Tunable biohybrid hydrogels from coacervation of hyaluronic acid and PEO‐based block copolymers

Accurately tuning the macroscopic properties of biopolymer‐based hydrogels remains challenging due to the ill‐defined molecular architecture of the natural building blocks. Here, we report a biohybrid coacervate hydrogel, combining the biocompatibility and biodegradability of naturally occurring hyaluronic acid (HA) with the tunability of a synthetic polyethylene oxide (PEO) ‐based ABA‐triblock copolymer. Coacervation of the cationic ammonium or guanidinium‐functionalized copolymer A‐blocks with the anionic HA leads to hydrogel formation. Both mechanical properties and water content of the self‐healing hydrogels can be controlled independently by altering the copolymer structure. By controlling the strength of the interaction between the polymer network and small‐molecule cargo, both release rate and maximum release are controlled. Finally, we show that coacervation of HA and the triblock copolymer leads to increased biostability upon exposure to hyaluronidase. We envision that noncovalent crosslinking of HA hydrogels through coacervation is an attractive strategy for the facile synthesis of tunable hydrogels for biomedical applications

A Low-Cost, Portable Fluorescence Correlation Spectrometer for Disease Diagnosis

The DVD team is developing a cost-effective technique for measuring HIV load in resource-restricted regions. Our client is Dr. Phil Thuma and the Macha Research Trust in Zambia. Our design is based on advanced fluorescence spectroscopy that utilizes a fluorescence protein probe, confocal optics, and low-cost, low-power electronics to assess viral load in a patient blood sample. Our timeline for a functional exploded prototype is Fall 2021. Specifically, we are employing a method of spectroscopy that seeks to identify individual viruses in dilute samples by characteristic “bursts” in fluorescent and elastically scattered light. We have assembled a housing for a custom-designed detector, associated electronics, and signal processing hardware. One project goal is to integrate this modular design into a single printed circuit board. Communication between signal processing hardware and a software-based user interface implemented on a Raspberry Pi and touchscreen is achieved by the use of a Serial Peripheral Interface (SPI) protocol. The entire system is battery-powered. This system will allow for fast, effective viral load determinations in remote settings.https://mosaic.messiah.edu/engr2021/1002/thumbnail.jp

Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Regular Insulin Admitted to the Hospital

OBJECTIVE: Patients using U-500 regular insulin are severely insulin resistant, requiring high doses of insulin. It has been observed that a patient\u27s insulin requirements may dramatically decrease during hospitalization. This study sought to systematically investigate this phenomenon. METHODS: We performed a retrospective chart review of patients with U-500 insulin outpatient regimens who were admitted to the San Antonio Military Medical Center over a 5-year period. Each patient\u27s outpatient total daily dose (TDD) of insulin was compared to the average inpatient TDD. The outpatient estimated average glucose (eAG) was calculated from the glycated hemoglobin (HbA1c) and compared to the average inpatient glucose. RESULTS: There were 27 patients with a total of 62 separate admissions. The average age was 64.4 years, with a mean body mass index of 38.9 kg/m CONCLUSION: U-500 insulin is prone to errors in the hospital setting, so conversion to U-100 insulin is a preferred option. Despite a significant reduction in insulin TDD, these patients had clinically similar glucose levels. Therefore, patients taking U-500 insulin as an outpatient can be converted to a U-100 basal-bolus regimen with at least a 50% reduction of their outpatient TDD. ABBREVIATIONS: BG = blood glucose eAG = estimated average glucose HbA1c = glycated hemoglobin NPO = nil per os SPSS = Statistical Package for the Social Sciences TDD = total daily dose

Quantifying HIV-1 Viral Load with Fluorescence Correlation Spectroscopy

The DVD team is working to develop a cost-effective technique for measuring HIV load in resource-restricted regions. Our client is Dr Phil Thuma and the Macha Research Centre in Zambia. Our design utilizes a fluorescence correlation spectroscopy (FCS) approach, including a protein-engineered probe, custom optics, a field programmable gate array (FPGA), and a graphical display to assess viral load in a patient blood sample. In this talk we will present on the design and testing of our optical FCS system, the method of processing and analyzing the signal, and creation of the user interface display. Our team is currently finalizing the design of each device component and looking towards device integration and prototyping in the Fall of 2020.https://mosaic.messiah.edu/engr2020/1015/thumbnail.jp

Evaluation and development of traffic control devices

"This project was established to provide a means of conducting small-scale research activities on an as needed basis so that the results could be available within months of starting the specific research. This report summarizes the small-scale research activities that were conducted between September 2008 and August 2009.

Leadership Training in Endocrinology Fellowship? A Survey of Program Directors and Recent Graduates

Context: There is growing recognition that more physician leaders are needed to navigate the next era of medicine. Objective: To determine current opinions about leadership training in endocrinology fellowship programs. Design/Participants: Twenty-seven-question survey addressing various aspects of leadership training to current nationwide fellowship program directors (PDs) and fellowship graduates since 2010. Intervention: In partnership with the Endocrine Society, the electronic survey was advertised primarily via direct e-mail. It was open from March through July 2016. Main Outcome Measures: The survey addressed leadership traits, importance of leadership training, preferred timing, and content of leadership training. Results: Forty-six of 138 PDs (33.3%) and 147 of 1769 graduates (8.3%) completed the survey. Among PDs and graduates, there was strong agreement (\u3e95%) about important leadership characteristics, including job knowledge, character traits, team-builder focus, and professional skills. PDs (64.5%) and graduates (60.8%) favored teaching leadership skills during fellowship, with PDs favoring mentoring/coaching (75.0%), direct observation of staff clinicians (72.5%), and seminars (72.5%). Graduates favored a variety of approaches. Regarding topics to include in a leadership curriculum, PDs responded that communication skills (97.5%), team building (95.0%), professional skills (90.0%), clinic management (87.5%), strategies to impact the delivery of endocrinology care (85.0%), and personality skills (82.5%) were most important. Graduates responded similarly, with \u3e80% agreement for each topic. Finally, most PDs (89%) expressed a desire to incorporate more leadership training into their programs. Conclusions: Our survey suggests a need for leadership training in endocrinology fellowships. More work is needed to determine how best to meet this need

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC. Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age \u3c 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required. Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study crossed the futility boundary for OS and was closed prior to meeting accrual target. Median follow-up was 9 months. One-year OS was not different between the groups: 60.1% [95% CI: 41.2–74.7%] for PCI and 50.8% [95% CI:34.0–65.3%] for PCI+cRT (p=0.21). Three and 12-month rates of progression were 53.3% and 79.6% for PCI, and 14.5% and 75% for PCI+cRT. Time to progression favored PCI+cRT, HR=0.53 (95% CI: 0.32–0.87, p=0.01). One-patient in each arm had Grade-4 therapy related toxicity and one had Grade-5 therapy related pneumonitis with PCI+cRT. Conclusions—OS exceeded predictions for both arms. Consolidative RT delayed progression but did not improve 1-year OS

Transcription factor TFEB cell-autonomously modulates susceptibility to intestinal epithelial cell injury in vivo

Understanding the transcription factors that modulate epithelial resistance to injury is necessary for understanding intestinal homeostasis and injury repair processes. Recently, transcription factor EB (TFEB) was implicated in expression of autophagy and host defense genes in nematodes and mammalian cells. However, the in vivo roles of TFEB in the mammalian intestinal epithelium were not known. Here, we used mice with a conditional deletion of Tfeb in the intestinal epithelium (Tfeb ΔIEC) to examine its importance in defense against injury. Unperturbed Tfeb ΔIEC mice exhibited grossly normal intestinal epithelia, except for a defect in Paneth cell granules. Tfeb ΔIEC mice exhibited lower levels of lipoprotein ApoA1 expression, which is downregulated in Crohn’s disease patients and causally linked to colitis susceptibility. Upon environmental epithelial injury using dextran sodium sulfate (DSS), Tfeb ΔIEC mice exhibited exaggerated colitis. Thus, our study reveals that TFEB is critical for resistance to intestinal epithelial cell injury, potentially mediated by APOA1