Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.

In materia reservoir computing with a fully memristive architecture based on self-organizing nanowire networks.

Neuromorphic computing aims at the realization of intelligent systems able to process information similarly to our brain. Brain-inspired computing paradigms have been implemented in crossbar arrays of memristive devices; however, this approach does not emulate the topology and the emergent behaviour of biological neuronal circuits, where the principle of self-organization regulates both structure and function. Here, we report on in materia reservoir computing in a fully memristive architecture based on self-organized nanowire networks. Thanks to the functional synaptic connectivity with nonlinear dynamics and fading memory properties, the designless nanowire complex network acts as a network-wide physical reservoir able to map spatio-temporal inputs into a feature space that can be analysed by a memristive resistive switching memory read-out layer. Computing capabilities, including recognition of spatio-temporal patterns and time-series prediction, show that the emergent memristive behaviour of nanowire networks allows in materia implementation of brain-inspired computing paradigms characterized by a reduced training cost.

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections.

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion-extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion-extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.

Identification of a Gait Pattern for Detecting Mild Cognitive Impairment in Parkinson's Disease.

The aim of this study was to determine a gait pattern, i.e., a subset of spatial and temporal parameters, through a supervised machine learning (ML) approach, which could be used to reliably distinguish Parkinson's Disease (PD) patients with and without mild cognitive impairment (MCI). Thus, 80 PD patients underwent gait analysis and spatial-temporal parameters were acquired in three different conditions (normal gait, motor dual task and cognitive dual task). Statistical analysis was performed to investigate the data and, then, five ML algorithms and the wrapper method were implemented: Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB), Support Vector Machine (SVM) and K-Nearest Neighbour (KNN). First, the algorithms for classifying PD patients with MCI were trained and validated on an internal dataset (sixty patients) and, then, the performance was tested by using an external dataset (twenty patients). Specificity, sensitivity, precision, accuracy and area under the receiver operating characteristic curve were calculated. SVM and RF showed the best performance and detected MCI with an accuracy of over 80.0%. The key features emerging from this study are stance phase, mean velocity, step length and cycle length; moreover, the major number of features selected by the wrapper belonged to the cognitive dual task, thus, supporting the close relationship between gait dysfunction and MCI in PD.

Agreement between Optoelectronic System and Wearable Sensors for the Evaluation of Gait Spatiotemporal Parameters in Progressive Supranuclear Palsy.

The use of wearable sensors for calculating gait parameters has become increasingly popular as an alternative to optoelectronic systems, currently recognized as the gold standard. The objective of the study was to evaluate the agreement between the wearable Opal system and the optoelectronic BTS SMART DX system for assessing spatiotemporal gait parameters. Fifteen subjects with progressive supranuclear palsy walked at their self-selected speed on a straight path, and six spatiotemporal parameters were compared between the two measurement systems. The agreement was carried out through paired data test, Passing Bablok regression, and Bland-Altman Analysis. The results showed a perfect agreement for speed, a very close agreement for cadence and cycle duration, while, in the other cases, Opal system either under- or over-estimated the measurement of the BTS system. Some suggestions about these misalignments are proposed in the paper, considering that Opal system is widely used in the clinical context.

A machine learning-based approach to directly compare the diagnostic accuracy of myocardial perfusion imaging by conventional and cadmium-zinc telluride SPECT.

BACKGROUND: We evaluated the performance of conventional (C) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride (CZT)-SPECT in a large cohort of patients with suspected or known coronary artery disease (CAD) and compared the diagnostic accuracy of the two systems using machine learning (ML) algorithms. METHODS AND RESULTS: A total of 517 consecutive patients underwent stress myocardial perfusion imaging (MPI) by both C-SPECT and CZT-SPECT. In the overall population, an excellent correlation between stress MPI data and left ventricular (LV) functional parameters measured by C-SPECT and by CZT-SPECT was observed (all P < .001). ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (NN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for k-NN) was greater than that of C-SPECT (88% for RF and 53% for k-NN). CONCLUSIONS: MPI data and LV functional parameters obtained by CZT-SPECT are highly reproducible and provide good correlation with those obtained by C-SPECT. ML approach showed that the accuracy and sensitivity of CZT-SPECT is greater than C-SPECT in detecting CAD.

Statistical Analysis and Kinematic Assessment of Upper Limb Reaching Task in Parkinson's Disease.

