One-shot diagnostic and prognostic assessment in intermediate- to high-risk acute pulmonary embolism: The role of multidetector computed tomography

INTRODUCTION: Contrast-enhanced multidetector computed tomography (MDCT) is useful for the diagnosis of pulmonary embolism (PE). However, current guidelines do not support its use for risk assessment in acute PE patients. OBJECTIVES: We compared the prognostic impact of MDCT-derived indices regarding medium-term mortality in a population of intermediate- to high-risk PE patients, mostly treated by thrombolysis. METHODS: Thirty-nine consecutive patients admitted to an intensive care unit with acute PE were studied. All patients had a pulmonary MDCT on admission to the emergency room as part of the diagnostic algorithm. We assessed the following MDCT variables: right ventricular/left ventricular diameter (RV/LV) ratio, arterial obstruction index, pulmonary artery-to-aorta diameter ratio and azygos vein diameter. A 33-month follow-up was performed. RESULTS: Mean age was 59.1±19.6 years, with 80% of patients receiving thrombolysis. Follow-up all-cause mortality was 12.8%. Of the MDCT-derived variables, only the RV/LV ratio had significant predictive value, being higher in patients who suffered the endpoint (1.6±0.5 vs. 1.9±0.4, p=0.046). Patients with an RV/LV ratio ≥1.8 had 11-fold higher medium-term all-cause mortality (3.8% vs. 38.8%, p<0.001). Regarding this endpoint, the c-statistic was 0.78 (95% CI, 0.60-0.96) for RV/LV ratio and calibration was good (goodness-of-fit p=0.594). No other radiological index was predictive of mortality. CONCLUSIONS: MDCT gives the possibility, in a single imaging procedure, of diagnosing and assessing the prognosis of patients with intermediate- to high-risk PE. Although further studies are needed, the simple-to-calculate RV/LV ratio has good discrimination and calibration for predicting poorer outcomes in patients with acute PE

Plant pathogenesis-related proteins of the cacao fungal pathogen Moniliophthora perniciosa differ in their lipid-binding specificities

Moniliophthora perniciosa is the causative agent of witches' broom disease, which devastates cacao cultures in South America. This pathogenic fungus infects meristematic tissues and derives nutrients from the plant apoplast during an unusually long-lasting biotrophic stage. In order to survive, the fungus produces proteins to suppress the plant immune response. Proteins of the Pathogenesis Related 1 (PR- 1)/CAP superfamily have been implicated in fungal virulence and immune suppression. The genome of M. perniciosa encodes eleven homologues of plant PR-1 proteins, designated MpPR-1 proteins, but their precise mode of action is poorly understood. In this study, we expressed MpPR-1 proteins in a yeast model lacking endogenous CAP proteins. We show that some members of the MpPR-1 family bind and promote secretion of sterols whereas others bind and promote secretion of fatty acids. Lipid-binding by purified MpPR-1 occurs with micromolar affinity and is saturable in vitro. Sterol binding by MpPR-1 requires the presence of a flexible loop region containing aromatic amino acids, the caveolin-binding motif. Remarkably, MpPR-1 family members that do not bind sterols can be converted to sterol binders by a single point mutation in the caveolin-binding motif. We discuss the possible implications of the lipid-binding activity of MpPR-1 family members with regard to the mode of action of these proteins during M. perniciosa infections

Differential post-transcriptional regulation of IL-10 by TLR2 and TLR4-activated macrophages

The activation of TLRs by microbial molecules triggers intracellular-signaling cascades and the expression of cytokines such as IL-10. Il10 expression is tightly controlled to ensure effective immune responses, while preventing pathology. Maximal TLR-induction of Il10 transcription in macrophages requires signaling through the MAPKs, ERK, and p38. Signals via p38 downstream of TLR4 activation also regulate IL-10 at the post-transcriptional level, but whether this mechanism operates downstream of other TLRs is not clear. We compared the regulation of IL-10 production in TLR2 and TLR4-stimulated BM-derived macrophages and found different stability profiles for the Il10 mRNA. TLR2 signals promoted a rapid induction and degradation of Il10 mRNA, whereas TLR4 signals protected Il10 mRNA from rapid degradation, due to the activation of Toll/IL-1 receptor domain-containing adaptor inducing IFN-ß (TRIF) and enhanced p38 signaling. This differential post-transcriptional mechanism contributes to a stronger induction of IL-10 secretion via TLR4. Our study provides a molecular mechanism for the differential IL-10 production by TLR2- or TLR4-stimulated BMMs, showing that p38-induced stability is not common to all TLR-signaling pathways. This mechanism is also observed upon bacterial activation of TLR2 or TLR4 in BMMs, contributing to IL-10 modulation in these cells in an infection setting.Fundação para a Ciência e a Tecnologia (FCT

Mismatch between midline shift and hematoma thickness as a prognostic factor of mortality in patients sustaining acute subdural hematoma.

