Minimally invasive computer-navigated total hip arthroplasty, following the concept of femur first and combined anteversion: design of a blinded randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Impingement can be a serious complication after total hip arthroplasty (THA), and is one of the major causes of postoperative pain, dislocation, aseptic loosening, and implant breakage. Minimally invasive THA and computer-navigated surgery were introduced several years ago. We have developed a novel, computer-assisted operation method for THA following the concept of "femur first"/"combined anteversion", which incorporates various aspects of performing a functional optimization of the cup position, and comprehensively addresses range of motion (ROM) as well as cup containment and alignment parameters. Hence, the purpose of this study is to assess whether the artificial joint's ROM can be improved by this computer-assisted operation method. Second, the clinical and radiological outcome will be evaluated.</p> <p>Methods/Design</p> <p>A registered patient- and observer-blinded randomized controlled trial will be conducted. Patients between the ages of 50 and 75 admitted for primary unilateral THA will be included. Patients will be randomly allocated to either receive minimally invasive computer-navigated "femur first" THA or the conventional minimally invasive THA procedure. Self-reported functional status and health-related quality of life (questionnaires) will be assessed both preoperatively and postoperatively. Perioperative complications will be registered. Radiographic evaluation will take place up to 6 weeks postoperatively with a computed tomography (CT) scan. Component position will be evaluated by an independent external institute on a 3D reconstruction of the femur/pelvis using image-processing software. Postoperative ROM will be calculated by an algorithm which automatically determines bony and prosthetic impingements.</p> <p>Discussion</p> <p>In the past, computer navigation has improved the accuracy of component positioning. So far, there are only few objective data quantifying the risks and benefits of computer navigated THA. Therefore, this study has been designed to compare minimally invasive computer-navigated "femur first" THA with a conventional technique for minimally invasive THA. The results of this trial will be presented as soon as they become available.</p> <p>Trial registration number</p> <p>DRKS00000739</p

Reassessment of CXCR4 Chemokine Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-2

BACKGROUND: The CXCR4 chemokine receptor regulates migration and homing of cancer cells to specific metastatic sites. Determination of the CXCR4 receptor status will provide predictive information for disease prognosis and possible therapeutic intervention. However, previous attempts to localize CXCR4 using poorly characterized mouse monoclonal or rabbit polyclonal antibodies have produced predominant nuclear and occasional cytoplasmic staining but did not result in the identification of bona fide cell surface receptors. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we extensively characterized the novel rabbit monoclonal anti-CXCR4 antibody (clone UMB-2) using transfected cells and tissues from CXCR4-deficient mice. Specificity of UMB-2 was demonstrated by cell surface staining of CXCR4-transfected cells; translocation of CXCR4 immunostaining after agonist exposure; detection of a broad band migrating at M(r) 38,000-43,000 in Western blots of homogenates from CXCR4-expressing cells; selective detection of the receptor in tissues from CXCR4+/+ but not from CXCR4-/- mice; and abolition of tissue immunostaining by preadsorption of UMB-2 with its immunizing peptide. In formalin-fixed, paraffin-embedded human tumor tissues, UMB-2 yielded highly effective plasma membrane staining of a subpopulation of tumor cells, which were often heterogeneously distributed throughout the tumor. A comparative analysis of the mouse monoclonal antibody 12G5 and other frequently used commercially available antibodies revealed that none of these was able to detect CXCR4 under otherwise identical conditions. CONCLUSIONS/SIGNIFICANCE: Thus, the rabbit monoclonal antibody UMB-2 may prove of great value in the assessment of the CXCR4 receptor status in a variety of human tumors during routine histopathological examination

CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival

Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repressor protein Rb, which is involved in the recruitment of chromatin modifiers (such as histone deacetylases (HDACs)) to gene promoters. In neurons, Rb controls activity-dependent genes essential to neuronal plasticity and survival, such as the N-methyl--aspartic acid (NMDA) receptor's subunit NR2B, the expression of which in the tetrameric ion channel largely affects calcium signaling by glutamate. In this study, we report that CXCL12 differentially modulates intracellular responses after stimulation of synaptic and extrasynaptic NMDA receptors, by a specific regulation of the NR2B gene that involves HDACs. Our results show that CXCL12 selectively inhibits NR2B expression in vitro and in vivo altering NMDA-induced calcium responses associated with neuronal death, while promoting prosurvival pathways that depend on stimulation of synaptic receptors. Along with previous studies, these findings underline the role of CXCL12/CXCR4 in the regulation of crucial components of glutamatergic transmission. These novel effects of CXCL12 may be involved in the physiological function of the chemokine in both developing and mature brains

Understanding discrepancies in parent-child reporting of emotional and behavioural problems: Effects of relational and socio-demographic factors

<p>Abstract</p> <p>Background</p> <p>Discrepancies between parents and children in their assessment of children's mental health affect the evaluation of need for services and must be taken seriously. This article presents the differences between parents' and children's reports of the children's symptoms and social impairment, based on the results of the Strengths and Difficulties Questionnaire (SDQ). The interrelationship between relational aspects and socio-demographic factors with patterns of disagreement are explored.</p> <p>Methods</p> <p>Differences in the prevalence and means of SDQ symptom and impact scores were obtained from 8,154 primary school children, aged between 10 and 13 years, and their parents. Agreement between matched pairs was measured using Pearson's and Spearman's rho correlations. Socio-demographic variables, communication patterns and parental engagement were analysed as possible correlates of informant discrepancies using bivariate and multivariate logistic regression models.</p> <p>Results</p> <p>In general, although children reported more symptoms, they reported less impact of perceived difficulties than parents. The parents were more consistent in their evaluation of symptoms and impact than were the children. Exploration of highly discrepant subgroups showed that, when children reported the most symptoms and impact, qualitative aspects of the parent-child relationship and family structure seemed to be more powerful predictors of disagreement than were gender of the child and socio-demographic variables. When parents reported the most symptoms and impact, low parental educational level, low income and male gender of the child played an additional role.</p> <p>Conclusions</p> <p>Our findings underline the importance of paying attention to child reports of emotional-behavioural difficulties, particularly when parents do not identify these problems. Considerations on what meaning parent-child discrepancy might have in the context of the parent-child relationship or the family's psychosocial status should be integrated in the overall understanding of the child's situation and subsequent recommendations.</p

HGF-Induced PKCζ Activation Increases Functional CXCR4 Expression in Human Breast Cancer Cells

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio