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1.
Ger Med Sci ; 22: Doc05, 2024.
Article in English | MEDLINE | ID: mdl-38883339

ABSTRACT

Background: Telephone counseling is an important form of support for informal carers of persons with dementia. The quality and benefit of this kind of service have rarely been evaluated in Germany. Methods: We developed a survey to assess the quality of telephone counseling. We conducted an online survey among 201 users of the telephone hotline "Alzheimer-Telefon" (Alzheimer's telephone service) provided by the German Alzheimer's Association after the consultation. The aim of the study was to determine whether this form of telephone support meets certain quality criteria and the callers' needs. Results: Of the 201 participants, 80% were female. The mean age of the callers was 51 years. 74% of cases were one-off consultations; 26% of the callers sought advice twice or more often. The most common reasons for calling included behavioral changes (45%) and finding a nursing home (41%). Other family members were significantly (p=0.036) more likely to seek local respite options. Based on the 201 online questionnaires evaluated, most callers were highly satisfied with the counseling services provided by the Alzheimer's telephone service. Those seeking advice were particularly satisfied with the appreciative and empathetic communication style of the advisors and their professional competence. This also applies to the accessibility of the telephone. More than three quarters were fully satisfied with the information they received. Almost half of the callers were sure that the advice would help to solve their issue. 14% of people seeking advice were uncertain about how to implement the suggested solutions.A further survey would be worthwhile to determine to what extent the topics of the consultation can be implemented. The feedback from relatives who use the Alzheimer's telephone repeatedly could be used for this purpose - the repetition rate is currently 25% and the trend is rising. Results could be interesting for successful counseling and for the development of further support services. Conclusion: The telephone hotline is a useful component of dementia care in Germany and an important contribution to the National Dementia Strategy.


Subject(s)
Alzheimer Disease , Caregivers , Counseling , Hotlines , Humans , Female , Male , Middle Aged , Alzheimer Disease/psychology , Alzheimer Disease/therapy , Germany , Caregivers/psychology , Caregivers/statistics & numerical data , Counseling/methods , Counseling/statistics & numerical data , Aged , Hotlines/statistics & numerical data , Telephone , Adult , Surveys and Questionnaires , Social Support , Self Care/methods , Patient Satisfaction/statistics & numerical data
2.
Lab Invest ; 104(6): 102049, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38513977

ABSTRACT

Although pathological tissue analysis is typically performed on single 2-dimensional (2D) histologic reference slides, 3-dimensional (3D) reconstruction from a sequence of histologic sections could provide novel opportunities for spatial analysis of the extracted tissue. In this review, we analyze recent works published after 2018 and report information on the extracted tissue types, the section thickness, and the number of sections used for reconstruction. By analyzing the technological requirements for 3D reconstruction, we observe that software tools exist, both free and commercial, which include the functionality to perform 3D reconstruction from a sequence of histologic images. Through the analysis of the most recent works, we provide an overview of the workflows and tools that are currently used for 3D reconstruction from histologic sections and address points for future work, such as a missing common file format or computer-aided analysis of the reconstructed model.


Subject(s)
Imaging, Three-Dimensional , Imaging, Three-Dimensional/methods , Humans , Software , Animals
3.
Eur J Cancer ; 193: 113294, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37690178

ABSTRACT

BACKGROUND: Historically, cancer diagnoses have been made by pathologists using two-dimensional histological slides. However, with the advent of digital pathology and artificial intelligence, slides are being digitised, providing new opportunities to integrate their information. Since nature is 3-dimensional (3D), it seems intuitive to digitally reassemble the 3D structure for diagnosis. OBJECTIVE: To develop the first human-3D-melanoma-histology-model with full data and code availability. Further, to evaluate the 3D-simulation together with experienced pathologists in the field and discuss the implications of digital 3D-models for the future of digital pathology. METHODS: A malignant melanoma of the skin was digitised via 3 µm cuts by a slide scanner; an open-source software was then leveraged to construct the 3D model. A total of nine pathologists from four different countries with at least 10 years of experience in the histologic diagnosis of melanoma tested the model and discussed their experiences as well as implications for future pathology. RESULTS: We successfully constructed and tested the first 3D-model of human melanoma. Based on testing, 88.9% of pathologists believe that the technology is likely to enter routine pathology within the next 10 years; advantages include a better reflectance of anatomy, 3D assessment of symmetry and the opportunity to simultaneously evaluate different tissue levels at the same time; limitations include the high consumption of tissue and a yet inferior resolution due to computational limitations. CONCLUSIONS: 3D-histology-models are promising for digital pathology of cancer and melanoma specifically, however, there are yet limitations which need to be carefully addressed.

4.
Med Image Anal ; 89: 102914, 2023 10.
Article in English | MEDLINE | ID: mdl-37544085

ABSTRACT

In the past years, deep learning has seen an increase in usage in the domain of histopathological applications. However, while these approaches have shown great potential, in high-risk environments deep learning models need to be able to judge their uncertainty and be able to reject inputs when there is a significant chance of misclassification. In this work, we conduct a rigorous evaluation of the most commonly used uncertainty and robustness methods for the classification of Whole Slide Images, with a focus on the task of selective classification, where the model should reject the classification in situations in which it is uncertain. We conduct our experiments on tile-level under the aspects of domain shift and label noise, as well as on slide-level. In our experiments, we compare Deep Ensembles, Monte-Carlo Dropout, Stochastic Variational Inference, Test-Time Data Augmentation as well as ensembles of the latter approaches. We observe that ensembles of methods generally lead to better uncertainty estimates as well as an increased robustness towards domain shifts and label noise, while contrary to results from classical computer vision benchmarks no systematic gain of the other methods can be shown. Across methods, a rejection of the most uncertain samples reliably leads to a significant increase in classification accuracy on both in-distribution as well as out-of-distribution data. Furthermore, we conduct experiments comparing these methods under varying conditions of label noise. Lastly, we publish our code framework to facilitate further research on uncertainty estimation on histopathological data.


Subject(s)
Benchmarking , Humans , Uncertainty , Probability
5.
Digit Health ; 9: 20552076231161962, 2023.
Article in English | MEDLINE | ID: mdl-36908377

ABSTRACT

Objective: Compared to late life dementia, Young Onset Dementia (YOD) has its own distinct challenges, including a lack of specialised and age-appropriate support services. Carers of people with YOD experience higher levels of psychological and physical symptoms, and lower quality of life. This study (RHAPSODY-Plus) assessed the acceptability and feasibility of combining RHAPSODY (Research to Assess Policies and Strategies for Dementia in the Young; a web-based information and skill-building programme for carers of people with YOD) with individually tailored support sessions with health professionals (a social worker and a clinical psychologist) provided via online videoconferencing. Methods: Participants (n = 20) were informal carers aged over 18 years, who were caring for a person with YOD (either Alzheimer's disease or frontotemporal dementia type). Participants used the RHAPSODY programme for 4 weeks, then attended 2 support sessions. Participants and the health professionals then attended individual feedback sessions. Feedback was collected via open-ended and Likert-style questions. Results: The majority of carers rated the RHAPSODY-Plus programme as good to very good, demonstrating a high level of acceptability. Positive feedback about the programme included being able to receive personal advice additionally to the information provided in RHAPSODY. The healthcare professionals also thought the programme was acceptable and beneficial for access to support. Some limitations in the feasibility of videoconferencing included network and technical issues and the loss of non-verbal communication. Conclusions: This online pilot study had a high level of acceptability, demonstrating the potential of an individualised multi-modal intervention for carers of people with YOD which offers opportunities to overcome geographical and service access barriers.

6.
Nanotoxicology ; 16(6-8): 812-827, 2022.
Article in English | MEDLINE | ID: mdl-36480659

ABSTRACT

The inclusion of nanoparticles can increase the quality of certain products. One application is the inclusion of Zinc oxide (ZnO) nanoparticles in a glass coating matrix to produce a UV-absorbing coating for glass sheets. Yet, the question is whether the inclusion of ZnO in the matrix induces toxicity at low exposure levels. To test this, mice were given single intratracheal instillation of 1) ZnO powder (ZnO), 2) ZnO in a glass matrix coating in its liquid phase (ZnO-Matrix), and 3) the matrix with no ZnO (Matrix). Doses of ZnO were 0.23, 0.67, and 2 µg ZnO/mouse. ZnO Matrix doses had equal amounts of ZnO, while Matrix was adjusted to have an equal volume of matrix as ZnO Matrix. Post-exposure periods were 1, 3, or 28 d. Endpoints were pulmonary inflammation as bronchoalveolar lavage (BAL) fluid cellularity, genotoxicity in lung and liver, measured by comet assay, histopathology of lung and liver, and global gene expression in lung using microarrays. Neutrophil numbers were increased to a similar extent with ZnO and ZnO-Matrix at 1 and 3 d. Only weak genotoxicity without dose-response effects was observed in the lung. Lung histology showed an earlier onset of inflammation in material-exposed groups as compared to controls. Microarray analysis showed a stronger response in terms of the number of differentially regulated genes in ZnO-Matrix exposed mice as compared to Matrix only. Activated canonical pathways included inflammatory and cardiovascular ones. In conclusion, the pulmonary toxicity of ZnO was not changed by formulation in a liquid matrix for glass coating.


Subject(s)
Lung Diseases , Nanoparticles , Pneumonia , Zinc Oxide , Mice , Animals , Zinc Oxide/toxicity , Zinc Oxide/metabolism , Lung , Lung Diseases/metabolism , Pneumonia/pathology , Nanoparticles/toxicity , Bronchoalveolar Lavage Fluid
7.
JMIR Med Inform ; 10(8): e36427, 2022 Aug 02.
Article in English | MEDLINE | ID: mdl-35916701

ABSTRACT

BACKGROUND: Deep neural networks are showing impressive results in different medical image classification tasks. However, for real-world applications, there is a need to estimate the network's uncertainty together with its prediction. OBJECTIVE: In this review, we investigate in what form uncertainty estimation has been applied to the task of medical image classification. We also investigate which metrics are used to describe the effectiveness of the applied uncertainty estimation. METHODS: Google Scholar, PubMed, IEEE Xplore, and ScienceDirect were screened for peer-reviewed studies, published between 2016 and 2021, that deal with uncertainty estimation in medical image classification. The search terms "uncertainty," "uncertainty estimation," "network calibration," and "out-of-distribution detection" were used in combination with the terms "medical images," "medical image analysis," and "medical image classification." RESULTS: A total of 22 papers were chosen for detailed analysis through the systematic review process. This paper provides a table for a systematic comparison of the included works with respect to the applied method for estimating the uncertainty. CONCLUSIONS: The applied methods for estimating uncertainties are diverse, but the sampling-based methods Monte-Carlo Dropout and Deep Ensembles are used most frequently. We concluded that future works can investigate the benefits of uncertainty estimation in collaborative settings of artificial intelligence systems and human experts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11936.

8.
Eur J Cancer ; 167: 54-69, 2022 05.
Article in English | MEDLINE | ID: mdl-35390650

ABSTRACT

BACKGROUND: Due to their ability to solve complex problems, deep neural networks (DNNs) are becoming increasingly popular in medical applications. However, decision-making by such algorithms is essentially a black-box process that renders it difficult for physicians to judge whether the decisions are reliable. The use of explainable artificial intelligence (XAI) is often suggested as a solution to this problem. We investigate how XAI is used for skin cancer detection: how is it used during the development of new DNNs? What kinds of visualisations are commonly used? Are there systematic evaluations of XAI with dermatologists or dermatopathologists? METHODS: Google Scholar, PubMed, IEEE Explore, Science Direct and Scopus were searched for peer-reviewed studies published between January 2017 and October 2021 applying XAI to dermatological images: the search terms histopathological image, whole-slide image, clinical image, dermoscopic image, skin, dermatology, explainable, interpretable and XAI were used in various combinations. Only studies concerned with skin cancer were included. RESULTS: 37 publications fulfilled our inclusion criteria. Most studies (19/37) simply applied existing XAI methods to their classifier to interpret its decision-making. Some studies (4/37) proposed new XAI methods or improved upon existing techniques. 14/37 studies addressed specific questions such as bias detection and impact of XAI on man-machine-interactions. However, only three of them evaluated the performance and confidence of humans using CAD systems with XAI. CONCLUSION: XAI is commonly applied during the development of DNNs for skin cancer detection. However, a systematic and rigorous evaluation of its usefulness in this scenario is lacking.


Subject(s)
Artificial Intelligence , Skin Neoplasms , Algorithms , Humans , Neural Networks, Computer , Skin Neoplasms/diagnosis
9.
Eur J Neurosci ; 54(3): 5038-5046, 2021 08.
Article in English | MEDLINE | ID: mdl-33966324

ABSTRACT

Non-invasive techniques are scarce with which human (motor) cortical mechanisms can be investigated. In a series of previous experiments, we have applied an advanced form of conditioning technique with transcranial magnetic stimulation (TMS) and peripheral nerve stimulation by which excitability changes at the laminar level in the primary motor cortex can be estimated. This method builds on the assumption that the first of subsequent corticospinal waves from TMS which is assessed with H-reflexes (called early facilitation) results from indirect excitation of corticospinal neurons in motor cortex (I-wave) and not direct excitation of corticospinal axons (D-wave). So far, we have not provided strong experimental evidence that this is actually the case. In the present study, we therefore compared temporal differences of the early facilitation between transcranial magnetic and electrical stimulation (TES). TES is known to excite the axons of corticospinal neurons. TES in our study caused a temporal shift of the early facilitation of H-reflexes in all subjects compared to TMS, which indicates that the early facilitation with TMS is indeed produced by an I-wave. Additionally, we investigated temporal shifts of the early facilitation with different TMS intensities and two TMS coils. It has long been known that TMS with higher intensities can induce a D-wave. Accordingly, we found that TMS with an intensity of 150% of resting motor threshold compared to 130%/110% results in a temporal shift of the early facilitation, indicating the presence of a D-wave. This effect was dependent on the coil type.


Subject(s)
Motor Cortex , Transcranial Magnetic Stimulation , Electric Stimulation , Electromyography , Evoked Potentials, Motor , H-Reflex , Humans , Muscle, Skeletal , Pyramidal Tracts
10.
J Neurosci Methods ; 350: 109061, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33370559

ABSTRACT

BACKGROUND: Speed of performance improvements and the strength of memory consolidation in humans vary with movement expertise. Underlying neural mechanisms of behavioural differences between levels of movement expertise are so far unknown. NEW METHOD: In this study, PET with [18F]fluorodeoxyglucose (FDG) was proposed as a powerful novel methodology to assess learning-related brain activity patterns during large non-restricted movements (ball throwing with a right hand). 24 male handball players ('Experts') and 24 male participants without handball experience ('Novices') performed visuomotor adaptations to prismatic glasses with or without strategic manoeuvres (i.e., explicit or implicit adaptation). RESULTS: Regional changes in FDG uptake as a marker of neuronal activity, relative to a control condition, were assessed. Prismatic adaptation, in general, was associated with decreased occipital neuronal activity as a possible response to misleading visual information. In 'Experts', the adaptation was associated with altered neuronal activity in a network comprising the right parietal cortex and the left cerebellum. In 'Novices', implicit adaptation resulted in an activation of the middle frontal and inferior temporal gyrus. COMPARISON WITH EXISTING METHODS: This study demonstrates the versatility of FDG PET for studying brain activations patterns in experimental settings with unrestricted movements that are not accessible by other techniques (e.g., fMRI or EEG). CONCLUSIONS: Observed results are consistent with the involvement of different functional networks related to strategic manoeuvres and expertise levels. This strengthens the assumption of different mechanisms underlying behavioural changes associated with movement expertise. Furthermore, the present study underscores the value of FDG PET for studying brain activation patterns during unrestricted movements.


