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Aim The Rett Syndrome Gross Motor Scale (RSGMS) is an observational measurement, assessing gross motor skills in individuals with Rett syndrome. A Dutch version is lacking. The current study aims to translate and cross-culturally adapt the original RSMGS to Dutch and assess its inter-rater and intra-rater reliability. Design Translation and cross-cultural adaptation were performed in concordance with internationally accepted guidelines. A pretest was performed, and expert validation was assured. Video data of three girls with Rett syndrome was independently assessed by 27 physiotherapists via an online webinar to measure inter-rater reliability. Additionally, videos of 17 individuals with Rett syndrome were scored twice by two raters to assess intra-rater reliability. The reliability of the total score, the three subscale scores and the new items were analyzed using Intraclass Correlation Coefficients (ICC). Results Good comprehensibility and expert validation of the RSMGS-NL was achieved, and four items were added to the original scale. Inter-rater reliability for the total score was excellent (ICC 0.97, 95% CI 0.89-0.99), and good to perfect inter-rater reliability for the three subscales; Sitting, Standing & walking and Challenge was found (ICC values 1.0 (95% CI 0), 0.98 (95% CI 0.91-0.99) and 0.82 (95% CI 0.93-0.99) respectively). The intra-rater reliability was excellent for the total test score (ICC 0.98, 95% CI 0.97-0.99) and good to excellent for the subscale scores (ICC values 0.87 (95% CI 0.75-0.94), 0.99 (95% CI 0.98-1.0) and 0.97 (95% CI 0.95-0.99) respectively). The four new items (Standing to sitting, walking down a slope, ascending the stairs, descending the stairs) showed good to excellent intra-rater reliability. Conclusion The RSGMS-NL is a reliable measure of gross motor skills in Dutch individuals with Rett syndrome.

PURPOSE: This study evaluated the long-term effects of Brainz, a community-based treatment programme for adults with acquired brain injury in the chronic phase of the injury.MATERIALS AND METHODS: The treatment consisted of group modules and biweekly individual home training sessions. Of the 62 subjects who participated in the original effect study, 30 subjects were available for follow-up assessment. Selection bias analysis of baseline characteristics revealed no significant differences between the included and the excluded group. Baseline measurements were compared with follow-up measurements to assess effect consolidation after treatment cessation.RESULTS: The increased level of patient satisfaction with social participation found one year after baseline, was maintained at follow-up. The positive effects on the number of perceived difficulties in daily life and need of care that were found one year after baseline measurements were no longer present. However, an additional improvement in self-reported overall health was observed. The decreased level of self-esteem measured one year after baseline, was no longer present at follow-up.CONCLUSIONS: Overall, this study suggests consolidation of the effects of this community-based treatment programme. Further enhancement of treatment effects could be established by the implementation of booster sessions or peer support groups. Future controlled studies are needed. Implications for rehabilitation Acquired brain injury can lead to consequences in a variety of life domains that can persist after patients return to their homes. A low-intensity community-based rehabilitation programme called Brainz demonstrated to improve patient satisfaction with societal participation and reduce perceived difficulties in daily life and need of care. This study suggests the consolidation of these effects.

Background: The contribution of gene-environment interactions that lead to excessive aggression is poorly understood. Environmental stressors and mutations of the gene encoding tryptophan hydroxylase-2 (TPH2) are known to influence aggression. For example, TPH2 null mutant mice (Tph2−/−) are naturally highly aggressive, while heterozygous mice (Tph2+/−) lack a behavioral phenotype and are considered endophenotypically normal. Here we sought to discover whether an environmental stressor would affect the phenotype of the genetically ‘susceptible’ heterozygous mice (Tph2+/−). Methods: Tph2+/− male mice or Tph2+/+ controls were subjected to a five-day long rat exposure stress paradigm. Brain serotonin metabolism and the expression of selected genes encoding serotonin receptors, AMPA receptors, and stress markers were studied. Results: Stressed Tph2+/− mice displayed increased levels of aggression and social dominance, whereas Tph2+/+ animals became less aggressive and less dominant. Brain tissue concentrations of serotonin, its precursor hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid were significantly altered in all groups in the prefrontal cortex, striatum, amygdala, hippocampus and dorsal raphe after stress. Compared to non-stressed animals, the concentration of 5-hydroxytryptophan was elevated in the amygdala though decreased in the other brain structures. The overexpression of the AMPA receptor subunit, GluA2, and downregulation of 5-HT6 receptor, as well as overexpression of c-fos and glycogen-synthase-kinase-3β (GSK3-β), were found in most structures of the stressed Tph2+/− mice. Limitations: Rescue experiments would help to verify causal relationships of reported changes. Conclusions: The interaction of a partial TPH2 gene deficit with stress results in pathological aggression and molecular changes, and suggests that the presence of genetic susceptibility can augment aggression in seemingly resistant phenotypes. © 2020 The Authors 602805 Seventh Framework Programme, FP7 Deutsche Forschungsgemeinschaft, DFG: CRC TRR 58 A1/A5 Horizon 2020 Framework Programme, H2020: 728018 Russian Foundation for Basic Research, RFBR: 15-04-03602 Deutsche Forschungsgemeinschaft, DFG Russian Foundation for Basic Research, RFBR The authors’ work reported here was supported Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A1/A5), the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant No. 602805 (Aggressotype) and the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE) (to KPL and TS), the “5-100” Russian Academic Excellence Project (to KPL and TS) and the Russian Foundation of Basic Research (RFBR Grant No. 15-04-03602 to TS). We appreciate the valuable technical help of Dr. Joao Costa-Nunes and Dolores Bonopartos with this project.

