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.

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

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

In this review, we will cover a general overview of the current panorama on lncRNAs with an actual or potential role as biological markers in cancer. We will discuss examples of multi-omics approaches that integrates information on somatic aberrations, gene expression and epigenomics, with the scope of providing a more comprehensive view of the functional impact of lncRNA profiles and how these paradigm can be exploited for the discovery and selection of lncRNAs with a functional role and their use as variables informing on progression and prognostic and help guiding the selection of therapeutic strategies for cancers. Finally, we propose a perspective for future evolution of the study of lncRNAs and the discovery of their functional and harnessing their potential to assist in clinical management of malignancies.

The collective considerations presented here lead to a crucial question: What truly constitutes the primary public health challenge posed by SARSCoV-2 infection and its variants?The findings of Bowen et al.(1) and Noé et al.(4) have offered us new insights into the actual repercussions of SARSCoV-2 virus infections on public health. They unmistakably point to the late sequelae and complications arising as secondary effects of the viral infection, causing severe and long-term damage to global public health. Rather than the acute infection which has a very low mortality rate in the general population, as initially and commonly believed.

Background: There are ongoing workforce challenges with the delivery of long-term care (LTC), such as staffing decisions based on arbitrary standards. The Synergy tool, a resident-centered approach to staffing, pro-vides objective, real-time acuity and dependency scores (Synergy scores) for residents. The purpose of this study was to implement and evaluate the impact of the Synergy tool on LTC delivery. Methods: A longitudinal mixed methods study took place within two publicly-funded LTC homes in British Columbia, Canada. Quantitative data included weekly Synergy scores for residents (24 weeks), monthly aggregated resident falls data (18 months) and a six-month economic evaluation. Qualitative data were gathered from family caregivers and thematically analyzed. Results: Quantitative findings from Synergy scores revealed considerable variability for resident acuity/dependency needs within and across units; and falls decreased during implementation. The six-month economic evaluation demonstrated some cost savings by comparing Synergy tool training and implementation costs with savings from resident fall rates reductions. Qualitative analyses yielded three positive impacts themes (improved care delivery, better communication, and improved resident-family-staff relationships), and two negative structural themes (language barrier and staff shortages). Conclusions: The Synergy tool provides useful data for enhancing a ‘fit’ between resident needs and available staff.

Conclusive evidence that specic long-term memory formation relies on den- dritic growth and structural synaptic changes has proven elusive. Connec- tionist models of memory based on this hypothesis are confronted with the so-called plasticity stability dilemma or catastrophic interference. Other fun- damental limitations of these models are the feature binding problem, the speed of learning, the capacity of the memory, the localisation in time of an event and the problem of spatio-temporal pattern generation. This paper suggests that the generalisation and long-term memory mechanisms are not correlated. Only the development and the improvement of the feature ex- tractors in the cortex involves structural synaptic changes. We suggest the long-term memory has a separate mechanism which involves protein synthe- sis to encode the information into the structure of these proteins. A model of memory should be capable of explaining the dierence between memorisation and learning. Learning has in our approach two dierent mechanisms. The generalisation in the brain is handled by the proper development of the links between neurons via synapses. The Hebbian learning rule could be applied only for this part of learning. Storing an internal ring pattern involves, in our approach, a new mechanism which puts the information regarding this ring pattern into the structure of special proteins in such a way that it can be retrieved later. The hypotheses introduced in this article includes a physiological assumption which has not been yet verified because it is not currently experimentally accessible. Keywords: Waves, Protein Synthesis, Resonance, Long Term Memory Preprint submitted to Neural Networks

The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.

The rainfall study in the long term is essential for climatic change understanding and socioeconomic development. The main goal of this study is to explore the spatial and temporal variations of precipitation in different time scales (seasonal and annual) in Cameroon. The Mann–Kendall and Pettitt tests were applied to analyze the precipitation variability. On temporal plan, the different regions of Cameroon have recorded significant drops in annual rainfall that Pet-titt's test generally situates around the 1970s. The decreases observed for the northern part of Cameroon regions are between –5.4% (Adamawa) and –7.4% (Far North). Those of west-ern part regions oscillate between –7.5% (South-West) and –12.5% (West). The southern part of Cameroon regions recorded decreases varying between –4.3% (East) and –5.9% (Center). On spatial plan, the divisions of the northern, western and southern parts of Cameroon respectively recorded after the 1970s (a pivotal period in the evolution of precipitation on temporal plan), a precipitation decrease towards the South, the South-West and the West. This study's findings could be helpful for planning and managing water resources in Cameroon.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

This paper deals with the analysis of trends in road accidents on major highways in Brazil. Using updated time series techniques, our results indicate that a low degree of long memory was detected in the series with shocks having transitory effects over time. We further find that the number of accidents taking place in Brazil has been reducing over time, though in the presence of negative shocks, the recovery is not going to be immediate due to the long memory nature of the data. Despite the absence of relevant investment relating to infrastructure expansion, it is worth mentioning the consolidation of a nationwide tolled road system in Brazil involving concessions to private administrators, alongside more severe traffic laws that can impose limitations on driving licences.

Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.

The whole genome sequencing (WGS) has become a crucial tool to understand genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on read length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be be used as a good reference. However, plant species have complex and large genomes compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool to overcome the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 using the MinION platform and obtained 895,678 reads and 17.9 gigabytes(Gb) (ca. 25X coverage of reference) from long-read sequence data. Through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome, a total of 6,124 contigs (covering 45.9%) were generated from Canu, and a total of 2,661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon pipeline. Our results provide a pipeline of long-read sequencing analysis for plant species using the MinION platform and a clue to determine the total sequencing scale for optimal coverage based on various genome sizes.

Here, we have discovered a X-ray excited long afterglow phosphor β-NaYF₄: Tb³⁺. After the irradiation of X-ray, the green emission can persist for more than 240 h. After 36 h, the afterglow intensity arrived at 0.69 mcd•m^-2, which can clearly be observed by naked eyes. Even after 84 h, the afterglow emission brightness still reached 0.087 mcd•m^-2. Also, combined with the results of thermoluminescence and photoluminescence, the super long afterglow emission of β-NaYF₄: Tb³⁺ can be ascribed to the tunneling model associated with F centers. More importantly, the super long green afterglow emission of β-NaYF₄: Tb³⁺ has been successfully used as in vivo light source to activate g-C₃N₄ for photodynamic therapy（PDT）and bacteria destruction. Furthermore, super long persistent luminescence of β-NaYF₄: Tb³⁺ could be repeatedly charged by X-ray for many circulations, which indicates that the phosphors have high photo stability under repeated cycles of alternating X-ray irradiation.

In this study, 6 residents of a long-term care facility were asked to try on Virtual Reality glasses and report their first experiences with Virtual Reality. The results show that Virtual Reality is of great interest to elderly residents of in-patient long-term care facilities. The wearing period was longer than expected and no symptoms of cyber sickness occurred. For the residents it was exciting to explore the virtual environments. Austrian destinations, nature scenes in the mountains and forests but also trips to the zoo, the museum, in churches or even densely populated areas like shopping streets or train stations would be places for the residents, they would like to explore virtually. Far-off destinations such as Rio de Janeiro or the Caribbean are more of an exception. Biographically relevant places such as the parental home or the location of their wedding were not named. Concerning the usability, an adjustment of the VR glasses is necessary for a longer-term use in any case.

Muscarinic acetylcholine receptors are well-known for their crucial involvement in hippocampus-dependent learning and memory, but the exact roles of the various receptor subtypes (M1-M5) are still not fully understood. Here, we studied how M1 and M3 receptors affect plasticity at the mossy fiber (MF)-CA3 pyramidal cell synapse. In hippocampal slices from M1/M3 receptor double knockout (M1/M3-dKO) mice, the signature short-term plasticity of the MF-CA3 synapse was not significantly affected. However, the rather unique, NMDA receptor-independent and presynaptic form of long-term potentiation (LTP) of this synapse was much larger in M1/M3-deficient slices compared to wild type slices, in both field potential and whole-cell recordings. Consistent with its presynaptic origin, induction of MF-LTP strongly enhanced the excitatory drive onto single CA3 pyramidal cells, with the effect being more pronounced in M1/M3-dKO cells. In an earlier study [1], we found that deletion of M2 receptors in mice disinhibits MF-LTP in a similar fashion, suggesting that endogenous acetylcholine employs both M1/M3 and M2 receptors to constrain MF-LTP. Importantly, such synergism was not observed for MF long-term depression (LTD). Low-frequency stimulation, which reliably induced LTD of MF synapses in control slices, failed to do so in M1/M3-dKO slices and gave rise to LTP instead. In striking contrast, loss of M2 augmented LTD when compared to control slices. Taken together, our data demonstrate convergence of M1/M3 and M2 receptors on MF-LTP, but functional divergence on MF-LTD, the net effect being well-balanced bidirectional plasticity of the MF-CA3 pyramidal cell synapse.

Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long Term Potentiation (LTP) and Long Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses, the ability to easily undergo NMDA-mediated LTP and LTD, that is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results pinpoint to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of few, key, molecular interactions typical of structural biology ones.

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.

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.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question as to whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots are cytotoxic by inducing hypoxia/reperfusion and other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

Introduction: Congenital heart defects (CHD) are the most frequent group of major congenital anomalies, accounting for almost 1% of all births. They comprise a very heterogeneous group of birth defects in terms of their severity, clinical management, epidemiology and embryologic origins. Taking this heterogeneity into account is an important imperative to provide reliable prognostic information to patients and their caregivers, as well as to compare results between centers or to assess alternative diagnostic and treatment strategies. The Anatomic and Clinical Classification of CHD (ACC-CHD) aims to facilitate both the CHD coding process and data analysis in clinical and epidemiological studies. Objectives: 1) To describe the long-term childhood survival of newborns with CHD and 2) To develop and validate predictive models of infant mortality based on the ACC-CHD. Materials and Methods: This study is based on data from a population-based, prospective cohort study: Epidemiological Study of Children with Congenital Heart Defects (EPICARD). The final study population comprised 1881 newborns with CHD after excluding cases that were associated with chromosomal and other anomalies. Statistical analysis included non-parametric survival analysis and flexible parametric survival models. The predictive performance of models was assessed by Harrell’s C index and the Royston-Sauerbrei R2 with internal validation by bootstrap. Results: The overall 8-year survival rate for newborns with isolated CHD was 0.96 [0.93- 0.95]. There was a substantial difference between the survival rate of the categories of ACC-CHD. The highest and lowest 8-year survival rates were 0.995 [0.989-0.997] and 0.34 [0.21-0.50] for “interatrial communication abnormalities and ventricular septal defects” and "functionally univentricular heart", respectively. Model discrimination as measured by Harrell’s C was 87% and 89% for the model with ACC-CHD alone and the full model, which included other known predictors of infant mortality, respectively. The predictive performance as measured by R2 was 45% and 50%, for the ACC-CHD alone and the full model. These measures were essentially the same after internal validation by bootstrap. Conclusion: The ACC-CHD classification provided the basis of a highly discriminant survival model with good predictive ability for the 8-year survival of newborns with CHD. Prediction of individual outcomes remains an important clinical and statistical challenge.

Permeable asphalt pavement refers to an asphalt mixture layer with an air void content of more than 18% and internal water permeability and drainage capabilities, which can quickly drain away water on the road surface, improve rainy day travel safety and ride comfort. This paper aims to explore the optimal asphalt mixture mix design for long longitudinal slope roads. By using CT scanning technology to analyze the air void content of different rotated and compacted asphalt mixture specimens, and extensively testing and evaluating the performance of permeable pavement mixtures, the following conclusions are drawn: Based on the research philosophy of functional integration, a new asphalt mixture gradation suitable for long longitudinal slope roads is proposed, with the optimal key factor composition being: 0.075mm passing rate of 7%, 2.36mm passing rate of 20%, 9.5mm passing rate of 55%, and oil-stone ratio of 4.8%. The FAM mixture was divided into three parts for air void analysis, with the upper part having a slightly higher air void content than the lower part. The air void distribution diagram of the FAM mixture is concave, with higher air void rate curves on both sides and a lower middle curve. Compared with laboratory dry measurement method, CT scanning test showed slightly higher air void content in specimens. Through dynamic modulus testing, the strength requirement for road asphalt mixture in pavement structure design was evaluated. It was found that at high temperature conditions (50℃), the minimum dynamic modulus value of the FAM mixture was 323 MPa, with a peak value of 22746MPa at a temperature of -10℃ and a frequency of 25HZ. The dynamic modulus value at high temperature conditions is lower than at low temperature conditions, while the dynamic modulus value at high frequency conditions is higher than at low frequency conditions. This study provides useful information and experimental data for the design of new asphalt mixtures for long longitudinal slope roads, and has conducted in-depth research on the air void distribution and performance of the mixture, providing strong support for related research fields and practical applications.

Landsat and Sentinel-2 data archives provide ever-increasing amounts of satellite data for studying land cover and land use change (LCLUC) over the past four decades. However, the availability of cloud-, shadow-, and snow-free observations varies spatially and temporally due to climate and satellite data acquisition schemes. Spatio-temporal heterogeneity poses a major issue for some time-series analysis approaches, but can be addressed with pixel-based compositing that generates temporally equidistant cloud-free or near-cloud free synthetic images. Although much consideration is given to methods identifying the ‘best’ pixel value for each composite, determining the aggregation period receives less attention and is often done arbitrary, or based on expert intuition. Here, we evaluated data compositing windows ranging from five days to one year for 1984-2021 Landsat and 2015-2021 Sentinel‑2 time series across Europe. We considered separate and joint use of both data archives and analyzed spatio-temporal availability of composites during each calendar year and pixel-specific growing season. We reported mean annual composites’ availability investigating differences among biogeographical regions, checked feasibility of pan‑European analyses for three LCLUC applications based on annual, monthly and 10-day composites, and analyzed the shortest feasible compositing window ensuring ≥50% temporal data availability and interpolation of the remaining composites for individual years and across a variety of medium- and long‑term time windows. Our results highlighted low data coverage in the 1980s, 1990s, and in 2012, as well as spatial variability in data availability driven by climate and orbit overlaps, which altogether impact spatio-temporal consistency of medium- and long-term time series, limiting feasibility of some LCLUC analyses. We demonstrated that prior to 2011 monthly composites ensured overall 50-62% data coverage for each calendar year, and ~75% afterwards, with further increase to ~82% when Landsat and Sentinel-2 were combined. Temporal consistency of monthly composites was overall low and temporal interpolation augmenting up to 50% missing data each year and across a time window of interest, ensured feasibility of analyses. Applications based on shorter than monthly composites were challenging without joining Landsat and Sentinel‑2 archives after 2015, and beyond the Mediterranean biogeographical region. Using pixel-specific growing season data typically boosted data availability in most geographies and diminished most of the latitudinal differences, but feasibility of complete time series with sub-monthly compositing windows was still restricted to the most recent years, and required data interpolation. Overall, our analyses provided a detailed assessment of Landsat and Sentinel-2 data availability over Europe, and based on selected application examples, highlighted often lacking spatio-temporal consistency of time series with sub-monthly compositing windows and long-time periods, which might hinder feasibility of some LCLUC applications.

