Background Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly-diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. Objective To test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. Methods We enrolled 40 children aged 9–36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/day in a double-blinded fashion. The primary endpoint, sustained unresponsiveness at four weeks after stopping E-OIT (4-SU), was assessed by DBPCFC either upon achieving four pre-specified criteria, or after three maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared to 154 matched standard-care controls. Results Of 40 consented subjects, three (7.5%) did not qualify. Overall, 29/37 (78%) in the intent-to-treat analysis achieved 4-SU (300 mg arm, 17/20 [85%]; 3000 mg, 12/17 [71%], p=0.43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29/32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgEs significantly increased (RR 19.42 [95%CI 8.7 – 43.7], p<0.001). Allergic side effects during E-OIT were common but all were mild-moderate. Conclusion At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.

Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were 13.3 ± 0.5 and 59.2 ± 0.8 µmol/g wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p<0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications.

Over 20 enzymes denoted as cyclomaltodextrinase, maltogenic amylase, or neopullulanase that share 40 -86% sequence identity with each other are found in public data bases. These enzymes are distinguished from typical ␣-amylases by containing a novel N-terminal domain and exhibiting preferential substrate specificities for cyclomaltodextrins (CDs) over starch. In this research field, a great deal of confusion exists regarding the features distinguishing the three groups of enzymes from one another. Although a different enzyme code has been assigned to each of the three different enzyme names, even a single differentiating enzymatic property has not been documented in the literature. On the other hand, an outstanding question related to this issue concerns the structural basis for the preference of these enzymes for CDs. To clarify the confusion and to address this question, we have determined the structures of two enzymes, one from alkalophilic Bacillus sp. I-5 and named cyclomaltodextrinase and the other from a Thermus species and named maltogenic amylase. The structure of the Bacillus enzyme reveals a dodecameric assembly composed of six copies of the dimer, which is the structural and functional unit of the Thermus enzyme and an enzyme named neopullulanase. The structure of the Thermus enzyme in complex with ␤-CD led to the conclusion that Trp 47 , a well conserved N-terminal domain residue, contributes greatly to the preference for ␤-CD. The common dimer formation through the novel N-terminal domain, which contributes to the preference for CDs by lining the active-site cavity, convincingly indicates that the three groups of enzymes are not different enough to preserve the different names and enzyme codes.

BackgroundTo investigate the sensitivity of various gamma criteria used in the gamma-index method for patient-specific volumetric modulated arc therapy (VMAT) quality assurance (QA) for stereotactic body radiation therapy (SBRT) using a flattening filter free (FFF) photon beam.MethodsThree types of intentional misalignments were introduced to original high-definition multi-leaf collimator (HD-MLC) plans. The first type, referred to Class Out, involved the opening of each bank of leaves. The second type, Class In, involved the closing of each bank of leaves. The third type, Class Shift, involved the shifting of each bank of leaves towards the ground. Patient-specific QAs for the original and the modified plans were performed with MapCHECK2 and EBT2 films. The sensitivity of the gamma-index method using criteria of 1%/1 mm, 1.5%/1.5 mm, 1%/2 mm, 2%/1 mm and 2%/2 mm was investigated with absolute passing rates according to the magnitudes of MLCs misalignments. In addition, the changes in dose-volumetric indicators due to the magnitudes of MLC misalignments were investigated. The correlations between passing rates and the changes in dose-volumetric indicators were also investigated using Spearman’s rank correlation coefficient (γ).ResultsThe criterion of 2%/1 mm was able to detect Class Out and Class In MLC misalignments of 0.5 mm and Class Shift misalignments of 1 mm. The widely adopted clinical criterion of 2%/2 mm was not able to detect 0.5 mm MLC errors of the Class Out or Class In types, and also unable to detect 3 mm Class Shift errors. No correlations were observed between dose-volumetric changes and gamma passing rates (γ < 0.8).ConclusionsGamma criterion of 2%/1 mm was found to be suitable as a tolerance level with passing rates of 90% and 80% for patient-specific VMAT QA for SBRT when using MapCHECK2 and EBT2 film, respectively.

The objective of this study was to investigate the hypoglycemic effects of quercetin (QE) in animal models of diabetes mellitus (DM). A starch solution (1 g/kg) with and without QE (100 mg/kg) or acarbose (40 mg/kg) was orally administered to streptozotocin (STZ)-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the effects of chronic feeding of QE, five-week-old db/db mice were fed an AIN-93G diet, a diet containing QE at 0.08%, or a diet containing acarbose at 0.03% for 7 weeks after 1 week of adaptation. Plasma glucose and insulin, blood glycated hemoglobin, and maltase activity of the small intestine were measured. Oral administration of QE (100 mg/kg) or acarbose (40 mg/kg) to STZ-treated rats significantly decreased incremental plasma glucose levels 30-180 min after a single oral dose of starch and the area under the postprandial glucose response, compared with the control group. QE (0.08% of diet) or acarbose (0.03% of diet) offered to db/db mice significantly reduced both plasma glucose and blood glycated hemoglobin compared to controls without significant influence on plasma insulin. Small intestine maltase activities were significantly reduced by consumption of QE or acarbose. Thus, QE could be effective in controlling fasting and postprandial blood glucose levels in animal models of DM.