The Concept of Psychological Distress and Its Assessment: A Clinimetric Analysis of the SCL-90-R

Many studies have been conducted on psychological distress but the question of how to conceptualize and assess this phenomenon still remains a controversial issue. Clinimetrics, the science of clinical measurements, may pave the ground for a substantial revision of the clinical conceptualization and assessment of this construct. A Rasch analysis was performed to evaluate whether the Symptom Checklist-90-Revised (SCL-90-R) and its subscales were valid indices of underlying dimensions of psychological distress. Based on the clinimetric validation of the SCL-90-R, as well as on a critical review of the available literature, a concept analysis of psychological distress was performed. The SCL-90-R total score misfitted the Rasch model but it was found to have a Person Separation Reliability Index of 0.94. Model fit was achieved after the exclusion of six misfitting items. Paired t tests indicated that all the subscales of the SCL-90-R were unidimensional. Psychological distress was defined as a subjective, unifying, dimensional, and transdiagnostic construct consisting in a unique experience of discomfort, which may involve a sense of demoralization, the experience of feeling broken or mental pain, a sense of anguish, symptoms of somatization and attention deficit hyperactivity disorder (ADHD), feelings of anger, self-perceived lack of control, and self-criticism. Our findings also showed that the SCL-90-R could reliably differentiate healthy stress from psychological distress, and identify individuals at risk of psychiatric disorders. The total score of the 84-item version of the SCL-90-R may be used as an overall indicator of psychological distress. The subscales are recommended to assess the severity of specific symptomatic manifestations of psychological distress

Diabetes Reduces Mesenchymal Stem Cells in Fracture Healing Through a TNFα-Mediated Mechanism

Aims/hypothesis Diabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair. Methods Fracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNFα inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA. Results Diabetes significantly increased TNFα levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNFα significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNFα alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNFα-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes. Conclusions/interpretation Diabetes-enhanced TNFα significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNFα reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNFα in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients

Assessment of the Kinematic Adaptations in Parkinson’s Disease Using the Gait Profile Score: Influences of Trunk Posture, a Pilot Study

Introduction: Postural abnormalities are common in patients with Parkinson’s disease (PD) and lead to gait abnormalities. Relationships between changes in the trunk posture of PD patients and gait profile score (GPS) and gait spatiotemporal parameters are poorly investigated. The aim of the current study was to investigate the relationships between trunk posture, GPS, and gait spatiotemporal parameters, in patients with PD. Materials and Methods: Twenty-three people with PD and nineteen age-matched healthy people participated in this study. A 3D gait kinematical analysis was applied to all participants using the Plug-In Gait Full Body™ tool. Trunk and limb kinematics patterns and gait spatio-temporal parameters of patients with PD and the control group were compared. Additionally, correlations between trunk kinematics patterns, gait spatio-temporal parameters, and GPS of the PD group were tested. Results: Cadence, opposite foot off, step time, single support, double support, foot off, gait speed, trunk kinematics, and GPS showed significant differences between the two groups (p ≤ 0.05). Posture of the trunk during gait was not related to the spatio-temporal parameters and gait profile score in the PD group. The trunk flexor pattern influenced GPS domains, mainly of the ankle and the knee. Discussion and Conclusions: Flexed posture of the trunk in patients with PD seems to influence both ankle and knee movement patterns during the gait. The GPS analysis provided direct and simplified kinematic information for the PD group. These results may have implications for understanding the importance of considering the positioning of the trunk during gait

Preoperative imaging findings in patients undergoing transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients’ age (rho = 483, p < 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating

Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling

Hypoxia and inflammation are implicated in the episodic induction of heterotopic endochondral ossification (HEO); however, the molecular mechanisms are unknown. HIFâ 1α integrates the cellular response to both hypoxia and inflammation and is a prime candidate for regulating HEO. We investigated the role of hypoxia and HIFâ 1α in fibrodysplasia ossificans progressiva (FOP), the most catastrophic form of HEO in humans. We found that HIFâ 1α increases the intensity and duration of canonical bone morphogenetic protein (BMP) signaling through Rabaptin 5 (RABEP1)â mediated retention of Activin A receptor, type I (ACVR1), a BMP receptor, in the endosomal compartment of hypoxic connective tissue progenitor cells from patients with FOP. We further show that early inflammatory FOP lesions in humans and in a mouse model are markedly hypoxic, and inhibition of HIFâ 1α by genetic or pharmacologic means restores canonical BMP signaling to normoxic levels in human FOP cells and profoundly reduces HEO in a constitutively active Acvr1Q207D/+ mouse model of FOP. Thus, an inflammation and cellular oxygenâ sensing mechanism that modulates intracellular retention of a mutant BMP receptor determines, in part, its pathologic activity in FOP. Our study provides critical insight into a previously unrecognized role of HIFâ 1α in the hypoxic amplification of BMP signaling and in the episodic induction of HEO in FOP and further identifies HIFâ 1α as a therapeutic target for FOP and perhaps nongenetic forms of HEO. © 2016 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134262/1/jbmr2848_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134262/2/jbmr2848.pd