Title: Body composition in patients with idiopatic inflammatory myopathies Objectives: The aim of this study was to compare selected parameters of body composition in patients with idiopathic inflammatory myopathies (IIM) with age- and sex-matched healthy controls (HC). Another objective was to evaluate the effect of selected clinical parameters in patients with IIM on the detectedvariability of the parameters of body composition and on physical activity of patients. Methods: The research sample consisted of 84 individuals (54 IIM, 30 HC). In anthropometry, we measured: body height (cm), weight (kg) and BMI (kg/m2 ). Using bioelectrical impedance analysis BIA 2000-M we obtained values: total body water (TBW in%), muscle mass (LBM in kg), body fat (BF in%) cell mass of lean body mass (BCM of FFM in%), and the proportion of extracellular/intracellular matrix (ECM/BCM). Using Lunar series iDXA we obtained values: muscle mass (LBM in kg), body fat (BF in %), bone mineral density (BMD in g/cm3 ), and visceral fat (Visceral in kg). To these measured values we added a questionnaire on physical activity Human Acitvity Profile (HAP). Statistics: T-test, Mann Whitney U test, Cohen's d, and Partialeta-squared. Results: Selected values (mean ± SD): body height: IIM 164.7 ± 9.1 cm, HC 170.3 ± 7 cm; body weight:...

Introduction: This work focused on two rare rheumatic diseases systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM). Skin and musculoskeletal involvement in patients with SSc leads to disability and loss of functional abilities of an individual. Chronic inflammation of the muscles, subsequent muscle atrophy and permanent muscle damage in patients with IIM are the cause of a decrease in muscle strength and endurance. Moreover, both diseases also affect internal organs and manifest often with impaired lung and heart function. All of these involvements in both diseases lead to a decrease in the quality of life of patients. The data on efficacy of non-pharmacological care in SSc and IIM are very limited due to the heterogeneity of the studied interventions and/or outcomes. However, due to limitations in pharmacological therapy, non-pharmacological interventions could help bring patients back into their everyday life and improve their quality of life. Objectives: The main objective of this project was to evaluate the impact of physical intervention on disease course and activity in a substantial number of SSc and IIM patients, with the aim of minimizing the limitations of available studies, thereby improving the quality and reliability of the obtained results. Methods: This is a...

Background. CoGNIT is a computerized test battery for cognitive assessment, used in diagnosing and treating patients with idiopathic normal pressure hydrocephalus (INPH). The disorder causes symptoms of dementia, among other things. Apart from other diseases with similar symptoms, like Alzheimer’s, INPH can be countered. CoGNIT is performed by a patient before and after drainage of cerebrospinal fluid. If a significant improvement in cognition is detected after the extraction, the patient receives shunt surgery which reduces all symptoms. The test battery is long and tedious, which makes it difficult for people with cognitive impairments to complete. Objectives. The objectives of this study are to rework original CoGNIT with carefully selected game design elements and analyze the effects of the alteration on performance and user experience. If users perform better in a gamified environment, the validity of gathered data will have improved as the data should better reflect their cognitive capabilities. Another objective is to introduce gamification to the medical field. Methods. Game design elements were picked and designed based on suitability for elderly people and with the impairments of INPH patients in mind. A gamified prototype was developed and put to test with healthy individuals against the original version in an experiment. The effects of gamification on performance was examined by comparing resulting score values from both versions of the test. Participants also filled in a questionnaire as proxy for the test’s target group, meaning that questions were answered with how the participants expected a cognitively impaired person to answer. Answers were used to investigate the effect of gamification ofuser experience. Results. The gamified version of CoGNIT shows an improvement in test segments regarding attention, psychomotor speed, executive function, and manual dexterity, but a negative inclination in segments regarding memory. Results from the user experience questionnaire indicates that the gamified version feels less dramatic, more playful, less "test-like" and less tedious compared to the non-gamified version. This suggests that the added game elementsare affecting the user experience in the desired way. Conclusions. An overall positive impact on both performance and user experience from gamification is concluded. The negative effect on memory tests could not be determined to be a cause of the gamification per se. / Bakgrund. CoGNIT är ett datoriserat testbatteri för kognitiv bedömning som används vid diagnos och behandling av patienter med idiopatisk normaltryckshydrocefalus (INPH). Sjukdomen orsakar bland annat symptom som demens. Till skillnad från andra sjukdomar med liknande symptom, som Alzheimers, kan INPH motverkas. CoGNIT utförs av en patient före och efter dränering av cerebrospinalvätska. Om en förbättring av patientens kognitiva förmågor upptäcks efter dräneringen, shuntoperaras patienten och alla symptom minskas. Testbatteriet är långt och tråkigt, vilket gör det svårt för personer med kognitiva nedsättningar att slutföra. Syfte. Syftet med denna studie är att omarbeta CoGNIT med noggrant utvalda speldesignelement och analysera hur prestation och användarupplevelse påverkas av förändringen. Om användare presterar bättre i en spelifierad miljö kommer validiteten av insamlad data att förbättras eftersom datan borde bättre återspegla deras kognitiva förmågor. Ett annat mål är att introducera spelifiering till det medicinska området. Metod. Speldesignelement valdes ut och utformades baserat på dess lämplighet för äldre och med de funktionsnedsättnigar som INPH-patienter har i åtanke. En spelifierad prototyp utvecklades och testades med friska individer mot originalversionen i ett experiment. Effekterna av spelifiering på prestation undersöktes genom att jämföra poängvärden från båda versionerna av testet. Deltagarna fyllde också i ett frågeformulär som "proxy" för testets målgrupp, vilket innebär att frågorna besvarades med hur deltagarna förväntade sig att en kognitivt nedsatt person hade svarat. Svaren användes för att undersöka effekten av spelifiering på användarupplevelsen. Resultat. Den spelifierade versionen av CoGNIT visar en förbättring i testsegmenten som utvärderar uppmärksamhet, psykomotorisk hastighet, exekutiva funktioner och fingerfärdighet, men en försämring i segmenten som utvärderar minne. Resultat från frågeformuläret indikerar att den spelifierade versionen upplevs mindre dramatisk, mer lekfull, mindre "testliknande" och mindre tråkig jämfört medden icke-spelifierade versionen. Detta visar att de tillagda spelelementen påverkar användarupplevelsen som önskat. Slutsatser. En övergripande positiv inverkan på både prestanda och användarupplevelse från spelfiering fastställs. Den negativa effekten på minnestesterna kunde inte bedömas vara en orsak av spelifiering i sig.

Denna rapport behandlar konstruktionen av en sensorbaserad skosula. Skosulan designades med en mängd trycksensorer som sedan visualiseras på en mobilapplikation. Mobilapplikationen anslöts till sulan via Bluetooth. Det är vanligt att majoriteten av små barn går på tå. Ifall barnet inte slutar gå på tå efter barnet fyllt 2–3 år bör man kontakta läkare. Det finns olika teorier angående vilken typ av behandling som är bäst för barnen. I dagsläget finns det ingen bra lösning för att följa upp behandlingarna på barnen. Prototypen är designad för att uppfylla de krav som behövs för att ge en bra bedömning ifall behandlingen som barnet fått förbättrat barnets belastning på foten. Rapporten går även in på andra användningsområden som sulan skulle kunna användas inom. Slutsatsen i rapporten är att utveckling av produkten är möjlig men kräver mer forskning inom området samt vidareutveckling av prototypen. Prototypen är i för tidigt stadie för att utföra riktiga tester på en försöksgrupp. För att validera sensorernas precision bör lämpliga testfall utvecklas. / This report goes through the development of a sensor-based insole. The insole was designed with multiple pressure sensors which are then visualized on a mobile application. The mobile application was connected to the insole via Bluetooth. It is common for toddlers to prefer toe walking. If the child does not stop toe walking after the age of 2-3 years, you should contact a doctor. There are different kinds of treatment for these children. Today there isn’t a good solution to evaluate the children post treatment. The prototype is designed to meet the requirements needed to give a good assessment of whether the child has improved or not. The report also addresses other use cases for the insole. The conclusion on the report is that development of the product is possible but requires more research in the field as well as further development of the prototype. The prototype is in a too early stage to perform true tests on a trial group. To validate the sensor's precision, appropriate test cases should be developed.

京都大学 / マギル大学 / 新制・課程博士 / 博士(ゲノム医学) / 甲第24203号 / 医博JD第1号 / 新制||医||JD1(附属図書館) / 京都大学大学院医学研究科京都大学マギル大学ゲノム医学国際連携専攻 / (主査)教授 稲垣 暢也, 教授 YOUSSEFIAN Shohab, 准教授 Majewski Jacek (マギル大学), 准教授 Gravel Simon (マギル大学), 教授 Gagneur Julien (ミュンヘン工科大学) / 学位規則第4条第1項該当 / Doctor of Philosophy in Human Genetics / Kyoto University / McGill University / DFAM

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease with no known cause or cure. IPF has an incidence of 75/1,000,000 of the population, predominately in men over the age of 60. This relatively rare disease develops in a chronic and progressive way, ultimately leading to death within two to five years of diagnosis. Our use of translatable methodologies in the bleomycin mouse model of IPF led to the novel identification of the similarities between the average percent loss of lung function in previous human clinical trials to that of our mouse model data. There is no treatment for IPF outside of lung transplantation, therefore our goal is to develop a protein therapy to halt the progression of IPF. B6_BP_dslf is a small, 93.36 kDa minibinder protein with a nanomolar affinity to αvβ6, an integrin of therapeutic potential for IPF when inhibited by halting αvβ6/TGF-β signaling. Our hypothesis is that B6_BP_dslf will halt the progression of pulmonary fibrosis induced in a mouse model of IPF. To test this hypothesis, a de novo design method was used resulting in the B6_BP_dslf minibinder having high β unit selectivity and nanomolar affinity for αvβ6, and maintenance of its secondary structure after aerosolization. These attributes led to testing in the bleomycin mouse model for IPF as an inhaled therapy. We found that B6_BP_dslf inhalation by mice with induced pulmonary fibrosis had reduced pathogenesis through the quantification of biomarkers for αvβ6/TGF-β mediated fibrosis, lowered histopathological scores, and improved lung function. These positive results from standard biochemical analysis and clinically translatable methods show that BP_B6_dslf has clinical potential as an inhaled therapy for IPF. Additionally, we tested the use of lung function tests in an animal model of chronic obstructive pulmonary disease (COPD), using secondhand smoke exposure to induce the disease and to identify inflammatory pathways. We found that smoke exposure increased inflammatory signaling through receptors for advanced glycation end-products, and inhibition of these receptors using a novel therapy of semi-synthetic glycosaminoglycan ethers (SAGEs) reduced inflammation and improved lung function. Together, the data from two different lung disease models supports the use of lung function as a preclinical efficacy variable for experimental drugs. The combination of biochemical and functional assessments of B6_BP_dslf and SAGEs gives weight to their therapeutic potential.

No description available.

Phenobarbital (PB) is one of the most important antiseizure drugs (ASDs) to treat canine idiopathic epilepsy (IE). The effect of PB on the taxonomic changes in gastrointestinal microbiota (GIM) and their functions is less known, which may explain parts of its pharmacokinetic and pharmacodynamic properties, especially its antiseizure effect and drug responsiveness or drug resistance as well as its effect on behavioral comorbidities. Fecal samples of 12 dogs with IE were collected prior to the initiation of PB treatment and 90 days after oral PB treatment. The fecal samples were analyzed using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based dysbiosis index (DI), and quantification of short-chain fatty acids (SCFAs). Behavioral comorbidities were evaluated using standardized online questionnaires, namely, a canine behavioral assessment and research questionnaire (cBARQ), canine cognitive dysfunction rating scale (CCDR), and an attention deficit hyperactivity disorder (ADHD) questionnaire. The results revealed no significant changes in alpha and beta diversity or in the DI, whereas only the abundance of Clostridiales was significantly decreased after PB treatment. Fecal SCFA measurement showed a significant increase in total fecal SCFA concentration and the concentrations of propionate and butyrate, while acetate concentrations revealed an upward trend after 90 days of treatment. In addition, the PB-Responder (PB-R) group had significantly higher butyrate levels compared to the PB-Non-Responder (PB-NR) group. Metagenomics of functional pathway genes demonstrated a significant increase in genes in trehalose biosynthesis, ribosomal synthesis, and gluconeogenesis, but a decrease in V-ATPase-related oxidative phosphorylation. For behavioral assessment, cBARQ analysis showed improvement in stranger-directed fear, non-social fear, and trainability, while there were no differences in ADHD-like behavior and canine cognitive dysfunction (CCD) scores after 90 days of PB treatment. While only very minor shifts in bacterial taxonomy were detected, the higher SCFA concentrations after PB treatment could be one of the key differences between PB-R and PB-NR. These results suggest functional changes in GIM in canine IE treatment.

Chronic pain is a significant public health problem. A large portion of those with chronic pain have had their acute postsurgical pain transition into a chronic postsurgical pain state. The mechanisms contributing to pediatric persistent postsurgical pain is not well understood; however, there is empirical support in the adult literature to suggest that psychosocial factors play a significant role in the maintenance and exacerbation of post-surgical pain. Recent research by our group found high pain prevalence rates up to 5-years post-surgery among children undergoing spinal fusion surgery, particularly among those reporting poor pre-surgical mental health. The current study aims to extend this research by exploring psycho-social functioning and pain among children (10-21 years) who underwent major orthopedic surgery and their parents (n=21 dyads; data collection is ongoing). Measures administered 1-3 years post-surgery included pain ratings, the Bath Adolescent Pain Questionnaire (Child; Parental Impact), Fear of Pain Questionnaire, Functional Disability Inventory, and the Adult Responses to Child Symptoms. Preliminary results found that 52% of patients reported pain in the moderate-severe range in the past 6 months. Additionally, increased child pain was associated with greater child-reported functional disability (p<.01), pain-specific anxiety (p<.01), and fear of pain (p<.05), as well as worse overall emotional functioning (p<.05). Parents of children with increased pain reported worse parental strain (e.g., "found my relationship with my child difficult," p<.05). Identifying correlates of poor long-term outcomes in children with postsurgical pain may prevent the development of chronic pain into adulthood. With recent economic costs of adult chronic pain estimated to be between $560-$635 billion per year research on the role of persistent pain in children is of upmost importance in order to positively impact pre-surgical preparation, postsurgical care, and in potentially preventing disabling pain into adulthood for a population at considerable risk. This investigation was supported by the Boston Children's Hospital Career Development Fellowship Award (CS).

Background: The aim of this cross-sectional study was to investigate oral health and functional status of adolescents with juvenile idiopathic arthritis (JIA) and its possible link to disease specific parameters. Methods: Patients with JIA were recruited (November 2012–October 2014) and disease specific information was extracted from patients’ records. Oral examination included: dental findings (decayed-, missing- and filled-teeth-index (dmf-t/DMF-T)), gingival inflammation (papilla-bleeding-index (PBI)) and periodontal screening index (PSI). Functional examination followed Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Additionally, modified Helkimo’s Clinical Dysfunction Index and radiographic scoring were recorded. Results: 59 JIA patients were included. The mean dmf-t/DMF-T was 2.6. Only one patient showed no signs of gingival inflammation, while 57.6% had a maximum PSI of 2 or less. Positive functional findings were assessed clinically in more than half of the patients. Major diagnosis by RDC/TMD was osteoarthrosis. Patients with at least one positive anamnestic or clinical functional finding revealed significantly higher radiographic scores (CI = 0.440, p = 0.022). Patients with increased c-reactive-protein had a significantly higher PBI (Z = –2.118, p = 0.034) and increased radiographic scores (CI = 0.408, p = 0.043). Conclusions: Adolescents suffering from JIA show high levels of caries experience and gingival inflammation. Temporomandibular joint dysfunction is often seen in JIA patients. Consequently, special dental care programs would be recommendable.