The Mediating Role of Cortical Atrophy on the Relationship between the Resilience Index and Cognitive Function: Findings from the Healthy Brain Initiative.

Background: Lifestyle factors are linked to differences in brain aging and risk for Alzheimer's disease, underscored by concepts like 'cognitive reserve' and 'brain maintenance'. The Resilience Index (RI), a composite of 6 factors (cognitive reserve, physical and cognitive activities, social engagement, diet, and mindfulness) provides such a holistic measure. Objective: This study aims to examine the association of RI scores with cognitive function and assess the mediating role of cortical atrophy. Methods: Baseline data from 113 participants (aged 45+, 68% female) from the Healthy Brain Initiative were included. Life course resilience was estimated with the RI, cognitive performance with Cognivue®, and brain health using a machine learning derived Cortical Atrophy Score (CAS). Mediation analysis probed the relationship between RI, cognitive outcomes, and cortical atrophy. Results: In age and sex adjusted models, the RI was significantly associated with CAS (ß= -0.25, p = 0.006) and Cognivue® scores (ß= 0.32, p < 0.001). The RI-Cognivue® association was partially mediated by CAS (ß= 0.07; 95% CI [0.02, 0.14]). Conclusions: Findings revealed that the collective effect of early and late-life lifestyle resilience factors on cognition are partially explained by their association with less brain atrophy. These findings underscore the value of comprehensive lifestyle assessments in understanding the risk and progression of cognitive decline and Alzheimer's disease in an aging population.

Factors associated with radiation-induced nausea and vomiting in head and neck cancer patients treated with intensity modulated radiation therapy.

BACKGROUND AND PURPOSE: To investigate factors associated with radiation-induced nausea and vomiting (RINV) in the setting of head and neck intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: Forty-three patients treated with IMRT for head and neck cancer between 2002 and 2007 comprise the cohort. The majority (79%) were treated with an accelerated altered fractionation scheme, and concurrent chemotherapy was delivered to 23. A retrospective review of factors associated with nausea was performed. RESULTS: Eighteen patients (42%) reported grade 1 acute nausea, and seven patients (16%) reported grade 2 nausea. Factors significant for grade 1-2 nausea on univariate analysis included dose to the dorsal vagal complex of the mid-medulla, younger age, use of a low neck field, and Amifostine use. Only young age retained significance on multivariate analysis. High-grade nausea was associated with use of Amifostine (p=0.003) and concurrent chemotherapy (p=0.015). CONCLUSIONS: In addition to previously recognized emetic factors, young age and radiation dose to the dorsal vagal complex of the brainstem may play a role in development of nausea during head and neck IMRT.

High-dose-rate brachytherapy for large prostate volumes (> or =50cc)-Uncompromised dosimetric coverage and acceptable toxicity.

PURPOSE: The purpose of this study was to review our single-institution experience using high-dose-rate (HDR) brachytherapy in patients with large-volume prostate glands (> or =50cc). METHODS AND MATERIALS: Fifty-four patients treated with HDR brachytherapy for prostate cancer at the Penrose Cancer Center between 2001 and 2006 were identified as having an ultrasound volume of at least 50cc at the time of implant (range, 50-97.3cc; mean, 61.5cc; median, 57cc; upper quartile, 83.3-97.3cc). Neoadjuvant hormones (17 patients) were not routinely recommended unless the initial ultrasound volume suggested pubic arch interference or the patient's Gleason score or prostate specific antigen prompted use. All patients received HDR brachytherapy as a boost before or after conformal external beam radiation therapy to 4500cGy. Boost brachytherapy doses ranged from 1600 to 1900cGy, given in two to three fractions. RESULTS: The median D(90) (minimal dose to 90% of the prostate) was 109% of prescription dose (range, 95-115%) and the median V(100) (volume receiving 100% of the dose) was 96% (range, 90-99%). V(150) ranged from 10% to 35%, with a median value of 18.3%. Six patients (11%) required temporary placement of a urinary catheter for acute obstructive symptoms after brachytherapy. With a median followup of 1.8 years, there has been a single case of Grade 2 gastrointestinal toxicity and 1 patient has developed a bulbo-urethral stricture requiring dilation. There have been no cases of rectal bleeding. CONCLUSIONS: Large prostate volume is not a contraindication to HDR brachytherapy. Excellent dosimetric coverage can be attained with acceptable acute toxicity.

Characterization of a novel metabolic strategy used by drug-resistant tumor cells.

Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.