Subject(s)
Adaptation, Physiological , Fluorodeoxyglucose F18 , Brain/diagnostic imaging , Hand , Humans , Male , Movement , Psychomotor Performance
11.
J Strength Cond Res ; 35(1): 247-252, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-29781935

ABSTRACT

ABSTRACT: Kurz, A, Lauber, B, Franke, S, and Leukel, C. Balance training reduces postural sway and improves sport-specific performance in visually impaired cross-country skiers. J Strength Cond Res 35(1): 247-252, 2021-Balance training is highly effective in reducing sport injuries and causes improvements in postural stability and rapid force production. So far, the positive effects of balance training have been described for healthy athletes. In the present experiments, we questioned whether athletes with disabilities of the visual system can also benefit from balance training. Fourteen visually impaired cross-country skiers participated in this randomized controlled study. The intervention group (N = 7) completed 8 sessions of balance training over a period of 4 weeks (2 times per week), whereas a waiting control group (N = 7) received no training during that time. After training, postural sway was significantly reduced in the intervention group but not in the waiting control group. In addition, sport-specific performance, which was assessed by a standardized Cooper's 12-minute test on roller skis or rollerblades, increased in the intervention group. The change in postural sway from the premeasurement to the postmeasurement correlated with the change in sport-specific performance in all subjects. Our results indicate that balance training is useful for improving postural stability and sport-specific performance in visually impaired cross-country skiers. We propose that balance training should therefore be implemented as part of the training routine in athletes with disabilities of the visual system.


Subject(s)
Postural Balance , Sports , Athletes , Humans
12.
JMIR Mhealth Uhealth ; 8(7): e16928, 2020 07 31.
Article in English | MEDLINE | ID: mdl-32735223

ABSTRACT

BACKGROUND: Modern technologies, including smartphone apps, have the potential to assist people with cognitive impairment with activities of daily living, allowing them to maintain their independence and reduce carer burden. However, such tools have seen a slow rate of uptake in this population, and data on the acceptability of assistive technologies in this population are limited. OBJECTIVE: This pilot study included older adults with cognitive impairment and their carers, and explored the perceived needs for and acceptability of an app that was designed to be a simple assistive tool for activities of daily living. In particular, this study aimed to assess the acceptability of common app functions such as communication, reminder, navigation, and emergency tools in this population, and to compare patients' and carers' responses to them. METHODS: A total of 24 German participants with mild cognitive impairment or dementia and their family carers separately completed two short questionnaires. The first questionnaire asked the participants with cognitive impairment and their carers to self-rate the patients' cognitive impairment levels and affinity to technology. Following a demonstration of the app, participants rated the usability and acceptability of the app and its functions in a second questionnaire. RESULTS: Participants rated themselves as much less cognitively impaired than their carers did (P=.01), and insight into the level of support they received was low. The majority of the participants (19/24, 79%) and their carers (20/24, 83%) had low affinity to technology, and even after the demonstration, 63% (15/24) of the participants had low interest in using the app. A breakdown of acceptability responses by app function revealed that participants were more amenable to the reminder function, the emergency feature, and a wearable form of the app. Features that centered around carers monitoring participants' movements were reported to be less acceptable to participants. CONCLUSIONS: This study highlights the importance of focusing on acceptability and the consumer's perceptions in the development of assistive technology for older adults with cognitive impairment. Participants showed an aversion to functions they perceived as eroding their independence, while functions that more closely aligned with independence and autonomy were perceived as more acceptable.


