PERI-INFARCT SUSCEPTIBILITY OF WHITE MATTER COMPARED TO GRAY MATTER FOLLOWING ISCHEMIC STROKE

Stroke is the second largest cause of death worldwide, with 80% being ischemic. Cells with no blood supply die via necrosis, forming the ischemic core. Adjacent to the ischemic core is an area of reduced blood flow, called the peri-infarct zone, which may have distinct injury/recovery processes. Thus, the study of the peri-infarct zone may improve stroke treatment. Neonatal white matter has a higher susceptibility to injury from ischemia than gray matter in rats. Therefore, white matter may require different treatment than gray matter. The purpose of the study was to discover whether peri-infarct white matter in adult rats is more susceptible than gray matter to ischemic changes. The hypothesis is that adult rat peri-infarct white matter is more susceptible to ischemic changes than gray matter following a stroke. Rose Bengal was injected into 22 Wistar adult rats and exposed to white light, causing blood coagulation. The rat brains were scanned by an MR machine and acquired as T2 weighted sequence images. Slices were visually assessed to determine anterior/posterior boundaries of peri-infarct zone and had three regions measured on five major slices. The T2 values were expressed as percentages of their respective controls. Histology slides of the brains were stained with Luxol Fast Blue and H&E. The three previously measured regions were visually assessed on the histology and scored YES or NO for signs of tissue injury/changes in myelination. Two general patterns of T2 values appeared, separated into two groups: posterior increased (PI) and core centered (CC). When comparing white matter T2 values between the two groups, posterior peri-infarct slices were significantly greater than anterior peri-infarct slices. There was a significant difference between white matter and upper cortex gray matter in posterior mild lesion slices of the PI group (p value = 0.031). The myelination score was NO for all central slices. 4/5 of the animals of the PI group had obvious signs of tissue injury at the deep cortex central lesion slice. There were no signs of injury in the CC group. There was, however, high correlation between deep cortex T2 values and H&E tissue injury rankings (p = 2.0 x 10-7). Meanwhile, white matter T2 values and H&E scores were not significant (p = 0.182). At posterior slices remote from the ischemic core, signs of ischemic T2changes of white matter was greater than gray matter in the PI group. These changes were not observed in the CC group. Comparing central slice of PI and CC groups showed greater T2 responses occurred in the PI group than in the CC group, suggesting a more severe ischemic insult occurred in animals of the PI group. However, posterior peri-infarct white matter did not show greater signs of tissue injury detectable by H&E than gray matter. The enhanced T2 ischemic changes in posterior peri-infarct white matter appears to be due to reasons other than tissue injury detectable by H&E staining, such as cerebral edema and microscopic axonal injury. In conclusion, the data supports that white matter in adult rats can be more susceptible than gray matter to peri-infarct ischemic changes detected in the form of T2 changes, specifically posterior to the ischemic lesion. Increased T2 changes are a reflection of ischemic changes that could benefit from novel treatments targeted at white matter

A wireless sEMG-based body-machine interface for assistive technology devices

Assistive technology (AT) tools and appliances are being more and more widely used and developed worldwide to improve the autonomy of people living with disabilities and ease the interaction with their environment. This paper describes an intuitive and wireless surface electromyography (sEMG) based body-machine interface for AT tools. Spinal cord injuries at C5-C8 levels affect patients' arms, forearms, hands, and fingers control. Thus, using classical AT control interfaces (keypads, joysticks, etc.) is often difficult or impossible. The proposed system reads the AT users' residual functional capacities through their sEMG activity, and converts them into appropriate commands using a threshold-based control algorithm. It has proven to be suitable as a control alternative for assistive devices and has been tested with the JACO arm, an articulated assistive device of which the vocation is to help people living with upper-body disabilities in their daily life activities. The wireless prototype, the architecture of which is based on a 3-channel sEMG measurement system and a 915-MHz wireless transceiver built around a low-power microcontroller, uses low-cost off-the-shelf commercial components. The embedded controller is compared with JACO's regular joystick-based interface, using combinations of forearm, pectoral, masseter, and trapeze muscles. The measured index of performance values is 0.88, 0.51, and 0.41 bits/s, respectively, for correlation coefficients with the Fitt's model of 0.75, 0.85, and 0.67. These results demonstrate that the proposed controller offers an attractive alternative to conventional interfaces, such as joystick devices, for upper-body disabled people using ATs such as JACO

The Impact of Experimental Pain on Shoulder Movement During an Arm Elevated Reaching Task in a Virtual Reality Environment

Background: People with chronic shoulder pain have been shown to present with motor adaptations during arm movements. These adaptations may create abnormal physical stress on shoulder tendons and muscles. However, how and why these adaptations develop from the acute stage of pain is still not well-understood. Objective: To investigate motor adaptations following acute experimental shoulder pain during upper limb reaching. Methods: Forty participants were assigned to the Control or Pain group. They completed a task consisting of reaching targets in a virtual reality environment at three time points: (1) baseline (both groups pain-free), (2) experimental phase (Pain group experiencing acute shoulder pain induced by injecting hypertonic saline into subacromial space), and (3) Post experimental phase (both groups pain-free). Electromyographic (EMG) activity, kinematics, and performance data were collected. Results: The Pain group showed altered movement planning and execution as shown by a significant increased delay to reach muscles EMG peak and a loss of accuracy, compared to controls that have decreased their mean delay to reach muscles peak and improved their movement speed through the phases. The Pain group also showed protective kinematic adaptations using less shoulder elevation and elbow flexion, which persisted when they no longer felt the experimental pain. Conclusion: Acute experimental pain altered movement planning and execution, which affected task performance. Kinematic data also suggest that such adaptations may persist over time, which could explain those observed in chronic pain populations

Genetic burden linked to founder effects in Saguenay–Lac-Saint-Jean illustrates the importance of genetic screening test availability

The Saguenay–Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product of a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes. We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Distribution of misfolded prion protein seeding activity alone does not predict regions of neurodegeneration

Protein misfolding is common across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conversion of normally folded protein to abnormal conformations. A central hypothesis is that misfolded protein accumulation, spread and distribution is restricted to specific neuronal populations of the central nervous system and thus predict regions of neurodegeneration. We examined this hypothesis using a highly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disease. Misfolded prion protein seeds were observed widespread throughout the brain accumulating in all brain regions examined irrespective of neurodegeneration. Importantly neither time of exposure nor amount of misfolded protein seeds present determined regions of neurodegeneration. We further demonstrate two distinct microglia responses in prion infected brains, a 11 novel homeostatic response in all regions and an innate immune response restricted to sites of 12 neurodegeneration. Therefore accumulation of misfolded prion protein alone does not define targeting 13 of neurodegeneration which instead results only when misfolded prion protein accompanies a specific 14 innate immune response

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe