Use of cloud radar Doppler spectra to evaluate stratocumulus drizzle size distributions in large-eddy simulations with size-resolved microphysics.

A case study of persistent stratocumulus over the Azores is simulated using two independent large-eddy simulation (LES) models with bin microphysics, and forward-simulated cloud radar Doppler moments and spectra are compared with observations. Neither model is able to reproduce the monotonic increase of downward mean Doppler velocity with increasing reflectivity that is observed under a variety of conditions, but for differing reasons. To a varying degree, both models also exhibit a tendency to produce too many of the largest droplets, leading to excessive skewness in Doppler velocity distributions, especially below cloud base. Excessive skewness appears to be associated with an insufficiently sharp reduction in droplet number concentration at diameters larger than ~200 µm, where a pronounced shoulder is found for in situ observations and a sharp reduction in reflectivity size distribution is associated with relatively narrow observed Doppler spectra. Effectively using LES with bin microphysics to study drizzle formation and evolution in cloud Doppler radar data evidently requires reducing numerical diffusivity in the treatment of the stochastic collection equation; if that is accomplished sufficiently to reproduce typical spectra, progress toward understanding drizzle processes is likely.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

BACKGROUND: An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. RESULTS: The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance.

Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor.

Advanced glycation endproducts (AGEs) and a receptor for AGEs (RAGE) have been linked in the pathogenesis of diabetic nephropathy. RAGE is usually localized to podocytes and is increased in diabetes. RAGE activation increases reactive oxygen species production, which mediates hyperglycemia-induced podocyte apoptosis in early diabetic nephropathy. Here, we examined the interaction of AGE and RAGE on podocyte apoptosis. When we exposed murine cultured podocytes to bovine serum albumin (BSA) that was modified by AGEs or to carboxymethyl-lysine BSA, more apoptosis was found when compared with unmodified BSA. Similarly, more podocytes underwent detachment and apoptosis when cultured on AGE-modified collagen IV than on native collagen IV. AGEs isolated from sera of patients with chronic kidney disease also caused apoptosis of podocytes. Apoptosis was diminished by small interference RNA (siRNA) for RAGE in podocytes exposed to AGE-BSA, but not to AGE-modified collagen IV. Both AGE- and carboxymethyl-lysine modified-BSA activated p38MAP kinase and inhibition of this kinase reduced the apoptotic effect of AGE-BSA. Exposure to AGE-BSA was associated with Akt dephosphorylation and FOXO4 transcriptional activation leading to an increase in the expression of an effector protein of apoptosis, Bim. siRNA for FOXO4 abolished AGE-BSA-induced apoptosis of podocytes. Our study suggests that an AGE-RAGE interaction contributes to podocyte apoptosis by activation of the FOXO4 transcription factor.

The effect of antiglaucoma drugs on rabbit aqueous humor proteins determined by gel electrophoresis.

Previous studies indicate that there may be differences in the protein composition of the aqueous humor in normal and glaucomatous human eyes. These differences in protein composition and concentration may be due to the topical antiglaucoma medications used to treat glaucoma. These differences should be distinguished from any possible protein composition changes due to glaucoma. In order to study the effects of topical antiglaucoma medications on aqueous humor protein composition, we analyzed the aqueous humor of rabbit eyes topically treated with various antiglaucoma medications (timolol, pilocarpine, and dipivefrin). One eye of each rabbit was treated with the experimental drug, and the fellow eye was treated with saline solution (control). Thirty-six aqueous humor samples from 18 rabbits were obtained after 24 hours and 36 samples were obtained from 18 additional rabbits after 7 days of topical drug treatment. The protein composition of the aqueous humor samples was analyzed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Significant protein differences in aqueous humor samples were found between the eyes treated with timolol and the control eyes, whereas no significant differences were found between the eyes treated with pilocarpine or dipivefrin and the controls. These protein differences ranged from 14,000 to 18,000 daltons in molecular weight.