Transcutaneous vagus nerve stimulation does not affect verbal memory performance in healthy volunteers

Introduction: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders. Methods: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition. Results: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores. Conclusion: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits

Evaluation of right ventricular function performed by 3d-echocardiography in scleroderma patients

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc

Characterization of PDF1 and its interaction with DELAY OF GERMINATION1 (DOG1) in the control of seed dormancy in Arabidopsis thaliana

Seed dormancy is defined as the incapacity of a viable seed to germinate under favourable conditions. It is established during seed maturation and reaches high levels in mature dry seeds. Dormancy is a complex adaptive trait that assures germination at proper time of the year at the onset of the favourable growing season. This trait is regulated by hormonal and environmental cues such as temperature and light. In Arabidopsis thaliana dormancy can be released by imbibing seeds at cold temperatures (stratification) or by storing seeds in dry conditions (after- ripening). The molecular mechanisms that regulate the induction and the release of dormancy are still poorly understood. Previous studies identified DELAY OF GERMINATION1 (DOG1) as a key regulator of seed dormancy in Arabidopsis. The dog1 mutant completely lacks seed dormancy and has no pleiotropic effects. DOG1 shows a seed-specific expression pattern and the abundance of its protein correlates with the dormancy level in freshly harvested seeds. However, this correlation is lacking in after-ripened seeds, suggesting that the protein activity is lost during after ripening (Nakabayashi et al., 2012). DOG1 encodes a protein with unknown function and unknown regulation. The phosphatase PDF1 was identified as an interactor of DOG1 in a yeast two hybrid assay. This thesis describes the relation between PDF1 and DOG1 which was investigated in order to gain further insights into the regulation of DOG1 and into the mechanisms controlling seed dormancy. A T-DNA insertion mutant named pdf1-1 showed increased dormancy. PDF1 and DOG1 were co-expressed during seed maturation, interacted in vivo and were shown to function in the same pathway independent from ABA. Two-dimensional gels analysis showed that DOG1 is targeted by two different post-translational modifications during after ripening and after imbibition. DOG1 shifted towards a lower pH during after-ripening, while imbibition caused a shift towards the basic side. In the pdf1-1 mutant DOG1 was detected at a lower pH in comparison to Columbia, indicating possible increased phosphorylation levels and implying a role of PDF1 in the dephosphorylation of DOG1. Moreover, the shift of DOG1 caused by the after-ripening was not observed in the pdf1-1 mutant, suggesting that the post-translational modifications of DOG1 are interdependent

Neuropsychological functioning in children with a surgically corrected congenital heart disease

Door een enorme vooruitgang in de pediatrische hartheelkunde over de laatste 35 jaren, worden we geconfronteerd met een steeds groter wordende groep kinderen met een aangeboren hartafwijking (AHA). Ondanks de toegenomen overlevingskansen, blijft morbiditeit echter een grote zorg. Aangeboren hartafwijkingen worden immers geassocieerd met neurologische tekorten en een ontwikkelingsachterstand. De mid-term functionele status van het kind blijft tot hiertoe echter onbekend. We onderzochten het neuropsychologische profiel, het gedrag, de emotionele beleving en zelfperceptie van kinderen met een chirurgisch gecorrigeerde AHA 6 tot 12 jaar postoperatief door ze te vergelijken met een gezonde controlegroep. We weerhouden bij kinderen met een AHA een neuropsychologisch profiel dat voornamelijk milde motorisch tekorten vertoont alsook discrete taalproblemen. Aandacht -en executief functioneren, mede als het geheugen blijken, hoewel in mindere mate, eveneens betrokken. Ouders van kinderen met een AHA beschrijven hun kinderen als minder schoolbekwaam, ze halen minder goede schoolresultaten en het overdoen van een schooljaar komt meer voor in deze groep. Op een cognitieve klachtenlijst rapporteren de ouders van AHA kinderen meer aandacht- en geheugenproblemen, alsook een minder goede grove motoriek. Op gebied van gedrag vertonen deze kinderen volgens hun ouders meer sociale en aandachtsproblemen, en eveneens meer agressief gedrag. Uit zelfrapportering door de kinderen leiden we af dat er geen verschil is in het zelfconcept van de kinderen met AHA ten opzichte van gezonde controlekinderen op gebied van schoolse vaardigheden, sociale aanvaarding, sportieve vaardigheden en met name motoriek, uiterlijk, gedrag en zelfwaardering. Ze rapporteren geen verhoogde angst, maar wel meer depressieve symptomen dan gezonde controlekinderen. Deze beschrijving van de volledige functionele status van kinderen met een chirurgisch gecorrigeerde AHA 6 tot 12 jaar postoperatief, biedt mogelijkheden om gespecialiseerde interventies op te zetten aangepast aan de noden van het kind en de familie. Op deze manier kan de functionele status van het kind verbeteren. De oorzaak van deze functionele tekorten moet verder worden bestudeerd en moet zowel pre-, peri- als postoperatieve variabelen opnemen. Hoogst waarschijnlijk veroorzaakt een combinatie van factoren negatieve resultaten op langere termijn. De studie bekrachtigt ook het gebruik van ouderlijke vragenlijsten en wijst op de nood aan een multidisciplinaire aanpak van de follow-up van kinderen met een AHA. Enkel op deze manier kunnen problemen vroeg worden geïdentificeerd en aangepakt wat zal leiden tot een verbeterde levenskwaliteit bij kinderen met AHA

