Effects of mutations and glycosylations on STS activity: a site-directed mutagenesis study

Steroid sulphatase (STS) catalyses the formation of active steroids from inactive steroid sulphates. High levels of intra-tumoural STS mRNA are associated with a poor prognosis in post-menopausal patients with oestrogen receptor positive breast cancer. In this study, analysis of the mutated STS protein showed that N- and C-terminal truncated STS constructs are inactive. Histidine 136, located inside the active site, is crucial for STS activity whereas proline 212, which allows the protein turn into the membrane, is not. Mutations in glycosylation sites asparagine 47 and 259 decreased STS activity while asparagine 333 and 459 mutations did not affect it. However, immunoblot studies revealed that all four N-linked sites are glycosylated to some extent. In addition, a polyclonal antibody raised in rabbits against human STS was developed and characterised. These data increase our knowledge of the STS enzyme structure and may help design new STS inhibitors.     

Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.     

Efficacy and safety of ixekizumab in patients with active psoriatic arthritis with and without concomitant conventional disease-modifying antirheumatic drugs: SPIRIT-P1 and SPIRIT-P2 3-year results

Clinical Rheumatology - To evaluate the three-year efficacy and safety of ixekizumab with and without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use in...     

Assessing rheumatologists’ attitudes and utilization of classification criteria for ankylosing spondylitis and axial spondyloarthritis: a global effort

Clinical Rheumatology - This study aims to assess rheumatologists’ perceptions, utilization patterns, and attitudes towards the modified New York (mNY) criteria for ankylosing spondylitis...     

Micro-array Analysis of Cold Tolerant Tomato Expressing Nicotiana tabacum Osmotin

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Our earlier studies have established improved cold tolerance in the transgenic tomato (Solanum lycopersicum...     

Lessons learnt from an obstetric and neonatal emergency simulation program in India

BackgroundCombined obstetric and neonatal emergency simulation based training is gaining popularity in healthcare settings. Methods: In this qualitative study, through semi-structured one to one interviews, we evaluated participant attitudes, perceptions of retention of learning, and application to clinical practice one year after a simulation workshop. Audio recordings of interviews were transcribed, collated and subjected to thematic analysis. Results: Five major themes were identified through the thematic analysis: comparing simulation to clinical practice; learning and working in teams; thinking retention and sustainability; relating relevance of simulation based education to roles; and managing leadership. Conclusions: Participants’ acknowledgement of training being relevant to their routine practice, and keenness to learn management of complicated births highlighted the sustained impact of obstetric and neonatal emergency simulation training.     

Cast index in predicting outcome of proximal pediatric forearm fractures

Background:Many pediatric forearm fractures can be treated in plaster following closed reduction. The cast index (CI, a ratio of anteroposterior to lateral internal diameters of the cast at the fracture site) is a simple, reliable marker of quality of molding and a CI of >0.8 correlates with increased risk of redisplacement. Previously, CI has been applied to all forearm fractures. We hypothesize that an acceptable CI is more difficult to achieve and does not predict outcome in fractures of the proximal forearm.Results:The mean CI was 0.77. Remanipulation was required in five cases (6%), all distal half fractures – mean CI 0.79. CI was higher in proximal half forearm fractures (0.83 vs. 0.76, P = 0.006), nonetheless these fractures did not re-displace more than distal fractures.Conclusion:Cast index is useful in predicting redisplacement of manipulated distal forearm fractures. We found that in proximal half forearm fractures it is difficult to achieve a CI of <0.8, but increased CI does not predict loss of position in these fractures. We therefore discourage the use of CI in proximal half forearm fractures.