BACKGROUND: Acute subdural hematoma (ASDH) is a traumatic lesion commonly found secondary to traumatic brain injury. Radiological findings on CT, such as hematoma thickness (HT) and structures midline shift (MLS), have an important prognostic role in this disease. The relationship between HT and MLS has been rarely studied in the literature. Thus, this study aimed to assess the prognostic accuracy of the difference between MLS and HT for acute outcomes in patients with ASDH in a low-income to middle-income country. METHODS: This was a post-hoc analysis of a prospective cohort study conducted in a university-associated tertiary-level hospital in Brazil. The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis) statement guidelines were followed. The difference values between MLS and HT (Zumkeller index, ZI) were divided into three categories (3). Logistic regression analyses were performed to reveal the OR of categorized ZI in predicting primary outcome measures. A Cox regression was also performed and the results were presented through HR. The discriminative ability of three multivariate models including clinical and radiological variables (ZI, Rotterdam score, and Helsinki score) was demonstrated. RESULTS: A total of 114 patients were included. Logistic regression demonstrated an OR value equal to 8.12 for the ZI >3 category (OR 8.12, 95% CI 1.16 to 40.01; p=0.01), which proved to be an independent predictor of mortality in the adjusted model for surgical intervention, age, and Glasgow Coma Scale (GCS) score. Cox regression analysis demonstrated that this category was associated with 14-day survival (HR 2.92, 95% CI 1.38 to 6.16; p=0.005). A multivariate analysis performed for three models including age and GCS with categorized ZI or Helsinki or Rotterdam score demonstrated area under the receiver operating characteristic curve values of 0.745, 0.767, and 0.808, respectively. CONCLUSIONS: The present study highlights the potential usefulness of the difference between MLS and HT as a prognostic variable in patients with ASDH. LEVEL OF EVIDENCE: Level III, epidemiological study

Operacionalização do conceito de classe social em estudos epidemiológicos

Procura-se demonstrar que é possível operacionalizar o conceito de classe social de forma a utilizá-lo em estudos epidemiológicos. Foi adaptado às características da formação social de Pelotas, RS (Brasil), modelo de classificação desenvolvido para o México e comparado com o desenvolvido para Ribeirão Preto, SP (Brasil). Mediu-se o poder discriminatório das duas classificações em termos do processo saúde-doença, tendo como variável dependente o crescimento de 5.384 crianças nascidas em 1982. As duas classificações estão associadas com diferenças significativas (PThe development of an operational classification of the Marxist concept of social class that could be used in epidemiological studies is attempted. Although such a classification will necessarily be restricted to the economic dimension of the concept, and leave aside its ideological and legal-political components, it is believed that it may lead to a better understanding of the distribution of ill-health in a given population. Two classifications are described - that developed in Ribeirão Preto, S. Paulo (Brazil), and a new classification based on work done in Mexico. These are compared in terms of how closely associated they are with the patterns of growth of 5,384 young children in the city of Pelotas in Southern Brazil. It is concluded that the proposed classification has greater power of discrimination in terms of child growth than that previously proposed

Mycobacterium tuberculosis strains are differentially recognized by TLRs with an impact on the immune response

Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.This work has been funded by Fundacao para a Ciencia e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 and PTDC/BIA-BCM/102776/2008. Personal grants: SFRH/BD/35981/2007 to JC; SFRH/BPD/3306/2007 to AC; SFRH/BPD/77399/2011 to LMT; SFRH/BI/33456/2008 to CS; and SFRH/BPD/33959/2009 to NSO. MS is a Ciencia 2007 fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas

Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer. In contrast to the classic dominant condition of familial adenomatous polyposis (FAP) due to germinal mutations in the APC gene, the MYH polyposis is an autosomal recessive disease. The identification of individuals affected by MYH polyposis brings new and important implications for the diagnostic, screening, genetic counseling, follow up and therapeutic options in these patients. In this study, screening for germinal mutations in the MYH gene was performed in 53 Portuguese individuals with multiple colorectal adenomas or classic adenomatous polyposis, in whom no mutation had been identified in the APC gene. The results revealed the presence of biallelic germline MYH mutations in 21 patients. In addition, we here report 3 mutations (c.340T>C [p.Y114H]; c.503G>A [p.R168H]; and c.1186_1187insGG [p.E396fsX437]) which, to our knowledge, have not been previously describe

Spontaneous CP Violation in Non-Minimal Supersymmetric Models

We study the possibilities of spontaneous CP violation in the Next-to-Minimal Supersymmetric Standard Model with an extra singlet tadpole term in the scalar potential. We calculate the Higgs boson masses and couplings with radiative corrections including dominant two loop terms. We show that it is possible to satisfy the LEP constraints on the Higgs boson spectrum with non-trivial spontaneous CP violating phases. We also show that these phases could account for the observed value of epsilonK.Comment: 21 pages, 7 Figures in Encapsulated Postscrip