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Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood–brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.

In this work, we study a technique of exploiting open-loop-generated trajectories for a constrained control problem, using them to shape suitable nonquadratic control Lyapunov functions (CLFs). These trajectories, generated offline, allow detecting a suitable domain of attraction (DOA) in which a candidate Lyapunov function has a negative derivative. Given suitably constructed basis functions, our working machinery is based on linear programming; hence, the technique can be applied to problems of nontrivial size in terms of the number of basis functions and points in the state space. For linear systems, we seek convex Lyapunov functions, which are homogeneous polynomials. Simulation and experimental results for drone control are given.

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health.

In his poetry, Michelangelo Buonarroti (1475–1564) explored the eye from both a physiological and a psychological perspective. This essay demonstrates that for him the organs of vision constituted a gateway to the intellect-soul, the eyes were a means by which lover and beloved, beholder and beheld touched, and the mind was their place of encounter and negotiation. Analyzing descriptions of the eye and the gaze in Michelangelo’s verse and elucidating the roots of his phenomenology of love in theories of Platonic intromission, Galenic-Mondinian anatomy, and Aristotelian-Avicennian psychology, this essay reveals that he subscribed to a nondualist, nonmaterialist worldview and understood humans as divinely created entities dependent upon the immaterial ground of their being.

As healthcare embraces the transformative potential of Artificial Intelligence (AI), it is imperative to safeguard patient and provider safety, equity, and trust in the healthcare system. This article outlines the approach taken by the British Columbia (BC) Provincial Health Services Authority (PHSA) to establish clinical governance for the responsible deployment of AI tools in healthcare. Leveraging its province-wide mandate and expertise, PHSA establishes the infrastructure and processes to proactively and systematically intake, assess, prioritize, and evaluate AI tools. PHSA proposes a coordinated approach in AI tool deployment in collaboration with regional health authorities to prevent duplication of efforts and ensure equitable access to existing and emerging AI tools across the province of BC, incorporating principles of anti-Indigenous racism, cultural safety, and humility. The proposed governance structure underscores the identification of clinical needs, proactive ethics review, rigorous risk assessment, data validation, transparent communication, provider training, and ongoing evaluation to ensure success.

Portable and efficient cognitive screening measures are needed to address the growing need for effective early detection of Alzheimer’s disease. The Neurotrack Cognitive Battery (NCB) offers an appealing, web-based application that may be sensitive to early cognitive changes associated with Alzheimer’s disease. The NCB contains measures that were conceptually derived from animal lesion studies. The current study sought to investigate the construct and diagnostic validity of the NCB among those with and without mild cognitive impairment (MCI). Participants (n= 47) with and without MCI were administered the NCB and traditional cognitive tests. Three of six NCB measures assessing domains of memory, processing speed, and executive functioning demonstrated moderate to strong associations with well-established cognitive performance tests. In classifying those with and without MCI, sensitivities of these three NCB measures ranged from 0.47 to 0.74, and specificities ranged from 0.78 to 1.00. For traditional cognitive measures, sensitivities ranged from 0.74 to 0.84, and specificities ranged from 0.74 to 0.94. Overall, web-based cognitive test measures pertaining to cognitive domains of memory, processing speed, and executive functioning may serve as highly portable screening tools for detecting the early stages of Alzheimer’s disease. Additionally, these cognitive domains may be valuable in informing back-translational research.

The article discusses emerging non-von Neumann computer architectures and their integration in the computing continuum for supporting modern distributed applications, including artificial intelligence, big data, and scientific computing. It provides a detailed summary of available and emerging non-von Neumann architectures, which range from power-efficient single-board accelerators to quantum and neuromorphic computers. Furthermore, it explores their potential benefits for revolutionizing data processing and analysis in various societal, science, and industry fields. The article provides a detailed analysis of the most widely used class of distributed applications and discusses the difficulties in their execution over the computing continuum, including communication, interoperability, orchestration, and sustainability issues.

