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.

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.

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.

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)

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.

Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases.

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.

Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2.

Advent of the acute respiratory coronavirus SARS-CoV-2 has resulted in the search for novel antiviral agents and in the repurposing of existing agents with demonstrated efficacy against other known coronaviruses in the search for an agent with antiviral activity for use during the COVID-19 pandemic. Adamantanes including amantadine, rimantadine, and memantine have well-established benefit in the treatment of neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD) and fatigue related to Multiple sclerosis (MS) all of which are known comorbidities related to COVID-19 Moreover, results of basic pharmacological studies both in vitro and in vivo reveal that amantadine has the potential to inhibit SARS-CoV-2 via down-regulation of host-cell proteases resulting in impaired viral genome release into the host cell and via amantadine's property as an NMDA receptor antagonist resulting in the prevention of the acute lung injury and respiratory distress that is characteristic of COVID-19. Cases suggestive of COVID-19 prophylaxis have been reported in patients with PD or MS or severe cognitive impairment treated in all cases for several months with an adamantane [amantadine or memantine] who were subsequently infected with SARS-CoV-2 confirmed by RT-PCR, and, in all cases, no signs of infectious disease were encountered. Amantadine is effective for the treatment of fatigue in MS and for the neurological complications of Traumatic Brain Injury (TBI).

Neurological Complications of COVID-19 in the Elderly.

SARS-CoV-2 virus is a ß-coronavirus and produces a severe viral pneumonia which can be complicated by acute respiratory distress syndrome and multiorgan failure. As knowledge of the new coronavirus infection (COVID-19) increases, it has become known that SARS-CoV-2 has pronounced neurotropism, producing a wide spectrum of neurological complications. This article addresses the characteristics of the neurological complications of COVID-19 in elderly people.

A Timeline of Ca2+/cAMP Signalling: From Basic Research to Potential Therapeutics for Dementia.

BACKGROUND: The hypothesis that a dyshomeostasis of Ca2+ increases the incidence of dementia has been established. Several discoveries have emphasized the concept that a decrease in the excess of Ca2+ could be an interesting pharmacological target to alleviate dementia symptoms. Aging along with a healthy brain can be supported by daily exercise, self-control in caloric ingestion, and participation in intellectually challenging events. These lifestyle factors may alleviate the excess of Ca2+ resulting from a Ca2+ dyshomeostasis. Curiously, epidemiological and clinical studies have also reported a clinical relationship between hypertension, diabetes, and other inflammatory processes, and a higher risk of cognition decline. Considering the cumulative data from the scientific literature, including data of high evidence such as meta-analysis and systematic reviews, we can now link a Ca2+ dyshomeostasis as an upstream factor for hypertension, diabetes and other inflammatory processes, and dementia. Several reports have also indicated that increasing cAMP levels may induce neuroprotective outcomes, thus alleviating dementia symptoms. METHODS: With these concepts in mind, we found that the pharmacological manipulation of Ca2+/cAMP signalling could be a novel plausible target to treat dementia. This article puts together fundamental concepts and current therapies to treat dementia, including novel therapeutics coming from the pharmacological manipulation of Ca2+/cAMP signalling. RESULTS: Then, combined with improvements in the lifestyle issues, these novel therapeutics may allow sustained improvements in the life quality of age-related neurological patients. CONCLUSIONS: In addition, considering coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviewed recent reports about Ca2+ channel blockers' role in restoring Ca2+ signalling disruption due to COVID-19. Finally, this article also presents a timeline of the major events in Ca2+/cAMP signaling.

Twitter use by the dementia community during COVID-19: a user classification and social network analysis

Purpose: The study aimed to examine how different communities concerned with dementia engage and interact on Twitter. Design/methodology/approach: A dataset was sampled from 8,400 user profile descriptions, which was labelled into five categories and subjected to multiple machine learning (ML) classification experiments based on text features to classify user categories. Social network analysis (SNA) was used to identify influential communities via graph-based metrics on user categories. The relationship between bot score and network metrics in these groups was also explored. Findings: Classification accuracy values were achieved at 82% using support vector machine (SVM). The SNA revealed influential behaviour on both the category and node levels. About 2.19% suspected social bots contributed to the coronavirus disease 2019 (COVID-19) dementia discussions in different communities. Originality/value: The study is a unique attempt to apply SNA to examine the most influential groups of Twitter users in the dementia community. The findings also highlight the capability of ML methods for efficient multi-category classification in a crisis, considering the fast-paced generation of data. Peer review: The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-04-2021-0208. © 2022, Emerald Publishing Limited.

COVID-19 and the central nervous system: What is the interplay?

Since the outbreak of COVID-19 in 2019-2020, the highly contiguous disease caused by coronavirus 2 (SARS-CoV-2) spread worldwide in a short life span causing a disastrous effect and nearly 5.8 million deaths until February 2022. This global health crisis caused concerns about the disease's aetiology, epidemiology, and management. Understanding the virus's long-and short-term consequences on diverse human body organs and systems was one of the scientist's concerns despite the virus' respiratory system principal effect. Thus, after reporting neurological symptoms in approximately one-third of hospitalised patients with COVID-19, demonstrating how COVID-19 infects the central nervous system (CNS), causing neurodegenerative diseases in various patients and how the virus affects CNS function became quintessential. There are various mechanisms for COVID-19 pathophysiology, some implicating the potential virus invasion of the blood-brain barrier (BBB). Trans-synaptic and hematogenous routes are the main routes for the virus to pass through the barrier. Binding to the BBB endothelial cells is causing significant alterations in the permeability and integrity properties of the barrier, which cause an elevation of the incidence rate of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis among COVI-19 patients. COVID-19 patients developed neurological manifestations ranging from mild symptoms to severe diseases such as headache and loss of smell, encephalitis and CNS-mediated respiratory distress. However, encephalitis is not a common complication, and it has a significant mortality rate in severely ill patients due to the hyperactivation of the host immune response. Although more investigations are needed, severe COVID-19 patients are considered at a high risk of neurodegenerative disorder as a long-term consequence of SARS-CoV-2 infection. © 2022, Neurotak Publishing. All rights reserved.

Optimizing CNN-LSTM hybrid classifier using HCA for biomedical image classification

In medical science, imaging is the most effective diagnostic and therapeutic tool. Almost all modalities have transitioned to direct digital capture devices, which have emerged as a major future healthcare option. Three diseases such as Alzheimer's (AD), Haemorrhage (HD), and COVID-19 have been used in this manuscript for binary classification purposes. Three datasets (AD, HD, and COVID-19) were used in this research out of which the first two, that is, AD and HD belong to brain Magnetic Resonance Imaging (MRI) and the last one, that is, COVID-19 belongs to Chest X-Ray (CXR) All of the diseases listed above cannot be eliminated, but they can be slowed down with early detection and effective medical treatment. This paper proposes an intelligent method for classifying brain (MRI) and CXR images into normal and abnormal classes for the early detection of AD, HD, and COVID-19 based on an ensemble deep neural network (DNN). In the proposed method, the convolutional neural network (CNN) is used for automatic feature extraction from images and long-short term memory (LSTM) is used for final classification. Moreover, the Hill-Climbing Algorithm (HCA) is implemented for finding the best possible value for hyper parameters of CNN and LSTM, such as the filter size of CNN and the number of units of LSTM while fixing the other parameters. The data-set is pre-processed (resized, cropped, and noise removed) before feeding the train images to the proposed models for accurate and fast learning. Forty-five MR images of AD, Sixty MR images of HD, and 600 CXR images of COVID-19 were used for testing the proposed model ‘CNN-LSTM-HCA'. The performance of the proposed model is evaluated using six types of statistical assessment metrics such as;Accuracy, Sensitivity, Specificity, F-measure, ROC, and AUC. The proposed model compared with the other three types of hybrid models such as CNN-LSTM-PSO, CNN-LSTM-Jaya, and CNN-LSTM-GWO and also with state-of-art techniques. The overall accuracy of the proposed model received was 98.87%, 85.75%, and 99.1% for COVID-19, Haemorrhage, and Alzheimer's data sets, respectively. © 2023 John Wiley & Sons Ltd.

SARS-CoV-2 induces pro-inflammatory cytokines with an impact on mental health

In December 2019, the novel coronavirus strain SARS-CoV-2 caused an outbreak that quickly spread worldwide and led to the COVID-19 pandemic. COVID-19, the severe infectious disease caused by SARS-CoV-2, often presents with symptoms including fever, cough, and mental confusion and can cause the acute respiratory inflammatory disorder. Additionally, viral infection with SARS-CoV-2 is associated with mental health, neuronal degeneration, and psychiatric complications. With infection by the virus, cytokines are released by immune cells, causing acute systemic inflammation affecting the lungs. Lung damage can occur, resulting in hypoxia, brain damage, and mental health dysfunction. In addition, a cascade of inflammatory cytokines, including IL-1, IL-6, and TNF, are released, a phenomenon termed the "cytokine storm" that causes serious pathological damage to tissues and organs and mental health. This exaggerated production of cytokines leads to lymphopenia and disrupts the balance of Treg and Th17 cells, weakening the immune system. The elderly population is particularly at risk for damage associated with the "cytokine storm", which can affect neurological functions or result in death. Copyright © by BIOLIFE.

SARS-CoV-2 induces pro-inflammatory cytokines with an impact on mental health

In December 2019, the novel coronavirus strain SARS-CoV-2 caused an outbreak that quickly spread worldwide and led to the COVID-19 pandemic. COVID-19, the severe infectious disease caused by SARS-CoV-2, often presents with symptoms including fever, cough, and mental confusion and can cause the acute respiratory inflammatory disorder. Additionally, viral infection with SARS-CoV-2 is associated with mental health, neuronal degeneration, and psychiatric complications. With infection by the virus, cytokines are released by immune cells, causing acute systemic inflammation affecting the lungs. Lung damage can occur, resulting in hypoxia, brain damage, and mental health dysfunction. In addition, a cascade of inflammatory cytokines, including IL-1, IL-6, and TNF, are released, a phenomenon termed the "cytokine storm" that causes serious pathological damage to tissues and organs and mental health. This exaggerated production of cytokines leads to lymphopenia and disrupts the balance of Treg and Th17 cells, weakening the immune system. The elderly population is particularly at risk for damage associated with the "cytokine storm", which can affect neurological functions or result in death. Copyright © by BIOLIFE.