The impact of neurodegenerative disorders is twofold; they affect both quality of life and healthcare expenditure. In the case of Parkinson's disease, several strategies have been attempted to support the pharmacological treatment with rehabilitation protocols aimed at restoring motor function. In this scenario, the study of upper limb control mechanisms is particularly relevant due to the complexity of the joints involved in the movement of the arm. For these reasons, it is difficult to define proper indicators of the rehabilitation outcome. In this work, we propose a methodology to analyze and extract an ensemble of kinematic parameters from signals acquired during a complex upper limb reaching task. The methodology is tested in both healthy subjects and Parkinson's disease patients (N = 12), and a statistical analysis is carried out to establish the value of the extracted kinematic features in distinguishing between the two groups under study. The parameters with the greatest number of significances across the submovements are duration, mean velocity, maximum velocity, maximum acceleration, and smoothness. Results allowed the identification of a subset of significant kinematic parameters that could serve as a proof-of-concept for a future definition of potential indicators of the rehabilitation outcome in Parkinson's disease.

Vascular growth factors as potential new treatment in cardiorenal syndrome in diabetes.

BACKGROUND: Cardiorenal syndrome in diabetes is characterised by alterations of the cardiovascular system paralleled by kidney disease with progressive renal function decline. In diabetes, chronic metabolic and haemodynamic perturbations drive endothelial dysfunction, inflammation, oxidative stress and progressive tissue fibrosis which, in turn, lead to heart and renal anatomo-functional damage. In physiology, vascular growth factors have been implicated in vascular homeostasis; their imbalance, in disease setting such as diabetes, leads to vascular dysfunction and cardiorenal damage. AIMS: To define the role of vascular growth factors and angiopoietins in cardiorenal syndrome. MATERIAL AND METHODS: We will focus on the two most studied vascular growth factors, vascular endothelial growth factor (VEGF) and angiopoietins (Angpt). The balance and crosstalk between these growth factors are important in organ development and in the maintenance of a healthy vasculature, heart and kidney. The observed alterations in expression/function of these vascular growth factors, as seen in diabetes, are a protective response against external perturbations. RESULTS: The chronic insults driving diabetes-mediated cardiorenal damage results in a paradoxical situation, whereby the vascular growth factors imbalance becomes a mechanism of disease. Studies have explored the possibility of modulating the expression/action of vascular growth factors to improve disease outcome. Experimental work has been conducted in animals and has been gradually translated in humans. DISCUSSION: Difficulties have been encountered especially when considering the magnitude, timing and duration of interventions targeting a selective vascular growth factor. Targeting VEGF in cardiovascular disease has been challenging, while modulation of the Angpt system seems more promising. CONCLUSION: Future studies will establish the translatability of therapies targeting vascular growth factors for heart and kidney disease in patients with diabetes.

Head-to-head comparison of diagnostic accuracy of stress-only myocardial perfusion imaging with conventional and cadmium-zinc telluride single-photon emission computed tomography in women with suspected coronary artery disease.

BACKGROUND: Breast attenuation may impact the diagnostic accuracy of stress myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT). We compared the performance of conventional (C)-SPECT and cadmium-zinc-telluride (CZT)-SPECT systems in women with low-intermediate likelihood of coronary artery disease (CAD). METHODS AND RESULTS: A total of 109 consecutive women underwent stress-optional rest MPI by both C-SPECT and CZT-SPECT. In the overall study population, a weak albeit significant correlation between total perfusion defect (TPD) measured by C-SPECT and CZT-SPECT was observed (r = 0.38, P < .001) and at Bland-Altman analysis the mean difference in TPD (C-SPECT minus CZT-SPECT) was 2.40% (P < .001). Overall concordance of semi-quantitative diagnostic performance between C-SPECT and CZT-SPECT was observed in 52 (48%) women with a κ value of 0.09. Normalcy rate was significantly higher using CZT-SPECT compared to C-SPECT (P < .001). Machine learning analysis performed through the implementation of J48 algorithm proved that CZT-SPECT has higher sensitivity, specificity, and accuracy than C-SPECT. CONCLUSIONS: In women with low-intermediate likelihood of CAD, there is a poor concordance of diagnostic performance between C-SPECT and CZT-SPECT, and CZT-SPECT allows better normalcy rate detection compared to C-SPECT.

The endoplasmic reticulum stress and the unfolded protein response in kidney disease: Implications for vascular growth factors.

Acute kidney injury (AKI) and chronic kidney disease (CKD) represent an important challenge for healthcare providers. The identification of new biomarkers/pharmacological targets for kidney disease is required for the development of more effective therapies. Several studies have shown the importance of the endoplasmic reticulum (ER) stress in the pathophysiology of AKI and CKD. ER is a cellular organelle devolved to protein biosynthesis and maturation, and cellular detoxification processes which are activated in response to an insult. This review aimed to dissect the cellular response to ER stress which manifests with activation of the unfolded protein response (UPR) with its major branches, namely PERK, IRE1α, ATF6 and the interplay between ER and mitochondria in the pathophysiology of kidney disease. Further, we will discuss the relationship between mediators of renal injury (with specific focus on vascular growth factors) and ER stress and UPR in the pathophysiology of both AKI and CKD with the aim to propose potential new targets for treatment for kidney disease.

Design and Validation of an E-Textile-Based Wearable Sock for Remote Gait and Postural Assessment.

This paper presents a new wearable e-textile based system, named SWEET Sock, for biomedical signals remote monitoring. The system includes a textile sensing sock, an electronic unit for data transmission, a custom-made Android application for real-time signal visualization, and a software desktop for advanced digital signal processing. The device allows the acquisition of angular velocities of the lower limbs and plantar pressure signals, which are postprocessed to have a complete and schematic overview of patient's clinical status, regarding gait and postural assessment. In this work, device performances are validated by evaluating the agreement between the prototype and an optoelectronic system for gait analysis on a set of free walk acquisitions. Results show good agreement between the systems in the assessment of gait cycle time and cadence, while the presence of systematic and proportional errors are pointed out for swing and stance time parameters. Worse results were obtained in the comparison of spatial metrics. The "wearability" of the system and its comfortable use make it suitable to be used in domestic environment for the continuous remote health monitoring of de-hospitalized patients but also in the ergonomic assessment of health workers, thanks to its low invasiveness.

MRI Radiomics for the Prediction of Fuhrman Grade in Clear Cell Renal Cell Carcinoma: a Machine Learning Exploratory Study.

The Fuhrman nuclear grade is a recognized prognostic factor for patients with clear cell renal cell carcinoma (CCRCC) and its pre-treatment evaluation significantly affects decision-making in terms of management. In this study, we aimed to assess the feasibility of a combined approach of radiomics and machine learning based on MR images for a non-invasive prediction of Fuhrman grade, specifically differentiation of high- from low-grade tumor and grade assessment. Images acquired on a 3-Tesla scanner (T2-weighted and post-contrast) from 32 patients (20 with low-grade and 12 with high-grade tumor) were annotated to generate volumes of interest enclosing CCRCC lesions. After image resampling, normalization, and filtering, 2438 features were extracted. A two-step feature reduction process was used to between 1 and 7 features depending on the algorithm employed. A J48 decision tree alone and in combination with ensemble learning methods were used. In the differentiation between high- and low-grade tumors, all the ensemble methods achieved an accuracy greater than 90%. On the other end, the best results in terms of accuracy (84.4%) in the assessment of tumor grade were achieved by the random forest. These evidences support the hypothesis that a combined radiomic and machine learning approach based on MR images could represent a feasible tool for the prediction of Fuhrman grade in patients affected by CCRCC.

Junction properties of single ZnO nanowires with asymmetrical Pt and Cu contacts.

Metal-semiconductor interfaces play a crucial role not only for regulating the electronic conduction mechanism but also in determining new functionalities in nanosized devices. In this work, we reported the investigation of the junction properties of single ZnO nanowires (NWs) asymmetrically contacted by means of a Pt electrochemically inert and a Cu electrochemically active electrode. At low applied voltages, these devices operate as diodes where the conduction mechanism was found to be dominated by the Schottky barrier at the Cu/ZnO interface. Junction parameters such as the Schottky barrier height, the ideality factor and the series resistance have been analyzed according to the thermionic emission theory. Different methods for parameter retrieval from I-V-T measurements are discussed and compared. A potential fluctuation model is considered in order to account for barrier inhomogeneities, revealing the presence of two Gaussian distribution of barrier heights. On the other hand, new device features arise from electrochemical dissolution and migration of Cu ions along the NW when high electric fields are implied. These electrochemical processes are underlaying the resistive switching and memristive behavior observed in single ZnO NWs, as suggested also by direct observation of Cu nanoclusters along the nanostructures after the switching events.

A multi-level memristor based on atomic layer deposition of iron oxide.

This work reports the fabrication of memristive devices based on iron oxide (Fe2O3) thin films grown by atomic layer deposition (ALD) using ferrocene as iron precursor and ozone as oxidant. An excellent control of the ALD process was achieved by using an experimental procedure based on a sequence of micro-pulses, which provided long residence time and homogeneous diffusion of precursors, allowing ALD of thin films with smooth morphology and crystallinity which was found to increase with layer thickness, at temperatures as low as 250 °C. The resistive switching of symmetric Pt/Fe2O3/Pt thin film devices exhibited bipolar mode with good stability and endurance. Multi-level switching was achieved via current and voltage control. It was proved that the ON state regime can be tuned by changing the current compliance while the OFF state can be changed to intermediate levels by decreasing the maximum voltage during RESET. The structural analysis of the switched oxide layer revealed the presence of nano-sized crystalline domains corresponding to different iron oxide phases, suggesting that Joule heating effects during I-V cycling are responsible for a crystallization process of the pristine amorphous layer.

Evolution of nanomechanical properties and crystallinity of individual titanium dioxide nanotube resonators.

Herein a complete characterization of single TiO2 nanotube resonator was reported for the first time. The modal vibration response analysis allows a non-invasive indirect evaluation of the mechanical properties of the TiO2 nanotube. The effect of post-grown thermal treatments on nanotube mechanical properties was investigated and carefully correlated to the chemico-physical parameters evolution. The Young's modulus of TiO2 nanotube rises linearly from 57 GPa up to 105 GPa for annealing at 600 °C depending on the compositional and crystallographic evolution of the nanostructure. Considering the growing interest in single nanostructure devices, the reported findings allow a deeper understanding of the properties of individual titanium dioxide nanotubes extrapolated from their standard arrayed architecture.

The Myth of Water and Salt: From Aquaretics to Tenapanor.

The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate. In chronic kidney disease, AVP contributes to glomerular hyperfiltration, arterial hypertension, and synthesis of renin, resulting in renal sclerosis. Increased water intake could reduce AVP activation determining a potential protective effect on the kidney, but its efficacy has not yet been clearly demonstrated. On the other side, sodium and potassium play an important role in the control of arterial blood pressure and are involved in the development and progression of chronic kidney disease. Reduction of sodium intake and increase of potassium intake determine a decrease of arterial blood pressure with a beneficial effect on the kidney; however, adherence to sodium restriction is very poor. Regarding this, sodium-hydrogen exchanger isoform 3 inhibitors may reduce sodium absorption in the gut. The most recent sodium-hydrogen exchanger isoform 3 inhibitor, known as tenapanor, reduces extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in experimental studies and increases fecal loss of sodium in humans.

Functionalized ZnO nanowires for microcantilever biosensors with enhanced binding capability.

An efficient way to increase the binding capability of microcantilever biosensors is here demonstrated by growing zinc oxide nanowires (ZnO NWs) on their active surface. A comprehensive evaluation of the chemical compatibility of ZnO NWs brought to the definition of an innovative functionalization method able to guarantee the proper immobilization of biomolecules on the nanostructured surface. A noteworthy higher amount of grafted molecules was evidenced with colorimetric assays on ZnO NWs-coated devices, in comparison with functionalized and activated silicon flat samples. ZnO NWs grown on silicon microcantilever arrays and activated with the proposed immobilization strategy enhanced the sensor binding capability (and thus the dynamic range) of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices. Graphical Abstract An efficient way to increase the binding capability of microcantilever biosensors is represented by growing zinc oxide nanowires (ZnO NWs) on their active surface. ZnO NWs grown on silicon microcantilever arrays and activated with an innovative immobilization strategy enhanced the sensor binding capability of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices.

Memristive behaviour in poly-acrylic acid coated TiO2 nanotube arrays.

This work investigates titanium dioxide nanotube arrays (TiO2-NTA) grown by anodic oxidation as an active material for memristive applications. In particular, metal-insulator-metal structures made of vertically oriented amorphous TiO2-NTA grown on titanium foil were exploited in Ti/TiO2-NTA/Pt devices. The deposition of a polymeric thin film between NTA and top electrodes significantly improved the stability of the devices and increased by more than double the off/on resistance ratio. The resistive switching of TiO2-NTA samples crystallised by thermal annealing was also studied. Such devices displayed nonlinear I-V curves characterised by a smooth rectifying behaviour, without any evident resistive switching (RS). Also in this case, the interposition of the polymeric layer enhanced the RS behaviour of TiO2-NTA samples, remarkably increasing the devices' off/on ratio and endurance. The rise of high resistance states can be simply related to the addition of the polymer as resistance in series, while the variation of the low resistance states is here attributed to the occurrence of surface chemical reactions between polymer functional groups and the metal oxide, which increase the charge carriers available for conduction.

Succinic anhydride functionalized microcantilevers for protein immobilization and quantification.

Microcantilever-based systems have been proposed as sensing platforms owing to their high sensitivity when used as mass sensors. The controlled immobilization on a surface of biomolecules used as recognition elements is fundamental in order to realize a highly specific and sensitive biosensor. Here, we introduce for the first time the application to a microcantilever-based system of a reliable chemical functionalization consisting of silanization with an aminosilane followed by a modification resulting in a carboxylated thin film. This chemical functionalization was tested for reproducibility of molecule deposition and for its protein grafting ability. Finally, this system was employed for the quantification of grafted proteins on the microcantilever surface. Moreover, a theoretical surface density of immobilized proteins estimated with bioinformatics tools was compared with the experimental surface density data, providing information about the orientation that the biomolecules assumed with respect to the sensing surface.

Sclerostin levels in uremic patients: a link between bone and vascular disease.

Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.