Switching on microglia with electro-conductive multi walled carbon nanotubes

We explored the mechanisms underlying microglia cell-carbon nanotube interactions in order to investigate whether electrical properties of Carbon-Nanotubes (CNTs) could affect microglia brain cells function and phenotype. We analyzed the effects induced by highly electro-conductive Multi-Walled-Carbon-Nanotubes (a-MWCNTs), on microglia cells from rat brain cortex and compared the results with those obtained with as prepared not conductive MWCNTs (MWCNTs) and redox-active Double-Walled-Carbon-Nanotubes (DWCNTs). Cell viability and CNT capacity to stimulate the release of nitric oxide (NO), pro-inflammatory (IL-1b, TNF-a) and anti-inflammatory (IL-10, TGF-b1) cytokines and neurotrophic factors (mNGF) were assessed. Electro-conductive MWCNTs, besides not being cytotoxic, were shown to stimulate, at 24 h cell exposure, classical "M100 microglia activation phenotype, increasing significantly the release of the main pro-inflammatory cytokines. Conversely, after 48 h cell exposure, they induced the transition from classical "M100 to alternative "M200 microglia phenotype, supported by anti-inflammatory cytokines and neuroprotective factor mNGF release. The analysis of cell morphology change, by tubulin and CD-206 þ labelling showed that M2 phenotype was much more expressed at 48 h in cells exposed to a-MWCNTs than in untreated cells. Our data suggest that the intrinsic electrical properties of CNTs could be exploited to modulate microglia phenotype and function stimulating microglia anti-inflammatory potential

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 +/- 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions

Primary motor cortex excitability is modulated by tactile adaptation in primary somatosensory cortex

We used transcranial magnetic stimulation (TMS) to study sensorimotor integration in humans in the context of a tactile adaptation paradigm. When two identical successive stimuli activate the same neuronal population a decrease in the overall neural response is observed. This type of neurophysiological response is known as an adaptation effect. Thus, when two tactile events are repeated on exactly the same skin region those neurons that have a strictly somatotopic response should show less activity. Moreover, previous reports suggest that the neurophysiological response of the primary motor cortex (M1) can be inhibited when a single tactile stimulus is presented 20 - 100 ms before a TMS pulse. This inhibition is measured as a decrease in the amplitude of the motor evoked potentials (MEPs) recorded from a given muscle. This phenomenon has been named short-latency afferent inhibition (SAI). Given this, we reasoned that repeating tactile events on the same finger (e.g. the index) should produce more adaptation in the primary somatosensory cortex (S1) than presenting stimuli to the middle and then index finger, which should in turn result in weaker inhibition of M1. Here, we tested whether SAI is sensitive to tactile adaptation effects and if so, whether these effects vary as a function of the stimulated finger pairs. We presented two consecutive electrocutaneous stimuli on homologous (i.e., left index finger stimulated twice) and non-homologous fingers (i.e., left middle and left index fingers) with fixed inter-stimulus intervals. Our results show a smaller reduction in the amplitude of MEPs recorded from the first dorsal interrosseus of the hand that received the tactile stimuli when stimuli were delivered to the same finger than to two different fingers. We interpret the presence of less SAI during same-finger than different-finger tactile stimulation as evidence that the excitability of the primary motor cortex can be differentially modulated by tactile adaptation effects that occur primarily within S1

Reaching to sounds in virtual reality: A multisensory-motor approach to promote adaptation to altered auditory cues

