Immune responses to gut bacteria associated with time to diagnosis and clinical response to T cell-directed therapy for type 1 diabetes prevention.

Immune-targeted therapies have efficacy for treatment of autoinflammatory diseases. For example, treatment with the T cell-specific anti-CD3 antibody teplizumab delayed disease onset in participants at high risk for type 1 diabetes (T1D) in the TrialNet 10 (TN-10) trial. However, heterogeneity in therapeutic responses in TN-10 and other immunotherapy trials identifies gaps in understanding disease progression and treatment responses. The intestinal microbiome is a potential source of biomarkers associated with future T1D diagnosis and responses to immunotherapy. We previously reported that antibody responses to gut commensal bacteria were associated with T1D diagnosis, suggesting that certain antimicrobial immune responses may help predict disease onset. Here, we investigated anticommensal antibody (ACAb) responses against a panel of taxonomically diverse intestinal bacteria species in sera from TN-10 participants before and after teplizumab or placebo treatment. We identified IgG2 responses to three species that were associated with time to T1D diagnosis and with teplizumab treatment responses that delayed disease onset. These antibody responses link human intestinal bacteria with T1D progression, adding predictive value to known T1D risk factors. ACAb analysis provides a new approach to elucidate heterogeneity in responses to immunotherapy and identify individuals who may benefit from teplizumab, recently approved by the U.S. Food and Drug Administration for delaying T1D onset.

Multi-criteria optimization for planning volumetric-modulated arc therapy for prostate cancer.

We aimed to compare the volumetric-modulated arc therapy (VMAT) plans with or without multi-criteria optimization (MCO) on commercial treatment-planning systems (Eclipse, Varian Medical System, Palo Alto, CA, USA) for patients with prostate cancer. We selected 25 plans of patients with prostate cancer who were previously treated on the basis of a VMAT plan. All plans were imported into the Eclipse Treatment Planning System version 15.6, and re-calculation and re-optimization were performed. The MCO plan was then generated. The dosimetric quality of the plans was evaluated using dosimetric parameters and dose indices that account for target coverage and sparing of the organs at risk (OARs). We defined the rectum, bladder, and bilateral femoral heads. The VMAT-MCO plan offers an improvement of gross treatment volume coverage with increased minimal dose and reduced maximal dose. In the planning treatment volume, the Dmean and better gradient, homogeneity, and conformity indexes improved despite the increasing hot and cold spots. When implemented through the MCO plan, a steeper fall off the adjacent OARs in the overlap area was achieved to obtain lower dose parameters. MCO generated better sparing of the rectum and bladder through a tradeoff of the increasing dose to the bilateral femoral heads within the tolerable dose constraints. Compared with re-optimization and re-calculation, respectively, significant dose reductions were observed in the bladder (241 cGy and 254 cGy; p<0.001) and rectum (474 cGy and 604 cGy, p<0.001) with the MCO. Planning evaluation and dosimetric measurements showed that the VMAT-MCO plan using visualized navigation can provide sparing of OAR doses without compromising the target coverage in the same OAR dose constraints.

[Effects of the personal stereo system on hearing in adolescents].

OBJECTIVES: This study was conducted to evaluate the effects of the personal stereo system on the hearing in adolescents. METHODS: A total of 68 adolescents (age: 13-18 years) who visited the ENT Department at a University Hospital in Daegu were personally interviewed. The questionnaires were about general characteristics of the subjects, the time of personal stereo system use (year, hour) and place. Cumulative exposure to the personal stereo system was calculated by the product of the total years and the daily hours of their use. Pure tone audiometry was performed and the hearing threshold was measured at 500, 1000, 2000, 4000 and 8000 Hz. RESULTS: The average time of using a personal stereo system a day was about 3 hours and 75% of the subjects used a personal stereo system for 2-5 years. The elevation of threshold was more prominent in the subjects who used personal stereo systems for 4 years and more compared with those subjects who used them for 3 years and under. The elevation of hearing threshold was also more prominent in the subjects who used personal stereo systems for 4 hours and more a day compared with those subjects who used personal stereo systems for 3 hours and under a day. The elevation of hearing threshold was more prominent in the subjects who used personal stereo systems for 13 hour x years and more compared to the subjects who used them 12 hour x years and under. CONCLUSIONS: These results suggest that the elevation of hearing threshold can happen to adolescents who used personal stereo systems for a long time. In order to prevent hearing loss, we need to teach adolescents appropriate usage of the personal stereo system and hearing tests should be included in the periodic school-based physical examination for the adolescents.