Atmospheric entry simulations of Mars lander bioload--experiments in support of Beagle 2

Simulations of the temperature and vacuum effects of Martian atmospheric entry upon Bacillus atrophaeus (formerly Bacillus subtilis var niger; 8058; NCIMB) endospores were carried out inside a purpose-built vacuum chamber. The work formed part of the study in support of planetary protection for the Beagle 2 Mars lander and investigated to what extent the outer surface of the lander's back heat shield would be sterilised during Mars atmospheric entry. The spores were heated to peak temperatures up to 300 degrees C over 30 s under vacuum conditions (10(-3) mbar). There was no effect on spore viability until peak temperatures reached 180-200 degrees C (12-15 s of heat exposure). Spore viability then fell rapidly with increasing temperature. Once peak temperatures exceeded 300 degrees C, no further spore viability was detected. The average heating rate was rapid (10 degrees C s(-1)); thus spores were exposed to peak temperatures for less than a second. These data inform on the process of determining bioburden reduction and control steps necessary for external surfaces of spacecraft which are non-sterile at launch, as well as providing new information about the ability of a model resistant organism to survive rapid, short-duration heating.     

TRANSFER RNA METHYLASES DURING MORPHOGENESIS IN THE CELLULAR SLIME MOLD

The enzymes that methylate tRNA were studied during the life cycle of the colonizing slime mold, Dictyostelium discoideum. Total and base specific tRNA methylase activities were determined in extracts from cells in morphogenetic synchrony. Eight hours after enforced aggregation, the total methylase capacity is reduced by about 40 per cent. The diminution appears to be due to the presence of inhibitors that do not inhibit the base specific enzymes to the same extent. There is a still greater diminution in enzyme activity in extracts of the mature fruiting bodies.     

Teaching Translational Research to Medical Students: The New York University School of Medicine's Master's of Science in Clinical Investigation Dual‐Degree Program

To develop the next generation of translational investigators, New York University School of Medicine (NYUSOM) and the NYU‐NYC Health and Hospitals Corporation Clinical and Translational Science Institute (NYU‐HHC CTSI) developed the Master''s of Science in Clinical Investigation dual‐degree (MD/MSCI) program. This 5‐year program dedicates 1 year to coursework and biomedical research, followed by a medical school/research overlap year, to prepare students for academic research careers. This paper details the MD/MSCI program''s curriculum and approach to mentorship, describes the research/professional interests of students, and reports student productivity. In the first 4 years of the program (2010–2014) 20 students were matriculated; 7 (35%) were women, and 12 (60%) research projects were in surgical specialties. To date, 14 students have applied to residency, and half pursued surgical residency programs. Our students have produced 68 accepted abstracts, 15 abstracts in submission, 38 accepted papers, and 24 papers in submission. Despite the time‐limited nature of this program, additional training in research design and implementation has promoted a high level of productivity. We conclude that dual‐degree training in medicine and translational research is feasible for medical students and allows for meaningful participation in valuable projects. Follow‐up is warranted to evaluate the academic trajectory of these students.     

Reproducibility of musculoskeletal ultrasound for determining monosodium urate deposition: concordance between readers

Objective

Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the interreader reproducibility of this modality is not well established. We therefore assessed agreement using a systematic approach.

Methods

Fifty male subjects ages 55–85 years were recruited during primary care visits to an urban Veterans Affairs hospital, and were assessed by musculoskeletal ultrasound (US) of the knees and first metatarsophalangeal (MTP) joints to evaluate for the double contour sign and tophi as evidence of MSU crystal deposition. Images were read by 2 blinded rheumatologists trained in musculoskeletal US, and the degree of concordance was determined for individual subjects, total joints, femoral articular cartilage (FAC), and first MTP joints. Subjects were further categorized into 3 diagnostic groups: gout, asymptomatic hyperuricemia (no gout, serum uric acid [UA] ≥6.9 mg/dl), and controls (no gout, serum UA ≤6.8 mg/dl), and reader concordance within these 3 groups was assessed.

Results

We observed almost perfect agreement between readers for 1) individual subjects (yes/no; n = 50, 100% agreement, κ = 1.000), 2) total joints (n = 200, 99% agreement, κ = 0.942), 3) FAC (n = 100, 99% agreement, κ = 0.942), and 4) first MTP joints (n = 100, 99% agreement, κ = 0.942). Furthermore, findings by side (right/left) and diagnostic group (gout, asymptomatic hyperuricemia, control) showed substantial to almost perfect concordance for all measures. MSU deposition was seen most commonly in gout patients, and deposition was also seen in some subjects with asymptomatic hyperuricemia, but in only 1 control.

Conclusion

Musculoskeletal US is reliable for detecting MSU deposition in FAC and first MTP joints in gout and asymptomatic hyperuricemia.     

Prevalence of contraindications and prescription of pharmacologic therapies for gout

Background

Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied.

Methods

A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease.

Results

The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III).

Conclusion

Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.     

The Role of Uric Acid and Other Crystals in Osteoarthritis

Clinicians have long assumed that an association exists between crystal arthropathies and the presence of osteoarthritis (OA). However, studies establishing an independent association between calcium pyrophosphate or uric acid crystal disease and OA are sparse. Even less is known about a possible pathogenic relationship. Whereas some studies suggest that the relationships between crystals and OA may not be incidental and that crystal deposition may contribute to the onset and/or acceleration of OA joint damage, other authors have challenged this assertion. In this review, we provide an overview of past and current research elucidating the role of crystal deposition, including monosodium urate, calcium pyrophosphate, and other crystals, in OA. Given the clinical frequency of gout and that agents exist to modulate serum UA levels, special attention is given to the role of monosodium urate crystals.