DFT insights into the oxygen-assisted selective oxidation of benzyl alcohol on manganese dioxide catalysts

The reactivity pattern of the MnO2 catalyst in the selective aerobic oxidation of benzyl alcohol is assessed by density functional theory (DFT) analysis of adsorption energies and activation barriers on a model Mn4O8 cluster. DFT calculations predict high reactivity of defective Mn(IV) sites ruling a surface redox mechanism, L-H type, involving gas-phase oxygen. Bare and promoted (i.e., CeOx and FeOx) MnOx materials with high surface exposure of Mn(IV) sites were synthesized to assess kinetic and mechanistic issues of the selective aerobic oxidation of benzyl alcohol on real catalysts (T, 333- 363K). According to DFT predictions, the experimental study shows: i) comparable activity of bare and promoted catalysts due to surface Mn(IV) sites; ii) the catalytic role of oxygen-atoms in the neighboring of active Mn(IV) sites; and iii) a 0th-order dependence on alcohol concentration, diagnostic of remarkable influence of adsorption phenomena on the reactivity pattern. Evidences of catalyst deactivation due to the over-oxidation of benzyl alcohol to benzoic acid, acting as poison of the active sites, are discussed

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Development of an Integrated In-Vehicle Driver Breath Ethanol System Based on α-Fe2O3 Sensing Material

Alcohol abuse is the dominant cause of fatal car accidents (about 25% of all road deaths in Europe). The large-scale implementation of systems aimed at the realization of in-vehicle driver breath ethanol detection is therefore in high demand. For this reason, we devoted our attention to the design of an inexpensive and reliable breath alcohol sensor for use in an Advanced Driver Assistance System (ADAS). The main challenge in the development of this sensor is related to the complexity of breath composition and its high humidity content, coupled with the high dilution of breath reaching the sensor. In this work, a simple α-Fe2O3 film-based sensor was developed and validated in laboratory tests. Tests were also performed by placing the ethanol sensor within the casing of the upper steering column of a car to simulate real driving conditions. Using an array provided with the developed ethanol sensor and humidity, temperature and CO2 sensors, it was possible to differentiate the signal of a driver’s breath before and after alcohol consumption

On the Role of Heterojunctions of Core-Shell Heterostructures in Gas Sensing

Heterostructures made from semiconducting metal oxides (SMOX) are fundamental for the development of high-performance gas sensors. Yet, despite the recognition of their importance in real applications, the understanding of the transduction mechanism either related to the heterojunction, or simply to the core and shell materials is still lacking. A better understanding of the sensing response of heterostructured nanomaterials requires the engineering of heterojunctions with well-defined core and shell layers. Here, we introduce a series of prototypes nSMOX-CNT, pSMOX-CNT, and pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT hierarchical core-shell heterostructures (CSHS) permitting us to directly relate the sensing response to the SMOX shell, or to the p-n heterojunction. The carbon nanotubes are here used as highly conductive substrates permitting to operate the devices at relatively low temperature and are not involved in the sensing response. NiO and SnO2 are selected as representative p- and n-type SMOX, respectively, and the response of a set of samples is studied toward hydrogen considered as model analyte. The n,pSMOX-CNT CSHS exhibit response related to the n,pSMOX-shell layer. On the other hand, the pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT CSHS show sensing responses, which in certain cases are governed by the heterojunctions between nSMOX and pSMOX and strongly depends on the thickness of the SMOX layers. Due to the fundamental nature of this study, these findings are important for the development of next generation gas sensing devices

Evidence for caspase-dependent programmed cell death along with repair processes in affected skeletal muscle fibres in patients with mitochondrial disorders

Abstract Mitochondrial disorders are heterogeneous multisystemic disorders due to impaired oxidative phosphorylation causing defective mitochondrial energy production. Common histological hallmarks of mitochondrial disorders are RRFs (ragged red fibres), muscle fibres with abnormal focal accumulations of mitochondria. In contrast with the growing understanding of the genetic basis of mitochondrial disorders, the fate of phenotypically affected muscle fibres remains largely unknown. We investigated PCD (programmed cell death) in muscle of 17 patients with mitochondrial respiratory chain dysfunction. We documented that in affected muscle fibres, nuclear chromatin is condensed in lumpy irregular masses and cytochrome c is released into the cytosol to activate, along with Apaf-1 (apoptotic protease-activating factor 1), caspase 9 that, in turn, activates effector caspase 3, caspase 6, and caspase 7, suggesting the execution of the intrinsic apoptotic pathway. Whereas active caspase 3 underwent nuclear translocation, AIF (apoptosis-inducing factor) mainly stayed within mitochondria, into which an up-regulated Bax is relocated. The significant increase in caspase 2, caspase 3 and caspase 6 activity strongly suggest that the cell death programme is caspase-dependent and the activation of caspase 2 together with PUMA (p53 up-regulated modulator of apoptosis) up-regulation point to a role for oxidative stress in triggering the intrinsic pathway. Concurrently, in muscle of patients, the number of satellite cells was significantly increased and myonuclei were detected at different stages of myogenic differentiation, indicating that a reparative programme is ongoing in muscle of patients with mitochondrial disorders. Together, these data suggest that, in patients with mitochondrial disorders, affected muscle fibres are trapped in a mitochondria-regulated caspase-dependent PCD while repairing events take place

EVIDENCE FOR CASPASE-DEPENDENT PROGRAMMED CELL DEATH ALONG WITH REPAIR PROCESSES IN AFFECTED SKELETAL MUSCLE FIBRES IN PATIENTS WITH MITOCHONDRIAL DISORDERS

ABSTRACT Mitochondrial disorders (MDs) are heterogeneous multisystemic disorders due to impaired oxidative phosphorylation causing defective mitochondrial energy production. Common histological hallmarks of MDs are ragged red fibers (RRFs), muscle fibers with abnormal focal accumulations of mitochondria. In contrast to the growing understanding of the genetic basis of MDs, the fate of phenotipically affected muscle fibers remains largely unknown. We investigated programmed cell death (PCD) in muscle of 17 patients with mitochondrial respiratory chain dysfunction. We documented that in affected muscle fibers, nuclear chromatin is condensed in lumpy irregular masses and cytochrome c is released into the cytosol to activate, along with Apaf-1, caspase-9 that, in turn, activates effector caspase-3, -6, and -7, suggesting the execution of the intrinsic apoptotic pathway. While active caspase-3 underwent nuclear translocation, AIF mainly stayed within mitochondria, into which an upregulated Bax is relocated. The significant increase in caspase-2, -3 and -6 activity strongly suggest that cell death program is caspase-dependent and the activation of caspase-2 together with PUMA up-regulation point to a role of oxidative stress in triggering the intrinsic pathway. Concurrently, in muscle of patients the number of satellite cells was significantly increased and myonuclei were detected in different stages of myogenic differentiation indicating that a reparative program is ongoing in MDs muscles. Together these data suggest that in MDs patients affected muscle fibers are trapped in a mitochondria-regulated caspase-dependent PCD while repairing events simultaneously take place. Abbreviations: COX, cytochrome c oxidase; COX-SDH, cytochrome c oxidase-succinate dehydrogenase; CPEO, chronic progressive external ophthalmoplegia; MDs, mitochondrial diseases; MELAS, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; MERRF, myoclonic epilepsy with ragged-red fibers; NADH-TR, nicotinamide adenine dinucleotide-tetrazolium reductase; PAS, Periodic Acid Schiff; PCD, programmed cell death; RRFs, ragged red fibers; ROS, reactive oxygen species; SDH, succinate dehydrogenase A c c e p t e d M a n u s c r i p