Asian dust (AD) events and total suspended particle (TSP) was observed at Kanazawa University Wajima Air Monitoring Station (KUWAMS), a Japanese background site, during the East Asian winter monsoon periods (from November to May of the following year) from 2010 to 2021. Nine kinds of polycyclic aromatic hydrocarbons (PAHs) were determined in each TSP sample. In this study, a total of 54 AD events were observed. According to the different pathways of long-range transportation, AD events were divided into AD-high (transported at higher altitude, around 4000 m) and AD-low (transported at lower altitude, around 2500 m). The TSP concentrations in-creased sharply in the AD and was higher in AD-high (39.8 ± 19.5 μg/m³) than that in AD-low (23.5 ± 10.5 μg/m³). While AD didn’t have significant effect on ΣPAHs characteristic variation, as ΣPAHs concentration in non-AD periods, AD-high, AD-low were 543 ± 374, 404 ± 221, 436 ± 265 pg/m³, respectively. PAHs compositions were also consistent. As a result, TSP concentration was affected by the input air mass transported at higher altitude from the desert region while PAHs concentration was under the impact of air mass at lower altitude which carried the PAHs emitted from fossil fuels and biomass combustion in northeastern China. Moreover, the health risks of PAHs were calculated by inhalation lifetime cancer risk which ranged from 10−6 to 10−5 ng/m3, in-dicating a potential carcinogenic risk at KUWAMS during the East Asian winter monsoon period.

To solve the problem that the common long-tailed classification method does not use the semantic features of the original label text of the image, and the difference between the classification accuracy of most classes and minority classes is large, the long-tailed image classification method based on enhanced contrast visual language trains the head class and tail class samples separately, uses text image to pre-train the information, and uses enhanced momentum contrast loss function and RandAugment enhancement to improve the learning of tail class samples. On the ImageNet-LT long-tailed dataset, the enhanced contrastive visual-language based long-tailed image classification method has improved all class accuracy, tail class accuracy, middle class accuracy, and F1 values by 3.4%, 7.6%, 3.5%, and 11.2%, respectively, compared to the BALLAD method. The difference in accuracy between the head class and tail class is reduced by 1.6% compared to the BALLAD method. The results of three comparative experiments indicate that the long-tailed image classification method based on enhanced contrastive visual-language has improved the performance of tail classes and reduced the accuracy difference between majority and minority classes.

Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the quality of life and increase the burden on healthcare systems. The long COVID neurological symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. EGCG-palmitate (EC16), a multifunctional compound, has the potential to become a novel intranasal-delivered drug for minimizing post-COVID neurologic symptoms. Method: EC16-containing formulations were developed and tested in vitro against human β coronavirus OC43 (CoV-OC43) using a TCID50 assay following three test protocols differing in exposure sequence. Results: EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium were found to effectively inhibit human β-coronavirus infection (&gt;99.99%) after a 30-min contact. A single 10-min application to cells after infection (i.e., without direct contact with the virus) resulted in &gt;99% inhibition of viral replication. Conclusion: With its antiviral, antioxidant, anti-inflammatory, and neuroprotective properties, EC16 in nasal formulations could be further developed for clinical applications to COVID-19 patients for minimizing long COVID neurological symptoms.

Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.

Memory is probably one of the most complex cognitive functions of the human, and in many years, thousands of studies have helped us to better recognize this brain function. One of the reference textbooks in neuroscience, which has also elaborated on the memory function, is written by Prof. Kandel and his colleagues. In this book, I encountered a number of ambiguities when it was explaining the memory system. Here, I am sharing those points, either to find an answer for them, or to let them be a suggestion for our future works. Prof. Kandel has spent most of his meritorious lifetime on studying the memory system; however, the brain is extremely complex, and as a result, we still have many years to comprehensively understand the neural mechanisms of brain functions.

The Eastern Mediterranean is a highly populated area with air quality problems as well where climate change already is noticed by higher temperatures and changing precipitation pattern. The anthropogenic aerosol affects health and changing concentra-tions and properties of the atmospheric aerosol affect radiation balance and clouds. Continuous long-term observations are essential in assessing the influence of anthro-pogenic aerosols on climate and health. We present 6 years of observations from Navarino Environmental Observatory (NEO), a new station located at the south west tip of Pelo-ponnese, Greece. The two sites at NEO, were evaluated to show the influence of the local meteorology but also to assess the general background aerosol possible. It was found that the background aerosol was originated from aged European aerosols and was strongly influenced by biomass burning, fossil fuel combustion, and industry. When subsiding into the boundary layer, local sources contributed in the air masses moving south. Mesoscale meteorology determined the diurnal variation of aerosol properties such as mass and number by means of typical sea breeze circulation, giving rise to pronounced morning and evening peaks in pollutant levels. While synoptic scale meteorology, mainly large-scale air mass transport and precipitation, strongly influenced the season-ality of the aerosol properties.

