Post-translational modifications regulate distinct functions of CARMA1 and BCL10.

Activation of the transcription factor nuclear factor (NF)-kappaB is essential for the normal functioning of the immune system. Deregulated NF-kappaB signalling in lymphocytes can lead to immunodeficiency, but also to autoimmunity or lymphomas. Many of the signalling components controlling NF-kappaB activation in lymphocytes are now known, but it is less clear how distinct molecular components of this pathway are regulated. Here, we summarize recent findings on post-translational modifications of intracellular components of this pathway. Phosphorylation of the CARMA1 and BCL10 proteins and ubiquitylation of BCL10 affect the formation and stability of the CARMA1-BCL10-MALT1 (CBM) complex, and also control negative feedback regulation of the NF-kappaB signalling pathway. Moreover, the study of BCL10 phosphorylation isoforms has revealed a new mechanism controlling BCL10 nuclear translocation and an unexpected role for BCL10 in the regulation of the actin cytoskeleton.

Gamma Knife radiosurgery after previous microvascular decompression decreases the chances of pain free in classical trigeminal neuralgia

Purpose: To evaluate the safety-efficacy of Gamma Knife surgery (GKS) as a second treatment for classical trigeminal neuralgia (CTN), and the influence of prior microvascular decompression (MVD). Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous history of MVD. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed on the basis of on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9-11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Here, the 45 patients with previous MVD and a follow-up longer than one year are evaluated (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also radiofrequency lesion (RFL) in 16 patients (35.6%), balloon microcompression in 7 (15.6%) and glycerol rhizotomy in 1 (2.2%). Thirty-five patients (77.8%) were initially pain free after GKS within a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in the long-term was of 44.3% at 10 years.

Changing the awareness of low vitamin D status in a rheumatology population: a pre/post-study.

INTRODUCTION: In 2009 hypovitaminosis D was highly prevalent in a population of Swiss rheumatology patients (86%). We aimed to evaluate the evolution of vitamin D status in the same population two years later, after the results of the first study were disseminated to local physicians and patients, in order to determine the evolution of the problem and the impact of physician information. METHOD: Patients in our rheumatology clinic were screened for 25-OH vitamin D. Results were categorised as: deficient (<10 ng/ml or <25 nmol/l), insufficient (10 to 30 ng/ml or 25 to 75 nmol/l) or normal (>30 ng/ml or >75 nmol/l). We also used another cut-off of 20 ng/ml (50 nmol/l). We evaluated the evolution of 25-OH vitamin D dosages and vitamin D3 prescriptions between 2008 and 2011 in our institution and the number of publications on vitamin D in three important medical journals of the French speaking part of Switzerland. RESULTS: Compared with 2009, significantly more patients had normal results in 2011. Fifty-two percent of patients had levels >20 ng/ml in 2009 and 66% in 2011, difference statistically significant (p = 0.001). During the years separating the two study periods the number of 25-OH vitamin D dosages and the prescription of high doses of vitamin D3 increased in our hospital. In addition the number of publications on vitamin D increased between 2008 and 2011. CONCLUSION: We concluded that lower prevalence in hypovitaminosis D is certainly related to better adherence to daily supplements, and to better information and awareness of the physicians about hypovitaminosis D.

Body dissatisfaction on top of depressive mood among adolescent with severe dysmenorrhea

Purpose: Dysmenorrhea is the leading cause of recurrent short-term school absenteeism among adolescent girls. Yet, studies of menstrual symptoms in the light of adolescent psychological background seldom appear in the recent literature. This study aims to determine whether adolescent girls with severe dysmenorrhea (SD) have different body perception on top of poorer psychological health. Methods: We analyzed data from the Swiss Multicentre Adolescent Survey on Health (SMASH 2002) among a nationally representative sample of adolescents (n = 7548; 3340 females) aged 16 to 20 years attending post-mandatory education. Dysmenorrhea was defined as presence of abdominal or back pain during menstruation on the last 12 months. The severity of dysmenorrhea was defined according to the impact on daily activity and was assessed by 3 questions on the way menstruations interfere with daily life: 1) "You feel well and have normal activities", 2)"you must stay at home" and 3) "you feel restricted in your school or professional activities". Studied variables were: depressive symptoms, suicidal attempt, sexual abuse, health perception in general, body satisfaction, desire to modify body shape, and disordered eating behavior (DEB) with restrictive or bulimic tendency. Controlling variables included socio-economic status (SES) as measured by both parent's level of education, gynecological age (age-age at menarche), academic track (student/apprentice) and age. Results: 12.4% (95% CI: 11.0-14) declared severe dysmenorrhea, 74.2% (95% CI: 71.8-76.5) mild to moderate dysmenorrhea and 13,4% (95% CI: 11.5-15.5) had no dysmenorrhea. Compared to their peers, controlling for confounding variables, subjects with SD were more numerous to report depressive symptoms (AOR: 1.73; 95% CI: 1.39-2.15), to feel in poor health (AOR: 1.44; 95% CI: 1.14-1.81). Moreover, the proportion of those reporting dissatisfaction with their body appearance was higher (AOR: 1.48; 95% CI: 1.00-2.18). Conclusion: Patients with SD not only show a different profile than their peers in terms of their mental health and health perception, but also a distinct relation to their body. Therefore clinicians should pay particular attention to patients with SD and offer them a global evaluation keeping in mind what can be associated with SD.

Evolution of endurance during a multidisciplinary treatment of chronic low back pain and its influence of work capacity

Introduction: Low back pain is a common disorder touching up to 80% of the population, with redundancies of up to 70%. A small proportion would go on to develop chronic low back pain (LBP) with reduced work capacity and they would count for the majority of the costs. Up to day, a multi-disciplinary treatment program is one of the best approaches. In the program one of the mile-stones is restoration of function. The aim of this study was to follow patients, according to the endurance change after the program and its influence on workability during one year after inclusion in a such program. Method: Patients were following a multidisciplinary treatment for 3 weeks including physiotherapy, occupation measures combined with an educational program with behavioural and psychological interventions on an outpatient program. We studied the endurance with the help of the Bruce test, accomplished at the beginning and at the end of the program. On the other hand the patients filled out pain questionnaires and PACT score according their own impression on workability. Results: There were a clear relation between the increase in the cardiovascular endurance and the increased workability. Almost every patient presented an increase in the VO2 max, even though the workability did not follow. This increase were associated with a decrease in pain apprehension. Conclusion: A multidisciplinary treatment program, teaching the patients how to care with their pain and to accept it even if it persist is successful in lowering the global pain. If the program allows the patients to strengthen the endurance, the workability will increase in parallel. In this way the patients were able to reduce the consummation of medicaments and to increase the work capacity.

The treatment of falciparum malaria in children with halofantrine suspension

Malaria treatment of children is particulary difficult because of the absence of palatable suspensions for young children. Halofantrine hydrochloride is available as a suspension which is both palatable and simple to administer, and has been studied in a number of trials in the past 5 years. Children (331) ranging from 4 months to 17 years of age (mean 4.7 years) were treated with the 5% suspension using various dose regimens and 364 children ranging from 4 months to 14 years of age (mean 5.7 years) were treated with the 2% suspension 6 hourly for 3 doses. Using the 3-dose regimen there were only 2/462 (0.4%) who failed to clear the initial parasitaemia. Recrudescence occurred in 28/367 (7.6%) children with evaluable follow up data. The mean parasite clearance time in this group was 57.1h (n = 417) and the mean fever clearance time was 50.9 h (n = 325). Symptoms related to malaria cleared rapidly following treatment generally by 24-48 h post treatment. Side effects possibly related to treatment were uncommon but were similar to those reported in adults. The frequency of diarrhoea and abdominal pain was lower than that seen in adults and was also less frequent following multiple doses and the use of the more dilute suspension. Since was evidence that the majority of recrudescences were seen in younger children or those living in areas with low or seasonal transmission it is recommended that a further course of treatment 7 days later is given to these patients to prevent recrudescence. Halofantrine suspension appears to be effective and well tolerated in children and is a useful addition to the drugs available for the treatment of paediatric malaria.

Cytomegalovirus infection and new-onset post-transplant diabetes mellitus.

We analyzed data from all consecutive kidney transplant patients at our institution between April 2003 and October 2006. We found 15 cases of late-onset cytomegalovirus (CMV) infection, two of which developed concurrent post-transplant diabetes mellitus (PTDM). In these two cases, PTDM was transient and normal glucose tolerance was achieved after an eight-wk therapeutic course of oral valganciclovir. These findings suggest that CMV infection after organ transplantation may be associated with concurrent PTDM. The distinct causative relationship is yet to be determined.

Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis mansoni

Schistosomiasis control seems to be different in countries were low parasitic burden and asymptomatic clinical patients are the features of majority of cases. Immunological methods must substitute the traditional coprologic techniques used for some decades in the Control Program. Circumoval Precipitin Test (COPT), intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using as tools for seroepidemiologic studies. COPT and ELISA were performed after treatment to known their utility when impact of chemotherapy must be assessed. One hundred sixty five persons were followed up 3, 6, 9 and 12 months after treatment. The mean sensitivity of CPT studied by age groups was 95.6% which is very important considering that 88.4% of the studied population excreted less than 100 egg/gr of feces, while sensitivity of intradermal test was 58.2%. Children showed the highest ractivity to COPT. When treatment is effective, COPT reactivity progressively disminish until become negative one year later. In the non cure group, the COPT reactivity disminished but never below 20%. ELISA-SEA did not modify one year after treatment. Effort should be made to isolate fractions of eggs Schistosoma mansoni whose antibodies disappear after treatment.

Post-traumatic mutism in children: clinical characteristics, pattern of recovery and clinicopathological correlations.

Among the numerous clinical syndromes observed after severe traumatic head injury, post-traumatic mutism is a disorder rarely reported in adults and not studied in any detail in children. We report seven children between the ages of 3 1/2 and 14 years who sustained severe head injury and developed post-traumatic mutism. We aim to give a precise clinical characterization of this disorder, discuss differential diagnosis and correlations with brain imaging and suggest its probable neurological substrate. After a coma lasting from 5 to 25 days, the seven patients who suffered from post-traumatic mutism went through a period of total absence of verbal production lasting from 5 to 94 days, associated with the recovery of non-verbal communication skills and emotional vocalization. During the first days after the recovery of speech, all patients were able to produce correct small sentences with a hypophonic and monotonous voice, moderate dysarthria, word finding difficulties but no signs of aphasia, and preserved oral comprehension. The neurological signs in the acute phase (III nerve paresis in three of seven patients, signs of autonomic dysfunctions in five of seven patients), the results of the brain imaging and the experimental animal data all suggest the involvement of mesencephalic structures as playing a key role in the aetiology of post-traumatic mutism.

Bimodal magmatism as a consequence of the post-collisional readjustment of the thickened Variscan continental lithosphere (Aiguilles Rouges - Mont Blanc Massifs, Western Alps)

High Precision U-Pb zircon and monazite dating in the Aiguilles Rouges-Mont Blanc area allowed discrimination of three short-lived bimodal magmatic pulses: the early 332 Ma Mg-K Pormenaz monzonite and associated 331 Ma peraluminous Montees Pelissier monzogranite; the 307 Ma cordierite-bearing peraluminous Vallorcine and Fully intrusions; and the 303 Fe-K Mont Blanc syenogranite. All intruded syntectonically along major-scale transcurrent faults at a time when the substratum was experiencing tectonic exhumation, active erosion recorded in detrital basins and isothermal decompression melting dated at 327-320 Ma. Mantle activity and magma mixing are evidenced in all plutons by coeval mafic enclaves, stocks and synplutonic dykes. Both crustal and mantle sources evolve through time, pointing to an increasingly warm continental crust and juvenile asthenospheric mantle sources. This overall tectono-magmatic evolution is interpreted in a scenario of post-collisional restoration to normal size of a thickened continental lithosphere. The latter re-equilibrates through delamination and/or erosion of its mantle root and tectonic exhumation/erosion in an overall extensional regime. Extension is related to either gravitational collapse or back-are extension of a distant subduction zone.

New Horizons in Forensic Imaging: Post Mortem CT Angiography - Benefits and Practical Application.

Puropse/Aim: To learn about the developement of post mortem CT angiography, its indications, benefits, pitfalls and practical application. Content Organization: A. Developement of post mortem CT angiography B. Technical prerequisites C. Practical application of post mortem CT angiography (preparation of the body, injection of contrast agent, examination protocol) D. Indications and benefits (including a comparison with conventional autopsy) E. Interpretation of imaging data (with case demonstrations) F. Artifacts, pitfalls and limitations G. Current and potential future use. Summary: This exhibit demonstrates the developement, application and interpretation of post mortem CT angiography. Teaching points: 1. post mortem CT angiography is feasible and useful for identification of the cause of death 2. depending on the indication it can be superior to autopsy 3. limitations and artifacts need to be known for interpreta

Three-dimensional cholangio-spiral CT demonstration of a post-traumatic bile leak in a child.

Bilioma is a rare complication of traumatic liver injury, and the precise site of bile leak is often difficult to demonstrate with a non-invasive technique. We report a case of post-traumatic bile leak in a 15-year-old girl in whom spiral CT after intravenous cholangiography allowed excellent preoperative demonstration of the extent of the liver rupture and an exact location of the bile leak. We think that spiral-CT cholangiography could be an accurate, non-invasive technique to investigate the biliary system in cases of paediatric liver trauma.

A novel tool for the assessment of pain: validation in low back pain.

BACKGROUND: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. METHODS AND FINDINGS: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. CONCLUSIONS: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.

Ruptured pseudo-aneurysm of a femoral artery in a drug abuser revealed by post-mortem CT angiography.

A 35-year-old drug addict was found dead in a public toilet with a ruptured groin, which was later diagnosed to be a leaking pseudo-aneurysm. Investigation at the scene revealed impressive external hemorrhage related to a groin wound. Post-mortem computed tomography angiography demonstrated an aneurysm of the right femoral artery with leak of contrast liquid. Signs of blood loss were evident at autopsy, and histological examination revealed necrosis and rupture of the pseudo-aneurysm. Toxicological analyses were positive for methadone, cocaine, citalopram, and benzodiazepines. This is the first case report in the literature of a ruptured femoral pseudo-aneurysm with a post-mortem radiological diagnosis.