Redefining the H-NS protein family: a diversity of specialized core and accessory forms exhibit hierarchical transcriptional network integration.

H-NS is a nucleoid structuring protein and global repressor of virulence and horizontally-acquired genes in bacteria. H-NS can interact with itself or with homologous proteins, but protein family diversity and regulatory network overlap remain poorly defined. Here, we present a comprehensive phylogenetic analysis that revealed deep-branching clades, dispelling the presumption that H-NS is the progenitor of varied molecular backups.

Measuring Competency of Pharmacy Residents: A Survey of Residency Programs' Methods for Assessment and Evaluation.

Background: The Canadian Pharmacy Residency Board (CPRB) specifies the competencies that pharmacy residents must attain and the need for assessment and evaluation. Methods of assessment and evaluation are left to the discretion of individual programs. There is a scarcity of published literature compiling and comparing the strategies used by Canadian residency programs.

The small RNA RssR regulates myo-inositol degradation by Salmonella enterica.

Small noncoding RNAs (sRNAs) with putative regulatory functions in gene expression have been identified in the enteropathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). Two sRNAs are encoded by the genomic island GEI4417/4436 responsible for myo-inositol (MI) degradation, suggesting a role in the regulation of this metabolic pathway.

Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica serovar Typhimurium during adaptation to acid stress.

DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4-5) macrophage vacuole and DNA relaxation correlates with the upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane-located inhibitor of proton-driven F F ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation.

Small RNA, Big Effect: Control of Flagellin Production.

Many bacteria move in their environment using a remarkable, rotating nanomachine - the flagellum. In a recent publication, Choi et al. report a new addition to the group of flagellar regulators, a trans-acting small RNA (sRNA).

The Global Regulatory Cyclic AMP Receptor Protein (CRP) Controls Multifactorial Fluoroquinolone Susceptibility in Salmonella enterica Serovar Typhimurium.

Fluoroquinolone antibiotics are prescribed for the treatment of infections, but resistance to this family of antibiotics is growing. Here we report that loss of the global regulatory protein cyclic AMP (cAMP) receptor protein (CRP) or its allosteric effector, cAMP, reduces susceptibility to fluoroquinolones. A Δ mutation was synergistic with the primary fluoroquinolone resistance allele , thus able to contribute to clinically relevant resistance.

Genetic Regulation of Virulence and Antibiotic Resistance in Acinetobacter baumannii.

Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance.

Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab.

Objective: Chronic pain and progressive loss of physical function with AS may adversely affect health-related quality of life (HRQoL). The objective of this study was to assess the 5-year data regarding spinal mobility, physical function and HRQoL in patients with AS who participated in the Adalimumab Trial Evaluating Long-term Efficacy and Safety for AS (ATLAS) study.

Methods: Patients received blinded adalimumab 40 mg or placebo every other week for 24 weeks, then open-label adalimumab for up to 5 years.

Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study.

Introduction: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise.

Methods: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices.

Transmission of an oxygen availability signal at the Salmonella enterica serovar Typhimurium fis promoter.

The nucleoid-associated protein FIS is a global regulator of gene expression and chromosome structure in Escherichia coli and Salmonella enterica. Despite the importance of FIS for infection and intracellular invasion, very little is known about the regulation of S. enterica fis expression.

Application and modifications of minimal disease activity measures for patients with psoriatic arthritis treated with adalimumab: subanalyses of ADEPT.

Objective: This posthoc analysis evaluated the percentage of patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) and compared the results with a modified MDA substituting the physician global assessment (PGA) for the Psoriasis Activity and Severity Index (PASI) using data from the ADalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT; NCT00646386).

Methods: Patients with active PsA were randomized to receive adalimumab 40 mg or placebo every other week for 24 weeks. MDA was defined as achieving ≥ 5 of the following criteria: tender joint count ≤ 1; swollen joint count ≤ 1; PASI ≤ 1 or body surface area ≤ 3%; patient pain score ≤ 15 [1-100 mm visual analog scale (VAS)]; patient global assessment (PGA) of disease activity ≤ 20 (1-100 mm VAS); Health Assessment Questionnaire ≤ 0.

Murine diacylglycerol acyltransferase-2 (DGAT2) can catalyze triacylglycerol synthesis and promote lipid droplet formation independent of its localization to the endoplasmic reticulum.

Triacylglycerol (TG) is the major form of stored energy in eukaryotic organisms and is synthesized by two distinct acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2. Both DGAT enzymes reside in the endoplasmic reticulum (ER), but DGAT2 also co-localizes with mitochondria and lipid droplets. In this report, we demonstrate that murine DGAT2 is part of a multimeric complex consisting of several DGAT2 subunits.

Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy.

Introduction: Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatment with infliximab (IFX) and/or etanercept (ETN).

