The Trail Making Test (TMT) is one of the most commonly administered tests in clinical and research neuropsychological settings. The two parts of the test [part A (TMT-A) and part B (TMT-B)] enable the evaluation of visuoperceptual tracking and processing speed (TMT-A), as well as divided attention, set-shifting and cognitive flexibility (TMT-B). The main cognitive processes that are assessed using TMT, i.e. processing speed, divided attention and cognitive flexibility, are often affected in patients with stroke. Considering the wide use of TMT in research and clinical settings since its introduction in neuropsychological practice, the purpose of our review was to provide a comprehensive overview on the use of TMT in stroke patients in an attempt to mainly identify its role for the evaluation of post-stroke cognitive dysfunction and progression over time, the identification of the underlying neuroanatomical pathology related to impaired TMT performance, and the association with other stroke outcomes, such motor function, driving ability and quality of life. Our comprehensive review underscores that the TMT stands as an invaluable asset in the stroke assessment toolkit, contributing nuanced insights into diverse cognitive, functional, and emotional dimensions. As research progresses, continued exploration of the TMT potential across these domains is encouraged, fostering a deeper comprehension of post-stroke dynamics, and enhancing patient-centered care across hospitals, rehabilitation centers, research institutions, and community health settings. Its integration into both research and clinical practice reaffirms TMT status as an indispensable instrument in stroke-related evaluations, enabling holistic insights that extend beyond traditional neurological assessments.

Stroke remains one of the leading causes of death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing ischaemic penumbra. Stem cell therapy offers a promising alternative. As a regenerative medicine, stem cells offer a wider range of treatment strategies, including long-term intervention for chronic patients, through the reparation and replacement of injured cells via mechanisms of differentiation and proliferation. The purpose of this review is to evaluate the therapeutic role of stem cells for ischaemic stroke. The paper discusses the pathology during acute, subacute, and chronic phases of cerebral ischaemic injury, highlights the mechanisms involved in mesenchymal, endothelial, haematopoietic, and neural stem cell-mediated cerebrovascular regeneration and evaluates the pre-clinical and clinical data concerning the safety and efficacy of stem cell-based treatments. Treatment of stroke patients with different type of stem cells appears to be safe and efficacious even at relatively higher concentrations irrespective of the route and timing of administration. Priming or preconditioning of cells prior to administration appears to help augment their therapeutic impact. However, larger patient cohorts and later phase trials are required to consolidate these findings.

Background and objectives: Although intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS) only a small proportion of stroke patients receive this drug. Low administration rate is mainly due to delayed presentation of patients to the emergency department (ED) or lack of a stroke team/unit in most of the hospitals. So, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors, influence administration of rt-PA we split the general sample (n=202) in two groups: group No rt-PA (n=137) and group rt-PA (n=65) based on performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all sample we found that the median onset-to-ED door time was 180 minutes (IQR, 120-217.5 minutes), door-to-physician time was 4 minutes (IQR, 3-7 minutes), door-to-CT time was 52 minutes (IQR, 48-55 minutes), and door-in-door-out time was 61 minutes (IQR, 59-65 minutes). ED time targets such as door-to physician time (p=0.245), door-to-CT time (p=0.219), door-to-door-out time (p=0.24), or NIHSS at admission to Neurology department (p=0.405), or NIHSS after 24 h (p=0.9) did not have a statistically significant effect on administration or no rt-PA treatment in patients included in our study. Only highest Door-to-CT time was statistically significantly correlated with death outcome. Conclusion: In our study, rt-PA administration rate was higher than expected. Statistically significant correlation between ED time targets was found between lower Onset-to-ED door time with administration of rt-PA treatment (p<0.001) and between highest Door-to-CT time and death outcome.

We used a mixed-method single-case experimental research design to examine the effect of modelling (peer versus non-peer) on exercise self-efficacy in stroke survivors who participated in a community-based exercise program. Quantitative data were obtained using a ABCA design: (A1) no model/baseline 1 (3 weeks); (B) peer model (6 weeks); (C) non-peer model (6 weeks); and (A2) no model/baseline 2 (3 weeks). Four participants completed self-efficacy questionnaires after each weekly session. Qualitative data were obtained using researcher diaries and two semi-structured interviews: after B and A2. Based on quantitative and qualitative results, participants reported higher exercise self-efficacy in the model conditions, with ratings appearing highest for the non-peer model. This finding could be due to a lack of full integration of the peer model and low feelings of similarity. Modelling in general could help people recovering from a stroke increase their exercise self-efficacy, but non-peer models may not be most advantageous.

The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

Acute ischemic stroke (AIS) is the loss of neurological function due to a sudden reduction in cerebral blood flow and is a leading cause of disability and death worldwide. In recent years, the field of radiological imaging has experienced an explosion that may reach unprecedented heights with the advent of artificial intelligence. One of the latest innovations in artificial intelligence is radiomics, which is based on the fact that a large amount of quantitative data can be extracted from radiological images, from which patterns can be identified and associated with specific pathologies. Since its inception, radiomics has been particularly associated with the field of oncology, with promising results in a wide range of clinical situations. The performance of radiomics in non-tumour pathologies has been increasingly explored in recent years and the results continue to be promising. The aim of this review is to explore the potential applications of radiomics in AIS patients and to theorise how radiomics may change the paradigm for these patients in the coming years.

The aim of this study was to measure one-year total cost of stroke and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first ever acute stroke, hemorrhagic and ischemic, (ICD-10 codes: I61, I63 and I64) admitted within 48 hours of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality and informal care costs were considered. We used an annual time horizon, including all costs for 2021 irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at €343.1 mil a year in 2021, (€10,722/patient or €23,308 per QALY). Out of €343.1 mil., 53.3% (€182.9 mil) consisted direct healthcare cost representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at €160.2 mil. The mean productivity losses were estimated to 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality and 42.4 days lost due to informal caregiving by family members.This study highlights the burden of stroke and underlines the need for stakeholders and policy makers to re-organize stroke care and promote interventions that have been proved as cost-effective

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.

The cortical motor system can be reorganized following a stroke, with an increasing recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments.  This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine hemispheric dominance of the SEP and re-confirmed with source localization.  The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 was negatively correlated with Fügl-Meyer Upper Extremity Motor Score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index.  These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions. This reorganization delays the latency of somatosensory processing after a stroke.  This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mo-bility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

This study used established biomarkers of death due to ischemic stroke (IS) and performed network, enrichment, and annotation analysis. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell surface interactions, and the proteoglycan-integrin-extra cellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, VEGFA, proteoglycan-integrin-ECM complex, NFKB/RELA and SP1.

This study used structural equation modelling (SEM) to evaluate the direct effect of sex and age on stroke types and outcomes in Tertiary Health Facilities in Rives State, Nigeria. The study was a cross-sectional retrospective hospital-based research that utilized specific stroke patients’ information between 2015-2019. The study obtained the sex and age, stroke type (ischemic/hemorrhagic), and outcomes (No disability/disability/death) from the records. The retrieved data was Microsoft Excel (2016), then analyzed using SPSS (version 21, Amos) and STATGRAPHICS centurion (Stat Point Tech., Inc.). From the result, out of the recorded 1916 stroke patients, 1229 (64.1%) were female, while 687 (35.9%) were males. The older adults (>55 years) had more recorded cases (n=1289) than young adults (ages 18–35 years; n=77) and middle-aged adults (ages 36–55 years, n=550). The SEM results showed that age was significantly associated with stroke type (P<0.001) and outcomes (P=0.038), while sex was significantly associated with stroke outcomes (P<0.001). The likelihood of death was 1.3 times higher in hemorrhagic stroke than ischemic stroke. In conclusion, age and sex had direct effects on stroke type, while age had a direct effect on stroke outcome. Hemorrhagic stroke was more likely to cause death than ischemic stroke in the studied population.

This study aimed to analyze the responsiveness of the 5STS test among stroke patients and to estimate the MCIDs for different severity levels of community ambulation and stages of recovery. The 5STS and comparator instruments [gait speed and Functional Ambulatory Category (FAC)] were evaluated at baseline. These measures were repeated at 4 (Stage 1) and 8 weeks (Stage 2), together with the Global Rating of Change (GROC). The MCIDs were calculated with two anchor-based methods using the GROC as the external criterion. Responsiveness to change for the 5STS was estimated analyzing the correlation with changes in the two comparator instruments and their capacity to discriminate improvement. For the 5STS test, while the MCIDs of the limited community ambulators were similar in the two stages (around 3 s), those of the household ambulators decreased from 1.9 s to 0.72 s. Spearman's rho coefficients showed an acceptable correlation between changes in 5STS and changes for both the FAC and gait speed changes in both stages of recovery. Our study revealed that the 5STS is responsive to functional changes in patients with stroke and that their degree of severity and stage of recovery influence the MCID values of the 5STS.

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

Migraine and stroke are neurological disorders with significant global prevalence and impact. Recent advances in migraine therapy have focused on calcitonin gene-related peptide (CGRP) pathway. This review examines the shared pathomechanisms between migraine and stroke, with emphasis on the role of CGRP. We analyze current literature on CGRP's functions in cerebrovascular regulation, edema formation, neuroinflammation, and neuroprotection. CGRP acts as a potent vasodilator and plays a crucial role in trigeminovascular activation during migraine attacks. In stroke, CGRP has demonstrated neuroprotective effects by improving collateral circulation and reducing ischemia-reperfusion injury. Concerns have been raised about the potential impact of CGRP inhibsitors on stroke risk and outcomes. Studies in animals suggest that CGRP receptor antagonists may worsen cerebral ischemia by impairing collateral flow. We discuss the implications of these findings for the use of CGRP-targeting therapies in migraine patients, especially those at increased risk of stroke. Additionally, we explore the complex interplay between CGRP, endothelial function, and platelet activity in both conditions. This review highlights the need for further research to elucidate the long-term cerebrovascular safety of CGRP pathway inhibitors and to identify potential subgroups of migraine patients who may be at higher risk of adverse cerebrovascular events with these novel therapies.

Background: Stroke is one of the leading causes of death and disability worldwide. The diagnosis of stroke remains largely clinical, yet widely used stroke scoring systems and brain imaging do not satisfactorily allow distinction of ischaemic stroke (IS) patients from stroke mimics (SM). Blood biomarkers are promising tools that could facilitate clinical triage. Methods: This study recruited 66 patients with IS and 24 SM. The levels of Glial fibrillary acidic protein (GFAP), Neuron-specific enolase (NSE), Neurofilament light chain (NfL) and blood-brain barrier (BBB) proteins [Occludin (OCLN), Zonula occludens 1 (ZO-1), Claudin-5] in blood serum were measured by enzyme-linked immunosorbent assay technique. Biomarker levels in IS patients and SM was compared using the Mann–Whitney U test. Multivariable logistic regression analysis was used to evaluate the diagnostic performance of biomarkers in combination with the National Institutes of Stroke Scale (NIHSS) score. Results: Significant differences in circulating GFAP, NfL, OCLN, ZO-1, and Claudin-5 but not NSE in IS patients compared to SM. The combination of circulating ZO-1, Claudin-5, and OCLN with NIHSS score gives the highest diagnostic accuracy, sensitivity, and specificity. Conclusion: A prediction model with Circulating BBB proteins in combination with NIHSS score differentiates between IS patients and SM.

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homologue, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives of the study of NOXs in CVDs.

Stroke survivors often face diverse unmet needs, highlighting the significance of identifying and addressing these needs to enhance rehabilitation outcomes and overall quality of life. This study aimed to validate the modified Needs Assessment Questionnaire (mNAQ) as a reliable and valid tool for assessing the needs of stroke patients in the Greek context. Additionally, the research sought to identify potential differences in the assessment of stroke patients' needs based on their stroke phase and National Institutes of Health Stroke Scale (NIHSS) scores. A sample of 71 adult stroke survivors, adhering to World Health Organization guidelines and providing autonomous consent, participated in the study. The mNAQ, comprising 141 items across 12 domains, was uti-lized to evaluate stroke patients' needs. The NIHSS and Barthel Index (BI) were employed for functional independence and mobility assessment. Data analysis incorporated confirmatory fac-tor analysis, exploratory factor analysis, and Cronbach's reliability analysis to establish con-struct validity and internal consistency. Concurrent and known-groups validity analyses were conducted, and Spearman’s rho correlation explored the relationship between mNAQ and BI scores. Non-parametric analyses were applied to identify differences based on stroke phase and NIHSS scores. The study revealed that the mNAQ initially lacked satisfactory psychometric properties in the Greek context. Subsequent modifications, guided by confirmatory and explora-tory factor analyses, resulted in a refined three-factor scale encompassing 31 items in the domains of communication, mobility, and social functioning needs. This adapted measure effectively dif-ferentiated between acute and chronic stroke patients and those with minor and moderate strokes. In conclusion, the validated 31-item Greek mNAQ emerges as a crucial tool for compre-hensively assessing the needs of stroke patients. Its application holds promise for optimizing post-stroke care, improving functional outcomes, and ultimately enhancing the overall well-being and quality of life for stroke survivors.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome," linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

According to the World Health Organisation ischemic stroke is the second leading cause of death in the world. More frequent it is caused by brachiocephalic arteries (BCA) atherosclerosis. Timely detection of the atherosclerosis and it`s unstable course can allow a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. The research included 90 blood plasma samples. The first group - 52 patients with severe atherosclerotic lesions, second group - 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of blood plasma was carried out. There is a statistically significant difference (р

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.

In the context of evaluating physical function in individuals with stroke, the 3-meter backward walk test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test-retest reliability and construct validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) three times by different physiotherapists. Results indicated the 3MBWT displayed high reliability (r=0.97-0.98) and showed significant construct validity with other established walking tests like the 6MWT (r=-0.78) and 10MWT (r=0.71), with a moderate correlation to the FGA (r=-0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and validates well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.

Introduction: The transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyze the evidence in the ap-plication of tDCS in the recovery of gait disturbance in stroke patients. Methods: This review was conducted according to the recommendations of the PRISMA statement. Three different elec-tronic databases were searched for relevant results: PubMed, Scopus, and Cochrane. We included reviews and meta-analyses that only considered randomized controlled trials (RCTs) that inves-tigated the effects of transcranial direct electrical stimulation, in combination or not with other physiotherapy treatment, on gait recovery. Results: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study re-ceived high certainty of evidence, 5 received low certainty of evidence and 7 received critically low certainty of evidence. Conclusions: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters, mobility, endurance, strength and motor function, there is insuf-ficient evidence to recommend this treatment.

Here we performed a comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and copper content in the injured and uninjured areas of the frontal lobes and the hippocampus of the brain of male Wistar rats, after modeling of combined brain and spinal cord injury. Brain and spinal cord injury were modelled by local destruction of the left precentral region of the brain using a stylet followed by hemorrhage injury at the level of the first lumbar vertebra of the spinal cord. We found a significant decrease in NO production 7 days after injury modeling in the injured and uninjured (contralateral) brain regions, but the copper content remained unchanged one week after injury modeling. Thus, combined brain and spinal cord injury is not accompanied by a radical change in the activity of the antioxidant system in the brain, which is also confirmed by the absence of changes in NO production and copper content in the hippocampus.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Coronavirus disease 2019 restrictions impacted Canadians' daily living, especially those at higher risk of compromised health conditions. This study aimed to describe the physical, psychological, and social well-being of adults with disabilities, and older adults from May to June 2020. An online survey was used to administer standardized measures of mobility, anxiety and depression, boredom, resilience, technology readiness, social support, social networks, and participation. Seventy-two participants were recruited, with a mean age (SD) of 61.2 (13.8). 69.4% of participants had a disability, and 51.4% were older adults. 27.8% and 16.7% of participants exceeded the anxiety and depression cut-off scores, respectively. Boredom and restriction in participation were experienced by 76.4% and 80.1% of participants, respectively. Participants' mean (SD) resilience and life space scores were 72.4 (14.0) and 51.9 (24.0), respectively. Individuals with disabilities have comparatively higher mean anxiety (5.5 to 3.3), depression (4.8 to 2.9), and boredom (92.2 to 72.3) scores than those without. Individuals with a disability had lower resilience (69.9 to 78.0) and felt more life space restrictions (45.4 to 67.6). Our findings revealed issues with anxiety, boredom, participation, and life space activity. This information may provide supporting evidence when creating policies to mitigate existent health and social inequities.

Robot-assisted gait training (RAGT) is a promising treatment for stroke rehabilitation. Although the coordination between the upper and lower limbs is important for locomotor training, commercially available robotics for gait training mainly focus on the restoration of lower limb function. We aimed to evaluate the feasibility and usability of complex upper and lower limb RAGT in stroke patients using the GTR-A®, end effector-type robotic device. Patients with subacute stroke (N=9) received 30-minute RAGT thrice a week for two weeks (six sessions). Functionally, the hand grip strength (HGS), Functional Ambulatory Categories, modified Barthel Index, muscle strength test sum score, Berg Balance Scale, Timed Up and Go test, and Short Physical Performance Battery were used. The heart rate and a structured questionnaire were used to evaluate cardiorespiratory fitness and the usability of RAGT. Among the nine patients, all functional parameters between the baseline and post-training were significantly improved after RAGT, except for HGS and the muscle strength test. The questionnaire’s mean scores for each domain were as follows: safety 4.40±0.35, effects 4.23±0.31, efficiency 4.22±0.77, and satisfaction 4.41±0.25. The GTR-A® is a feasible and safe robotic device for patients with gait impairment after stroke. It showed functional improvement with endurance training effects.

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

Background: Many randomized controlled trials (RCTs) and systematic reviews (SRs) on acupuncture treatment for post-acute stroke dysphagia have been published. Due to conflicting results an overview of SRs to summarize and assess the quality of this evidence to determine whether acupuncture is effective for this disease was conducted. Methods: Seven databases were searched for SRs and/or Meta-analysis of RCTs and quasi-RCTs on acupuncture for post-acute stroke dysphagia. Two authors independently identified SRs and meta-analyses, collected data to assess the quality of included SRs and meta analyses according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the revised Assessment of Multiple Systematic Reviews (AMSTAR 2). Results: 31 SRs were identified. Quality of 22 SRs was critically low, 5 SRs were low, and 4 Cochrane SRs were moderate when evaluated by AMSTAR2. 17 SRs reported 85.2-96.3% items of PRISMA. Five SRs included explanatory RCTs, 16 SRs included pragmatic RCTs, and 10 SRs included both. Conclusion: Currently evidence on the effectiveness of acupuncture on post-acute stroke dysphagia is low quality. Type of study appeared to have no direct influence on the result, but the primary outcome measures showed a relationship with the quality of SRs. High quality trials with large sample sizes should be the focus of future research. PROSPERO REGISTRATION NUMBER: CRD42019134163

(1) Background: The COVID-19 pandemic has raised concerns about the impact of underlying medical conditions on the health outcomes of people living with HIV (PLWH). This study aimed to assess how pre-existing chronic medical conditions affect the health outcomes of PLWH infected with COVID-19. (2) Methods: A retrospective study using data from the Minnesota Fairview network (January 1, 2020 - December 31, 2022) was conducted. Fisher’s Exact Test, Kruskal-Wallis rank sum test, and ordinal logistic regressions with Benjamini-Hochberg (BH) adjustment on p-values were used to assess the influence of chronic conditions on COVID-19 severity, adjusting for age and gender. (3) Results: Among 216 records, significant associations were found for stroke, chronic kidney disease, lung disease, and neurologic conditions (p<0.05). Type 1 diabetes was marginally significant (0.05<p<0.1). After adjusting for age and sex, stroke (p=0.0008, BH-adjusted p=0.0044) and chronic kidney disease (p=0.0003, BH-adjusted p=0.0033) significantly increased the risk of severe COVID-19 outcomes. (4) Conclusions: Pre-existing medical conditions should be considered in the clinical management and public health interventions for PLWH with COVID-19. Tailored strategies are essential to mitigate the higher risk of severe outcomes in PLWH with specific chronic comorbidities.

This paper explores the application of machine learning (ML) in predicting functional recovery in patients with ischemic stroke. As technology advances, ML shows significant potential in the field of stroke medicine, especially in the areas of big data analytics and personalized medicine. Studies have shown that ML algorithms can improve the accuracy of stroke image analysis, subtype classification, risk assessment, treatment guidance, and prognosis prediction. However, the widespread use of ML still faces challenges such as data standardization, model validation, privacy, and bias. This paper reviews the current application status of ML in the field of stroke, discusses the challenges faced, and looks forward to the future development direction, aiming to promote the practical application of ML technology in the diagnosis and treatment of stroke to improve the prognosis and quality of life of patients.

The therapeutic, attenuative, and morphological effects of proprietary neural stem cell-derived extracellular vesicles (NSC EVs, AB126) produced by Aruna Bio, Inc. were assessed in a range of in vitro and in vivo models of stroke. We emphasize that modulation of neuroinflammation is a key target and suggest further studies to advance our understanding of the mechanisms of action and ultimately how best to dose and monitor the benefits of AB126 in stroke patients.

Despite the fact that SMA restrainers exhibit a superelastic strain capacity of 7%, this capacity appears inadequate for isolated bridges due to the typically greater than 20cm relative dis-placements between girders during intense seismic events. In order to perform such a stroke, a SMA restrainer of greater than 3 metres in length might be required. In order to reduce the length of restrainers, a novel honeycomb damper constructed from superelastic shape memory alloy (SMA) is proposed. The proposed device, denoted as the superelastic SMA honeycomb damper (SHD), is comprised of steel plates to prevent the SMA plane from collapsing and superelastic SMA honeycomb to provide self-centering capability. By incorporating the large strain capacity of SMA and the geometrically nonlinear deformation of honeycomb structures, SHD has been developed to satisfy the requirements of bridge restrainers with large strokes. It is capable of functioning as a restrainer and energy dissipation device when subjected to dynamic tension and compression loads. The SHD was initially investigated from a theoretical perspective. Following this, a mul-ti-cell SHD specimen was manufactured. The specimen underwent axial tensile and compressive experiments in order to examine the mechanical properties of SHDs. Finally, experimental results were investigated through numerical simulation analyses of the SHDs using a three-dimensional high-fidelity finite element model. Additionally, a method for enhancing SHD was proposed. The findings indicate that SHD is capable of exhibiting superior self-centering capability and sta-ble hysteretic responses when subjected to earthquakes.

Background: Citicoline, a medical food, lacks proven efficacy for ischemic stroke and has uncertainties around its harms. The continued prescription should be reevaluated given the more robust, high-quality Evidence against that medical food. This essay is based on a recent Cochrane review and uses only one all-cause mortality as the primary outcome. Therefore, the essay should be considered as something other than an updated Cochrane review but like a reflection based on Evidence-based Medicine and Philosophy of Science analysis. Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.? Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties. Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials. Data collection and analysis: We identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. We estimated risk ratios (RRs) for that outcome. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed effect model. We did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. We used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. We used a Trial Sequential Analysis with Copenhagen Trial Unit Software. We estimated a Bayes factor from the relative risk and 95% confidence interval. Results: We identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. We conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I2 = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline. Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Traditional end-effector robots for arm rehabilitation are usually attached a­t the hand, primarily focusing on coordinated multi-joint training. Therapy at an individual joint level of the arm for severely impaired stroke survivors is not always possible with existing end-effector robots. The Arm Rehabilitation Robot (AREBO)—an end-effector robot—was designed to provide both single and multi-joint assisted training while retaining the advantages of traditional end-effector robots, such as ease of use and cost-effectiveness (compared to exoskeletons). This work presents the design, optimization, and characterization of AREBO for training single-joint movements of the arm. The AREBO has three actuated and three unactuated degrees of freedom, allowing it to apply forces in any arbitrary direction at its endpoint and self-align to arbitrary orientations within its workspace. The AREBO’s link lengths were optimized to maximize its workspace and manipulability. The AREBO provides single-joint training in both unassisted and adaptive weight support modes using a human arm model to estimate the human arm's kinematics and dynamics without using additional sensors. The characterization of the robot’s controller and the algorithm for estimating the human arm parameters were performed using a two degrees of freedom mechatronic model of the human shoulder joint. The results demonstrate that: (a) the movements of the human arm can be estimated using a model of the human arm and robot’s kinematics, (b) the AREBO has similar transparency to that of existing arm therapy robots in the literature, and (c) the adaptive weight support mode control can adapt to different levels of impairment in the arm. This work demonstrates how an appropriately designed end-effector robot can be used for single-joint training, which can be easily extended to multi-joint training. Future work will focus on the evaluation of the system on patients with any neurological condition requiring arm training.

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

Controlling Nutritional Status (CONUT) Score is useful for the nutritional screening. We aimed to explore whether the CONUT score may predict a 3-month functional outcome in hemorrhagic stroke (AHS). Totally, 349 patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. Poor functional outcomes were defined as the modified Rankin Scale (mRS) score of ≥ 3 at 3 months. A total of 328 patients (mean age, 60.4 ± 12.83 years; 66.8% male) were included, 172 (52.40%) patients at malnutrition risk and 104 (31.7%) patients with a poor prognosis. High-CONUT patients had lower total lymphocyte counts and total cholesterol levels than low-CONUT patients (p &lt; 0.001 and p = 0.012). At 3-month post discharge, patients with malnutrition risk had higher hospitalization costs (p = 0.021), lower Barthel Index (p = 0.001), and more infectious complications (p = 0.002) than those without, and there was a greater risk for poor functional outcomes in the high-CONUT compared with the low-CONUT patients at admission (adjusted odds ratio: 2.32, 95% confidence interval: 1.28-4.17). High-CONUT scores predict a 3-month poor prognosis in AHS, which may help identify the AHS patients who need additional nutritional managements.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

General characteristics of K changes together with their fine structure associated with ground flashes in Sri Lanka in the tropics are presented. It is found that on average there are about 2 K changes associated with each return stroke. Analysis of the fine structure of the K changes shows that the K change is a chaotic pulse burst. Some of these chaotic pulse bursts start and the others end as a regular pulse bursts. Sometimes the chaotic part occurs in between two regular pulse bursts. This is in agreement with the recent published results that claim that chaotic pulse bursts are a random superposition of regular pulse bursts. The results show that the small step fields identified in the literature as K changes are the static fields associated with these pulse bursts.

Background/Objectives: Stroke patients generally have balance and gait dysfunction due to decreased range of motion (ROM) and muscle strength of the ankle joint. A therapist can apply a floss band to enhance ROM, pain control, jumping performance, strength, myofascial release, and recovery from fatigue. This study compared the immediate effects of floss band application on ankle ROM, balance, and gait ability in stroke patients.; Methods: This study randomized 40 chronic stroke patients to either the floss (n = 20) or sham (n = 20) band group. Outcome measures were ankle ROM, weight bearing lunge test (WBLT) performance, standing balance, and gait ability. Outcome measures were assessed at baseline and immediately after applying the floss or placebo band.; Results: There were significant improvements in dorsiflexion (DF), WBLT, static balance, and foot strike in those who used the floss band compared to the sham group (all p &lt; 0.05).; Conclusions: The floss band improved ankle DF, balance, and gait, indicating that it is a feasible therapeutic method for improving ankle DF, balance, and gait in chronic stroke patients.

Atherosclerosis is associated with vascular diseases, diabetes, and cancers. The Jumonji C-domain-containing 6 (JMJD6) gene plays an important role in diverse biological processes. In addition, autoantibodies are reportedly useful in the early diagnosis and treatment of many diseases. Here, JMJD6 was identified by serological identification of antigens by recombinant cDNA expression cloning as an antigen recognized by serum IgG from patients with unstable angina pectoris. Then, we performed amplified luminescent proximity homogeneous assay-linked immunosorbent assay using purified recombinant antigens and found elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with atherosclerosis-related diseases including ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers including esophageal cancer (EC), gastric cancer, lung cancer, and mammary cancer, compared with those in healthy donors. The s-JMJD6-Ab levels were closely associated with hypertension, habitual smoking, and the intima-media thickness, an atherosclerosis index. The better postoperative survival status was shown in patients with EC from the JMJD6-Ab-positive group than the negative group, especially from JMJD6-Ab-positive/PD-L1-negative group and JMJD6-Ab-positive/p53-Ab-negative group than JMJD6-Ab-negative/PD-L1-positive group and JMJD6-Ab-negative/p53-Ab-positive group, respectively. Hence, JMJD6 autoantibodies may reflect atherosclerosis severity, thereby a potential biomarker for atherosclerosis-related diseases including ischemic stroke, AMI, DM, and cancers and for predicting EC prognosis.

We study the work fluctuations in ergotropic heat engines, namely two-strokes quantum Otto engines where the work stroke is designed to extract the ergotropy (the maximum amount of work by a cyclic unitary evolution) from a couple of quantum systems at canonical equilibrium at two different temperatures, whereas the heat stroke thermalizes back the systems to their respective reservoirs. We provide an exaustive study for the case of two qutrits whose energy levels are equally spaced at two different frequencies by deriving the complete work statistics. By varying the values of temperatures and frequencies, only three kinds of optimal unitary strokes are found: the swap operator U1, an idle swap U2 (where one of the qutrits is regarded as an effective qubit), and a non trivial permutation of energy eigenstates U3, which indeed corresponds to the composition of the two previous unitaries, namely U3 = U2U1. While U1 and U2 are Hermitian (and hence involutions), U3 is not. This point has an impact on the thermodynamic uncertainty relations (TURs) which bound the signal-to-noise ratio of the extracted work in terms of the entropy production. In fact, we show that all TURs derived from a strong detailed fluctuation theorem are violated by the transformation U3.

Cardiovascular and cerebrovascular disease incidence has risen mainly due to poor control of preventable risk factors and still constitutes a significant financial and health burden worldwide. ChatGPT is an artificial intelligence language-based model developed by OpenAI. Due to the model’s unique cognitive capabilities beyond data processing and the production of high-quality text, there has been a surge of research interest concerning its role in the scientific community and contemporary clinical practice. To fully exploit ChatGPT's potential benefits and reduce its possi-ble misuse, extreme caution must be taken to ensure its implications ethically and equitably. In this article, we explore the language model's possible applications and limitations while empha-sizing its potential value for diagnosing, managing, and prognosis cardiovascular and cerebro-vascular disease.

Binarization of degraded documents is an important preprocessing task for various document analysis such as OCR and historical document analysis. Existing studies have applied various convolutional neural network (CNN) models and generative models for document binarization, but they do not show generalized performance for noise that the model has not seen and it suffers from extracting elaborate text strokes. In this paper, to overcome these challenges, we utilize latent diffusion model (LDM), which is known for high-quality image generation model, for the first time in document binarization. By utilizing the iterative diffusion-denoising process in latent space, it shows high-quality cleaned binarized image generation and high generalized performance through using both data distribution and time step while training. Additionally, we apply gated U-Net to the backbone network to preserve text strokes using trainable gating value. Gated convolution can extract elaborate text stroke by allowing the model to focus on text region by combining gating value and feature. Furthermore, we maximize the effectiveness of the proposed model by training it with a combination of LDM loss and pixel-level loss, which is suitable for the model structure. Experiments on H-DIBCO and DIBCO benchmark datasets show that the proposed model outperforms existing methods.

Upper limb paresis is very common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients’ movements in ecological scenarios. These systems are, however, very expensive and, as such, not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. 14 stroke patients executed ecologically relevant upper limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest’s and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1. Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper limb kinematic parameters in stroke patients.

An early hypothesis in robot-assisted stroke therapy was that sensorimotor stimulation through robotic assistance is beneficial for recovery. Despite 25 years of upper-limb rehabilitation robotics research, this hypothesis remains untested barring a few studies with small sample sizes. This review aims to provide a critical summary of the current state of this hypothesis by collating evidence from rehabilitation robotics and other related therapeutic approaches. The review starts with a causal model to expose the various direct and indirect routes through which robotic assistance can aid sensorimotor recovery. The indirect routes include the influence of robotic assistance on therapy intensity, patient motivation, and active participation. The direct route is through changes in cortical networks through Hebbian(-like) learning and changes in peripheral tissue properties. There is currently mixed evidence for the direct causal effect of robotic assistance on recovery from the upper-limb rehabilitation robotics literature. However, evidence from the neuromuscular electrical stimulation literature provides some support for this causal role. Based on the data at hand, we hypothesize that the enhanced movement-related sensory feedback from robotic assistance has a direct, possibly small, causal role in the sensorimotor recovery of the upper-limb, and this effect might be detectable with high-intensity therapy. Large, high-intensity, controlled studies are warranted to support or refute the role of robotic assistance on recovery, which is both scientifically and practically important.

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

Acute ischemic strokes are the third leading cause of death and the leading cause of neurological disability worldwide. The oxygen and glucose deprivation associated with ischemic strokes not only leads to neuronal cell death, but also increases the inflammatory response and decreases functional output of the brain. The only intervention approved by US Federal Drug and Food Administration for treatment of ischemic strokes is tissue plasminogen activator (tPA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its application, and it also might induce detrimental rather than beneficial effects to stroke patients by treatment of the tPA. In order to reduce the infarct volume of an acute ischemic stroke while increasing the time period for treatment, emerging therapies reveal great potential by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors with monoclonal antibody (MAB). With successfully application in the treatment of cancer patient by MAB, in this review, we will focus on recent advances on stroke therapy by using MAB on the treatment of stroke by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors. Therefore, developing specific MAB targeting the signaling pathway of stroke will contribute to stroke therapy.

