Early Components Research Articles

Attributed network embedding with dual fusion strategies

ABSTRACT Attributed network embedding (ANE) maps nodes in a network into a low-dimensional space while preserving the intrinsic essence of node attribute and network topology. Incorporating node attribute and network topology with more deeply and more harmoniously is a critical and challenging issue in the ANE, because node attribute and network topology are two kinds of heterogeneous information. Existing approaches fuse two kinds of heterogeneous information at different stages: i.e. before, during or after the learning process. In fact, fusions at different stages have their own advantages and disadvantages. To maximise the profit of utilising the attributed and networked information in ANE, we propose an Attributed Network Embedding model with Dual Fusion strategies (abbr. ANEDF), which consists of both mutually beneficial components: early fusion component for capturing the latent complementarity and late fusion component for extracting the unique and distinctive information from node attribute and network topology. The two components are co-trained during the learning process, which promotes information interaction and captures the consensus of heterogeneous information. Extensive experiments with the tasks of node classification, node clustering, link prediction and visualisation on eight publicly available networks have been conducted to evaluate the effectiveness and rationality of the proposed model. The experimental results demonstrate that ANEDF obtains the best classification, clustering and link prediction performance on 6–7 of 8 datasets, respectively.

Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice

Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) to satisfy regional energy demand. Ca2+ elevation in astrocytes can drive arteriole dilation to increase CBF, yet affirmative evidence for the necessity of astrocytes in functional hyperemia in vivo is lacking. In awake mice, we discovered that functional hyperemia is bimodal with a distinct early and late component whereby arteriole dilation progresses as sensory stimulation is sustained. Clamping astrocyte Ca2+ signaling in vivo by expressing a plasma membrane Ca2+ ATPase (CalEx) reduces sustained but not brief sensory-evoked arteriole dilation. Elevating astrocyte free Ca2+ using chemogenetics selectively augments sustained hyperemia. Antagonizing NMDA-receptors or epoxyeicosatrienoic acid production reduces only the late component of functional hyperemia, leaving brief increases in CBF to sensory stimulation intact. We propose that a fundamental role of astrocyte Ca2+ is to amplify functional hyperemia when neuronal activation is prolonged.

UNDERSTANDING LEADERSHIP IN NURSING HOME CONTEXT THROUGH ADAPTIVE LEADERSHIP FRAMEWORK FOR CHRONIC ILLNESS

Abstract The case studies were conducted as an early component of a pan-Canada project entitled Translating Research in Elder Care (TREC). This sub-project provided insights into the challenges and leadership of facilitating care model changes, care quality improvement, and quality of work enhancement of three long-term care (LTC) facilities in Canada. Through the lens of Adaptive Leadership Framework for Chronic Illness (ALFCI), leadership emerged as a critical element of their organizational context. Staff reported that contextual factors of high intensity of work and inadequate staff were barriers that added to the complexity of challenges facing them. Data collectors observed that frontline staff exhibited leadership behaviors in knowledge transmission, information sharing, teamwork, and person-centered strategies to address challenges. However, top-down facilitation can lead to misunderstanding and a lack of motivation from the frontline staff to follow the facilitation. The findings also suggested tailored facilitation about including frontline staff in formal interactions.

ERPs responses to dominance features from human faces

Social dominance is an important feature of social life. Dominance has been proposed to be one of two trait dimensions underpinning social judgments of human faces. Yet, the neural bases of the ability to identify different dominance levels in others based on intrinsically facial cues remains poorly understood. Here, we used event-related potentials to determine the temporal dynamics of facial dominance evaluation based on facial features signaling physical strength/weakness in humans. Twenty-seven participants performed a dominance perception task where they passively viewed faces with different dominance levels. Dominance levels did not modulate an early component of face processing, known as the N170 component, but did modulate the late positive potential (LPP) component. These findings indicate that participants inferred dominance levels at a late stage of face evaluation. Furthermore, the highest level of dominant faces and the lowest level of submissive faces both elicited higher LPP amplitudes than faces with a neutral dominance level. Taken together, the present study provides new insights regarding the dynamics of the neurocognitive processes underlying facial dominance evaluation.

Human hippocampal responses to network intracranial stimulation vary with theta phase.

Hippocampal-dependent memory is thought to be supported by distinct connectivity states, with strong input to the hippocampus benefitting encoding and weak input benefitting retrieval. Previous research in rodents suggests that the hippocampal theta oscillation orchestrates the transition between these states, with opposite phase angles predicting minimal versus maximal input. We investigated whether this phase dependence exists in humans using network-targeted intracranial stimulation. Intracranial local field potentials were recorded from individuals with epilepsy undergoing medically necessary stereotactic electroencephalographic recording. In each subject, biphasic bipolar direct electrical stimulation was delivered to lateral temporal sites with demonstrated connectivity to hippocampus. Lateral temporal stimulation evoked ipsilateral hippocampal potentials with distinct early and late components. Using evoked component amplitude to measure functional connectivity, we assessed whether the phase of hippocampal theta predicted relatively high versus low connectivity. We observed an increase in the continuous phase-amplitude relationship selective to the early and late components of the response evoked by lateral temporal stimulation. The maximal difference in these evoked component amplitudes occurred across 180 degrees of separation in the hippocampal theta rhythm; i.e., the greatest difference in component amplitude was observed when stimulation was delivered at theta peak versus trough. The pattern of theta phase dependence observed for hippocampus was not identified for control locations. These findings demonstrate that hippocampal receptivity to input varies with theta phase, suggesting that theta phase reflects connectivity states of human hippocampal networks. These findings confirm a putative mechanism by which neural oscillations modulate human hippocampal function.

Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer’s disease

Impairments in neural lysosomal- and autophagic-mediated degradation of cellular debris contribute to neuritic dystrophy and synaptic loss. While these are well-characterized features of neurodegenerative disorders such as Alzheimer's disease (AD), the upstream cellular processes driving deficits in pathogenic protein mishandling are less understood. Using a series of fluorescent biosensors and optical imaging in model cells, AD mouse models and human neurons derived from AD patients, we reveal a previously undescribed cellular signaling cascade underlying protein mishandling mediated by intracellular calcium dysregulation, an early component of AD pathogenesis. Increased Ca2+ release via the endoplasmic reticulum (ER)-resident ryanodine receptor (RyR) is associated with reduced expression of the lysosome proton pump vacuolar-ATPase (vATPase) subunits (V1B2 and V0a1), resulting in lysosome deacidification and disrupted proteolytic activity in AD mouse models and human-induced neurons (HiN). As a result of impaired lysosome digestive capacity, mature autophagosomes with hyperphosphorylated tau accumulated in AD murine neurons and AD HiN, exacerbating proteinopathy. Normalizing AD-associated aberrant RyR-Ca2+ signaling with the negative allosteric modulator, dantrolene (Ryanodex), restored vATPase levels, lysosomal acidification and proteolytic activity, and autophagic clearance of intracellular protein aggregates in AD neurons. These results highlight that prior to overt AD histopathology or cognitive deficits, aberrant upstream Ca2+ signaling disrupts lysosomal acidification and contributes to pathological accumulation of intracellular protein aggregates. Importantly, this is demonstrated in animal models of AD, and in human iPSC-derived neurons from AD patients. Furthermore, pharmacological suppression of RyR-Ca2+ release rescued proteolytic function, revealing a target for therapeutic intervention that has demonstrated effects in clinically-relevant assays.

Tibial Component Subsidence in a Total Ankle System Comparing Standard Technique Versus a Hybrid Technique

Total ankle arthroplasty (TAA) is a viable treatment option for end-stage ankle arthritis. However, implant survivorship remains an important consideration. Concerns regarding early component loosening with the low-profile tibial tray utilized by fourth-generation TAA systems have been raised in the literature. We have previously described our preliminary outcomes of a hybrid technique combining a stemmed intramedullary tibial component with a chamfer-cut talar component for TAA. A retrospective study comparing short-term outcomes of the tibial component between a standard fourth-generation TAA system versus our hybrid technique was performed. 46 patients with a minimum of 1-year follow up were included in the analyses. There were 25 subjects in the standard implant cohort utilizing a low-profile tibial tray, and 21 subjects in the hybrid group utilizing a stemmed intramedullary tibial component. No statistically significant difference between the demographics of each group was found. The rate of tibial component subsidence was 8% (n = 2) in the standard implant group, and 0% (n = 0) in the hybrid group, though this did not meet statistical significance (p = .49). Mean time to subsidence was 6 months, and revision rate due to tibial component subsidence was 2.1% (n = 1). Periprosthetic lucency was present on most recent follow-up radiographs in 32% and 9.5% of ankles in the standard and hybrid groups, respectively (p = .08). Despite prior concerns for tibial component subsidence with the standard fourth-generation system, we demonstrated low rates in both implant groups. Additional studies are needed to further explore factors that may predispose patients to early tibial component subsidence and resulting implant failure.

Using Event-Related Potentials (ERP) to identify the purchase intention of a consumer for familiar brands

Several neurological processes are undergoing on a conscious and subconscious level every time a consumer likes or dislikes a product. There is presently significant research in Consumer Neuroscience based on consumer behaviour and understanding of these processes. In this study, we have used Electroencephalography (EEG) and Event-Related Potentials (ERP) to capture consumer responses to highly familiar product images. EEG analysed from the 27 participants was used to extract P1, N1, P300, N400 and Late Posterior components. The analysis showed that the early ERP components viz., P1, N1 and P300 can differentiate between consumer liking and disliking of products. In contrast, the late ERP components N400 and Late Posterior components could not differentiate in the highly familiar product category. The results indicate that after continuous exposure, consumer preference towards highly-familiar products occurs as a part of automatic, unconscious mental processes irrespective of the product properties. Further research in this direction can test for the transference of consumer preference: from a conscious mental process to a subconscious mental process due to excessive and continuous product exposure and marketing repetition. Our study demonstrates that consumer behaviour in response to highly-familiar products can be classified using early ERP components only.

Impact of reduced-dimensionality independent components analysis on event-related potential measurements.

Independent components analysis (ICA) is an effective and ubiquitous tool for cleaning EEG. To reduce computation time, many analysis pipelines decrease EEG dimensionality prior to ICA. A 2018 report by Artoni and colleagues detailed the deleterious effects of such reduced-dimensionality ICA (rdICA) on the dipolarity and reliability of independent components. Though valuable for researchers interested in directly analyzing independent components, ICA is more commonly used for cleaning EEG. Thus, a direct examination of the impact of artifact removal via rdICA on EEG data quality is needed. We conducted a registered analysis of 128 electrode recordings of 43 healthy subjects performing an active auditory oddball task. We preprocessed each subject's data under the following conditions: (1) ICA without dimension reduction, (2) ICA with only 64 electrodes included, (3) ICA preceded by PCA retaining 99% of the original data variance and (4) ICA preceded by PCA retaining 90% variance. We then quantified ERP data quality by measuring mean-amplitude, standardized measurement error (SME) of the single-trial mean-amplitudes, and split-half reliability of the N1 and P3 components. We then attempted to replicate our findings in an independent validation dataset. We observed statistically and practically significant changes in the mean amplitude of early sensory components for the 90% condition. Unexpectedly, the SME was only larger for the 64 electrode condition. Also unexpectedly, the effect of rdICA on split-half reliability was inconsistent between datasets. Based on the observed data, we argue that PCA-based rdICA is justifiable when used cautiously.

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice.

