An automated system for the objective evaluation of human gustatory sensitivity using tongue biopotential recordings

The goal of this work is to develop an automatic system for the evaluation of the gustatory sensitivity of patients using an electrophysiological recording of the response of bud cells to taste stimuli. In particular, the study aims to evaluate the effectiveness and limitations of supervised classifiers in the discrimination between subjects belonging to the three 6-n-pro-pylthiouracil (PROP) taster categories (supertasters, medium tasters, and non-tasters), exploiting features extracted from electrophysiological recordings of the tongue. Thirty-nine subjects (equally divided into the three PROP status classes by standard non-objective scaling methods) underwent a non-invasive, differential, biopotential recording of their tongues during stimulation with PROP by using a custom-made, flexible, silver electrode. Two different classifiers were trained to recognize up to seven different features extracted from the recorded depolarization signal. The classification results indicate that the identified set of features allows to distinguish between PROP tasters and non-tasters (average accuracy of 80% ± 18% and up to 94% ± 15% when only supertasters and non-tasters are considered), but medium tasters were difficult to identify. However, these apparent classification errors are related to uncertainty in the labeling procedures, which are based on non-objective tests, in which the subjects provided borderline evaluations. Thus, using the proposed method, it is possible, for the first time, to automatically achieve objective PROP taster status identification with high accuracy. The simplicity of the recording technique allows for easy reproduction of the experimental setting; thus the technique can be used in future studies to evaluate other gustatory stimuli. The proposed approach represents the first objective and automatic method to directly measure human gustatory responses and a milestone for physiological taste studies, with applications ranging from basic science to food tasting evaluations

Bone Marrow Concentrate in the Treatment of Aneurysmal Bone Cysts: A Case Series Study

Introduction. A recent attractive option regarding mesenchymal stem cells (MSC) application is the treatment of bone cystic lesions and in particular aneurysmal bone cysts (ABC), in order to stimulate intrinsic healing. We performed a retrospective evaluation of the results obtained at our institution.Methods. The study group consisted of 46 cases with an average follow-up of 33 months. Forty-two patients underwent percutaneous treatment as the first approach; four patients had curettage as first treatment. In all cases, autologous bone marrow concentrate (BMC) was associated too. The healing status was followed up through a plain radiograph 45 days and 2 months after the procedure.Results and Conclusions.At the final follow-up, thirty-six patients healed with a Neer type II aspect, nine healed with a type I aspect, and one patient was not classified having total hip arthroplasty. Bone marrow concentrate is easy to obtain and to manipulate and can be immediately available in a clinical setting. We can assert that the use of BMC must be encouraged being harmless and having an unquestionable high osteogenic and healing potential in bone def

Parylene C-based, breathable tattoo electrode for high-quality biopotential measurements

A breathable tattoo electrode for bio-potential recording based on a Parylene C nanofilm is presented in this study. The proposed approach allows for the fabrication of micro-perforated epidermal submicrometer-thick electrodes that conjugate the unobtrusiveness of Parylene C nanofilms and the very important feature of breathability. The electrodes were fully validated for electrocardiography (ECG) measurements showing performance comparable to that of conventional disposable gelled Ag/AgCl electrodes, with no visible negative effect on the skin even many hours after their application. This result introduces interesting perspectives in the field of epidermal electronics, particularly in applications where critical on-body measurements are involved

Modelling the cascade of biomarker changes in progranulin‐related frontotemporal dementia

AbstractBackgroundProgranulin related frontotemporal dementia (FTD‐GRN) is a fast progressive disorder, in which pathophysiological changes precede overt clinical symptoms in only a short time period. Modelling the cascade of multimodal biomarker changes aids in understanding the etiology of this disease, enables monitoring of individual mutation carriers, and would give input for disease‐modifying treatments. In this cross‐sectional study, we estimated the temporal cascade of biomarker changes for FTD‐GRN, in a data‐driven way.MethodWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non‐carriers. Of the symptomatic subjects, 17 had behavioural variant FTD (bvFTD), 16 presented as non‐fluent variant primary progressive aphasia (nfvPPA). The selected biomarkers for establishing the cascade of changes were neurofilament light chain, regional grey matter volumes, fractional anisotropy of white matter tracts, and cognitive domains. We used a data‐driven analysis called discriminative event‐based modelling (Venkatraghavan, NeuroImage, 2019) with a novel modification to its Gaussian Mixture Model (GMM) called Siamese GMM, to estimate the cascade of biomarker changes for FTD‐GRN. Using cross‐validation, we estimated disease severities of individual mutation carriers in the test set based on their progression along the biomarker cascade established on the training set.ResultNeurofilament light chain and white matter tracts were the earliest biomarkers to become abnormal in FTD‐GRN mutation carriers. Attention and executive functioning were also affected early on in the disease process. Based on the estimated individual disease severities, presymptomatic mutation carriers could be distinguished from symptomatic mutation carriers with a sensitivity of 95% and specificity of 100% in the cross‐validation experiment. There was a high correlation (r=0.94, p<0.001) between estimated disease severity and years since symptom onset in nfvPPA, but not in bvFTD (r=0.33, p=0.46).ConclusionIn this study, we unravelled the temporal cascade of multimodal biomarker changes for FTD‐GRN. Our results suggest that axonal degeneration is one of the first disease events in FTD‐GRN, which calls for designing disease modifying treatments that strengthens the axons. We also demonstrated a good delineation between symptomatic and presymptomatic carriers using the estimated disease severities, which suggest that our model could enable monitoring of individual mutation carriers

