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Violence in correctional facilities is an important issue for both prisoners and prison staff. Risk assessment instruments have demonstrated their accuracy in predicting the risk of (re) offending and institutional violence in psychiatric settings, but less is known about their ability to predict violent misconduct in prison. The present study applied four risk assessment instruments (Structured Assessment of Protective Factors for violence risk, Historical Clinical Risk Management-20, Psychopathy checklist - Revised, and Violent Risk Appraisal Guide) to 52 violent offenders in a Swiss prison in order to evaluate the instruments' predictive validities. Outcomes were instances of physically violent, other and any misconduct as recorded in prison files during the 12 months following the prisoners' assessments. Approximately 15% of offenders committed physically violent misconduct and approximately 42% committed any misconduct. The results show that mainly dynamic assessment tools are as good predictors of physically violent misconduct as mainly static assessment tools. Targeting dynamic factors could increase the effectiveness of interventions to reduce the risk of physical violence in prison., (© 2018 John Wiley & Sons, Ltd.)

This article explores the impact of neuroscience evidence on how expert reports are perceived and their effects on the decisions made by trial judges. Experimental psychology has demonstrated a number of cognitive effects arising from exposure to neuroimaging data which may bias judgments and lead to (mis)interpretations that can affect decisions. We conducted a study on a sample of 62 Swiss and French judges in order to determine whether their perceptions of the credibility, quality and scientific basis of a psychiatric evaluation of a criminal defendant vary according to whether or not the evaluation includes neuroscientific data. Quantitative analyses were conducted in order to evaluate significant differences between the two conditions (one-way analyses of variance) and moderation and conditional analyses to examine whether the participants' sex and length of professional experience moderated the effect of the conditions. Terminological and thematic analyses were carried out on open questions. Quantitative and qualitative results suggest that the presence of neuroscience data in an expert report affects judges' perceptions of the quality, credibility, and scientificity (reliability, objectivity, scientific basis) of the report, and the persuasiveness of the evidence it provided. Moreover, this phenomenon was stronger in more experienced judges than in less experienced judges., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The way the potential adverse effects are presented during the introduction of a new medication in the context of psychiatric care can be decisive for subsequent care. This issue is approached from the testimonies of patients who have received multiple treatments over a long period of time and by several therapists. After describing the main adverse effects of psychotropic drugs, this article proposes a method to help patients documenting the adverse effects they experienced, in a way which should improve the dialogue with their therapists., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The issue of the credibility of a child's or adolescent's testimony in judicial sexual allegations has already been developed in many articles and books of the scientific literature. This article reports on the expert practices in the field of child psychology and legal psychiatry for credibility expertise in Switzerland. After illustrating the issues at stake in the analysis of various testimonies in the context of a recent trial (the Outreau case), we will describe the Statement Validity Analysis, a credibility assessment methodology recognized by the scientific literature and Swiss case law., Competing Interests: Les auteurs sont responsables de la formation qui est annoncée dans la conclusion de l’article.

Psychiatric treatments often involve numerous partners. The organization of coordination meetings during in-patient admissions is necessary in order to harmonize interventions. The expectations of each partner during such meetings may however differ and some issues that may seem important to some of them may be neglected. In this paper, we report the results of a survey conducted among the various partners involved in psychiatric patient's treatment in order to identify their expectations, the challenges they may have faced and the solutions they would propose. If perfection ca not be warrantied in all situations, taking these elements into account may improve these meetings and allow to better respect the role of each actor while giving to the patient the central role that they should play when defining their treatment., Competing Interests: Les auteurs n’ont déclarer aucun conflit d’intérêt en relation avec le contenu de cet article.

The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning ("Causal Reasoning Analytical Framework for Target discovery"-CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy.

Background: Previous literature suggests that prevalence of cannabis use in the early phase of psychosis is high, and that early psychosis patients are at high-risk for violent behavior. However, the link between cannabis use and violent behavior in early psychosis patients is unclear. We carried out a study on a sample of early psychosis patients, in order to explore the impact of cannabis use on the risk of violent behavior (VB), while taking into account (1) potential confounding factors and, (2) interactions with other dynamic risk factors of VB. Method: In a sample of 265 early psychosis patients, treated at the Treatment and Early Intervention in Psychosis Program (TIPP) in Lausanne, we used logistic regression models to explore the link between various dynamic risk factors of VB [positive symptoms, substance use disorder (drugs including cannabis, alcohol and others drugs), insight, impulsivity, affective instability, and treatment adherence], and VB occurring during treatment. In order to understand hierarchical effects attributable to the combinations of risk factors on VB we conducted a Classification and Regression Tree (CART). Results: Our results show that cannabis use disorder is a risk factor for VB. The associations among risk factors suggest the presence of two patient profiles with an increased rate of VB: the first is composed of patients with cannabis use disorder and impulsivity, and the second of patients combining cannabis use disorder, absence of insight and non-adherence to treatment. The results also show the moderating role of insight and adherence to treatment on the rate of VB in patients with cannabis use disorder. Conclusion: This study suggests that cannabis use disorder is a significant risk factor for VB amongst early psychosis patients, particularly when combined with either impulsivity, lack of insight and non-adherence to treatment. These results suggest that preventive strategies could be developed on the basis of such patient profiles.

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2 ., (© 2017 by the American Diabetes Association.)

Phytoplasmoses such as apple proliferation (AP) and European stone fruit yellows (ESFY) cause severe economic losses in fruit production. A common symptom of both phytoplasma diseases is early yellowing or leaf chlorosis. Even though chlorosis is a well-studied symptom of biotic and abiotic stresses, its biochemical pathways are hardly known. In particular, in this context, a potential role of the senescence-related pheophorbide a oxygenase/phyllobilin (PaO/PB) pathway is elusive, which degrades chlorophyll (Chl) to phyllobilins (PBs), most notably to colorless nonfluorescent Chl catabolites (NCCs). In this work, we identified the Chl catabolites in extracts of healthy senescent apple and apricot leaves. In extracts of apple tree leaves, a total of 12 Chl catabolites were detected, and in extracts of leaves of the apricot tree 16 Chl catabolites were found. The seven major NCC fractions in the leaves of both fruit tree species were identical and displayed known structures. All of the major Chl catabolites were also found in leaf extracts from AP- or ESFY-infected trees, providing the first evidence that the PaO/PB pathway is relevant also for pathogen-induced chlorosis. This work supports the hypothesis that Chl breakdown in senescence and phytoplasma infection proceeds via a common pathway in some members of the Rosaceae family.

Age of onset, callous-unemotional (CU) traits and anger dysregulation have separately been proposed as relevant factors in explaining the heterogeneity of antisocial behaviour (ASB). Taking a dimensional perspective, this study examined the specific contributions and the mutual influences (i.e., interactions) of these three characteristics on specific dimensions of ASB (i.e., criminal behaviours and externalizing symptoms). Assessments were conducted on 536 youths from institutions with the youth psychopathic traits inventory (CU traits), the Massachusetts youth screening instrument-second version (anger dysregulation), the criminology questionnaire (criminal behaviours) and the child behavior checklist (externalizing symptoms), rated by both the youths and their carers. Using Bayes as estimators, the results revealed that the number and frequency of crimes (and, more specifically, damage to property, property offenses and media crimes) were explained by a specific contribution of each factor (age of onset, CU traits and anger dysregulation). Additionally, the interactions between age of onset and CU traits or anger dysregulation were relevant predictors of some types of crimes (i.e., damage to property, property offences and media crimes). Furthermore, when rated by youths, externalizing symptoms were explained by CU traits and anger dysregulation. However, when rated by the carer, anger dysregulation was more important in explaining externalizing symptoms. This study highlights the importance of considering these factors altogether and the value of using a dimensional perspective when examining the structure of ASB in youths. Consequently, future classifications should take into account the mutual account of these characteristics, which were previously studied separately.

Onychomycosis is one of the most common dermatological diseases, primarily caused by dermatophytes, and sometimes, also by yeast and moulds. This study aims to clarify the frequency of isolated pathogens from mycotic toenails in the reference centre of the central Alpine mountain region of South Tyrol, northern Italy. Age and gender differences, types of pathogens and initial therapy used were also investigated. This is a retrospective study from 2004 to 2013 on the files of all patients with suspected onychomycosis in whom a cultural pathogen detection was performed. A total of 1565 patients were studied (943 women; 622 men), with a median age of 55 years. Fungal pathogens could be detected by culture in 49.5%. Significantly more pathogens could be grown in men (63.8%) than in women (39.9%, P < 0.0001). The most common pathogens grown were dermatophytes (53.3%), especially T. rubrum and T. interdigitale, followed by moulds (24.7%) and yeast (22%). Therapies prescribed were topical in 64.2% and systemic in 35.8% of the cases. Topical treatment was more frequent in older patients (P < 0.05). In northern Italy, dermatophytes are the most common causative agents for onychomycosis. Fungal pathogens were more commonly found in men than in women and topical treatment was more frequent in older patients., (© 2016 Blackwell Verlag GmbH.)

Suicide in the mental hospital is first a human tragedy that affects the patients' families and relatives but also touches all medical staff involved. As for suicide prevention, it is a key issue of public health, and the canton of Vaud has made it a top priority of his mental health policy. We will present some epidemiologic data general of suicide and some specific elements to our institution, the Psychiatry Department of the Centre Hospitalier Universitaire Vaudois (DP-CHUV). Then we will show how our institution addresses the issue of suicide prevention through the analysis of so-called « adverse clinical events » and the systematic training of its caregivers., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Neuroscientific evidence is increasingly being used in criminal trials as part of psychiatric testimony. Up to now, "neurolaw" literature remained focused on the use of neuroscience for assessments of criminal responsibility. However, in the field of forensic psychiatry, responsibility assessments are progressively being weakened, whereas dangerousness and risk assessment gain increasing importance. In this paper, we argue that the introduction of neuroscientific data by forensic experts in criminal trials will be mostly be used in the future as a means to evaluate or as an indication of an offender's dangerousness, rather than their responsibility. Judges confronted with the pressure to ensure public security may tend to interpret neuroscientific knowledge and data as an objective and reliable way of evaluating one's risk of reoffending. First, we aim to show how the current socio-legal context has reshaped the task of the forensic psychiatrist, with dangerousness assessments prevailing. In the second part, we examine from a critical point of view the promise of neuroscience to serve a better criminal justice system by offering new tools for risk assessment. Then we aim to explain why neuroscientific evidence is likely to be used as evidence of dangerousness of the defendants. On a theoretical level, the current tendency in criminal policies to focus on prognostics of dangerousness seems to be "justified" by a utilitarian approach to punishment, supposedly revealed by new neuroscientific discoveries that challenge the notions of free will and responsibility. Although often promoted as progressive and humane, we believe that this approach could lead to an instrumentalization of neuroscience in the interest of public safety and give rise to interventions which could entail ethical caveats and run counter to the interests of the offenders. The last part of this paper deals with some of these issues-the danger of stigmatization for brain damaged offenders because of adopting a purely therapeutic approach to crime, and the impact on their sentencing, in particular., (Copyright © 2016. Published by Elsevier Ltd.)

Aim: In the past few years, spectacular progress in neuroscience has led to the emergence of a new interdisciplinary field, the so-called "neurolaw" whose goal is to explore the effects of neuroscientific discoveries on legal proceedings and legal rules and standards. In the United States, a number of neuroscientific researches are designed specifically to explore legally relevant topics and a case-law has already been developed. In Europe, neuroscientific evidence is increasingly being used in criminal courtrooms, as part of psychiatric testimony, nourishing the debate about the legal implications of brain research in psychiatric-legal settings. Though largely debated, up to now the use of neuroscience in legal contexts had not specifically been regulated by any legislation. In 2011, with the new bioethics law, France has become the first country to admit by law the use of brain imaging in judicial expertise. According to the new law, brain imaging techniques can be used only for medical purposes, or scientific research, or in the context of judicial expertise. This study aims to give an overview of the current state of the neurolaw in the US and Europe, and to investigate the ethical issues raised by this new law and its potential impact on the rights and civil liberties of the offenders., Method: An overview of the emergence and development of "neurolaw" in the United States and Europe is given. Then, the new French law is examined in the light of the relevant debates in the French parliament. Consequently, we outline the current tendencies in Neurolaw literature to focus on assessments of responsibility, rather than dangerousness. This tendency is analysed notably in relation to the legal context relevant to criminal policies in France, where recent changes in the legislation and practice of forensic psychiatry show that dangerousness assessments have become paramount in the process of judicial decision. Finally, the potential interpretations of neuroscientific data introduced into psychiatric testimonies by judges are explored., Results: The examination of parliamentary debates showed that the new French law allowing neuroimaging techniques in judicial expertise was introduced in the aim to provide a legal framework that would protect the subject against potential misuses of neuroscience. The underlying fear above all, was that this technology be used as a lie detector, or as a means to predict the subject's behaviour. However, the possibility of such misuse remains open. Contrary to the legislator's wish, the defendant is not fully guaranteed against uses of neuroimaging techniques in criminal courts that would go against their interests and rights. In fact, the examination of the recently adopted legislation in France shows that assessments of dangerousness and of risk of recidivism have become central elements of the criminal policy, which makes it possible, if not likely that neuroimaging techniques be used for the evaluation of the dangerousness of the defendant. This could entail risks for the latter, as judges could perceive neuroscientific data as hard evidence, more scientific and reliable than the soft data of traditional psychiatry. If such neuroscientific data are interpreted as signs of potential dangerousness of a subject rather than as signs of criminal responsibility, defendants may become subjected to longer penalties or measures aiming to ensure public safety in the detriment of their freedom., Conclusion: In the current context of accentuated societal need for security, the judge and the expert-psychiatrist are increasingly asked to evaluate the dangerousness of a subject, regardless of their responsibility. Influenced by this policy model, the judge might tend to use neuroscientific data introduced by an expert as signs of dangerousness. Such uses, especially when they subjugate an individual's interest to those of society, might entail serious threats to an individual's freedom and civil liberties., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Here we present results of studies conducted by the Research Unit of Legal Psychiatry and Psychology of Lausanne about risk assessment and protective factors in the evaluation of violence recidivism. It aims to help experts in considering the relevance and use of tools at their disposal. Particular attention is given to the significance of protective factors and impulsive dimensions, as to the inter-raters process that leads to the final deliberations.

PTH is indicated for the treatment of severe osteoporosis. Elderly osteoporotic patients frequently suffer from protein malnutrition, which may contribute to bone loss. It is unknown whether this malnutrition may affect the response to PTH. Therefore, the aim of the present study was to assess whether an isocaloric low-protein (LP) diet may influence the bone anabolic response to intermittent PTH in 6-month-old female rats. Six-month-old female rats were either pair fed an isocaloric LP diet (2.5% casein) or a normal-protein (NP) diet (15% casein) for 2 weeks. The rats continued on their respective diet while being treated with 5- or 40-μg/kg recombinant human PTH amino-terminal fragment 1-34 (PTH-[1-34]) daily, or with vehicle for 4 weeks. At the end of this period, areal bone mineral density, bone mineral content, microstructure, and bone strength in axial compression of proximal tibia or 3-point bending for midshaft tibia tests were measured. Blood was collected for the determination of IGF-I and osteocalcin. After 4 weeks of PTH-(1-34), the dose-dependent increase of proximal tibia bone mineral density, trabecular microstructure variables, and bone strength was attenuated in rats fed a LP diet as compared with rats on a NP intake. At the level of midshaft tibia cortical bone, PTH-(1-34) exerted an anabolic effect only in the NP but not in the LP diet group. Protein malnutrition was associated with lower IGF-I levels. Protein malnutrition attenuates the bone anabolic effects of PTH-(1-34) in rats. These results suggest that a sufficient protein intake should be recommended for osteoporotic patients undergoing PTH therapy.

Background: Beach volleyball is an intensive sport with high impact on the lumbar spine. Low back pain (LBP) is frequent among elite players. Increased prevalence of pathological changes on magnetic resonance imaging (MRI) in the lumbar spine of elite athletes has been reported., Hypothesis: There is an increased prevalence of disc degeneration and spondylolysis in the MRI of the lumbar spine of professional beach volleyball players., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Twenty-nine fully competitive professional male volleyball players (mean age, 28 years) completed outcomes questionnaires and underwent a complete clinical examination and an MRI of their lumbar spine., Results: Whereas 86% of players suffered from LBP during their career, the incidence of LBP in the last 4 weeks was 35%. Pain rated using a visual analog scale (VAS) averaged 3 points (range, 0-8). Twenty-three of 29 players (79%) had at least 1 degenerated disc of Pfirrmann grade ≥3. The most affected spinal levels were L4-5 in 14 (48%) and L5-S1 in 15 players (52%); both levels were involved in 5 players (17%). Six of 29 (21%) players showed a spondylolysis grade 4 according to the Hollenburg classification; there was evidence of spondylolisthesis in 2 players. There was no significant correlation between LBP and MRI abnormalities., Conclusion: In the lumbar spine MRI of professional beach volleyball players, the prevalence of disc degeneration is 79%. Spondylolysis (21%) is up to 3 times higher compared with the normal population. Abnormal MRI findings did not correlate with LBP, thus MRIs have to be interpreted with caution.

The legislatives evolutions imply an important recourse to the psychiatric expertise in order to evaluate the potential dangerousness of a subject. However, in spite of the development of techniques and tools for this evaluation, the dangerousness assessment of a subject is in practice extremely complex and discussed in the scientific literature. The evolution of the concept of dangerousness to the risk assessment involved a technicisation of this evaluation which should not make forget the limits of these tools and the need for restoring the subject, the meaning and the clinic in this evaluation.

Rodent models of immune-mediated arthritis (RMIA) are the conventional approach to evaluating mechanisms of inflammatory joint disease and the comparative efficacy of antiarthritic agents. Rat adjuvant-induced (AIA), collagen-induced (CIA), and streptococcal cell wall-induced (SCW) arthritides are preferred models of the joint pathology that occurs in human rheumatoid arthritis (RA). Lesions of AIA are most severe and consistent; structural and immunological changes of CIA best resemble RA. Lesion extent and severity in RMIA depends on experimental methodology (inciting agent, adjuvant, etc.) and individual physiologic parameters (age, genetics, hormonal status, etc.). The effectiveness of antiarthritic molecules varies with the agent, therapeutic regimen, and choice of RMIA. All RMIA are driven by overactivity of proinflammatory pathways, but the dominant molecules differ among the models. Hence, as with the human clinical experience, the efficacy of various antiarthritic molecules differs among RMIA, especially when the agent is a specific cytokine inhibitor.

Obesity is a risk factor for breast cancer, and low blood concentrations of adiponectin are associated with high incidence and poor prognosis of breast cancer. However, the molecular mechanisms underlying such inhibitory effects of adiponectin remain to be defined. By using MCF7 cells, we investigated the mechanisms underlying the inhibitory effects of adiponectin on breast cancer cells, particularly in the context of opposing IGF-1-induced proliferation. We found that adiponectin, at 20 and 40 μg/ml, reduced MCF7 cell growth in the absence and presence of IGF-1. These inhibitory effects were primarily the result of the significant increase of cells at G(1)/G(0) phase and concomitant decrease of cells at S phase. In addition, the percentage of apoptotic cells increased more than two-fold. Within 30-min of adiponectin addition, the phosphorylation of AMPKα was sharply elevated, and the level of IGF-1-activated Akt was decreased. Prolonged exposure to adiponectin resulted in reduction of cyclin D1 and cyclin E2 expression. Adiponectin also increased intracellular levels of cAMP and the activity of protein kinase-A (PKA). The inhibitors of PKA completely abolished the adiponectin's effects on cell growth. In conclusion, our studies revealed an important cellular mechanism underlying the relationship between reduced adiponectin concentrations and breast cancer development.

Parkinson's disease (PD) is associated with a reduction of health-related quality of life (HrQoL). Demographic and clinical determinants of HrQoL in PD have been previously investigated, but less is known about its social determinants. Data on HrQoL in Austrian patients with PD are not available. The objective of this cross-sectional survey was to evaluate HrQoL of Austrian patients with PD and to provide a comprehensive analysis of its social and clinical determinants. Outpatients (n = 100) with idiopathic PD were recruited in the Department of Neurology of the University Innsbruck. Clinical status was estimated using the Unified Parkison's Disease Rating Scale (UPDRS). HrQoL was evaluated using a generic instrument, the EuroQol (EQ5D and EQ-VAS). Independent determinants of HrQoL were assessed in multivariate regression analysis. The proportion of PD patients with moderate or severe problems in at least one dimension of the EQ5D was significantly higher than in the general population (90.1 vs. 35.1%, P < 0.001). The mean EQ-VAS score in PD was lower than in the general population (48.9 +/- 19.6 vs. 77.0 +/- 20.8, P < 0.001). Social support (number of household members) was identified as an independent social determinant of HrQoL. Demographic and clinical determinants were age, depression, UPDRS and motor fluctuations. The analysis of determinants of HrQoL showed that a greater attention should be paid to social support and home care. Our data on HrQoL in PD should be considered in the development of new health care programs.

Fetal magnetic resonance imaging is increasingly being used as an adjunct to ultrasound. It allows for better visualization of in utero brain development and intracranial abnormalities (especially cerebral malformations). Hypothalamic hamartoma is a nonneoplastic malformation resembling normal hypothalamic tissue both histologically and on magnetic resonance imaging. Although it is rare, this entity is important to recognize for appropriate management and genetic counseling. We describe a unique patient in whom magnetic resonance imaging of the fetal brain allowed a prenatal diagnosis of Pallister-Hall syndrome.

Objectives: Chronic inflammation is a major risk factor for systemic bone loss leading to osteoporotic fracture and substantial morbidity and mortality. Inflammatory cytokines, particularly tumour necrosis factor (TNF) and interleukin-1 (IL1), are thought to play a key role in the pathogenesis of inflammation-induced bone loss, but their exact roles are yet to be determined., Methods: To determine whether TNF directly triggers bone loss or requires IL1, human TNFalpha mice (hTNFtg) were crossed with mice lacking IL1alpha and IL1beta (IL1(-/-)hTNFtg). Systemic bone architecture was evaluated using CT scanning, static and dynamic bone histomorphometry and serum markers of bone metabolism., Results: hTNFtg mice developed severe bone loss accompanied by a severe distortion of bone microarchitecture. Bone trabeculae were thinner and decreased in numbers, resulting in increased trabecular separation. Histomorphometric analyses revealed strongly increased bone resorption in hTNFtg mice compared with wild-type mice. In contrast, IL1(-/-)hTNFtg mice were fully protected from systemic bone loss despite still developing inflammation in their joints. Lack of IL1 completely reversed increased osteoclast formation and bone resorption in hTNFtg mice and the increased levels of RANKL in these mice. Structural parameters and osteoclast and osteoblast numbers were indistinguishable from wild-type mice., Conclusions: These data indicate that IL1 is essential for TNF-mediated bone loss. Despite TNF-mediated inflammatory arthritis, systemic bone is fully protected by the absence of IL1, which suggests that IL1 is an essential mediator of inflammatory osteopenia.

Background and Purpose: Blood-pool agents are promising in the imaging of small vessels with slow or complex flow. Our aim was to compare blood-pool contrast-enhanced MR angiography (BPCE-MRA) using gadofosveset trisodium (Vasovist) with 3D time-of-flight MRA (TOF-MRA) in the follow-up of intracranial aneurysms after endovascular therapy., Materials and Methods: We included 32 patients with a total of 37 coiled aneurysms. MRAs in the early steady-state phase were performed on a 1.5T scanner within 8 days of digital subtraction angiography (DSA). Two radiologists independently analyzed TOF-MRA and BPCE-MRA images. Consensus was reached by review involving a third neuroradiologist. DSA images were interpreted separately by an interventional radiologist. Findings were assigned to 1 of 3 categories: 1) complete occlusion, 2) residual neck, and 3) residual aneurysm., Results: Follow-up DSA demonstrated 13 complete obliterations (class 1), 13 residual necks (class 2), and 11 residual aneurysms (class 3). Weighted kappa statistics showed substantial concordance of TOF-MRA and DSA (0.664) as well as BPCE-MRA and DSA (0.724) ratings. Comparison between TOF-MRA and BPCE-MRA found excellent agreement (0.818) with only 6 (16.2%) discrepancies. For detecting residual flow, the difference in accuracy of both MRA techniques (83.8% versus 91.9%) was not significant (McNemar, P = 1.000). BPCE-MRA showed a tendency towards higher sensitivity and specificity (91.7% and 92.3%, respectively) compared with TOF-MRA (87.5% and 76.9%)., Conclusions: In classifying the completeness of endovascular cerebral aneurysm therapy, we found that BPCE-MRA and 3D TOF-MRA showed very good agreement. The use of Vasovist did not lead to a significantly increased accuracy of MRA follow-up.