Objective: In long-term electroencephalogram (EEG) signals, automated classification of epileptic seizures is desirable in diagnosing epilepsy patients, as it otherwise depends on visual inspection. To the best of the author's knowledge, existing studies have validated their algorithms using cross-validation on the same database and less number of attempts have been made to extend their work on other databases to test the generalization capability of the developed algorithms. In this study, we present the algorithm for cross-database evaluation for classification of epileptic seizures using five EEG databases collected from different centers. The cross-database framework helps when sufficient epileptic seizures EEG data are not available to build automated seizure detection model.Methods: Two features, namely successive decomposition index and matrix determinant were extracted at a segmentation length of 4 s (50% overlap). Then, adaptive median feature baseline correction (AMFBC) was applied to overcome the inter-patient and inter-database variation in the feature distribution. The classification was performed using a support vector machine classifier with leave-one-database-out cross-validation. Different classification scenarios were considered using AM-FBC, smoothing of the train and test data, and post-processing of the classifier output.Results: Simulation results revealed the highest area under the curve-sensitivity-specificity-false detections (per hour) of 1-1-1-0.15, 0.89-0.99-0.82-2.5, 0.99-0.73-1-1, 0.95-0.97-0.85-1.7, 0.99-0.99-0.9 2-1.1 using the Ramaiah Medical College and Hospitals, Children's Hospital Boston-Massachusetts Institute of Technology, Temple University Hospital, Maastricht University Medical Centre, and University of Bonn databases respectively.Conclusions: We observe that the AM-FBC plays a significant role in improving seizure detection results by overcoming inter-database variation of feature distribution.Significance: To the best of the author's knowledge, this is the first study reporting on the cross-database evaluation of classification of epileptic seizures and proven to be better generalization capability when evaluated using five databases and can contribute to accurate and robust detection of epileptic seizures in real-time. (C) 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Objectives To assess the supraspinal working mechanisms of the burst spinal cord stimulation (SCS) mode, we used functional magnetic resonance imaging (fMRI) in chronic neuropathic rats. We hypothesized that active recharge burst SCS would induce a more profound blood oxygenation level-dependent (BOLD) signal increase in areas associated with cognitive-emotional aspects of pain, as compared to tonic SCS.Methods Sprague Dawley rats (n = 17) underwent a unilateral partial sciatic nerve ligation, which resulted in chronic neuropathic pain. Quadripolar SCS electrodes were epidurally positioned on top of the dorsal columns at Th13. Isoflurane-anesthetized (1.5%) rats received either tonic SCS (n = 8) or burst SCS (n = 9) at 66% of motor threshold. BOLD fMRI was conducted before, during, and after SCS using a 9.4-T horizontal bore scanner.Results Overall, both tonic and burst SCS induced a significant increase of BOLD signal levels in areas associated with the location and intensity of pain, and areas associated with cognitive-emotional aspects of pain. Additionally, burst SCS significantly increased BOLD signal levels in the raphe nuclei, nucleus accumbens, and caudate putamen. Tonic SCS did not induce a significant increase in BOLD signal levels in these areas.Conclusions In conclusion, active recharge burst and tonic SCS have different effects on the intensity and localization of SCS-induced activation responses in the brain. This work demonstrates that active recharge burst is another waveform that can engage brain areas associated with cognitive-emotional aspects of pain as well as areas associated with location and intensity of pain. Previous studies showing similar engagement used only passive recharge burst.

Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30-day-old) stress memory. Here, the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice 1 month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in post mortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.

BACKGROUND Diagnosing long QT syndrome (LQTS) remains challenging because of a considerable overlap in QT interval between patients with LQTS and healthy subjects. Characterizing T-wave morphology might improve LQTS diagnosis.OBJECTIVE The purpose of this study was to improve LQTS diagnosis by combining new polynomial-based T-wave morphology parameters with the corrected QT interval (QTc), age, and sex in a model.METHODS A retrospective cohort consisting of 333 patients with LQTS and 345 genotype-negative family members was used in this study. For each patient, a linear combination of the first 2 Hermite-Gauss (HG) polynomials was fitted to the STT segments of an average complex of all precordial leads and limb leads I and II. The weight coefficients as well as the error of the best fit were used to characterize T-wave morphology. Subjects were classified as patients with LQTS or controls by clinical QTc cutoffs and 3 support vector machine models fed with different features. An external cohort consisting of 72 patients and 45 controls was finally used to check the robustness of the models.RESULTS Baseline QTc cutoffs were specific but had low sensitivity in diagnosing LQTS. The model with T-wave morphology features, QTc, age, and sex had the best overall accuracy (84%), followed by a model with QTc, age, and sex (79%). The model with T-wave morphology features especially performed better in LQTS type 3 patients (69%).CONCLUSION T-wave morphologies can be characterized by fitting a linear combination of the first 2 Hermite-Gauss polynomials. Adding T-wave morphology characterization to age, sex, and QTc in a support vector machine model improves LQTS diagnosis.

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness. ispartof: ACTA PSYCHIATRICA SCANDINAVICA vol:141 issue:5 pages:465-475 ispartof: location:United States status: published

Aims: Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 of CD34+ cells), which showed anti-inflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle. Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Cell-treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion: The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd We thank ?5-100? Russian Excellence Program, Prof. Daniel C. Anthony, Diana Babayevskaya, and Arina Kosakova for their highly valuable contribution. ?Neuro-Cells? preparation was provided by Neuroplast BV, Maastricht, Netherlands.

OBJECTIVE Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed. RESEARCH DESIGN AND METHODS In the Maastricht Study, a type 2 diabetes–enriched population-based cohort study (1,361 subjects with normal glucose metabolism, 348 with prediabetes, and 510 with type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors. RESULTS Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = −0.055 [95% CI −0.172, 0.062], stβType2diabetes = −0.256 [−0.379, −0.133], Ptrend < 0.001). Prediabetes was associated with lower local efficiency (stβ = −0.084 [95% CI −0.159, −0.008], P = 0.033) and lower clustering coefficient (stβ = −0.097 [95% CI −0.189, −0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008). CONCLUSIONS These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections.

Objective: To identify determinants within 3 different domains (ie, somatic comorbidities, cognitive functioning, and neuropsychiatric symptoms [NPS]) of health-related quality of life (HRQoL) over time in memory clinic patients without dementia. Methods: This longitudinal multicenter cohort study with a 3-year observation period recruited 315 individuals (age: 69.8 ± 8.6, 64.4% males, Mini-Mental State Examination score 26.9 ± 2.6). A multivariable explanatory model was built using linear mixed effects models (forward selection per domain) to select determinants for self-perceived HRQoL over time, as measured by the EuroQoL-5D visual analogue scale (EQ VAS). Results: Mean HRQoL at study entry was 69.4 ± 15.6. The presence of agitation, appetite and eating abnormalities, and eyes/ears/nose (ie, sensory impairment) comorbidities were associated with a change in HRQoL over time. Agitation was most strongly associated with HRQoL over time. Conclusions: The association of somatic comorbidities and NPS in memory clinic patients with course of HRQoL shows that these should receive more awareness, detection, and monitoring by clinicians.

Objectives:The aim of this study was to investigate survival time and life-expectancy in people with young-onset dementia (YOD) and to examine the relationship with age, sex, dementia subtype and comorbidity.Design, Setting and Participants:Survival was examined in 198 participants in the Needs in Young-onset Dementia study, including participants with Alzheimer’s dementia (AD), vascular dementia (VaD) and frontotemporal dementia (FTD).Measures:The primary outcomes were survival time after symptom onset and after date of diagnosis. Cox proportional hazards models were used to explore the relationship between survival and age, sex, dementia subtype and comorbidity. Additionally, the impact on remaining life expectancy was explored.Results:During the six-year follow-up, 77 of the participants died (38.9%), 78 participants survived (39.4%) and 43 were lost to follow-up (21.7%). The mean survival time after symptom onset and diagnosis was 209 months (95% CI 185-233) and 120 months (95% CI 110-130) respectively. Participants with AD had a statistically significant shorter survival compared with VaD participants, both regarding survival after symptom onset (p = 0.047) as well as regarding survival after diagnosis (p = 0.049). Younger age at symptom onset or at diagnosis was associated with longer survival times. The remaining life expectancy, after diagnosis, was reduced with 51% for males and 59% for females compared to the life expectancy of the general population in the same age groups.Conclusion/Implications:It is important to consider the dementia subtype when persons with YOD and their families are informed about the prognosis of survival. Our study suggests longer survival times compared to other studies on YOD, and survival is prolonged compared to studies on LOD. Younger age at symptom onset or at diagnosis was positively related to survival but diagnosis at younger ages, nevertheless, still diminishes life expectancy dramatically.

Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.

Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16-26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win ((sic)3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops. (C) 2019 Elsevier B.V. and ECNP. All rights reserved.

status: published

This dissertation focusses on the functioning of our memory. Various memory processes and the ways to examine these are treated. Furthermore, the role α7 nicotinic acetylcholine receptors (α7 nAChRs) play in various memory processes is discussed in detail. Receptors are proteins which in this case are located on the surfaces of brain cells. Specific molecules (such as drugs) may attach to these receptors. Subsequently, the receptors may cause the brain cells to react. Focussing on α7 nAChRs is therefore relevant with regard to the development of new drugs aimed at treating memory problems in Alzheimer’s disease and/or schizophrenia, for instance.It was found that the blockade of α7 nAChRs with very low doses of so-called selective antagonists results in an improvement in memory performance and memory formation in rodents.

