Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

Demographic and Practice Characteristics of Physicians Who Care for Medically Underserved People: A National Survey.

OBJECTIVES: Few national studies have examined the influence of role models as a potential predictor for caring for medically underserved (MUS) patients. This study tested associations between previous physician role model exposure and caring for MUS populations, as well as examines the practice environments of these physicians. METHODS: Between October and December 2011, we mailed a confidential questionnaire to a representative sample of 2000 US physicians from various specialties. The primary criterion variable was "Is your patient population considered medically underserved?" We assessed demographic and other personal characteristics (calling, spirituality, and reporting a familial role model). We also asked about their practice characteristics, including a validated measure that assessed whether their work environment was considered chaotic/hectic or calm. RESULTS: The survey response rate was 64.5% (1289/2000). Female physicians and African American physicians were more likely to report working in MUS settings (multivariate odds ratio [OR] 1.32, confidence interval [CI] 1.00-1.76 and OR 2.65, CI 1.28-5.46, respectively). Physicians with high spirituality (OR 1.69, CI 1.02-2.79) and who reported familial role model exposure (OR 1.91, CI 1.11-3.30) also were associated with working with MUS populations. Physicians who worked in academic medical centers (OR 1.93, CI 1.45-2.56) and in chaotic work environments (OR 3.25, CI 1.64-6.44) also were more likely to report working with MUS patients. CONCLUSIONS: Familial role models may be influencing physicians to work with MUS patients, but the quality of their current work environments raises concerns about the long-term retention of physicians in MUS settings.

Molecular rotors as conditionally fluorescent labels for rapid detection of biomolecular interactions.

We demonstrate the use of fluorescent molecular rotors as probes for detecting biomolecular interactions, specifically peptide-protein interactions. Molecular rotors undergo twisted intramolecular charge transfer upon irradiation, relax via the nonradiative torsional relaxation pathway, and have been typically used as viscosity probes. Their utility as a tool for detecting specific biomolecular interactions has not been explored. Using the well characterized p53-Mdm2 interaction as a model system, we designed a 9-(2-carboxy-2-cyanovinyl) julolidine-based p53 peptide reporter, JP1-R, which fluoresces conditionally only upon Mdm2 binding. The reporter was used in a rapid, homogeneous assay to screen a fragment library for antagonists of the p53-Mdm2 interaction, and several inhibitors were identified. Subsequent validation of these hits using established secondary assays suggests increased sensitivity afforded by JP1-R. The fluorescence of molecular rotors contingent upon target binding makes them a versatile tool for detecting specific biomolecular interactions.

Contrast water therapy and exercise induced muscle damage: a systematic review and meta-analysis.

The aim of this systematic review was to examine the effect of Contrast Water Therapy (CWT) on recovery following exercise induced muscle damage. Controlled trials were identified from computerized literature searching and citation tracking performed up to February 2013. Eighteen trials met the inclusion criteria; all had a high risk of bias. Pooled data from 13 studies showed that CWT resulted in significantly greater improvements in muscle soreness at the five follow-up time points (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Despite comparing CWT to a large number of other recovery interventions, including cold water immersion, warm water immersion, compression, active recovery and stretching, there was little evidence for a superior treatment intervention. The current evidence base shows that CWT is superior to using passive recovery or rest after exercise; the magnitudes of these effects may be most relevant to an elite sporting population. There seems to be little difference in recovery outcome between CWT and other popular recovery interventions.

In vivo antitumor activity of biosynthesized silver nanoparticles using Ficus religiosa as a nanofactory in DAL induced mice model.

Ficus religiosa leaf extract was chosen as a reducing agent to fabricate silver nanoparticles (AgNPs) by a simple, cost-effective and eco-friendly process with the aim of treating Dalton's ascites lymphoma (DAL) in mice model. The formation of synthesized nanoparticles were characterized by UV-visible analysis (UV-vis), Fourier transform infra-red (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD) and zeta potential analyses. A peak at 431nm indicated the surface plasmon resonance of AgNPs. FTIR studies indicated polyphenols and proteins as possible encapsulates. TEM analysis showed particles size in the range of 5-35nm. Healthy Swiss Albino mice (30-35g) were intraperitoneally induced with DAL cells and treated with F. religiosa derived AgNPs at a dose of 50µg/ml. Blood and liver tissues were collected subsequent to dissection and subjected to hematological, biochemical and anticancer assays. Hematological and biochemical analyses revealed revival after treating with F. religiosa derived AgNPs. Antioxidant activity results further proved supportive evidence. The apoptosis inducing effect of AgNPs was observed through acridine orange staining (AO and EB) and DNA fragmentation assay. Anti- angiogenic activity was confirmed by observing vessel development. All these observations indicate that the AgNPs were effective in treatment of DAL.