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p &lt; 0.0001), and showed positive correlation with disease progression (r = 0.394, p &lt; 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

Great Britain’s stocks of coal, natural gas, and petroleum have seen major changes to the levels of stored energy over the years 2005 to 2019, a reduction of 200 TWh (35%) from 570 TWh to 370 TWh. The transformation of its electrical system over this timeframe saw a reduction in coal generation, leading to a corresponding reduction of the levels of stockpiled coal of 85 TWh (68%), partially offset by an increase in the stocks of biomass for electrical generation. The reduction in natural gas storage of 24 TWh (44%) was primarily due to the closure of Britain’s only long-term seasonal natural gas storage facility in January 2018. This was partially offset by the construction of medium-term natural gas storage facilities and the use of LNG storage in the years preceding its closure. For stocks of crude oil and oil products the reduction was 35 TWh (21%), linked to the overall reduction in demand.

Background: Glioblastomas (GBM) is generally burdened, to date, by a dismal prognosis, although Long Term Survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variable on Survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our Institution and classified according their Overall Survival in LTS (Long Term Survivors) and STS (Short Term Survivors). A thorough Review of our surgical series was conducted to compare the oncologic results of the patients in regards to 1. Surgical , 2. Molecular, and 3.Treatment related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the Histochemical point of view, Ki67(%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of 8 prognostic subgroups according to the molecular patterns of Ki67 overexpression and EGFR, p53 and IDH mutations. Conclusions: On the ground of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: KPS, Age, Volume of the lesion, Motor disorder at presentation, a Ki67 overexpression. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.

Long non-coding RNAs (lncRNAs) have been found to be involved in many biological processes, including the regulation of cell differentiation, but a complete characterization of lncRNA is still lacking. Additionally, there is evidence that lncRNAs interact with ribosomes, raising questions about their functions in cells. Here, we used a developmentally staged protocol to induce cardiogenic commitment of hESCs and then investigated the differential association of lncRNAs with polysomes. Our results identified lncRNAs in both the ribosome-free and polysome-bound fractions during cardiogenesis and showed a very well-defined temporal lncRNA association with polysomes. Clustering of lncRNAs was performed according to the gene expression patterns during the five timepoints analyzed. In addition, differential lncRNA recruitment to polysomes was observed when comparing the differentially expressed lncRNAs in the ribosome-free and polysome-bound fractions or when calculating the polysome-bound vs ribosome-free ratio. The association of lncRNAs with polysomes could represent an additional cytoplasmic role of lncRNAs, e.g., in translational regulation of mRNA expression.

Long memory plays an important role in many fields by determining the behaviour and predictability of systems; for instance, climate, hydrology, finance, networks and DNA sequencing. In particular, it is important to test if a process is exhibiting long memory since that impacts the accuracy and confidence with which one may predict future events on the basis of a small amount of historical data. A major force in the development and study of long memory was the late Benoit B. Mandelbrot. Here we discuss the original motivation of the development of long memory and Mandelbrot's influence on this fascinating field. We will also elucidate the sometimes contrasting approaches to long memory in different scientific communities

The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. As a result, to monitor the health of individuals affected by these conditions, they must maintain up-to-date health records using digital health informatics apps for surveillance. In this review, we provide an overview of the existing literature on identifying long COVID manifestations through hierarchical classification and the characterization of long COVID by different hierarchical groups based on the Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) in artificial intelligence (AI) to identify long COVID. Knowledge exploration, using the concept map for the clinical pathways of long COVID presented in this paper, provides an overview of the data needed to explore tackling the long-term effect of COVID-19 by integrating innovative cohesive frameworks and designing health informatics-based applications. To the best of our knowledge, this is the first paper to explore the potential incorporation of long COVID as a variable risk factor within a digital health informatics application.

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.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.

It is generally accepted that atherosclerosis is a chronic inflammatory disease. The link between atherosclerosis and other inflammatory diseases such as psoriasis, type 2 diabetes mellitus (T2DM), and rheumatoid arthritis (RA) via metabolic, inflammatory, and immunoregulatory pathways is well established. The aim of our review was to summarize the associations between selected microRNAs (miRs) and long non-coding RNAs (lncRNAs) and atherosclerosis, psoriasis, T2DM, and RA. MicroRNAs are short noncoding RNA molecules involved in cell signaling, intracellular communication, and gene expression. We reviewed the role of miR-146a, miR-210, miR-143, miR-223, miR-126, miR-21, miR-155, miR-145, miR-200, miR-133, miR-135, miR-221, miR-424, and let-7 in atherosclerosis, psoriasis, T2DM, and RA. LncRNAs are RNA transcripts longer than 200 nucleotides that are involved in cellular processes such as apoptosis, metabolism, inflammation, cell differentiation, and proliferation. We evaluated the role of lncRNA-H19, lncRNA-MEG3, lncRNA-UCA1, and lncRNA-XIST in atherosclerosis and psoriasis, T2DM, and RA. Extracellular vesicles (EVs) are a method of intracellular signal transduction. Their function depends on surface expression, cargo, and the cell from which they originate.

THz radiation has assumed a great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here we propose a reflecting bi-mirror axicon-like device with wavelength-independent long focusing performances in the THz band, by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation permits to achieve significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film, acting as heater thanks to its absorption for wavelengths below ~500 nm . An invariance property of the Fresnel integral has been exploited to verify experimentally the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property allowed also to verify experimentally that the axicon focus has a longitudinal extension much greater than that one exhibited by a benchmark cylindrical mirror with the same optical power. The axicon is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with a minor degradation of the optical performances.

SARS-CoV-2, the virus that causes theCOVID-19 disease, has been demonstrated to cause immune suppression in certain individuals. This can manifest as a reduced ability for the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm," an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely comprehended at this time, and ongoing research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this work, we propose the hypothesis that the IgG4 antibody produced by B cells in response to infection by SARS-CoV2 generates immunological tolerance that prevents its elimination, and leads to persistence and chronic infection. In sum, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.

The atmospheric concentrations of sodium, aluminum, silicon, sulphur, chlorine, potassium, calcium, titanium, vanadium, chromium, manganese, iron, nickel, copper, zinc, bromine and lead were measured in air filters at the Finnish Meteorological Institute station, in Helsinki, Finland, during a period of 44 years (1962-2005). The mean annual concentrations were calculated and are presented from the lowest values to the highest ones Cr&lt;Ni&lt;Ti&lt;Br&lt;V&lt;Mn&lt;Cu&lt;Zn&lt;Cl&lt;Al&lt;Fe&lt;K&lt;Ca&lt;Na&lt;Pb&lt;Si&lt;S. Most of the elements (Fe, Si, Ti, K, Ca, Zn, Br, Pb, V, Ni, S, Cr, Na, Al, Cl) present higher values during spring and winter season while in summer the elements (Ti, Ca, S, Na) are found in higher concentrations. There is a strong correlation between the elements (V-Ni, Si-Pb, Fe-Ca, V-Cr, Si-K, K-Ca, Fe-Ti, K-Na, Si-Ca, V-S), indicating their common source. The identification of the sources of trace elements was performed based on positive matrix factorization analysis, using SoFi software. Four PM sources were identified: road dust (due to usage of leaded fuel), heavy oil combustion/secondary sulfates, traffic emissions and natural dust (soil). For the total of 44 years studied, significant decreases in concentrations were observed for all trace elements, most of which were over 50%: Na (-74%), Al (-86%), Si (-88%), S (-82%), K (-82%), Ca (-89%), Ti (-80%), V (-89%), Cr (-82%), Mn (-77%), Fe (-77%), Ni (-61%), Zn (-72%), Pb (-95%). The current data are consistent with previous air studies covering the whole territory of Finland. Finally, a significant decline has been observed in the majority of the elemental concentrations since the end of 70s, underlying the effectiveness of different environmental policies that have been applied during the last decades.