International audienceWhen localising sounds in space the brain relies on internal models that specify the correspondence between the auditory input reaching the ears, initial head-position and coordinates in external space. These models can be updated throughout life, setting the basis for re-learning spatial hearing abilities in adulthood. In addition, strategic behavioural adjustments allow people to quickly adapt to atypical listening situations. Until recently, the potential role of dynamic listening, involving head-movements or reaching to sounds, have remained largely overlooked. Here, we exploited visual virtual reality (VR) and real-time kinematic tracking, to study the role of active multisensory-motor interactions when hearing individuals adapt to altered binaural cues (one ear plugged and muffed). Participants were immersed in a VR scenario showing 17 virtual speakers at ear-level. In each trial, they heard a sound delivered from a real speaker aligned with one of the virtual ones and were instructed to either reach-to-touch the perceived sound source (Reaching group), or read the label associated with the speaker (Naming group). Participants were free to move their heads during the task and received audio-visual feedback on their performance. Most importantly, they performed the task under binaural or monaural listening. Results show that both groups adapted rapidly to monaural listening, improving sound localisation performance across trials and changing their head-movement behaviour. Reaching the sounds induced faster and larger sound localisation improvements, compared to just naming its position. This benefit was linked to progressively wider head-movements to explore auditory space, selectively in the Reaching group. In conclusion, reaching to sounds in an immersive visual VR context proved most effective for adapting to altered binaural listening. Head-movements played an important role in adaptation, pointing to the importance of dynamic listening when implementing training protocols for improving spatial hearing

Efficacy of the New Inotropic Agent Istaroxime in Acute Heart Failure

: Current therapeutic strategies for acute heart failure (AHF) are based on traditional inotropic agents that are often associated with untoward effects; therefore, finding new effective approaches with a safer profile is dramatically needed. Istaroxime is a novel compound, chemically unrelated to cardiac glycosides, that is currently being studied for the treatment of AHF. Its effects are essentially related to its inotropic and lusitropic positive properties exerted through a dual mechanism of action: activation of the sarcoplasmic reticulum Ca2+ ATPase isoform 2a (SERCA2a) and inhibition of the Na+/K+-ATPase (NKA) activity. The advantages of istaroxime over the available inotropic agents include its lower arrhythmogenic action combined with its capability of increasing systolic blood pressure without augmenting heart rate. However, it has a limited half-life (1 hour) and is associated with adverse effects including pain at the injection site and gastrointestinal issues. Herein, we describe the main mechanism of action of istaroxime and we present a systematic overview of both clinical and preclinical trials testing this drug, underlining the latest insights regarding its adoption in clinical practice for AHF

Single suture-mediated closure system after transfemoral transcatheter aortic valve implantation: A single-center real-world experience

Background: Despite the use of two crossed Perclose ProGlideTM (Abbott Vascular Devices) is the most widespread technique to close the main arterial access in transfemoral transcatheter aortic valve implantation (TF-TAVI), the safest and most effective strategy still remains much debated. Aims: The aim of the present study was to evaluate the performance of a single Perclose ProGlide suture-mediated closure device to obtain femoral hemostasis after sheathless implantation of self-expanding transcatheter heart valves through their 14 F-equivalent fix delivery systems. Methods: This prospective observational study included 439 patients undergoing TF-TAVI at the "Montevergine" Clinic of Mercogliano, Italy. All patients underwent hemostasis of the large-bore access using a single Perclose ProGlide with preclose technique, after sheathless implantation of self-expanding transcatheter heart valves through 14 F-equivalent fix delivery systems. A multidetector computed tomography analysis of size, tortuosity, atherosclerotic, and calcification burdens of the ilio-femoral access route was made by a dedicated corelab. Vascular complications (VCs), percutaneous closure device (PCD) failure, and bleedings were adjudicated by a clinical events committee. Results: A total of 81 different VCs were observed in 60 patients (13.7%); among these, 41 (5% of patients) were categorized as major. PCD failure occurred in 14 patients (3.2%). At the logistic regression analysis, no predictors of PCD failure have been identified. Conclusion: This registry suggests that the use of a single suture-mediated closure device could be considered a safe and efficient technique to achieve access site hemostasis in patients undergoing TF-TAVI through 14 F-equivalent fix delivery systems

Combined use of directional atherectomy and drug-coated balloon for the endovascular treatment of common femoral artery disease: immediate and one-year outcomes

Surgical endarterectomy is the therapy of choice for atherosclerotic common femoral artery (CFA) obstruction. Recently, some large single-centre series have shown encouraging results for the percutaneous treatment of CFA obstructions. The purpose of this study was to evaluate the safety, feasibility, and one-year efficacy of the endovascular treatment of CFA obstructions with combined use of directional atherectomy (DA) and a paclitaxel-coated balloon (DCB)