The rapid aging of the world population will lead to an increase in cases of Parkinson's disease, challenging health systems in the coming decades. Some medications compensate for this lack of dopamine, but they are far from being perfect. Thus, it is necessary the research focus on the mechanisms involved in the cell death, as the neuroinflammatory processes, in order to develop new therapeutic strategies. One of the most promising ideas is the so-called “drug repositioning” which consists in the process of developing a compound for use in a different disease. In this work, we found that N-acetil-L-cysteine (a common mucolitic drug with anti-oxidant properties) protects against neuroinflammation and neuronal death. Thus, these data point out the importance in the development of this strategy to slow down the progression of the neurodegeneration in Parkinson's disease.

Cerebral microvascular abnormalities play a key role in people with Alzheimer’s disease. The condition of these small blood vessels can be assessed by means of an MRI scan with contrast. It is shown that there is a minor but measurable contrast leakage from the blood circulation into the brain. The so-called blood-brain barrier should ensure that the contrast agent remains within the blood circulation. The leakage observed is a sign, therefore, that this barrier is damaged in Alzheimer’s disease – even in people who show no signs of vascular damage at first sight.

Peripheral Neuropathy outcome measure Standardization (PeriNomS) studies the outcome measures for nerve conditions (polyneuropathy). Objective results require an objective measure (outcome). This method can be used to determine how a patient feels and the effects of a certain treatment. Unfortunately, no objective measures exist for most chronic disorders. This study led to the development of a measure that was internationally recognised as the best way to determine the effects of a treatment. This will make it easier to compare studies in the future and can be used for multiple diseases.

This dissertation examines whether a ketogenic diet (KD) is an effective treatment option for children, teens and adults with refractory epilepsy. KD consists of a high-fat, low-carb diet. The breakdown of fats releases ketones that the brain uses as a source of energy instead of carbohydrates.Based on the research results, it can be concluded that KD is an effective treatment that can decrease the total number of attacks, the number of cluster attacks and the severity of the attacks. Gastrointestinal issues are the most troubling symptom and tend to occur during the early stages of treatment. KD is well-tolerated with prolonged use. However, adults find it more difficult to follow the diet strictly. Incidentally, an EEG in individual patients is not an accurate predictor of who will benefit from this diet.

This dissertation investigates the hypothesis whether in a small subgroup of patients with psychotic symptoms, the immune system is attacking the brain. Some autoantibodies have been reported to target specific proteins in the brain and thereby induce neurological and psychotic symptoms. Our results indicate that the presence of these previously described autoantibodies are very rare in the blood of patients with psychotic diagnoses and that the currently used diagnostic methods are of limited use in these cohorts. However, we identified the presence of novel autoantibodies with unclear target in the brain. We further describe two methods to clone autoantibodies from patients immune-cells to be able to produce autoantibodies in the laboratory for further analysis of their pathological function.

In more than 50% of patients with chronic obstructive pulmonary disease (COPD), cognitive impairment is found. Various cognitive domains are affected, such as psychomotor speed, planning, working memory, verbal memory and cognitive flexibility. However, cognitive impairment does not affect outcome measures used in pulmonary rehabilitation, such as psychological well-being, functional status, health status, knowledge of and need for information about the disease. Patients with cognitive impairment are less likely to complete a pulmonary rehabilitation programme. Active screening for cognitive impairment in COPD patients is necessary, because its presence could not be predicted based on demographic and clinical features.

Parkinson´s Disease (PD) is the second most common neurodegenerative disease worldwide. Yet, the exact pathophysiology of neuronal degeneration observed in this disease still remains unknown. Many models (cellular and animal models) have been used to understand explain PD and find the exact mechanism of behind its neurodegeneration. While these models are exogenous and produce a severe Parkinson´s Disease in just a few days or even hours, the development of PD in patients is characterised by a slow progress. In this conferral, the use of an endogenous compound (Aminochrome) is demonstrated. A model with slow progression and a progressive dopaminergic neuronal death is created, which fits more to the reality that patients face.

Alzheimer disease is the most common cause of dementia in the world. Despite intensive research efforts, no cure is available yet. In this thesis, a therapeutic approach using antibodies was investigated. These antibodies target a protein called amyloidβ, which plays a central role in the disease process. While this approach has been tried before, it has met with very little success so far, and there is still room for improvement. In this research antibodies were developed and tested that cause less inflammation than normal antibodies and thereby less side-effects in an animal model of Alzheimer’s disease. Unfortunately, these new type of antibodies did not perform better than the previous type. It was also investigated whether antibodies could be used to diagnose the disease using PET imaging. It was shown that antibodies in mice are promising to diagnose the disease and to gain further knowledge about how antibodies might be used to combat the disease.

Cardiac surgery in its current form is a complex and labour-intensive pursuit within the medical profession. Efficiency and effectiveness are important to cost management and optimisation is imperative given the increasing age of patients. This dissertation identifies a number of logistical measures that can help. For example, a patient group can be selected that requires fewer ICU beds and hospital staff and fewer bags of donor blood. If complications arise, such as kidney dialysis, age plays a crucial role, as the recovery and survival rate of patients aged 75 and older is virtually zero. Finally, this dissertation describes relatively cheap and simple laboratory tests that can help determine the survival rate of patients following cardiac surgery. Lactic acid and cholesterol tests in the ICU can be used to supplement existing risk analyses before surgery.

Achtergrond: Farmacotherapie bij ouderen met persoonlijkheidsstoornissen (PS) vormt een nieuw en belangrijk aandachtsgebied. Vooralsnog wordt de symptoomgerichte farmacotherapeutische behandeling van ouderen met PS vormgegeven aan de hand van de multidisciplinaire richtlijn Persoonlijkheidsstoornissen, die gebaseerd is op onderzoeken bij patiënten met PS tot circa 50 jaar oud. Het ontbreekt aan een richtlijn specifiek voor ouderen.Doel: Het leveren van een beschrijving van patiëntkenmerken: aantal comorbide psychiatrische stoornissen, medicatiegebruik, inclusief polyfarmacie, bij ouderen (≥ 65 jaar) met persoonlijkheidsstoornissen.Methode: Een retrospectieve cross-sectionele dossierstudie (n = 50) binnen een topklinisch centrum voor ouderen met persoonlijkheidsstoornissen (ambulante setting).Resultaten: Uit de dossierstudie blijkt 1) de ongespecificeerde/andere gespecificeerde persoonlijkheidsstoornis en de borderline persoonlijkheidsstoornis (BPS) het meest voor te komen, 2) er een trend (geen statistisch significant verschil) te zijn dat patiënten met BPS meer somatische medicatie en psychofarmaca gebruiken en 3) er een trend (geen statistisch significant verschil) te zijn dat polyfarmacie het meest voorkomt bij oudere patiënten met BPS.Conclusie: Het medicatiegebruik in bepaalde subgroepen van ouderen met PS lijkt hoog te zijn. Vervolgonderzoek is essentieel om farmacotherapie bij ouderen met PS te verbeteren.

Absence epilepsy (AE) has been associated with lower than average cognitive functioning, which are clinically relevant in some and may predispose to problems later in life. This study aimed to assess cognitive development during long-term follow-up in children with AE. Thirty-one children with AE, who had undergone two neuropsychological assessments between 2010 and 2017 were analyzed retrospectively. Cognitive measurements were 1.7 +/- 0.95 years apart. The difference in neurocognitive test scores was assessed on a group level and on an individual level using reliable change methodology. Results show that sustained attention was lower at the first measurement compared to the normative mean. Sustained attention improved during follow-up and 7 out of 14 children showed improvement after correction for practice effects. Receptive vocabulary showed a decline over time, but did not differ from the normative mean. Significant lower mean group scores were present for performance IQ, perceptual organization, processing speed, simple reaction times, and visual motor integration, while being stable over time in the majority of children. Cognitive development was not associated with seizure freedom. Mild-to-severe academic underachievement was present in 65% and comorbidities that might affect learning in 38%. This study in children with AE showed improvement in sustained attention during long-term follow-up while other cognitive weaknesses persisted over time, regardless of seizure freedom.

BackgroundIndividuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies.MethodsIndividuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan–Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337).ResultsOf the individuals with ASD, 23.50% (95% confidence interval 21.87–25.22) were diagnosed with NAPD and 3.79% (3.06–4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63–1.28) and 0.13% (0.08–0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33–2.61) being diagnosed with NAPD and 0.57% (0.21–1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44–0.86) and 0.08% (0.05–0.12).ConclusionsIndividuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.

OBJECTIVES: The examination of retinal microvascular abnormalities through fundus photography is currently the best available non-invasive technique for assessment of cerebral vascular status. Several studies in the last decade have reported higher incidences of adverse cerebrovascular events in Schizophrenia (SCZ) and bipolar disorder (BD). However, retinal microvasculature abnormalities in SCZ and BD have remained under-explored, and no study has compared this aspect of SCZ and BD till date.METHODS: Retinal Images of 100 SCZ patients, BD patients, and healthy volunteers each were acquired by trained individuals using a non-mydriatic camera with a 40-degree field of view. The retinal images were quantified using a valid semi-automated method. The average of left and right eye diameters of the venules and arterioles passing through the extended zone between 0.5 and 2 disc diameters from the optic disc were calculated.RESULTS: The groups differed significantly with respect to average diameters of both retinal venules (P < 0.001) and retinal arterioles (P < 0.001), after controlling for age and sex. Both SCZ and BD patients had significantly narrower arterioles and wider venules compared to HV. There were also significant differences between SCZ and BD patients; patients with BD had narrower arterioles and wider venules.CONCLUSION: Considering the affordability and easy accessibility of the investigative procedure, retinal microvascular examination could serve as a potential screening tool to identify individuals at risk for adverse cerebrovascular events. The findings of the current study also provide a strong rationale for further systematic examination of retinal vascular abnormalities in SCZ and BD.

Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. 4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid. A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization. The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition. This research was conducted as part of the EMIF-AD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007-2013), and EFPIA companies’ in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l’Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The authors acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIBCMN is funded in part by the University of Antwerp Research Fund. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215).

Objectives: The aim of the present study was to investigate the association between trait gratitude and loneliness in a Dutch population sample of adults over 40 years. In addition, the mediating role of psychological flexibility and engaged living between trait gratitude and loneliness was assessed. Method: A total sample of 163 adults of which 65 men (40%) and 98 women (60%) between 41 and 92 years (Mage = 66, SDage = 12) participated in this study. Data from the Loneliness Questionnaire, Flexibility Index Test, Engaged Living Scale and the Short Gratitude, Resentment, and Appreciation Test were used. Mediation analysis was performed.Results: Analysis showed a negative association between trait gratitude and loneliness. In addition, after adjusting for the demographic variables age, gender and educational level, the association between trait gratitude and loneliness was fully mediated by psychological flexibility, and partially mediated by engaged living.Conclusion: This study endorses the importance of trait gratitude and psychological flexibility in relation to experiencing loneliness. Further research is needed to replicate these findings in a more diverse sample and to investigate the causal relationships between these constructs. It would also be interesting to further investigate the role of different age groups and goal (dis)engagement strategies in this relation.

Inflammatory Rasch-built overall disability scale (I-RODS) seems to be a valid activity measure for use in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our aim was to translate and validate the I-RODS for use in CIDP patients from Serbia. Study comprised 83 patients diagnosed with CIDP. I-RODS was translated and cross-culturally validated using the standard guidelines. Following scales were also administered: Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Krupp's Fatigue Severity Scale, Beck Depression Inventory, Visual Analogue Scale for pain, and health survey-36 (SF-36) as a quality of life measure. According to the I-RODS, significant proportion of our patients reported that "running" (51%), "dancing" (41%), and "standing for hours" (40%) were impossible tasks to perform, while "teeth brushing" (94%), "eating" (88%), and "reading a newspaper/book" (82%) were noted as the easiest items. Patients with more muscle weakness (lower MRC sum score) and more severe INCAT sensory score had lower I-RODS score (P 1 (P

As patient/survivor movements continue to challenge reductionist biological views of mental health and psychosis, there is rising skepticism toward psychiatric medications and growing interest in withdrawal and alternatives. This new perspective also calls for a rethinking of reductionist assumptions about psychiatric medications themselves. General medical patient experience with collaborative decision making for other conditions has broad implications for psychiatric drug withdrawal, and by recognizing psychiatric medications as psychoactive substances, addiction science also suggests a central role for social context and therapeutic common factors in medication withdrawal response. New understandings of madness and medications support an emerging reconsideration of what constitutes the very definition of “health,” where measuring the absence of disease symptoms gives way to a systems-based focus on self-management, social relationships, and adaptability.

Introduction With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition. Methods Dystrophin distribution was evaluated in rat bladders by immunohistochemical colocalization with smooth muscle, interstitial, urothelial, and neuronal markers. Protein levels of Dp140, Dp71, and smooth muscle were quantitated by Western blotting of neonatal to adult rat bladders. Results Dystrophin colocalized with smooth muscle cells and afferent nerve fibers. Dp71 was expressed two‐ to threefold higher compared with Dp140, independently of age. Age‐related muscle mass changes did not influence isoform expression levels. Discussion Dystrophin is expressed in smooth muscle cells and afferent nerve fibers in the urinary bladder, which underscores that micturition problems in DMD may have not solely a myogenic but also a neurogenic origin. Muscle Nerve 60: 202–210, 2019

BackgroundEvidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming ‘complicated’ by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms.MethodsData were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was ‘complicated’ by low-grade psychotic experiences (‘attenuated psychosis’ – moderately severe) and, overt psychotic symptoms leading to help-seeking (‘clinical psychosis’ – most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction.ResultsIn proxy gene–environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation.ConclusionKnown environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.

Objectives: To define ultrastructural features accompanying to antitumor effects of gemcitabine, vinorelbine and cyclooxygenase inhibitors in C6 glioma cells in vitro. Vinorelbine is a semisynthetic vinca alkaloid and recent studies showed its antitumor activity in pediatric optic and pontine gliomas. Vinorelbine infusion induces a severe tumor site-pain in systemic cancers, but it is unknown whether algesia and inflammation contribute to its antitumor effects. Gemcitabine is a nucleoside-chemotherapeutic which was recently shown to act as a radiosensitizer in high-grade glioma. Some studies showed synergism of anti-inflammatory cyclooxygenase-inhibitors with microtubule inhibitors and gemcitabine. DMSO is a solvent and blocks both cylooxygenase and ribonucleotide reductase, another target of gemcitabine. Rofecoxib is withdrawn from the market, yet we used it for investigational purposes, since it blocks cylooxygenase-2 1000-times more potently than cylooxygenase-1 and is also a selective inhibitor of crinophagy.Methods: Plating efficacy, 3D-spheroid S-phase analysis with BrdU labelling and transmission electron micro-scopical analyses were performed.Results: Vinorelbine induced frequent mitotic slippage/apoptosis and autophagy. Despite both DMSO and rofecoxib induced autophagy alone and in synergy, they reduced mitotic catastrophe and autophagy triggered by vinorelbine, which was also reflected by reduced inhibition of spheroid S-phase. Gemcitabine induced karyolysis and margination of coarse chromatin towards the nuclear membrane, abundant autophagy, gutta adipis formation and decrease in mitochondria, which were enhanced by DMSO and rofecoxib.Conclusions: Detailed ultrastructural analysis of the effects of chemotherapeutic drugs may provide a broader insight about their actions and pave to develop better strategies in treatment of glioblastoma.

BackgroundThe jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs.MethodsData were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs.ResultsCompared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported.ConclusionThe findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

Contains fulltext : 205886.pdf (Publisher’s version ) (Open Access) Objectives: Memory clinics (MCs) have been established to improve diagnosis and treatment of cognitive disorders, including dementia. The aim of this study was to determine the characteristics and working methods of MCs in the Netherlands in 2016. More insight into different working methods can be used to improve the quality of care in Dutch MCs. Additionally, the findings will be compared with earlier results to investigate the development of MCs since 1998. Methods: A survey was sent in 1998, 2004, 2009, and 2017 to all operational Dutch MCs with questions about organization, collaboration, patients, and diagnostic procedures. Results: From 1998 to 2016, the number of MCs increased substantially from 12 to 91. The capacity increased from 1,560 patients to 24,388. In 1998, most patients received a dementia diagnosis (85%), while in 2016, half of the patients were diagnosed with milder cognitive problems. MCs are more often part of regional care chains and are better embedded within regional care organizations. Diagnostic tools, such as blood tests (97%), neuropsychological assessment (NPA) (95%) and neuroimaging (92%), were used in nearly all MCs. The number of patients in whom these tools were used differed greatly between MCs (NPA: 5-100%, neuroimaging: 10-100%, CSF: 0.5-80%). There was an increase in the use of NPA, while the use of neuroimaging, CSF, and EEG/ECG decreased by 8 to 15% since 2009. Conclusions: Since 1998, MCs have developed substantially and outgrown the primarily research-based university settings. They are now accepted as regular care facilities for people with cognitive problems. 8 p.

Objective: An epileptic seizure is recognized as a neurological disorder caused by transient and unexpected disturbance resulting from the excessive synchronous activity of the neurons in the brain. Analysis of epileptic seizures derived from long-term recordings of electroencephalogram (EEG) is cumbersome and time consuming for a neurologist. Therefore, introducing an automated detection system surrogate the neurologist involvement all time and speed up the treatment procedure.Methods: This study introduces a matrix determinant of EEG as a significant feature for recognition of epileptic seizures. Initially, artifact-free filtered EEG time series was arranged sequentially to form a square matrix of order, namely 13, 16, 23, and 32 and determinant was estimated. Assumed that the total elements in the square matrix represent a typical segmentation length. The experiment was conducted using EEG database obtained from the University of Bonn and Ramaiah Medical College and Hospital (RMCH). In total, eleven classification problems among non-epileptic group and epileptic EEG were composed to examine temporal dynamics of brain activity in different states of the epileptic activity. Next, the extracted feature was classified using support vector machine (SVM), K-nearest neighbor (K-NN), multilayer perceptron (MLP) classifiers with 10-fold cross-validation.Results: Experimental results revealed the highest classification accuracy of 99.45% (using University of Bonn) and 97.56% (using RMCH). between normal and epileptic EEG. In addition, other classification problems and matrix orders showed better results using all the classifiers. Further, descriptive analysis, histogram plot in polar coordinates and the bivariate histogram analysis was performed. In conclusion, matrix determinant found to be a potential biomarker for the real-time detection of epileptic seizure with minimal computational complexity. (C) 2019 Elsevier Ltd. All rights reserved.

Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting.We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values.First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06 min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83 at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30 min still provides an excellent reproducibility.

The medical device industry is a niche field globally and among the fastest growing industries in India. It requires specialised and interdisciplinary skills, as well as knowledge for innovation of new product development. New product development has four key phases: need finding, concept generation, engineering and validation. The first two phases require broad vertical and lateral thinking to come up with innovative plus appropriate solutions. Thus, multidisciplinary teams made up of experienced individuals with interdisciplinary knowledge enhance the phase outputs. The next two phases are iterative, usually requiring management of multiple subsystems, across technical disciplines and system integration. Without interdisciplinary product members and technical leaders, product development is not optimised. This leads to numerous iterations - loss of time, money. The industry struggles to find these interdisciplinary resources and building this capacity today takes a decade in India, with the entire burden falling on the industry. In well-developed medical device markets, higher education has introduced application-centric courses with cross-disciplinary curriculums. Such a structure allows students to gain valuable skills and understanding of the industry as a whole. Developed ecosystems have no shortage of experts available who serve as technical leaders. Developing countries like India have a very young indigenous medical device industry. In such nations, private companies struggle to find experienced individuals capable of interdisciplinary thinking and problem-solving. In this paper, we present India's current Medtech perspective, and the industry member's experiences through case studies and interviews. An outline for an academic model to meet the requirement of the industry has been presented.