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This review summarizes the evidence on strategies that can be applied to treat both long and vaccine injuries based on similar mechanisms of action.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

Introduction Early prediction of long term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and after six months. Methods We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36°C and after rewarming at 37°C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favorable functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results Of 171 resuscitated patients, 75 were excluded due to missing of data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good outcome (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up) Predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good outcome) to any combination of two tests or any single test. Conclusion Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia ad off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone.

Objectives: A wealth of literature has established risk factors for social isolation among older people, however much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.

In higher eukaryotes, enhancers determine the activation of developmental gene transcription in specific cell types and stages of embryogenesis. Enhancers transform the signals produced by various transcription factors within a given cell, activating the transcription of the targeted genes. Often, developmental genes can be associated with dozens of enhancers, some of which are located at large distances from the promoters that they regulate. Currently, the mechanisms that underly the specific distance interactions between enhancers and promoters remain unknown. This review describes the properties and activities of enhancers and discusses the mechanisms of distance interactions and potential proteins involved in this process.

Refractive surgery is an increasingly popular procedure to decrease spectacle or contact lens dependency. The two most commonly used surgical techniques to correct myopia is Photorefractive keratectomy (PRK) and Femtosecond- Lasik (FS-LASIK)There are few publications that gathers such a long term follow up of both surgical techniques (2) Methods It has been performed a retrospective non-randomized study 509 PRK eyes and 310 FS-LASIK surgeries were followed for 10 years for the treatment of myopia and compound myopic astigmatism. Patients were followed up three months, one year, 2 years, 5 and 10 years. The safety index of both procedures was defined as a quotient between the postoperative BCVA (Best Corrected Visual Acuity) and the preoperative BCVA. The predictability is calculated as difference between the expected spherical equivalent and the achieved spherical equivalent. The efficacy index was calculated as a quotient between postoperative UCVA divided by the preoperative BCVA (3) Results. The results were: a safety index higher than 100% (109%) and an efficacy index of 82.4% after 10 years of PRK surgery in both groups. FS-LASIK was the safest surgery after 10 years and the most efficacy technique although in this case there were no statistically significant differences (4) Conclusions. All these data demonstrated better indexes for FS-LASIK

This paper studies long economic series to assess the long-lasting effects of pandemics. We analyze if periods of time that cover pandemics have a change in trend and persistence in growth, and in level and persistence in unemployment. We find that there is an upward trend in the persistence level of growth across the centuries. In particular, shocks originated by pandemics in recent times seem to have permanent effect in growth. Moreover, our results show that the unemployment rate increases and it becomes more persistent after a pandemic. In this regard, our findings support the design and implementation of counter-cyclical policies to soften the shock of the pandemic.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

Research background: Relationship between inflation rate, unemployment rate, interest rate and real gross domestic product per capita in Nigeria. However, there seems to be a short-run or long-run relationship among the macroeconomic variables.Purpose: This study investigated the impact of the inflation rate, unemployment rate and interest rate on real gross domestic product per capita (RGDPPC) (proxy for economic growth) and proffered recommendations towards enhancing economic growth and to reduce the distasteful effects of inflation rate, unemployment rate and interest rate in Nigeria in this present time economic challenges.Research methodology: This study applied a linear dynamic model Autoregressive Distributed Lag (ARDL) modeling technique to analyze the short-run dynamics and long-run relationship of the economic growth in Nigeria over the sample period between 1984 and 2017 using annual secondary data extracted from World Bank Development Indicators Report (last updated January 2019).Results: The empirical results showed that there was long-run relationship between inflation rate, unemployment rate and interest rate on real gross domestic product per capita (proxy for economic growth) in Nigeria. The result further revealed that only unemployment rate had a significant positive impact on real gross domestic product per capita in the long-run and inflation rate had a significant negative impact on real gross domestic product per capita in the short-run.Novelty: Therefore, the study concluded that unemployment rate and inflation rate proved to have significant impacts on economic growth in the long-run and short-run respectively. Formulation of policies to reduce unemployment through the adoption of labour concentrated technique of production, entrepreneurship development and policy to keep the inflation rate at single digit.

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.