An axisymmetric mathematical model was established for millisecond-pulsed Nd:YAG laser heating of silicon-based positive-intrinsic-negative photodiode. The transient temperature fields were obtained by using the finite element method. The temperature dependences of the material parameters and the absorption coefficient were taken into account in the calculation. The results indicate that the optical absorption coefficient and the thermal conductivity are the two key factors for the temperature evolution. The diffusion of boron in the liquid phase and the introduction of deep-level defects in the depletion region of the photodiode were the two reasons for the millisecond laser-induced electrical degradation of the photodiode. The morphological damage threshold and electrical degradation threshold of the photodiode were obtained numerically. Meanwhile, the influence of the antireflection coating, the doping concentration, and the junction depth were also considered. The results show that the morphological damage threshold decreases with adding an antireflection coating, the increase of the doping concentration, and junction depth. The electrical degradation threshold increases only with the junction depth.

OBJECTIVES To investigate levels of S100A4 protein in plasma and S100A4 mRNA in tumours from patients with clear cell renal cell carcinoma (CCRCC), and correlate these with metastasis, survival and levels of vascular endothelial growth factor (VEGF). METHODS Plasma S100A4 and VEGF protein concentrations were measured using enzyme-linked immuno sorbent assays in 39 healthy subjects and 68 consecutive patients with untreated CCRCC. Levels of S100A4 and VEGF mRNA in tumour and matched control (healthy) tissue samples were measured using realtime quantitative reverse transcription- polymerase chain reaction. Findings were analysed with respect to clinico pathological characteristics. RESULTS Plasma VEGF concentrations were higher in patients with CCRCC than in healthy subjects. S100A4 and VEGF mRNA levels were up-regulated in CCRCC tumour tissue compared with control tissue samples. Logistic regression analysis revealed that up-regulated tumour S100A4 and VEGF mRNA levels were independent risk factors for the presence of invasion and/or metastasis. CONCLUSIONS S100A4 and VEGF are associated with tumour invasion and metastasis, and may be useful prognostic markers in patients with CCRCC. S100A4 and VEGF may represent potential targets for therapeutic intervention.

Drug-loaded nanoparticles have shown great potential in the study of carriers for disease-targeting drug delivery. Drug-loaded nanoparticles are excellent in keeping the drug in the systemic circulation for a prolonged period of time, introducing targeting molecules to improve targeting efficiency and to reduce side effects. A general review on active drug targeting of cancerous diseases by nanoparticles functionalized with ligands to folate receptors is presented including the (1) materials and methods for nanoparticle preparation,(2) methods for drug encapsulation,(3) surface functionalization of the nanoparticle with ligand to folate receptors, and (4) in vitro and in vivo experiments.

Aims:  There are growing data and a continuing controversy over the efficacy of folic acid supplementation in stroke prevention. We conducted a meta-analysis based on relevant, up-to-date published randomised trials to further examine this issue. Methods:  Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke with a fixed-effects model. Results:  Overall, folic acid supplementation reduced the risk of stroke by 8%(n = 55,764; RR: 0.92; 95% CI: 0.86-1.00, p = 0.038). In the 10 trials with no or partial folic acid fortification (n = 43,426), the risk of stroke was reduced by 11%(0.89; 0.82-0.97, p = 0.010). Within these trials, a greater beneficial effect was observed among trials with a lower percent use of statins [≤ 80%(median); 0.77; 0.64-0.92, p = 0.005], and a meta-regression analysis also suggested a positive dose-response relationship between percent use of statins and log-RR for stroke associated with folic acid supplementation (p = 0.013). A daily dose of 0.4-0.8mg folic acid appeared to be adequate for stroke prevention in comparison with larger doses. In the remaining five trials conducted in populations with folic acid fortification (n = 12,338), folic acid supplementation had no effect on stroke risk (1.03; 0.88-1.21, p = 0.69). Conclusions:  Our analysis indicated that folic acid supplementation is effective in stroke prevention in populations with no or partial folic acid fortification. In addition, a greater beneficial effect was observed among trials with a lower percent use of statins. Our findings underscore the importance of identifying target populations that can particularly benefit from folic acid therapy.

Clostridium difficile infection (CDI) is a serious diarrheal disease that often develops following prior antibiotic usage. One of the major problems with current therapies (oral vancomycin and metronidazole) is the high rate of recurrence. Nitazoxanide (NTZ), an inhibitor of pyruvate: ferredoxin oxidoreductase (PFOR) in anaerobic bacteria, parasites, Helicobacter pylori and Campylobacter jejuni also shows clinical efficacy against CDI. From a library of ∼250 analogues of NTZ, we identified leads with increased potency for PFOR. MIC screens indicated in vitro activity in the 0.05 - 2 μg/ml range against C. difficile. To improve solubility, we replaced the 2-acetoxy group with propylamine producing amixicile, a soluble (10 mg/ml), non-toxic (cell-based assays) lead that produced no adverse effects in mice by oral or i.p. routes at 200 mg/kg/day. In efficacy testing in mice treated (20 mg/kg/day: 5 days each) one day after receiving a lethal inoculum of C. difficile, amixicile showed slightly less protection than vancomycin by Day 5; mice treated with vancomycin displayed recurrence that resulted in significantly greater survival by amixicile than vancomycin on Day 12. Fidaxomicin, a newly approved CDI drug, showed similar activity to vancomycin in this model. All three drugs were comparable by weight loss/gain and severity of disease measures. Recurrence of CDI was common for mice treated with vancomycin or fidaxomicin, but not with mice receiving amixicile or NTZ. These results suggest that gut repopulation with beneficial (non-PFOR) bacteria, considered essential for protection against CDI, rebounds much sooner with amixicile therapy than with vancomycin or fidaxomicin. If the mouse model is indeed predictive of human CDI disease, then amixicile, a novel PFOR inhibitor, appears to be a very promising new candidate for treatment of CDI.

The sera of a retrospective cohort (n=41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in São Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients.

Candiduria is common in hospitalised patients, but the clinical relevance is still unclear. This study was done to further our knowledge on detection of and host responses to candiduria. Urines and clinical data from 136 patients in whom presence of yeast was diagnosed by microscopic urinalysis were collected. Diagnosis by standard urine culture methods on blood and MacConkey agar as well as on fungal culture medium (Sabouraud dextrose agar) was compared. Inflammatory parameters (IL-6 and IL-17, Ig) were quantified in the urine and compared with levels in control patients without candiduria. Standard urine culture methods detected only 37% of Candida spp. in urine. Sensitivity was especially low (23%) for C. glabrata and was independent of fungal burden. Candida specific IgG but not IgA was significantly elevated when compared with control patients (P < 0.0001 and 0.07 respectively). In addition, urine levels of IL-6 and IL-17 were significantly higher in candiduric patients when compared with control patients (P < 0.001). Multivariate analysis documented an independent association between an increased IgG (odds ratio (OR) 136.0, 95% confidence interval (CI) 25.7-719.2; P < 0.0001), an increased IL-17 (OR 17.4, 95% CI 5.3-57.0; P < 0.0001) and an increased IL-6 level (OR 4.9, 95% CI 1.9-12.4; P = 0.001) and candiduria. In summary, our data indicate that clinical studies on candiduria should include fungal urine culture and that inflammatory parameters may be helpful to identify patients with clinically relevant candiduria.

Oral Diseases (2012) Objective:  The aim of this study was to determine the expression of N-Glycolyl GM3 (NeuGcGM3) ganglioside in oral mucosal melanomas. Materials and Methods:  To assess the presence of cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mRNA, an RT-PCR assay was performed in melanoma cell line (ME), an oral mucosal ME, and two fresh oral mucosal melanoma tissues. Expression of NeuGcGM3 ganglioside was evaluated by immunohistochemistry in 44 primary oral mucosal melanomas and 10 oral melanotic nevi. Also, the expression of NeuGcGM3 was examined in ME by immunocytochemistry. Results:  We first checked the expression of CMAH in ME and two fresh oral mucosal melanoma tissues. Presence of NeuGcGM3 ganglioside was evident in 37 of 44 cases (84.1%), showing a diffuse cytoplasmic and membranous staining. Patients with primary occurrence showed high levels of NeuGcGM3 ganglioside compared to patients with secondary occurrence. On the other hand, negative immunoreaction was evidenced in oral melanotic nevi. ME also presented the expression of NeuGcGM3 by immunocytochemistry. Conclusions:  In this work, we for the first time evaluated the expression of 14F7 MAb immunorecognition in oral mucosal melanomas. Our results were in agreement with the assumption that NeuGcGM3 ganglioside may be considered as target for passive and active immunotherapy in oral mucosal melanomas expressing this molecule and indicate less risk of recurrence and a better prognosis. Moreover, ME provides a platform for more studies on the specific function of NeuGcGM3 in oral mucosal melanomas.

ABSTRACT: The diversity of posttraumatic auricular deformity caused by various factors often makes reconstruction exacting for the surgeon. During the past 10 years (from 2001 to 2010), a total of 60 patients (75 ears) were treated. The etiology of the deformities included burns (n = 35), traffic accidents (n = 10), cuts during fight (n = 8), and human bite injuries (n = 7). Based on previously published ones, we set a classification taking into consideration the involved tissue components, size of defects, and status of surrounding soft tissues, which categorized posttraumatic auricular deformities into 5 types. Different reconstruction modalities used for each type are described and discussed with examples. During follow-up, the degree of patients' satisfaction was high, and most reconstructed ears were accepted, barring a few complications. It must be admitted that achieving satisfactory outcome in the treatment of posttraumatic ear deformity similar to that of microtia is difficult, especially in the presence of extensive scar. Our 10-year experience suggested that proper classification and careful selection of techniques would be helpful.

BACKGROUND: Although αβ T cells are known to participate in the development of acute cardiac allograft rejection, the role of γδ T cells remains poorly understood. We hypothesized that γδ T cells contribute to acute allograft rejection thru interleukin (IL)-17 production. METHODS: Donor hearts from FVB mice (H-2(q)) were heterotopically transplanted into C57BL/6-wild type (WT) and γδ T cell-deficient (TCRδ(-/-)) recipient mice (H-2(b)). Overall graft survival was monitored. Graft infiltrating cell profile, including γδ T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6. RESULTS: Graft survival was prolonged in TCRδ(-/-) recipients compared with WT controls. Graft infiltrating cells, including CD45(+), CD4(+), CD8(+), and Gr1(+) cells were significantly decreased in TCRδ(-/-) recipients compared with WT. Donor hearts transplanted into TCRδ(-/-) recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCRδ(-/-) recipients. Finally, Vγ1(+) and Vγ4(+) T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating γδ T cells. CONCLUSIONS: The γδ T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The γδ T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.