Experimental platform utilising melting curve technology for detection of mutations in Mycobacterium tuberculosis isolates.

Tuberculosis (TB) remains one of the most deadly infections with approximately a quarter of cases not being identified and/or treated mainly due to a lack of resources. Rapid detection of TB or drug-resistant TB enables timely adequate treatment and is a cornerstone of effective TB management. We evaluated the analytical performance of a single-tube assay for multidrug-resistant TB (MDR-TB) on an experimental platform utilising RT-PCR and melting curve analysis that could potentially be operated as a point-of-care (PoC) test in resource-constrained settings with a high burden of TB. Firstly, we developed and evaluated the prototype MDR-TB assay using specimens extracted from well-characterised TB isolates with a variety of distinct rifampicin and isoniazid resistance conferring mutations and nontuberculous Mycobacteria (NTM) strains. Secondly, we validated the experimental platform using 98 clinical sputum samples from pulmonary TB patients collected in high MDR-TB settings. The sensitivity of the platform for TB detection in clinical specimens was 75% for smear-negative and 92.6% for smear-positive sputum samples. The sensitivity of detection for rifampicin and isoniazid resistance was 88.9 and 96.0% and specificity was 87.5 and 100%, respectively. Observed limitations in sensitivity and specificity could be resolved by adjusting the sample preparation methodology and melting curve recognition algorithm. Overall technology could be considered a promising PoC methodology especially in resource-constrained settings based on its combined accuracy, convenience, simplicity, speed, and cost characteristics.

Cysteamine toxicity in patients with cystinosis.

OBJECTIVE: To report new adverse effects of cysteamine. STUDY DESIGN: Detailed clinical information was obtained from the patients' physicians. RESULTS: New adverse events were reported in 8 of 550 patients with cystinosis treated with cysteamine in Europe during the last 5 years. Detailed clinical information was not available for 2 of these patients, 1 of whom died from cerebral ischemia. The 6 evaluable patients developed vascular elbow lesions (6/6), neurologic symptoms (1/6), bone and muscle pain (2/6), and/or skin striae (2/6). Analysis of biopsy specimens from the elbow lesions demonstrated angioendotheliomatosis with irregular collagen fibers. In 3 of the 6 patients, the daily cysteamine dose exceeded the recommended maximum of 1.95 g/m(2)/day. Dose reduction led to improvement of signs and symptoms in all 6 patients, suggesting a causal relationship with cysteamine administration. CONCLUSION: Cysteamine administration can be complicated by the development of skin, vascular, neurologic, muscular, and bone lesions. These lesions improve after cysteamine dose reduction. Doses >1.95 g/m(2)/day should be prescribed with great caution, but underdosing is not advocated.

Development and evaluation of a brief educational cartoon on trainee clinicians' awareness of risks of ionising-radiation exposure: a feasibility pre-post intervention study of a novel educational tool to promote patient safety.

BACKGROUND: Over recent decades, CT scans have become routinely available and are used in both acute medical and outpatient environments. However, there is a small increase in the risk of adverse consequences, including an increase in the risk of both malignancy and cataracts. Clinicians are often unaware of these facts, and this represents a challenge for medical educators in England, where almost 5 million CT scans are done annually. New whiteboard methodologies permit development of innovative educational tools that are efficient and scalable in communicating simple educational messages that promote patient safety. METHODS: A short educational whiteboard cartoon was developed to explore the prior observation that adolescents under the care of paediatricians had a much lower risk of receiving a CT scan than those under the care of clinicians who care for adults. This explored the risks after receiving a CT scan and strategies that can be used to avoid them. The educational cartoon was piloted on new doctors who were attending induction training at a busy teaching hospital. RESULTS: The main output was the educational whiteboard cartoon itself. Before the new medical trainees' induction, 56% (25/45) had received no formal training in radiation awareness, and this decreased to 26% (6/23) after the exposure to the educational cartoon (p=0.02). At baseline, 60% (27/45) of respondents considered that young females were at highest risk from exposure to ionising radiation, and this increased to 87% (20/23) after exposure to the educational cartoon (p=0.06). CONCLUSIONS: This proof-of-concept feasibility study demonstrates that whiteboard cartoons provide a novel and feasible approach to efficiently promote patient safety issues, where a short succinct message is often appropriate.

Mesoporous matrix encapsulation for the synthesis of monodisperse Pd5P2 nanoparticle hydrodesulfurization catalysts.

The synthesis of monodisperse 5-10 nm Pd5P2 catalytic particles by encapsulation in a mesoporous silica network, along with preliminary data on hydrodesulfurization (HDS) activity, is reported. Precursor Pd-P amorphous nanoparticles are prepared by solution-phase reaction of palladium(II) acetylacetonate with trioctylphosphine at temperatures up to 300 °C. Direct crystallization of Pd5P2 in solution by increasing the temperature to 360 °C leads to sintering, but particle size can be maintained during the transformation by encapsulation of the amorphous Pd-P particles in a mesoporous silica shell, followed by treatment of the solid at 500 °C under a reducing atmosphere, yielding Pd5P2@mSiO2. The resultant materials exhibit high BET surface areas (>1000 m(2)/g) and an average pore size of 3.7 nm. Access to the catalyst surface is demonstrated by dibenzodithiophene (DBT) HDS testing. Pd5P2@mSiO2 shows a consistent increase in HDS activity as a function of temperature, with DBT conversion approaching 60% at 402 °C. The ability to control particle size, phase, and sintering is expected to enable the fundamental catalytic attributes that underscore activity in Pd5P2 to be assessed.