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.
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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
ABSTRACT
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.