Methotrexate reduces HbA1c concentration but does not produce chronic accumulation of ZMP in patients with rheumatoid or psoriatic arthritis.

OBJECTIVES: The mechanism by which methotrexate (MTX) improves glucose homeostasis in patients with rheumatoid (RA) and psoriatic arthritis (PsA) remains undetermined. Animal studies indicate a role for intracellular accumulation of 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranosyl 5'-monophosphate (ZMP) but this has not been directly demonstrated in humans. We explored whether accumulation of ZMP is associated with improvements in glucose homeostasis during MTX therapy. METHOD: MTX-naïve, non-diabetic RA (n = 16) and PsA (n = 10) patients received uninterrupted MTX treatment for 6 months. To evaluate whether ZMP accumulated during MTX therapy, we measured the concentration of ZMP in erythrocytes and the concentration of its dephosphorylated derivative 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) in urine using liquid chromatography mass spectrometry (LC-MS/MS). To assess glucose homeostasis, we determined the concentration of glycated haemoglobin (HbA1c) and homeostasis model assessment of insulin resistance [HOMA-IR: fasting glucose (mmol/L) × fasting insulin (µU/mL)/22.5]. RESULTS: Erythrocyte ZMP and urinary AICAR concentrations did not increase during 6 months of MTX therapy. HbA1c concentration was reduced from 5.80 ± 0.29% at baseline to 5.51 ± 0.32% at 6 months (p < 0.001), while HOMA-IR remained unaltered. Reduction in HbA1c concentration was not associated with increased ZMP or AICAR concentrations. CONCLUSIONS: MTX therapy probably does not produce a chronic increase in erythrocyte ZMP or urinary AICAR concentrations. Collectively, our data do not support the hypothesis that MTX improves glucose homeostasis through chronic accumulation of ZMP.

Exercise-induced effects on a gym atmosphere.

We report results of analysis of a month-long measurement of indoor air and environment quality parameters in one gym during sporting activities such as football, basketball, volleyball, badminton, boxing, and fitness. We have determined an average single person's contribution to the increase of temperature, humidity, and dust concentration in the gym air volume of 12500 m(3) : during 90-min exercise performed at an average heart rate of 143 ± 10 bpm, a single person evaporated 0.94 kg of water into the air by sweating, contributed 0.03 K to the air temperature rise and added 1.5 µg/m(3) and 5 ng/m(3) to the indoor concentration of inhalable particles (PM10 ) and Ca concentration, respectively. As the breathing at the observed exercise intensity was about three times faster with respect to the resting condition and as the exercise-induced PM10 concentration was about two times larger than outdoors, a sportsman in the gym would receive about a sixfold higher dose of PM10 inside than he/she would have received at rest outside.

The impact of subjective image quality evaluation in mammography.

INTRODUCTION: According to the guidelines, the mammograms obtained in a screening program must be evaluated to ensure that the quality of the images obtained is above 75% of score 1 (perfect and good) and less than 3% of score 3 (inadequate). This is performed by a person (usually a radiographer), so subjectivity may influence the final evaluation of the images. The aim of this study was to evaluate the impact of subjectivity on breast positioning assessments on resultant screening mammograms. MATERIALS AND METHODS: Five radiographers evaluated a total of 1000 mammograms. One radiographer was an expert in assessing mammography images, while the other four evaluators had varying levels of experience. All images were anonymized, and the ViewDEX software was used for visual grading analysis. The evaluators were divided into two groups, each with two evaluators. Each group evaluated 600 images, with 200 images identical between the two groups. All images had already been evaluated by the expert radiographer. All scores were compared using the Fleiss' and Cohen's kappa coefficient and accuracy score. RESULTS: The results from Fleiss' kappa showed fair agreement in the mediolateral oblique (MLO) projection in the first group of evaluators whereas the other results showed poor agreement. When comparing the results from Cohen's kappa a maximum value of agreement between the evaluators was moderate 0.433 [95% CI 0.264-0.587] for the craniocaudal (CC) projection and 0.374 [95% CI 0.212-0.538] for the MLO projection. CONCLUSIONS: Based on our results, we can conclude that the agreement between all five raters was poor for both CC (κ = 0.165) and MLO (κ = 0.135) projections, based on the results of Fleiss' kappa statistic. The results show that the influence of subjectivity has a great impact on the evaluation of the quality of mammography images. IMPLICATIONS FOR PRACTICE: Thus, the images are evaluated by a person, which has a high impact on subjectivity in the assessment of positioning in mammography. To achieve a more objective assessment of the images and the resulting agreement between the evaluators, we would propose to change the method of assessment. The images could be evaluated by two persons, and in the event of a discrepancy, the images would be evaluated by a third person. A computer programme could also be developed that would allow a more objective evaluation based on the geometric characteristics of the image (angle and length of the pectoral muscle, symmetry, etc.).

Ablative fractional laser alters biodistribution of ingenol mebutate in the skin.

Topically applied ingenol mebutate (IngMeb) is approved for field-treatment of actinic keratosis and is currently being investigated for treatment of non-melanoma skin cancer (NMSC). Ablative fractional lasers (AFXLs) generate microscopic ablation zones (MAZs) in the skin, which may help induce a deep penetration needed for effective treatment of NMSC. Using Franz diffusion cells, uptake and bio-distribution were investigated over 21 h in intact (n = 9) and AFXL-exposed porcine skin (n = 58). A 2940-nm fractional Er:YAG laser generated intraepidermal (11.2 mJ/MAZ; 66 µm deep, 177 µm wide) and intradermal (128 mJ/MAZ; 570 µm deep, 262 wide) MAZ's with 16, 97, and 195 MAZs/cm(2). Surface ablation densities corresponded to 0.5, 2.5, and 5 % for intraepidermal MAZs, and corresponded to 1, 5, and 10.5 % for intradermal MAZs. Liquid-chromatography-mass-spectrometry quantified deposition of IngMeb in stratum corneum, epidermis, dermis, and receiver chamber. In intact skin, IngMeb readily penetrated to the epidermal layer (1,314 ng, 41 % of the applied IngMeb), while dermal deposition was limited (508 ng, 16 %). In AFXL-exposed skin, a profound dermal deposition of IngMeb was achieved, while less accumulated in SC and epidermis. Uptake depended entirely on laser density; increasing coverage from 0 % to 0.5 %, 1 %, 2.5 %, 5 %, and 10.5 % enhanced dermal uptake 1.6-, 2.1-, 3.1-, 3.4-, and 3.9-fold, respectively (p < 0.0001). Channel depth did not influence drug uptake; at 5 % density, dermal deposition with intraepidermal and intradermal MAZs was analogous (1801 vs. 1744; p = 0.447). In conclusion, IngMeb readily distributes to superficial layers of intact skin, whereas dermal uptake is limited. Independent of channel depth, AFXL enhances dermal drug deposition, providing for customized topical delivery and potential use of IngMeb for treatment of NMSC.