Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease.

The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional changes in brain regions involved with memory and autonomic/emotional regulation are implicated in the vasoconstrictive stress response, including the medial prefrontal cortex (anterior cingulate), insula, and dorsolateral prefrontal cortex. Subjects with a history of coronary artery disease (N = 59) underwent measurement of microvascular vasomotor tone with the EndoPAT device and O-15 positron emission tomography (PET) imaging of the brain during exposure to mental stress and control conditions. The peripheral arterial tonometry (PAT) ratio was calculated as the mean peripheral vasomotor tone during stress divided by the mean tone during rest. Whole brain contrasts were performed between groups above and below the median PAT ratio, and significant contrasts were defined with cutoff p < 0.005. Stress-induced peripheral vasoconstriction (below median PAT ratio) was associated with increased stress activation in insula and parietal cortex, and decreased activation in the medial prefrontal cortex with stress tasks compared to control tasks. These findings demonstrate that stress-induced vasoreactivity is associated with changes in brain responses to stress in areas involved in emotion and autonomic regulation. These findings have important implications on possible treatments for mental stress-induced vascular toxicity.

Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia.

Previous work has demonstrated that a single subcutaneous dose of salmon calcitonin leads to a transient decline in circulating levels of FGF23 in patients with X-linked hypophosphatemia (XLH). Since the calcitonin receptor is expressed on osteocytes, this raises the possibility that interdicting signals through that receptor could modulate circulating levels of FGF23 in XLH. In the present study, 21 subjects with XLH were randomly assigned to receive either placebo nasal spray or 400 IU of nasal salmon calcitonin daily for three months. On the first and last day of the study, serial measurements of FGF23, 1,25-dihydroxyvitamin D, and TmP/GFR were made over 27 h. At the beginning of Visit 2 (the first day of month 2) and the beginning of Visit 3 (the first day of month 3), single, first-morning, fasting measurements of these same parameters were made before the next administered dose of study drug. Following the initial or final dose of study drug, there were no differences in area under the curve, based on treatment assignment, for the three principal outcome variables. Similarly, there were no differences in the fasting measures taken at the beginning of Visit 2 or Visit 3 compared to the fasting values on either day 2 of Visit 1 or the fasting values on day 2 of Visit 4. There were also no significant changes over time in serum phosphorus, serum calcium, circulating levels of PTH, CTx, or P1NP. The reasons why nasal salmon calcitonin did not recapitulate the findings with subcutaneously administered drug may relate to the kinetics of drug delivery, the bioavailability of drug or peak drug dose achieved. It remains possible, however, that other means of altering calcitonin receptor signaling may still provide an opportunity for regulating FGF23 production.

Adenosquamous Carcinoma of the Esophagus: An NCDB-Based Investigation on Comparative Features and Overall Survival in a Rare Tumor.

OBJECTIVES: Esophageal adenosquamous carcinoma (ASC) is a rare tumor with characteristics of adenocarcinoma (AC) and squamous cell carcinoma (SCC), the two most common esophageal cancers. Its behavior is aggressive but poorly understood. Using the National Cancer Database (NCDB), the clinical features and overall survival of ASC were compared with AC and SCC. METHODS: The NCDB was queried for patients with esophageal ASC, AC, and SCC. Univariate association of histology with patient characteristics and overall survival were analyzed and socioeconomic characteristics were balanced. RESULTS: Clinical M stage was 0 in a significantly lower proportion of ASC (69.0%) than in AC (70.9%) or SCC (75.6%) (p < 0.001). Median survival was lower in patients with ASC (9.6 months) than with AC (13.5) or SCC (9.7) and 2-year OS was lower in patients with ASC (23.8%) than with AC (34.6%) or SCC (26.5%) (p < 0.001). The OS hazard ratio for ASC was 1.14 when compared to AC (95% CI = 1.016-1.267, p = 0.025) and 1.10 when compared to SCC, but the latter was not significant (95% CI = 0.980-1.222, p = 0.111). CONCLUSION: ASC is a rare tumor among esophageal carcinomas with a greater burden of metastatic disease than AC or SCC and worse OS than AC.

False-Positive Error Rates for Reliable Digit Span and Auditory Verbal Learning Test Performance Validity Measures in Amnestic Mild Cognitive Impairment and Early Alzheimer Disease.

OBJECTIVE: The objective is to examine failure on three embedded performance validity tests [Reliable Digit Span (RDS), Auditory Verbal Learning Test (AVLT) logistic regression, and AVLT recognition memory] in early Alzheimer disease (AD; n = 178), amnestic mild cognitive impairment (MCI; n = 365), and cognitively intact age-matched controls (n = 206). METHOD: Neuropsychological tests scores were obtained from subjects participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: RDS failure using a ≤7 RDS threshold was 60/178 (34%) for early AD, 52/365 (14%) for MCI, and 17/206 (8%) for controls. A ≤6 RDS criterion reduced this rate to 24/178 (13%) for early AD, 15/365 (4%) for MCI, and 7/206 (3%) for controls. AVLT logistic regression probability of ≥.76 yielded unacceptably high false-positive rates in both clinical groups [early AD = 149/178 (79%); MCI = 159/365 (44%)] but not cognitively intact controls (13/206, 6%). AVLT recognition criterion of ≤9/15 classified 125/178 (70%) of early AD, 155/365 (42%) of MCI, and 18/206 (9%) of control scores as invalid, which decreased to 66/178 (37%) for early AD, 46/365 (13%) for MCI, and 10/206 (5%) for controls when applying a ≤5/15 criterion. Despite high false-positive rates across individual measures and thresholds, combining RDS ≤ 6 and AVLT recognition ≤9/15 classified only 9/178 (5%) of early AD and 4/365 (1%) of MCI patients as invalid performers. CONCLUSIONS: Embedded validity cutoffs derived from mixed clinical groups produce unacceptably high false-positive rates in MCI and early AD. Combining embedded PVT indicators lowers the false-positive rate.