Electrode displacement after intracerebral hematoma as a complication of a deep brain stimulation procedure

Domenico Servello1, Marco Sassi1, Stefano Bastianello2, Guy Umberto Poloni2, Francesca Mancini3, Claudio Pacchetti31Functional Neurosurgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico Galeazzi, Milan, Italy; 2Neuroradiology Unit; 3Parkinson Disease and Movement Disorder Unit, Istituto di Ricovero e Cura a Carattere Scientifico Mondino, Institute of Neurology, Pavia, Italy Objectives: Deep brain stimulation (DBS) is nowadays considered a safe and effective procedure for various movement disorders in which conservative treatments have failed to show significant therapeutic results. One of the most common complications of definitive electrode positioning is intraparenchymal hemorrhage.Materials and methods: Authors report the case of a 55-year-old female patient treated for Parkinson’s disease in which intraparenchymal hemorrhage developed after DBS procedure, leading to significant (about 8 mm at the neuroradiological controls) displacement of an otherwise correctly positioned DBS electrode.Results: After conservative management, the hematoma spontaneously resolved. Late neuroradiological controls documented correct, symmetrically positioned electrodes, comparable to the immediate postoperative controls.Conclusions: Six months follow-up endpoint results of the DBS treatment were considered satisfying by an independent neurologist, with modest residual neurological deficits, demonstrating that re-positioning of the electrode was unnecessary in this rare complication.Keywords: deep brain stimulation, electrodes, outcomes, implant, case repor

Electrochromic Polymer Ink Derived from a Sidechain-Modified EDOT for Electrochromic Devices with Colorless Bright State

AbstractPrintable organic electrochromic materials are the key component of flexible low power and low weight displays and dynamic shading systems. A vast number of more or less well‐performing materials is reported in the literature, but only a very limited number of them have been tested in an industrially‐relevant environment so far. Upscaling requires simplicity of synthesis, overall sustainability, low cost and compatibility with simple and high throughput wet‐chemical deposition techniques, such as slot‐die coating or inkjet printing. In the present paper, an original process is described that enables the controlled oxidative polymerization of a water insoluble, functionalized 3,4‐ethylene dioxythiophene (EDOT) derivative. This process leads to the formation of an ink that consists solely of active polymeric material (no dispersing agents) and has suitable rheological properties for use in roll‐to‐roll slot‐die coating or ink‐jet printing. The straightforward deposition, followed by a simple thermal treatment, directly yields stable and homogeneous thin films with state‐of‐the‐art electrochromic performance

Assessing efficiency and innovation in the 3PL industry: an empirical analysis

The Third-party Logistics (3PL) industry is facing both important growth rates and increasing competitive pressure. 3PL providers are required to continuously sustain a more and more competitive cost structure (i.e. efficiency) and develop capabilities to improve their services (i.e. innovation); hence, the evaluation of these key success factors is considered a key issue. This paper develops a quantitative analysis of 71 Italian 3PL providers by using Data Envelopment Analysis to jointly assess efficiency and innovation. Furthermore, through a case study research, it corroborates the quantitative results by investigating the strategies of best-in-class companies. Results allowed identifying 13 3PL providers as efficiency leaders and 6 as leaders from both the efficiency and the innovation side. Their input composition indicates a diversification of the business models. A breakdown of the analysis by size and industry focus, along with empirical evidence on the strategies enhancing efficiency and innovation, is also provided

Investigating APOE, APP-Aβ metabolism genes and Alzheimer’s disease GWAS hits in brain small vessel ischemic disease

Alzheimer’s disease and small vessel ischemic disease frequently co-exist in the aging brain. However, pathogenic links between these 2 disorders are yet to be identified. Therefore we used Taqman genotyping, exome and RNA sequencing to investigate Alzheimer’s disease known pathogenic variants and pathways: APOE ε4 allele, APP-Aβ metabolism and late-onset Alzheimer’s disease main genome-wide association loci (APOE, BIN1, CD33, MS4A6A, CD2AP, PICALM, CLU, CR1, EPHA1, ABCA7) in 96 early-onset small vessel ischemic disease Caucasian patients and 368 elderly neuropathologically proven controls (HEX database) and in a mouse model of cerebral hypoperfusion. Only a minority of patients (29%) carried APOE ε4 allele. We did not detect any pathogenic mutation in APP, PSEN1 and PSEN2 and report a burden of truncating mutations in APP-Aß degradation genes. The single-variant association test identified 3 common variants with a likely protective effect on small vessel ischemic disease (0.54>OR > 0.32, adj. p-value  1, adj. p-val<0.05) together with Apoe, Ms4a cluster and Cd33 during brain hypoperfusion and their overexpression correlated with the ischemic lesion size. Finally, the detection of Aβ oligomers in the hypoperfused hippocampus supported the link between brain ischemia and Alzheimer’s disease pathology

Au-Coated Ni80Fe20 Submicron Magnetic Nanodisks: Interactions With Tumor Cells

Effective interaction and accumulation of nanoparticles (NPs) within tumor cells is crucial for NP-assisted diagnostic and therapeutic biomedical applications. In this context, the shape and size features of NPs can severely influence the strength of adhesion between NPs and cell and the NP internalization mechanisms. This study proved the ability of the PT45 and A549 tumor cells to uptake and retain magnetic Au-coated Ni80Fe20 nanodisks (NDs) prepared by means of a bottom–up self-assembling nanolithography technique assisted by polystyrene nanospheres. The chosen geometrical parameters, i.e., diameter (≈650 nm) and thickness (≈30 nm), give rise to magnetic domain patterns arranged in vortex state at the magnetic remanence. PT45 and A549 cell lines were cultured in the presence of different concentrations of Au-coated Ni80Fe20 nanodisks, and their biocompatibility was evaluated by viability and proliferation tests. Electron microscopy techniques and a combined CARS (Coherent Anti-stokes Raman Scattering) and TPL (two-photon photoluminescence) microscopy allow localizing and distinguishing the NDs within or attached to the tumor cells, without any labeling. A quantitative measurement of ND amount retained within tumor cells as a function of ND concentrations was performed by the Instrumental Neutron Activation Analysis (INAA) characterization technique

Predicting human cardiac QT alterations and pro-arrhythmic effects of compounds with a 3D beating heart-on-chip platform

Determining the potential cardiotoxicity and pro-arrhythmic effects of drug candidates remains one of the most relevant issues in the drug development pipeline. New methods enabling to perform more representative pre-clinical in vitro studies by exploiting induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are under investigation to increase the translational power of the outcomes. Here we present a pharmacological campaign conducted to evaluate the drug-induced QT alterations and arrhythmic events on uHeart, a 3D miniaturized in-vitro model of human myocardium encompassing iPSC-CM and dermal fibroblasts embedded in fibrin. uHeart was mechanically trained resulting in synchronously beating cardiac microtissues in one week, characterized by a clear field potential (FP) signal that was recorded by means of an integrated electrical system. A drug screening protocol compliant with the new International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines was established and uHeart was employed for testing the effect of 11 compounds acting on single or multiple cardiac ion channels and well-known to elicit QT prolongation or arrhythmic events in clinics. The alterations of uHeart's electrophysiological parameters such as the beating period, the FP duration, the FP amplitude and the detection of arrhythmic events prior and after drug administration at incremental doses were effectively analyzed through a custom developed algorithm. Results demonstrated the ability of uHeart to successfully anticipate clinical outcome and to predict the QT prolongation with a sensitivity of 83.3%, a specificity of 100% and an accuracy of 91.6%. Cardiotoxic concentrations of drugs were notably detected in the range of the clinical highest blood drug concentration (Cmax), qualifying uHeart as a fit-to-purpose pre-clinical tool for cardiotoxicity studies

New Roll‐to‐Roll Processable PEDOT‐Based Polymer with Colorless Bleached State for Flexible Electrochromic Devices

Conjugated electrochromic (EC) polymers for flexible EC devices (ECDs) generally lack a fully colorless bleached state. A strategy to overcome this drawback is the implementation of a new sidechain-modified poly(3,4-ethylene dioxythiophene) derivative that can be deposited in thin-film form in a customized high-throughput and large-area roll-to-roll polymerization process. The sidechain modification provides enhanced EC properties in terms of visible light transmittance change, Δτv = 59% (ΔL* = 54.1), contrast ratio (CR = 15.8), coloration efficiency (η = 530 cm² C−1), and color neutrality (L* = 83.8, a* = −4.3, b* = −4.1) in the bleached state. The intense blue-colored polymer thin films exhibit high cycle stability (10 000 cycles) and fast response times. The design, synthesis, and polymerization of the modified 3,4-ethylene dioxythiophene derivative are discussed along with a detailed optical, electrochemical, and spectroelectrochemical characterization of the resulting EC thin films. Finally, a flexible see-through ECD with a visible light transmittance change of Δτv = 47% (ΔL* = 51.9) and a neutral-colored bleached state is developed

CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system

Motivation: The transition from evaluating a single time point to examining the entire dynamic evolution of a system is possible only in the presence of the proper framework. The strong variability of dynamic evolution makes the definition of an explanatory procedure for data fitting and clustering challenging. Results: We developed CONNECTOR, a data-driven framework able to analyze and inspect longitudinal data in a straightforward and revealing way. When used to analyze tumor growth kinetics over time in 1599 patient-derived xenograft growth curves from ovarian and colorectal cancers, CONNECTOR allowed the aggregation of time-series data through an unsupervised approach in informative clusters. We give a new perspective of mechanism interpretation, specifically, we define novel model aggregations and we identify unanticipated molecular associations with response to clinically approved therapies. Availability and implementation: CONNECTOR is freely available under GNU GPL license at https://qbioturin.github.io/connector and https://doi.org/10.17504/protocols.io.8epv56e74g1b/v1

An exploratory investigation of brain collateral circulation plasticity after cerebral ischemia in two experimental C57BL/6 mouse models

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2 weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60 minute transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size