Effects of prosthetic stiffness and added mass on metabolic power and asymmetry in female runners with a leg amputation.

Similar to nonamputees, female athletes with unilateral transtibial amputation (TTA) using running-specific leg prostheses (RSPs) may have worse running economy and higher rates of running-related injury than male athletes. Optimizing RSP configuration for female athletes could improve running economy and minimize biomechanical asymmetry, which has been associated with running-related injury. Nine females with a TTA ran at 2.

A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors.

A majority of patients with cancer receive radiotherapy as part of their treatment regimens whether using external beam therapy or locally-delivered radioisotopes. While often effective, some tumors are inadequately controlled with radiation and radiotherapy has significant short-term and long-term toxicities for cancer survivors. Insights into molecular mechanisms involved in cellular responses to DNA breaks introduced by radiation or other cancer therapies have been gained in recent years and approaches to manipulate these responses to enhance tumor cell killing or reduce normal tissue toxicity are of great interest.

Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology.

Pharmacogenomics (PGx), the study of inherited genomic variation and drug response or safety, is a vital tool in precision medicine. In oncology, testing to identify PGx variants offers patients the opportunity for customized treatments that can minimize adverse effects and maximize the therapeutic benefits of drugs used for cancer treatment and supportive care. Because individuals of shared ancestry share specific genetic variants, PGx factors may contribute to outcome disparities across racial and ethnic categories when genetic ancestry is not taken into account or mischaracterized in PGx research, discovery, and application.

Vibrotactile Feedback for a Person with Transradial Amputation and Visual Loss: A Case Report.

After major upper-limb amputation, people face challenges due to losing tactile information and gripping function in their hands. While vision can confirm the success of an action, relying on it diverts attention from other sensations and tasks. This case report presents a 30-year-old man with traumatic, complete vision loss and transradial left forearm amputation.

Comparison of targeted vs. expanded pharmacogenomic testing: What are we missing?

Background: Pharmacogenomics (PGx) is used as a medication management strategy by a small but growing number of institutions. PGx allows prescribers to individually treat patients concordant with their genes. Recent litigation for preventable PGx-mediated adverse events highlights the need to accelerate PGx implementation for patient safety.

Validation of Pharmacogenomic Interaction Probability (PIP) Scores in Predicting Drug-Gene, Drug-Drug-Gene, and Drug-Gene-Gene Interaction Risks in a Large Patient Population.

Utilizing pharmacogenomic (PGx) testing and integrating evidence-based guidance in drug therapy enables an improved treatment response and decreases the occurrence of adverse drug events. We conducted a retrospective analysis to validate the YouScript PGx interaction probability (PIP) algorithm, which predicts patients for whom PGx testing would identify one or more evidence-based, actionable drug-gene, drug-drug-gene, or drug-gene-gene interactions (EADGIs). PIP scores generated for 36,511 patients were assessed according to the results of PGx multigene panel testing.

Implementing comprehensive pharmacogenomics in a community hospital-associated primary care setting.

Background: Pharmacogenomics (PGx) is an emerging field. Many drug-gene interactions are known but not yet routinely addressed in clinical practice. Therefore, there is a significant gap in care, necessitating development of implementation strategies.

Characterizing the Mechanical Stiffness of Passive-Dynamic Ankle-Foot Orthosis Struts.

People with lower limb impairment can participate in activities such as running with the use of a passive-dynamic ankle-foot orthosis (PD-AFO). Specifically, the Intrepid Dynamic Exoskeletal Orthosis (IDEO) is a PD-AFO design that includes a carbon-fiber strut, which attaches posteriorly to a custom-fabricated tibial cuff and foot plate and acts in parallel with the impaired biological ankle joint to control sagittal and mediolateral motion, while allowing elastic energy storage and return during the stance phase of running. The strut stiffness affects the extent to which the orthosis keeps the impaired biological ankle in a neutral position by controling sagittal and mediolateral motion.

Assessment of a Manual Method versus an Automated, Probability-Based Algorithm to Identify Patients at High Risk for Pharmacogenomic Adverse Drug Outcomes in a University-Based Health Insurance Program.

We compared patient cohorts selected for pharmacogenomic testing using a manual method or automated algorithm in a university-based health insurance network. The medication list was compiled from claims data during 4th quarter 2018. The manual method selected patients by number of medications by the health system's list of medications for pharmacogenomic testing.

Unmanaged Pharmacogenomic and Drug Interaction Risk Associations with Hospital Length of Stay among Medicare Advantage Members with COVID-19: A Retrospective Cohort Study.

