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In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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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.
ABSTRACT
In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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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.
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Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic COVID-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.Copyright © 2023 Elsevier B.V.
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The new COVID-19 presents some comorbidities, such as obesity, Alzheimer's, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the para-doxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipopro-tein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proin-flammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like beta-amyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications;and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.Copyright © 2022 Bentham Science Publishers.
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- Alzheimer's disease (AD) is an irreversible degenerative illness of the central nervous system with characteristic histological alterations, known as amyloid plaques and plaques and tangles in the brain induces neurotoxicity and synaptic dysfunction, ev
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The study aimed to determine the levels of Tau, amyloid beta, dynorphin, and number of biochemical variables in men with COVID-19. The study groups included 30 men with COVID-19, 30 men who recovered from COVID -19, and 30 healthy men as a control group. Protein and biochemical assays include: tau, amyloid beta, dynorphin, zinc, triglycerides, HDL-C, VLDL-C and cholesterol. The results were a significant increase (P 0.05) in the levels of amyloid beta, dynorphin, HDL-C, cholesterol and LDL-C in patients. Those infected with COVID-19 compared to the control group, while in the recovery group, amyloid beta was low compared to the control group, while zinc and lipid profile were high in the recovered. While tau protein, zinc, triglycerides and VLDL-C showed a significant decrease at (P< 0.05) in the affected men group compared to the control group.
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The study aimed to determine the levels of Tau,amyloid beta, dynorphin, and number of biochemical variables in men with COVID-19. The study groups included 30 men with COVID-19, 30 men who recovered from COVID -19, and 30 healthy men as a control group. Protein and biochemical assays include: Tau, amyloid beta, dynorphin, zinc, triglycerides, HDL-C, VLDL-C and cholesterol. The results were a significant increase (P 0.05) in the levels of amyloid beta, dynorphin, HDL-C, cholesterol and LDL-C in patients. Those infected with COVID-19 compared to the control group, while in the recovery group, amyloid beta was low compared to the control group, while zinc and lipid profile were high in the recovered. While tau protein, zinc, triglycerides and VLDL-C showed a significant decrease at (P< 0.05) in the affected men group compared to the control group. © 2023, ResearchTrentz Academy Publishing Education Services. All rights reserved.
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The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies is investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation is established, but the role of various infectious agents in the development of this process is much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including long-term persistent in nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either A beta or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of proinflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. The reactivation of latent infection, such as herpes, in APOE4 carriers significantly increases the risk of development of Alzheimer's disease. Class-II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. An increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.
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COVID-19, which primarily affects the pulmonary system, turned out to be a global pandemic, whereas the effects on other systems are still unknown. SARS-CoV-2, binds to angiotensin-converting enzyme 2 (ACE2) receptors in the lungs, causing pneumonia-like symptoms. The same ACE receptors are also present in organs other than the lungs. Therefore, there is a need to study the impact of coronavirus on other human body organs. Recently, UK Biobank reports on the genetic risk factor of the virus attack. A double mutation in the apolipoprotein E (APOE4) allele has shown a significant role in COVID-19. The same APOE4 mutation has already been proven to hold a key role in developing early-onset Alzheimer's disease (EOAD). Despite this data, Alzheimer's disease is believed to be a comorbidity of COVID-19. Previous virus attacks on the same viral family, Coronaviridae, produced neurological effects like neurodegeneration, neuronal inflammation, and other central nervous system-related dysfunctions. Since the long-term implications of COVID-19 are unknown, more research into the impact of the virus on the central nervous system is needed. Both COVID-19 and AD share a common genetic factor, so that AD patients may have a greater risk of SARS-CoV-2. Here, in this review, we have briefly discussed the role of APOE4 in the pathogenesis of AD and SARS-CoV-2, along with their treatment strategy, current scenario, and possible future directions.
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In light of the rising evidence of the association between viral and bacterial infections and neurodegeneration, we aimed at revisiting the infectious hypothesis of Alzheimer's disease and analyzing the possible implications of COVID-19 neurological sequelae in long-term neurodegeneration. We wondered how SARS-CoV-2 could be related to the amyloid-ß cascade and how it could lead to the pathological hallmarks of the disease. We also predict a paradigm change in clinical medicine, which now has a great opportunity to conduct prospective surveillance of cognitive sequelae and progression to dementia in people who suffered severe infections together with other risk factors for Alzheimer's disease.
