Biomedical prostheses coated by tailored MWPECVD nanocrystalline diamond films

Different aspects concerning the use of nanocrystalline diamond (NCD) film, as coating for biomedical prostheses, is discussed. An overview is done on diamond implementation in prostheses, on the NCD mechanical properties and on the technological aspects concerning the NCD growth process i.e. Microwave Plasma Enhanced Chemical Vapor deposition. Then, the attention is focused on a possible improvement of NCD growth on titanium (Ti) substrate. Further, a theoretical study by finite element method is discussed in order to model the adhesion properties of a NCD layer on Ti and Ti/Titanium Carbide (TiC) substrates. The goal of the proposed work is to provide a study about the use of thin NCD coating on Ti based prostheses. The function of the NCD coating on Ti material is to improve the implanted prosthesis with a long duration time, thus decreasing the total costs and the invasive surgery treatments

Validation of a new data-analysis software for multiple-peak analysis of γ spectra at ISIS pulsed Neutron and Muon Source

© 2019 Elsevier B.V. In this work, we present a multi-peak fitting code in order to establish a new protocol for the analysis of γ spectra at ISIS pulsed Neutron and Muon Source. The protocol, relying on the ROOT framework developed at CERN, has been tailored for the analysis of two specific gamma emitters – 241Am and 133Ba – and its results have been compared to those generated by Hypermet PC, a dedicated software package specifically devoted to the analysis of neutron induced γ-ray spectra and of widespread use since late 1990s. This new fitting procedure is scheduled for integration into the software for time-resolved prompt-gamma activation analysis, T-PGAA, currently under development at ISIS. T-PGAA allows for the simultaneous acquisition of photon energy and neutron time of flight, respectively, when prompt gamma rays are emitted by a sample after neutron absorption, essentially combining neutron resonance capture analysis (NRCA) and prompt gamma activation analysis (PGAA)

Adapting and implementing training, guidelines and treatment cards to improve primary care-based hypertension and diabetes management in a fragile context: results of a feasibility study in Sierra Leone

Background Sierra Leone, a fragile country, is facing an increasingly significant burden of non-communicable diseases (NCDs). Facilitated by an international partnership, a project was developed to adapt and pilot desktop guidelines and other clinical support tools to strengthen primary care-based hypertension and diabetes diagnosis and management in Bombali district, Sierra Leone between 2018 and 2019. This study assesses the feasibility of the project through analysis of the processes of intervention adaptation and development, delivery of training and implementation of a care improvement package and preliminary outcomes of the intervention. Methods A mixed-method approach was used for the assessment, including 51 semi-structured interviews, review of routine treatment cards (retrieved for newly registered hypertensive and diabetic patients from June 2018 to March 2019 followed up for three months) and mentoring data, and observation of training. Thematic analysis was used for qualitative data and descriptive trend analysis and t-test was used for quantitative data, wherever appropriate. Results A Technical Working Group, established at district and national level, helped to adapt and develop the context-specific desktop guidelines for clinical management and lifestyle interventions and associated training curriculum and modules for community health officers (CHOs). Following a four-day training of CHOs, focusing on communication skills, diagnosis and management of hypertension and diabetes, and thanks to a CHO-based mentorship strategy, there was observed improvement of NCD knowledge and care processes regarding diagnosis, treatment, lifestyle education and follow up. The intervention significantly improved the average diastolic blood pressure of hypertensive patients (n = 50) three months into treatment (98 mmHg at baseline vs. 86 mmHg in Month 3, P = 0.001). However, health systems barriers typical of fragile settings, such as cost of transport and medication for patients and lack of supply of medications and treatment equipment in facilities, hindered the optimal delivery of care for hypertensive and diabetic patients. Conclusion Our study suggests the potential feasibility of this approach to strengthening primary care delivery of NCDs in fragile contexts. However, the approach needs to be built into routine supervision and pre-service training to be sustained. Key barriers in the health system and at community level also need to be addressed

