Anticipated Long-Term Neurobehavioral Outcomes Following COVID-19

First identified in December 2021, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-the virus causing COVID-19, is responsible for significant morbidity and mortality rates. Given the worldwide impact of COVID-19, there is much interest in the anticipated long-term effects for those with history of SARS-CoV-2 infection. While initially presumed as a respiratory infection, there is now evidence of a broader array of pathophysiological mechanisms which result in a wide spectrum of reported acute and chronic symptoms in patients with confirmed COVID-19. These include including memory and other neurocognitive changes as well as psychiatric and behavioral symptoms. These nonspecific, but often debilitating, sequalaeare complex and difficult to disentangle from more common causes of neurobehavioral change. The goal of this chapter is to discuss anticipated chronic neurocognitive and psychiatric outcomes of COVID-19 survivors based on emerging peer-reviewed literature, data from prior pandemics, and outcome studies from well-characterized, clinically similar syndromes. This unpacking of long-term complications from COVID-19 will seek to set expectations and provide guidance for clinicians who will undoubtably encounter increased volumes of patients with residual post-COVID-19 neurobehavioral changes. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

Role of Citicoline in Patients With Mild Cognitive Impairment.

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.

Creutzfeldt-Jakob disease in a post-COVID-19 patient: did SARS-CoV-2 accelerate the neurodegeneration?

Background: Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder, with few months as a usual duration from onset to death. Case presentation: In this case report, a patient of Sporadic CJD (sCJD) who presented one month after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The diagnosis of this case was established after confirming findings from clinical, neurophysiology, radiological, and laboratory features of this disease. Conclusion: Putting in mind all the updated data on the pathogenesis of CJD and the immune responses to SARS-CoV-2, we can suggest that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of this fatal neurodegenerative disease.

Ultra-sensitive Detection of Alzheimer's Biosmarkers Using Plasmonic Optical Fiber Sensors

The emergence of the Covid-19 pandemic has drawn great attention to vulnerable people affected by major diseases. Among them, Alzheimer's disease (AD) is the most prevalent disease. However, a long-standing challenge is to achieve early diagnosis of AD by detecting biomarkers such as amyloid beta (Aβ42), thus avoiding the labor of specialized hospital personnel and the high cost of imaging examinations using positron emission tomography. In this paper, we report a straightforward approach to realize a non-invasive lab-around fiber (LaF) optical sensor for AD biomarker detection, which is based on a tilted fiber Bragg grating (TFBG) combined with a nanoscale metallic thin film. We successfully demonstrated the detection of Aβ42 in complex biological matrices with a detection limit of 5 pg/mL. Therefore, our TFBG-SPR biosensor platform enables large-scale early disease screening and has great potential for clinical applications in early AD diagnosis. © 2022 IEEE.

Adipose tissue, systematic inflammation, and neurodegenerative diseases

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Interplay of cGAS with micronuclei: Regulation and diseases.

In higher eukaryotes, sophisticate regulation of genome function requires all chromosomes to be packed into a single nucleus. Micronucleus (MN), the dissociative nucleus-like structure frequently observed in aging and multiple disease settings, has critical, yet under-recognized, pathophysiological functions. Micronuclei (MNi) have recently emerged as major sources of cytosolic DNA that can activate the cGAS-STING axis in a cell-intrinsic manner. However, MNi induced from different genotoxic stressors display great heterogeneity in binding or activating cGAS and the signaling responses downstream of the MN-induced cGAS-STING axis have divergent outcomes including autoimmunity, autoinflammation, metastasis, or cell death. Thus, full characterization of molecular network underpinning the interplay of cGAS and MN is important to elucidate the pathophysiological roles of immunogenic MN and design improved drugs that selectively target cancer via boosting the MN-derived cGAS-STING axis. Here, we summarize our current understanding of the mechanisms for self-DNA discrimination by cGAS. We focus on discussing how MN immunogencity is dictated by multiple mechanisms including integrity of micronuclear envelope, state of nucleosome and DNA, competitive factors, damaged mitochondrial DNA and micronucleophagy. We also describe emerging links between immunogenic MN and human diseases including cancer, neurodegenerative diseases and COVID-19. Particularly, we explore the exciting concept of inducing immunogenic MN as a therapeutic approach in treating cancer. We propose a new theoretical framework to describe immunogenic MN as a biological sensor to modulate cellular processes in response to genotoxic stress and provide perspectives on developing novel experimental approaches to unravel the complexity of MN immunogenicity regulation and immunogenic MN pathophysiology.

Enriching Social Sharing for the Dementia Community: Insights from In-Person and Online Social Programs

The dementia community faces major challenges in social engagements, which have been further complicated by the prolonged physical distancing measures due to the COVID-19 pandemic. Designing digital tools for in-person social sharing in family and care facility settings has been well explored, but comparatively little HCI work has focused on the design of community-based social technologies for virtual settings. We present our virtual fieldwork on remote social activities explored by one dementia community in response to the impacts of the pandemic. Building upon our previously published on-site fieldwork in this community, we expand on our initial publication by follow-up interviewing caregivers and facilitators and reflecting on a virtual social program. Through thematic analysis and contrasting in-person and online formats of the program, we deepened the understanding of virtual social engagements of the dementia community, examining their efforts to leverage physical objects and environments, enhance open and flexible experiences, and expand collaborative space. We propose to open new design opportunities through holistic approaches, including reimagining community social spaces, rethinking agency in people with dementia and caregivers, and diversifying HCI support across communities and stakeholders. © 2023 Copyright held by the owner/author(s). Publication rights licensed to ACM.

The possibilities of using the effects of ozone therapy in neurology

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHOD(S): The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULT(S): Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION(S): Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.Copyright © 2021 Neuroendocrinology Letters.

Exploration of multifaceted molecular mechanism of angiotensin-converting enzyme 2 (ACE2) in pathogenesis of various diseases.

Angiotensin converting enzyme 2 (ACE2) is a homolog of ACE (a transmembrane bound dipeptidyl peptidase enzyme). ACE2 converts angiotensinogen to the heptapeptide angiotensin-(1-7). ACE2 and its product, angiotensin-(1-7), have counteracting effects against the adverse actions of other members of renin-angiotensin system (RAS). ACE2 and its principal product, angiotensin-(1-7), were considered an under recognized arm of the RAS. The COVID-19 pandemic brought to light this arm of RAS with special focus on ACE2. Membrane bound ACE2 serves as a receptor for SARS-CoV-2 viral entry through spike proteins. Apart from that, ACE2 is also involved in the pathogenesis of various other diseases like cardiovascular disease, cancer, respiratory diseases, neurodegenerative diseases and infertility. The present review focuses on the molecular mechanism of ACE2 in neurodegenerative diseases, cancer, cardiovascular disease, infertility and respiratory diseases, including SARS-CoV-2. This review summarizes unveiled roles of ACE2 in the pathogenesis of various diseases which further provides intriguing possibilities for the use of ACE2 activators and RAS modulating agents for various diseases.

NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer's disease, Parkinson's disease, Huntington's disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3's and other inflammasomes' regulation, while minimizing failure risks in candidate drug trials.

Uncovering the Correlation between COVID-19 and Neurodegenerative Processes: Toward a New Approach Based on EEG Entropic Analysis.

COVID-19 is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although it primarily attacks the respiratory tract, inflammation can also affect the central nervous system (CNS), leading to chemo-sensory deficits such as anosmia and serious cognitive problems. Recent studies have shown a connection between COVID-19 and neurodegenerative diseases, particularly Alzheimer's disease (AD). In fact, AD appears to exhibit neurological mechanisms of protein interactions similar to those that occur during COVID-19. Starting from these considerations, this perspective paper outlines a new approach based on the analysis of the complexity of brain signals to identify and quantify common features between COVID-19 and neurodegenerative disorders. Considering the relation between olfactory deficits, AD, and COVID-19, we present an experimental design involving olfactory tasks using multiscale fuzzy entropy (MFE) for electroencephalographic (EEG) signal analysis. Additionally, we present the open challenges and future perspectives. More specifically, the challenges are related to the lack of clinical standards regarding EEG signal entropy and public data that can be exploited in the experimental phase. Furthermore, the integration of EEG analysis with machine learning still requires further investigation.

The challenge of managing parkinson's disease patients during the COVID-19 pandemic

The 2019 novel coronavirus (nCoV) pandemic is rapidly developing across the globe and new information is emerging expeditiously and constantly, particularly in relation to neurological illnesses. Both central and peripheral nervous system involvement has been reported including headache, dizziness, hyposmia/anosmia, taste disturbances, seizures, stroke, alteration of the sensorium, and even acute hemorrhagic necrotizing leukoencephalopathy. Varying degrees of olfactory disturbances may pre-empt the diagnosis of COVID-19. Although no direct effect of 2019 nCoV has been reported yet on Parkinson's disease, there are enormous possible indirect effects and implications. We examine the potential effects and challenges posed by this pandemic to individuals with Parkinson's disease, particularly in the Indian context where telecommunication access or support group access may be lacking for these patients. Additionally, lockdown and social distancing may pose hurdles in the provision of optimum medical therapy, particularly if patients experience motor and non-motor deteriorations due to diverse reasons.

Proactive dysphagia management of patients with neurodegenerative diseases: Early identification and intervention

Patients with neurodegenerative diseases (ND) frequently experience concomitant impairments in pulmonary, cough, and swallow function. These impairments can lead to accelerated morbidity and mortality due to adverse events (e.g. aspiration pneumonia, respiratory failure, malnutrition/dehydration). Historically, exercise-based interventions have been avoided in patients with ND due to fear that they may lead to faster disease progression and increased fatigue, yet, emerging evidence has revealed moderate exercise training in patients with ND may prolong function, life, and quality of life. This has led to the proposal of a paradigm shift from reactive to proactive management of these patients. Therefore, there is high demand for noninvasive, portable methods for continuously monitoring pulmonary and swallow function in patients with ND to proactively implement palliative interventions and mitigate adverse events. Yet, few exist. Gold standard assessments (e.g. spirometry, videofluoroscopy) require in-person clinic visits, which can be challenging for patients with ND to attend due to physical mobility impairments, transportation issues, multifactorial health problems, and compromised immune systems (e.g. COVID-19 pandemic). Therefore, this dissertation examined: 1) The safety, tolerability, and impact of exercise-based interventions on function and quality of life in patients with amyotrophic lateral sclerosis (PALS);and 2) The ability of a novel, non-invasive, sensor-based technology (high-resolution cervical auscultation [HRCA]) to characterize swallow function in patients with ND. To examine Aim 1, the first experiment examined the impact of respiratory interventions on pulmonary, cough, and surrogates of swallow function in PALS and the second experiment investigated the impact of exercise-based interventions on function and quality of life in PALS via a systematic review. To investigate Aim 2, the third experiment explored HRCA's ability to differentiate between swallows from patients with ND and healthy age-matched adults and the fourth experiment compared temporal and spatial swallow kinematic measures between patients with ND and healthy adults and investigated HRCA's ability to annotate specific swallow kinematic events in patients with ND. Findings revealed: 1) Exercise-based interventions are well-tolerated and may be beneficial for PALS with mild-moderate disease severity, and 2) HRCA has high potential as a noninvasive, accurate method for characterizing swallow function in patients with ND. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Smell and taste

This chapter provides an up-to-date overview of the nature and causes of chemosensory disturbances in older age, tools for their evaluation, and approaches useful for counselling patients and treating the underlying dysfunction. In addition to the sensory innervation of the olfactory nerve, free nerve endings of the trigeminal nerve are distributed throughout the nasal mucosa. Threshold tests establish the lowest concentration of an odorant that can be perceived or recognised as a quality. Odour identification tests determine the degree of a person's olfactory function. The loss of smell can be quite severe in patients with nasal sinus disease, with most being anosmic or profoundly hyposmic. Severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, affects chemosensory functions. During the last decade, more extensive research in the area of central nervous diseases has accumulated evidence on neurodegenerative processes and impaired olfaction. Taste function, like olfactory function, declines over the lifespan. © 2022 John Wiley & Sons Ltd. All rights reserved.