This study assessed whether state gratitude and high and low-arousal positive affect show reciprocal relationships in daily life, and whether these relationships are dependent of inter-individual differences in positive mental health or psychopathology. 106 participants reported on momentary gratitude and positive affects throughout 7 consecutive days, using the Experience Sampling Method. Multilevel time-lagged regression analyses showed that state gratitude, cheerfulness and satisfaction reciprocally predict one another from one moment to the next. The strength of the prospective relationships between state gratitude(t-1) and both cheerfulness(t) and satisfaction(t) did not vary as a function of inter-individual differences in positive mental health or psychopathology. However, the prospective effects of both cheerfulness(t-1) and satisfaction(t-1) on state gratitude(t) were significantly stronger for individuals with low vs. high levels of psychopathology. In addition, the prospective effect of cheerfulness(t-1) on state gratitude(t) was significantly stronger for those with high vs. low positive mental health.

The continuous monitoring of Parkinsons's disease (PD) symptoms would allow to automatically adjust medication or deep brain stimulation parameters to a patient's momentary condition. Wearable sensors have been proposed to monitor PD symptoms and have been validated in a number of lab and hospital settings. However, taking these sensors into the daily life of patients introduces a number of difficulties, most notably the absence of an observable ground truth of what the user is currently doing. In this pilot study, we investigate PD symptoms by combining wearable sensors on both wrist and the chest with a questionnaire based evaluation of PD symptoms, in the form of experience sampling method. For a tremor dominant patient, we show that experienced tremor severity can be predicted from the sensor data with correlations of up to r = 0.43. We evaluated different window lengths to calculate the features in and see better results for longer window lengths. Our results show that continuous monitoring of PD symptoms in daily life is feasible using wearable sensors.

The electroencephalogram (EEG) signal contains useful information on physiological states of the brain and has proven to be a potential biomarker to realize the complex dynamic behavior of the brain. Epilepsy is a brain disorder described by recurrent and unpredictable interruption of healthy brain function. Diagnosis of patients with epilepsy requires monitoring and visual inspection of long-term EEG by the neurologist, which is found to be a time-consuming procedure. Therefore, this study proposes an automated seizure detection model using a novel computationally efficient feature named sigmoid entropy derived from discrete wavelet transforms. The sigmoid entropy was estimated from the wavelet coefficients in each sub-band and classified using a non-linear support vector machine classifier with leave-one-subject-out cross-validation. The performance of the proposed method was tested with the Ramaiah Medical College and Hospital (RMCH) database, which consists of the 58 Hours of EEG from 115 subjects, the University of Bonn (UBonn), and CHB-MIT databases. Results showed that sigmoid entropy exhibits lower values for epileptic EEG in contrary to other existing entropy methods. We observe a seizure detection rate of 96.34%, a false detection rate of 0.5/h and a mean detection delay of 1.2 s for the RMCH database. The highest sensitivity of 100% and 94.21% were achieved for UBonn and CHB-MIT databases respectively. The performance comparison confirms that sigmoid entropy was found to be better and computationally efficient as compared to other entropy methods. It can be concluded that the proposed sigmoid entropy could be used as a potential biomarker for recognition and detection of epileptic seizures.

Background/Aims: The available episodic memory tests are not specifically constructed to examine older subjects. Their use in outpatient memory clinics may result in aborted test administration. We used a strict adherence to the test protocol in cognitively healthy, amnestic mild cognitive impairment (aMCI), and Alzheimer’s disease dementia subjects to assess the possibility of preventing this. Methods: This is a cross-sectional study in memory outpatient subjects with a mean age of 74.5 years. Primary study outcomes were: number of missing values and test results in the Visual Association Test (VAT) and the 15 Word Test (15WT). Results: A strict adherence to the test protocol resulted in a 10-fold decrease in the number of missing values in the VAT. For the 15WT this could not be realized mostly because the test was deemed too demanding for 1 in 6 patients. Conclusions: This study is one of the few examining the applicability of well-known episodic memory tests in older subjects. A strict adherence to the test protocol reduced the number of missing values. Floor effects were stronger for the 15WT than for the VAT. Results favor the use of the VAT in senior subjects and show the unsuitability of the 15WT in this group.

Background Success rates of up to 80% have been reported for the SNM screening period in the treatment of fecal incontinence (FI). Some patients who have an unsuccessful index implantation are successfully treated with SNM after a lead revision. There is a lack of studies comparing the outcomes of successful index implantations and successful lead revision. Therefore, the results of index implantations were compared with lead revisions in a single-center cohort.Methods Patients treated with SNM for FI between 2008 and 2016 were retrospectively reviewed. Patients with a successful index implantation were compared with patients who underwent lead revision after SNM screening. Primary outcome was a decrease in episodes of fecal incontinence of >= 50% documented by a 3-week bowel habit diary.Results Two hundred sixty-one patients (232 index group, 29 revision group) were eligible for SNM. Two hundred thirty-one patients (208 index group, 23 revision group) received permanent SNM. Follow-up was 68.8 months for the index group and 62.2 months for the revision group. The number of episodes of FI decreased from 20.6 (SD 19.3) to 3.4 (SD 4.2) in the index group and from 12.6 (SD 5.8) to 2.0 (SD 2.3) in the revision group. This effect was maintained up to 5 and 2 years in the index and revision group, respectively. Adverse events such as loss of efficacy which required surgical intervention did not differ between the two groups.Conclusion Lead revision during the test phase is a valid option in patients with FI treated by SNM who suffer from loss of efficacy of the index electrode.