Effects of exercise training on cardiovascular adrenergic system

In heart failure (HF), exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac β-adrenergic receptor (β-AR) dysfunction. It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2) which is known to be involved in both β1-AR and β2-AR dysregulation in HF. Similar alterations of β-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/α-2AR/catecholamine (CA) production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores β-AR-dependent vasodilatation by increasing vascular β-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50% of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favorable effects of exercise on blood pressure control

Care pathways models and clinical outcomes in disorders of consciousness

Objective: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care path-way for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients’ clinical outcomes. Materials and Methods: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by ask-ing 90 patients’ caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received.Results: Seventy- three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diag-nosis. In long- term care units, the diagnosis at admission and the number of caregivers available for each patient (median value=3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non- Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. Conclusion: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and ac-tions are needed to guarantee equity and standardization of the care process in all European countries

Neuro-hormonal effects of physical activity in the elderly

22/07/14 meb.OA paper, author retains copyright.Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer. The favorable effects of exercise on cardiovascular homeostasis can be at least in part ascribed to the modulation of the neuro-hormonal systems implicated in cardiovascular pathophysiology. In the elderly, exercise has been shown to affect catecholamine secretion and biosynthesis, to positively modulate the renin-angiotensin-aldosterone system and to reduce the levels of plasma brain natriuretic peptides. Moreover, drugs modulating the neuro-hormonal systems may favorably affect physical capacity in the elderly. Thus, efforts should be made to actually make physical activity become part of the therapeutic tools in the elderly. © 2013 Femminella, de Lucia, Iacotucci, Formisano, Petraglia, Allocca, Ratto, DAmico, Rengo, Pagano, Bonaduce, Rengo and Ferrara

Structural connectivity in a single case of progressive prosopagnosia: The role of the right inferior longitudinal fasciculus

Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy. Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP

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

Prep1 Controls Insulin Glucoregulatory Function in Liver by Transcriptional Targeting of SHP1 Tyrosine Phosphatase

AbstractObjective. We have investigated the function of the Prep1 gene in insulin-dependent glucose homeostasis in liver. Research design and methods. Prep1 action on insulin glucoregulatory function has been analyzed in liver of Prep1-hypomorphic mice (Prep1(i/i)), which express 2 to 3% of Prep1 mRNA. Results. Based on euglycemic hyperinsulinemic clamp studies, pyruvate tolerance tests and measurement of glycogen content, livers from Prep1(i/i) mice feature increased sensitivity to insulin. Tyrosine phosphorylation of both insulin receptor (IR) and IRS1/2 was significantly enhanced in Prep1(i/i) livers accompanied by a specific down-regulation of the SYP and SHP1 tyrosine phosphatases. Prep1 overexpression in HepG2 liver cells upregulated SYP and SHP1 and inhibited insulin-induced IR and IRS1/2 phosphorylation and was accompanied by reduced glycogen content. Consistently, overexpression of the Prep1 partner Pbx1 but not of p160MBP, mimicked Prep1 effects on tyrosine phosphorylations, glycogen content and on SYP and SHP1 expression. In Prep1 overexpressing cells, antisense silencing of SHP1, but not that of SYP, rescued insulin-dependent IR phosphorylation and glycogen accumulation. Both Prep1 and Pbx1 bind SHP1 promoter at a site located between nt -2113 and -1778. This fragment features enhancer activity and induces luciferase function by 7, 6 and 30-fold, respectively, in response to Prep1, Pbx1 or both. Conclusions. SHP1, a known silencer of insulin signal, is a transcriptional target of Prep1. In liver, transcriptional activation of SHP1 gene by Prep1 attenuates insulin signal transduction and reduces glucose storage

Neurorehabilitation of severe acquired brain injury in the time of COVID-19: impact of the absence of caregivers

Introduction. During the COVID-19 pandemic, several restrictions were imposed to limit the circulation of the infection within communities. Hospitals denied access to the family and friends of inpatients, and thus to caregivers. This observational study evaluated the impact of the physical absence of caregivers during the lockdown period due to the COVID-19 emergency on the neurorehabilitation of inpatients with severe acquired brain injury (sABI). Methods. The functional outcome at discharge was measured in 25 inpatients with sABI through the DRS, GOS, and LCF standard scales after neuropsychological rehabilitation in an Adult Inpatient Neurorehabilitation Unit for Post-coma. Fourteen patients were directly assisted by their informal caregivers physically present in the neurorehabilitation ward. Eleven patients were indirectly supported via remote connection because during the lockdown period (from March to July 2020) caregivers could not be admitted to the rehabilitation hospital. The Caregiving Impact on Neuro-Rehabilitation Scale was also used to evaluate both the change since the admission and the impact of the caregiver from the perspective of the cognitive therapist. Demographic characteristics, time since injury, injury severity (duration of impaired consciousness measured by the time to follow commands), level of functioning at the beginning of the neurorehabilitation, and duration of the neurorehabilitation treatment were comparable between the groups. Results. Both groups improved after the treatment; however, the improvement was consistently greater in the group directly assisted by the caregivers. The results showed that although the caregivers ensured their virtual presence at distance, their physical absence played a role in hindering the functional outcome of the patients. Conclusions. The role of the caregiver of patients with sABI is underlined in being not only a person handing out generic aid, cares, and affection, but also an integral part of the neurorehabilitation process.   Keywords: Brain injuries, Neurorehabilitation, Informal caregivers, COVID-19 pandemic, SARS-CoV-2, Lockdown &nbsp

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age