Development and feasibility testing of a Pain Neuroscience Education program for children with chronic pain: treatment protocol

Background

Current treatment for adults with chronic pain often includes Pain Neuroscience Education (PNE) to make people understand the nature underlying their pain and thus provides a clear rational for a biopsychosocial approach. Despite recommendations to use Pain Neuroscience Education as well in children with chronic pain, a specific program, tailored to children aged 6–12 years is lacking.

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.Cardiovascular disease remains the most important cause of death among patients with CKD,¹ and it is associated with a baseline inflammatory status.^2,3 Atherosclerosis is highly prevalent and advances more rapidly in individuals with renal dysfunction compared with the general population.^4–6 A key role in the development of atherosclerosis is played by leukocyte–endothelial interactions.²CKD is characterized by the progressive retention of a host of solutes. A substantial number of these compounds is protein-bound.^7,8 The indole indoxylsulfate (IS) and the phenolic conjugates p-cresylsulfate (pCS) and p-cresylglucuronide (pCG) are prototype members of this group. Observational data associate these solutes with enhanced cardiovascular damage and progression of kidney failure, and in in vitro experiments, several underlying isolated molecular mechanisms support the link with these observational data.^8–12 Although for all three compounds, one of two key mechanisms of vascular damage (i.e., leukocyte activation or endothelial dysfunction) have been shown in separate in vitro models, they were, to the best of our knowledge, never directly assessed by evaluating the complicated crosstalk between endothelium and leukocytes in an in vivo situation. Intravital microscopy permits in vivo visualization of leukocyte recruitment in translucent tissues in real time. This technique was already applied successfully by our group to study harmful effects of peritoneal dialysis solutions on peritoneal membrane physiology.¹³The present study evaluates the effects of an acute peritoneal superfusion of the protein-bound uremic compounds IS, pCS, and pCG and also, continuous intravenous infusion of IS on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using this intravital microscopic method.     

The added value of cognitive behavioral therapy for insomnia to current best evidence physical therapy for chronic spinal pain: protocol of a randomized controlled clinical trial

Background

Insomnia is a highly prevalent and debilitating comorbidity that is often not addressed in therapy for chronic spinal pain (CSP). Given the close interaction between insomnia and CSP severity and related disability, targeting sleep problems during therapy could improve treatment outcomes in these patients.

Review on solving the forward problem in EEG source analysis

Background

The aim of electroencephalogram (EEG) source localization is to find the brain areas responsible for EEG waves of interest. It consists of solving forward and inverse problems. The forward problem is solved by starting from a given electrical source and calculating the potentials at the electrodes. These evaluations are necessary to solve the inverse problem which is defined as finding brain sources which are responsible for the measured potentials at the EEG electrodes.

Methods

While other reviews give an extensive summary of the both forward and inverse problem, this review article focuses on different aspects of solving the forward problem and it is intended for newcomers in this research field.

Results

It starts with focusing on the generators of the EEG: the post-synaptic potentials in the apical dendrites of pyramidal neurons. These cells generate an extracellular current which can be modeled by Poisson's differential equation, and Neumann and Dirichlet boundary conditions. The compartments in which these currents flow can be anisotropic (e.g. skull and white matter). In a three-shell spherical head model an analytical expression exists to solve the forward problem. During the last two decades researchers have tried to solve Poisson's equation in a realistically shaped head model obtained from 3D medical images, which requires numerical methods. The following methods are compared with each other: the boundary element method (BEM), the finite element method (FEM) and the finite difference method (FDM). In the last two methods anisotropic conducting compartments can conveniently be introduced. Then the focus will be set on the use of reciprocity in EEG source localization. It is introduced to speed up the forward calculations which are here performed for each electrode position rather than for each dipole position. Solving Poisson's equation utilizing FEM and FDM corresponds to solving a large sparse linear system. Iterative methods are required to solve these sparse linear systems. The following iterative methods are discussed: successive over-relaxation, conjugate gradients method and algebraic multigrid method.

Conclusion

Solving the forward problem has been well documented in the past decades. In the past simplified spherical head models are used, whereas nowadays a combination of imaging modalities are used to accurately describe the geometry of the head model. Efforts have been done on realistically describing the shape of the head model, as well as the heterogenity of the tissue types and realistically determining the conductivity. However, the determination and validation of the in vivo conductivity values is still an important topic in this field. In addition, more studies have to be done on the influence of all the parameters of the head model and of the numerical techniques on the solution of the forward problem.     

Recurrent copy number alterations in BRCA1-mutated ovarian tumors alter biological pathways

Array CGH was used to identify recurrent copy number alterations (RCNA) characteristic of either BRCA1-related or sporadic ovarian cancer. After preprocessing, both groups of patients were modeled using a recurrent Hidden Markov Model to detect RCNA. RCNA with a probability higher than 80% were called. After removing RCNA present in both groups, the genes present in the remaining RCNA were investigated for enrichment of pathways from external databases. More RCNA were observed in the BRCA1 group, and they display more losses than gains compared to the sporadic group. When focusing on the type of RCNA, no significant difference in length was seen for the gains, but there was a statistically significant difference for the losses. In the sporadic group, a great proportion of the altered regions contain genes known to have a function in cell adhesion and complement activation, whereas the BRCA1 samples are characterized by alterations in the HOX genes, metalloproteinases, tumor suppressor genes, and the estrogen-signaling pathways. We conclude that BRCA1 ovarian tumors present a different type, number, and length of RCNA; a huge amount of the genome is lost, resulting in important genomic instability. Moreover, important biological pathways are altered differentially when compared to the sporadic group. Hum Mutat 30:1–10, 2009. © 2009 Wiley-Liss, Inc.     

Validation and predictive capacity of a Dutch version of the FLARE-RA questionnaire within the context of a TNFi-tapering trial

Clinical Rheumatology - Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to...