Subject(s)
Activities of Daily Living , Cognitive Dysfunction , Mobile Applications , Adult , Aged , Aged, 80 and over , Caregivers/psychology , Cognitive Dysfunction/therapy , Female , Humans , Male , Middle Aged , Pilot Projects , Surveys and Questionnaires
13.
Hum Mov Sci ; 72: 102655, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32721374

ABSTRACT

PURPOSE: Acute whole-body vibration (WBV) is known to enhance neuromuscular activation. Especially mechanisms which act presynaptically are discussed to be involved in this modulation, but evidence is still limited. Therefore, this study aimed to investigate if 2 min of WBV might impact the premotoneuronal mechanism of post-activation depression (PAD). METHODS: PAD in m. soleus was assessed by paired-pulse stimulation in 28 healthy participants prior, 2 min, 4 min and 10 min after 2 min of side-alternating WBV (10 Hz, 2 mm). Methodologies involved electromyography (m. soleus, m. tibialis anterior) and goniometric recordings (ankle, knee joint). H-reflexes were elicited with peripheral nerve stimulation and assessed by means of conditioned H-reflexes (ISI 1 s, Hcond) versus control H-reflexes (ISI10, H). RESULTS: Hcond/H was significantly enhanced by +55% (2 min), +32% (4 min) and +35% (10 min) following WBV (P < 0.05). Baseline muscle activity and joint positions were shown to be reliable (Cronbach's α values >0.990) throughout the testing procedure. CONCLUSION: Vibratory-induced spinal inhibition is accompanied by diminished PAD at the presynaptic terminals which interconnect the Ia afferents with the α-motoneuron. Functionally, the PAD reduction might explain enhanced motor performance following vibration therapy, but future studies will be needed to verify this assumption.


Subject(s)
H-Reflex , Long-Term Synaptic Depression , Motor Neurons/physiology , Muscle, Skeletal/physiology , Presynaptic Terminals/physiology , Psychomotor Performance , Vibration , Adult , Ankle/physiology , Biomechanical Phenomena , Electromyography , Female , Healthy Volunteers , Humans , Knee Joint/physiology , Leg/physiology , Male , Muscle Contraction , Young Adult
14.
Alzheimers Dement ; 16(5): 759-769, 2020 05.
Article in English | MEDLINE | ID: mdl-32270596

ABSTRACT

INTRODUCTION: In mice there might be an association between sleep deprivation and amyloid ß plasma levels. Hence, we examined whether amyloid plasma levels are associated with sleep duration or fragmentation in 17 psychiatrists on-call. METHODS: Amyloid ß (Aß)42, Aß40, and soluble amyloid precursor protein ß (sAPP-ß) plasma concentrations were measured at the beginning and end of 90 on-call nights, and analyzed using generalized linear models. RESULTS: In on-call nights, a 10.7% reduction of Aß42 was revealed overnight. Every single short sleep interruption diminished this reduction by 5.4%, as well as every pg/mL of sAPP-ß by 1.2%, each copy of APOE ε4 by 10.6%, and each year of professional experience by 3.0%. DISCUSSION: The extent of sleep fragmentation diminishes the physiological overnight reduction of Aß42 but not Aß40 plasma levels in the same direction as the enzyme for Aß42 production, the genetic risk factor for Alzheimer's disease (AD), and on-call experience. Might on-call duty and sleep fragmentation in general alter the risk for AD?