Unmanaged pharmacogenomic and drug interaction risk can lengthen hospitalization and may have influenced the severe health outcomes seen in some COVID-19 patients. To determine if unmanaged pharmacogenomic and drug interaction risks were associated with longer lengths of stay (LOS) among patients hospitalized with COVID-19, we retrospectively reviewed medical and pharmacy claims from 6025 Medicare Advantage members hospitalized with COVID-19. Patients with a moderate or high pharmacogenetic interaction probability (PIP), which indicates the likelihood that testing would identify one or more clinically actionable gene-drug or gene-drug-drug interactions, were hospitalized for 9% (CI: 4-15%; < 0.

Impact of prostatic radiation therapy on bladder contractility and innervation.

Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.

Methods: Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT.

Democratizing genomics: Leveraging software to make genetics an integral part of routine care.

Genetic testing can provide definitive molecular diagnoses and guide clinical management decisions from preconception through adulthood. Innovative solutions for scaling clinical genomics services are necessary if they are to transition from a niche specialty to a routine part of patient care. The expertise of specialists, like genetic counselors and medical geneticists, has traditionally been relied upon to facilitate testing and follow-up, and while ideal, this approach is limited in its ability to integrate genetics into primary care.

Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in -deleted Mouse Models of Sarcoma.

Purpose: Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations.

Experimental Design: New drug formulations can be tested in animal models of sarcomas where the therapeutic response of different formulations can be compared using mice with identical tumor-initiating mutations.

A copy number gain on 18q present in primary prostate tumors is associated with metastatic outcome.

Background: Most prostate cancers (CaPs) grow slowly and remain indolent, yet some become aggressive and metastasize. Clinical decision-making requires prognostic markers that can be utilized at the time of diagnosis to identify aggressive tumors. Previous studies have shown a correlation between genomic alterations on the long arm of chromosome 18 (18q) and metastatic CaP.

Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer.

Background: Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED.

Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.

Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC.

Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival.

Introduction: High folate has an association with advanced prostate cancer and levels of testosterone. Herein, we perform a translational study to investigate the inverse response of serum folate in prostate cancer patients initiating androgen deprivation therapy (ADT) and a mirrored animal model.

Methods: A retrospective study was performed using the South Texas Veterans Healthcare System to identify patients with prostate cancer on ADT.

Can Exercise-Induced Modulation of the Tumor Physiologic Microenvironment Improve Antitumor Immunity?

The immune system plays an important role in controlling cancer growth. However, cancers evolve to evade immune detection. Immune tolerance and active immune suppression results in unchecked cancer growth and progression.

Investigating a chimeric anti-mouse PDGFRα antibody as a radiosensitizer in primary mouse sarcomas.

Background: Olaratumab (LY3012207/IMC-3G3/Lartruvo™) is a fully human monoclonal antibody specific for platelet-derived growth factor receptor alpha (PDGFRα). Phase Ib/II trial results of olaratumab plus doxorubicin in adult patients with advanced soft tissue sarcoma (STS) supported accelerated FDA approval of this regimen. Radiation therapy (RT) is frequently used for high-risk localized STS.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated.

Aim: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model.

Exercise as Adjunct Therapy in Cancer.

Data from observational studies indicate that both physical activity as well as exercise (ie, structured physical activity) is associated with reductions in the risk of recurrence and cancer mortality after a diagnosis of certain forms of cancer. Emerging evidence from preclinical studies indicates that physical activity/exercise paradigms regulate intratumoral vascular maturity and perfusion, hypoxia, and metabolism and augments the antitumor immune response. Such responses may, in turn, enhance response to standard anticancer treatments.

Clarifying the Relative Impacts of Vascular and Nerve Injury That Culminate in Erectile Dysfunction in a Pilot Study Using a Rat Model of Prostate Irradiation and a Thrombopoietin Mimetic.

Purpose: Radiation therapy (RT) offers an important and curative approach to treating prostate cancer, but it is associated with a high incidence of erectile dysfunction (ED). It is not clear whether the etiology of radiation-induced ED (RI-ED) is driven by RT-mediated injury to the vasculature, the nerves, or both. This pilot study sought to distinguish the effects of vascular and nerve injury in RI-ED by applying a vascular radioprotectant in a rat model of prostate RT.

Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer.

Background: While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in human cancers. In our current study, we generated six colorectal patient patient-derived xenografts (CRC PDXs) models and treated each PDX to voluntary wheel running (exercise) for 6-8 weeks or no exposure to the wheel (control).

Development and Preliminary Evaluation of a Murine Model of Chronic Radiation-Induced Proctitis.

Purpose: Radiotherapy (RT) is commonly used to treat most pelvic malignancies. While treatment is often effective, curative radiation doses to the rectum can result in chronic radiation-induced proctitis, which is characterized by diarrhea, tenesmus, and/or rectal bleeding, recently termed pelvic radiation disease. An animal model of chronic radiation-induced proctitis would be useful to test both preventative and therapeutic strategies to limit this morbidity but has been elusive because of the high rodent mortality associated with acute bowel RT injury.