Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

BACKGROUND: Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. METHODS: Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. RESULTS: Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small. Interestingly, lack of between-group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. CONCLUSION: These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials.

Sustained attention abnormalities in breast cancer survivors with cognitive deficits post chemotherapy: An electrophysiological study.

OBJECTIVE: Many breast cancer survivors (BCS) report cognitive problems following chemotherapy, yet controversy remains concerning which cognitive domains are affected. This study investigated a domain crucial to daily function: the ability to maintain attention over time. METHODS: We examined whether BCS who self-reported cognitive problems up to 3 years following cancer treatment (n=19) performed differently from healthy controls (HC, n=12) in a task that required sustained attention. Participants performed a target detection task while periodically being asked to report their attentional state. Electroencephalogram was recorded during this task and at rest. RESULTS: BCS were less likely to maintain sustained attention during the task compared to HC. Further, the P3 event-related potential component elicited by visual targets during the task was smaller in BCS relative to HC. BCS also displayed greater neural activity at rest. CONCLUSIONS: BCS demonstrated an abnormal pattern of sustained attention and resource allocation compared to HC, suggesting that attentional deficits can be objectively observed in breast cancer survivors who self-report concentration problems. SIGNIFICANCE: These data underscore the value of EEG combined with a less traditional measure of sustained attention, or attentional states, as objective laboratory tools that are sensitive to subjective complaints of chemotherapy-related attentional impairments.

Preoperative evaluation and predictive value of fine-needle aspiration and frozen section of thyroid nodules.

BACKGROUND: We sought to evaluate the predictive value of preoperative fine-needle aspiration (FNA) on surgical decision making by evaluating the final pathologic diagnosis and comparing it to the preoperative diagnosis. Further, we wished to calculate the predictive accuracy of each of several types of preoperative FNA diagnosis. STUDY DESIGN: A retrospective chart review of 151 thyroid resections between July 1990 and April 1996 at the University of Virginia was undertaken. The mean age was 45 years (range, 11 to 85 years). Preoperative laboratory values, presenting symptoms, imaging studies, and predictive values of preoperative FNA and intraoperative frozen section were analyzed. RESULTS: Symptomatology was poorly predictive of a benign versus malignant postoperative final pathologic diagnosis. Sensitivity, specificity, and accuracy of frozen section versus FNA was 86% versus 86%; 99% versus 93%, and 96% versus 92%, respectively, if the reading "cancer" or "suspicious" were predicted as positive for malignancy and "benign" or "follicular" were predicted as negative for malignancy. If only the reading "cancer" was predicted as positive for malignancy and only "benign" was predicted as negative for malignancy, sensitivity and specificity for FNA were 100% and 96%, respectively, and 100% and 99%, respectively, for frozen section. Forty-nine "follicular" lesions obtained by preoperative FNA resulted in 46 benign diagnoses after surgical resection. CONCLUSIONS: The use of preoperative FNA is a powerful diagnostic tool in the hands of skilled pathologists. There is increasing evidence that intraoperative frozen section adds little to intraoperative decision making in patients diagnosed with thyroid cancer by preoperative FNA. Less definitive interpretations decrease the sensitivity, specificity, and accuracy of the FNA diagnosis.

Characterization of an Escherichia coli gene encoding betaine aldehyde dehydrogenase (BADH): structural similarity to mammalian ALDHs and a plant BADH.

An open reading frame of 1476 nucleotides, cloned from a region of the Escherichia coli genome encoding betaine biosynthesis functions, was shown to encode a betaine aldehyde dehydrogenase (BADH; EC 1.2.1.8). Either of two adjacent codons (5'-GTGATG) could function as a start codon, producing a presumptive polypeptide of 491 or 490 amino acids. The deduced primary structure of the E. coli BADH showed 39-43% positional identity, over its entire length, to aldehyde dehydrogenases (ALDH: EC 1.2.1.3) of mammalian origin. This similarity increased to 75-77% when conservative aa substitutions were also taken into consideration. Spinach BADH was also similar to the bacterial BADH, showing 38% identity and 80% overall similarity. Other homologs included a fungal and a putative bacterial ALDH. Although E. coli BADH was specific for the substrate, betaine aldehyde, it showed the highest levels of similarity to the prototype human ALDH-2. Only one gap in each sequence had to be introduced for optimal alignment. The conservation between E. coli BADH and the ALDHs was also evident in the predicted secondary structures and hydrophilicity profiles of the polypeptides, suggesting a similarity in the overall folding patterns of ALDH and BADH. These observations suggest a common ancestry for BADH and ALDH, preceding prokaryote-eukaryote divergence.