A \u201cnoisy\u201d electrical stimulation protocol favors muscle regeneration in vitro through release of endogenous ATP

An in vitro system of electrical stimulation was used to explore whether an innovative \u201cnoisy\u201d stimulation protocol derived from human electromyographic recordings (EMGstim)could promote muscle regeneration. EMGstim was delivered to cultured mouse myofibers isolated from Flexor Digitorum Brevis, preserving their satellite cells. In response to EMGstim, immunostaining for the myogenic regulatory factor myogenin, revealed an increased percentage of elongated myogenin-positive cells surrounding the myofibers. Conditioned medium collected from EMGstim-treated cell cultures, promoted satellite cells differentiation in unstimulated myofiber cell cultures, suggesting that extracellular soluble factors could mediate the process. Interestingly, the myogenic effect of EMGstim was mimicked by exogenously applied ATP (0.1 \u3bcM), reduced by the ATP diphosphohydrolase apyrase and prevented by blocking endogenous ATP release with carbenoxolone. In conclusion, our results show that \u201cnoisy\u201d electrical stimulations favor muscle progenitor cell differentiation most likely via the release of endogenous ATP from contracting myofibres. Our data also suggest that \u201cnoisy\u201d stimulation protocols could be potentially more efficient than regular stimulations to promote in vivo muscle regeneration after traumatic injury or in neuropathological diseases

Tinnitus revival during COVID‑19 lockdown: how to deal with it?

To the Editor, The novel Coronavirus Disease, officially designated as COVID-19 by the WHO, is a serious issue for public health. To contain the COVID-19, the Italian Government stated on March 9th 2020 the prohibition of any movement throughout the national area unless for work/health reasons and the obligation to remain as much as possible inside one’s own home. With the start of the so-called “Phase Two” on May 4th 2020, circulation within the same region was allowed again, due to the progressive slowdown of the outbreak. Therefore, since lockdown measures were relaxed and access to the emergency room or ENT clinic became less worrying for patients, specialists of Otolaryngology Units in Bari (Italy) observed an increase in the amount of subjects complaining of the revival of intense tinnitus. We attempt in this letter to focus on patients affected by chronic subjective tinnitus, that already had a diagnosis and self-stabilized without a massive treatment. Research studies have reported tinnitus wide impact on quality of life of subjects experiencing it, involving their emotional state, concentration and sleep quality; at this regard, Tinnitus Handicap Inventory (THI) is a self-reported tool regularly used to quantify the grade of perceived handicap as slight (0–16), mild (18–36), moderate (38–56), severe (58–76) or catastrophic (78–100) on the basis of 25 questions [1]. During the past 2 weeks, we have collected data from 16 patients among our population of chronic sufferers: THI observed was moderate in 62.5% and severe in 18.75% of cases, catastrophic in 12.5% and mild in 6.25% of subjects. Interestingly, the grade of handicap resulted increased by one-level in 12 out of 16 patients (75%); in particular, THI shifted from mild to moderate in 9 patients and from moderate to severe in 3 patients. As shown in the literature, tinnitus generation, maintenance and recrudescence are still debated. A cortical reorganization secondary to sensory deprivation has been proposed as one on the most frequent cause of tinnitus [2]. The avoidance of silence and acoustic masking have been proposed as effective measures to overcome sensory deprivation and increase masking of the symptom [3]. It is reasonable to think that, during the lockdown, the absence of environmental masking sounds from everyday life may have enhanced the tinnitus perception. Furthermore, proneness to worry and incoming stress during pandemic could be included as further potential risk factors for tinnitus worsening. As proficiently reviewed in a recent work [4], some internet/smartphone-based applications provide in tinnitus patients adequate counseling and interactive information together with sound therapy. As brain networks implicated in adaptive responses to sound stimuli and to worry are shared in many cases, an early decrease of anxiety status may release neural resources crucial for tinnitus habituation/distress perception [5]. In general, interactive platforms have been widely implemented during lockdown period due to the forced lack of real personal and working relationships; since smart-working seems to be successful for future plans, the development of smart applications and mobile services in the health care field may be promising in terms of cost-effectiveness, tolerability and simplicity of use

Effects of biochar addition on long-term behaviour of concrete and mortar

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Solid-state phase transformations in thermally treated Ti-6Al-4V alloy fabricated via laser powder bed fusion

Laser Powder Bed Fusion (LPBF) technology was used to produce samples based on the Ti-6Al-4V alloy for biomedical applications. Solid-state phase transformations induced by thermal treatments were studied by neutron diffraction (ND), X-ray diffraction (XRD), scanning transmission electron microscopy (STEM) and energy-dispersive spectroscopy (EDS). Although, ND analysis is rather uncommon in such studies, this technique allowed evidencing the presence of retained \u3b2 in \u3b1' martensite of the as-produced (#AP) sample. The retained \u3b2 was not detectable byXRDanalysis, nor by STEM observations. Martensite contains a high number of defects, mainly dislocations, that anneal during the thermal treatment. Element diffusion and partitioning are the main mechanisms in the \u3b1 \u2194 \u3b2 transformation that causes lattice expansion during heating and determines the final shape and size of phases. The retained \u3b2 phase plays a key role in the \u3b1' \u2192 \u3b2 transformation kinetics

