Beta-blocker treatment guided by head-up tilt test in neurally mediated syncope

This study was an open-label, uncontrolled, dose-escalation trial of beta-blockers in patients with a history of syncope without warning or syncope resulting in trauma (malignant vasovagal syncope) who had positive head-up tilt test (HUT) responses, with or without isoproterenol infusion. Thirty patients (mean age, 37 +/- 21 years) with recurrent syncopal and near-syncopal episodes of unexplained origin in the previous year (6 +/- 14 syncopal episodes and 17 +/- 3 near-syncopes) underwent HUT for diagnostic purposes and for guiding prophylactic treatment. After patients were given a 10-minute rest in a recumbent position, rye performed an WT at 70 degrees for 25 minutes; if indicated, isoproterenol testing was performed at incremental dosages (dye steps at 10-minute intervals at 80 degrees), AU patients experienced syncope during HUT, 15 (50%) at baseline HUT and 15 (50%) during isoproterenol infusion (1 to 3 mu g/min; mean, 1.6 mu g/min). Sixteen syncopes were of vasodepressor type, 10 were mixed, and 4 were of cardioinhibitory type. After baseline HUT, betablocking drugs were prescribed to all patients as follows: 1 patient was given propranolol (160 mg daily), and 29 patients were given metoprolol (246 +/- 49 mg daily), with a dose titration period of 14 days. HUT was repeated after 3 weeks, and 24 patients (80%) had negative results (no syncope or anomalous responses). After further dosage adjustment of beta-blockers in nonresponders, a negative HUT was obtained in 28 patients (93%). Overall mean metoprolol daily dose was 262 +/- 60 mg (29 patients), and propranolol was administered at 160 mg daily in 1 patient. Thirteen patients (43%) reported side effects, none of which required drug withdrawal. At an average follow-up of 16 +/- 4 months, none of the patients experienced syncope, a statistically significant reduction. Moreover, a statistically significant reduction in the number of near-syncopal episodes was observed in comparison to the previous year. None of the patients discontinued treatment because of long-term side effects. Beta-blockers were well tolerated and achieved a high rate of efficacy, even in cardioinhibitory syncopes. In conclusion, in selected patients with malignant vasovagal syncope, treatment with metoprolol or propranolol at relatively high doses is feasible and, if guided by HUT results, is associated with a favorable outcome in terms of freedom from syncopal recurrences. Appropriate titration to achieve the full beta-blocking effect appears to be advisable

Semantic-specific and domain-general mechanisms for integration and update of contextual information.

Recent research has highlighted the importance of domain-general processes and brain regions for language and semantic cognition. Yet, this has been mainly observed in executively demanding tasks, leaving open the question of the contribution of domain-general processes to natural language and semantic cognition. Using fMRI, we investigated whether neural processes reflecting context integration and context update-two key aspects of naturalistic language and semantic processing-are domain-specific versus domain-general. Thus, we compared neural responses during the integration of contextual information across semantic and non-semantic tasks. Whole-brain results revealed both shared (left posterior-dorsal inferior frontal gyrus, left posterior inferior temporal gyrus, and left dorsal angular gyrus/intraparietal sulcus) and distinct (left anterior-ventral inferior frontal gyrus, left anterior ventral angular gyrus, left posterior middle temporal gyrus for semantic control only) regions involved in context integration and update. Furthermore, data-driven functional connectivity analysis clustered domain-specific versus domain-general brain regions into distinct but interacting functional neural networks. These results provide a first characterisation of the neural processes required for context-dependent integration during language processing along the domain-specificity dimension, and at the same time, they bring new insights into the role of left posterior lateral temporal cortex and left angular gyrus for semantic cognition

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction.

Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered an important risk factor for acute myocardial infarction in aged patients (55-80 years old). On the other hand, in spite of a not different genotypic and allelic distribution for the Leiden FV G1691A mutation, the presence of one or both the two polymorphisms is significantly higher among cases than in controls. In conclusion, our data suggest that FII G20210A and/or Leiden FV might be involved as risk factor for arterial disorders in about 5% of old subjects, justifying the opportunity of a genetic screening and an eventual preventive treatment, in particular in old subjects in which other and major risk factors, as hypertension and atherosclerosis, are detected

Management of patients with atrial fibrillation: different therapeutic options and role of electrophysiology-guided approaches.

At present the approach to atrial fibrillation treatment is based on the electrophysiological patterns of atrial fibrillation (on the basis of multiple intra-atrial recordings or sophisticated new mapping techniques) only in a restricted minority of patients, those who are candidate to ablation of the substrate and/or of the triggers. Atrial fibrillation has a broad spectrum of clinical presentations and a heterogeneous electrophysiological pattern. The treatment of this arrhythmia, both with drugs and non pharmacological treatments, has been based, classically, on empirical basis and on a clinically-guided staged-approach. The limitations of pharmacological treatment led in recent years to the development of a wide spectrum of non pharmacological treatments. This implies a change in the approach to atrial fibrillation and the need to identify potentially ideal candidates to complex and expensive treatments. In this view it is currently under investigation the possibility to identify potential responders to a definitive treatment or a combination of treatments (both pharmacological and non-pharmacological) on the basis of the electrophysiological pattern

Precursor-Dependent Photocatalytic Activity of Carbon Dots

This work systematically compares both structural features and photocatalytic performance of a series of graphitic and amorphous carbon dots (CDs) prepared in a bottom-up manner from fructose, glucose, and citric acid. We demonstrate that the carbon source and synthetic procedures diversely affect the structural and optical properties of the CDs, which in turn unpredictably influence their photo electron transfer ability. The latter was evaluated by studying the photo-reduction of methyl viologen. Overall, citric acid-CDs were found to provide the best photocatalytic performance followed by fructose- and glucose-CDs. However, while the graphitization of glucose- and citric acid-CDs favored the photo-reaction, a reverse structure-activity dependence was observed for fructose-CDs due to the formation of a large graphitic-like supramolecular assembly. This study highlights the complexity to design in advance photo-active bio-based carbon nanomaterials

Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography

OBJECTIVES: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 931 patients who experienced stress induced myocardial ischaemia during DSE. RESULTS: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). CONCLUSIONS: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate

A Cultural Quest: A Study of Organizational Use of New Cultural Resources in Strategy Formation.

Our study was motivated by the growing influence in cultural sociology and organizational research of the view of culture as a “toolkit”, from which individuals draw resources flexibly to develop strategies of action that address different circumstances. To investigate if and how organizations can also use new and diverse cultural resources, we undertook a historical case study of the incorporation of new cultural resources in an organization’s cultural repertoire. In-depth analysis of four rounds of incorporation of new cultural resources led to the development of a robust theoretical model that identifies cultural repertoire enrichment and organizational identity redefinition as two core mechanisms that facilitate the use of new cultural resources for the development of unconventional strategies and strategic versatility. Our model contributes to organizational research novel theoretical understanding regarding the use of cultural resources in strategy formation and change