Objective: The objective of this study was to analyse the costs and the situation of care in patients with idiopathic Parkinson's disease (PD) in Austria. Continuously increasing healthcare costs and the fact that the prevalence of PD is expected to double in the next 25 years highlight the importance of health-economic evaluation in PD., Method: Patient survey with 81 patients with idiopathic Parkinson's disease. A bottom-up approach has been used to calculate direct and indirect costs from a societal perspective. Cost-driving factors were identified by multiple regression analysis., Results: The overall costs from the perspective of society was 9280 per patient within a six-month period and consisted of 60% direct costs (5910 ) and 40% indirect costs (3910 ). The major part (59%) of direct costs was paid by the national healthcare. Co-payments of patients were 810 per six-months. The annual nationwide costs of PD in Austria are estimated to be approximately 320 million ., Conclusion: PD is an economic challenge for the Austrian healthcare system. Direct costs account for the most part and are on account of the national healthcare system. In addition, patients bear considerable costs by personal contribution.

Central nervous system (CNS) tumors are the most common solid neoplasms in childhood and the second most common malignancies after leukemia in the pediatric age group. Supratentorial tumors are more common in children younger than 2 years old and in adolescents, whereas in patients between 2 and 12 years of age brain tumors originating in the posterior fossa dominate. This implies a relationship between the type of tumor, its location and the age of the patient, which has to be considered in differential diagnoses. Medulloblastoma represents the most common malignant brain tumor in childhood. In the posterior fossa medulloblastomas are approximately as frequent as astrocytomas. Supratentorial astrocytomas are by far the main tumor type. In this report some typical CNS neoplasms in children are discussed and their neuroradiological features are demonstrated.

Unlabelled: In a substudy of the HORIZON pivotal fracture trial, in which yearly intravenous zoledronic acid 5 mg was found to significantly reduce risk of various fracture types in patients with postmenopausal osteoporosis, 152 patients underwent bone biopsy. Zoledronic acid reduced bone turnover by 63% and preserved bone structure and volume, with evidence of ongoing bone remodeling in 99% of biopsies obtained., Introduction: In the HORIZON pivotal fracture trial (PFT), enrolling 7,736 women with postmenopausal osteoporosis, three annual intravenous infusions of the bisphosphonate zoledronic acid (5 mg) significantly reduced morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively. Whereas 79% of patients received zoledronic acid/placebo only (stratum I, n = 6,113), 21% received concomitant treatment with other antiresorptive drugs, excluding other bisphosphonates, PTH, and strontium (stratum II, n = 1,652)., Materials and Methods: To determine effects on bone remodeling and bone architecture, iliac crest bone biopsies were obtained in 152 patients on active treatment or placebo at 3 yr after double tetracycline labeling. In five patients, only qualitative histology was performed, leaving 147 biopsy cores (79 on active treatment and 68 on placebo) for microCT analysis and histomorphometry., Results: Analysis of bone structure by microCT revealed higher trabecular bone volume (BV/TV) in the zoledronic acid group (median, 16.6% versus 12.8%; p = 0.020). In addition, patients treated with zoledronic acid exhibited higher trabecular numbers (p = 0.008), decreased trabecular separation (p = 0.011), and a trend toward improvement in connectivity density (p = 0.062), all indicating better preservation of trabecular structure after treatment with zoledronic acid. Qualitative analysis revealed presence of tetracycline label in 81 of 82 biopsies from patients on zoledronic acid and all 70 biopsies from placebo patients, indicative of continued bone remodeling. No bone pathology was observed. Zoledronic acid induced a 63% median (71% mean) reduction of the activation frequency (Ac.f; p < 0.0001) and reduced mineralizing surface (MS/BS; p < 0.0001) and volume referent bone formation rate (BFR/BV) versus placebo, indicating reduced bone turnover. Mineral appositional rate was higher in the zoledronic acid group (p = 0.0002), suggesting improved osteoblast function compared with placebo. Mineralization lag time was similar in the two groups, whereas osteoid volume (OV/BV; p < 0.0001) and osteoid thickness (O.Th; p = 0.0094) were lower in zoledronic acid-treated patients, indicating normal osteoid formation and mineralization of newly formed bone. Concomitant administration of other antiresorptive osteoporosis therapies (e.g., raloxifene, tamoxifen, tibolone, ipriflavone) did not significantly alter the tissue level response to zoledronic acid., Conclusions: Annual dosing for 3 yr with zoledronic acid 5 mg intravenously resulted in a median 63% (mean, 71%) reduction of bone turnover and preservation of bone structure and mass without any signs of adynamic bone. Concomitant treatment with other osteoporosis therapies did not significantly affect the bone response to zoledronic acid.

The new text of the Swiss penal code, which entered into effect at the beginning of 2007, has many incidences on the practice of the psychiatrists realizing expertises in the penal field or engaged in the application of legal measures imposing a treatment. The most notable consequences of this text are, on the one hand, a new definition of the concept of penal irresponsibility which is not necessarily any more related to a psychiatric diagnosis and, on the other hand, a new definition of legal constraints that justice can take to prevent new punishable acts and which appreciably modifies the place of the psychiatrists in the questions binding psychiatric care and social control.

Obesity is one of the well-established risk factors for endometrial cancer. Recent clinical studies have demonstrated that circulating adiponectin concentrations are inversely correlated with the incidence of endometrial carcinoma. Such epidemiological findings are consistent with the paradoxical observations that adiponectin levels are reduced in obesity. This study investigated the direct effects of adiponectin on two endometrial carcinoma cell lines, HEC-1-A and RL95-2. These cell lines express both variants of adiponectin receptors, adipo-R1 and adipo-R2. Adiponectin treatment leads to suppression of cell proliferation in both cell types, which is primarily due to the significant increase of cell populations at G(1)/G(0)-phase and to the induction of apoptosis. The inhibition of growth in these two cell lines appears to be mediated by different signaling pathways. Although adiponectin treatment markedly increases the phosphorylation (Thr172) of AMP-activated protein kinase alpha in both HEC-1-A and RL95-2 within 30 min, prolonged exposure (48 h) leads to inactivation of Akt as well as reduction of cyclin D1 protein expression in HEC-1-A cells. In contrast, similar treatment of RL95-2 cells with adiponectin, while having no effects on Akt activity and cyclin D1 expression, causes a decrease in cyclin E2 expression and the activity of mitogen-activated kinase (p42/44). We conclude that adiponectin exerts direct anti-proliferative effects on HEC-1-A and RL95-2 cells by inducing cell cycle arrest and apoptosis. Depending on the genotypes of the endometrial cancer cells, the inhibitory effects of adiponectin are associated with the reduction of different pro-growth regulators of cell cycle and signaling proteins. Our study thus provides a cellular mechanism underlying the linkages between endometrial cancer and obesity.

Blocking TNF effectively inhibits inflammation and structural damage in human rheumatoid arthritis (RA). However, so far it is unclear whether the effect of TNF is a direct one or indirect on up-regulation of other mediators. IL-1 may be one of these candidates because it has a central role in animal models of arthritis, and inhibition of IL-1 is used as a therapy of human RA. We removed the effects of IL-1 from a TNF-mediated inflammatory joint disease by crossing IL-1alpha and beta-deficient mice (IL-1-/-) with arthritic human TNF-transgenic (hTNFtg) mice. Development of synovial inflammation was almost unaffected on IL-1 deficiency, but bone erosion and osteoclast formation were significantly reduced in IL-1-/-hTNFtg mice, compared with hTNFtg mice based on an intrinsic differentiation defect of IL-1-deficient monocytes. Most dramatically, however, cartilage damage was absent in IL-1-/-hTNFtg mice. Chimera studies revealed that protection of cartilage is based on the loss of IL-1 on hematopoietic, but not mesenchymal, cells, leading to decreased expression of ADAMTS-5 and MMP-3. These data show that TNF-mediated cartilage damage is completely and TNF-mediated bone damage is partially dependent on IL-1, suggesting that IL-1 is a crucial mediator for inflammatory cartilage and bone degradation.

Development of the aorta takes place during the third week of gestation. It is a complex process that can lead to a variety of congenital variants and pathological anomalies. In diagnostic and interventional radiology, knowledge of aortic abnormalities and variant branching sequence is crucially important. This article gives a systematic overview of anatomical variability of the aorta.

Background: Bisphosphonates exhibit direct antitumor activity in animal models, but only at high doses that are incompatible with the clinical dosing regimens approved for the treatment of cancer patients with skeletal metastases. We compared the antitumor effects of clinical dosing regimens of the bisphosphonates zoledronic acid and clodronate in a mouse model of bone metastasis., Methods: Mice (n = 6-10 per group) were treated with zoledronic acid, clodronate, or vehicle starting before (preventive protocols) or after (treatment protocols) intravenous injection with human B02/GFP.2 breast cancer cells, which express green fluorescent protein (GFP) and luciferase and metastasize to bone. Zoledronic acid was given as daily, weekly, or single doses at a cumulative dose of 98-100 microg/kg body weight, equivalent to the 4-mg intravenous dose given to patients. Clodronate was given as a daily dose (530 microg/kg/day), equivalent to the daily 1600-mg oral clinical dose given to patients. Bone destruction was measured by radiography, x-ray absorptiometry or tomography, and histomorphometry (as the ratio of bone volume to tissue volume). Skeletal tumor burden was measured by histomorphometry (as the ratio of tumor burden to soft tissue volume [TB/STV]) and luciferase activity. All statistical tests were two-sided., Results: In treatment protocols, daily clodronate was less effective at decreasing the TB/STV ratio than daily (53% versus 87%, difference = 34%, 95% confidence interval [CI] = 16% to 44%, P < .001) or weekly (53% versus 90%, difference = 37%, 95% CI = 19% to 46%, P < .001) zoledronic acid-dosing regimens. Compared with vehicle, a single dose of zoledronic acid decreased tumor burden by only 16% (95% CI = 9% to 22%, P < .001). In preventive protocols, daily clodronate and daily or weekly zoledronic acid decreased the TB/STV ratio by 49% (95% CI = 40% to 57%, P = .006), 83% (95% CI = 68% to 98%, P < .001), and 66% (95% CI = 47% to 84%, P < .001), respectively, compared with vehicle, whereas a single dose of zoledronic acid decreased tumor burden by only 13% (95% CI = -2% to 28%, P = .84). Mice treated with a daily preventive regimen of clodronate or with a daily or weekly preventive regimen of zoledronic acid showed a decreased B02/GFP.2 cell tumor burden compared with vehicle, whereas a single preventive dose of zoledronic acid had no effect., Conclusion: Daily or repeated intermittent therapy with clinical doses of bisphosphonates inhibits skeletal tumor growth in a mouse model.

Morphogenesis and remodeling of bone involve synthesis of bone matrix by osteoblasts and coordinate resorption of bone by osteoclasts. Defective bone remodeling caused by altered osteoclast activity underlies a multitude of osteopenic disorders. Receptor activator of NF-kappaB (RANK) and its ligand RANKL have been identified as essential factors involved in osteoclast development and bone remodeling, but their mechanism and interacting factors have not been fully characterized. Here we report that the molecular adapter Grb-2-associated binder-2 (Gab2) associates with RANK and mediates RANK-induced activation of NF-kappaB, Akt and Jnk. Inactivation of the gene encoding Gab2 in mice results in osteopetrosis and decreased bone resorption as a result of defective osteoclast differentiation. We also show that Gab2 has a crucial role in the differentiation of human progenitor cells into osteoclasts. We have thus identified a new, key regulatory scaffold molecule, Gab2, that controls select RANK signaling pathways and is essential for osteoclastogenesis and bone homeostasis.

Objective: Increased osteoclast activity is a key factor in bone loss in rheumatoid arthritis (RA). This suggests that osteoclast-targeted therapies could effectively prevent skeletal damage in patients with RA. Zoledronic acid (ZA) is one of the most potent agents for blocking osteoclast function. We therefore investigated whether ZA can inhibit the bone loss associated with chronic inflammatory conditions., Methods: Human tumor necrosis factor (TNF)-transgenic (hTNFtg) mice, which develop severe destructive arthritis as well as osteoporosis, were treated with phosphate buffered saline, single or repeated doses of ZA, calcitonin, or anti-TNF, at the onset of arthritis., Results: Synovial inflammation was not affected by ZA. In contrast, bone erosion was retarded by a single dose of ZA (-60%) and was almost completely blocked by repeated administration of ZA (-95%). Cartilage damage was partly inhibited, and synovial osteoclast counts were significantly reduced with ZA treatment. Systemic bone mass dramatically increased in hTNFtg mice after administration of ZA, which was attributable to an increase in trabecular number and connectivity. In addition, bone resorption parameters were significantly lowered after administration of ZA. Calcitonin had no effect on synovial inflammation, bone erosion, cartilage damage, or systemic bone mass. Anti-TNF entirely blocked synovial inflammation, bone erosion, synovial osteoclast formation, and cartilage damage but had only minor effects on systemic bone mass., Conclusion: ZA appears to be an effective tool for protecting bone from arthritic damage. In addition to their role in antiinflammatory drug therapy, modern bisphosphonates are promising candidates for maintaining joint integrity and reversing systemic bone loss in patients with arthritis.

Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow composition revealed a total absence of marrow adipocytes in HSD1(-/-) mice. Cells from Wt and HSD1(-/-) mice exhibited similar growth rates as well as similar levels of production of osteoblastic markers. The adipocyte-forming capacity of in vitro cultured bone marrow stromal cells and trabecular osteoblasts was similar in HSD1(-/-) and Wt mice. In conclusion, our results suggest that 11betaHSD1 amplification of intracellular GC actions in mice may be required for bone marrow adipocyte formation, but not for bone formation. The clinical relevance of this observation remains to be determined.

The objective of the study was to investigate bone strength at four different skeletal sites in a chronic animal model of urinary diversion. Young male Wistar rats (120) were allocated randomly to four groups undergoing ileocystoplasty; ileocystoplasty and resection of the ileocecal segment; colocystoplasty; or sham operation (controls). After 8 months the lumbar vertebrae, femora, and tibiae were harvested at necropsy. Bone strength was assessed biomechanically at four different skeletal sites: vertebra L3, femoral middiaphysis, femoral neck, and distal femoral metaphysis. Bone mass and architecture were assessed using standard static histomorphometry of the proximal tibial metaphysis (trabecular bone volume [BV/TV]; trabecular number [Tb.N]) and ash weight. Statistically significant differences of biomechanical parameters between groups were observed at three skeletal sites with corresponding changes in tibial histomorphometry. Isolated ileocystoplasty resulted in decreased maximum load values of L3 (-16.4%; p < 0.0035) and a substantial reduction in tibial BV/TV (-34.7%; p < 0.05). Ileocystoplasty combined with resection of the ileocecal segment led to a significant loss of bone strength of L3 (-32.4%; p < 0.0015) and a dramatic reduction of tibial BV/TV (-45.9%; p < 0.01). Loss of tibial metaphyseal bone mass was predominantly caused by a decrease in Tb.N. (p < 0.01). Colonic augmentation had no significant effect on bone strength or histomorphometric values. In conclusion, this is the first experimental study to demonstrate the relevance of histomorphometrically proven bone loss after enterocystoplasty in terms of biomechanical variables.