Machine learning to predict overall short-term mortality in cutaneous melanoma

Background: Cutaneous malignant melanoma (CMM) ranks among the ten most frequent malignancies, clinicopathological staging being of key importance to predict prognosis. Artificial intelligence (AI) has been recently applied to develop prognostically reliable staging systems for CMM. This study aims to provide a useful machine learning based tool to predict the overall CMM short-term survival. Methods: CMM records as collected at the Veneto Cancer Registry (RTV) and at the Veneto regional health service were considered. A univariate Cox regression validated the strength and direction of each independent variable with overall mortality. A range of machine learning models (Logistic Regression classifier, Support-Vector Machine, Random Forest, Gradient Boosting, and k-Nearest Neighbors) and a Deep Neural Network were then trained to predict the 3-years mortality probability. Five-fold cross-validation and Grid Search were performed to test the best data preprocessing procedures, features selection, and to optimize models hyperparameters. A final evaluation was carried out on a separate test set in terms of balanced accuracy, precision, recall and F1 score. The best model was deployed as online tool. Results: The univariate analysis confirmed the significant prognostic value of TNM staging. Adjunctive clinicopathological variables not included in the AJCC 8th melanoma staging system, i.e., sex, tumor site, histotype, growth phase, and age, were significantly linked to overall survival. Among the models, the Neural Network and the Random Forest models featured the best prognostic performance, achieving a balanced accuracy of 91% and 88%, respectively. According to the Gini importance score, age, T and M stages, mitotic count, and ulceration appeared to be the variables with the greatest impact on survival prediction. Conclusions: Using data from patients with CMM, we developed an AI algorithm with high staging reliability, on top of which a web tool was implemented (unipd.link/melanomaprediction). Being essentially based on routinely recorded clinicopathological variables, it can already be implemented with minimal effort and further tested in the current clinical practice, an essential phase for validating the model’s accuracy beyond the original research context

Comparison of Two Autonomous AC-DC Converters for Piezoelectric Energy Scavenging Systems

International audiencePiezoelectric Energy Scavenging Systems (PESS) are used to convert the energy of mechanical vibrations into electrical energy exploiting the piezoelectric effect. Their output is a voltage which strongly varies in time; to obtain a suitable supply source an AC-DC conversion of the output voltage of these transducers is needed. Since the output power level of the energy transducer can be very low, the conversion should be as efficient as possible. The paper describes an active AC-DC converter, based on the voltage doubler topology, in which two different driving circuitries have been implemented. The proposed solutions are fully autonomous, i.e. they are supplied by the energy that they harvest. To reduce and to optimize their power consumption a bias circuit has been designed to make the total bias current supply independent. A test chip has been diffused using STMicroelectronics 5V CMOS technology. The performances of the two solutions were compared with the ones of a passive Schottky based voltage doubler. The figures of merit were the average power supplied by the piezoelectric transducer and the average power delivered on a load resistance. Furthermore, the significance of such parameters is also discussed, and a more general figure of merit is defined with the advantage of also weighting the ability of the converter to harvest all the power available at the transducer terminals

Active self supplied AC-DC converter for piezoelectric energy scavenging systems with supply independent bias

Abstract- The paper focuses on an electronic interface which can be used into Piezoelectric Energy Scavenging Systems (PESS). These systems convert the energy of mechanical vibrations into electrical energy using a piezoelectric transducer to realize a power supply for low power electronic systems. To obtain a suitable supply source an AC-DC conversion of the output signal of these transducers is needed and, since the output power level of the energy scavenger can be very low, the conversion should be as efficient as possible. This paper shows an active voltage doubler AC-DC converter for PESSs. A novel driving circuitry topology is presented; it has the advantage to be tolerant with respect to the process variations. The converter uses exclusively a fraction of the harvested energy to supply itself and a bias circuit has been designed to make the total current consumption supply independent. The simulation results show that the efficiency of the AC-DC converter can be as high as 94%. The circuit will be diffused in 0.35µm CMOS STMicroelectronics technology. I

The electrophysiological correlates of phoneme perception in primary progressive aphasia : a preliminary case series

Aims: This study aimed to investigate phoneme perception in patients with primary progressive aphasia (PPA) by using the event-related potential (ERP) technique. These ERP components might contribute to the diagnostic process of PPA and its clinical variants (NFV: nonfluent variant, SV: semantic variant, LV: logopenic variant) and reveal insights about phoneme perception processes in these patients. Method: Phoneme discrimination and categorization processes were investigated by the mismatch negativity (MMN) and P300 in eight persons with early- and late-stage PPA (3 NFV, 2 LV, 2 SV, and 1 PPA-NOS; not otherwise specified) and 30 age-matched healthy adults. The mean amplitude, the onset latency, and the topographic distribution of both components in each patient were compared to the results of the control group. Results: The MMN was absent or the onset latency of the MMN was delayed in the patients with the NFV, LV, and PPA-NOS in comparison to the control group. In contrast, no differences in mean amplitudes and onset latencies of the MMN were found between the patients with the SV and the control group. Concerning the P300, variable results were found in the patients with the NFV, SV, and PPA-NOS, but the P300 of both patients with the LV was delayed and prolonged with increased mean amplitude in comparison to the control group. Conclusion: In this preliminary study, phoneme discrimination deficits were found in the patients with the NFV and LV, and variable deficits in phoneme categorization processes were found in all patients with PPA. In clinical practice, the MMN might be valuable to differentiate the SV from the NFV and the LV and the P300 to differentiate the LV from the NFV and the SV. Further research in larger and independent patient groups is required to investigate the applicability of these components in the diagnostic process and to determine the nature of these speech perception deficits in the clinical variants of PPA