Education modulates brain maintenance in presymptomatic frontotemporal dementia

Objective Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time. Methods Two-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling. Results Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline;moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers. Conclusions This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD

Ultra-Efficient PrPSc Amplification Highlights Potentialities and Pitfalls of PMCA Technology

In order to investigate the potential of voles to reproduce in vitro the efficiency of prion replication previously observed in vivo, we seeded protein misfolding cyclic amplification (PMCA) reactions with either rodent-adapted Transmissible Spongiform Encephalopathy (TSE) strains or natural TSE isolates. Vole brain homogenates were shown to be a powerful substrate for both homologous or heterologous PMCA, sustaining the efficient amplification of prions from all the prion sources tested. However, after a few serial automated PMCA (saPMCA) rounds, we also observed the appearance of PK-resistant PrPSc in samples containing exclusively unseeded substrate (negative controls), suggesting the possible spontaneous generation of infectious prions during PMCA reactions. As we could not definitively rule out cross-contamination through a posteriori biochemical and biological analyses of de novo generated prions, we decided to replicate the experiments in a different laboratory. Under rigorous prion-free conditions, we did not observe de novo appearance of PrPSc in unseeded samples of M109M and I109I vole substrates, even after many consecutive rounds of saPMCA and working in different PMCA settings. Furthermore, when positive and negative samples were processed together, the appearance of spurious PrPSc in unseeded negative controls suggested that the most likely explanation for the appearance of de novo PrPSc was the occurrence of cross-contamination during saPMCA. Careful analysis of the PMCA process allowed us to identify critical points which are potentially responsible for contamination events. Appropriate technical improvements made it possible to overcome PMCA pitfalls, allowing PrPSc to be reliably amplified up to extremely low dilutions of infected brain homogenate without any false positive results even after many consecutive rounds. Our findings underline the potential drawback of ultrasensitive in vitro prion replication and warn on cautious interpretation when assessing the spontaneous appearance of prions in vitro

ANALISIS SISTEM PENGENDALIAN INTERN PENERIMAAN DAN PENGELUARAN KAS PADA PT. ASURANSI BRINGIN SEJAHTERA ARTAMAKMUR CABANG MEDAN

Penelitian ini bertujuan untuk mengetahui sejauh mana sistem pengendalian intern penerimaan dan pengeluaran kas yang dilakukan PT. Asuransi Bringin Sejahtera Artamamakmur Cabang Medan dalam menjalankan kegiatan usahanya guna mencapai tujuan perusahaan. Teori yang digunakan dalam penelitian ini adalah teori Mulyadi. Metode yang digunakan dalam penelitian ini adalah Penelitian Kualitatif, dengan teknik analisis data Deskriptif, yaitu dengan terlebih dahulu mengumpulkan data, mengklasifikasikan serta menafsirkan data sehingga dapat memberikan gambaran yang jelas mengenai masalah yang diteliti. Dalam pengumpulan data menggunakan teknik wawancara dan dokumentasi, dimana data yang diambil merupakan data primer yang berupa bukti catatan atau laporan historis yang telah tersusun dalam arsip yang dipublikasi maupun yang tidak dipublikasikan. Hasil penelitian ini menunjukan bahwa pengendalian intern penerimaan dan pengeluaran kas PT. Asuransi Bringin Sejahtera Artamakmur Cabang Medan belum sepenuhnya memenuhi unsur-unsur pengendalian intern, karena masih adanya beberapa hal yang tidak sesuai dengan teori yang ada. Diantaranya, masih ada perangkapan tugas yang dilakukan bagian kasir dengan bagian akuntansi. Demikian juga dalam hal pembagian tugas, dimana bagian kasir diberi tanggung jawab dalam hal penagihan premi, yang sebaiknya tugas ini bukan dipegang unit tersebut. Praktik-praktik ini ditakutkan akan mengurangi keakuratan pencatatan dan juga akan membuka peluang terjadinya penyelewengan terhadap kas yang mengakibatkan kerugian perusahaan. Hal ini juga akan mengurangi keefektifan dalam praktik kerja bagian kasir, karena terlalu banyak memegang fungsi