L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers

Purpose: Nonalcoholic fatty liver disease (NAFLD) is defined by excessive lipid accumulation in the liver and involves an ample spectrum of liver diseases, ranging from simple uncomplicated steatosis to cirrhosis and hepatocellular carcinoma. Accumulating evidence demonstrates that high fructose intake enhances NAFLD development and progression promoting inhibition of mitochondrial \u3b2-oxidation of long-chain fatty acids and oxidative damages. l-Carnitine (LC), involved in \u3b2-oxidation, has been used to reduce obesity caused by high-fat diet, which is beneficial to ameliorating fatty liver diseases. Moreover, in the recent years, various studies have established LC anti-oxidative proprieties. The objective of this study was to elucidate primarily the underlying anti-oxidative mechanisms of LC in an in vitro model of fructose-induced liver steatosis. Methods: Human hepatoma HepG2 cells were maintained in medium supplemented with LC (5 mM LC) with or without 5 mM fructose (F) for 48 h and 72 h. In control cells, LC or F was not added to medium. Fat deposition, anti-oxidative, and mitochondrial homeostasis were investigated. Results: LC supplementation decreased the intracellular lipid deposition enhancing AMPK activation. However, compound C (AMPK inhibitor-10 \u3bcM), significantly abolished LC benefits in F condition. Moreover, LC, increasing PGC1 \u3b1 expression, ameliorates mitochondrial damage-F induced. Above all, LC reduced ROS production and simultaneously increased protein content of antioxidant factors, SOD2 and Nrf2. Conclusion: Our data seemed to show that LC attenuate fructose-mediated lipid accumulation through AMPK activation. Moreover, LC counteracts mitochondrial damages and reactive oxygen species production restoring antioxidant cellular machine. These findings provide new insights into LC role as an AMPK activator and anti-oxidative molecule in NAFLD

Modulation of cell cycle progression by 5-azacytidine is associated with early myogenesis induction in murine myoblasts

Myogenesis is a multistep process, in which myoblasts withdraw from the cell cycle, cease to divide, elongate and fuse to form multinucleated myotubes. Cell cycle transition is controlled by a family of cyclin-dependent protein kinases (CDKs) regulated by association with cyclins, negative regulatory subunits and phosphorylation. Muscle differentiation is orchestrated by myogenic regulatory factors (MRFs), such as MyoD and Myf-5. DNA methylation is crucial in transcriptional control of genes involved in myogenesis. Previous work has indicated that treatment of fibroblasts with the DNA-demethylating agent 5-azacytidine (AZA) promotes MyoD expression. We studied the effects of AZA on cell cycle regulation and MRFs synthesis during myoblast proliferation and early myogenesis phases in C2C12 cells. During the proliferation phase, cells were incubated in growth medium with 5\u3bcM AZA (GMAZA) or without AZA (GM) for 24 hours. At 70% confluence, cells were kept in growth medium in order to spontaneously achieve differentiation or transferred to differentiation medium with 5\u3bcM AZA (DMAZA) or without AZA (DM) for 12 and 24 hours. Cells used as control were unstimulated. In the proliferation phase, AZA-treated cells seemed to lose their characteristic circular shape and become elongated. The presence of AZA resulted in significant increases in the protein contents of Cyclin-D (FC:1.23 GMAZA vs GM p 640.05), p21 (FC: 1.23 GMAZA vs GM p 640.05), Myf-5 (FC: 1.21 GMAZA vs GM p 640.05) and MyoD (FC: 1.20 GMAZA vs GM p 640.05). These results propose that AZA could inhibit cell proliferation. During 12 hours of differentiation, AZA decreased the downregulation of genes involved in cell cycle arrest and in restriction point (G1 and G1/S phase) and the expression of several cyclins, E2F Transcription Factors, cyclin-dependent kinase inhibitors, specific genes responsible of cell cycle negative regulation. During 24 hours of differentiation, AZA induced an increment in the protein expression of Myf-5 (FC: 1.57 GMAZA vs GM p 640.05), MyoD (FC: 1.14 DM vs GM p 640.05; FC: 1.47 DMAZA vs GM p 640.05), p21 (FC: 1.36 GMAZA vs GM p 640.01; FC: 1.49 DM vs GM p 640.05; FC: 1.82 DMAZA vs GM p 640.01) and MyHC (FC: 1.40 GMAZA vs GM p 640.01; FC: 2.39 DM vs GM p 640.05; FC: 3.51 DMAZA vs GM p 640.01). Our results suggest that AZA-induced DNA demethylation can modulate cell cycle progression and enhance myogenesis. The effects of AZA may open novel clinical uses in the field of muscle injury research and treatment

A Multicentre Study: The Use of Micrografts in the Reconstruction of Full-Thickness Posttraumatic Skin Defects of the Limbs - A Whole Innovative Concept in Regenerative Surgery

