Structural and ultrastructural alterations in human olfactory pathways and possible associations with herpesvirus 6 infection

Publisher Copyright: © 2017 Skuja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.publishersversionPeer reviewe

STAMINA: Bioinformatics Platform for Monitoring and Mitigating Pandemic Outbreaks

Data Availability Statement: All data driven applications used the our world in data COVID-19 datasets, complimented by proprietary datasets share by the STAMINA consortium.Copyright © 2022 by the authors. This paper presents the components and integrated outcome of a system that aims to achieve early detection, monitoring and mitigation of pandemic outbreaks. The architecture of the platform aims at providing a number of pandemic-response-related services, on a modular basis, that allows for the easy customization of the platform to address user’s needs per case. This customization is achieved through its ability to deploy only the necessary, loosely coupled services and tools for each case, and by providing a common authentication, data storage and data exchange infrastructure. This way, the platform can provide the necessary services without the burden of additional services that are not of use in the current deployment (e.g., predictive models for pathogens that are not endemic to the deployment area). All the decisions taken for the communication and integration of the tools that compose the platform adhere to this basic principle. The tools presented here as well as their integration is part of the project STAMINA.The paper presented is based on research undertaken as part of the European Commission-funded project STAMINA (Grant Agreement 883441)

Neuronal tumour necrosis factor-α and interleukin-1β expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G

Tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) are important mediators of intracerebral haemorrhage (ICH) inflammatory response. Lazaroids, established antioxidants and neuroprotectants, have been studied in several brain pathologies. The present study was designed to investigate: a) TNF-α and IL-1β changes, in neurons and b) U-74389G effects, 4 and 24 h after haematoma induction in a porcine model of intracerebral haemorrhage. In twenty male landrace pigs (swines) aged 135-150 days old, autologous whole blood was injected around the right basal ganglia territory; in ten of the pigs the lazaroid compound U-74389G was administered. Brain TNF-α and IL-1β immunopositive neurons were determined by immunoarray techniques at 4 and 24 h timepoints. After the haematoma induction the number of TNF-α immunopositive neurons ipsilateral to the haematoma was significantly higher compared to the contralateral site at 4 h (p<0.0005), while U-74389G significantly reduced the number of TNF-α immunopositive neurons, ipsilateral to the haematoma, at 4 h (p=0.002); at 24 h, TNF-α immunopositive neurons were found significantly lower in the control group ipsilateral to the haematoma in comparison to 4 h timepoint(p<0.0005). The number of IL-1β immunopositive neurons at 4 h after the hematoma induction was significantly higher ipsilateral to the haematoma site (p<0.0005). U-74389G had no statistical significant effect. TNF-α and IL-1β, increase in neurons, 4 h after the haematoma induction, ipsilateral to the haematoma site. The administration of the antioxidant compound U-74389G, results in early (at 4 h) decrease of TNF-α immunopositive neurons but shows no statistical significant effect to IL-1β immunopossitive neurons. © 2015 Elsevier B.V. All rights reserved

Glycemia management in acute ischemic stroke: current concepts and novel therapeutic targets

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

High-resolution Intracranial Vessel Wall Imaging in Monitoring Treatment Response in Primary CNS Angiitis

Introduction:High-resolution vessel wall imaging (HR-VWI) is emerging as a tool of notable utility in the diagnosis of intracranial vessel pathology. Its role in monitoring vessel wall disease response to treatment, however, is less well-established.Case Report:We report the case of a 45-year-old man with left middle and anterior cerebral artery infarcts and an National Institute of Health Stroke Scale (NIHSS) score of 2. Time-of-flight magnetic resonance angiography and digital subtraction angiography showed multifocal intracranial vessel pathology without extracranial vessel involvement. Comprehensive investigation with echocardiography and 24 hours Holter electrocardiography was unrevealing and the coagulation and routine autoimmune panel results were within normal limits. Cerebrospinal fluid showed mildly elevated protein and a diagnosis of probable primary central nervous system (PCNS) angiitis was made. The diagnosis was corroborated by intracranial HR-VWI, which showed homogenous, concentric enhancement of the left supraclinoid internal carotid artery (ICA) wall. The patient received high-dose IV methylprednisolone and cyclophosphamide. Repeat brain magnetic resonance imaging with HR-VWI at 3 and 9 months showed reduction and final resolution of vessel wall enhancement without recurrent infarcts. He has since remained clinically stable with an NIHSS score of 0 on low-dose oral glucocorticoids.Conclusions:Our report illustrates the utility of HR-VWI in diagnosing a case of PCNS angiitis through the demonstration of a vasculitic pattern of mural enhancement. Furthermore, it has provided evidence of disease response to treatment, assisting us in modifying treatment accordingly. Tracking disease activity and response to treatment in cases of central nervous system vasculitis can be another important use of HR-VWI in clinical practice besides assisting in establishing the diagnosis. © 2018 Lippincott Williams and Wilkins

Magnetic resonance imaging reveals Creutzfeldt-Jakob disease in a patient with apparent dementia with Lewy bodies

The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt-Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB, while other cases may fulfill the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal fluid (CSF) and neuropathology findings necessitate diagnostic revision to CJD. We describe a 79-year old patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of subacute cognitive decline, visual hallucinations and Parkinsonian features, who presented with increasing agitation. Brain neuroimaging with MRI raised the diagnostic suspicion of CJD and subsequent diagnostic work-up with electroencephalography (EEG) and CSF analysis led to the establishment of CJD diagnosis. The present case highlights the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging findings in the diagnostic CJD panel. © 2014 Elsevier B.V. All rights reserved

Association of psychometric indices and normal electrodiagnostic studies in referral for suspected carpal tunnel syndrome

Background/Aim: The aim of this study was to investigate psychometric indices and their association with electrodiagnostic studies (EDX). Patients and Methods: A total of 100 patients referred for EDX testing of the upper limbs were prospectively enrolled. Demographic data, laboratory test results, referral physician specialty, main symptom, WHODAS 2.0-12 item version, Hospital Anxiety and Depression Scale (HADS), Boston Carpal Tunnel Questionnaire (BCTQ) and a Numeric Rating Scale (NRS) indicating the extent of their discomfort were collected. Results: Normal EDX results were elicited from 56% of patients. Only the presence of numbness in the right hand, pain in the left hand and older age were significantly associated with an abnormal EDX result. The more depressed and anxious the patients were, the more they scored on psychometric scales. Conclusion: The large prevalence of normal EDX studies raises the issue of unnecessary referrals. A proportion of patients are referred only according to their reported symptoms. Psychological factors affect the way a person expresses physical discomfort, leading to unnecessary EDX referrals and inevitably with normal results. © 2021 International Institute of Anticancer Research. All rights reserved