Crystallization of YIoQ, a GTPase of unknown function essential for Bacillus subtilis viability

YLoQ is a putative ATP/GTP-binding protein of unknown function identified from the complete sequence of the Bacillus subtilis genome. A gene-knockout programme established that yloQ is one of a set of some 270 indispensable genes for the viability of this organism. Crystals of YloQ have been grown from HEPES-buffered solutions at pH 7.5 containing polyethylene glycol and diffraction data have been collected extending to 2.5 Angstrom spacing

Models of self-organizing bacterial communities and comparisons with experimental observations

Simulations numériques de différents modèles de réaction-diffusion. Analyse critique des differents modéles et des expériences menées sur le Bacillus subtilis.Bacillus subtilis swarms rapidly over the surface of a synthetic medium creating hyperbranched dendritic communities. Models to reproduce such effects have been proposed under the form of parabolic Partial Differential Equations representing the dynamics of the active cells (both motile and multiplying), the passive cells (non-motile and non-growing) and the nutrient concentration. We test the numerical behavior of such models and compare them to relevant experimental data together with a critical analysis of the validity of the model based on recent observations of the swarming bacteria which show that nutrients are not limitating but distinct subpopulations growing at different rates are likely present

Ultrasound imaging of the carpal tunnel during median nerve compression

Median nerve (MN) compression is a recognized component of carpal tunnel syndrome (CTS). In order to document compressive changes in the MN during hand activity, the carpal tunnel was imaged with neuromuscular ultrasound (NMUS). Ten patients with CTS and five normal controls underwent NMUS of the MN at rest and during dynamic stress testing (DST). DST maneuvers involve sustained isometric flexion of the distal phalanges of the first three digits. During DST in the CTS patients, NMUS demonstrated MN compression between the contracting thenar muscles ventrally and the taut flexor tendons dorsally. The mean MN diameter decreased nearly 40%, with focal narrowing in the mid-distal carpal canal. Normal controls demonstrated no MN compression and a tendency towards MN enlargement, with an average diameter increase of 17%. Observing the pathologic mechanism of MN injury during common prehensile hand movements could help better understand how to treat and prevent CTS

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome

BACKGROUND. Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects. METHODS. This 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab. RESULTS. Overall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo. CONCLUSION. The safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes

Anterior interosseous nerve syndrome: retrospective analysis of 14 patients

Introduction: The anterior interosseous nerve (AIN) is a only motor nerve innervating the deep muscles of the forearm. Its compression is rare. We present a retrospective analysis of 14 patients with an AIN syndrome with a variety of clinical manifestations who underwent operative and conservative treatment. Patients and methods: Fourteen patients (six female, eight male, mean age 48 ± 9 years) were included. In six patients, the right limb was affected, and in eight patients the left limb. Conservative treatment was started for every patient. If no signs of recovery appeared within 3 months, operative exploration was performed. Final assessment was performed between 2 and 9 years after the onset of paralysis (mean duration of follow-up 46 ± 11 months). Patients were examined clinically for return of power, range of motion, pinch and grip strengths. Also the disability of the arm, shoulder, and hand (DASH) score was calculated. Results: Seven of our 14 patients had incomplete AIN palsy with isolated total loss of function of flexor pollicis longus (FPL), five of FPL and flexor digitorum profundus (FDP)1 simultaneously, and two of FDP1. Weakness of FDP2 could be seen in four patients. Pronator teres was paralysed in two patients. Pain in the forearm was present in nine patients. Four patients had predisposing factors. Eight patients treated conservatively exhibited spontaneous recovery from their paralysis during 3-12 months after the onset. In six patients, the AIN was explored 12 weeks after the initial symptoms and released from compressing structures. Thirteen patients showed good limb function. In one patient with poor result a tendon transfer was necessary. The DASH score of patients treated conservatively and operatively presented no significant difference. Conclusion: AIN syndrome can have different clinical manifestations. If no signs of spontaneous recovery appear within 12 weeks, operative treatment should be performed

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome

OBJECTIVE To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. RESULTS The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis

S.11.1 Influence of digital ulcer healing on disability and daily activity limitations in SSc

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of D