Evaluating Gait Impairment in Parkinson's Disease from Instrumented Insole and IMU Sensor Data.

Parkinson's disease (PD) is characterized by a variety of motor and non-motor symptoms, some of them pertaining to gait and balance. The use of sensors for the monitoring of patients' mobility and the extraction of gait parameters, has emerged as an objective method for assessing the efficacy of their treatment and the progression of the disease. To that end, two popular solutions are pressure insoles and body-worn IMU-based devices, which have been used for precise, continuous, remote, and passive gait assessment. In this work, insole and IMU-based solutions were evaluated for assessing gait impairment, and were subsequently compared, producing evidence to support the use of instrumentation in everyday clinical practice. The evaluation was conducted using two datasets, generated during a clinical study, in which patients with PD wore, simultaneously, a pair of instrumented insoles and a set of wearable IMU-based devices. The data from the study were used to extract and compare gait features, independently, from the two aforementioned systems. Subsequently, subsets comprised of the extracted features, were used by machine learning algorithms for gait impairment assessment. The results indicated that insole gait kinematic features were highly correlated with those extracted from IMU-based devices. Moreover, both had the capacity to train accurate machine learning models for the detection of PD gait impairment.

A User-Centric approach for Personalization based on Human Activity Recognition.

The objective of this work focuses on multiple independent user profiles that capture behavioral, emotional, medical, and physical patterns in the working and living environment resulting in one general user profile. Depending on the user's current activity (e.g. walking, eating, etc.), medical history, and other influential factors, the developed framework acts as a supplemental assistant to the user by providing not only the ability to enable supportive functionalities (e.g. image filtering, magnification, etc.) but also informative recommendations (e.g. diet, alcohol, etc.). The personalization of such a profile lies within the user's past preferences using human activity recognition as a base, and it is achieved through a statistical model, the Bayesian belief network. Training and real-time methodological pipelines are introduced and validated. The employed deep learning techniques for identifying human activities are presented and validated in publicly available and in-house datasets. The overall accuracy of human activity recognition reaches up to 86.96 %.

Real Time Human Activity Recognition Using Acceleration and First-Person Camera data.

The aim of this work is to present an automated method, working in real time, for human activity recognition based on acceleration and first-person camera data. A Long-Short-Term-Memory (LSTM) model has been built for recognizing locomotive activities (i.e. walking, sitting, standing, going upstairs, going downstairs) from acceleration data, while a ResNet model is employed for the recognition of stationary activities (i.e. eating, reading, writing, watching TV working on PC). The outcomes of the two models are fused in order for the final decision, regarding the performed activity, to be made. For the training, testing and evaluation of the proposed models, a publicly available dataset and an "in-house" dataset are utilized. The overall accuracy of the proposed algorithmic pipeline reaches 87.8%.

Association of Genetic Variation in the 3'UTR of LHX6, IMMP2L, and AADAC With Tourette Syndrome.

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder that presents with motor and vocal tics early in childhood. The aim of this study was to investigate genetic variants in the 3' untranslated region (3'UTR) of TS candidate genes with a putative link to microRNA (miRNA) mediated regulation or gene expression. Methods: We used an in silico approach to identify 32 variants in the 3'UTR of 18 candidate genes putatively changing the binding site for miRNAs. In a sample composed of TS cases and controls (n = 290), as well as TS family trios (n = 148), we performed transmission disequilibrium test (TDT) and meta-analysis. Results: We found positive association of rs3750486 in the LIM homeobox 6 (LHX6) gene (p = 0.021) and rs7795011 in the inner mitochondrial membrane peptidase subunit 2 (IMMP2L) gene (p = 0.029) with TS in our meta-analysis. The TDT showed an over-transmission of the A allele of rs1042201 in the arylacetamide deacetylase (AADAC) gene in TS patients (p = 0.029). Conclusion: This preliminary study provides further support for the involvement of LHX6, IMMP2L, and AADAC genes, as well as epigenetic mechanisms, such as altered miRNA mediated gene expression regulation in the etiology of TS.

Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology.

Although the genetic basis of Tourette Syndrome (TS) remains unclear, several candidate genes have been implicated. Using a set of 382 TS individuals of European ancestry we investigated four candidate genes for TS (HDC, SLITRK1, BTBD9, and SLC6A4) in an effort to identify possibly causal variants using a targeted re-sequencing approach by next generation sequencing technology. Identification of possible disease causing variants under different modes of inheritance was performed using the algorithms implemented in VAAST. We prioritized variants using Variant ranker and validated five rare variants via Sanger sequencing in HDC and SLITRK1, all of which are predicted to be deleterious. Intriguingly, one of the identified variants is in linkage disequilibrium with a variant that is included among the top hits of a genome-wide association study for response to citalopram treatment, an antidepressant drug with off-label use also in obsessive compulsive disorder. Our findings provide additional evidence for the implication of these two genes in TS susceptibility and the possible role of these proteins in the pathobiology of TS should be revisited.

Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families.

BACKGROUND: Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. METHODS: Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. RESULTS AND CONCLUSIONS: Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.

The role of hepatic stimulator substance (HSS) on liver regeneration arrest induced by cadmium.

BACKGROUND: The mechanism of cadmium-induced liver regeneration arrest in relation to hepatic stimulator substance (HSS) biological activity was investigated. MATERIALS AND METHODS: In Wistar rats subjected to 65 - 70% partial hepatectomy, saline, cadmium, cadmium and HSS were administered. The rats were also subjected to 30 - 34% partial hepatectomy. Mitotic index, immunochemistry for PCNA, 3[H]-thymidine incorporation into DNA and thymidine kinase activity were used as indices of liver regeneration. HSS biological activity was evaluated in all groups of rats using a bioassay. RESULTS: Liver regeneration and HSS activity were arrested by cadmium during the first 24 h after partial hepatectomy. Both in normal and in cadmium-treated rats, the HSS activity was increased and liver regeneration coincided. HSS activity was stable in 30 - 34% hepatectomized rats. HSS administration was able to restore liver regeneration arrest induced by cadmium. CONCLUSION: The biological activity of HSS increased at the time of G1/S transition of hepatocytes in the cell cycle and no increase was observed with asynchronous G1/S transition (30 - 34% partial hepatectomy). The suppression of HSS biological activity by cadmium seems to represent an important factor for liver regeneration arrest induced by the metal and HSS administration is able to restore liver regeneration.

The hepatoprotective effect of hepatic stimulator substance (HSS) against liver regeneration arrest induced by acute ethanol intoxication.

Male Wistar rats were randomized to receive ethanol (2.5 ml/kg by gastric intubation every 8 hr; group I), equal volumes of isocaloric to ethanol sucrose solution (group II), or ethanol and HSS (100 mg/kg intraperitoneally 10 and 16 hr after partial hepatectomy; groups III and IV, respectively) for up to 96 hr after partial hepatectomy, with ethanol administration starting 1 hr prior to partial hepatectomy. Animals were killed at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, and 96 hr after partial hepatectomy. The rate of liver regeneration was evaluated by the mitotic index in H&E-stained sections, immunochemical detection of Ki67 nuclear antigen, rate of [3H]thymidine incorporation into hepatic DNA, and liver thymidine kinase enzymatic activity. The biological activity of HSS in groups I and II rats was evaluated using a bioassay. Ethanol administration arrested liver regeneration during the first 32 hr after partial hepatectomy and suppressed HSS activity throughout the period examined. Liver regeneration progressed after 32 hr despite the low levels of HSS activity. HSS administration at 10 and 16 hr reversed liver regeneration arrest induced by ethanol. Acute ethanol administration induces cell cycle arrest during the first 32 hr after partial hepatectomy and suppression of HSS biological activity seems to contribute to this effect. HSS administration reversed the inhibitory effect of ethanol on liver regeneration and caused synchronized entrance of hepatocytes in the S phase of the cell cycle. HSS seems to participate in the network of growth factors controlling the G1/S cell cycle checkpoint.