Novel orthobunyavirus in Cattle, Europe, 2011

In 2011, an unidentified disease in cattle was reported in Germany and the Netherlands. Clinical signs included fever, decreased milk production, and diarrhea. Metagenomic analysis identified a novel orthobunyavirus, which subsequently was isolated from blood of affected animals. Surveillance was initiated to test malformed newborn animals in the affected region.     

Mitral effective regurgitant orifice area versus left ventricular ejection fraction as prognostic indicators in patients with dilated cardiomyopathy and heart failure.

BACKGROUND: This study aimed at investigating the relative powers of the quantitative evaluation of functional mitral regurgitation (FMR) and ejection fraction (EF) in predicting the clinical changes and prognosis of dilated cardiomyopathy (DCM) with severe systolic dysfunction. METHODS: A total of 81 patients with DCM, EF < 0.40 and at least mild FMR were prospectively evaluated during a mean follow-up of 24 +/- 7 months. Twenty cardiac deaths were recorded. At the time of enrolment all patients underwent echocardiographic evaluation of the effective regurgitant orifice area (ERO), EF, left atrial area, and tenting area. In 42/81 patients, the data obtained at enrolment were compared to those measured at a mean follow-up of 10 +/- 2 months. A multivariate analysis was performed to determine the best predictor of NYHA class and mortality. RESULTS: There was a correlation between the NYHA class and the ERO (chi2 = 26.1, p = 0.0001) but not with EF (chi2 = 4.3, p = 0.22) and at multivariate analysis, the ERO was found to be the main determinant of the NYHA class (r = 0.64, standard error 0.6, p = 0.0001). The NYHA class remained unchanged or improved in 28/42 (67%) and deteriorated in 14/42 (33%) patients. In the first group, the ERO increased from 22.3 +/- 10 to 30.2 +/- 16.4 mm2 (p = 0.05) and the tenting area from 5.8 +/- 1.8 to 6.8 +/- 1.8 cm2 (p = 0.001); in the second group, the ERO increased from 25.1 +/- 5.6 to 39.0 +/- 14.5 mm2 (p = 0.04) and the tenting area from 5.9 +/- 2.1 to 7.6 +/- 1.8 cm2 (p = 0.0001), in both groups without significant changes in EF. The mortality was 8.1% in patients with an ERO < 21 mm2, 30.3% in patients with an ERO of 21-30 mm2, and 50% in those with an ERO > 30 mm2. The EF was similar in the three subgroups. At Cox multivariate analysis the best predictors of mortality were the ERO (chi2 = 13.83, p = 0.0001), EF (chi2 = 5.48, p = 0.019), and left atrial area (chi2 = 4.52, p = 0.04). CONCLUSIONS: FMR in DCM well correlated with the clinical status of the patients and its worsening was suggestive of progression of the disease. The ERO was found to be the best predictor of the NYHA class and mortality.     

Community action against asthma

BACKGROUND: Community Action Against Asthma (CAAA) is a community-based participatory research (CBPR) project that assesses the effects of outdoor and indoor air quality on exacerbation of asthma in children, and tests household- and neighborhood-level interventions to reduce exposure to environmental asthma triggers. Representatives of community-based organizations, academia, an integrated health system, and the local health department work in partnership on CAAA's Steering Committee (SC) to design and implement the project. OBJECTIVE: To conduct a process evaluation of the CAAA community-academic partnership. DESIGN: In-depth interviews containing open-ended questions were conducted with SC members. Analysis included established methods for qualitative data, including focused coding and constant comparison methods. SETTING: Community setting in Detroit, Michigan. PARTICIPANTS: Twenty-three members of the CAAA SC. MEASUREMENTS: Common themes identified by SC members relating to the partnership's ability to achieve project goals and the successes and challenges facing the partnership itself. MAIN RESULTS: Identified partnership accomplishments included: successful implementation of a complex project, identification of children with previously undiagnosed asthma, and diverse participation and community influence in SC decisions. Challenges included ensuring all partners' influence in decision-making, the need to adjust to "a different way of doing things" in CBPR, constraints and costs of doing CBPR felt by all partners, ongoing need for communication and maintaining trust, and balancing the needs of science and the community through intervention. CONCLUSIONS: CBPR can enhance and facilitate basic research, but care must be given to trust issues, governance issues, organizational culture, and costs of participation for all organizations involved.     

Lesiones cutáneas y terapia biológica con antagonistas del factor de necrosis tumoral

The efficacy shown by biological therapy with tumor necrosis factor (TNF) antagonists has led in the recent years to its increased and extended use in different inflammatory arthopathies. Initially, safety studies of these drugs were mainly focused on the risk of infection and the development of malignancies. Recently, several cases of skin lesions induced by anti-TNF drugs have been reported with an increased incidence, highlighting the importance of the skin as a major target of the side effects of these drugs. In addition to skin lesions directly related to drug administration there is a wide spectrum of skin lesions of different morphology and etiology, especially the development of cutaneous immune-mediated conditions, an emergent phenomenon associated with this treatment. We describe the main skin lesions associated with treatment with anti-TNF drugs according to an extensive review of the literature.     

The human gene connectome as a map of short cuts for morbid allele discovery

High-throughput genomic data reveal thousands of gene variants per patient, and it is often difficult to determine which of these variants underlies disease in a given individual. However, at the population level, there may be some degree of phenotypic homogeneity, with alterations of specific physiological pathways underlying the pathogenesis of a particular disease. We describe here the human gene connectome (HGC) as a unique approach for human Mendelian genetic research, facilitating the interpretation of abundant genetic data from patients with the same disease, and guiding subsequent experimental investigations. We first defined the set of the shortest plausible biological distances, routes, and degrees of separation between all pairs of human genes by applying a shortest distance algorithm to the full human gene network. We then designed a hypothesis-driven application of the HGC, in which we generated a Toll-like receptor 3-specific connectome useful for the genetic dissection of inborn errors of Toll-like receptor 3 immunity. In addition, we developed a functional genomic alignment approach from the HGC. In functional genomic alignment, the genes are clustered according to biological distance (rather than the traditional molecular evolutionary genetic distance), as estimated from the HGC. Finally, we compared the HGC with three state-of-the-art methods: String, FunCoup, and HumanNet. We demonstrated that the existing methods are more suitable for polygenic studies, whereas HGC approaches are more suitable for monogenic studies. The HGC and functional genomic alignment data and computer programs are freely available to noncommercial users from http://lab.rockefeller.edu/casanova/HGC and should facilitate the genome-wide selection of disease-causing candidate alleles for experimental validation.