Methods: Both trials were 12-week, open-label studies with an optional extension period up to week 20.

Clinical manifestations and responsiveness to adalimumab are similar in patients with ankylosing spondylitis with and without concomitant psoriasis.

Objectives: To compare the clinical manifestations of spinal disease, peripheral arthritis and enthesitis, and to evaluate the effectiveness of adalimumab in a large cohort of patients with AS in relation to the presence or absence of psoriasis.

Methods: Patients aged > or = 18 years with active AS were enrolled in an open-label study of adalimumab 40 mg every other week. Clinical symptoms were measured at baseline and Week 12 using standard assessment criteria.

Effectiveness of adalimumab in treating patients with ankylosing spondylitis associated with enthesitis and peripheral arthritis.

Introduction: The purpose of this study was to investigate the effectiveness of adalimumab in enthesitis and peripheral arthritis in patients with ankylosing spondylitis (AS).

Methods: Adults with active AS (Bath ankylosing spondylitis disease activity index [BASDAI] > or = 4) received adalimumab 40 mg every other week with standard antirheumatic therapies in a 12-week, open-label study. Effectiveness in enthesitis was assessed using the Maastricht ankylosing spondylitis enthesitis score (MASES, 0-13) and by examining the plantar fascia in patients with enthesitis (> or = 1 inflamed enthesis) at baseline; effectiveness in peripheral arthritis was evaluated using tender and swollen joint counts (TJC, 0-46; SJC, 0-44) in patients with peripheral arthritis (> or = 1 swollen joint) at baseline.

Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions.

Objectives: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions.

Methods: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI).

Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis.

Objective: We evaluated the effectiveness and safety of adalimumab in a large cohort of patients with active ankylosing spondylitis (AS) and identified clinical predictors of good clinical response.

Methods: Patients with active AS [Bath AS Disease Activity Index (BASDAI)>or=4] received adalimumab 40 mg every other week in addition to their standard antirheumatic therapies in a multinational 12-week, open-label study. We used 3 definitions of good clinical response: 50% improvement in the BASDAI (BASDAI=50), 40% improvement in the ASsessments of SpondyloArthritis International Society criteria (ASAS40), or ASAS partial remission.

Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion.

Objectives: To evaluate the effectiveness and safety of adalimumab in treating patients with AS and advanced structural damage.

Methods: Patients with active AS [Bath AS Disease Activity Index (BASDAI) > or =4] received 40 mg of adalimumab every other week plus their standard anti-rheumatic therapies in this 12-week, open-label study. Investigators documented the presence or absence of advanced ankylosis based on previous radiographs.

Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study.

Objective: To evaluate the effect of adalimumab on the frequency of anterior uveitis (AU) flares in patients with active ankylosing spondylitis (AS).

Methods: We determined the history of ophthalmologist-diagnosed AU in 1250 patients with active AS who were enrolled in a multinational, open-label, uncontrolled clinical study of treatment with adalimumab, 40 mg every other week for up to 20 weeks. All AU flares were documented throughout the adalimumab treatment period plus 70 days.

An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status.

This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index.

Clinical remission and/or minimal disease activity in patients receiving adalimumab treatment in a multinational, open-label, twelve-week study.

Objective: To evaluate the effect of adalimumab treatment on clinical remission and/or minimal disease activity (MDA) in 6,610 patients with active rheumatoid arthritis (RA) who were enrolled in the Research in Active RA trial, a multinational, open-label, 12-week study with an optional extension period.

Methods: Clinical remission was defined as a Disease Activity Score in 28 joints (DAS28)<2.6, Simplified Disease Activity Index (SDAI) score View Article and Find Full Text PDF

Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice.

Objective: To evaluate the effectiveness and safety of adalimumab in patients with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor (TNF) antagonists for any reason in clinical practice.

Methods: ReAct (Research in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled adults with active RA who had previously been treated with traditional disease-modifying anti-rheumatic drugs or biological response modifiers. Patients self-administered adalimumab 40 mg subcutaneously every other week for 12 weeks and were allowed to enter an optional long-term extension phase.

Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial.

Objective: To evaluate the safety and effectiveness of adalimumab alone or in combination with standard disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA).

Methods: Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre, open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase. Patients were allowed to continue with pre-existing traditional DMARDs.

Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists.

Background: Patients with rheumatic diseases receiving antitumour necrosis factor (TNF)-alpha-based treatment may develop cutaneous reactions.

Objectives: To analyse the new onset or aggravation of skin lesions in patients with a rheumatic disease during treatment with TNF-alpha antagonists.

Methods: We conducted a prospective analysis of 35 of 150 patients with a long history of rheumatic disease, including rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) and psoriatic arthritis, to test for the development of cutaneous manifestations during anti-TNF-alpha (infliximab, adalimumab or etanercept) treatment.