Pulse pressure is more susceptible to the white coat effect than is systolic blood pressure: observations from real-life ambulatory blood pressure monitoring

BACKGROUND: Pulse pressure is a derivative of arterial stiffness. We have previously demonstrated ambulatory pulse pressure to be relatively independent from the blood pressure (BP) lowering during sleep, and thus of a neurogenic effect. On the other hand, white coat BP effects are thought to involve neurogenic activation. The aim of this work was to analyze white coat induced variability in pulse pressure. METHODS: Percent clinic-awake differences in systolic BP (SBP) and pulse pressure (white coat effects) were calculated for 688 consecutive subjects (mean age 60 +/- 16 years, 58% female). Of the subjects, 23% had controlled hypertension, 45% uncontrolled hypertension, 8% normotension, and 4% isolated office hypertension; all were referred to our unit for 24 h ambulatory BP monitoring. RESULTS: Pulse pressure highly correlated with SBP (r = 0.82, P <.00001). We found a larger white coat effect on pulse pressure than on SBP (8.3% and 5.2%, respectively, P < or =.0001). This was true in all subgroups except in normotensive subjects. Specifically, the magnitude of the white coat effect on pulse pressure was greater than on SBP in subjects with treated hypertension, untreated hypertension, and isolated office hypertension, and in young hypertensive subjects, older subjects, and those with diabetes. CONCLUSIONS: Although pulse pressure is related to the mechanical properties of large arteries, it is also influenced by the white coat effect, a neurogenic process. Furthermore, in hypertensive but not in normotensive subjects, the white coat effect on pulse pressure is significantly more pronounced than on SBP.     

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma

Journal of Neuro-Oncology - We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were...     

Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: Focus on davunetide (NAP)

This review focuses on the therapeutic effects and mechanisms of action of NAP (davunetide), an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP) which was discovered in our laboratory. We have recently described the effects of NAP in neurodegenerative disorders, and we now review the beneficial effects of NAP and other microtubule-stabilizing agents on impairments in axonal transport. Experiments in animal models of microtubule-deficiency including tauopathy (spanning from drosophila to mammals) showed protection of axonal transport by microtubule-stabilizers and NAP, which was coupled to motor and cognitive protection. Clinical trials with NAP (davunetide) are reviewed paving the path to future developments.     

Blunted heart rate dip during sleep and all-cause mortality

BACKGROUND: Although it has been somewhat overlooked, resting heart rate is an established predictor of cardiovascular and noncardiovascular outcome. We assessed the determinants and mortality associations of heart rate measured during ambulatory blood pressure monitoring (ABPM) to evaluate its informativeness during activity and sleep. METHODS: We studied a cohort of 3957 patients aged 55 +/- 16 (mean +/- SD) years (58% treated for hypertension) who were referred for ABPM during 1991 to 2005. Heart rate nondipping was defined as follows: (awake value - sleep value)/awake value < 0.1. Linear and logistic regression models assessed covariate associations with ambulatory heart rate indices. All-cause mortality was analyzed by Cox proportional hazards modeling. RESULTS: Female sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and treated diabetes were positively related to awake and sleep heart rate, whereas age and treated hypertension were inversely associated. All these variables were associated with lower sleep-related heart rate dipping magnitude. Multivariate-adjusted odds ratios (95% confidence intervals) for heart rate nondipping were 1.02 (1.02-1.03) per year of age; 1.05 (1.03-1.06) for body mass index; 1.39 (1.20-1.60) for women; 1.30 (1.12-1.51) for nappers; 2.19 (1.87-2.57) for treated hypertensive patients; and 1.38 (1.09-1.76) for treated diabetic patients. Mortality analysis according to deciles of the different heart rate variables showed a robust linear relationship only for heart rate dip and a hazard ratio of 2.67 (1.31-5.47) for the lowest vs the highest decile. CONCLUSIONS: In clinical practice, ambulatory heart rate adds prognostic information beyond that of other ABPM predictors. Heart rate measures during sleep, and in particular the absence of dipping of heart rate to sleep levels, were independently associated with all-cause mortality.     

A Progressive Mouse Model of Parkinson’s Disease: The Thy1-aSyn (“Line 61”) Mice

Identification of mutations that cause rare familial forms of Parkinson’s disease (PD) and subsequent studies of genetic risk factors for sporadic PD have led to an improved understanding of the pathological mechanisms that may cause nonfamilial PD. In particular, genetic and pathological studies strongly suggest that alpha-synuclein, albeit very rarely mutated in PD patients, plays a critical role in the vast majority of individuals with the sporadic form of the disease. We have extensively characterized a mouse model over-expressing full-length, human, wild-type alpha-synuclein under the Thy-1 promoter. We have also shown that this model reproduces many features of sporadic PD, including progressive changes in dopamine release and striatal content, alpha-synuclein pathology, deficits in motor and nonmotor functions that are affected in pre-manifest and manifest phases of PD, inflammation, and biochemical and molecular changes similar to those observed in PD. Preclinical studies have already demonstrated improvement with promising new drugs in this model, which provides an opportunity to test novel neuroprotective strategies during different phases of the disorder using endpoint measures with high power to detect drug effects.     

Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations

We profiled microRNAs (miRNAs) in cell-free serum and plasma samples from human volunteers using deep sequencing of barcoded small RNA cDNA libraries. By introducing calibrator synthetic oligonucleotides during library preparation, we were able to calculate the total as well as specific concentrations of circulating miRNA. Studying trios of samples from newborn babies and their parents we detected placental-specific miRNA in both maternal and newborn circulations and quantitated the relative contribution of placental miRNAs to the circulating pool of miRNAs. Furthermore, sequence variation in the placental miRNA profiles could be traced to the specific placenta of origin. These deep sequencing profiles, which may serve as a model for tumor or disease detection, allow us to define the repertoire of miRNA abundance in the circulation and potential uses as biomarkers.