The skin graft is a surgical technique commonly used in the reconstructive surgery of the limbs, in order to repair skin loss, as well as to repair the donor area of the flaps and cover the dermal substitutes after engraftment. The unavoidable side effect of this technique consists of unaesthetic scars. In order to achieve the healing of posttraumatic ulcers by means of tissue regeneration and to avoid excessive scarring, a new innovative technology based on the application of autologous micrografts, obtained by Rigenera technology, was reported. This technology was able to induce tissue repair by highly viable skin micrografts of 80 micron size achieved by a mechanical disaggregation method. The specific cell population of these micrografts includes progenitor cells, which in association with the fragment of the Extracellular Matrix (ECM) and growth factors derived by patients' own tissue initiate biological processes of regeneration enhancing the wound healing process. We have used this technique in 70 cases of traumatic wounds of the lower and upper limbs, characterized by extensive loss of skin substance and soft tissue. In all cases, we have applied the Rigenera protocol using skin micrografts, achieving in 69 cases the complete healing of wounds in a period between 35 and 84 days. For each patient, the reconstructive outcome was evaluated weekly to assess the efficacy of this technique and any arising complication. A visual analogue scale (VAS) was administered to assess the amount of pain felt after the micrografts' application, whereas we evaluated the scars according to the Vancouver scale and the wound prognosis according to Wound Bed Score. We have thus been able to demonstrate that Rigenera procedure is very effective in stimulating skin regeneration, while reducing the outcome scar

Potential therapeutic role of L-carnitine in skeletal muscle oxidative stress and atrophy conditions

The targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrial \u3b2-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhance \u3b2-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. This in vitro study aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging

Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

Background: Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications.Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio- and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, prevention of mitochondrial disorder, avoidance of obesity-related diseases. In skeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but its action mechanisms and protein targets in myogenesis process are not completely known. Myogenesis is a dynamic multistep process regulated by Myogenic Regulator Factors (MRFs), responsible of the commitment of myogenic cell into skeletal muscle: mononucleated undifferentiated myoblasts break free from cell cycle, elongate and fuse to form multinucleated myotubes. Skeletal muscle hypertrophy can be defined as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by increased protein synthesis, mainly regulated by Insulin Like Growth Factor 1 (IGF-1), PI3-K/AKT signaling pathways.Aim of this work was the study of RSV effects on proliferation, differentiation process and hypertrophy in C2C12 murine cells.Methods: To study proliferative phase, cells were incubated in growth medium with/without RSV (0.1 or 25 \u3bcM) until reaching sub confluence condition (24, 48, 72 h). To examine differentiation, at 70% confluence, cells were transferred in differentiation medium both with/without RSV (0.1 or 25 \u3bcM) for 24, 48, 72, 96 hours. After 72 hours of differentiation, the genesis of hypertrophy in neo-formed myotubes was analyzed.Results: Data showed that RSV regulates cell cycle exit and induces C2C12 muscle differentiation. Furthermore, RSV might control MRFs and muscle-specific proteins synthesis. In late differentiation, RSV has positive effects on hypertrophy: RSV stimulates IGF-1 signaling pathway, in particular AKT and ERK 1/2 protein activation, AMPK protein level and induces hypertrophic morphological changes in neo-formed myotubes modulating cytoskeletal proteins expression.Conclusions: RSV might control cell cycle promoting myogenesis and hypertrophy in vitro, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment

Chronic neural interfacing with cerebral cortex using single-walled carbon nanotube-polymer grids

Objective. The development of electrode arrays able to reliably record brain electrical activity is a critical issue in brain machine interface (BMI) technology. In the present study we undertook a comprehensive physico-chemical, physiological, histological and immunohistochemical characterization of new single-walled carbon nanotubes (SWCNT)-based electrode arrays grafted onto medium-density polyethylene (MD-PE) films. Approach. The long-term electrical stability, flexibility, and biocompatibility of the SWCNT arrays were investigated in vivo in laboratory rats by two-months recording and analysis of subdural electrocorticogram (ECoG). Ex-vivo characterization of a thin flexible and single probe SWCNT/polymer electrode is also provided. Main results. The SWCNT arrays were able to capture high quality and very stable ECoG signals across 8 weeks. The histological and immunohistochemical analyses demonstrated that SWCNT arrays show promising biocompatibility properties and may be used in chronic conditions. The SWCNT-based arrays are flexible and stretchable, providing low electrode-tissue impedance, and, therefore, high compliance with the irregular topography of the cortical surface. Finally, reliable evoked synaptic local field potentials in rat brain slices were recorded using a special SWCNT-polymer-based flexible electrode. Significance. The results demonstrate that the SWCNT arrays grafted in MD-PE are suitable for manufacturing flexible devices for subdural ECoG recording and might represent promising candidates for long-term neural implants for epilepsy monitoring or neuroprosthetic BMI