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Motor impairment in Parkinson's disease (PD) reflects changes in the basal ganglia-thalamocortical circuit converging on the primary motor cortex (M1) and supplementary motor area (SMA). Previous studies assessed M1 excitability in PD using transcranial magnetic stimulation (TMS)-evoked electromyographic activity. TMS-evoked electroencephalographic activity may unveil broader motor cortical network changes in PD.The aim was to assess motor cortical network excitability in PD.We compared TMS-evoked cortical potentials (TEPs) from M1 and the pre-SMA between 20 PD patients tested off and on medication and 19 healthy controls (HCs) and investigated possible correlations with bradykinesia.Off PD patients compared to HCs had smaller P30 responses from the M1s contralateral (M1+) and ipsilateral (M1-) to the most bradykinetic side and increased pre-SMA N40. Dopaminergic therapy normalized the amplitude of M1+ and M1- P30 as well as pre-SMA N40. We found a positive correlation between M1+ P30 amplitude and bradykinesia in off PD patients.Changes in M1 P30 and pre-SMA N40 in PD suggest that M1 excitability is reduced on both sides, whereas pre-SMA excitability is increased. The effect of dopaminergic therapy and the clinical correlation suggest that these cortical changes may reflect abnormal basal ganglia-thalamocortical activity. TMS electroencephalography provides novel insight into motor cortical network changes related to the pathophysiology of PD. © 2022 International Parkinson and Movement Disorder Society.

Insomnia and circadian dysregulation during adolescence represent important risk factors for emotional and psychological problems. Recent studies have shown that the coronavirus disease 2019 (COVID-19) pandemic has been linked to a high prevalence of behavioural sleep problems in the general population. This study aimed to provide two pictures of two different time points of the pandemic regarding the prevalence of sleep problems in adolescents and their association with psychological health variables. Two different independent large samples of Italian adolescents aged 13-17 years were recruited at two pandemic time points. A total of 1,146 adolescents at Time 1 (T1; April 2020) and 1,406 at Time 2 (T2; April 2021) took part in the study. Measures of insomnia symptoms, sleep hygiene, chronotype, psychological distress and emotion regulation were collected. Prevalence of insomnia was 12.13% at T1 and 23.19% at T2. Furthermore, high levels of poor sleep habits (late bedtime, poor sleep hygiene, use of electronic devices at bedtime) were also detected at both time points. Insomnia symptoms strongly correlated with poor sleep hygiene, higher psychological distress, and emotional suppression at both time points. Results highlighted an alarming picture for two large samples at two different time points of the pandemic that showed a potential negative impact of the COVID-19 pandemic, in both the first outbreak and in the later phase of the pandemic, on sleep habits, psychological distress and insomnia symptoms in adolescents. This strongly suggests the need for monitoring these variables and their interaction in the post-pandemic period and to develop and promote interventions for insomnia and circadian disturbances during adolescence.

Background Parkinson's disease patients may show a tremor that appears after a variable delay while the arms are kept outstretched (re-emergent tremor). The objectives of this study were to investigate re-emergent tremor pathophysiology by studying the role of the primary motor cortex in this tremor and making a comparison with rest tremor. Methods We enrolled 10 Parkinson's disease patients with both re-emergent and rest tremor. Tremor was assessed by spectral analysis, corticomuscular coherence and tremor-resetting produced by transcranial magnetic stimulation over the primary motor cortex. We also recorded transcranial magnetic stimulation-evoked potentials generated by motor cortex stimulation during rest tremor, tremor suppression during wrist extension, and re-emergent tremor. Spectral analysis, corticomuscular coherence, and tremor resetting were compared between re-emergent tremor and rest tremor. Results Re-emergent tremor showed significant corticomuscular coherence, causal relation between motor cortex activity and tremor muscle and tremor resetting. The P60 component of transcranial magnetic stimulation-evoked potentials reduced in amplitude during tremor suppression, recovered before re-emergent tremor, was facilitated at re-emergent tremor onset, and returned to values similar to those of rest tremor during re-emergent tremor. Compared with rest tremor, re-emergent tremor showed similar corticomuscular coherence and tremor resetting, but slightly higher frequency. Conclusions Re-emergent tremor is causally related with the activity of the primary motor cortex, which is likely a convergence node in the network that generates re-emergent tremor. Re-emergent tremor and rest tremor share common pathophysiological mechanisms in which the motor cortex plays a crucial role. © 2020 International Parkinson and Movement Disorder Society.

Background Movement execution in healthy individuals increases the somatosensory temporal discrimination threshold. These changes are a result of mechanisms of sensory gating at the subcortical level. Although the somatosensory temporal discrimination threshold is abnormally increased in patients with focal dystonias, the effect of movement execution on somatosensory temporal discrimination in dystonic patients is unknown. Objectives The objective of this study was to determine whether somatosensory temporal discrimination threshold modulation induced by voluntary movement is normal in different forms of focal dystonia. Methods We enrolled 71 dystonic patients (24 with blepharospasm, 31 with cervical dystonia, and 16 with focal hand dystonia) and 39 age-matched healthy participants. Paired stimuli for the somatosensory temporal discrimination threshold were triggered by movement execution at movement onset and at various time intervals thereafter. We analyzed the kinematic features of the motor task to ascertain whether tactile input induces changes in movement parameters. Results Movement execution led to greater and longer lasting increases in somatosensory temporal discrimination threshold values, both upon movement onset and at various time intervals thereafter, in patients with cervical dystonia and focal hand dystonia than in those with blepharospasm or the healthy participants. Somatosensory temporal discrimination testing did not induce any changes in the mean velocity of index finger movements in either patients or healthy participants. Conclusions Somatosensory temporal discrimination threshold changes induced by movement execution are abnormal in focal dystonias. This abnormality is related to the type of dystonia. Abnormal gating of sensory information is likely involved in movement-induced triggering or worsening of different forms focal dystonia. © 2018 International Parkinson and Movement Disorder Society.

Objective Fear of recurrence is a crucial issue in cancer care. On the one hand, the increase of cancer-survival rates and complexity of care is exposing patients to this type of fear. On the other hand, it is a distressing and recurrent psychosocial risk that affects quality of life and adherence to follow-up. Patients should have access to targeted psychological interventions aimed at reducing or preventing fear of recurrence. This mixed-methods pilot study reports the preliminary results of a novel mindfulness- and metacognition-based intervention specifically targeting fear of recurrence. Methods The study was composed of an individual (n = 76) and a group (n = 38) intervention, both lasting 8 weeks, that were evaluated through a preassessment and postassessment and a 1-month follow-up. We enrolled women recovering from breast cancer (n = 114) in follow-up care, with significant psychosocial distress. Patients with more severe psychopathology were assigned to the individual treatment, whereas the less severe ones were assigned to the group treatment. We explored the distress and the fear of recurrence through standardized measures and in-depth qualitative interviews. Results Results showed that depressive, anxious, and post-traumatic symptoms were reduced significantly in the entire sample. Patients reported a significant reduction of fear of recurrence, which was described in terms of loss of control, increase of uncertainty, and decrease of metacognitive and interpersonal skills. Conclusions Although further studies are needed, these findings provide preliminary proof-of-concept results for the potential of integrated mindfulness- and metacognition-based interventions to reduce fear of recurrence in cancer patients.

In this article, we present a discontinuous Galerkin (DG) method designed to improve the accuracy and efficiency of steady solutions of the compressible fully coupled Reynolds-averaged Navier–Stokes and k − ω turbulence model equations for solving all-speed flows. The system of equations is iterated to steady state by means of an implicit scheme. The DG solution is extended to the incompressible limit by implementing a low Mach number preconditioning technique. A full preconditioning approach is adopted, which modifies both the unsteady terms of the governing equations and the dissipative term of the numerical flux function by means of a new preconditioner, on the basis of a modified version of Turkel's preconditioning matrix. At sonic speed the preconditioner reduces to the identity matrix thus recovering the non-preconditioned DG discretization. An artificial viscosity term is added to the DG discretized equations to stabilize the solution in the presence of shocks when piecewise approximations of order of accuracy higher than 1 are used. Moreover, several rescaling techniques are implemented in order to overcome ill-conditioning problems that, in addition to the low Mach number stiffness, can limit the performance of the flow solver. These approaches, through a proper manipulation of the governing equations, reduce unbalances between residuals as a result of the dependence on the size of elements in the computational mesh and because of the inherent differences between turbulent and mean-flow variables, influencing both the evolution of the Courant Friedrichs Lewy (CFL) number and the inexact solution of the linear systems. The performance of the method is demonstrated by solving three turbulent aerodynamic test cases: the flat plate, the L1T2 high-lift configuration and the RAE2822 airfoil (Case 9). The computations are performed at different Mach numbers using various degrees of polynomial approximations to analyze the influence of the proposed numerical strategies on the accuracy, efficiency and robustness of a high-order DG solver at different flow regimes.

Fractal geometry was deployed to analyse water retention curves (WRC). The three models used to estimate the curves were the general pore-solid fractal (PSF) model and two specific cases of the PSF model: the Tyler & Wheatcraft (TW) and the Rieu & Sposito (RS) models. The study was conducted on 30 undisturbed, sandy loam soil samples taken from a field and subjected to laboratory analysis. The fractal dimension, a non-variable scale factor characterizing each water retention model proposed, was estimated by direct scaling. The method for determining the fractal dimension proposed here entails limiting the analysis to the interval between an upper and lower pressure head cut-off on a log-log plot, and defining the dimension itself as the straight regression line that interpolates the points in the interval with the largest coefficient of determination, R2. The scale relative to the cut-off interval used to determine the fractal behaviour in each model used is presented. Furthermore, a second range of pressure head values was analysed to approximate the fractal dimension of the pore surface. The PSF model exhibited greater spatial variation than the TW or RS models for the parameter values typical of a sandy loam soil. An indication of the variability of the fractal dimension across the entire area studied is also provided. © 2010 The Authors. Journal compilation © 2010 British Society of Soil Science.

In this paper we present a Discontinuous Galerkin (DG) method designed to improve the accuracy and efficiency of laminar flow simulations at low Mach numbers using an implicit scheme. The algorithm is based on the flux preconditioning approach, which modifies only the dissipative terms of the numerical flux. This formulation is quite simple to implement in existing implicit DG codes, it overcomes the time-stepping restrictions of explicit multistage algorithms, is consistent in time and thus applicable to unsteady flows. The performance of the method is demonstrated by solving the flow around a NACA0012 airfoil and on a flat plate, at different low Mach numbers using various degrees of polynomial approximations. Computations with and without flux preconditioning are performed on different grid topologies to analyze the influence of the spatial discretization on the accuracy of the DG solutions at low Mach numbers. The time accurate solution of unsteady flow is also demonstrated by solving the vortex shedding behind a circular cylinder at the Reynolds number of 100.

Aims: Several studies have documented an involvement of Neuropeptide Y (NPY) in stress‐related disorders. Stress‐related disorders are also characterized by changes in brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant‐like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production. Methods: Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme‐linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma. Results: The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma. Discussion: Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant‐like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic–pituitary–adrenal (HPA) axis. Conclusion: These findings, while confirming the involvement of the NPY system in stress‐related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans.

Plasma treatments in H2 and NH3 RF (13.56 MHz) glow discharges have been used for modifying the surface of PEEK-WC-PU membranes. Water contact angle (WCA) and X-Ray photoelectron spectroscopy (XPS) analyses were performed to study the compositional changes of PEEK-WC-PU membranes after grafting. Cell culture experiments with human hepatocytes clearly show that grafting N-containing groups improves the cyto-compatibility of the membranes.

The viability and liver specific functions of human hepatocytes in a multibore fiber bioreactor are reported. Human hepatocytes were cultured in the intraluminal compartment of the bioreactor. Human hepatocytes on the membranes maintained their round shape and showed focal adhesions as sites of interaction with the membrane surface. Cells in the bioreactor expressed liver specific functions, including synthetic and detoxification activity up to 14 d of culture. The results demonstrate that human hepatocytes cultured in the multibore fiber bioreactor are able to sustain the same in vivo liver functions in vitro.

Progresses in polymeric membrane preparation and in the understanding and control of their transport properties make possible the design of novel membranes to be used for cell culture (e.g., hepatocytes, lymphocytes, pancreatic islets) in biohybrid systems such as therapeutic device or as in vitro model systems for studying the effects of various drugs and chemicals on cell metabolism. Special attention is paid to the design of the membrane with defined microstructure and physicochemical properties as well as to the importance of transport and physicochemical properties of the membrane in contact with the cells. The development of new biomaterials and bioreactors able to activate a specific response of the cells and to maintain cell differentiation for a long time is one of the most pertinent issues in the field of tissue engineering and regenerative medicine. Polymeric membranes are attractive for their selectivity and biostability characteristics in the use of biohybrid systems for cell culture. Semipermeable membranes act as a support for the adhesion of anchorage-dependent cells and allow the specific transport of metabolites and nutrients to cells and the removal of catabolites and specific products. Moreover, new membrane systems that have been recently realized as the membrane contactors might also potentially contribute to regenerative medicine and tissue engineering.

Molybdenum is a trace element essential to life. Nevertheless, little information is available on its metabolism in humans. A methodology based on stable isotope administration that combines compartmental analysis, simultaneous use of two tracers, and proton nuclear activation (PNA) is presented. A four-compartment metabolic model was adopted. The compartments are stomach, small intestine, transfer compartment, and unquantified tissue pool. The employment of two different stable isotopes of the element under investigation as tracers was made possible by PNA. Optimization of the technique for molybdenum determination in plasma led to the choice of 95Mo and 96Mo as tracers. Their concentrations in plasma can be determined measuring the disintegration gamma lines of the corresponding technetium radioisotopes produced via (p,n) reaction. In the adopted experimental conditions, a minimum detectable concentration of 2 ng isotope/ml plasma was attained. A kinetics study was performed on two healthy volunteers. To both subjects one tracer was orally administered, and the other intravenously injected. Venous blood samples were withdrawn at different postinjection times and the concentrations for both isotopes determined. The model parameters describing molybdenum kinetics were obtained for the two individuals. Total absorbed fraction was found to be 0.84 +/- 0.03 and 0.86 +/- 0.07, respectively.

In this work we present a Discontinuous Galerkin (DG) method designed to improve the accuracy and efficiency of the solution at very low Mach number flows using an explicit scheme for the temporal discretization of the compressible Euler equations. The algorithm is based on a perturbed formulation of the governing equ ations and employs the preconditioning of both the instationary term of the governing equations and the dissipative term of the numerical flux function (full preconditioning approach). The performance of the method is demonstrated by solving an inviscid flow past a NACA0012 airfoil at different very low Mach numbers using various degrees of polynomial approximations. We present numerical results computed with and without perturbed variables which illustrate the influence of the cancellation errors on both the convergence and the accuracy of the DG solutions at low Mach numbers.

An investigation on molybdenum metabolism by administration of molybdenum stable isotopes was performed. Fractional intestinal absorption was determined in animals by the double tracer technique. The investigated subjects were given an enriched solution of Mo-96 orally and, a few minutes later, an enriched solution of Mo-95 intravenously. Blood samples were drawn at different times following the tracer administration. The Mo-95 and Mo-96 contents in plasma samples were determined by proton nuclear activation. The described methodology offers a means for the study of molybdenum metabolism in humans without radiation risk.