Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients

ObjectivesTo evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).MethodsMulticentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year.ResultsWe studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6 +/- 11.7 years. The IMID included were: spondyloarthritis (n=43), Behcet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1),ConclusionsCZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Effectiveness of rotavirus vaccination in Spain

With the aim of determining rotavirus vaccine effectiveness (RVVE) in Spain, from Oct-2008/Jun-2009, 467 consecutive children below 2 years old with acute gastroenteritis (AGE) were recruited using a pediatric research network (ReGALIP-www.regalip.org) that includes primary, emergency and hospital care settings. Of 467 enrolled children, 32.3% were rotavirus positive and 35.0% had received at least one dose of any rotavirus vaccine. RRVE to prevent any episode of rotavirus AGE was 91.5% (95% CI: 83.7%-95.6%). RVVE to prevent hospitalization by rotavirus AGE was 95.6% (85.6-98.6%). No differences in RVVE were found regarding the vaccine used. Rotavirus vaccines have showed an outstanding effectiveness in Spain

Biology of moderately halophilic aerobic bacteria

The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

The antimicrobial activity of many of their natural products has brought prominence to the Streptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments. In the natural environment, antimicrobial compounds are likely to limit the growth of competitors, thereby offering a selective advantage to the producer, in particular when nutrients become limited and the developmental programme leading to spores commences. The study of the control of this secondary metabolism continues to offer insights into its integration with a complex lifecycle that takes multiple cues from the environment and primary metabolism. Such information can then be harnessed to devise laboratory screening conditions to discover compounds with new or improved clinical value. Here we provide an update of the review we published in NPR in 2011. Besides providing the essential background, we focus on recent developments in our understanding of the underlying regulatory networks, ecological triggers of natural product biosynthesis, contributions from comparative genomics and approaches to awaken the biosynthesis of otherwise silent or cryptic natural products. In addition, we highlight recent discoveries on the control of antibiotic production in other Actinobacteria, which have gained considerable attention since the start of the genomics revolution. New technologies that have the potential to produce a step change in our understanding of the regulation of secondary metabolism are also described

Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD

Paula Rodriguez-Miguelez,1 Nichole Seigler,1 Leon Bass,2 Thomas A Dillard,2 Ryan A Harris1,3 1Division of Clinical and Translational Sciences, Georgia Prevention Institute, Georgia Regents University, Augusta, GA, USA; 2Pulmonary and Critical Care Medicine, Department of Medicine, Georgia Regents University, Augusta, GA, USA; 3Sport and Exercise Science Research Institute, University of Ulster, Jordanstown, Northern Ireland, UK Background: Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population.Objectives: This study sought to examine the within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD.Methods: Baseline diameter, peak diameter, flow-mediated dilation, augmentation index, augmentation index at 75 beats per minute, and pulse wave velocity were assessed three times in 17 patients with COPD (six males, eleven females, age range 47–75 years old; forced expiratory volume in 1 second =51.5% predicted). Session A and B were separated by 3 hours (within-day), whereas session C was conducted at least 7 days following session B (between-day). Reproducibility was assessed by: 1) paired t-tests, 2) coefficients of variation, 3) coefficients of variation prime, 4) intra-class correlation coefficient, 5) Pearson’s correlations (r), and 6) Bland–Altman plots. Five acceptable assessments were required to confirm reproducibility. Results: Six out of six within-day criteria were met for endothelial function and arterial stiffness outcomes. Six out of six between-day criteria were met for baseline and peak diameter, augmentation index and pulse wave velocity, whereas five out of six criteria were met for flow-mediated dilation. Conclusion: The present study provides evidence for within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD. Keywords: arterial stiffness, endothelial function, flow-mediated dilation, pulse-wave velocity, chronic obstructive pulmonary diseas

Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review.

Exercise intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced exercise and functional capacity are the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction. We herein review the different modalities to quantify exercise intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in exercise and functional capacity, highlighting the fact that distinct causes may coexist and variably contribute to exercise intolerance in patients with HF