Drew Carrillo (agendaangle32)

Excessive hypothalamic de novo ceramide synthesis has been shown to result in the establishment of central insulin resistance, endoplasmic reticulum stress, and inflammation. Additionally, excessive hypothalamic de novo ceramide synthesis has also been associated with changes in the activity of the autonomic nervous system. Such dysregulation of hypothalamic de novo ceramide synthesis forms the key starting point for the initiation of pathophysiological conditions such as obesity - which may or may not be associated with type 2 diabetes.The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 × 106 viable cells/mL with over 90 % viability 12 days post-inoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody. To highlight the needs for better intraoperative educational video recording in head and neck reconstructive surgery and to provide some information to standardize camera positioning in operative room. The Authors compared the Osmo Pocket© and the VITOM® 0° Telescope, evaluating the faculty and trainees point of view through specific questionnaires. The study was performed during two Masterclasses on Head and Neck Reconstructive Surgery that took place in the Hospital Casa Sollievo della Sofferenza in 2018 e 2019. Bulevirtide Camera positioning in the Operative Room was also assessed. In the faculty group, Osmo Pocket© was reported as frequently interfering with surgical intervention; the need for repositioning was reported more frequently in recording with VITOM®, that was evaluated as better in keeping a good "recording flow". In trainees' group, the perceived image quality with VITOM® was more appreciated, while Osmo Pocket© was considered superior in surgical field vision. Regarding the systems' positioning in lows a better view of anatomical details with less discomfort for the surgeon. Moreover it's important a standardization of the video means positioning in the operative room to reduce the pre-operative times and to aid in the choice of the most useful method for educational video recording. Adults with cerebral palsy (CP) in the United States die much earlier than those without CP, a health inequality likely shaped by causes of death. Existing research has not considered demographic differences in mortality patterns. To analyze differences in cause of death for adults who did/did not have CP reported on their death certificates and