Subjectivity has been an inherent issue in the conventional Fugl-Meyer assessment, which has been the focus of recognition research in several studies. This paper continues our previous work on a recognition method of finger movement impairment levels using EMG. In contrast to our previous work, this paper provided a better recognition result with an improved experimental setting, such as higher sampling frequency and number of EMG channels. A large number of patients was recruited to provide a reliable recognition performance. This paper employed two data processing mechanisms, inter-subject cross-validation (ISCV) and data-scaled inter-subject cross-validation (DS-ISCV), resulting in two evaluation methods. The employed machine-learning algorithms are SVM, random forest (RF), and multi-layer perceptron (MLP). The highest average recall score across impairment levels of 0.73 was achieved by MLP_ISCV in the spherical grasp task. Subsequently, the highest average recall score of non-majority classes of 0.72 was achieved by the SVM_DS-ISCV in the mass extension task. The cross-validation result showed that the proposed method effectively handled the imbalanced dataset without being biased toward the majority class. The proposed method demonstrated the potential to assist doctors in clarifying the finger movement impairment level.

Cardiovascular disease (CVD) is a major global health concern. The number of people with CVD is expected to rise due to aging populations and increasing risk factors such as obesity and diabetes. Identifying new molecular markers is crucial for early diagnosis and treatment. Among these, plasma levels of some miRNAs specifically expressed in cardiac and skeletal muscle known as myomiRs, has gained attention for their roles in cardiovascular health. This study analyzed the plasma levels of myomiR-133a, -133b, and -206 in the pathogenesis of cardiovascular diseases. Exploiting of a case-control study design with patients recruited from several nursing homes form Calabria (Southern Italy) characterized by different types of CVD compared to non-CVD controls, we found downregulation of miR-133a in heart failure and miR-133b in stroke, along with the overall decreased expression of miR-133b and miR-206 in CVD patients. In silico functional characterization of their targets and signaling pathways revealed their involvement in critical cardiovascular processes. Although further research is necessary to fully elucidate their mechanisms and clinical utility, the results here reported support the idea that myomiRs could serve not only as biomarkers but also as therapeutic targets, offering new avenues for managing and potentially preventing CVD progression.

The Atlantic Canada Together Enhancing Acute Stroke Treatment (ACTEAST) project is a Modified Quality Improvement Collaborative (mQIC) designed to improve ischemic stroke treatment rates and time-based efficiency in Atlantic Canada. This study specifically evaluates the implementation of the mQIC in Nova Scotia using qualitative methods. The mQIC spanned six months and included two Learning Sessions, multiple webinars, and a per-site virtual visit. Each session was followed by an action planning period to guide implementation efforts over the following 2-4 months. The Consolidated Framework for Implementation Research (CFIR) was utilized to develop a pre-tested, semi-structured interview guide, which aimed to uncover barriers and facilitators to mQIC implementation. Interviews were conducted with 14 healthcare professionals, generating 454 references that were coded into 28 CFIR constructs. Notably, 84% of these references were positively framed as facilitators. Despite this, significant barriers were identified, including resource availability, competing priorities, communication challenges, and difficulties engaging key stakeholders. Some barriers were particularly prominent during specific phases of implementation. The study findings offer valuable insights into the implementation of quality improvement initiatives in stroke care. They underscore the importance of recognizing and addressing context-specific barriers, while also leveraging identified facilitators to drive successful implementation and ultimately improve patient outcomes.

Delve into the dynamic realms of neuroscience, neurology, and psychiatry with this groundbreaking editorial, unveiling the intricate mechanisms of brain function and dysfunction. Explore the latest advancements in molecular biology, genetics, epigenetics, pharmacology, and neuroimaging that are revolutionizing our understanding of neurological and psychiatric disorders. Uncover the challenges and gaps in translating cutting-edge research into practical clinical applications, aiming to enhance the lives of patients and their families. Discover the pivotal role of neuroplasticity in reshaping the brain's adaptability throughout life, alongside the promising potential of non-invasive brain stimulation techniques like transcranial magnetic stimulation and transcranial direct current stimulation. Embark on a journey of innovation and collaboration as researchers and clinicians strive to bridge the gap between bench and bedside, offering hope for improved diagnosis, prevention, and treatment of complex neurological and psychiatric conditions. Join us in this exploration of transformative ideas and novel interventions that hold the key to a brighter future for individuals and society.

Stroke is a major leading cause of chronic disability, often affecting patients’ motor and sensory functions. Functional magnetic resonance imaging (fMRI) is the most commonly used method of functional neuroimaging and allows the non-invasive study of brain activity. The time-dependent coactivation of different brain regions at rest is described as resting-state activation. As a non-invasive task-independent functional neuroimaging approach, resting-state fMRI (rs-fMRI) may provide therapeutically useful information on both the focal vascular lesion and the connectivity-based reorganization and subsequent functional recovery in stroke patients. Considering the role of prompt and accurate prognosis in stroke survivors along with the potential of rs-fMRI in identifying patterns of neuroplasticity in different post-stroke phases, this review provides a comprehensive overview of the latest literature regarding the role of rs-fMRI in stroke prognosis in terms of motor and sensory outcome. Our comprehensive review suggests that with the advancement of MRI acquisition and data analysis methods, rs-fMRI emerges as a promising tool to study the motor and sensory outcome in stroke patients and evaluate the effect of different interventions.

Background and Objectives: Cardiovascular events are the leading cause of morbidity and mortal-ity in hemodialysis (HD) patients. Identifying risk factors can help in the effort to reduce cardi-ovascular risk and improve life expectancy. The purpose of this study was to evaluate the ability of CHA2DS2-VASc score [risk index of stroke in atrial fibrillation (AF)] in patients with end stage kidney disease, to predict stroke, major cardiovascular events and mortality. Materials and Meth-ods: CHA2DS2-VASc and HAS-BLED (bleeding risk from use of anticoagulation in AF) scores were calculated in 237 HD patients, [99 women, median age 76 (15) years], at time they com-menced on HD. The scores’ ability to predict long term cardiovascular morbidity and mortality was estimated, both in those with and without AF. Results: CHA2DS2-VASc score was signifi-cantly increased in AF (n=69) compared to non-AF (n=168) patients, 5 (2.5) versus 4 (2), p<0.0001, respectively. Increased CHA2DS2-VASc score was associated with heart failure (p=0.007, p=0.024), stroke (p<0.0001, p<0.0001) and risk of all-cause mortality (p<0.0001, p<0.0001), in both groups, respectively. C statistics indicated that CHA2DS2-VASc score performed modest discrimination in this HD population with and without AF for heart failure, stroke, and all-cause mortality, but for cardiovascular mortality in AF group only. Conclusions: Increased CHA2DS2-VASc score at time starting on HD, can predict stroke, heart failure and all-cause mortality in HD patients in-dependent of the presence of AF. Risk of cardiovascular mortality could be predicted only on patients with AF.

With growing regulations on ship emissions, specifically carbon dioxide and nitrogen oxides, this study emphasizes the critical need for improving the performance of existing ship diesel engines. Focusing on easily modifiable injection conditions within the fuel system, the research aims to enhance combustion characteristics for operational ships. The study provides a concise analysis of the combustion performance improvements achievable in the field. The study employed a range of calculation conditions, spanning from fuel injection pressures of 20 MPa to 160 MPa, injection timing from 15 degrees before top dead center (BTDC) to 5 degrees after top dead center (ATDC), and spray angles varying between 10 degrees and 50 degrees. A comprehensive analysis was conducted, focusing on fuel distribution behavior, combustion dynamics, carbon monoxide (CO) production and extinction, as well as nitrogen oxide (NO) production. This thorough examination aimed to provide insights into the complex interplay of these factors in order to optimize combustion performance in ship diesel engines. The analysis indicated that substantial unburned fuel occurred at injection pressures below 40 MPa and spray angles less than 20 degrees. This issue was significantly mitigated when injection pressures exceeded 80 MPa or a spray angle of 40 degrees was employed. High flame propagation speeds were observed at injection pressures over 80 MPa and injection timings before BTDC 10. Carbon monoxide emissions were notably low when injection pressures exceeded 80 MPa and a 40-degree spray angle was used. Nitrogen oxide emissions were minimized under conditions of injection pressure below 40 MPa, injection timing after BTDC 5 degrees, and a spray angle between 30 and 40 degrees. The study concludes that the most effective injection conditions for concurrently reducing fuel consumption, minimizing incomplete combustion products, and lowering nitrogen oxide emissions in the target engine are optimal when the injection pressure is set at 80 MPa, the injection timing is positioned at 5 degrees before top dead center (BTDC), and the spray angle is maintained at 40 degrees.

Background: The oldest old people (≥ 85 years) represent the fastest growing age group in Western populations. Knowledge on early outcomes of acute ischemic stroke (AIS) in very old female patients remains limited. Methods: We assessed gender differences and female-specific clinical data and in-hospital mortality in very old patients with AIS. Acute cerebral infarction was diagnosed in 506 very old female patients from a total of 4,600 acute cerebrovascular infarctions available in an ongoing 24-year hospital stroke data bank. A comparative analysis of vital status at discharge (alive versus dead) was performed in terms of cardiovascular risk factors, clinical data, and early outcomes. Results: The overall in-hospital mortality rate was 20.4%. In multivariate analysis, sudden onset, altered level of consciousness, and neurological, respiratory, cardiological or hemorrhagic complications, and lacunar infarcts appeared to be independent predictors of in-hospital mortality. Conclusions: Female patients ≥85 years with AIS are an unfavorable subgroup of stroke patients with a high risk of early mortality, which may be due to comorbidity, stroke subtype distribution, and higher frequency of medical complications. However, the presence of lacunar infarcts showed a significant protective effect.

Lesion studies are crucial in establishing brain-behavior relationships, and accurately segmenting the lesion represents the first step in achieving this. Manual lesion segmentation is the gold standard for chronic strokes. However, it is labor-intensive, subject to bias, and limits sample size. Therefore, our objective is to develop an automatic segmentation algorithm for chronic stroke lesions on T1-weighted MR images. Methods: To train our model, we utilized an open-source dataset: ATLAS v2.0 (Anatomical Tracings of Lesions After Stroke). We partitioned the dataset of 655 T1 images with manual segmentation labels into five subsets and performed a 5-fold cross-validation to avoid overfitting of the model. We used a deep neural network (DNN) architecture for model training. Results: To evaluate the model performance, we used three metrics that pertain to diverse aspects of volumetric segmentation including shape, location, and size. The Dice similarity coefficient (DSC) compares the spatial overlap between manual and machine segmentation. The average DSC was 0.65 (0.61- 0.67; 95% bootstrapped CI). Average symmetric surface distance (ASSD) measures contour distances between the two segmentations. ASSD between manual and automatic segmentation was 12mm. Finally, we compared the total lesion volumes and the Pearson correlation coefficient (ρ) between the manual and automatically segmented lesion volumes, which was 0.97(p-value &lt; 0.001). Conclusions: We present the first automated segmentation model trained on a large multicentric dataset. This model will enable automated on-demand processing of MRI scans and quantitative chronic stroke lesion assessment.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Objective: to evaluate the effects of excitatory repetitive transcranial magnetic stimulation (rTMS) of the international 10-20 system P3 point (intraparietal sulcus region) in chronic patients with a frontal lesion and parietal sparing due to stroke on the impaired upper (UL) and lower limb (LL) as measured by Fugl-Meyer Assessment (FMA). Methods: three patients (C1: 49.83/2.75, C2: 53.17/3.83, C3: 63.33/3.08 years-old at stroke/ years post-stroke, respectively) received two weeks (five days/ week) of rTMS at 10 Hz of P3. A patient was treated in similar conditions with a sham coil (S1: 56.58/4.33). No complimentary therapy was delivered during the study. Patients were evaluated before, after- and two months post-treatment (A1, A2 and A3, respectively). Results: we found increased scores for LL in motor function subsection for C1 and C3 and in sensory function for C2 by A2 that remained at A3. We also found an increased score for UL motor function for C2 and C3, but the score decreased by A3 for C2. C3 score for UL range of motion increased by A3 compared to A1 and A2. Conclusion: In a variable way, P3 excitatory rTMS increased FMA scores in different upper and lower limb subsections of our three treated patients.

This paper explores the application of machine learning (ML) in predicting functional recovery in patients with ischemic stroke. As technology advances, ML shows significant potential in the field of stroke medicine, especially in the areas of big data analytics and personalized medicine. Studies have shown that ML algorithms can improve the accuracy of stroke image analysis, subtype classification, risk assessment, treatment guidance, and prognosis prediction. However, the widespread use of ML still faces challenges such as data standardization, model validation, privacy, and bias. This paper reviews the current application status of ML in the field of stroke, discusses the challenges faced, and looks forward to the future development direction, aiming to promote the practical application of ML technology in the diagnosis and treatment of stroke to improve the prognosis and quality of life of patients.

Stroke causes disability and significantly affects patient quality of life. Post-stroke rehabilitation of upper limb function is crucial, as it affects daily activities and individual autonomy. Traditional rehabilitation methods often require frequent visits to specialized centers, which can be costly and challenging. This study investigated the effectiveness of a home-based self-training device, "Kenko Yusuri," in improving upper limb function in patients with chronic stroke. This multicenter prospective intervention study used a quasi-randomized controlled trial design. Ninety-three outpatients from five hospitals in Japan were enrolled and assigned to either the intervention group who used the "Kenko Yusuri" device or the control group who underwent conventional rehabilitation. All patients received botulinum toxin type A (BoNT-A) injections to treat upper limb spasticity. The primary outcome measure was the Fugl-Meyer Assessment (FMA) of upper-extremity motor function. Secondary outcomes included the modified Ashworth scale (MAS) score, range of motion (ROM), and chronic pain assessments. The intervention group demonstrated significantly greater improvements in FMA total scores than the control group. Patients with moderate paralysis experienced the greatest benefits from the intervention. There were no significant between-group differences in MAS scores or ROM measurements. Pain and wrist ROM showed improvement in the intervention group. Home-based training with a shaking device significantly improved upper limb function in patients with moderate chronic post-stroke paralysis. This approach aligns with the principles of use-dependent plasticity and offers a feasible and cost-effective alternative to traditional rehabilitation methods.

Stroke is a global leading cause of death and disability. Knowledge of related guidelines is crucial for Emergency Department (ED) staff, influencing early diagnosis and timely treatment. We investigated Greek-Cypriot ED healthcare professionals' (nurses and physicians) knowledge in recognizing and managing stroke. A descriptive cross-sectional study spanned November 2019 to April 2020, encompassing four private and seven public EDs in the Republic of Cyprus. The data were collected through a self-reported questionnaire developed by the research team, consisting of 37 questions. Eight questions focused on sociodemographic and employment characteristics, 28 assessed knowledge in stroke recognition and management (each item was equally weighted without deliberate prioritization), and one question addressed self-assessment of knowledge in stroke care. 255 nurses [Response Rate (RR): 74.1%] and 26 physicians (RR: 47.3%) completed the questionnaire. The average correct response rate was 12.9 out of 28 statements (SD: 4.2), with nurses and physicians scoring 12.6 (SD: 4.1) and 15.7 (SD: 4), respectively. Work experience significantly influenced stroke knowledge, with all groups demonstrating superiority over those with less than one year of experience. Participants with previous training scored an average of 1.45 additional correct answers while educational attainment did not significantly influence stroke knowledge. Investigating stroke knowledge among Emergency Department nurses and physicians in the Republic of Cyprus revealed significant deficits. The study stresses targeted interventions, including, education, yearly examinations, workshops with hands-on training, and repeated training, to address these gaps and enhance the overall stroke care capabilities of the healthcare professionals.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Taking care of stroke survivors can be taxing, however, it was understudied in Malaysia. This study aims to describe the burden of informal stroke caregivers within three months after hospital discharge. A longitudinal study design was conducted. Acute stroke survivors and their informal caregivers were recruited prior to hospital discharge, and the caregivers were interviewed by phone. Self-reported caregiver burdens were measured with Zarit Caregiver Burden Interview – Malay version (MZBI) and Caregiver Assessment of Function and Upset – Malay version (Malay-CAFU). The MZBI and Malay-CAFU scores were collected four times within three months. A total of 85 stroke survivors and 155 informal caregivers were recruited, with 58.1% of the caregivers were female. The stroke survivors had two caregivers on average. The mean (SD) scores for the three scales show a reduction, from 27.42 (12.73) in the first week to 17.77 (11.20) in the third month for MZBI, from 1.14 (0.94) to 0.62 (0.64) for instrumental activities of daily livings (IADL) of Malay-CAFU upset scale and 1.36 (1.00) to 0.78 (0.65) for activities of daily living (ADL) of Malay-CAFU upset scale in the same period. Stroke survivors may have several caregivers, usually their spouses or children. Within a short period, the caregiver’s burden was reduced. Early psychosocial support to alleviate the caregiver burden may be necessary.

Early stroke diagnosis remains a big challenge in healthcare partly due to the lack of reliable diagnostic blood biomarkers, which in turn leads to increased rates of mortality and disability. Current screening methods are optimised to identify patients with a high risk of cardio-vascular disease, especially among the elderly. However, in young adults and children, these methods suffer low sensitivity and specificity and contribute to further delays in their triage and diagnosis. Accordingly, there is an urgent need to develop reliable blood biomarkers for triaging patients suspected of stroke in all age groups, especially children and young adults. This review explores some of the existing blood biomarkers, as single biomarkers, or biomarker panels, and examine their sensitivity and specificity for predicting stroke. A review was performed on PubMed and Web of Science for journal articles published in English during the period 2001 to 2021 which contained information regarding biomarkers of stroke. In this review article, we provide comparative information on the availability, clinical usefulness, and time-window periods of eight single blood biomarkers and six biomarker panels that have been used for predicting stroke in emergency situations. The outcomes of this review can be used in future research for developing more effective stroke biomarkers.

Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.

Ischemia stroke is one of a clinically common cerebrovascular disease. And Inhibition of brain tissue ischemia and reperfusion-induced damage, especially apoptosis, has an irreplaceable protective effect on ischemic nerves, and has special significance for the treatment of patients after treatment. However, the development of neuroprotective drugs still has certain challenges. Radix scrophulariae as a valuable medicine, has been discovered to has neuroprotective effects. Our researches initially proved that Radix scrophulariae aqueous extract (RSAE) exerting a neuroprotective effects on cerebral ischemia and reperfusion (I/R) injury in oxygen glucose deprivation and reperfusion (OGD/R)-induced PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) model mice, were associated with attenuation of infarct volume, brain water content, nitric oxide (NO) and malondialdehyde (MDA), inhibiting I/R-induced damage by reducing the levels of LDH release, improving anti-oxidant capacity by upregulating the SOD, GSH-Px and CAT activity, stabilizing mitochondrial membrane potential, reducing neuronal apoptosis, necrosis and neuronal loss by regulating the expression of anti-apoptotic BCL-2and pro-apoptotic protein Bax, and elucidating downregulate the phosphorylation levels of MAPK pathways. Our findings may elaborate the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Since, Radix scrophulariae, as a potential neuroprotective natural plant, has originally been identified to, our results may offer directions and clues for discovering new active compounds or drugs for treatment of ischemic stroke, which allows us to discover many new natural active chemicals by chemical separation and identification, and provide new insights into therapeutic targets in stroke patients.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. Methods: An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. Results and Discussion: The presented case concerns a 46 years old man admitted to the Stroke Unit because of acute is-chemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet defined and each case should be individually addressed in a pragmatic clinical road map.

Herein, we examined the effects of weather parameters and individual clinicodemographic risk factors on hemorrhagic stroke (HS) incidence, severity on admission, and disability at discharge in a harsh desert climate. In a retrospective design we studied patients admitted to a stroke unit in Arab Emirates in 2016-2019. With a distributed lag nonlinear model we explored immediate and delayed effects of weather on stroke incidence. Supervised machine learning was used to build models predictive of scores in NIHSS and mRS scales. We assessed model performance by calculating ROC AUC, F1 scores, specificity, and sensitivity. HS risk increased after a significant change in any weather parameter. The risk was reduced below baseline after 1-week adjustment to environmental changes. Climate input from the previous 3 days yielded reliable classification models. Humidex was a better predictor of severity than air temperature, whereas body mass index, age, and time of day at stroke onset were the strongest clinical predictors. Weather parameters before admission were stronger predictors of disease severity than individual clinical factors. We addressed limitations of previous studies by analyzing a full set of climate parameters: ambient temperature, relative humidity, humidex, atmospheric pressure, and wind speed. Predictive models may help to optimize patient management and develop preventative strategies.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

The home is becoming a key location for healthcare delivery, including the use of technology driven by autonomous systems (AS) to monitor and support healthcare plans. Using the example of a smart mirror, this paper describes the outcomes of focus groups with people with multiple sclerosis (MS; n=6) and people who have had a stroke (n=15) to understand their attitudes towards the use of AS for healthcare in the home. We thematic analysis to analyse the data. The results indicate that the use of such technology depends on the level of adaptability and responsiveness to the users’ specific circumstances, including their relationships with the healthcare system. A smart mirror would need to support manual entry, responsive goal setting, effective aggregation of data sources and integration with other technology, have a range of input methods, be supportive rather than prescriptive in messaging, and give the user full control of their data. Barriers to adoption include a perceived lack of portability and practicality, lack of accessibility and inclusivity, a sense of redundancy, being overwhelmed by multiple technological devices, and a lack of trust in data sharing. These results inform the development and deployment of future health technologies based on the lived experiences of people with health conditions who require ongoing care.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the apparent effect due to “regression dilution.” Here we evaluate how follow-up time affects the relationship between serum 25-hydroxyvitamin D [25(OH)D] concen-tration and incidence of stroke and major cardiovascular events (MCEs). Methods: Findings re-garding the relative risk (RR) of stroke and MCEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke, with nine studies for MCEs. Linear regression analyses were performed for follow-up periods of up to 10 years. Results: For stroke, the linear regression fit for 1–10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r2 = 0.67, p <0.001. No significant change was evident for studies with follow-up periods of 10–20 years. For MCEs, the linear fir for 1–8.1 years is RR = 1.61 ‒ (0.074 × follow-up [years]), r = 0.75, adjusted r2 = 0.49, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of vitamin D in reducing risk of stroke and MCEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as high as the estimate based on averaging the results for all studies without considering follow-up time. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MCEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MCE, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D’s role in reducing risk of stroke and MCE can be considered causal on the basis of an evaluation of the evidence with respect to Hill’s criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MCEs in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should be recommended for everyone likely to be at risk for stroke or MCE and indeed in the general population.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Background: In recent years, whole blood parameters and derivatives have been used as prognostic criteria in the course of the disease in various diseases. The prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR) have been adapted as an indicator of inflammation and have been widely studied to define the severity of inflammation in some diseases. The aim of this study was to evaluate the relationship between parameters such as NLR, SII, PNI, controlling nutritional status (CONUT) score, nutritional risk index (NRI) and with immunonutrition status and disease activity in patients with ischemic stroke of small vessel, large vessel and other etiologies. Methods: We retrospectively evaluated the records of 1454 consecutive ischemic stroke patients hospitalized in the emergency department of Gaziosmanpasa Education and Research Hospital from 2019 to 2023. Results: Of the 1350 SVO patients included in the study, 58.8% had small vessel, 29.3% had large vessel and 11.9% had other etiologies. There was a significant difference between the 3 etiology groups for PNI and CONUT. The median PNI was 47.03 (41.33-52.85) in the other etiology group, 35.29 (33.69-37.25) in the small vessel group, and 34.11 (30.23-36.87) in the large vessel group. The CONUT median was 5(5-6) in the small vessel group, 5(4-6) in the large vessel group and 4(4-4) in the other etiology group. In addition, CONUT and PNI were also found to be independent risk factors for death. A negative significant correlation was observed between PNI and NLR (r:-0.692), SII (r:-0.591), CONUT (r:-0.685). Significant correlations were observed between CONUT and NLR (r:0.402), SII (r:0.312). Conclusion: PNI and SII were significantly associated with disease activity. PNI, CONUT and NRI as a more accurate prognostic indicator of nutritional status in patients with ischemic stroke of small vessel, large vessel and other etiologies. NLR and SII may be important predictive markers in the course and prognosis of stroke.

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

A growing number of clinical data suggests that the use of antiplatelets and/or statins pre-stroke are associated with reduced severity and better functional outcomes for ischemic stroke. Studies have shown that the long-term use of ACEI/ARB pre-stroke is beneficial in reducing severity at onset and improving functional outcomes. We aimed to compare stroke severity and early functional outcome between patients taking ACEI/ARB and those who were not, and to identify any additional effects to taking ACEI/ARB with antiplatelets, statins, or both. In this retrospective case-control study, we assessed 218 patients who presented with ischemic stroke to the stroke unit in Padeh-Poriyah Hospital between 2019-2020. Of these patients, 119 took ACEI/ARB pre-stroke. A significantly higher percentage of ACEI/ARB-treated patients had a history of hypertension (HTN) and hyperlipidemia and were taking antiplatelets and/or statins, compared to the non-ACEI/ARB group. We observed that pre-stroke treatment with ACEI/ARB is associated with worsened stroke severity and reduced early functional outcomes. No significant benefit to taking ACEI/ARB with antiplatelets and/or statins pre-stroke was observed. Due to the nature of our study, the data should be interpreted as suggestive. Thus, prospective studies of these medications on ischemic stroke severity and early outcomes are warranted.

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

Technology-based approaches for upper limb (UL) motor rehabilitation after stroke are designed mostly for severely affected patients to increase their recovery chances. However, the available randomised controlled trials (RCTs) focused on efficacy of technology-based interventions often include patients with a wide range of motor impairment. This scoping review aims at overviewing the actual severity of stroke patients enrolled in RCTs which claim to specifically address UL severe motor impairment. The literature search was conducted on Scopus and PubMed databases and included articles from 2008 to May 2024, specifically RCTs investigating the impact of technology-based interventions on UL motor functional recovery after stroke. Forty-eight studies were selected. They showed that upon patients’ enrolment the values of the UL Fugl-Meyer Assessment and Action Research Arm Test covered the whole range of both scales, thus revealing the non-selective inclusion of severe impaired patients. Heterogeneity in terms of numerosity, characteristics of enrolled patients, trial design, implementation, and reporting were present across studies. No clear difference in the severity of the included patients according to the intervention type was found. Patient stratification upon enrolment is crucial to best direct resources to those patients who will benefit the most from a given technology-assisted approach (personalised rehabilitation).

Sickle cell disease (SCD) is a hereditary blood disorder characterized by abnormal hemoglobin, leading sickle shape of red blood cells. It has several vascular complications and the cerebrovascular ones are among the most frequent and severe both in children and in adults. This review summarizes the main neurovascular manifestations of SCD, including acute stroke, silent cerebral infarction, large vessel diseases (moyamoya arteriopathy and aneurysms) and brain bleeding. Both epidemiology, pathophysiology and treatment issues are addressed and prevention of cerebrovascular events, including silent cerebral infarctions, is particularly relevant in SCD patients, being associated to poor functional outcome and cognitive complaints. Transfusions and hydroxyurea are the main available therapy at the moment, but contraindications, availability and complications might prevent their long term use, particularly in low income countries. The role of Transcranial Doppler in monitoring the patients (mainly children) is analyzed and a practical approach has been selected in order to give the main messages from the actual knowledge for a better management of the SCD patients.

We present our experience with the implantation of flow diverter stents (FDSs) for the management of intern carotid artery (ICA) dissections in tortuous tonsillar loop segments. 16 patients (10 women, 62.5%; mean age 39±8 years; median baseline NIHSS 13; median ASPECTS 8.5) with acute ischemic stroke due to ICA dissection in a tortuous tonsillar loop segment, with/without large intracranial vessel thrombotic occlusion, from 6/2015−2/2022 were included in this retrospective study under a waiver of informed consent. An FDS device was deployed from the petrous ICA toward the upper cervical ICA, completely covering the tonsillar loop. Stentriever-assisted thrombectomy was performed when indicated. A dual antiplatelet regimen was used during and after the procedure. Thrombocyte inhibition levels were evaluated before, during, and after the intervention. The ICA occlusion/near occlusion was successfully recanalized in all 16 patients with postangioplasty residual stenosis of 34±14% (range 0−50%). Stent-assisted embolectomy was performed in 15/16 patients (93.7%), achieving revascularization (TICI 2b−3) in all. There were no procedural complications and no intraprocedural embolic events; one asymptomatic petechial hemorrhage was detected. At 3-month follow-up, mRS 0−2 was seen in all patients. This report provides pilot data for a subsequent study on the use of flow diverter stents for ischemic cerebrovascular conditions. Our encouraging preliminary results await confirmation from further experience and prospective randomized studies.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Mirror Therapy (MT) and Cognitive Therapeutic Exercise (CTE) are two neurorehabilitation techniques based on neuroplasticity and designed to enhance the functionality of the upper limb. Therefore, the aim is to assess the effectiveness of the combination of CTE and MT with task-oriented training (TOT) on fine and gross motor skills of the affected hand, as well as the functionality of the affected upper limb, autonomy, independence, and quality of life (QoL) in patients with acute stroke. This longitudinal and multicenter study involved a sample of 120 participants selected randomly and consecutively. Three groups were formed, including a control group (CG) and two treatment groups, one with MT and the other with CTE. The functionality of the upper limb, fine and gross motor skills, the quantity and quality of use of the affected upper limb, autonomy, and QoL were evaluated using various scales validated in the Spanish population at the baseline, after 20 treatment sessions, and at three months of follow-up. ANCOVA analysis was conducted, revealing statistically significant differences between assessments in the CG compared to the experimental groups (GEs), indicating a notable improvement in overall functionality, fine and gross motor skills, autonomy, and QoL in the latter. However, there were no significant differences between the GEs. Therefore, the application of either of these experimental combinations is crucial for the motor recovery, functionality, and improvement of the quality of life of individuals who have suffered a stroke.

CT scans are currently the most common imaging modality used for suspected stroke patients due to their short acquisition time and wide availability. However, MRI offers superior tissue contrast and image quality. In this study, eight deep learning models are developed, trained, and tested using a dataset of 181 CT/MR pairs from stroke patients. The resultant synthetic MRIs generated by these models are compared through a variety of qualitative and quantitative methods. The synthetic MRIs generated by a 3D UNet model consistently demonstrated superior performance across all methods of evaluation. Overall, the generation of synthetic MRIs from CT scans using the methods described in this paper produces realistic MRIs that can guide the registration of CT scans to MRI atlases. The synthetic MRIs enable the segmentation of white matter, gray matter, and cerebrospinal fluid using algorithms designed for MRIs, exhibiting a high degree of similarity to true MRIs.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

Medical brain image analysis is a necessary step in the Computers Assisted /Aided Diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of White Matter Hyperintensities (WMHs) of brain MRI images specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used the bibliometric networks. Out of a total of 140 documents we selected 38 articles that deal with the main objectives of this study. Based on the analysis and discussion of the revised documents, there is constant growth in the research and proposal of new models of deep learning to achieve the highest accuracy and reliability of the segmentation of ischemic and demyelinating lesions. Models with indicators (Dice Score, DSC: 0.99) were found, however with little practical application due to the uses of small datasets and lack of reproducibility. Therefore, the main conclusion is to establish multidisciplinary research groups to overcome the gap between CAD developments and their complete utilization in the clinical environment.

Objectives: Studies evaluating machine learning (ML) algorithms on cross-lingual RadLex® mappings for developing context-sensitive radiological reporting tools are lacking. Therefore, we investigated whether ML-based approaches can be utilized to assist radiologists in providing key imaging biomarkers – such as The Alberta stroke programme early CT score (APECTS). Material and Methods: A stratified random sample (age, gender, year) of CT reports (n=206) with suspected ischemic stroke was generated out of 3997 reports signed off between 2015-2019. Three independent, blinded readers assessed these reports and manually annotated clinico-radiologically relevant key features. The primary outcome was whether ASPECTS should have been provided (yes/no: 154/52). For all reports, both the findings and impressions underwent cross-lingual (German to English) RadLex®-mappings using natural language processing. Well-established ML-algorithms including classification trees, random forests, elastic net, support vector machines (SVMs) and boosted trees were evaluated in a 5 x 5-fold nested cross-validation framework. Further, a linear classifier (fastText) was directly fitted on the German reports. Ensemble learning was used to provide robust importance rankings of these ML-algorithms. Performance was evaluated using derivates of the confusion matrix and metrics of calibration including AUC, brier score and log loss as well as visually by calibration plots. Results: On this imbalanced classification task SVMs showed the highest accuracies both on human-extracted- (87%) and fully automated RadLex® features (findings: 82.5%; impressions: 85.4%). FastText without pre-trained language model showed the highest accuracy (89.3%) and AUC (92%) on the impressions. Ensemble learner revealed that boosted trees, fastText and SVMs are the most important ML-classifiers. Boosted trees fitted on the findings showed the best overall calibration curve. Conclusions: Contextual ML-based assistance suggesting ASPECTS while reporting neuroradiological emergencies is feasible, even if ML-models are restricted to be developed on limited and highly imbalanced data sets.