Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India

Clinical Rheumatology - Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from...     

Methotrexate patient education: A quality improvement study

Objective . To determine patients' knowledge of the safe use and toxicity of methotrexate (MTX) and to define educational interventions implemented by a rheumatology nurse that improved patients' understanding of MTX therapy. Methods . One hundred eighty-three patients from a university-based rheumatology clinic who were taking MTX completed an initial knowledge questionnaire concerning the proper use and possible toxicity of MTX. Following completion, a nurse reviewed the correct answers with each patient and provided written information on MTX. One hundred thirty-eight of these patients completed a followup questionnaire at the next visit or by mail. The questionnaires were analyzed, and a total MTX knowledge score was calculated. Results . MTX knowledge improved significantly between questionnaires; mean total score (±SD) increased from 7.32 ± 3.99 to 10.23 ± 3.29 (P < 0.001). After accounting for a person's initial questionnaire score, the addition of a supplemental “MTX pocketcard” was associated with a higher score on the followup questionnaire (adjusted odds ratio [OR] = 2.37; 95% confidence interval [CI] 1.14, 4.95; P = 0.021). Patients over age 55 were 4 times more likely to have a poorer score compared with patients under age 45 (adjusted OR = 0.23; 95% CI 0.07, 0.73; P = 0.013). Conclusion . Knowledge of the toxicity and safe use of MTX was significantly improved by a patient education program utilizing a rheumatology nurse. Older individuals appear to be at higher risk for knowledge deficits. A supplemental MTX pocket-card proved to be a simple but beneficial addition to our MTX educational program.     

Correction to: Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme

In the published version, the Acknowledgements section was missing a funding note of co-author Dr C Verrill. The corrected version should read as follows.     

Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects

RAS mutations prevalent in high-risk leukemia have been linked to relapse and chemotherapy resistance. Efforts to directly target RAS proteins have been largely unsuccessful. However, since RAS-mediated transformation is dependent on signaling through the RAS-related C3 botulinum toxin substrate (RAC) small GTPase, we hypothesized that targeting RAC may be an effective therapeutic approach in RAS mutated tumors. Here we describe multiple small molecules capable of inhibiting RAC activation in acute lymphoblastic leukemia cell lines. One of these, DW0254, also demonstrates promising anti-leukemic activity in RAS-mutated cells. Using chemical proteomics and biophysical methods, we identified the hydrophobic pocket of phosphodiester 6 subunit delta (PDE6D), a known RAS chaperone, as a target for this compound. Inhibition of RAS localization to the plasma membrane upon DW0254 treatment is associated with RAC inhibition through a phosphatidylinositol-3-kinase/AKT-dependent mechanism. Our findings provide new insights into the importance of PDE6D-mediated transport for RAS-dependent RAC activation and leukemic cell survival.Subject terms: Acute lymphocytic leukaemia, Acute myeloid leukaemia, Drug development, Targeted therapies     

“We’ve Got Our Own Beliefs,Attitudes, Myths”: A Mixed Methods Assessment of Rural South African Health Care Workers' Knowledge of and Attitudes Towards PrEP Implementation

AIDS and Behavior - South Africa maintains the world’s largest HIV prevalence, accounting for 20.4% of people living with HIV internationally. HIV Pre-exposure prophylaxis (PrEP) has...     

Risk factors and associated problems in the management of infections with methicillin resistant Staphylococcus aureus

Purpose: It is necessary to define the problem of methicillin resistant Staphylococcus aureus (MRSA) in every hospital to evolve control strategies. The objectives of this study were to determine factors influencing the persistence of MRSA in patients with hospital acquired infection and to identify alternate cost effective antibiotics. Methods: A six month study was carried out for 50 patients with MRSA infection. Treatment modalities and risk factors were determined by a preset protocol. Minimum inhibitory concentration of commonly used antibiotics was determined. Results: The risk factors were prolonged postoperative morbidity, prior antibiotic therapy and emergency admissions. Seventy percent of the isolates were from postoperative cases undergoing emergency surgeries. Isolation was highest during the second week of hospital stay. Emergency admissions had a significantly higher chance of early isolation. Prior treatment with multiple antibiotics in 38% was found to be another major risk factor. Ofloxacin was seen to be efficacious in a small percentage of cases. Rifampicin in combination with ofloxacin and clindamycin were found to be other good alternatives. Ofloxacin was found to be the cheapest and vancomycin the most expensive, for a full course of treatment. Conclusions: Minimizing risk factors and attention to alternate cost effective combination therapy may ease the problem of management of infections with MRSA.