that over the 21st century the Antarctic interior will warm by 3.4° ± 1°C, and sea ice extent will decrease by ∼30%. Ice sheet models are not yet adequate enough to answer pressing questions about the effect of projected warming on mass balance and sea level. Considering the potentially major impacts of a warming climate on Antarctica, vigorous efforts are needed to better understand all aspects of the highly coupled Antarctic climate system as well as its influence on the Earth\u27s climate and oceans

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe