Accuracy of the Modified Somatic Perception Questionnaire and Pain Disability Index in the Detection of Malingered Pain-Related Disability in Chronic Pain

The Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI) are both popular clinical screening instruments in general orthopedic, rheumatologic, and neurosurgical clinics and are useful for identifying pain patients whose physical symptom presentations and disability may be non-organic. Previous studies found both to accurately detect malingered pain presentations; however, the generalizability of these results is not clear. This study used a criterion groups validation design (retrospective cohort of patients with chronic pain, n = 328) with a simulator group (college students, n = 98) to determine the accuracy of the MSPQ and PDI in detecting Malingered Pain Related Disability. Patients were grouped based on independent psychometric evidence of MPRD. Results showed that MSPQ and PDI scores were not associated with objective medical pathology. However, they accurately differentiated Not-MPRD from MPRD cases. Diagnostic statistics associated with a range of scores are presented for application to individual cases. Data from this study can inform the clinical management of chronic pain patients by screening for psychological overlay and malingering, thus alerting clinicians to the possible presence of psychosocial obstacles to effective treatment and triggering further psychological assessment and/or treatment.     

uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease.     

Th17 lymphocyte-dependent degradation of joint cartilage by synovial fibroblasts in a humanized mouse model of arthritis and reversal by secukinumab

How T-helper (Th) lymphocyte subpopulations identified in synovial fluid from patients with juvenile idiopathic arthritis (JIA) (Th17, classic Th1, or nonclassic Th1) drive joint damage is of great interest for the possible use of biological drugs that inhibit the specific cytokines. Our objective was to clarify the role of such Th subpopulations in the pathogenesis of articular cartilage destruction by synovial fibroblasts (SFbs), and the effect of Th17 blockage in an animal model. SFbs were isolated from healthy subjects and patients with JIA, and peripheral blood Th lymphocytes subsets were obtained from healthy subjects. Fragments of human cartilage from healthy subjects in a collagen matrix containing JIA or normal SFbs grafted underskin in SCID mice were used to measure cartilage degradation under the effects of Th supernatants. JIA SFbs overexpress MMP9 and MMP2 and Th17 induce both MMPs in normal SFbs, while nonclassic Th1 upregulate urokinase plasminogen activator (uPA) activity. In vitro invasive phenotype of normal SFbs is stimulated with conditioned medium of Th17 and nonclassic-Th1. In the in vivo “inverse wrap” model, normal SFbs stimulated with supernatants of Th17-lymphocytes and nonclassic Th1 produced a cartilage invasion and degradation similar to JIA SFbs. Secukinumab inhibits the cartilage damage triggered by factors produced by Th17.     

Latent structure of the Wisconsin Card Sorting Test in a clinical sample.

The aims of this study were to: (a) examine the consistency of the published Wisconsin Card Sorting Test (WCST) factor structures; (b) determine the factor structure of the WCST in a large, heterogeneous sample; and (c) compare the WCST factor analytically with other neuropsychological procedures. Two WCST factors (concept formation/perseveration and Failure-to-Maintain-Set [FMS]) were consistently reported in the literature. Our analysis of data from 473 clinical cases replicated the two factors previously reported and revealed a third on which nonperseverative errors (NPE) was the sole salient variable. This pattern was maintained in three of four diagnostically distinct subgroups. These factors are potentially clinically meaningful, with each seeming to reflect one of three qualitatively different performance styles. In the construct validation factor analysis, WCST scores loaded independently of other neuropsychological variables, indicating that the WCST contributes uniquely to neuropsychological evaluation. Nevertheless, despite the rational interpretation of the factors, the cognitive processes underlying WCST performance remain poorly understood. Future directions for the application of these factor analytic findings are discussed.     

Looking for the compass in a case of developmental topographical disorientation: A behavioral and neuroimaging study

Developmental topographical disorientation (DTD) is the presence of navigational deficits in the context of normal intellectual ability and in the absence of any perinatal, neurological, or psychiatric disorder. As only three cases of DTD have been fully described thus far, we are still unable to draw definitive conclusions about its nature and relationship with other visuospatial competencies, such as mental rotation. The case of Mr. L.A., a 38-year-old man with no history of neurological or psychiatric disorders, sheds some light on these open questions. A neuropsychological assessment including IQ, memory, visuospatial, visuoconstructive, and navigational tests showed that Mr. L.A. has pure navigational deficits affecting both route knowledge and cognitive map processing. Unlike previously described cases of DTD, Mr. L.A. was not affected by any other visuospatial or visuoconstructive deficits. In a functional magnetic resonance imaging (fMRI) task involving the recall of route knowledge, Mr. L.A. showed activation in the occipital areas, involved in low-level perceptual analysis of the stimuli, and showed no activation in the areas activated in controls with regard to route knowledge. The present case suggests that different types of DTD exist, which are characterized by different navigational difficulties and anomalous/lacking functional brain activities in specific navigational networks.     

Physiological responses to acute silver exposure in the freshwater crayfish (Cambarus diogenes diogenes)--a model invertebrate?

Adult crayfish (Cambarus diogenes diogenes) exposed to 8.41 +/- 0.17 microg silver/L (19.4% as Ag+) in moderately hard freshwater under flow-through conditions for 96 h exhibited ionoregulatory disturbance, elevated metabolic ammonia (T(amm)) production and substantial silver accumulation in the gills, hemolymph, and hepatopancreas. The ionoregulatory disturbance included both a generally reduced unidirectional Na+ influx and an increased unidirectional Na+ efflux, leading to a substantial net loss of Na+ from the silver-exposed crayfish. The Na+ uptake in silver-exposed crayfish differed overall from controls, while the increased Na+ efflux recovered to control values 48 h into the 96 h of exposure. The general inhibition of Na+ uptake could be explained by a reduced sodium/potassium-adenosine triphosphatase (Na/K-ATPase) activity in terminally obtained gill samples from the silver-exposed crayfish. The silver-induced effect on Na+ uptake and loss translated to reduced hemolymph Na+ concentrations but not significantly reduced hemolymph Cl- concentrations. Hemolymph T(anim) and T(amm) efflux both increased in silver-exposed crayfish, indicating an increased metabolic T(amm) production. The present study demonstrates that the toxic mechanism of waterborne silver exposure in freshwater crayfish resembles that of freshwater teleost fish. The crayfish might therefore be a useful model system for extending current environmental regulatory strategies, currently based on teleost fish, to invertebrates.     

Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I) to Daphnia magna. Part 1: description of the chemical system

Experiments were designed to assess the potential protective effect of the presence of sulfide against the acute (48-h) toxicity of silver(I) to Daphnia magna. Tests were conducted in borosilicate glass beakers (250 ml) in moderately hard synthetic water. Toxicity solutions were replaced after 24 h by static renewal method. This paper describes the chemical system, and the acute toxicity results are presented in a companion paper. Sulfide was below detection limit (<5 nM) in controls with no sulfide added. Sulfide, added as zinc sulfide clusters at approximately 35- or approximately 350-nM concentration, dropped in concentration to approximately 25 and 250 nM, respectively, over the 24-h period of measurements. Silver also decreased in concentration during the experiment (up to 59%), and the rate of loss was greater in the absence of sulfide compared with the presence of sulfide. A filtration experiment indicated a 1:1 binding ratio of silver to sulfide and a conditional stability constant for the Ag(I)-zinc sulfide complex of log K' = 8.9. The losses of sulfide and silver during the experiments highlighted the need for regular monitoring of the important chemical components of the system, even during short (48-h) toxicity tests.     

Thyroid tissue: US-guided percutaneous interstitial laser ablation-a feasibility study

PURPOSE: To evaluate percutaneous interstitial laser photocoagulation (ILP) as a palliative treatment of recurrent thyroid carcinoma untreatable with surgery or radioiodine administration. MATERIALS AND METHODS: By using 18 resected thyroid glands, the volume and histologic pattern of ILP-induced thyroid damage were assessed. In vivo treatment feasibility was evaluated by using a low-energy laser in two volunteers before thyroidectomy for huge autonomously functioning nodules. With ultrasonographic (US) monitoring, a 21-gauge spinal needle was inserted into the thyroid nodules. A 300-microm quartz fiberoptic guide was inserted through the needle lumen, and the fiber tip was placed in direct contact with the tissue. Laser irradiation was performed with a 1.064-nm Nd:YAG laser in surgically resected glands, which were treated with 2, 3, 5, or 7 W. RESULTS: Tissue ablation was well-defined histologically, and its area was related to laser irradiation parameters (range, 0-26 mm). No correlation was found between US images and the actual extent of laser-induced lesions. Large colloid or fluid collections did not permit regular heat diffusion within the tissue. In vivo low-energy ILP was performed without technical difficulties or complications. CONCLUSION: ILP induces well-defined tissue ablation correlated with energy parameters in thyroid glands devoid of cystic areas. ILP could be a therapeutic tool for highly selected problems in thyroid tumor treatment.