Prevalence of Masked Hypertension Among US Adults With Nonelevated Clinic Blood Pressure

Masked hypertension (MHT), defined as nonelevated blood pressure (BP) in the clinic setting and elevated BP assessed by ambulatory monitoring, is associated with increased risk of target organ damage, cardiovascular disease, and mortality. Currently, no estimate of MHT prevalence exists for the general US population. After pooling data from the Masked Hypertension Study (n = 811), a cross-sectional clinical investigation of systematic differences between clinic BP and ambulatory BP (ABP) in a community sample of employed adults in the New York City metropolitan area (2005-2012), and the National Health and Nutrition Examination Survey (NHANES; 2005-2010; n = 9,316), an ongoing nationally representative US survey, we used multiple imputation to impute ABP-defined hypertension status for NHANES participants and estimate MHT prevalence among the 139 million US adults with nonelevated clinic BP, no history of overt cardiovascular disease, and no use of antihypertensive medication. The estimated US prevalence of MHT in 2005-2010 was 12.3% of the adult population (95% confidence interval: 10.0, 14.5)-approximately 17.1 million persons aged ≥21 years. Consistent with prior research, estimated MHT prevalence was higher among older persons, males, and those with prehypertension or diabetes. To our knowledge, this study provides the first estimate of US MHT prevalence-nearly 1 in 8 adults with nonelevated clinic BP-and suggests that millions of US adults may be misclassified as not having hypertension

Somatic piRNAs and Transposons are Differentially Regulated During Skeletal Muscle Atrophy and Programmed Cell Death [preprint]

PiWi-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta. These piRNAs are abundantly expressed, are ~27 nt long, map antisense to transposons, are oxidation resistant, exhibit a uridine bias at their first nucleotide, and amplify via the canonical ping-pong pathway. An RNA-seq analysis demonstrated that 20 piRNA pathway genes are expressed in the ISMs and are developmentally regulated. The abundance of piRNAs does not change when the muscles initiate developmentally-regulated atrophy, but are repressed when cells become committed to undergo programmed cell death at the end of metamorphosis. This change in piRNA expression is associated with the targeted repression of several retrotransposons and the induction of specific DNA transposons. The developmental changes in the expression of piRNAs, piRNA pathway genes, and transposons are all regulated by 20-hydroxyecdysone, the steroid hormone that controls the timing of ISM death. Taken together, these data provide compelling evidence for the existence of piRNA in somatic tissues and suggest that they may play roles in developmental processes such as programmed cell death

Somatic piRNAs and Transposons are Differentially Expressed Coincident with Skeletal Muscle Atrophy and Programmed Cell Death

PIWI-interacting RNAs (piRNAs) are small single-stranded RNAs that can repress transposon expression via epigenetic silencing and transcript degradation. They have been identified predominantly in the ovary and testis, where they serve essential roles in transposon silencing in order to protect the integrity of the genome in the germline. The potential expression of piRNAs in somatic cells has been controversial. In the present study we demonstrate the expression of piRNAs derived from both genic and transposon RNAs in the intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta. These piRNAs are abundantly expressed, ∼27 nt long, map antisense to transposons, are oxidation resistant, exhibit a 5’ uridine bias, and amplify via the canonical ping-pong pathway. An RNA-seq analysis demonstrated that 19 piRNA pathway genes are expressed in the ISMs and are developmentally regulated. The abundance of piRNAs does not change when the muscles initiate developmentally-regulated atrophy, but are repressed coincident with the commitment of the muscles undergo programmed cell death at the end of metamorphosis. This change in piRNA expression is correlated with the repression of several retrotransposons and the induction of specific DNA transposons. The developmentally-regulated changes in the expression of piRNAs, piRNA pathway genes, and transposons are all regulated by 20-hydroxyecdysone, the steroid hormone that controls the timing of ISM death. Taken together, these data provide compelling evidence for the existence of piRNA in somatic tissues and suggest that they may play roles in developmental processes such as programmed cell death

Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation.

Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction

Optical imaging of the chorioretinal vasculature in the living human eye

Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler’s and Haller’s layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study

Background - Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. Methods - To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the ‘ABP-International’ registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. Results - During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24 h HR (p = 0.007 and = 0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p = 0.07 and = 0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04–1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05–1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05–1.45) were excluded from analysis. Conclusions - At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR

Why Effective Medium Theory Fails in Granular Materials

Experimentally it is known that the bulk modulus, K, and shear modulus, \mu, of a granular assembly of elastic spheres increase with pressure, p, faster than the p^1/3 law predicted by effective medium theory (EMT) based on Hertz-Mindlin contact forces. To understand the origin of these discrepancies, we perform numerical simulations of granular aggregates under compression. We show that EMT can describe the moduli pressure dependence if one includes the increasing number of grain-grain contacts with p. Most important, the affine assumption (which underlies EMT), is found to be valid for K(p) but breakdown seriously for \mu(p). This explains why the experimental and numerical values of \mu(p) are much smaller than the EMT predictions.Comment: 4 pages, 5 figures, http://polymer.bu.edu/~hmaks