Myocardial infarction (MI) is the major cause of mortality around the world. We recently demonstrated that chick early amniotic fluid (ceAF) can effectively rescue ischemic heart injury, indicating that it has a therapeutic function in MI. However, its functional components and the underlying mechanisms remain to be clarified. Here, we demonstrated that a fraction of ceAF, peak 8 (P8), had a protective effect on acute MI. P8 significantly decreased cardiomyocyte cross-sectional areas and cardiomyocyte apoptosis in MI mice. Using a human embryonic stem cell-derived cardiomyocyte model, which was subjected to hypoxia and reoxygenation, mimicking MI state, we found that P8 treatment reduced apoptosis and reversed myocardial contractility. Mechanistically, P8 improved cardiac function by inhibiting NF-κB signaling and downregulating inflammatory cytokine expression. Using mass spectrometry, we identified that guanosine and deoxynucleoside were the main functional components of P8 that suppressed the inflammatory response in human embryonic stem cell-derived cardiomyocytes. Collectively, our data suggest that specific components from ceAF are promising therapeutic agents for ischemic heart injury and could be a potential supplement to current medications for MI.

Chinese patients’ response to doctor–patient relationship stimuli: evidence from an event-related potential study

BackgroundWith improvements in medical technology, the doctor–patient relationship should be further improved. However, disputes between doctors and patients have increased, with the two groups frequently hurting each other. Therefore, we sought to explore the perception of Chinese patients regarding the stimuli of doctor–patient relationships with different valence.MethodsWe used event-related potential (ERP) to explore the brain electrical activity of 19 undergraduate participants who had a clinical experience in the previous 6 months where they perceived negative, neutral, and positive doctor–patient relationships. The ERPs were recorded, and the early ERP components (P2) and late positive potential (LPP) were measured.ResultsCompared with the stimuli of negative doctor–patient relationships, those of positive doctor–patient relationships would attract more attention and have larger P2 amplitude; LPP was larger for the stimuli of negative doctor–patient relationships than neutral ones in the 500–800 ms, while in the 1100–1500 ms, the stimuli of neutral doctor–patient relationships elicited larger LPP amplitude than positive ones.ConclusionPatients paid more attention to the stimuli of positive doctor–patient relationships because they expected to have the same positive relationship. Although threatening elements in negative doctor–patient relationships would catch patients’ attention and make them have implicit emotional regulation, neutral stimuli with poker-faced doctors would cause lasting attention. These results illustrate the patients’ real perception of the different valence of doctor–patient relationship stimuli.

Complement inhibition prevents glial nodal membrane injury in a GM1 antibody-mediated mouse model.

The involvement of the complement pathway in Guillain-Barré syndrome pathogenesis has been demonstrated in both patient biosamples and animal models. One proposed mechanism is that anti-ganglioside antibodies mediate neural membrane injury through the activation of complement and the formation of membrane attack complex pores, thereby allowing the uncontrolled influx of ions, including calcium, intracellularly. Calcium influx activates the calcium-dependent protease calpain, leading to the cleavage of neural cytoskeletal and transmembrane proteins and contributing to subsequent functional failure. Complement inhibition has been demonstrated to provide effective protection from injury in anti-ganglioside antibody-mediated mouse models of axonal variants of Guillain-Barré syndrome; however, the role of complement in the pathogenesis of demyelinating variants has yet to be established. Thus, it is currently unknown whether complement inhibition would be an effective therapeutic for Guillain-Barré syndrome patients with injuries to the Schwann cell membrane. To address this, we recently developed a mouse model whereby the Schwann cell membrane was selectively targeted with an anti-GM1 antibody resulting in significant disruption to the axo-glial junction and cytoplasmic paranodal loops, presenting as conduction block. Herein, we utilize this Schwann cell nodal membrane injury model to determine the relevance of inhibiting complement activation. We addressed the early complement component C2 as the therapeutic target within the complement cascade by using the anti-C2 humanized monoclonal antibody, ARGX-117. This anti-C2 antibody blocks the formation of C3 convertase, specifically inhibiting the classical and lectin complement pathways and preventing the production of downstream harmful anaphylatoxins (C3a and C5a) and membrane attack complexes. Here, we demonstrate that C2 inhibition significantly attenuates injury to paranodal proteins at the node of Ranvier and improves respiratory function in ex vivo and in vivo Schwann cell nodal membrane injury models. In parallel studies, C2 inhibition also protects axonal integrity in our well-established model of acute motor axonal neuropathy mediated by both mouse and human anti-GM1 antibodies. These data demonstrate that complement inhibition prevents injury in a Schwann cell nodal membrane injury model, which is representative of neuropathies associated with anti-GM1 antibodies, including Guillain-Barré syndrome and multifocal motor neuropathy. This outcome suggests that both the motor axonal and demyelinating variants of Guillain-Barré syndrome should be included in future complement inhibition clinical trials.

Visual P2p component responds to perceived numerosity

Numerosity perception is a key ability for human and non-human species, probably mediated by dedicated brain mechanisms. Electrophysiological studies revealed the existence of both early and mid-latency components of the Electrophysiological (EEG) signal sensitive to numerosity changes. However, it is still unknown whether these components respond to physical or perceived variation in numerical attributes. We here tackled this point by recording electrophysiological signal while participants performed a numerosity adaptation task, a robust psychophysical method yielding changes in perceived numerosity judgments despite physical numerosity invariance. Behavioral measures confirmed that the test stimulus was consistently underestimated when presented after a high numerous adaptor while perceived as veridical when presented after a neutral adaptor. Congruently, EEG results revealed a potential at around 200 ms (P2p) which was reduced when the test stimulus was presented after the high numerous adaptor. This result was much prominent over the left posterior cluster of electrodes and correlated significantly with the amount of adaptation. No earlier modulations were retrievable when changes in numerosity were illusory while both early and mid-latency modulations occurred for physical changes. Taken together, our results reveal that mid-latency P2p mainly reflects perceived changes in numerical attributes, while earlier components are likely to be bounded to the physical characteristics of the stimuli. These results suggest that short-term plastic mechanisms induced by numerosity adaptation may involve a relatively late processing stage of the visual hierarchy likely engaging cortical areas beyond the primary visual cortex. Furthermore, these results also indicate mid-latency electrophysiological correlates as a signature of the internal representation of numerical information.

Characterization of vagus nerve stimulation-induced pupillary responses in epileptic patients

BackgroundModulation of the locus coeruleus (LC)-noradrenergic system is a key mechanism of vagus nerve stimulation (VNS). Activation of the LC produces pupil dilation, and the VNS-induced change in pupil diameter was demonstrated in animals as a possible dose-dependent biomarker for treatment titration. ObjectiveThis study aimed to characterize VNS-induced pupillary responses in epileptic patients. MethodsPupil diameter was recorded in ten epileptic patients upon four stimulation conditions: three graded levels of VNS intensity and a somatosensory control stimulation (cutaneous electrical stimulation over the left clavicle). For each block, the patients rated the intensity of stimulation on a numerical scale. We extracted the latency of the peak pupil dilation and the magnitude of the early (0–2.5 s) and late components (2.5–5 s) of the pupil dilation response (PDR). ResultsVNS elicited a peak dilation with longer latency compared to the control condition (p = 0.043). The magnitude of the early PDR was significantly correlated with the intensity of perception (p = 0.046), whereas the late PDR was not (p = 0.19). There was a significant main effect of the VNS level of intensity on the magnitude of the late PDR (p = 0.01) but not on the early PDR (p = 0.2). The relationship between late PDR magnitude and VNS intensity was best fit by a Gaussian model (inverted-U). ConclusionsThe late component of the PDR might reflect specific dose-dependent effects of VNS, as compared to control somatosensory stimulation. The inverted-U relationship of late PDR with VNS intensity might indicate the engagement of antagonist central mechanisms at high stimulation intensities.

Investigating the Origin of TMS-evoked Brain Potentials Using Topographic Analysis.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) represents an increasingly popular tool to non-invasively probe cortical excitability in humans. TMS-evoked brain potentials (TEPs) are composed of successive components reflecting the propagation of activity from the site of stimulation, thereby providing information on the state of brain networks. However, TMS also generates peripherally evoked sensory activity which contributes to TEP waveforms and hinders their interpretation.In the present study, we examined whether topographic analysis of TEPs elicited by stimulation of two distinct cortical targets can disentangle confounding signals from the genuine TMS-evoked cortical response. In 20 healthy subjects, TEPs were evoked by stimulation of the left primary motor cortex (M1) and the left angular gyrus (AG). Topographic dissimilarity analysis and microstate analysis were used to identify target-specific TEP components. Furthermore, we explored the contribution of cortico-spinal activation by comparing TEPs elicited by stimulation below and above the threshold to evoke motor responses.We observed topographic dissimilarity between M1 and AG TEPs until approximately 80 ms post-stimulus and identified early TEP components that likely reflect specific TMS-evoked activity. Later components peaking at 100 and 180 ms were similar in both datasets and attributed to sensory-evoked activity. Analysis of sub- and supra-threshold M1 TEPs revealed a component at 17 ms that possibly reflects the cortico-spinal output of the stimulated area. Moreover, supra-threshold M1 activation influenced the topography of almost all later components. Together, our results demonstrate the utility of topographic analysis for the evaluation and interpretation of TMS-evoked EEG responses.

Foreign language learning and the mismatch negativity (MMN): A longitudinal ERP study

An early component of the auditory event-related potential (ERP), the mismatch negativity (MMN), has been shown to be sensitive to native phonemic sound contrasts. The potential changes to this neural sensitivity from foreign language learning have only been marginally studied. The existing research seems to suggest that the neural sensitivity as indexed by the MMN can adapt to foreign language sound contrasts with very target-specific training, but whether the effects are long-lasting or generalize to proper foreign language learning is yet to be investigated in a viable longitudinal study design. We therefore recorded electroencephalography (EEG) from two groups of language officer cadets (learning either Arabic (n = 8) or Dari (n = 12)) while they listened to speech sound contrasts from both languages. We recorded their EEG four times over the course of 19 months of intensive foreign language training (immediately before they started, after three weeks, after six months, and after 19 months).We did not find any language-specific effects of learning on the cadets’ MMNs to the speech sound contrasts. We did, however, elicit statistically reliable MMNs to both sound contrasts for both groups at most of the four times of measurement. Furthermore, we found that the Arabic learners’ MMNs to the Arabic stimuli diminished over time, and that the Dari learners’ P3a responses to the Arabic stimuli diminished over time. Correlating the participants’ MMNs with their behavioral responses to the language stimuli did not reveal any strong links between behavior and neurophysiology. However, those Dari learners whose MMNs to the Dari stimuli increased the most within the first three weeks, also received the highest grades on a listening task after 17 weeks.

Speech Perception Performance in Cochlear Implant Recipients Correlates to the Number and Synchrony of Excited Auditory Nerve Fibers Derived From Electrically Evoked Compound Action Potentials.

