Arthroscopic treatment of osteochondral knee defects with resorbable biphasic synthetic scaffold: clinical and radiological results and long-term survival analysis.

Purpose: The aim of our study is to evaluate the long-term results in patients treated with a fully arthroscopic TruFit system for osteochondral lesions of the femoral condyle, analyzing the clinical and radiological outcomes, survival rate, complications, and correlations.

Methods: The study included all patients treated with the TruFit system with a full-thickness focal lesion of the knee cartilage (grade IV according to the ICRS classification), entirely arthroscopically with a minimum follow-up of five years. All patients were evaluated clinically prior to surgery (T) and at two consecutive follow-ups (T 36.

Small molecule inhibition of dipeptidyl peptidase-4 enhances bone marrow progenitor cell function and angiogenesis in diabetic wounds.

In diabetes, stromal cell-derived factor-1 (SDF-1) expression and progenitor cell recruitment are reduced. Dipeptidyl peptidase-4 (DPP-4) inhibits SDF-1 expression and progenitor cell recruitment. Here we examined the impact of the DPP-4 inhibitor, MK0626, on progenitor cell kinetics in the context of wound healing.

Controlled Viscosity in Dense Granular Materials.

We experimentally investigate the fluidization of a granular material subject to mechanical vibrations by monitoring the angular velocity of a vane suspended in the medium and driven by an external motor. On increasing the frequency, we observe a reentrant transition, as a jammed system first enters a fluidized state, where the vane rotates with high constant velocity, and then returns to a frictional state, where the vane velocity is much lower. While the fluidization frequency is material independent, the viscosity recovery frequency shows a clear dependence on the material that we rationalize by relating this frequency to the balance between dissipative and inertial forces in the system.

Synchronized oscillations and acoustic fluidization in confined granular materials.

According to the acoustic fluidization hypothesis, elastic waves at a characteristic frequency form inside seismic faults even in the absence of an external perturbation. These waves are able to generate a normal stress which contrasts the confining pressure and promotes failure. Here, we study the mechanisms responsible for this wave activation via numerical simulations of a granular fault model.

Rattler-induced aging dynamics in jammed granular systems.

Granular materials jam when developing a network of contact forces able to resist the applied stresses. Through numerical simulations of the dynamics of the jamming process, we show that the jamming transition does not occur when the kinetic energy vanishes. Rather, as the system jams, the kinetic energy becomes dominated by rattler particles, which scatter within their cages.

Methylglyoxal-Induced Endothelial Cell Loss and Inflammation Contribute to the Development of Diabetic Cardiomyopathy.

The mechanisms for the development of diabetic cardiomyopathy remain largely unknown. Methylglyoxal (MG) can accumulate and promote inflammation and vascular damage in diabetes. We examined if overexpression of the MG-metabolizing enzyme glyoxalase 1 (GLO1) in macrophages and the vasculature could reduce MG-induced inflammation and prevent ventricular dysfunction in diabetes.

Mechanical origin of aftershocks.

Aftershocks are the most striking evidence of earthquake interactions and the physical mechanisms at the origin of their occurrence are still intensively debated. Novel insights stem from recent results on the influence of the faulting style on the aftershock organisation in magnitude and time. Our study shows that the size of the aftershock zone depends on the fault geometry.

Dynamic Weakening by Acoustic Fluidization during Stick-Slip Motion.

The unexpected weakness of some faults has been attributed to the emergence of acoustic waves that promote failure by reducing the confining pressure through a mechanism known as acoustic fluidization, also proposed to explain earthquake remote triggering. Here we validate this mechanism via the numerical investigation of a granular fault model system. We find that the stick-slip dynamics is affected only by perturbations applied at a characteristic frequency corresponding to oscillations normal to the fault, leading to gradual dynamical weakening as failure is approaching.

GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.

The assumption underlying current diabetes treatment is that lowering the level of time-averaged glucose concentrations, measured as HbA1c, prevents microvascular complications. However, 89% of variation in risk of retinopathy, microalbuminuria, or albuminuria is due to elements of glycemia not captured by mean HbA1c values. We show that transient exposure to high glucose activates a multicomponent feedback loop that causes a stable left shift of the glucose concentration-reactive oxygen species (ROS) dose-response curve.

Urea-induced ROS cause endothelial dysfunction in chronic renal failure.

Objective: The pathogenic events responsible for accelerated atherosclerosis in patients with chronic renal failure (CRF) are poorly understood. Here we investigate the hypothesis that concentrations of urea associated with CRF and increased ROS production in adipocytes might also increase ROS production directly in arterial endothelial cells, causing the same pathophysiologic changes seen with hyperglycemia.

Methods: Primary cultures of human aortic endothelial cells (HAEC) were exposed to 20mM urea for 48 h.

Early assessment of patient perception of outcome in total knee replacement.

Purpose: the aim of the present study was to measure patient perception in the early period after knee replacement surgery and to correlate health status with the surgery-related outcome.

Methods: thirty-eight consecutive patients who underwent total knee replacement were evaluated before surgery; at the time Radiographic evaluation was used to assess limb alignment and the Oxford Knee Score (OKS) to assess objective outcome. Health outcome was measured with the three-level version of the EuroQol - five dimension (EQ-5D-3L) self-administered questionnaire, a standardized instrument used to measure patient's perception of health status.

Non-monotonic dependence of the friction coefficient on heterogeneous stiffness.

The complexity of the frictional dynamics at the microscopic scale makes difficult to identify all of its controlling parameters. Indeed, experiments on sheared elastic bodies have shown that the static friction coefficient depends on loading conditions, the real area of contact along the interfaces and the confining pressure. Here we show, by means of numerical simulations of a 2D Burridge-Knopoff model with a simple local friction law, that the macroscopic friction coefficient depends non-monotonically on the bulk elasticity of the system.

Knockdown of glyoxalase 1 mimics diabetic nephropathy in nondiabetic mice.

Differences in susceptibility to diabetic nephropathy (DN) between mouse strains with identical levels of hyperglycemia correlate with renal levels of oxidative stress, shown previously to play a central role in the pathogenesis of DN. Susceptibility to DN appears to be genetically determined, but the critical genes have not yet been identified. Overexpression of the enzyme glyoxalase 1 (Glo1), which prevents posttranslational modification of proteins by the glycolysis-derived α-oxoaldehyde, methylglyoxal (MG), prevents hyperglycemia-induced oxidative stress in cultured cells and model organisms.

Effects of Poisson noise in a IF model with STDP and spontaneous replay of periodic spatiotemporal patterns, in absence of cue stimulation.

We consider a network of leaky integrate and fire neurons, whose learning mechanism is based on the Spike-Timing-Dependent Plasticity. The spontaneous temporal dynamic of the system is studied, including its storage and replay properties, when a Poissonian noise is added to the post-synaptic potential of the units. The temporal patterns stored in the network are periodic spatiotemporal patterns of spikes.

Associative memory of phase-coded spatiotemporal patterns in leaky Integrate and Fire networks.

We study the collective dynamics of a Leaky Integrate and Fire network in which precise relative phase relationship of spikes among neurons are stored, as attractors of the dynamics, and selectively replayed at different time scales. Using an STDP-based learning process, we store in the connectivity several phase-coded spike patterns, and we find that, depending on the excitability of the network, different working regimes are possible, with transient or persistent replay activity induced by a brief signal. We introduce an order parameter to evaluate the similarity between stored and recalled phase-coded pattern, and measure the storage capacity.

Solid-on-solid single-block dynamics under mechanical vibration.

The suppression of friction between sliding objects, modulated or enhanced by mechanical vibrations, is well established. However, the precise conditions of occurrence of these phenomena are not well understood. Here we address these questions focusing on a simple spring-block model, which is relevant to investigate friction both at the atomistic as well as the macroscopic scale.

PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms.

Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts.

Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance.

Clinical and experimental evidence indicates that atypical antipsychotics impair glucose metabolism. We investigated whether clozapine may directly affect insulin action by analyzing insulin signaling in vitro and in vivo. Clozapine reduced insulin-stimulated glucose uptake in PC12 and in L6 cells, representative models of neuron and skeletal muscle, respectively.

Oxidative stress and diabetic complications.

Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway.

Storage of Phase-Coded Patterns via STDP in Fully-Connected and Sparse Network: A Study of the Network Capacity.

We study the storage and retrieval of phase-coded patterns as stable dynamical attractors in recurrent neural networks, for both an analog and a integrate and fire spiking model. The synaptic strength is determined by a learning rule based on spike-time-dependent plasticity, with an asymmetric time window depending on the relative timing between pre and postsynaptic activity. We store multiple patterns and study the network capacity.

In skeletal muscle advanced glycation end products (AGEs) inhibit insulin action and induce the formation of multimolecular complexes including the receptor for AGEs.

Chronic hyperglycemia promotes insulin resistance at least in part by increasing the formation of advanced glycation end products (AGEs). We have previously shown that in L6 myotubes human glycated albumin (HGA) induces insulin resistance by activating protein kinase Calpha (PKCalpha). Here we show that HGA-induced PKCalpha activation is mediated by Src.

AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice.

Diabetes mellitus (DM) derives from either insulin deficiency (type 1) or resistance (type 2). Insulin regulates glucose metabolism and homeostasis by binding to a specific membrane receptor (IR) with tyrosine kinase activity, expressed by its canonical target tissues. General or tissue-specific IR ablation in mice results in complex metabolic abnormalities, which give partial insights into the role of IR signaling in glucose homeostasis and diabetes development.

PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.

The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia.

Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1.

Platelet components have found successful clinical utilization to initiate or to accelerate tissue-repair mechanisms. However, the molecular pathways by which platelet factors contribute to tissue regeneration have not been fully elucidated. We have studied the effect of thrombin-activated platelets (TAPs) on cell growth in vivo and in cultured cell systems.

Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action.

The antiapoptotic protein PED/PEA-15 features an Akt phosphorylation motif upstream from Ser(116). In vitro, recombinant PED/PEA-15 was phosphorylated by Akt with a stoichiometry close to 1. Based on Western blotting with specific phospho-Ser(116) PED/PEA-15 antibodies, Akt phosphorylation of PED/PEA-15 occurred mainly at Ser(116).