Recent research has highlighted the adoption of blockchain technology (BCT) and the increasing recognition of its multiple capabilities for users. The main objective of this paper is to delineate different consumer segments based on their BCT beliefs and attitudes. Using a survey method, 934 questionnaires were collected and subjected to hierarchical and K-Means cluster analysis and contingency analysis. The results reveal four identifiable user segments with respect to BCT adoption: Innovators (enthusiastic about BCT), Cautious (careful about BCT), Sceptics (doubtful about BCT), and Suspicious (very distrustful about BCT). These results provide valuable insights into understanding behavioral intentions and serve as a basis for future research.

The emerging concept of big data pipelines provides relevant solutions and is one of the main enablers of telemedicine. We present a data pipeline for remote patient monitoring and show a real-world example of how data pipelines help address the stringent requirements of telemedicine.

In this article, we explore a novel architecture for distributing health monitoring computations over distributed cloud regions, both for constantly online patients and offline for several hours daily. We propose a conceptual architecture for a use-case example capable of processing thousands of simultaneous incoming streams with electrocardiogram signals.

Online social media enables low cost, easy access, rapid propagation, and easy communication of information, including spreading low-quality fake news. Fake news has become a huge threat to every sector in society, and resulting in decrements in the trust quotient for media and leading the audience into bewilderment. In this paper, we proposed a new framework called Message Credibility (MCred) for fake news detection that utilizes the benefits of local and global text semantics. This framework is the fusion of Bidirectional Encoder Representations from Transformers (BERT) using the relationship between words in sentences for global text semantics, and Convolutional Neural Networks (CNN) using N-gram features for local text semantics. We demonstrate through experimental results a popular Kaggle dataset that MCred improves the accuracy over a state-of-the-art model by 1.10% thanks to its combination of local and global text semantics.

It is unclear what effect the pattern of health-care use before admission to hospital with COVID-19 (index admission) has on the long-term outcomes for patients. We sought to describe mortality and emergency readmission to hospital after discharge following the index admission (index discharge), and to assess associations between these outcomes and patterns of health-care use before such admissions.

The program of matrix product states on tensor powers A⊗Zof C∗-algebras is carried under the assumption that Ais an arbitrary nuclear C*-algebra. For any shift invariant state ω, we demonstrate the existence of an order kernel ideal Kω, whose quotient action reduces and factorizes the initial data (A⊗Z,ω)to the tuple (A,Bω=A⊗N×/Kω,Eω:Å⊗Bω→Bω,ω¯:Bω→C), where Bωis an operator system and Eωand ω¯are unital and completely positive maps. Reciprocally, given a (input) tuple (A,S,E,ϕ)that shares similar attributes, we supply an algorithm that produces a shift-invariant state on A⊗Z. We give sufficient conditions in which the so constructed states are ergodic and they reduce back to their input data. As examples, we formulate the input data that produces AKLT-type states, this time in the context of infinite dimensional site algebras A, such as the C∗-algebras of discrete amenable groups.

Objective.Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population.

Emerging evidence from both clinical and preclinical studies underscores the role of aging in potentiating the detrimental effects of hypertension on cerebral microhemorrhages (CMHs, or cerebral microbleeds). CMHs progressively impair neuronal function and contribute to the development of vascular cognitive impairment and dementia. There is growing evidence showing accumulation of senescent cells within the cerebral microvasculature during aging, which detrimentally affects cerebromicrovascular function and overall brain health. We postulated that this build-up of senescent cells renders the aged cerebral microvasculature more vulnerable, and consequently, more susceptible to CMHs. To investigate the role of cellular senescence in CMHs’ pathogenesis, we subjected aged mice, both with and without pre-treatment with the senolytic agent ABT263/Navitoclax, and young control mice to hypertension via angiotensin-II and L-NAME administration. The aged cohort exhibited a markedly earlier onset, heightened incidence, and exacerbated neurological consequences of CMHs compared to their younger counterparts. This was evidenced through neurological examinations, gait analysis, and histological assessments of CMHs in brain sections. Notably, the senolytic pre-treatment wielded considerable cerebromicrovascular protection, effectively delaying the onset, mitigating the incidence, and diminishing the severity of CMHs. These findings hint at the potential of senolytic interventions as a viable therapeutic avenue to preempt or alleviate the consequences of CMHs linked to aging, by counteracting the deleterious effects of senescence on brain microvasculature.

Cerebral microhemorrhages (CMHs, microbleeds), a manifestation of age-related cerebral small vessel disease, contribute to the pathogenesis of cognitive decline and dementia in older adults. Histological studies have revealed that CMHs exhibit distinct morphologies, which may be attributed to differences in intravascular pressure and the size of the vessels of origin. Our study aimed to establish a direct relationship between the size/morphology of CMHs and the size/anatomy of the microvessel of origin. To achieve this goal, we adapted and optimized intravital two-photon microscopy-based imaging methods to monitor the development of CMHs in mice equipped with a chronic cranial window upon high-energy laser light-induced photodisruption of a targeted cortical arteriole, capillary, or venule. We assessed the time course of extravasation of fluorescently labeled blood and determined the morphology and size/volume of the induced CMHs. Our findings reveal striking similarities between the bleed morphologies observed in hypertension-induced CMHs in models of aging and those originating from different targeted vessels via multiphoton laser ablation. Arteriolar bleeds, which are larger (> 100 μm) and more widely dispersed, are distinguished from venular bleeds, which are smaller and exhibit a distinct diffuse morphology. Capillary bleeds are circular and smaller (< 10 μm) in size. Our study supports the concept that CMHs can occur at any location in the vascular tree, and that each type of vessel produces microbleeds with a distinct morphology. Development of CMHs resulted in immediate constriction of capillaries, likely due to pericyte activation and constriction of precapillary arterioles. Additionally, tissue displacement observed in association with arteriolar CMHs suggests that they can affect an area with a radius of ~ 50 μm to ~ 100 μm, creating an area at risk for ischemia. Longitudinal imaging of CMHs allowed us to visualize reactive astrocytosis and bleed resolution during a 30-day period. Our study provides new insights into the development and morphology of CMHs, highlighting the potential clinical implications of differentiating between the types of vessels involved in the pathogenesis of CMHs. This information may help in the development of targeted interventions aimed at reducing the risk of cerebral small vessel disease-related cognitive decline and dementia in older adults.

Objective.Over the past four decades, the prevalence of obesity has tripled and limited genetic studies with specific SNPs have been conducted, but no investigations using ghrelin and obestatin prepropeptide (GHRL) gene have been reported in the Ukrainians population. The aim of this study was to evaluate changes in the level of metabolic hormones in the blood of obese patients in relation to the GHRL (rs696217) polymorphism.

As part of TIV's DHW on Vehicle 5.0, this letter introduces a novel concept, Logistics 5.0, to address high complexities in logistics Cyber-Physical-Social Systems (CPSS). Building upon the theory of parallel intelligence and leveraging advanced technologies and methods such as blockchain, scenarios engineering, Decentralized Autonomous Organizations and Operations (DAOs), Logistics 5.0 promises to accelerate the paradigm shift towards intelligent and sustainable logistics. First, the parallel logistics framework is proposed, and the logistics ecosystem is discussed. Then, the human-oriented operating systems (HOOS) are suggested to providing intelligent Logistics 5.0 solutions. Logistics 5.0 serves as a critical catalyst in realizing the “6S” objectives, i.e. Safety, Security, Sustainability, Sensitivity, Service, and Smartness, within the logistics industry.

This article proposes a fully distributed energy management algorithm for dc microgrids, resilient to different faults. Specifically, we employ distributed model-predictive control to deal with the uncertainty that characterizes the microgrid operation. The optimization problem is solved at each time step through a distributed optimization algorithm, which has three main advantages: 1) agents of the network require a small computational power; 2) local information is not shared among the network nodes, hence preserving a certain level of privacy; and 3) it is suitable for implementation in large-scale systems. The resilience property of the algorithm stems from additional constraints that are enforced in order to store in the system enough energy to sustain the microgrid in the case of utility grid or line fault. Simulation results show that the algorithm is suitable to schedule the operation of agents that are always connected to the microgrid (e.g., loads) as well as agents that may be connected and disconnected (e.g., electric vehicles).

BackgroundFetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.MethodsWe performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.ResultsWe identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21Agene (KIF21A) was found.ConclusionOur study underlines the broad locus heterogeneity of FA with well-established and atypical genotype–phenotype associations. We describe KIF21Aas a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets.

Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women’s Heart Centre (WHC).

Corporate entrepreneurship can be considered important for organisational performance. While being recognised as being important for the development of innovations and technologies of small- and medium-sized firms and for the innovation/technology strategies of large firms, inter-organisational relationships in terms of networks and alliances have received inadequate research attention in the context of corporate entrepreneurship in general and in corporate technological entrepreneurship in particular. This study developed and tested a model of alliance-driven corporate technological entrepreneurship activities that impact on organisational performance. The model was tested on 226 usable responses from mail survey data from a sample of manufacturing firms from Slovenia. The model indicates the value of engagement in strategic alliances for the development of corporate technological entrepreneurship activities and consequential performance improvements. Keywords: Corporate technological entrepreneurship; Alliances; Performance; Slovenia

There's a peculiar ebb and flow that comes with life on "the grind." One week, you're riding high off a finals berth in front of your hometown crowd, a sea […]

One key characteristic that is frequently studied in composite sandwich structure mechanics is low-velocity impact performance.

In the era of the IoT revolution, applications are becoming ever more sophisticated and accompanied by diverse functional and non-functional requirements, including those related to computing resources and performance levels. Such requirements make the development and implementation of these applications complex and challenging. Computing models, such as cloud computing, can provide applications with on-demand computation and storage resources to meet their needs. Although cloud computing is a great enabler for IoT and endpoint devices, its limitations make it unsuitable to fulfill all design goals of novel applications and use cases. Instead of only relying on cloud computing, leveraging and integrating resources at different layers (like IoT, edge, and cloud) is necessary to form and utilize a computing continuum. The layers’ integration in the computing continuum offers a wide range of innovative services, but it introduces new challenges (e.g., monitoring performance and ensuring security) that need to be investigated. A better grasp and more profound understanding of the computing continuum can guide researchers and developers in tackling and overcoming such challenges. Thus, this paper provides a comprehensive and unified view of the computing continuum. The paper discusses computing models in general with a focus on cloud computing, the computing models that emerged beyond the cloud, and the communication technologies that enable computing in the continuum. In addition, two novel reference architectures are presented in this work: one for edge–cloud computing models and the other for edge–cloud communication technologies. We demonstrate real use cases from different application domains (like industry and science) to validate the proposed reference architectures, and we show how these use cases map onto the reference architectures. Finally, the paper highlights key points that express the authors’ vision about efficiently enabling and utilizing the computing continuum in the future.

ObjectiveAlthough gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngeniito be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngeniiL2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.DesignIn this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring.ResultsA. soehngeniitreatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngeniitreatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1Bexpression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngeniiintake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngeniiduodenal administration was safe and well tolerated.ConclusionsA single dose of A. soehngeniiimproves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1Bexpression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.Trial registration numberNTR-NL6630.

