Effects of ageing, a high-fat diet and physical exercise on skeletal muscle morphology

Age-related loss of skeletal muscle mass and strength can lead to reduced independence, quality of life and life expectancy, which may be exacerbated by an increased high-fat intake and a low physical exercise. This thesis investigated the effects of ageing, high-fat diet (HFD) and regular physical training on muscle morphology. Specifically, in study I, we compared intramyocellular lipid (IMCL) levels, capillarisation, fibre type and size, and oxidative capacity of fibres in locomotor (soleus and EDL) and respiratory (diaphragm) muscles in 20- (young-adult) and 79-week-old (early ageing) mice. Early ageing was characterised by an absence of muscle wasting in soleus, the EDL atrophied while the diaphragm hypertrophied without changes in the capillary numbers supplying a fibre, or their oxidative capacity. In study II, we studied the effects of a HFD on the morphology of the soleus, EDL and diaphragm in 20- and 79-week-old mice. Old mice were more susceptible to morphological alterations with a HFD compared to young mice. All fibre types showed similar adaptations in response to a HFD but they were muscle-specific with the EDL being least responsive. In study III, we assessed fibre type grouping in the vastus lateralis of athletes and nonathletes (19 - 85 years old) and evaluated to what extent any observed grouping, indicative of cycles of denervation and reinnervation following motor neuron loss, is more than expected from the fibre type composition of the muscle. Since regular physical exercise may stimulate fibre reinnervation, we hypothesised that master athletes have larger fibre groups than agematched non-athletes. An ‘enclosed fibre’ was any muscle fibre of a given type surrounded by fibres of the same type only. A ‘fibre group’ was defined as a group of fibres with at least one enclosed fibre. The prevalence of observed fibre type grouping was similar to that expected from the fibre type composition. No age-related effect on group size and group number in athletes or non-athletes was found. In conclusion, the current thesis described the morphological changes of CD-1 mouse skeletal muscles during ageing as muscle specific. Additionally, using the same mouse model, HFDinduced muscle morphological alterations depending on diet duration and age, varied between muscles. Moreover, the results of the current thesis do not show evidence for improved reinnervation of muscle fibres with regular physical training. Nevertheless, histological examination may not provide the full extent of ageing related motor unit remodelling

A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats

The brain is still maturing during adolescence and interfering with such a vulnerable period may lead to structural and functional consequences. We investigated the effect of a single cocaine exposure on dendritic spine structure and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats 7 days after a single cocaine administration. We found a reduced number of dendritic spines, suggesting that cocaine lowers the density of dendritic spines in the mPFC of adolescent rats. Since dendritic spines are postsynaptic glutamatergic protrusions, we investigated the main determinants of glutamate postsynaptic responsiveness. In the postsynaptic density, cocaine reduced the expression of the NMDA receptor subunits GluN1, GluN2A and GluN2B as well as of the AMPA GluA1 and GluA2 subunits. Cocaine also impaired their synaptic stability since the expression of the scaffolding proteins SAP102 and SAP97, critical for the anchoring of such receptors at the postsynaptic membrane, was reduced as well. The expression of PSD-95 and Arc/Arg3.1, which play structural and functional roles in glutamate neurons, was also similarly reduced. Such changes were not found in the whole homogenate, ruling out a translational effect of cocaine and implying, rather, an impaired synaptic retention at the active zones of the synapse. Notably, neither these critical glutamate determinants nor the density and morphology of the dendritic spines were altered in the mPFC of adult animals, suggesting that a single cocaine exposure selectively impairs the developmental trajectory of the glutamate synapse. These results indicate a dynamic impairment of mPFC glutamate homeostasis during a critical developmental window that persists for at least one week after a single cocaine administration. Our results identify dysfunctional glutamate synapse as a major contributor to the mechanisms that distinguish adolescent vs. adult outcomes of a single cocaine exposure

Towards the Assessment of the Predictive Capacity of the β-σ Two-Fluid Model for Pseudo-Homogeneous Slurry Flow in Pipes

This paper focuses on the numerical simulation of turbulent, pseudo-homogeneous slurry flows in pipes through the β-σ two-fluid model, developed by the authors and collaborators in previous research. The two-fluid model gives its name to the presence of two main calibration coefficients, namely, σ, associated with the turbulent dispersion of the particles, and β, related to the inter-phase friction and to the wall shear stress produced by the solid phase. In a recently published article, the role played by β and σ on different features of the CFD solution has been established for different flow conditions, and a procedure for the calibration of the two coefficients has been proposed. The present contribution investigates the extrapolability of previously calibrated coefficients to different conditions in terms of pipe diameter, particle type, and in-situ concentration. The experimental data used to support the conclusions and recommendations from the numerical study were obtained from previously published literature. The findings of this study not only contribute to a deeper comprehension of the β-σ two-fluid model, but they also provide a methodological background for the development of computational tools for industrial practitioners and academic researchers

A combined CFD-experimental method for abrasive erosion testing of concrete

Serious damage may occur to concrete hydraulic structures, such as water galleries, spillways, and stilling basins, due to the abrasive erosion caused by the presence of solid particles in the flow. This underlines the importance of being capable in providing characterization of the concrete from the point of view of its vulnerability to abrasive erosion, in order to improve the design of the structure and the material selection. Nevertheless, the existing apparatus for concrete abrasive erosion testing are either far from allowing realistic simulation of the actual environment in which this phenomenon occurs, or show a large degree of complexity and cost. An alternative method has been developed with the aid of Computational Fluid Dynamics (CFD). CFD was first employed to verify the effectiveness of a new laboratory equipment. Afterwards, a parameter has been introduced which, by successful comparison against preliminary experiments, proved suitable to quantify the effect of the fluid dynamic conditions on the concrete abrasive erosion, thereby opening the way to CFD-based customization of the apparatus. In the future, the synergy of numerical and physical modelling will allow developing predictive models for concrete erosion, making it possible to reliably simulate real structures66112112

Iterative Depth-First Search for Fully Observable Non-Deterministic Planning

Fully Observable Non-Deterministic (FOND) planning models uncertainty through actions with non-deterministic effects. Existing FOND planning algorithms are effective and employ a wide range of techniques. However, most of the existing algorithms are not robust for dealing with both non-determinism and task size. In this paper, we develop a novel iterative depth-first search algorithm that solves FOND planning tasks and produces strong cyclic policies. Our algorithm is explicitly designed for FOND planning, addressing more directly the non-deterministic aspect of FOND planning, and it also exploits the benefits of heuristic functions to make the algorithm more effective during the iterative searching process. We compare our proposed algorithm to well-known FOND planners, and show that it has robust performance over several distinct types of FOND domains considering different metrics

Practical indications for the prevention and management of SARS-CoV-2 in ambulatory dialysis patients : lessons from the first phase of the epidemics in Lombardy

Confronting the SARS-CoV-2 outbreak has allowed us to appreciate how efficiently highly-resourced settings can respond to crises. However even such settings are not prepared to deal with the situation, and lessons are only slowly being learnt. There is still an urgent need to accelerate protocols that lead to the implementation of rapid point-of-care diagnostic testing and effective antiviral therapies. In some high-risk populations, such as dialysis patients, where several individuals are treated at the same time in a limited space and overcrowded areas, our objective must be to ensure protection to patients, the healthcare team and the dialysis ward. The difficult Italian experience may help other countries to face the challenges. The experience of the Lombardy underlines the need for gathering and sharing our data to increase our knowledge and support common, initially experience-based, and as soon as possible evidence-based position to face this overwhelming crisis

Exposure to novel coronavirus in patients on renal replacement therapy during the exponential phase of COVID-19 pandemic: survey of the Italian Society of Nephrology

Background: Between February and April 2020, Italy experienced an overwhelming growth of the COVID-19 pandemic. Little is known, at the country level, where and how patients on renal replacement therapy (RRT) have been mostly affected. Methods: Survey of the network of Nephrology centers using a simplified 17 items electronic questionnaire designed by Italian Society of Nephrology COVID-19 Research Group. We used spatial epidemiology and geographical information systems to map SARS-CoV-2 spread among RRT patients in Italy. Results: On April 9th 2020, all nephrology centers (n = 454) listed in the DialMap database were invited to complete the electronic questionnaire. Within 11 days on average, 365 centers responded (80.4% response rate; 2.3% margin of error) totaling 60,441 RRT patients. The surveyed RRT population included 30,821 hemodialysis (HD), 4139 peritoneal dialysis (PD), and 25,481 transplanted (Tx) patients respectively. The proportion of SARS-CoV-2 positive RRT patients in Italy was 2.26% (95% CI 2.14\u20132.39) with significant differences according to treatment modality (p < 0.001). The proportion of patients positive for SARS-CoV-2 was significantly higher in HD (3.55% [95% CI 3.34\u20133.76]) than PD (1.38% [95% CI 1.04\u20131.78] and Tx (0.86% [95% CI 0.75\u20130.98]) (p < 0.001), with substantial heterogeneity across regions and along the latitude gradient (p < 0.001). In RRT patients the highest rate was in the north-west (4.39% [95% CI 4.11\u20134.68], followed by the north-east (IR 2.06% [1.79\u20132.36]), the center (0.91% [0.75\u20131.09]), the main islands (0.67% [0.47\u20130.93]), and the south (0.59% [0.45\u20130.75]. During the COVID-19 pandemic, among SARS-Cov-2 positive RRT patients the fatality rate was 32.8%, as compared to 13.3% observed in the Italian population as of April 23rd. Conclusions: A substantial proportion of the 60,441 surveyed RRT patients in Italy were SARS-Cov-2 positive and subsequently died during the exponential phase of COVID-19 pandemic. Infection risk and rates seems to differ substantially across regions, along geographical latitude, and by treatment modality