Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development.

Chronic fetal hypoxia and infection are examples of adverse conditions during complicated pregnancy, which impact cardiac myogenesis and increase the lifetime risk of heart disease. However, the effects that chronic hypoxic or inflammatory environments exert on cardiac pacemaker cells are poorly understood. Here, we review the current evidence and novel avenues of bench-to-bed research in this field of perinatal cardiogenesis as well as its translational significance for early detection of future risk for cardiovascular disease

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy.

KEY POINTS: We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy. ABSTRACT: Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O2 , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ∼145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4-fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4-fold reduction in the scale-dependent Lyapunov exponent slope. We also detected a 2-fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end-diastolic pressure across both groups (average R2  = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale-dependent higher complexity in iFHRV.British Heart Foundatio

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study

BACKGROUND AND PURPOSE: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). METHODS: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. RESULTS: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. CONCLUSION: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs

Improvement in the sustainability and stability of acrylic protective coatings for outdoor bronze artworks

Outdoor bronze artworks are an entrenched part of our urban landscape. They are usually covered by a patina resulting from their exposition to the environment. This patina plays an important aesthetic role and may provide some passivation on the surface, nonetheless it does not prevent the degradation processes promoted by external factors such as pollution, light and humidity. One of the strategies to slow down these unwanted processes is the application of protective coatings. The products currently available have some limitations due to the loss of effectiveness over time and poor environmental sustainability. With the aim of proposing more performing alternatives, coatings based on Paraloid (R) B44 modified with corrosion inhibitors and light stabilizers were prepared and characterized. Two non-toxic corrosion inhibitors were studied, 5-mercapto-1-pheniltetrazole (MPT) and 5-ethyl-1,3,4-thiadiazol-2-amine (AEDTA), comparing them with the traditional benzotriazole (BTA). The approach used aimed to identify the blend providing the most stable coatings. The chemical and physical properties of the coatings, such as colour, solubility, glass transition and composition, were studied and monitored over time. All coatings have shown adequate visual properties; however, corrosion inhibitors degrade some other properties of the coatings and need to be used in conjunction with light stabilizers. The permanence of corrosion inhibitors in the coatings over time was also studied by investigating the role of the support. The establishment of specific interactions between inhibitors and the bronze surface lengthens their permanence in the coatings compared to what happens with inert supports. Especially for AEDTA, the inhibitor retention within the coating and at the coating-bronze interface is better than for BTA and MPT. The effect of each of the additives on the photooxidation stability of the coating was evaluated and the most promising inhibitor and stabilizer combination was identified

Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve

ObjectiveTo assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years.MethodsPatients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated.ResultsPatients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 ± 3.9 mm Hg to 103.5 ± 4.6 mm Hg (P < .00001) and from 87.6 ± 4.3 mm Hg to 94.0 ± 4.5 mm Hg (P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group (P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease.ConclusionsCarotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely

Isotope analysis in central heavy ion collisions at intermediate energies

Symmetry energy is a key quantity in the study of the equation of state of asymmetric nuclear matter. Heavy ion collisions at low and intermediate energies, performed at Laboratori Nazionali di Legnaro and Laboratori Nazionali del Sud, can be used to extract information on the symmetry energy coefficient Csym, which is currently poorly known but relevant both for astrophysics and for structure of exotic nuclei.Comment: 2 pages, 1 figure. Proceedings of 7th International Conference on Radioactive Nuclear Beams (RNB7), to be published in The European Physical Journal

Miniaturized NIR Spectrometers in a Nutshell: Shining Light over Sources of Variance

The increasing portability and accessibility of miniaturized NIR spectrometers are promoting the spread of in-field and online applications. Alongside the successful outcomes, there are also several problems related to the acquisition strategies for each instrument and to experimental factors that can influence the collected signals. An insightful investigation of such factors is necessary and could lead to advancements in experimental set-up and data modelling. This work aimed to identify variation sources when using miniaturized NIR sensors and to propose a methodology to investigate such sources based on a multivariate method (ANOVA-Simultaneous Component Analysis) that considers the effects and interactions between them. Five different spectrometers were chosen for their different spectroscopic range and technical characteristics, and samples of worldwide interest were chosen as the case study. Comparing various portable sensors is interesting since results could significantly vary in the same application, justifying the idea that this kind of spectrometer is not to be treated as a general class of instruments

Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Background: In recent years there have been significant advances in the diagnosis, management and treatment of intracranial aneurysms (IAs) in Italy. Changes in prevalence of several epigenetic risk factors in the population as well as in environmental factors may have influenced the epidemiological burden of this disease. No long-term, population-based study about the incidence of treated ruptured IAs (rIAs) in Italy has yet been reported in literature. Methods: A long-term (January 2015 - December 2020), nationwide epidemiology study was performed by using discharge data collected by the Italian National Agency for Regional Healthcare Services with a particular focus on the treatment incidence of rIAs. A sub-analysis per macro-areas (north, center, and south and islands) was also performed, including the data about regional healthcare systems organization. The prevalence of common epigenetic and environmental risk factors has been also assessed. Results: Over 6 years, the mean incidence of rIAs treatment was 2.7 x 100.000 per year (ds ± 0.1; range: 2.6-2.9). In 2020, there was a significant north-south decreasing gradient in incidence (north vs center vs south and islands: 3.4 vs 2.4 vs 1.8 x 100.000/year; all p<0.001). There were no meaningful differences between macro-areas in terms of access to emergency care and number of neurosurgical wards per population. The rate of unruptured IAs (uIAs) treatment did not show a correlation to that of ruptured ones. Minor regional differences were retrieved for high-risk hypertension as well as for alcohol abuse prevalence. Air pollutants and temperature charts showed a north-south gradient similar to that of the incidence in the treated rIAs. Conclusions: The mean incidence of treated rIAs was stable over the 2015-2020 period in Italy. A north-south decreasing gradient in rIAs treatment incidence was reported. Neither the Regional healthcare organizations nor the rate of uIAs treatment were significant factors explaining the regional differences in the incidence of rIAs treatment. Minor differences in epigenetic and environmental risk factors may be synergistically involved