EVIDENCE FOR CASPASE-DEPENDENT PROGRAMMED CELL DEATH ALONG WITH REPAIR PROCESSES IN AFFECTED SKELETAL MUSCLE FIBRES IN PATIENTS WITH MITOCHONDRIAL DISORDERS

ABSTRACT Mitochondrial disorders (MDs) are heterogeneous multisystemic disorders due to impaired oxidative phosphorylation causing defective mitochondrial energy production. Common histological hallmarks of MDs are ragged red fibers (RRFs), muscle fibers with abnormal focal accumulations of mitochondria. In contrast to the growing understanding of the genetic basis of MDs, the fate of phenotipically affected muscle fibers remains largely unknown. We investigated programmed cell death (PCD) in muscle of 17 patients with mitochondrial respiratory chain dysfunction. We documented that in affected muscle fibers, nuclear chromatin is condensed in lumpy irregular masses and cytochrome c is released into the cytosol to activate, along with Apaf-1, caspase-9 that, in turn, activates effector caspase-3, -6, and -7, suggesting the execution of the intrinsic apoptotic pathway. While active caspase-3 underwent nuclear translocation, AIF mainly stayed within mitochondria, into which an upregulated Bax is relocated. The significant increase in caspase-2, -3 and -6 activity strongly suggest that cell death program is caspase-dependent and the activation of caspase-2 together with PUMA up-regulation point to a role of oxidative stress in triggering the intrinsic pathway. Concurrently, in muscle of patients the number of satellite cells was significantly increased and myonuclei were detected in different stages of myogenic differentiation indicating that a reparative program is ongoing in MDs muscles. Together these data suggest that in MDs patients affected muscle fibers are trapped in a mitochondria-regulated caspase-dependent PCD while repairing events simultaneously take place. Abbreviations: COX, cytochrome c oxidase; COX-SDH, cytochrome c oxidase-succinate dehydrogenase; CPEO, chronic progressive external ophthalmoplegia; MDs, mitochondrial diseases; MELAS, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; MERRF, myoclonic epilepsy with ragged-red fibers; NADH-TR, nicotinamide adenine dinucleotide-tetrazolium reductase; PAS, Periodic Acid Schiff; PCD, programmed cell death; RRFs, ragged red fibers; ROS, reactive oxygen species; SDH, succinate dehydrogenase A c c e p t e d M a n u s c r i p

Evidence for caspase-dependent programmed cell death along with repair processes in affected skeletal muscle fibres in patients with mitochondrial disorders

Mitochondrial disorders (MDs) are heterogeneous multisystemic disorders due to impaired oxidative phosphorylation causing defective mitochondrial energy production. Common histological hallmarks of MDs are ragged red fibers (RRFs), muscle fibers with abnormal focal accumulations of mitochondria. In contrast to the growing understanding of the genetic basis of MDs, the fate of phenotipically affected muscle fibers remains largely unknown. We investigated programmed cell death (PCD) in muscle of 17 patients with mitochondrial respiratory chain dysfunction. We documented that in affected muscle fibers, nuclear chromatin is condensed in lumpy irregular masses and cytochrome c is released into the cytosol to activate, along with Apaf-1, caspase-9 that, in turn, activates effector caspase-3, -6, and -7, suggesting the execution of the intrinsic apoptotic pathway. While active caspase-3 underwent nuclear translocation, AIF mainly stayed within mitochondria, into which an upregulated Bax is relocated. The significant increase in caspase-2, -3 and -6 activity strongly suggest that cell death program is caspase-dependent and the activation of caspase-2 together with PUMA up-regulation point to a role of oxidative stress in triggering the intrinsic pathway. Concurrently, in muscle of patients the number of satellite cells was significantly increased and myonuclei were detected in different stages of myogenic differentiation indicating that a reparative program is ongoing in MDs muscles.Together these data suggest that in MDs patients affected muscle fibers are trapped in a mitochondria-regulated caspase-dependent PCD while repairing events simultaneously take place