Practical Application of a Translation Tool from UML/OCL to Java Skeleton with JML Annotation

ICEIS 2012 - Proceedings of the 14th International Conference on Enterprise Information Systems, Volume 2, Wroclaw, Poland, 28 June - 1 July, 201

Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

Surgical Outcomes of Posterior Short Segment Fixation for Thoracolumbar Burst Fractures: A Study of Patients Treated without Vertebroplasty

There is no widespread agreement regarding the treatment of thoracolumbar burst fractures. While performing posterior short segment fixation of thoracolumbar burst fractures, we evaluated therapeutic outcomes in patients treated with screw insertion into fractured vertebral bodies without vertebroplasty. We also investigated the limitations associated with the treatment of burst fractures when vertebroplasty is not performed. Twenty-one of 51 patients with thoracolumbar burst fractures who were treated surgically in Ohta Nishinouchi Hospital were evaluated in the present study. These patients underwent posterior short segment fixation with screw insertion into the fractured vertebral bodies (only pedicle screws were inserted one level above and one level below the fractured vertebral bodies) without vertebroplasty. Vertebral angles were measured before surgery, immediately after surgery, and at the final follow-up examination. Changes in vertebral angles were compared and analyzed. The mean vertebral angles before and after surgery and at the final follow-up examination were 15.4°, 6.6°, and 9.1°, respectively. The mean postoperative correction loss was 2.5°. The therapeutic outcomes of posterior short segment fixation with screw insertion into fractured vertebral bodies without vertebroplasty were generally favorable

Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes

WSTĘP. Celem badania była ocena wpływu procesu zapalnego o małym nasileniu na wczesną fazę rozwoju zaawansowanej miażdżycy tętnic szyjnych u młodych chorych na cukrzycę typu 1. MATERIAŁ I METODY. U 55 chorych na cukrzycę typu 1 (22 mężczyzn i 33 kobiety, w wieku 22,1 &plusmn; 3,6 lat (&plusmn; SD), z cukrzycą trwającą 14,2 &plusmn; 5,7 lat) oraz u 75 osób bez cukrzycy z tej samej grupy wiekowej (28 mężczyzn i 47 kobiet) wykonano pomiar średniej i maksymalnej grubości kompleksu błony wewnętrznej i środkowej (IMT, intima-media thickness) w tętnicy szyjnej przy użyciu ultrasonograficznej prezentacji B. Stężenie białka C-reaktywnego dużej czułości (hs-CRP, high-sensitive C-reactive protein) oznaczano za pomocą immunonefelometru z zastosowaniem lateksu. WYNIKI. U chorych na cukrzycę typu 1 stężenie hs-CRP (mediana 0,35, zakres 0,05&#8211;1,47 mg/l u chorych na cukrzycę; mediana 0,14, zakres 0,05&#8211;1,44 mg/l u osób bez cukrzycy; p = 0,001) oraz średnia i maksymalna IMT (średnia IMT 0,76 &plusmn; 0,09 vs. 0,72 &plusmn; 0,04 mm, p = 0,003; maksymalna IMT 0,84 &plusmn; 0,11 vs. 0,77 &plusmn; 0,06, p < 0,0001) były wyraźnie większe niż u osób bez cukrzycy. Stężenie hs-CRP wykazywało wyraźną zależność ze średnią i maksymalną IMT u chorych na cukrzycę typu 1 oraz z maksymalną IMT u osób bez cukrzycy. Analiza metodą regresji wielowymiarowej przeprowadzona łącznie dla grupy chorych na cukrzycę oraz osób bez cukrzycy wykazała, że stężenie hs-CRP niezależnie koreluje ze średnią oraz maksymalną IMT (odpowiednio: p = 0,002 i p = 0,023), jak również z rozkurczowym ciśnieniem tętniczym, płcią i czasem trwania cukrzycy. WNIOSKI. Dane uzyskane w badaniu wskazują, że u młodych chorych na cukrzycę typu 1 stężenie hs- -CRP jest podwyższone, co może mieć związek z wczesną fazą rozwoju zaawansowanej miażdżycy tętnic szyjnych.INTRODUCTION. To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes. MATERIAL AND METHODS. The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 &#177; 3.6 years (&#177; SD), duration of diabetes 14.2 &#177; 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer. RESULTS. The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05&#8211;1.47 mg/l vs. median 0.14, range 0.05&#8211;1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 &#177; 0.09 vs. 0.72 &#177; 0.04 mm, P = 0.003; max IMT 0.84 &#177; 0.11 vs. 0.77 &#177; 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes. CONCLUSIONS. Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis

Prophylactic antibiotics for variceal hemorrhage: Clostridium difficile infection still can be a risk

Bron et al presented a retrospective study regarding the prophylactic use of antibiotics for variceal hemorrhage. Antibiotics appeared to improve the survival rate of patients without increasing clostridium difficile infection (CDI). We argue against the conclusion of the authors and consider that this result may be simply due to concurrent use of metronidazole, a therapeutic agent against CDI