Expression, Purification, Crystallization and Preliminary X-Ray Analysis of \u3cem\u3ePseudomonas aeuginosa\u3c/em\u3e AlgX

AlgX is a periplasmic protein required for the production of the exopolysaccharide alginate in Pseudomonas sp. and Azotobacter vinelandii. AlgX has been overexpressed and purified and diffraction-quality crystals have been grown using iterative seeding and the hanging-drop vapor-diffusion method. The crystals grew as flat plates with unit-cell parameters a=46.4, b=120.6, c=86.9Å, β=95.7°. The cyrstals exhibited the symmetry of space group P21 and diffracted to a minimimum d-spacing of 2.1Å. On the basis of the Matthews coefficient (VM=2.25Å3 Da-1), two molecules were estimated to be present in the asymmetric unit

Differential Sensitivity Between a Virtual Reality Balance Module and Clinically Used Concussion Balance Modalities

Balance assessments are part of the recommended clinical concussion evaluation, along with computerized neuropsychological testing and self-reported symptoms checklists. New technology has allowed for the creation of virtual reality (VR) balance assessments to be used in concussion care, but there is little information on the sensitivity and specificity of these evaluations. The purpose of this study is to establish the sensitivity and specificity of a VR balance module for detecting lingering balance deficits clinical concussion care

Multiple Sclerosis and Depression: Translation and Adaptation of the Spanish Version of the Chicago Multiscale Depression Inventory and the Study of Factors Associated with Depressive Symptoms

Objective: Depressive disorder occurs in up to 50% of persons with Multiple Sclerosis (PwMS). Accurate assessment of depression in MS is essential in clinical settings because depressive symptomatology can affect the clinical course of the disease. Methods: We translated, adapted, and tested the Spanish version of the Chicago Multiscale Depression Inventory (CMDI), a specific test to assess depression in neurological disorders. We compare our results with those obtained with previous versions of the questionnaire (English and Italian). Finally, we also analyze the relationship between the results obtained on the CMDI and demographic, clinical, and cognitive variables. Results: The results obtained with the Spanish version of the CMDI were similar to those observed in previous published versions. We also observed higher depression scores in PwMS (especially in progressive forms) compared with healthy controls. Moreover, depression symptomatology was related to higher disability and fatigue and worse cognitive performance in PwMS. Conclusions: The results support the validity of the CDMI in the Spanish population, as well as the association between depression and other characteristic symptoms of MS. These findings also emphasize the importance of good assessment and multidisciplinary treatment of depression in PwMS.We appreciate the collaboration of the Associació Esclerosis Múltiple de Castelló (AEMC).MCI/AEI (UJI B2020-02 to CF and CS-S); UJI (PREDOC/2020/22 to SFA). These funding sources did not play any role in designing the study or in the collection, analysis, and interpretation of the data

Heightened immune response to autocitrullinated porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. Objectives: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. Methods: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Results: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. Conclusions: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy

Does changing examiner stations during UK postgraduate surgery objective structured clinical examinations influence examination reliability and candidates' scores?

Objective Objective structured clinical examinations (OSCE) are widely used for summative assessment in surgery. Despite standardizing these as much as possible, variation, including examiner scoring, can occur which may affect reliability. In study of a high-stakes UK postgraduate surgical OSCE, we investigated whether examiners changing stations once during a long examining day affected marking, reliability, and overall candidates’ scores compared with examiners who examined the same scenario all day. Design, Setting, and Participants An observational study of 18,262 examiner-candidate interactions from the UK Membership of the Royal College of Surgeons examination was carried at 3 Surgical Colleges across the United Kingdom. Scores between examiners were compared using analysis of variance. Examination reliability was assessed with Cronbach’s alpha, and the comparative distribution of total candidates’ scores for each day was evaluated using t-tests of unit-weighted z scores. Results A significant difference was found in absolute scores differences awarded in the morning and afternoon sessions between examiners who changed stations at lunchtime and those who did not (p < 0.001). No significant differences were found for the main effects of either broad content area (p = 0.290) or station content area (p = 0.450). The reliability of each day was not affected by examiner switching (p = 0.280). Overall, no difference was found in z-score distribution of total candidate scores and categories of examiner switching. Conclusions This large study has found that although the range of marks awarded varied when examiners change OSCE stations, examination reliability and the likely candidate outcome were not affected. These results may have implications for examination design and examiner experience in surgical OSCEs and beyond

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star

The acceleration of the expansion of the universe, and the need for Dark Energy, were inferred from the observations of Type Ia supernovae (SNe Ia). There is consensus that SNe Ia are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that accrete matter from a companion star, although the nature of this companion remains uncertain. SNe Ia are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger -- they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass -- 1.4 solar masses. Here we show that the high redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar mass progenitor. Super-Chandrasekhar mass SNe Ia should preferentially occur in a young stellar population, so this may provide an explanation for the observed trend that overluminous SNe Ia only occur in young environments. Since this supernova does not obey the relations that allow them to be calibrated as standard candles, and since no counterparts have been found at low redshift, future cosmology studies will have to consider contamination from such events.Comment: 9 pages, 4 figures. To appear in Nature Sept. 21. Accompanying News & Views in same issue. Supplementary information available at www.nature.com/natur

Clinical audit of foot problems in patients with rheumatoid arthritis treated at Counties Manukau District Health Board, Auckland, New Zealand

<p>Abstract</p> <p>Background</p> <p>At diagnosis, 16% of rheumatoid arthritis (RA) patients may have foot joint involvement, increasing to 90% as disease duration increases. This can lead to joint instability, difficulties in walking and limitation in functional ability that restricts activities of daily living. The podiatrist plays an important role in the multidisciplinary team approach to the management of foot problems. The aim of this study was to undertake a clinical audit of foot problems in patients with RA treated at Counties Manukau District Health Board.</p> <p>Methods</p> <p>Patients with RA were identified through rheumatological clinics run within CMDHB. 100 patients were eligible for inclusion. Specific foot outcome tools were used to evaluate pain, disability and function. Observation on foot lesions were noted and previous history of foot assessment, footwear/insoles and foot surgery were evaluated.</p> <p>Results</p> <p>The median age of the cohort was 60 (IQR: 51–64) years old with median disease duration of 15 (IQR: 7.3–25) years. Over 85% presented with foot lesions that included corns and callus over the forefoot region and lesser toe deformities. Moderate to high disability was noted. High levels of forefoot structural damage were observed. 76% had not seen a podiatrist and 77% reported no previous formal foot assessment. 40% had been seen at the orthotic centre for specialised footwear and insoles. 27% of RA patients reported previous foot surgery. A large proportion of patients wore inappropriate footwear.</p> <p>Conclusion</p> <p>This clinical audit suggests that the majority of RA patients suffer from foot problems. Future recommendations include the provision of a podiatrist within the current CMDHB multidisciplinary rheumatology team to ensure better services for RA patients with foot problems.</p