Subject(s)
Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Psychiatry , Sleep Deprivation/physiopathology , Adult , Alzheimer Disease/genetics , Amyloid beta-Peptides/blood , Amyloid beta-Protein Precursor/blood , Apolipoprotein E4/genetics , Female , Humans , Male
15.
J Physiol ; 598(6): 1235-1251, 2020 03.
Article in English | MEDLINE | ID: mdl-32057108

ABSTRACT

KEY POINTS: Discrete and rhythmic dynamics are inherent components of (human) movements. We provide evidence that distinct human motor cortex circuits contribute to discrete and rhythmic movements. Excitability of supragranular layer circuits of the human motor cortex was higher during discrete movements than during rhythmic movements. Conversely, more complex corticospinal circuits showed higher excitability during rhythmic movements than during discrete movements. No task-specific differences existed for corticospinal output neurons at infragranular layers. The excitability differences were found to be time(phase)-specific and could not be explained by the kinematic properties of the movements. The same task-specific differences were found between the last cycle of a rhythmic movement period and ongoing rhythmic movements. ABSTRACT: Human actions entail discrete and rhythmic movements (DM and RM, respectively). Recent insights from human and animal studies indicate different neural control mechanisms for DM and RM, emphasizing the intrinsic nature of the task. However, how distinct human motor cortex circuits contribute to these movements remains largely unknown. In the present study, we tested distinct primary motor cortex and corticospinal circuits and proposed that they show differential excitability between DM and RM. Human subjects performed either 1) DM or 2) RM using their right wrist. We applied an advanced electrophysiological approach involving transcranial magnetic stimulation and peripheral nerve stimulation to test the excitability of the neural circuits. Probing was performed at different movement phases: movement initiation (MI, 20 ms after EMG onset) and movement execution (ME, 200 ms after EMG onset) of the wrist flexion. At MI, excitability at supragranular layers was significantly higher in DM than in RM. Conversely, excitability of more complex corticospinal circuits was significantly lower in DM than RM at ME. No task-specific differences were found for direct corticospinal output neurons at infragranular layers. The neural differences could not be explained by the kinematic properties of the movements and also existed between ongoing RM and the last cycle of RM. Our results therefore strengthen the hypothesis that different neural control mechanisms engage in DM and RM.


Subject(s)
Motor Cortex/physiology , Movement , Electromyography , Humans , Transcranial Magnetic Stimulation , Wrist
16.
Mol Psychiatry ; 25(10): 2608-2619, 2020 10.
Article in English | MEDLINE | ID: mdl-30120417

ABSTRACT

18F-FIBT, 2-(p-Methylaminophenyl)-7-(2-[18F]fluoroethoxy)imidazo-[2,1-b]benzothiazole, is a new selective PET tracer under clinical investigation to specifically image ß-amyloid depositions (Aß) in humans in-vivo that binds to Aß with excellent affinity (Kd 0.7 ± 0.2) and high selectivity over tau and α-synuclein aggregates (Ki > 1000 nM). We aimed to characterize 18F-FIBT in a series of patients with different clinical-pathophysiological phenotypes and to compare its binding characteristics to the reference compound PiB. Six patients (mild late-onset and moderate early-onset AD dementia, mild cognitive impairment due to AD, intermediate likelihood, mild behavioral variant of frontotemporal dementia, subjective memory impairment without evidence of neurodegeneration, and mild dementia due to Posterior Cortical Atrophy) underwent PET imaging with 18F-FIBT on PET/MR. With the guidance of MRI, PET images were corrected for partial volume effect, time-activity curves (TACs) of regions of interest (ROIs) were extracted, and non-displaceable binding potentials (BPnd), standardized uptake value ratios (SUVR), and distribution volume ratio (DVR) were compared. Specific binding was detected in the cases with evidence of the AD pathophysiological process visualized in images of BPnd, DVR and SUVR, consistently with patterns of different tracers in previous studies. SUVR showed the highest correlation with clinical severity. The previous preclinical characterization and the results of this case series suggest the clinical usefulness of FIBT as a selective and highly affine next-generation 18F-labeled tracer for amyloid-imaging with excellent pharmacokinetics in the diagnosis of neurodegenerative diseases. The results compare well to the gold standard PiB and hence support further investigation in larger human samples.


Subject(s)
Neurodegenerative Diseases/diagnostic imaging , Positron-Emission Tomography/methods , Aged , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/analysis , Aniline Compounds , Female , Humans , Male , Middle Aged
17.
Mol Psychiatry ; 25(3): 629-639, 2020 03.
Article in English | MEDLINE | ID: mdl-29988083

ABSTRACT

Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.


Subject(s)
ADAM17 Protein/genetics , Alzheimer Disease/genetics , ADAM17 Protein/metabolism , Aged , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Protein Precursor/genetics , Case-Control Studies , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Germany , Humans , Loss of Function Mutation/genetics , Male , Middle Aged , Mutation , Exome Sequencing
18.
Mol Psychiatry ; 25(10): 2643, 2020 Oct.
Article in English | MEDLINE | ID: mdl-30464328

ABSTRACT

The author listing has been updated to indicate that Timo Grimmer and Kuangyu Shi are equally contributing authors.

19.
Front Hum Neurosci ; 13: 359, 2019.
Article in English | MEDLINE | ID: mdl-31649520

ABSTRACT

The relation between primary motor cortex (M1) activity and (muscular) force output has been studied extensively. Results from previous studies indicate that activity of a part of yet unidentified neurons in M1 are positively correlated with increased force levels. One considerable candidate causing this positive correlation could be circuits at supragranular layers. Here we tested this hypothesis and used the combination of H-reflexes with transcranial magnetic stimulation (TMS) to investigate laminar associations with force output in human subjects. Excitability of different M1 circuits were probed at movement onset and at peak torque while participants performed auxotonic contractions of the wrist with different torque levels. Only at peak torque we found a significant positive correlation between excitability of M1 circuits most likely involving neurons at supragranular layers and joint torque level. We argue that this finding may relate to the special role of upper layer circuits in integrating (force-related) afferent feedback and their connectivity with task-relevant pyramidal and also extrapyramidal pathways projecting to motoneurones in the spinal cord.

20.
Neuropsychiatr Dis Treat ; 15: 2503-2511, 2019.
Article in English | MEDLINE | ID: mdl-31507321

ABSTRACT

BACKGROUND: Dementia is a particularly severe societal challenge in several countries of the Danube Region due to higher-than-average increment in population longevity, disproportionate increase of the old-age dependency ratio, and selective outward migration of health care professionals. A survey was conducted among dementia experts to obtain a deeper understanding of the dementia care structures and services in this geographical area, and to identify the educational needs of health care professionals, and the availability of assistive technology. SUBJECTS AND METHODS: A standardized questionnaire was sent out to 15 leading dementia experts/clinicians in 10 Danube Region countries inquiring about professional groups involved in dementia care, availability and reimbursement of services, inclusion of dementia in professional education and training, acceptability of Internet-based education, and availability of assistive technology. The authors are the survey respondents. RESULTS: The majority of individuals with dementia receive care in the community rather than in institutions. The roles of medical specialties are disparate. General practitioners usually identify dementia symptoms while specialists contribute most to clinical diagnosis and treatment. Health care professionals, particularly those who work closely with patients and carers, have limited access to dementia-specific education and training. The greatest need for dementia-specific education is seen for general practitioners and nurses. An Internet-based education and skill-building program is considered to be equivalent to traditional face-to-face but offer advantages in terms of convenience of access. Assistive technology is available in countries of the Danube Region but is significantly underused. CONCLUSION: Dementia care in the Danube Region can be improved by an educational and skill-building program for health care professionals who work in the frontline of dementia care. Such a program should also attempt to enhance interdisciplinary and intersectorial collaboration, to intensify the interaction between primary care and specialists, and to promote the implementation of assistive technology.

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