Disparate response of articular- and auricular-derived chondrocytes to oxygen tension

Purpose/Aim: To determine the effect of reduced (5%) oxygen tension on chondrogenesis of auricular-derived chondrocytes. Currently, many cell and tissue culture experiments are performed at 20% oxygen with 5% carbon dioxide. Few cells in the body are subjected to this supra-physiological oxygen tension. Chondrocytes and their mesenchymal progenitors are widely reported to have greater chondrogenic expression when cultured at low, more physiological, oxygen tension (1–7%). Although generally accepted, there is still some controversy, and different culture methods, species, and outcome metrics cloud the field. These results are, however, articular chondrocyte biased and have not been reported for auricular-derived chondrocytes. Materials and Methods: Auricular and articular chondrocytes were isolated from skeletally mature New Zealand White rabbits, expanded in culture and differentiated in high density cultures with serum-free chondrogenic media. Cartilage tissue derived from aggregate cultures or from the tissue engineered sheets were assessed for biomechanical, glycosaminoglycan, collagen, collagen cross-links, and lysyl oxidase activity and expression. Results: Our studies show increased proliferation rates for both auricular and articular chondrocytes at low (5%) O₂ versus standard (20%) O₂. In our scaffold-free chondrogenic cultures, low O₂ was found to increase articular chondrocyte accumulation of glycosaminoglycan, but not cross-linked type II collagen, or total collagen. Conversely, auricular chondrocytes accumulated less glycosaminoglycan, cross-linked type II collagen and total collagen under low oxygen tension. Conclusions: This study highlights the dramatic difference in response to low O₂ of chondrocytes isolated from different anatomical sites. Low O₂ is beneficial for articular-derived chondrogenesis but detrimental for auricular-derived chondrogenesis.     

L’examen clinique psychiatrique standardisé pour l’étudiant,c’est possible !

The systematic approach and the examination of patients are central for the teaching of medicine. However, a very large proportion of medical students are not taught to examine patients with psychiatric disorders. This article summarizes the didactic reflection behind the development of a guide for medical observation in psychiatry for medical students. This guide was built from the framework of a classic medical examination (history of illness, biography, etc.). It also incorporates the different steps from the Mental Status Examination (MSE) as well as questions from several standardized tools. This guide document is intended to be simple and easy to use (check box system) to facilitate the interviews of medical students and residents in psychiatry. Master the clinical examination is an essential step in the process of learning medicine that will then allow to integrate, with experience, the flexibility and adaptability necessary for a psychiatric interview.     

fMRI capture of auditory hallucinations: Validation of the two‐steps method

Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two‐steps strategy including (1) multivariate data‐driven analysis of per‐hallucinatory fMRI recording and (2) selection of the components of interest based on a post‐fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two‐steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination‐related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis‐driven and data‐driven analysis methods (as used in the two‐steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two‐steps method with the online button‐press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory‐related networks detected using the two‐steps method on two independent samples. By validating the two‐steps method, we advance toward the possible transfer of such technology to new image‐based therapies for hallucinations. Hum Brain Mapp 38:4966–4979, 2017. © 2017 Wiley Periodicals, Inc.     

Targeting Improves MSC Treatment of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), which includes Crohn''s disease and ulcerative colitis, is an inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs) have the potential to rescue IBD owing to their immunosuppressive capabilities and clinical studies have shown positive influence on intestinal graft versus host disease. We demonstrate here a new method to coat MSCs with antibodies against addressins to enhance their delivery to the colon and thereby increase the therapeutic effectiveness. Bioluminescence imaging (BLI) demonstrated that vascular cell adhesion molecule antibody (Ab)-coated MSCs (Ab_VCAM-1- MSCs) had the highest delivery efficiency to inflamed mesenteric lymph node (MLN) and colon compared to untreated MSCs, Ab_isotype-MSCs, and Ab_MAdCAM-MSCs. Therapeutically, when mice with IBD were injected with addressin Ab-coated MSCs, they showed dramatically improved survival rates, higher IBD therapeutic scores, and significantly improved body weight gain compared to mice injected with MSCs only, isotype Ab, free Ab plus MSCs, or vehicle-only controls. These data demonstrate that anti-addressin Ab coating on MSC increased cell delivery to inflamed colon and increased the efficacy of MSC treatment of IBD. This is the first study showing an increased therapeutic efficacy when stem cells are first coated with antibodies specifically target them to inflamed sites.     

The effect of learning to drum on behavior and brain function in autistic adolescents

This current study aimed to investigate the impact of drum training on behavior and brain function in autistic adolescents with no prior drumming experience. Thirty-six autistic adolescents were recruited and randomly assigned to one of two groups. The drum group received individual drum tuition (two lessons per week over an 8-wk period), while the control group did not. All participants attended a testing session before and after the 8-wk period. Each session included a drumming assessment, an MRI scan, and a parent completing questionnaires relating to the participants’ behavioral difficulties. Results showed that improvements in drumming performance were associated with a significant reduction in hyperactivity and inattention difficulties in drummers compared to controls. The fMRI results demonstrated increased functional connectivity in brain areas responsible for inhibitory control, action outcomes monitoring, and self-regulation. In particular, seed-to-voxel analyses revealed an increased functional connectivity in the right inferior frontal gyrus and the right dorsolateral prefrontal cortex. A multivariate pattern analysis demonstrated significant changes in the medial frontal cortex, the left and right paracingulate cortex, the subcallosal cortex, the left frontal pole, the caudate, and the left nucleus accumbens. In conclusion, this study investigates the impact of a drum-based intervention on neural and behavioral outcomes in autistic adolescents. We hope that these findings will inform further research and trials into the potential use of drum-based interventions in benefitting clinical populations with inhibition-related disorders and emotional and behavioral difficulties.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and social interactions as well as a range of restricted, repetitive interests, activities, and behaviors (1). Over recent decades, incidence estimates for ASD have increased (2), with a prevalence of 1 in 59 children in the United States (3) and over 600,000 people in the United Kingdom, which is equivalent to a population prevalence of ∼1% (4, 5). In this context of increased autism prevalence, there is an existing need to develop interventions that offer new insights and perspectives and help address the specifically high demand for services for autistic adolescents and young adults (6). [The term “autistic” is used throughout this paper because of a large percentage of the UK autism community’s preference for the identity-first construction (e.g., “autistic person”) over the person-first phrase (e.g., “person with autism”) (7).] Indeed, autistic young people often face discontinuity in care provision in the transitionary period from child and adolescent services to adult services, just when their care needs are most pressing, making their transition into adulthood particularly difficult (8). In particular, mismatches across services, such as differences in eligibility criteria or age cutoffs, mean that many autistic young adults fall through the care gap after exiting high school (8). Autistic individuals are particularly vulnerable during this period because they often face high unemployment rates, increased levels of comorbid psychiatric diagnoses such as anxiety and depression, and, more broadly, greater reliance on assistance from others when it comes to carrying out adulthood-related daily activities (9–11).A growing body of research suggests that key social domains of the ASD symptomatology may be related to atypical executive functioning (12, 13). Inhibitory control, one of the core executive functions (EFs), corresponds to the ability to delay the onset of behavioral responses, or withhold behaviors that are prepotent but contextually inappropriate (14, 15). It works in concert with other EFs, such as cognitive flexibility and working memory, to exert top-down control on behavioral responses, enable self-regulation, and help navigate social relationships, therefore supporting transition into adulthood and independent living (16, 17). More specifically, it is thought that atypical inhibitory control in autism may underlie significant strengths but may also exacerbate key features of the ASD symptomatology, such as struggling with change and uncertainty, or having difficulty interpreting social cues (18–21). Impaired performance on inhibitory control tasks is frequent in autistic individuals (12, 13, 22, 23). In particular, it has been associated with severe restricted and repetitive behaviors (19, 24, 25), as well as a deficit in proactive response slowing [the ability to slow the initiation of a behavioral response in preparation for stopping during conditions of uncertainty (19)]. At the neuroimaging level, prior studies have revealed atypical recruitment of frontal regions in autistic adolescents (20), and impaired functional connectivity (FC) of the inferior frontal junction, key regions for inhibitory control, in autistic children (26).Autistic individuals often report being preoccupied with certain topics (27) and struggling with anxiety and anger management (28, 29). In a study by Van Hees et al. (30), higher-education autistic students described feeling overwhelmed by the demands placed on them while facing significant difficulties with planning, information processing, time management, organizational skills, and sensory overload. These difficulties may reflect impaired attention and inhibition abilities, complementary processes that allow individuals to pursue the achievement of a particular goal while remaining flexibly responsive to environmental demands (21, 31). A research study on a population-based twin sample of 17,000 children (9 y to 12 y old) concluded that the vast majority of children with ASD traits also exhibit cooccurring attention deficit and hyperactivity disorder (ADHD) traits (32). More specifically, the authors demonstrated that 82% of the boys and 95% of the girls with high ASD traits on all three ASD domains (social impairments, communication impairments, and restricted repetitive behaviors and interests) exhibited difficulties on at least one of the three ADHD domains (attentional difficulties, hyperactivity, and impulsivity). Additionally, they reported that repetitive and restricted behaviors in ASD correlated with ADHD domains, particularly with impulsivity and attentional difficulties. This is in line with a previous twin study in adults, which reported the highest phenotypic and genetic overlap between ADHD traits and “nonsocial” autistic-like traits such as attention switching difficulties (33).Music has long been known to promote cognitive and emotional wellbeing in both clinical and healthy populations (34, 35). Rhythm-based musical training, in particular, has been shown to enhance higher-order cognition and motor control (31). There is growing evidence that activities designed to improve beat synchronization skills may provide an effective approach to developing neurological processes that underpin self-regulation and EF skills (36). Indeed, EF deficits have been linked with poor rhythm perception in children (37) and poor sensorimotor synchronization in young adults (38). Using the Integrated Visual and Auditory Plus Continuous Performance Test (39), Slater et al. (31) highlighted that drumming practice is associated with better scores in inhibitory control and selective attention in adult percussionists compared to nonmusicians.More specifically, learning to drum requires error monitoring and temporal accuracy and therefore both attentional and inhibitory control (31, 40). In a recent study, Lowry et al. (40) used a mixed-methods analysis to investigate behavioral changes in children with emotional and behavioral difficulties, after learning to drum. Following drum training, the participants displayed enhanced attentional focus and reduced hyperactivity and peer problems (40). These results concur with Draper et al.’s (41) recent findings showing that drumming improves motor control and attentional focus and reduces emotional and peer problems in autistic children. It is important to note that motor control is particularly relevant in the context of ASD. Indeed, recent studies have consistently demonstrated motor impairments across the autism spectrum (42, 43), including gross and fine motor difficulties (44, 45) and delays with motor planning (46). Sokhadze et al. (47) showed that ∼80% of autistic individuals also present with clumsiness or motor dyspraxia, which can manifest as having difficulty with motor coordination as well as concentration, planning, and organization. These difficulties may impact the individual’s ability to carry out daily activities, which, in turn, can lead to rejection from peers and social isolation (48). Similarly, motor impairments in balance, motor accuracy, and object manipulation scores have been reported to be predictive of social dysfunction in young autistic boys (49). In this context, learning to drum could be regarded as particularly beneficial because it involves not only musicality but also the development of multimodal skills such as body coordination, sensorimotor integration, and cardiovascular exercise processes (50). Additionally, it is appealing and accessible to everyone regardless of age, gender, ethnicity, or musical background (51, 52).In our proof-of-concept study, Amad et al. (53) showed that the brain is capable of neuroplastic modifications through drum-based practice in neurotypical adolescents. In particular, changes in FC were observed post drum training in brain regions known to exhibit atypical functioning in autism, such as areas associated with motor skills and the mirror neuron system.In the present study, we investigated the impact of drum training on brain function in 36 autistic adolescents who were split into two age- and gender-matched groups: a drum group (n = 19), who were evaluated before and after learning to drum, and a control group (n = 17), who were also evaluated longitudinally but with no intervention. We explored behavioral outcomes related to drum practice in this clinical population and examined their association with changes in FC between the two groups (i.e., drum group vs. control group) over time (i.e., before vs. after drum training).We hypothesized that drumming performance would improve in the drum group over time, while no improvement would be observed in the control group. Furthermore, we hypothesized that changes in hyperactivity, attentional difficulties, problem behaviors, and repetitive and restricted behaviors would be observed in the drum group. We also hypothesized that cooccurring changes in FC in brain areas responsible for attentional focus and inhibitory control would be identified following drum training.     

Dietary survey “HEUREKA” 1991: Dietary intake of a Swiss collective assessed by a self-administered 24-hour recall questionnaire

Summary Food consumption (divided into 10 food groups) as well as energy and main nutrient intake of a Swiss collective (n=3653) aged 7 years and older was studied. The caloric density was much improved for all five age groups considered as compared with findings in former studies. Carbohydrates gained and alcohol lost significance as main energy suppliers. These results indicate a positive trend in the dietary habits of the collective and suggest an improvement in the dietary habits of the Swiss population as a whole.

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Zusammenfassung Der nach 10 Lebensmittelgruppen aufgeschlüsselte Lebensmittelverzehr sowie die Aufnahme an Energie und Hauptnährstoffen wurden für ein Schweizer Kollektiv (n=3653) im Alter von 7 jahren und mehr untersucht. Die Energie-Nährstoffrelation war im Vergleich zu früheren. Studien für alle 5 betrachteten Altersklassen günstiger. Kohlenhydrate haben als Energielieferanten an Bedeutung gewonnen. Alkohol verloren. Diese Resultate weisen auf ejnen positiven. Trend in den Ernährungsgewohnheiten des Kollektives hin, und deuten eine Verbesserung der Ernährungsgewohnheiten der Schweize Bevölkerung an.

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Résumé La consommation alimentaire répartie sur 10 groupes d'aliments, l'apport énergétique et des nutriments principaux ontété étudiés pour un collectif Suisse (n=3653) agé 7 ans et plus. La part relative des nutriments dans la ration énergétique a été plus favorable pour toutes cing classes d'âge considerées par rapport aux études précédentes. Les glucides ont prit de l'importance et l'alcool a perdu de l'importance comme source d'énergie. Ces résultats indiquent une tendance positive des habitudes alimentaires du collectif et suggèrent une amélioration des habitudes alimentaires de toute la population suisse.

     

Psychogenic non-epileptic seizures treated with guided transcranial direct current stimulation: A case report

Introduction

Psychogenic non-epileptic seizures (PNES) are paroxysms of either altered subjective or objective manifestations that may mimic epileptic seizures (ES), without abnormal neuronal epileptiform activity. In this report, we present the case of a 39-year-old woman with PNES and functional movement disorders, who was successfully treated with neuro-guided transcranial direct current stimulation (tDCS).

Imaging of mesenchymal stem cell transplant by bioluminescence and PET.

Dynamic measurements of infused stem cells generally require animal euthanasia for single-time-point determinations of engraftment. In this study, we used a triple-fusion reporter system for multimodal imaging to monitor human mesenchymal stem cell (hMSC) transplants. METHODS: hMSCs were transduced with a triple-fusion reporter, fluc-mrfp-ttk (encoding firefly luciferase, monomeric red fluorescent protein, and truncated herpes simplex virus type 1 sr39 thymidine kinase) by use of a lentiviral vector. Transduced cells were assayed in vitro for the expression of each functional component of the triple-fusion reporter. Transduced and control hMSCs were compared for their potential to differentiate into bone, cartilage, and fat. hMSCs expressing the reporter were then loaded into porous, fibronectin-coated ceramic cubes and subcutaneously implanted into NOD-SCID mice along with cubes that were loaded with wild-type hMSCs and empty cubes. Mice were imaged repeatedly over 3 mo by bioluminescence imaging (BLI), and selected animals underwent CT and PET imaging. RESULTS: Osteogenic, adipogenic, and chondrogenic potential assays revealed retained differentiation potentials between transduced and wild-type hMSCs. Signals from the cubes loaded with reporter-transduced hMSCs were visible by BLI over 3 mo. There was no signal from the empty or wild-type hMSC-loaded control cubes. PET data provided confirmation of the quantitative estimation of the number of cells at one spot (cube). Cubes were removed from some animals, and histologic evaluations showed bone formation in cubes loaded with either reporter-transduced or wild-type hMSCs, whereas empty controls were negative for bone formation. CONCLUSION: The triple-fusion reporter approach resulted in a reliable method of labeling stem cells for investigation in small-animal models by use of both BLI and small-animal PET imaging. It has the potential for translation into future human studies with clinical PET.