Decreases in acute stroke presentations have been reported during the coronavirus disease 2019 (COVID-19) pandemic surges. A recent study by Bojti et al. (GeroScience. 2021;43:2231–2248) sought to understand the relationship of public health mandates in Hungary as they were implemented with acute ischemic stroke admissions and interventions during two separate COVID-19 waves. We sought to perform a similar analysis of changes in ischemic stroke care at two distinct medical institutions in the USA. Two separate institutions and systems of ischemic stroke care were evaluated through a regional comprehensive stroke center telestroke service and a Veterans Affairs (VA) inpatient stroke and neurorehabilitation service. Telestroke consultations in a single system in Chicago, IL, were significantly decreased during the first COVID-19 wave during severely restricted public health mandates (z-score <  − 2), and were less depressed during a subsequent wave with less severe restrictions (z-score approaching − 1), which resembles findings in Hungary as reported by Bojti et al. In contrast, inpatient admissions during the first and second COVID-19 waves to a VA stroke and neurorehabilitation service in Oklahoma City remained unchanged. The Chicago and Hungary patterns of stroke presentations suggest that public perceptions, as informed by regional health mandates, might influence healthcare-seeking behavior. However, the VA experience suggests that specific patient populations may react differently to given public health mandates. These observations highlight that changes in stroke presentation during the COVID-19 pandemic may vary regionally and by patient population as well as by the severity of public health mandates implemented. Further study of COVID-19-related public health policies on acute stroke populations is needed to capture the long-term impact of such policies. Learning from the real-time impact of pandemic surges and public health policy on presentation of acute medical conditions, such as ischemic stroke, may prove valuable for designing effective policies in the future.

This paper considers a class of systems admitting several flat representations and proposes a trajectory tracking controller design which accounts for disturbance rejection. Set invariance is used for characterizing the tracking and estimation error dynamics. Furthermore, some insights on the disturbance propagation in case of different flat representations for a fixed-wing Unmanned Aerial Vehicle (UAV) system are highlighted via simulations and comparisons.

We revisit and enhance previous work pertaining to the use of polyhedral potential fields for motion planning in a receding horizon framework. We adapt the standard vertex-based mixed-integer (MI) representations of piecewise affine functions and propose three equivalent formulations which balance the complexity of the geometric representation with the size of the associated MI representation. In all cases, we arrive at formulations whose polyhedral support comes (either directly or as a refinement of it) from an associated hyperplane arrangement induced by the hyperplanes bounding the polyhedral obstacles.

How should an agency proactively identify and prioritize rail-highway grade crossings for intervention in relation to their likely performance benefits for the community and the system? Performance is mainly related to two factors: (i) the likelihood and duration of “blockage,” that is, the temporary obstruction of a road link when a train blocks the intersecting grade crossing, and (ii) the “hazard condition” of the crossing itself, with regard to its design and asset quality. Existing analytical grade crossing prioritization models focus almost solely on safety and crash prevention by addressing the “hazard condition” aspect of performance. The paper develops a quantitative multi-criteria approach that not only considers and builds on existing analytical safety-based approaches, but goes beyond and also includes considerations such as blocked crossings. The model calculates a multi-dimensional adaptive capacity score (ACS) for each crossing, which can then be used to rank a set of crossings, as well as test different policy scenarios and their effect on prioritization. The model is applied to approximately 5,700 grade crossings in the State of Ohio and detailed pilot validations with stakeholders in two counties conducted. Based on the validation process, the model provides comprehensive and cohesive results and is being deployed statewide. Next steps involve incorporating considerations for truck traffic and pedestrians/bicycles (non-motorized users) in calculating the ACS as well as developing mitigation measures for blocked crossings that can be considered from the model.

Hypertension affects two-thirds of people aged >60 years and significantly increases the risk of both vascular cognitive impairment and Alzheimer’s disease. Hypertension compromises the structural and functional integrity of the cerebral microcirculation, promoting microvascular rarefaction, cerebromicrovascular endothelial dysfunction and neurovascular uncoupling, which impair cerebral blood supply. In addition, hypertension disrupts the blood–brain barrier, promoting neuroinflammation and exacerbation of amyloid pathologies. Ageing is characterized by multifaceted homeostatic dysfunction and impaired cellular stress resilience, which exacerbate the deleterious cerebromicrovascular effects of hypertension. Neuroradiological markers of hypertension-induced cerebral small vessel disease include white matter hyperintensities, lacunar infarcts and microhaemorrhages, all of which are associated with cognitive decline. Use of pharmaceutical and lifestyle interventions that reduce blood pressure, in combination with treatments that promote microvascular health, have the potential to prevent or delay the pathogenesis of vascular cognitive impairment and Alzheimer’s disease in patients with hypertension.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan–Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2–12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680–1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.