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Background: The universal risk to mankind, coronavirus disease 2019 (COVID-19), shares etiological cofactors with a variety of diseases, including anemic chronic kidney disease patients (CKD) with cognitive dysfunction like Alzheimer disease (AD). Understanding the shared links between COVID-19 and CKD, as well as cognitive impairment such as AD, might aid in designing therapeutic ways to combat both. Given the need of developing COVID-19 medicine, the connection and symptoms of CKD with cognitive impairment have been reviewed here, with a focus on memory and learning disturbance. Objective(s): COVID-19 and CKD with cognitive dysfunction share angiotensin-converting enzyme 2 receptors, and AD indicators include amyloid, tau protein, and glycogen synthase kinase-3beta. Anemia in patients with CKD and pulmonary fibrosis is frequently treated with recombinant human erythropoietin (rHuEPO). Through nitric oxide stimulation, neuroprotection, and various organ hypoxias, rHuEPO promotes red blood cells (RBC) growth while also assisting oxygen delivery. Results and Conclusion(s): In COVID-19, rHuEPO may be advantageous. The common etiological variables and manifestations outlined in this review could aid in the development of therapeutic options for COVID-19 and CKD with cognitive impairment, such as AD, and so help to eliminate the ongoing universal risk. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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Human herpesviruses (HHVs) have been implicated as possible risk factors in Alzheimer's disease (AD) pathogenesis. Persistent lifelong HHVs infections may directly or indirectly contribute to the generation of AD hallmarks: amyloid beta (Aß) plaques, neurofibrillary tangles composed of hyperphosphorylated tau proteins, and synaptic loss. The present review focuses on summarizing current knowledge on the molecular mechanistic links between HHVs and AD that include processes involved in Aß accumulation, tau protein hyperphosphorylation, autophagy, oxidative stress, and neuroinflammation. A PubMed search was performed to collect all the available research data regarding the above mentioned mechanistic links between HHVs and AD pathology. The vast majority of research articles referred to the different pathways exploited by Herpes Simplex Virus 1 that could lead to AD pathology, while a few studies highlighted the emerging role of HHV 6, cytomegalovirus, and Epstein-Barr Virus. The elucidation of such potential links may guide the development of novel diagnostics and therapeutics to counter this devastating neurological disorder that until now remains incurable.
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Modern lifestyle and fast-food consumption nature increase the cholesterol consumption and deposition in our body. It is becoming one of the key risk factors in AD development. Several genes and receptors play crucial roles in such developments. Consumption of high-fat diet and absence of physical activity can lead to obesity. Higher BMI is the indicator of obesity. Higher BMI accelerates AD development due to brain atrophy, neuroinflammation, and oxidative stress in the hippocampus. Obesity in childhood and adolescence leads to dementia and AD in later life. COVID harmfully affects Alzheimer's patients, and it is also reported that COVID related dementia and neurodegeneration is one of the prominent post-COVID complications. This review summarises the role of cholesterol in Alzheimer's disease development and the importance of genes, receptors, and diet behind this.
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The objective of this mini review was to discuss the relationship between nutritional deficiencies and mental health, and to present a structure that helps to visualize these associations based on a literature review and the scenarios of the COVID-19 pandemic. The study was conducted to demonstrate the effect of the nutritional deficiencies on the occurrence and/or worsening of mental health problems, mainly related to the most drastic measures of social distance during the COVID-19 pandemic. Studies have already shown that a nutritionally unbalanced diet may be associated with greater chances of mental health problems. Insufficient levels of micronutrients can, by regulating the stress response, immune and oxidative systems, negatively affect brain functions and, consequently, cognitive functions and mental health of individuals. The current pandemic of COVID-19 reveals an increase in food and nutritional insecurity, and a worsening of this situation among already vulnerable populations. Micronutrient deficiencies may be exacerbated in a context of increased food insecurity and the COVID-19 pandemic, which may contribute to increased mental health problems.
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Keywords: Soft tissue trauma, Advanced Practice Physiotherapist, Fracture Clinic Purpose: A large amount of patients were identified in Fracture Clinic with soft tissue trauma who did not necessarily need to see a doctor. We proposed that we could reduced the demands on doctors in Fracture Clinic and the foot-fall through the hospital, whilst improving patient outcomes and patient satisfaction by having these patients seen instead in an advanced practice physiotherapist-led STTC. Aims of the pilot: 1. Reduce the number of patients in Fracture Clinic requiring medical review 2. Standardise pathways of care 3. Provide patients with earlier specialised physiotherapy management 4. Maintain or improve outcomes and patient satisfaction Methods: A quality improvement approach was used with an Action Research Methodology. Results: Less patients with Soft tissue trauma required medical review. Reduced patient foot-fall through the hospital (59% of patients discharged at first contact compared to 35% of patients in Fracture Clinic). Management pathways for patients with soft tissue trauma were standardised. Patients received early specialist physiotherapy management. Also reduced number of referrals to physiotherapy and a reduced average number of subsequent physiotherapy follow-up appointments. We received outstanding patient satisfaction (95% rated extremely likely to recommend the service to friends and family;97/100 achieved on the VSQ-9 satisfaction questionnaire) Conclusion(s): The Soft Tissue Trauma Clinic utilises expert clinicians who provide a highly effective and cost-efficient service that reduces demand on Fracture Clinic whilst delivering excellent patient outcomes and satisfaction. Depending on funding, we are hoping the service can be made substantive, and then expanded to be included in the Trust's Trauma management pathway. Impact: We’ve demonstrated that patients with Soft tissue trauma can be successfully managed without needing to see a doctor in Fracture Clinic. Adopting an APP led-soft tissue trauma clinic could aid the post-COVID Orthopaedic Recovery Plan by releasing a Registrar from Fracture clinic to do other activities, such as elective orthopaedic clinics or additional theatre lists. We were able to reduce the footfall through the hospital. More patients were discharged at first contact in the STTC with fewer requiring additional follow-up appointments because patients were seeing the right person at the right time. 59% of patients were appropriately discharge at their first attendance in the STTC compared to 35% in Fracture clinic. We managed to agree with the Orthopaedic team Standardised care pathways for patients with STT. In line with the NHS Long-term plan, if we can standardise care pathways we can:- Reduced unwarranted variation which in-turn will reduce variations in outcomes and inequalities. - We can ensure an evidenced base and best practice model is followed as suggested by the ‘GIRFT’ as opposed to research literature and anecdotal evidence that suggests a lot of variation in patient management by current fracture clinic services. We were able to provide patients with earlier specialist physiotherapy management. We know the earlier we can provide suitable management advice we are more likely to improve a patient's function and their return to work, reduce patient anxiety, and reduce long-term pain and disability. We also reduced the length of a patient's rehabilitation and need for further physiotherapy. Funding acknowledgements: Not funded
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INTRODUCTION/HYPOTHESIS: COVID-19 has been associated with distinct types of neuronal damage. We hypothesize that the progression of neurological damage will be related to an imbalance between neurodegeneration, neuroinflammatory, and neuroprotective markers, therefore suggesting a potential mechanism for the emergence of adverse, chronic outcomes. METHODS: 105 patients admitted to an urban, academic hospital with a diagnosis of COVID-19 were enrolled. Serum neuroprotective (clusterin, fetuin), neurodegenerative (τ, phosphorylated τ, amyloids, TDP43, NRGN, NCAM-1, and KLK6), and neuroinflammatory (CCL23, YKL40, MIF) markers were collected. These were analyzed longitudinally in conjunction with immune system activators (RAGE, IL-34) using the multiplex platform. Electronic medical records were used to collect demographic and clinical data. RESULTS: Of the 105 patients, 5 were diagnosed with stroke within 28 days of admission, followed by an additional 6 strokes occurring by 6 months, or a 9.5% occurrence of stroke overall. Serum levels of Amyloid β42 declined significantly for the general population 7 days after admission when compared to initial collections (p< 0.001), while Amyloid β40, KLK6, and MIF declined and recovered within the same 7 days (p< 0.001, p< 0.001, p=0.003). The neuroprotective markers fetuin and clusterin were particularly dynamic with fetuin decreasing and restoring in less than 7 days (p=0.02) and clusterin remaining low after admission (p< 0.001). Most patients had persistently elevated CCL23 levels, with the stroke patient cohort having the highest values (p=0.018). The IL-6 levels of stroke patients were significantly higher compared to their non-stroke counterparts one week after admission (p=0.001), while IL-8 levels fluctuated before declining (p< 0.001). CONCLUSIONS: Our data reveals elevations in neuronal damage in the 7 days following hospital admission for COVID-19 patients. The down-regulation of fetuin and clusterin is particularly compelling as their declines may be linked to the elevated neuronal injury seen with increased neuroinflammatory markers, specifically CCL23 and IL-6. Serum levels of neurodegeneration markers proved complex, therefore possibly suggesting a more dynamic relationship to the neural abnormalities seen in COVID-19 patients.