Postsynaptic α1-Adrenergic vasoconstriction is impaired in young patients with vasovagal syncope and is corrected by nitric oxide synthase inhibition

BACKGROUND: Syncope is a sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). During VVS, gravitational pooling excessively reduces central blood volume and cardiac output. In VVS, as in hemorrhage, impaired adrenergic vasoconstriction and venoconstriction result in hypotension. We hypothesized that impaired adrenergic responsiveness because of excess nitric oxide can be reversed by reducing nitric oxide. METHODS AND RESULTS: We recorded cardiopulmonary dynamics in supine syncope patients and healthy volunteers (aged 15-27 years) challenged with a dose-response using the α1-agonist phenylephrine (PE), with and without the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA). Systolic and diastolic pressures among control and VVS were the same, although they increased after L-NMMA and saline+PE (volume and pressor control for L-NMMA). Heart rate was significantly reduced by L-NMMA (P<0.05) for control and VVS compared with baseline, but there was no significant difference in heart rate between L-NMMA and saline+PE. Cardiac output and splanchnic blood flow were reduced by L-NMMA for control and VVS (P<0.05) compared with baseline, while total peripheral resistance increased (P<0.05). PE dose-response for splanchnic flow and resistance were blunted for VVS compared with control after saline+PE, but enhanced after L-NMMA (P<0.001). Postsynaptic α1-adrenergic vasoconstrictive impairment was greatest in the splanchnic vasculature, and splanchnic blood flow was unaffected by PE. Forearm and calf α1-adrenergic vasoconstriction were unimpaired in VVS and unaffected by L-NMMA. CONCLUSIONS: Impaired postsynaptic α1-adrenergic vasoconstriction in young adults with VVS can be corrected by nitric oxide synthase inhibition, demonstrated with our use of L-NMMA

Методи оцінки ризиків в інформаційній системі аналізу екологічного стану басейну малої ріки

В інформаційній системі аналізу стану басейну малої ріки запропоновано методи оцінки ризиків на основі імовірнісних та статистичних оцінок, формалізації моделі гри з природою, прогнозування процесів підтоплення земель з використанням ланцюгів Маркова, розглянуто багато критеріальні моделі ризиків.In informational and analytical system of the small rivers’ ecological condition estimation the methods of risks modelling on the basis of likelihood and statistical estimations, formalization of models of game with nature, risk modelling and forecasting processes flooded lands using Markov chains are offered, multicriteria models of risks are considered

A questionnaire to identify patellofemoral pain in the community: an exploration of measurement properties

Background Community-based studies of patellofemoral pain (PFP) need a questionnaire tool that discriminates between those with and those without the condition. To overcome these issues, we have designed a self-report questionnaire which aims to identify people with PFP in the community. Methods Study designs: comparative study and cross-sectional study. Study population: comparative study: PFP patients, soft-tissue injury patients and adults without knee problems. Cross-sectional study: adults attending a science festival. Intervention: comparative study participants completed the questionnaire at baseline and two weeks later. Cross-sectional study participants completed the questionnaire once. The optimal scoring system and threshold was explored using receiver operating characteristic curves, test-retest reliability using Cohen’s kappa and measurement error using Bland-Altman plots and standard error of measurement. Known-group validity was explored by comparing PFP prevalence between genders and age groups. Results Eighty-four participants were recruited to the comparative study. The receiver operating characteristic curves suggested limiting the questionnaire to the clinical features and knee pain map sections (AUC 0.97 95 % CI 0.94 to 1.00). This combination had high sensitivity and specificity (over 90 %). Measurement error was less than the mean difference between the groups. Test–retest reliability estimates suggest good agreement (N = 51, k = 0.74, 95 % CI 0.52–0.91). The cross-sectional study (N = 110) showed expected differences between genders and age groups but these were not statistically significant. Conclusion A shortened version of the questionnaire, based on clinical features and a knee pain map, has good measurement properties. Further work is needed to validate the questionnaire in community samples

A systematic comparison of software dedicated to meta-analysis of causal studies

<p>Abstract</p> <p>Background</p> <p>Our objective was to systematically assess the differences in features, results, and usability of currently available meta-analysis programs.</p> <p>Methods</p> <p>Systematic review of software. We did an extensive search on the internet (Google, Yahoo, Altavista, and MSN) for specialized meta-analysis software. We included six programs in our review: Comprehensive Meta-analysis (CMA), MetAnalysis, MetaWin, MIX, RevMan, and WEasyMA. Two investigators compared the features of the software and their results. Thirty independent researchers evaluated the programs on their usability while analyzing one data set.</p> <p>Results</p> <p>The programs differed substantially in features, ease-of-use, and price. Although most results from the programs were identical, we did find some minor numerical inconsistencies. CMA and MIX scored highest on usability and these programs also have the most complete set of analytical features.</p> <p>Conclusion</p> <p>In consideration of differences in numerical results, we believe the user community would benefit from openly available and systematically updated information about the procedures and results of each program's validation. The most suitable program for a meta-analysis will depend on the user's needs and preferences and this report provides an overview that should be helpful in making a substantiated choice.</p

Atlantic overturning in decline?

Global ocean circulation is an important factor in climate variability and change. In particular, changes in the strength of the Atlantic meridional overturning circulation (AMOC) have been implicated in ancient climate events, as well as in recent climate anomalies such as the rapid warming of the North Atlantic Ocean in the mid-1990s. A series of moored current meters and temperature sensors deployed in the Atlantic at 26° N known as the RAPID-MOCHA array has been used to monitor the strength of meridional overturning since 2004. The data indicate a decline in this strength over the period 2004–20123. Here, using additional observations and climate model simulations we suggest that this measured decline is not merely a short-term fluctuation, but is part of a substantial reduction in meridional overturning occurring on a decadal timescale

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA