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1.  A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children 
Brain research  2010;1358:172-183.
Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO2 max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain.
doi:10.1016/j.brainres.2010.08.049
PMCID: PMC3953557  PMID: 20735996
Brain; Children; Exercise; Hippocampus; MRI; Physical activity
2.  Functional connectivity: a source of variance in the association between cardiorespiratory fitness and cognition? 
Neuropsychologia  2010;48(5):1394-1406.
Over the next twenty years the number of Americans diagnosed with dementia is expected to more than double (CDC 2007). It is, therefore, an important public health initiative to understand what factors contribute to the longevity of a healthy mind. Both default mode network (DMN) function and increased aerobic fitness have been associated with better cognitive performance and reduced incidence of Alzheimer’s disease among older adults. Here we examine the association between aerobic fitness, functional connectivity in the DMN, and cognitive performance. Results showed significant age-related deficits in functional connectivity in both local and distributed DMN pathways. However, in a group of healthy elderly adults, almost half of the age-related disconnections showed increased functional connectivity as a function of aerobic fitness level. Finally, we examine the hypothesis that functional connectivity in the DMN is one source of variance in the relationship between aerobic fitness and cognition. Results demonstrate instances of both specific and global DMN connectivity mediating the relationship between fitness and cognition. We provide the first evidence for functional connectivity as a source of variance in the association between aerobic fitness and cognition, and discuss results in the context of neurobiological theories of cognitive aging and disease.
doi:10.1016/j.neuropsychologia.2010.01.005
PMCID: PMC3708614  PMID: 20079755
cognitive aging; fMRI; functional connectivity; aerobic exercise; executive function; spatial memory
3.  Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy 
Journal of Clinical Oncology  2010;28(9):1481-1488.
Purpose
Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy.
Patients and Methods
Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing.
Results
Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed ≥ 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses.
Conclusion
Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted.
doi:10.1200/JCO.2009.24.1281
PMCID: PMC2849769  PMID: 20159824
4.  Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children 
The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9–12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3–0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3–0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.
doi:10.1089/ped.2010.0014
PMCID: PMC3281290  PMID: 22375277
5.  Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults 
Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.
doi:10.3389/fnagi.2010.00032
PMCID: PMC2947936  PMID: 20890449
exercise; aging; functional connectivity; fMRI; default mode network; executive function; aerobic fitness

Results 1-5 (5)