Clinical prediction of normotension in borderline hypertensive men--a 10 year study

OBJECTIVE: To investigate 24-h ambulatory blood pressure measurements (ABPM) as a tool for long-term prediction of future blood pressure (BP) status in high normal and low stage 1 hypertensives. DESIGN, SETTING AND PARTICIPANTS: A total of 165 men from a population screening program with diastolic BP (DBP) 85-94 mmHg and a systolic BP (SBP) < 150 mmHg performed a 24-h ABPM. Ten years later, 120 participants (73%) returned for renewed measurements. MAIN OUTCOME MEASURES: Blood pressure status at 10 years. RESULTS: At the 10-year follow-up, 53% of the participants were classified as hypertensive (HT) (BP > or = 140/90 or taking anti-hypertensive medication) and 47% were classified as normotensive (NT) (BP < 140/90 mmHg). There was no significant baseline differences in office SBP levels between those who were normotensive or hypertensive at follow-up (136/91 versus 138/92 mmHg), whereas both SBP and DBP night-time levels were significantly lower in the future normotensives as compared to the future hypertensives (107/69 versus 112/74 mmHg, P < 0.01). Using recommended normalcy night-time ABP levels of < 120/75 mmHg in addition to office BP (140/90) at baseline, over 85% of the subjects were correctly classified provided they met both clinic and ambulatory night-time criteria for HT and NT classification at baseline. CONCLUSION: The use of ABPM in addition to office BP's in patients with borderline hypertension greatly increases the possibility of identifying those individuals who are at a very small risk of developing future hypertension. This could potentially lead to considerable savings in both patient anxiety, physician time and resource consumption.     

Asthma outcomes are poor among older adults with low health literacy

Objective: To examine the association of health literacy (HL) with asthma outcomes among older asthmatics. Methods: The study included adults ages ≥60 with moderate to severe asthma in New York City and Chicago. We assessed asthma control with the Asthma Control Questionnaire (ACQ) and the percent predicted forced expiratory volume at 1?s (FEV₁) by spirometry, hospitalizations and emergency department (ED) visits in the past 6 months, and quality of life. HL was assessed with the Short Test of Functional Health Literacy in Adults (S-TOFHLA). Multivariate logistic regression models controlled for age, sex, race, income, general health and years with asthma. Results: Among 433 individuals, 36% had low HL, 55% were over age 65, 38% were Hispanic and 22% were black. Poor asthma control was reported by 40% and 32% had FEV₁ <70% of predicted; 9% had a hospital stay, 23% had an ED and 38% had poor quality of life. In multivariable analysis, individuals with low HL were more likely to have FEV₁ <70% predicted (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.39–3.94, p?=?0.001), hospitalizations (OR 2.53, 95% CI 1.17–5.49, p?=?0.02) and ED visits for asthma (OR 1.81, 95% CI 1.05–3.10, p?=?0.03). There were no differences in self-reported asthma control and quality of life. Conclusions: Low HL is associated with poor asthma control by objective measure, and greater likelihood of ED visits and hospitalization. HL is a modifiable target for interventions to improve asthma outcomes in the elderly.     

Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder

One of the most widely cited features of the neural phenotype of autism is reduced “integrity” of long-range white matter tracts, a claim based primarily on diffusion imaging studies. However, many prior studies have small sample sizes and/or fail to address differences in data quality between those with autism spectrum disorder (ASD) and typical participants, and there is little consensus on which tracts are affected. To overcome these problems, we scanned a large sample of children with autism (n = 52) and typically developing children (n = 73). Data quality was variable, and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow standard data analysis practices (i.e., without matching head motion between groups), we replicate the finding of lower fractional anisotropy (FA) in multiple white matter tracts. However, when we carefully match data quality between groups, all these effects disappear except in one tract, the right inferior longitudinal fasciculus (ILF). Additional analyses showed the expected developmental increases in the FA of fiber tracts within ASD and typical groups individually, demonstrating that we had sufficient statistical power to detect known group differences. Our data challenge the widely claimed general disruption of white matter tracts in autism, instead implicating only one tract, the right ILF, in the ASD phenotype.What is the key difference in the brains of individuals with autism that accounts for the distinctive cognitive profile of this disorder? One of the most widely claimed brain signatures of autism spectrum disorder (ASD), reported in dozens of papers that used diffusion-weighted imaging (DWI), is reduced integrity of long-range fiber tracts (1). This finding has been taken as evidence that autism is fundamentally a “disconnection” syndrome, in which the core cognitive deficits result from reduced integration of information at the neural and cognitive levels (2–5). For example, it has been argued that the characteristic deficits in social cognition and language arise because these functions require rapid integration of information across spatially distant brain areas (3, 6, 7), which would likely be affected if major white matter tracts are compromised.Evidence for a general reduction in the “integrity”^* of white matter in autism has come primarily from diffusion imaging studies that report reduced directionality of the diffusion of water molecules, or fractional anisotropy (FA), and increased speed of diffusion, or mean diffusivity (MD) of many major fiber bundles. However, the literature reveals little actual agreement on the existence and direction of group differences in diffusion parameters (reviewed in ref. 1). White-matter differences have been reported in various brain regions in positive and negative directions. Possible reasons for these inconsistent findings include small sample sizes [mean of ∼20 in each group, with 40% of studies scanning 15 or fewer participants with ASD (1)], the heterogeneity of ASD itself, variations across studies in the age of the cohort tested, and the type of DTI analysis performed. Another potential problem that few diffusion studies of autism address or even mention is data quality. Indeed, to our knowledge, only two studies (9, 10) report quantitative analyses of the amount of motion in their DWI data. Group differences in head motion could be a serious confounding factor, given that head motion is likely to be greater in children with autism, and group differences in head motion can lead artifactually to just the effects most often reported: reduced FA in white matter tracts in ASD (11).To address these concerns, we scanned a relatively large sample of children with and without ASD, and evaluated data quality from each participant by visual inspection of the data and quantification of head motion (11). We then excluded scans that did not reach our data quality criterion, and matched the remaining participants across groups for data quality. These data were used to determine whether people with autism do in fact show widespread differences in the known white matter tracts in ASD. We further tested the specific hypothesis that individuals with ASD show changes in one particular tract, the inferior longitudinal fasciculus (ILF), a white matter tract important for face recognition (12, 13), a mental function selectively disrupted in ASD (ref. 14; but see ref. 15).     

Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes

Background and aims

Reduction of biliary serotonin N-acetyltransferase (AANAT) expression and melatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression of SR, CFTR and Cl^–/HCO₃^– AE2. The balance between biliary proliferation/damage is regulated by several autocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFs are secreted by several epithelia, where they modulate cell growth by autocrine and paracrine mechanisms. No data exists regarding the effect of AANAT modulation on the expressions of VEGFs by cholangiocytes.

Methods

In this study, we evaluated the effect of local modulation of biliary AANAT expression on the cholangiocytes synthesis of VEGF-A/C.

Results

The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocytes was associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte lines decreased the expression of VEGF-A/C.

Conclusions

Modulation of melatonin synthesis may affect the expression of VEGF-A/C by cholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/C expression regulating biliary functions.