Peripheral Routes to Neurodegeneration : Passing Through the Blood–Brain Barrier

A bidirectional crosstalk between peripheral players of immunity and the central nervous system (CNS) exists. Hence, blood–brain barrier (BBB) breakdown is emerging as a participant mechanism of dysregulated peripheral–CNS interplay, promoting diseases. Here, we examine the implication of BBB damage in neurodegeneration, linking it to peripheral brain-directed autoantibodies and gut–brain axis mechanisms. As BBB breakdown is a factor contributing to, or even anticipating, neuronal dysfunction(s), we here identify contemporary pharmacological strategies that could be exploited to repair the BBB in disease conditions. Developing neurovascular, add on, therapeutic strategies may lead to a more efficacious pre-clinical to clinical transition with the goal of curbing the progression of neurodegeneration.Peer reviewe

A Filtering technique based on a DLMS algorithm for ultrasonography video

It is well known that ultrasonography is a diagnostic method for visualizinginside human tissues by spreading ultrasounds and measuring their return time tothe sensor. However, the interface between the human skin and this ultrasoundtransducer attenuates the received signal and the medical image quality deterioratessignificantly. In this paper we propose a filtering technique in order to compensatethis attenuation. A finite impulse response filter (FIR) based on a Delayed LeastMean Square (DLMS) was optimized and implemented. The main contribution ofour work consists of finding the order and the coefficients of the filter that minimizethe attenuation error. We validate our method first on simulated data and later on areprogrammable FPGA device for a real time performance testing. Among others,we show that incrementing the order of the filter, not always is the best way toreduce image quality errors

The role of shear stress in Blood-Brain Barrier endothelial physiology

<p>Abstract</p> <p>Background</p> <p>One of the most important and often neglected physiological stimuli contributing to the differentiation of vascular endothelial cells (ECs) into a blood-brain barrier (BBB) phenotype is shear stress (SS). With the use of a well established humanized dynamic <it>in vitro </it>BBB model and cDNA microarrays, we have profiled the effect of SS in the induction/suppression of ECs genes and related functions.</p> <p>Results</p> <p>Specifically, we found a significant upregulation of tight and adherens junctions proteins and genes. Trans-endothelial electrical resistance (TEER) and permeability measurements to know substances have shown that SS promoted the formation of a tight and highly selective BBB. SS also increased the RNA level of multidrug resistance transporters, ion channels, and several p450 enzymes. The RNA level of a number of specialized carrier-mediated transport systems (e.g., glucose, monocarboxylic acid, etc.) was also upregulated.</p> <p>RNA levels of modulatory enzymes of the glycolytic pathway (e.g., lactate dehydrogenase) were downregulated by SS while those involved in the Krebs cycle (e.g., lactate and other dehydrogenases) were upregulated. Measurements of glucose consumption versus lactate production showed that SS negatively modulated the glycolytic bioenergetic pathways of glucose metabolism in favor of the more efficient aerobic respiration. BBB ECs are responsive to inflammatory stimuli. Our data showed that SS increased the RNA levels of integrins and vascular adhesion molecules. SS also inhibited endothelial cell cycle via regulation of BTG family proteins encoding genes. This was paralleled by significant increase in the cytoskeletal protein content while that of membrane, cytosol, and nuclear sub-cellular fractions decreased. Furthermore, analysis of 2D gel electrophoresis (which allows identifying a large number of proteins per sample) of EC proteins extracted from membrane sub-cellular endothelial fractions showed that SS increased the expression levels of tight junction proteins. In addition, regulatory enzymes of the Krebb's cycle (aerobic glucose metabolism) were also upregulated. Furthermore, the expression pattern of key protein regulators of the cell cycle and parallel gene array data supported a cell proliferation inhibitory role for SS.</p> <p>Conclusions</p> <p>Genomic and proteomic analyses are currently used to examine BBB function in healthy and diseased brain and characterize this dynamic interface. In this study we showed that SS plays a key role in promoting the differentiation of vascular endothelial cells into a truly BBB phenotype. SS affected multiple aspect of the endothelial physiology spanning from tight junctions formation to cell division as well as the expression of multidrug resistance transporters. BBB dysfunction has been observed in many neurological diseases, but the causes are generally unknown. Our study provides essential insights to understand the role played by SS in the BBB formation and maintenance.</p

On the Query Strategies for Efficient Online Active Distillation

Deep Learning (DL) requires lots of time and data, resulting in high computational demands. Recently, researchers employ Active Learning (AL) and online distillation to enhance training efficiency and real-time model adaptation. This paper evaluates a set of query strategies to achieve the best training results. It focuses on Human Pose Estimation (HPE) applications, assessing the impact of selected frames during training using two approaches: a classical offline method and a online evaluation through a continual learning approach employing knowledge distillation, on a popular state-of-the-art HPE dataset. The paper demonstrates the possibility of enabling training at the edge lightweight models, adapting them effectively to new contexts in real-time

A Tiny Convolutional Neural Network driven by System Identification for Vibration Anomaly Detection at the Extreme Edge

Vibration data analysis is the driving tool for the Structural Health Monitoring (SHM) of structures in the dynamic regime, i.e., structures showing important oscillatory behaviours, which largely dominate the transportation back-bone: from terrestrial/aerial vehicles (e.g., trains, aircraft, etc.) to the supporting infrastructures (e.g., bridges, viaducts, etc.). Outstanding opportunities have recently been disclosed in the field of Intelligent Transportation Systems (ITS) by the advent of sensor-near processing functionalities, eventually empowered by Artificial Intelligence (AI). The latter allow for the extraction of damage-sensitive features at the extreme edge, without the need of transmitting long time series over the monitoring network. In this work, we explore for the first time a novel anomaly detection workflow for on-sensor vibration diagnostics, which combines the unique advantages of embedded System Identification (eSysId) as a data compression strategy with the computational/energy advantages of Tiny Machine Learning (TinyML). Experimental results conducted on a representative SHM dataset demonstrate that the proposed pipeline can achieve high classification scores (above 90%) for the health assessment of the well-known Z24 bridge. In particular, the minimal inference time (less than 44 ms) and power consumption performed while running on three different general-purpose microprocessors make it a promising solution for the development of the next generation of SHM-oriented ITS

The Etiological Role of Blood-Brain Barrier Dysfunction in Seizure Disorders

A wind of change characterizes epilepsy research efforts. The traditional approach, based on a neurocentric view of seizure generation, promoted understanding of the neuronal mechanisms of seizures; this resulted in the development of potent anti-epileptic drugs (AEDs). The fact that a significant number of individuals with epilepsy still fail to respond to available AEDs restates the need for an alternative approach. Blood-brain barrier (BBB) dysfunction is an important etiological player in seizure disorders, and combination therapies utilizing an AED in conjunction with a “cerebrovascular” drug could be used to control seizures more effectively than AED therapy alone. The fact that the BBB plays an etiologic role in other neurological diseases will be discussed in the context of a more “holistic” approach to the patient with epilepsy, where comorbidity variables are also encompassed by drug therapy

Sporotrichoid Mycobacterium marinum infection in an elderly woman

We describe the case of an elderly woman who acquired a Mycobacterium marinum infection following skin exposure to the bacteria through a small wound on her right ring finger, obtained while preparing fish. The resultant sporotrichoid nodules of the right hand and the distal forearm, refractory to the initial therapy with doxycycline and rifampicin, were successfully treated with oral regimen of clarithromycin

Misdiagnosis of anomalous pulmonary venous connections in a patient with lung cancer and a review of the literature

A partial anomalous pulmonary venous connection (PAPVC) is a rare congenital defect in which at least one pulmonary vein doesn't drain into the left atrium but into a systemic vein or even into the right atrium, causing a left-to right shunt. PAPVC with a small amount of shunt are usually asymptomatic, and can not be detected during lifetime. Nevertheless, if those patients undergo a major lung resection, the surgical procedure could precipitate right heart failure if this anomalous shunt remains uncorrected. Therefore, it is considered to be very important preoperative diagnosis. In case report, we present a case of a 54-year-old woman with a right upper lobe non-small cell lung cancer and previous history of left lung resection for tuberculosis. During surgery, an anomalous pulmonary vein branch draining into the superior vena cava was incidentally detected. The abnormality was diagnosed as a PAPVC. A right upper open lobectomy was performed. The anomaly was corrected and the surgery was successful without postoperative complications. Surgeons should be aware of this rare anomaly and carefully evaluate preoperative images CT scans of the pulmonary veins

Serum S100B: A Potential Biomarker for Suicidality in Adolescents?

Background: Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function. Methods: We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C). Results: Serum S100B levels were significantly higher (p,0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1–4 (low suicidality) had mean serum S100B values +/2 SEM of 0.152+/20.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5–7 (high suicidality) with a mean of 0.354+/20.044 ng/mL (n = 30). This difference was statistically significant (p,0.05). Conclusion: Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia