Effects of Diet and Exercise-Induced Weight Loss on Biomarkers of Inflammation in Breast Cancer Survivors: A Systematic Review and Meta-analysis.

BACKGROUND: Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence. METHODS: We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies. RESULTS: 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33; P = 0.04]. CONCLUSIONS: Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence. IMPACT: This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.

Risk Factors and Medical Symptoms Associated With Electronic Vapor Product Use Among Adolescents and Young Adults.

The use of electronic vapor products (EVPs) has increased dramatically in the past decade. The objectives of our study were to examine the frequency of EVP use; to identify demographic characteristics, risk-taking behaviors, and beliefs about vaping; and to determine symptoms associated with EVPs among adolescents. A questionnaire addressing these objectives was administered to a convenience sample of subjects aged 12 to 23 years. Among 494 completed questionnaires, 80% of responders were considered experimenters/nonusers (never tried or tried one time) and 20% were considered frequent users (at least once a month). We identified demographic features and risk-taking behaviors associated with EVP use. In the previous 6 months, frequent users were more likely to report headache, cough, sleep disturbances, dehydration, weakness, racing heart, chest pain, and tremors. Our findings provide evidence to support efforts to decrease EVP use through screening, education, and preventative strategies.

Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults.

OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

The Relationship Between Dopamine Neurotransmitter Dynamics and the Blood-Oxygen-Level-Dependent (BOLD) Signal: A Review of Pharmacological Functional Magnetic Resonance Imaging.

Functional magnetic resonance imaging (fMRI) is widely used in investigations of normal cognition and brain disease and in various clinical applications. Pharmacological fMRI (pharma-fMRI) is a relatively new application, which is being used to elucidate the effects and mechanisms of pharmacological modulation of brain activity. Characterizing the effects of neuropharmacological agents on regional brain activity using fMRI is challenging because drugs modulate neuronal function in a wide variety of ways, including through receptor agonist, antagonist, and neurotransmitter reuptake blocker events. Here we review current knowledge on neurotransmitter-mediated blood-oxygen-level dependent (BOLD) fMRI mechanisms as well as recently updated methodologies aimed at more fully describing the effects of neuropharmacologic agents on the BOLD signal. We limit our discussion to dopaminergic signaling as a useful lens through which to analyze and interpret neurochemical-mediated changes in the hemodynamic BOLD response. We also discuss the need for future studies that use multi-modal approaches to expand the understanding and application of pharma-fMRI.

Elevated medial temporal lobe and pervasive brain tau-PET signal in normal participants.

INTRODUCTION: Medial temporal lobe (MTL) uptake on tau-positron emission tomography (PET) is seen not only in Alzheimer's disease (AD) dementia but also in the aging population. The relationship of these findings to the development of AD dementia needs to be better understood. METHODS: Tau-PET with AV-1451 was performed on 576 cognitively unimpaired (CU) participants aged 50-94 years. The number of CUs with and without abnormal MTL regions and those with or without extra-MTL abnormalities was determined. Left and right regions were compared within each subject. RESULTS: Of CUs, 58% (334/576) had abnormal tau-PET findings. MTL abnormalities were present in 41% (238/576) of subjects. DISCUSSION: MTL tau-PET signal is often associated with abnormal extra-MTL tau-PET signal in CU participants and may represent neurofibrillary tangle development that could identify participants most likely to develop AD dementia. Tau-PET signal exclusively outside of the MTL is seen in 17% of CU participants and could be the initial findings in participants in different AD dementia pathways. Significant (P < .001) differences in tau-standardized uptake value ratio between sides were noted in 26 of 41 examined brain regions implicating further study of side-specific deficits.

Uptake of AV-1451 in meningiomas.

AIM: AV-1451 is an imaging agent labeled with the positron-emitting radiolabel Fluorine-18. 18F-AV-1451 binds paired helical filament tau (PHF-tau), a pathology related to Alzheimer's disease. In our study of AV-1451 uptake in the brains of cognitively normal subjects, we noted a case of a meningioma with visually significant uptake of AV-1451. OBJECTIVE: We initiated the present retrospective study to further examine cases of meningioma that underwent AV-1451 imaging. METHODS: We searched the patient records of 650 patients who had undergone AV-1451 at our institution for the keyword "meningioma" to identify potential cases. PET/CT and MRI results were visually reviewed and semi-quantitative analysis of PET was performed. A paired student's t test was run between background and tumor standard uptake values. Fisher's exact test was used to examine the association between AV-1451 uptake and presence of calcifications on CT. RESULTS: We identified 12 cases of meningioma, 58% (7/12) of which demonstrated uptake greater than background using both visual analysis and tumor-to-normal cortex ratios (T/N + 1.90 ± 0.83). The paired student's t test revealed no statistically significant difference between background and tumor standard uptake values (p = 0.09); however, cases with a T/N ratio greater than one showed statistically higher uptake in tumor tissue (p = 0.01). A significant association was noted between AV-1451 uptake and presence of calcifications (p = 0.01). CONCLUSION: AV-1451 PET imaging should be reviewed concurrently with anatomic imaging to prevent misleading interpretations of PHF-tau distribution due to meningiomas.