Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice

Coherent network oscillations (GDPs), generated in the immature hippocampus by the synergistic action of GABA and glutamate, both depolarizing and excitatory, play a key role in the construction of neuronal circuits. In particular, GDPs-associated calcium transients act as coincident detectors for enhancing synaptic efficacy at emerging GABAergic and glutamatergic synapses. Here, we show that, immediately after birth, in the CA3 hippocampal region of the BTBR T+tf/J mouse, an animal model of idiopathic autism, GDPs are severely impaired. This effect was associated with an increased GABAergic neurotransmission and a reduced neuronal excitability. In spite its depolarizing action on CA3 pyramidal cells (in single channel experiments EGABA was positive to Em), GABA exerted at the network level an inhibitory effect as demonstrated by isoguvacine-induced reduction of neuronal firing. We implemented a computational model in which experimental findings could be interpreted as the result of two competing effects: a reduction of the intrinsic excitability of CA3 principal cells and a reduction of the shunting activity in GABAergic interneurons projecting to principal cells. It is therefore likely that premature changes in neuronal excitability within selective hippocampal circuits of BTBR mice lead to GDPs dysfunction and behavioral deficits reminiscent of those found in autistic patients

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy

Natural Products for the Prevention, Treatment and Progression of Breast Cancer

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy

LHF Connect: a DIY telepresence robot against COVID-19

This contribution describes a case study of a “do-it-yourself” (DIY) opensource service and related product to help combating the COVID-19 emergency. It illustrates the birth of LHF Connect, a project designed to facilitate communication between patients isolated in COVID-19 hospitals’ ward and their relatives. LHF Connect is a teleoperated robot that can move in autonomy around the hospital. A User Centered Design approach, methods and specific tools helped in managing crucial steps of the design process such as i) the collection of needs coming from the context, stakeholders and end-users; ii) defining the service blueprint; iii) imagining finishing concepts; and iv) managing the communication activities. The initiative has been promoted by a multidisciplinary team of researchers (mainly roboticists with the help of specific competences coming from Design discipline)

Knowledge, Attitudes, and Practices on Energy Drink Consumption and Side Effects in a Cohort of Medical Students

The purpose of this study was to evaluate knowledge, attitudes, and practices concerning energy drink consumption and the prevalence of side effects among medical students. Twenty-two percent of respondents were regular users, particularly men (p <.0005). Users were younger (p =.027) and drank alcohol more frequently (p =.008) than "non-users." Forty-nine percent consumed alcohol associated with energy drinks. Forty-five percent of medical students declared side effects after energy drink consumption, such as palpitations (35%), insomnia (21%), and irritability (20%). The study confirms a large use of energy drinks among students and the occurrence of side effects. The use of energy drinks may influence the ingestion of large amounts of alcohol

In vitro detection of herpes simplex virus -1 and -2 infection with immunospecific GD3+-CL6-enhanced magnetic resonance imaging.

Herpes simplex virus infections are prevalent viral infections in humans. HSVs are also the most common cause of sporadic viral encephalitis (HSE). Magnetic resonance is the imaging method of choice for HSE because it provides the most sensitive method for detecting early lesions. The objective of this study is to set-up and in vitro test an experimental contrast agent specific for antigens present on HSV-infected cells, bound with a paramagnetic agent detectable by MR imaging. A selected anti-HSV HrFab was labelled with Alexa Fluor 488, 125I and Gd3+Cl6. In order to assess anti-HSV affinity and specificity, ELISA assays were performed. Vero cells infected with HSV strains were visualized by MRI using anti-HSV HrFab/Gd3+Cl6 complex. Results of the ELISA tests demonstrated that the anti-HSV HrFab labelled with Gd3+Cl6 showed similar affinity for the antigens while the 125I immunoconjugate showed reduced affinity. MRI confirmed high affinity and specificity of antibody for the detection of HSV infections

Systemic thrombolysis of portal vein thrombosis in cirrhotic patients: A pilot study

Background: Portal vein thrombosis is a frequent complication in liver cirrhosis. Encouraging reports of systemic thrombolysis in non-cirrhotic patients suffering from acute portal vein thrombosis led us to start a pilot study on the efficacy and safety of systemic low dose recombinant tissue plasminogen activator (Actilyse (R), Boheringer Ingelheim, Florence, Italy). Patients: Nine cirrhotic patients (6 males and 3 females) with recent portal vein thrombosis were enrolled. Exclusion criteria were portal cavernomatosis, recent (30 days) surgery, active bleeding, hepatocellular carcinoma and cancer in other sites. Methods: All cases were treated for a maximum of 7 clays by continuous i.v. infusion of 0.25 mg/kg/die of r-tPA plus subcutaneous low molecular weight heparin. Efficacy was evaluated by colour doppler sonography monitoring and confirmed by contrast enhanced computerized tomography. Results: The combined r-tPA/LMWH treatment was well tolerated without clinically significant side effects. Complete resolution of thrombosis occurred in 4 cases, partial regression in 4 and none in 1. Retreatment of a complete recurrence in 1 patient was successful. Variceal pressure dropped from 30.7 +/- 4.5 mmHg to 21.2 +/- 6.6 mmHg (p = 0.012). Conclusions: Our preliminary data demonstrate that thrombolytic treatment of recent portal vein thrombosis with iv. r-tPA and LMWH in patients with cirrhosis appears to be safe and effective and can significantly reduce pressure in oesophageal varices. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved