Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.

Advancing Resident Education: Experiential Success in the Creation of a Comprehensive Clinical Didactic Series in Radiation Oncology.

Purpose: An effective didactic curriculum is a cornerstone for a successful residency program, as it is the basis upon which residents acquire the necessary knowledge and perspective to provide high-quality, evidence-based care. Here we describe our success in creating a standardized curriculum in clinical radiation oncology - one that was well-received and led to significantly improved performance on the national in-service examination. Methods and Materials: One-hundred and fifty topics were outlined in accordance with the American Board of Radiology; to accommodate this breadth of material, didactic frequency was increased from biweekly to daily. As a clinical correlate to these sessions, a teaching library of over 100 real-world cases was compiled for individual learning. Finally, comprehensive dosimetric constraints were compiled to aid residents in radiation therapy plan evaluation. To evaluate these curricular changes, anonymous questionnaires were provided to all residents and faculty, and de-identified resident clinical performance from the annual in-service examination was analyzed. Results: Before the introduction of the standardized curriculum, the mean clinical percentage on the in-service examination was 46%, equivalent to the 17th percentile. Within 2 years of implementation of the new curriculum, both the mean percentage and percentile were significantly improved, with the mean percentage correct at 69.3% and the mean percentile at the 59th percentile (P < .001 and P = .034, respectively). Feedback showed the curriculum to be well-received and used frequently outside of standard didactic hours. Conclusions: This is the first report of the creation of a standardized curriculum and outcomes in radiation oncology. Although there are certainly developmental challenges, addressing these barriers creates an education model that effectively imparts knowledge, fosters multidisciplinary thinking, and prepares residents for the diverse challenges of clinical practice. We present our institutional experience with the intent of publishing this curriculum on a national platform in the coming years.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O2-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O2-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2-GeMs. In vivo evaluation confirmed robust insertion and positioning of O2-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.

Modulation of diabetic wound healing using carbon monoxide gas-entrapping materials.

Diabetic wound healing is uniquely challenging to manage due to chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, is also known to provide unique therapeutic immune modulating effects. To facilitate delivery of CO, we have designed hyaluronic acid-based CO-gas-entrapping materials (CO-GEMs) for topical and prolonged gas delivery to the wound bed. We demonstrate that CO-GEMs promote the healing response in murine diabetic wound models (full-thickness wounds and pressure ulcers) compared to N2-GEMs and untreated controls.

Case report: Robotically visualized and biopsy-confirmed peritoneal carcinomatosis as initial identification of metastatic prostate adenocarcinoma in a patient with a history of prostatic urethral lift.

Background: Peritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure. Case presentation: A 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease-for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations. Conclusion: Our patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning.