Electrocardiographic Criteria for Left Ventricular Hypertrophy in Children

Previous studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete limits of normal for the ECG parameters were used. Furthermore, left ventricular mass (LVM) was taken as the reference standard for LVH, with no regard for other clinical evidence. The study population consisted of 832 children from whom a 12-lead ECG and an M-mode echocardiogram were taken on the same day. The validity of the ECG criteria was judged on the basis of an abnormal LVM index, either alone or in combination with other clinical evidence. The ECG criteria were based on recently established age-dependent normal limits. At 95% specificity, the ECG criteria have low sensitivities (<25%) when an elevated LVM index is taken as the reference for LVH. When clinical evidence is also taken into account, the sensitivity improved considerably (<43%). Sensitivities could be further improved when ECG parameters were combined. The sensitivity of the pediatric ECG in detecting LVH is low but depends strongly on the definition of the reference used for validation

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

"You've got a friend in me": can social networks mediate the relationship between mood and MCI?

engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. Methods: This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010-2013 by conducting structured interviews with older people aged over 65 years of age living in urban and rural areas of Wales, and included questions that assessed cognitive functioning, mood, and social networks. Regression analyses were used to investigate the associations between individual variables and the mediating role of social networks. Results: Having richer social networks was beneficial to both mood and cognition. Participants in the MCI category had weaker social networks than participants without cognitive impairment, whereas stronger social networks were associated with a decrease in the odds of experiencing mood problems, suggesting that they may offer a protective effect against anxiety and depression. Regression analyses revealed that social networks are a significant mediator of the relationship between MCI and mood problems. Conclusions: These findings are important, as mood problems are a risk factor for progression from MCI to dementia, so interventions that increase and strengthen social networks may have beneficial effects on slowing the progression of cognitive decline

Prevalence of dementia and Alzheimer's disease in elders of nursing homes and a senior center of Durango City, Mexico

BACKGROUND: Epidemiological reports about dementia and Alzheimer's disease (AD) in elderly people from developing countries are scarce. Therefore, we sought to determine the prevalences of dementia and AD in a population of nursing home residents and senior center attendees of Durango City, Mexico, and to determine whether any socio-demographic characteristics from the subjects associated with dementia or AD exist. METHODS: One hundred and fifty-five residents of two nursing homes and 125 attendees of a senior center were examined for dementia and Alzheimer's disease. All subjects were tested by the mini-mental state examination, and those who scored twenty-four or less underwent psychiatric and neurological evaluations. Diagnosis of dementia, AD and vascular dementia (VaD) was based on the DSM-IV criteria. Socio-demographic characteristics from each participant were also obtained. RESULTS: Residents of nursing homes found to suffer from dementia were 25 out of 155 (16.1%). Eighteen of them (11.6%) had AD, and seven (4.5%) had VaD. None of the attendees of the senior center suffered from dementia. Dementia (pooled AD and VaD cases) correlated with white ethnicity (OR = 3.2; 95%CI = 1.28–8.31), and a history of unemployment (OR = 6.46; 95%CI = 1.42–25.97), while AD correlated with journeymen occupations (OR = 4.55; 95%CI = 1.00–19.29). CONCLUSION: Prevalence of dementia in residents of nursing homes found in this study is much lower than reported from more industrialized countries. AD was more frequent than VaD. Ethnicity and occupation showed effects on the prevalence figures. The prevalence of dementia found has implications for the optimum kind of health care that nursing homes should provide to their residents

Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age

During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18–28 years) and 16 elderly (E: 68–78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33°C. Next, local temperature was reduced to 24°C. After 15 min of local cooling, noradrenalin (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: −76 ± 3 vs. E: −60 ± 5 (P < 0.01), dorsal hand Y: −74 ± 4 vs. E: −72 ± 4 (n.s.), ventral hand Y: −80 ± 7 vs. E: −70 ± 11 (n.s.)]. In conclusion, in contrast to results from the ventral forearm, elderly did not show a blunted response to local cooling and noradrenalin at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age

Assessment of normal tricuspid valve anatomy in adults by real-time three-dimensional echocardiography

Background: The tricuspid valve (TV) is a complex structure. Unlike the aortic and mitral valve it is not possible to visualize all TV leaflets simultaneously in one cross-sectional view by standard two-dimensional echocardiography (2DE) either transthoracic or transesophageal due to the position of TV in the far field. Aim: Quantitative and qualitative assessment of the normal TV using real-time 3-dimensional echocardiography (RT3DE). Methods: RT3DE was performed for 100 normal adults (mean age 30 ± 9 years, 65% males). RT3DE visualization was evaluated by 4-point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent). Measurements included TV annulus diameters (TAD), TV area (TVA), and commissural width. Results: In 90% of patients with good 2DE image quality, it was possible to analyse TV anatomy by RT3DE. A detailed anatomical structure including unique description and measurement of tricuspid annulus shape and size, TV leaflets shape, and mobility, and TV commissural width were obtained in majority of patients. Identification of each TV leaflet as seen in the routine 2DE views was obtained. Conclusion: RT3DE of the TVis feasible in a large number of patients. RT3DE may add to functional 2DE data in description of TV anatomy and providing highly reproducible and actual reality (anatomical and functional) measurements

Mechanisms of Vasorelaxation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72633/1/j.1527-3466.1992.tb00249.x.pd

Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation

Nitric Oxide (NO) is an intracellular signalling mediator, which affects many biological processes via the posttranslational modification of proteins through S-nitrosation. The availability of NO and NOS-derived reactive oxygen species (ROS) from enzymatic uncoupling are determined by the NO synthase cofactor Tetrahydrobiopterin (BH4). Here, using a global proteomics “biotin-switch” approach, we identified components of the ubiquitin-proteasome system to be altered via BH4-dependent NO signalling by protein S-nitrosation. We show S-nitrosation of ubiquitin conjugating E2 enzymes, in particular the catalytic residue C87 of UBC13/UBE2N, leading to impaired polyubiquitylation by interfering with the formation of UBC13~Ub thioester intermediates. In addition, proteasome cleavage activity in cells also seems to be altered by S-nitrosation, correlating with the modification of cysteine residues within the 19S regulatory particle and catalytic subunits of the 20S complex. Our results highlight the widespread impact of BH4 on downstream cellular signalling as evidenced by the effect of a perturbed BH4-dependent NO-Redox balance on critical processes within the ubiquitin-proteasome system (UPS). These studies thereby uncover a novel aspect of NO associated modulation of cellular homeostasis

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial

<p>Abstract</p> <p>Background</p> <p>Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release.</p> <p>Methods</p> <p>We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period.</p> <p>Results</p> <p>Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications.</p> <p>Conclusion</p> <p>We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism.</p> <p>Trial Registration</p> <p>This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01331486">NCT01331486</a>.</p