Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC

N-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus Branchiostoma lanceolatum

<p>Abstract</p> <p>Background</p> <p>NMDA (<it>N</it>-methyl-D-aspartic acid) is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland.</p> <p>Results</p> <p>In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus <it>Branchiostoma lanceolatum</it>. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle). As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp) by a NMDA synthase (also called D-aspartate methyl transferase).</p> <p>Conclusion</p> <p>Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.</p

Assessing safety functionalities in the design and validation of driving automation

This paper aims to contribute to the comprehensive and systematic safety assessment of Automated Driving Systems (ADSs) by identifying unknown hazardous areas of operation. The current methodologies employed in this domain typically involve estimating the distributions of situational variables based on human-centered field test, crash databases, or expert knowledge of critical values. However, due to the lack of a-priori knowledge regarding the influential factors, their critical ranges, and their distributions, these approaches may not be entirely suitable for the assessment of emerging automated driving technologies. To deal with this challenging problem, here we propose a testing methodology incorporating realistic yet unobserved driving conditions, distinguished by numerous situational variables, so to encompass unknown unsafe conditions comprehensively. Our methodology utilizes stochastic simulation and uncertainty modeling techniques to account for the variability of realistic driving conditions and their impact on ADSs' performances. By doing so, we aim to identify unsafe operational regions and triggering conditions that can lead to hazardous behaviors, thus improving the development and safety of automated driving functions. For our purposes, the Latin Hypercube Sampling technique and the recently proposed PAWN density-based sensitivity analysis method are employed. We apply this methodology for the first time in the specific field of ADSs design and validation, using an exemplificative use case. We discuss and compare the results obtained from our approach with those obtained from a traditional approach

Situation identification in smart wearable computing systems based on machine learning and Context Space Theory

Wearable devices and smart sensors are increasingly adopted to monitor the behaviors of human and artificial agents. Many applications rely on the capability of such devices to recognize daily life activities performed by the monitored users in order to tailor their behaviors with respect to the occurring situations. Despite the constant evolution of smart sensing technologies and the numerous research in this field, an accurate recognition of in-the-wild situations still represents an open research challenge. This work proposes a novel approach for situation identification capable of recognizing the activities and the situations in which they occur in different environments and behavioral contexts, processing data acquired by wearable and environmental sensors. An architecture of a situation-aware wearable computing system is proposed, inspired by Endsley's situation-awareness model, consisting of a two-step approach for situation identification. The approach first identifies the daily life activities via a learning-based technique. Simultaneously, the context in which the activities are performed is recognized using Context Space Theory. Finally, the fusion between the context state and the activities allows identifying the complex situations in which the user is acting. The knowledge regarding the situations forms the basis on which novel and smarter applications can be realized. The approach has been evaluated on the ExtraSensory public dataset and compared with state-of-the-art techniques, achieving an accuracy of 96% for the recognition of situations and with significantly low computational time, demonstrating the efficacy of the two-step situation identification approach

Individual differences and knockout in zebrafish reveal similar cognitive effects of BDNF between teleosts and mammals

The remarkable similarities in cognitive performance between teleosts and mammals suggest that the underlying cognitive mechanisms might also be similar in these two groups. We tested this hypothesis by assessing the effects of the brain-derived neurotrophic factor (BDNF), which is critical for mammalian cognitive functioning, on fish's cognitive abilities. We found that individual differences in zebrafish's learning abilities were positively correlated with bdnf expression. Moreover, a CRISPR/Cas9 mutant zebrafish line that lacks the BDNF gene (bdnf(-/-)) showed remarkable learning deficits. Half of the mutants failed a colour discrimination task, whereas the remaining mutants learned the task slowly, taking three times longer than control bdnf(+/+) zebrafish. The mutants also took twice as long to acquire a T-maze task compared to control zebrafish and showed difficulties exerting inhibitory control. An analysis of habituation learning revealed that cognitive impairment in mutants emerges early during development, but could be rescued with a synthetic BDNF agonist. Overall, our study indicates that BDNF has a similar activational effect on cognitive performance in zebrafish and in mammals, supporting the idea that its function is conserved in vertebrates

Quality of Life and Respiratory Performance in the Laryngectomized Patient: Role of the HME Filters during Physical Activity

Background: Permanent tracheostomy because of total laryngectomy surgery entails significant consequences for patients regarding respiratory physiopathology, such as the loss of the filtering, humidifying, and heating of air by the nose. The use of special stomal filters can provide adequate protection of the tracheal–bronchopulmonary system with a reduction in respiratory pathologies. In fact, in most cases, laryngectomy patients are first cigarette smokers who for this reason also already have respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, as reported in the literature, patients often tend to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for laryngectomy patients during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® LifeTM Energy HME and Provox® LifeTM Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomy patients, subjected to medium–high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT), which involves a sustained walk lasting six minutes, with an evaluation of heart rate, oxygen saturation, and meters traveled every 60 s; furthermore, we examined two subjective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index. Conclusions: The multidisciplinary approach of the laryngectomee patient must also take pulmonary rehabilitation into consideration. It is the task of the medical team and speech therapy support to help the patient in the correct choice of HME filters taking into account daily needs

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Effects of Linseed Supplementation on Milk Production, Composition, Odd-and Branched-Chain Fatty Acids, and on Serum Biochemistry in Cilentana Grazing Goats

The purpose of this study was to investigate the effects of linseed supplementation on milk yield and quality, serum biochemistry and, in particular, to evaluate its possible effects on the production of odd-and branched-chain fatty acids (OBCFA) in the milk of Cilentana grazing goats. Twelve pregnant Cilentana dairy goats were divided into two groups (CTR, control, and LIN, linseed supplementation group). After kidding, the goats had free access to the pasture and both groups received a supplement of 400 g/head of concentrate, but the one administered to the LIN group was characterized by the addition of linseed (in a ratio of 20% as fed) to the ingredients. During the trial, milk samples were taken from April to August in order to evaluate milk production, composition, and fatty acid profile. In addition, blood samples were taken for evaluating the effects of linseed supplementation on goats’ health status. The health status of the goats was not influenced by the linseed supplementation, as confirmed by blood analyses. Concerning the effects on milk, the supplementation positively affected (p < 0.001) milk production and fat percentage and the fatty acid profile was markedly influenced by the lipid supplementation. In particular, milk from the LIN group was characterized by significantly lower concentrations of saturated fatty acids (FA; p < 0.001) and higher proportions of monounsaturated FA, polyunsaturated FA, and conjugated linoleic acids (CLAs) than milk from the CTR group (p < 0.001). In contrast, the OBCFA were negatively influenced by the linseed supplementation (p < 0.0001). Further studies are needed to test the effects of different fat sources and other nutrients on the diets

Effects of ecotrofin™ on milk yield, milk quality and serum biochemistry in lactating goats

A nutritional supplement (Ecotrofin™, by Vetoquinol Italia S.r.l) recommended in ruminants feeding to strengthen the physiological condition and improve digestive performance was tested in 20 pluriparae grazing goats divided in two groups (control and treated) to assess its possible effects on milk yield and quality and to assess eventual adverse effects. Animals from both groups also received 400&nbsp;g/day of corn meal, and the treated group was supplemented with 20&nbsp;g/head/day of the nutritional supplement. At the doses suggested by the manufacturer, despite a transient increase after 30&nbsp;days of supplementation, Ecotrofin™ did not show significant effects on milk yield and, although some changes were found in the fatty acids profile, no significant improvement of MUFA and PUFA, as well as of omega-6:omega-3 ratio and CLA content were seen. Therefore, in our experimental conditions the supplementation of diet with Ecotrofin™ did not appear useful to improve goat's performance. A significant effect on kidney health markers (27 vs. 22.5 for urea and 0.83 vs. 0.76 for creatinine, p&nbsp;&lt;&nbsp;0.05) suggested a beneficial effect on renal function but, since levels fell in the normal ranges in both groups, such hypothesis would need further studies to be addressed