ADPT: An Automated Disease Prognosis Tool Towards Classifying Medical Disease Using Hybrid Architecture of Deep Learning Paradigm

The Covid 19 beta coronavirus, commonly known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently one of the most significant RNA-type viruses in human health. However, more such epidemics occurred beforehand because they were not limited. Much research has recently been carried out on classifying the disease. Still, no automated diagnostic tools have been developed to identify multiple diseases using X-ray, Computed Tomography (CT) scan, or Magnetic Resonance Imaging (MRI) images. In this research, several Tate-of-the-art techniques have been applied to the Chest-Xray, CT scan, and MRI segmented images' datasets and trained them simultaneously. Deep learning models based on VGG16, VGG19, InceptionV3, ResNet50, Capsule Network, DenseNet architecture, Exception and Optimized Convolutional Neural Network (Optimized CNN) were applied to the detecting of Covid-19 contaminated situation, Alzheimer's disease, and Lung infected tissues. Due to efforts taken to reduce model losses and overfitting, the models' performances have improved in terms of accuracy. With the use of image augmentation techniques like flip-up, flip-down, flip-left, flip-right, etc., the size of the training dataset was further increased. In addition, we have proposed a mobile application by integrating a deep learning model to make the diagnosis faster. Eventually, we applied the Image fusion technique to analyze the medical images by extracting meaningful insights from the multimodal imaging modalities. © 2022 IEEE.

Spike proteins . . . and other stories

Among 30 000 people whose dietary habits were assessed with food diaries, food frequency questionnaires, and interviews, adherence neither to conventional dietary recommendations nor to a modified Mediterranean diet was associated with subsequent likelihood of Alzheimer's disease or any other type of dementia (Neurology doi:10.1212/WNL.0000000000201336). Assessments of functional development at age of school entry and subsequent performance on tests of literacy and numeracy in the fourth year of primary school found no evidence that IVF led to an increased risk of developmental vulnerability or poorer educational outcomes (PLoS Med doi:10.1371/journal.pmed.1004148). Renal denervation for resistant hypertension A few weeks ago, Minerva noted a registry study showing that the modest fall in blood pressure induced by catheter based radio frequency renal nerve ablation was sustained over three years of follow-up.

[Current approaches in the treatment and rehabilitation of patients with neurological diseases after COVID-19. Resolution of the International Experts Forum]. / Lechenie i reabilitatsiya bol'nykh s nevrologicheskimi narusheniyami posle perenesennogo COVID-19. Rezolyutsiya Mezhdunarodnogo foruma ekspertov.

Despite the significant shift in global attention away from the pandemic, the problem of a new coronavirus infection remains important in the medical community. Almost 3 years after the start of the COVID-19 pandemic the issues of rehabilitation and management of delayed manifestations and sequelae of the disease are especially important. According to numerous available data, the new coronavirus infection is characterized by multiorgan lesions. Respiratory dysfunction, clotting disorders, myocardial dysfunction and various arrhythmias, acute coronary syndrome, acute renal failure, GI disorders, hepatocellular damage, hyperglycemia and ketosis, dermatological complications, ophthalmological symptoms and neurological disorders may be found. Significant prevalence of the latter in the post-coronavirus period necessitated this International Expert Forum to develop unified approaches to the management of patients with neurological complications and sequelae of new coronavirus infection based on practical experience and considering the scientific information available on COVID-19. The expert council developed a resolution formulating the tactics for the management of patients with neurological manifestations of COVID-19.

Roles of RNA-binding proteins in neurological disorders, COVID-19, and cancer.

RNA-binding proteins (RBPs) have emerged as important players in multiple biological processes including transcription regulation, splicing, R-loop homeostasis, DNA rearrangement, miRNA function, biogenesis, and ribosome biogenesis. A large number of RBPs had already been identified by different approaches in various organisms and exhibited regulatory functions on RNAs' fate. RBPs can either directly or indirectly interact with their target RNAs or mRNAs to assume a key biological function whose outcome may trigger disease or normal biological events. They also exert distinct functions related to their canonical and non-canonical forms. This review summarizes the current understanding of a wide range of RBPs' functions and highlights their emerging roles in the regulation of diverse pathways, different physiological processes, and their molecular links with diseases. Various types of diseases, encompassing colorectal carcinoma, non-small cell lung carcinoma, amyotrophic lateral sclerosis, and Severe acute respiratory syndrome coronavirus 2, aberrantly express RBPs. We also highlight some recent advances in the field that could prompt the development of RBPs-based therapeutic interventions.