Many studies have assessed the performance of individuals with cochlear implants (CIs) with electrically evoked compound action potentials (eCAPs). These eCAP-based studies have focused on the amplitude information of the response, without considering the temporal firing properties of the excited auditory nerve fibers (ANFs), such as neural latency and synchrony. These temporal features have been associated with neural health in animal studies and, consequently, could be of importance to clinical CI outcomes. With a deconvolution method, combined with a unitary response, the eCAP can be mathematically unraveled into the compound discharge latency distribution (CDLD). The CDLD reflects both the number and the temporal firing properties of excited ANFs. The present study aimed to determine to what extent the CDLD derived from intraoperatively recorded eCAPs is related to speech perception in individuals with CIs. This retrospective study acquired data on monosyllabic word recognition scores and intraoperative eCAP amplitude growth functions from 124 adult patients with postlingual deafness that received the Advanced Bionics HiRes 90K device. The CDLD was determined for each recorded eCAP waveform by deconvolution. Each of the two Gaussian components of the CDLD was described by three parameters: the amplitude, the firing latency (the average latency of each component of the CDLD), and the variance of the CDLD components (an indication of the synchronicity of excited ANFs). Apart from these six CDLD parameters, the area under the CDLD curve (AUCD) and the slope of the AUCD growth function were determined as well. The AUCD was indicative of the total number of excited ANFs over time. The slope of the AUCD growth function indicated the increases in the number of excited ANFs with stimulus level. Associations between speech perception and each of these eight CDLD-related parameters were investigated with linear mixed modeling. In individuals with CIs, larger amplitudes of the two CDLD components, greater AUCD, and steeper slopes of the AUCD growth function were all significantly associated with better speech perception. In addition, a smaller latency variance in the early CDLD component, but not in the late, was significantly associated with better speech recognition scores. Speech recognition was not significantly dependent on CDLD latencies. The AUCD and the slope of the AUCD growth function provided a similar explanation of the variance in speech perception (R 2 ) as the eCAP amplitude, the slope of the amplitude growth function, the amplitude, and variance of the first CDLD component. The results demonstrate that both the number and the neural synchrony of excited ANFs, as revealed by CDLDs, are indicative of postimplantation speech perception in individuals with a CI. Because the CDLD-based parameters yielded a higher significance than the eCAP amplitude or the AGF slope, the authors conclude that CDLDs can serve as a clinical predictor of the survival of ANFs and that they have predictive value for postoperative speech perception performance. Thus, it would be worthwhile to incorporate the CDLD into eCAP measures in future clinical applications.

Opsonization of Early Apoptotic Cells by IgG from Lupus Nephritis Amplifies Activation of Early Complement Components and Promotes Inflammatory Phagocytosis

Introduction: SSARo 60 has been reported to be exposed on the surface of early apoptotic cells and recognized by auto antibodies from lupus. The aim of this study was to explore the subsequent effects of the binding of IgG from anti-SSA positive LN patients on the fate of early apoptotic cells.

Electrophysiological evidence of subclinical trigeminal dysfunction in patients with COVID-19 and smell impairment: A pilot study.

BackgroundSmell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing.MethodsWe enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem.ResultsMasseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients.ConclusionsPatients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction.

Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury

Traumatic brain injury (TBI) is a leading cause of mortality, sensorimotor morbidity, and neurocognitive disability. Neuroinflammation is one of the key drivers causing secondary brain injury after TBI. Therefore, attenuation of the inflammatory response is a potential therapeutic goal. This review summarizes the most important neuroinflammatory pathophysiology resulting from TBI and the clinical trials performed to attenuate neuroinflammation. Studies show that non-selective attenuation of the inflammatory response, in the early phase after TBI, might be detrimental and that there is a gap in the literature regarding pharmacological trials targeting specific pathways. The complement system and its crosstalk with the coagulation system play an important role in the pathophysiology of secondary brain injury after TBI. Therefore, regaining control over the complement cascades by inhibiting overshooting activation might constitute useful therapy. Activation of the complement cascade is an early component of neuroinflammation, making it a potential target to mitigate neuroinflammation in TBI. Therefore, we have described pathophysiological aspects of complement inhibition and summarized animal studies targeting the complement system in TBI. We also present the first clinical trial aimed at inhibition of complement activation in the early days after brain injury to reduce the risk of morbidity and mortality following severe TBI.