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Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance. During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)–and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A–are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions. Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders. This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process. [ABSTRACT FROM AUTHOR]

LiNi 0.5 Mn 1.5 O 4 (LNMO) composite electrodes having the same formulation as to percentage of active material mass, binder and carbons, including reduced graphene oxide, were characterized in EC: DMC – 1M LiPF 6 by cyclic voltammetry, charge/discharge cycles and impedance spectroscopy. The results demonstrate the beneficial effect on the electrode cycling stability in increasing C-rate to 1C, in limiting the charge voltage at 4.8 V and in covering the LNMO by partially reduced graphene oxide. The paper also discusses the evaluation of lithium diffusion coefficient in LNMO from cyclic voltammetry data in regard to the discrepancies reported in literature on this matter. [ABSTRACT FROM AUTHOR]

Abstract: The paper reports and discusses the results of electrochemical tests carried out according to the DOE Battery Test Manual for plug-in Hybrid Electric Vehicles (PHEVs) on laboratory high-voltage graphite/LiNi0.4Mn1.6O4 cells with electrode formulation and mass-loading suitable for scale-up, and mixed ethylene carbonate–dimethyl carbonate with two diverse lithium salts, lithium tris(pentafluoroethyl)trifluorophosphate and LiPF6, as electrolytes. The cells, assembled with two different separators, a polypropylene monolayer separator (Celgard®2400) and a reinforced polyvinylidene fluoride macroporous membrane (PVdF-NCC), were also tested by deep charge/discharge cycles. The results show the strong impact of the separator on high-rate cell functioning in PHEVs. [Copyright &y& Elsevier]

Abstract: The performance of full cells featuring high-voltage LiNi0.4Mn1.6O4 cathode and graphite anode with carbonate-based electrolytes, ethylene carbonate (EC) -dimethyl carbonate (DMC) with conventional LiPF6 and non-conventional Li[(C2F5)3PF3] (LiFAP) lithium salts with and without SEI-forming additives 1-fluoro ethylene carbonate (F1EC) and succinic anhydride (SA) is investigated. The results evidence the beneficial impact of EC-DMC-1M LiFAP electrolyte (LF30), with respect to EC-DMC-1M LiPF6 electrolyte (LP30), also in presence of 1.6% F1EC-2% SA additives, on charge retention over cycling and on self-discharge of full cells. After the 25 cycles of the charge capability test, the charge retention reached values up to 70% with LF30 and 87% with LF30 and additives, and fully charged cells with LF30-additives delivered 53% of the stored charge after one week in OCV. [Copyright &y& Elsevier]

Power generation and storage in electronics require flexible, thin micro-electrochemical energy storage/conversion systems. Micro-supercapacitors (μSCs) with double-layer capacitance carbon electrodes are attracting much attention for their capability of delivering short power pulses with high stability over repeated charge/discharge cycling. Supersonic Cluster Beam Deposition (SCBD) is an effective strategy for the development of nanostructured, binder-free porous carbon electrodes on temperature sensitive substrates including polymers. We exploited SCBD for the development of a flexible, planar μSC featuring nanostructured carbon (ns-C) electrodes deposited on a plastic Mylar substrate and N-trimethyl-N-propyl-ammonium bis(trifluoromethanesulfonyl) imide (N 1113 TFSI) ionic liquid electrolyte. The electrochemical performance at different temperatures of the μSC which operates at 3 V above RT up to 80 °C with a capacitance density approaching 10 F cm −3 and delivering maximum specific energy and power densities of 10 mWh cm −3 and 8-10 W cm −3 with long cycling stability over 2 × 10 4 cycles is here reported and discussed. [ABSTRACT FROM AUTHOR]

Graphite/LiNi0.4Mn1.6O4 cells assembled with a new reinforced polyvinylidene fluoride (pVDF)–nano crystalline cellulose (NCC) separator and EC–DMC 1 M LiFAP electrolyte with additives were tested by deep charge/discharge cycles at different C-rates and by the FreedomCAR DOE protocol to simulate the dynamic functioning of the batteries in power-assist full hybrid electric vehicles (HEVs). The results of this study evidence the beneficial impact of the pVDF–NCC macroporous membrane with respect to the polypropylene monolayer Celgard®2400 separator on the high C-rate cell performance. The deep charge/discharge of the cell with pVDF–NCC at C/1 effective rate provided 101 W h kg−1 to be compared with 85 W h kg−1 of the cell with Celgard®2400 (the cell weight was considered twice the composite electrode weight of both electrodes). Also hybrid pulse power characterization tests based on the FreedomCAR protocol at 5 C and 10 C demonstrated the superior performance of the cells with pVDF–NCC with respect to that of the cells with Celgard®2400 even if both cells exceed the FreedomCAR goals of power and energy for minimum and maximum power-assist HEV. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this project was to evaluate the Cozart® RapiScan Oral fluid Drug Testing System as an on-site screening tool for vitreous humor samples collected during post-mortem examinations. Vitreous humor is easy to collect and as it is contained within the eye it is almost completely unaffected by post-mortem redistribution. The ability to carry out an initial drug screen on vitreous humor at the earliest stage of the death investigation process could contribute significantly to the assessment of the role drugs may have played prior to confirmation with toxicological analyses at the laboratory. Vitreous humor (n =146) was collected from autopsy examinations (111 males and 35 females) with a specific focus on cases where death occurred following a road traffic accident or where an overdose was suspected. All samples were screened using the five-panel methadone Cozart® RapiScan Cartridge with an overall positive rate of 29%. Of the positive results, 43% screened positive for benzodiazepines, 17% for cocaine, 7% for methadone and 33% for opiates. Positive samples, with the exception of benzodiazepines, and 20% of negative samples were analysed by GC/MS. This is the first reported use of this system as an on-site forensic tool in death investigation and for screening for drugs of abuse in vitreous humor. The conclusions from this study show that the Cozart® RapiScan System could play an important role in obtaining information on the toxicological state of the person at the time of death. [Copyright &y& Elsevier]

Objective: In our previous work, patients affected by SSc were treated with intravenous urokinase and showed clinical improvement. In this study we used microscopy to document ultrastructural alterations occurring in sclerodermic skin from SSc patients treated with urokinase.Methods: Ten patients with SSc were selected for this study. Skin biopsies were taken from the medial side of the right forearm on the third proximal on the volar surface. The patients were then treated with urokinase for 7 consecutive days. At the end of the treatment, the patients were examined and a new skin biopsy was taken close to the above-mentioned zone of the forearm for optic and electron microscopy examination.Results: The patients showed a gradual improvement of the skin after urokinase treatment. Raynaud's appeared to be less intense, and they had an increased articular range, with the restoration of movements that had previously been limited. Histological findings showed that, after treatment, skin alterations appeared attenuated, in particular the connective tissue showed a decreased density and inflammatory infiltrate was slight. Electron microscopy findings showed that collagen fibres appeared to have a more regular diameter, and the capillary vessels' lining was thicker, with fewer pinocytotic vesicles.Conclusion: These observations show that urokinase treatment seems to be an interesting therapeutic strategy to consider for the treatment of SSc. [ABSTRACT FROM AUTHOR]

Background: T-lymphocyte activation within atherosclerotic plaque, and widespread to the myocardium, has been shown in patients with acute coronary syndromes. Objective: To investigate the presence of T-lymphocyte infiltrate at different stages of acute coronary syndromes by studying patients with sudden coronary death, acute myocardial infarction IAMI) and healed infarction, in comparison with patients with myocarditis and patients with non-ischaemic heart failure. Methods: 72 cases were studied at autopsy: 12 dying of sudden coronary death (group 1), 12 dying <4 weeks (group 2) and 12 dying >4 months after AMI (group 3), 12 with active lymphocytic myocarditis (group 4), 12 with hypertensive heart disease (group 51, and 12 control subjects (group 6). Light microscopy was performed to measure the number of activated T-lymphocytes ICD3+/ DR+l in the myocardium and coronary artery wall, and intercellular adhesion molecule-i (ICAM-1) expression in the myocardium. Results: Activated T-lymphocyte infiltrates and CAM-i myocardial expression in both remote and pen-infarction regions and activated T-lymphocytes within the epicardial coronary artery wall of both the infarct- and non-infarct- related arteries were found in groups 1, 2 and 3, whereas myocardial, but not coronary, infiltrates were found in groups 4 (p'

Objective: To test the hypothesis that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and left ventricular (LV) remodelling. Methods and results: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography, and signal intensity (SI) and the rate of SI rise (β) were measured at myocardial contrast echocardiography in 11 patients with severe aortic stenosis and LV hypertrophy. In the same patients, biopsies were obtained from the anterolateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV (CBFVI) was significantly lower in patients than in controls (median 0.100 cm g/s (interquartile range 0.07–0.115) v 0.130 cm g/s (0.130–0.160), p = 0.002). Similarly, SI*β was significantly lower in patients than in controls (11 1/s (8–66) v 83 1/s (73–95), p = 0.001). Apoptotic rate was increased in aortic stenosis more than 100-fold versus controls (1.2% (0.8–1.4) v 0.01% (0.01–0.01), p < 0.001) and inversely correlated with lower CBFVI and SI*β (r = -0.77, p = 0.001 for both). Conclusions: Patients with severe aortic stenosis and LV hypertrophy have impaired myocardial perfusion, which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion and the ensuing oxygen demand-supply imbalance may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling, and heart failure. [ABSTRACT FROM AUTHOR]

Background: Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown. Am: To evaluate survivin expression after acute myocardial infarction (AMI). Methods: Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in Four control hearts. Results: Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infard regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. Conclusions: Survivin myocardial expression after AM! may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling. [ABSTRACT FROM AUTHOR]

MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01–15 mg/kg i.p.) on motor and sensorimotor (visual, acoustic and tactile) responses, mechanical and thermal analgesia, muscle strength and body temperature in CD-1 male mice. Higher doses of MT-45 (6–30 mg/kg i.p.) were used to investigate cardiorespiratory changes (heart rate, respiratory rate, SpO 2 saturation and pulse distention). All effects of MT-45 were compared with those of morphine. In vitro DMR assay results demonstrated that at human recombinant opioid receptors MT-45 behaves as a potent selective mu agonist with a slightly higher efficacy than morphine. In vivo results showed that MT-45 progressively induces tail elevation at the lowest dose tested (0.01 mg/kg), increased mechanical and thermal antinociception (starting from 1 to 6 mg/kg), decreased visual sensorimotor responses (starting from 3 to 6 mg/kg) and reduced tactile responses, modulated motor performance and induced muscle rigidity at higher doses (15 mg/kg). In addition, at higher doses (15–30 mg/kg) MT-45 impaired the cardiorespiratory functions. All effects were prevented by the administration of the opioid receptor antagonist naloxone. These findings reveal the risks associated with the ingestion of opioids and the importance of studying these drugs and undertaking more clinical studies of the current molecules to better understand possible therapeutic interventions in the case of toxicity. • MT-45 behaves as a potent selective mu agonist in DMR assay. • MT-45 and morphine dose-dependently increased mechanical and thermal analgesia. • MT-45 progressively impaired the motor-sensorimotor responses in mice as morphine. • MT-45 altered cardiorespiratory responses in mice at higher doses. [ABSTRACT FROM AUTHOR]