Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine function.     

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.     

Local electron heating in nanoscale conductors

The electron current density in nanoscale junctions is typically several orders of magnitude larger than the corresponding one in bulk electrodes. Consequently, the electron-electron scattering rate increases substantially in the junction. This leads to local electron heating of the underlying Fermi sea in analogy to the local ionic heating that is due to the increased electron-phonon scattering rates. We predict the bias dependence of local electron heating in quasi-ballistic nanoscale conductors and its effect on ionic heating and discuss possible experimental tests of our results.     

Thermionic emission from the 2DEG assisted by image-charge-induced barrier lowering in AlInN/AlN/GaN heterostructures

The effect of image charges on current transport mechanisms investigated at the nanoscale in Al(1-x)In(x)N/GaN heterostructures was studied. Current-voltage (I-V) measurements were performed locally using a conductive AFM-tip as a nanoprobe and the conduction mechanism was modeled to explain the observed behavior. This model suggests that current transport is controlled by thermionic emission (TE) of the two-dimensional electron gas (2DEG) across the potential barrier at the heterointerface, where the image charges generated by the 2DEG induce a barrier lowering at the Al(1-x)In(x)N/GaN interface, enhancing electron transport. This barrier lowering depends on the 2DEG characteristics, such as 2DEG density n(2D), first subband energy E? and the average distance x? of the 2DEG from the interface. By fitting the experimental I-V curves with the present model the 2DEG density was evaluated. The obtained results were in very good agreement with the Hall measurements.     

Effect of cross sectional shape during condensation in a single square minichannel

The objective of this work is to present new condensation heat transfer coefficients measured inside a single square cross section minichannel, having a 1.18 mm side length, and compare them to the ones previously measured in a circular minichannel. Tests have been performed with R134a at 40 °C saturation temperature, at mass velocity ranging between 200 and 800 kg m^?2 s^?1. As compared to the heat transfer coefficients measured in the circular cross section channel, for the same hydraulic diameter, in the square minichannel the authors find a heat transfer enhancement at the lowest value of mass velocity, which must be due to the effect of surface tension. No heat transfer coefficient increase has been found at the highest values of the mass velocity where condensation is shear stress dominated.     

Heat transfer during air flow in aluminum foams

This paper presents experimental heat transfer coefficients measured during air flow heating in seven different aluminum open-cell foam samples with different number of pores per inch (PPI), porosity and foam core height under a wide range of air mass velocity. Three imposed heat fluxes are considered for each foam sample: 25.0, 32.5 and 40.0 kW m^?2. The collected heat transfer data are analyzed to obtain the global heat transfer coefficient and the normalized mean wall temperature. A model from the open literature has been selected and compared with the experimental database. A new simple heat transfer model, based on the present data, for the global heat transfer coefficient and the foam-finned surface area efficiency estimations has then been developed and compared against the experimental measurements.     

A k, k-ε optimality selection based multi objective genetic algorithm with applications to vehicle engineering

In the paper, a multi objective genetic algorithm based on the concept of k-optimality and k-ε-optimality (KEMOGA) is introduced and applied. Pareto optimality alone is not always adequate for selecting a final solution because the Pareto optimal set can be very large. The k-optimality approach and the more general k-ε-optimality method, can be used to rank the Pareto-optimal solutions. The two methods have been included into a genetic algorithm selection procedure. The k-optimality method searches for points which remain Pareto-optimal when all of the subsets of n-k objectives (n is the number of objective functions) are optimised. The k-ε approach considers not only if an objective is worse than the others but also the entity of this variation through the introduction of a vector of indifference thresholds. The KEMOGA has been applied for the solution of two engineering problems. The selection of the stiffness and damping of a passively suspended vehicle in order to get the best compromise between discomfort, road holding and working space and a complex problem related to the optimisation of the tyre/suspension system of a sport car. The final design solution, found by means of the KEMOGA seems consistent with the solution selected by skilled suspensions specialists. The proposed approach has been tested and validated on a complex optimization problem. The solved problem deals with the optimization of the tyre/suspension system of a sport car. The proposed approach (KEMOGA) has shown to be very effective in terms of computational efficiency and accuracy.     

Shell-and-Tube Minichannel Condenser for Low Refrigerant Charge

The design of an innovative shell-and-tube heat pump condenser using 2 mm ID minichannels is presented. This condenser has been designed aiming at the minimization of the charge, which can be required by safety or environmental restrictions. Nevertheless, minichannels represent also a solution to the high-pressure challenge when using carbon dioxide as a refrigerant. The present prototype was realized for the use with propane in the framework of the European project SHERHPA, concerning the development of heat pumps working with natural fluids. Experimental data for heat transfer and pressure drop are reported in the present paper. The measurements have been obtained using refrigerant R22, which displays a temperature versus pressure saturation curve pretty close to the one of propane. The data have also been compared against a computational procedure for shell-and-tube heat exchangers design. The refrigerant charge has been computed by means of different void fraction correlations, showing that the expected charge is less than half the quantity required by a brazed plate condenser giving the same capacity.