Neuronal Agrin Promotes Proliferation of Primary Human Myoblasts in an Age-Dependent Manner

Neuronal agrin, a heparan sulphate proteoglycan secreted by the -motor neurons, promotes the formation and maintenance of the neuromuscular junction by binding to Lrp4 and activating muscle-specific kinase (MuSK). Neuronal agrin also promotes myogenesis by enhancing differentiation and maturation of myotubes, but its effect on proliferating human myoblasts, which are often considered to be unresponsive to agrin, remains unclear. Using primary human myoblasts, we determined that neuronal agrin induced transient dephosphorylation of ERK1/2, while c-Abl, STAT3, and focal adhesion kinase were unresponsive. Gene silencing of Lrp4 and MuSK markedly reduced the BrdU incorporation, suggesting the functional importance of the Lrp4/MuSK complex for myoblast proliferation. Acute and chronic treatments with neuronal agrin increased the proliferation of human myoblasts in old donors, but they did not affect the proliferation of myoblasts in young donors. The C-terminal fragment of agrin which lacks the Lrp4-binding site and cannot activate MuSK had a similar age-dependent effect, indicating that the age-dependent signalling pathways activated by neuronal agrin involve the Lrp4/MuSK receptor complex as well as an Lrp4/MuSK-independent pathway which remained unknown. Collectively, our results highlight an age-dependent role for neuronal agrin in promoting the proliferation of human myoblasts

A systematic review of the biological processes involved in deep-brain stimulation for parkinson’s disease: A focus on the potential disease-modifying effects

Deep-Brain Stimulation (DBS) is an important treatment option for the management of Parkinson’s disease (PD) and is a common symptomatic treatment. However, an increasing number of studies have examined the biological processes to assess if DBS can also modify the natural history of PD by acting on its pathophysiological mechanisms. Relevant literature published up to November 2020 was systematically searched on databases such as PubMed, ISI Web of Knowledge, Academic Search Index, and Science Citation Index. The following predefined inclusion criteria were applied to the full-text versions of the selected articles: I) recruiting and monitoring of PD subjects that were previously treated with DBS and ii) investigating the electrophysiological, biochemical, epigenetic, or neuroimaging effects of DBS. Studies focusing exclusively on motor and clinical changes were excluded. Reviews, case reports, studies on animal models, and computational studies were also not considered. Out of 2,960 records screened, 43 studies met the inclusion criteria. Only three studies described a potential disease-modifying effect of DBS. However, a wide heterogeneity was observed in the investigated biomarkers, and the design and methodological issues of several studies limited their ability to find potential disease-modifying features. Specifically, 60.4% of the trials followed-up subjects for no more than 1 year from the surgical intervention, and 67.4% observed patients with PD only once after DBS. Moreover, 64.2% of the studies enrolled late-stage PD patients. Most of the studies (88.4%) reported that DBS only had a symptomatic effect, with several of them showing some limitations in the study design and recruitment of patients. Further studies using shared biomarkers are encouraged to assess if and how DBS might affect the progression of PD. Based on the existing preclinical literature, prospective clinical trials examining the course of PD in early-stage patients are needed

In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40\u2009nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine

Adenosine Promotes Endplate nAChR Channel Activity in Adult Mouse Skeletal Muscle Fibers via Low Affinity P1 Receptors

© 2018 IBRO Adenosine is a powerful modulator of skeletal neuromuscular transmission, operating via inhibitory or facilitatory purinergic-type P1 receptors. To date, studies have been focused mainly on the effect of adenosine on presynaptic P1 receptors controlling transmitter release. In this study, using two-microelectrode voltage-clamp and single-channel patch-clamp recording techniques, we have explored potential postsynaptic targets of adenosine and their modulatory effect on nicotinic acetylcholine receptor (nAChR)-mediated synaptic responses in adult mouse skeletal muscle fibers in vitro. In the whole-mount neuromuscular junction (NMJ) preparation, adenosine (100 μM) significantly reduced the frequency of the miniature endplate currents (MEPCs) and slowed their rising and decay time. Consistent with a postsynaptic site of action, adenosine and the potent P1 receptor agonist NECA significantly increased the open probability, the frequency and the open time of single nAChR channels, recorded at the endplate region. Using specific ligands for the P1 receptor subtypes, we found that the low-affinity P1 receptor subtype A2B was responsible for mediating the effects of adenosine on the nAChR channel openings. Our data suggest that at the adult mammalian NMJ, adenosine acts not only presynaptically to modulate acetylcholine transmitter release, but also at the postsynaptic level, to enhance the activity of nAChRs. Our findings open a new scenario in understanding of purinergic regulation of nAChR activity at the mammalian endplate region

The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ39Vδ2 T cell activation by dendritic cells

V\uce\ub339V\uce\ub42 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce V\uce\ub339V\uce\ub42 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXR\uce\ub1 nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune V\uce\ub339V\uce\ub42 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation

The Italian fund for Alzheimer's and other dementias: strategies and objectives to face the dementia challenge

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper