Magnetic Resonance Imaging of Mouse Cerebral Cavernomas Reveal Differential Lesion Progression and Variable Permeability to Gadolinium.

BACKGROUND: Cerebral cavernous malformations, also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurological deficits, whereas others remain asymptomatic. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood. METHODS: We established a chronic mouse model of cerebral cavernous malformations, induced by postnatal ablation of Krit1 with Pdgfb-CreERT2, and examined lesion progression in these mice with T2-weighted 7T magnetic resonance imaging (MRI). We also established a modified protocol for dynamic contrast-enhanced MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. After terminal imaging, brain slices were stained with antibodies against microglia, astrocytes, and endothelial cells. RESULTS: These mice develop cerebral cavernous malformations lesions gradually over 4 to 5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed nonmonotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and after about 2 months followed a power trend. Using dynamic contrast-enhanced MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. MRI properties of the lesions were correlated with cellular markers for endothelial cells, astrocytes, and microglia. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial and glial cells revealed that increased cell density surrounding lesions correlates with stability, whereas denser vasculature within and surrounding the lesions may correlate with high permeability. CONCLUSIONS: Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive preclinical platform for testing new drug and gene therapies for controlling cerebral cavernous malformations.

Investigating factors affecting the evaluation of teachers' medical universities from the students' point of view: a systematic review.

BACKGROUND: Faculty evaluation is essential as a principle in educational organizations because it helps measure the quantity and quality of education in universities and educational institutions. There are various ambiguities regarding the desirable and deserving characteristics of a good teacher. Therefore, this study was conducted with the aim of investigating factors affecting the evaluation of teachers' medical universities from the perspective of students. METHODS: A systematic review study was conducted by searching for studies in both Persian and English languages from 2014 to 2022 in the following databases: Pubmed, Web of Science, Scopus, Cochrane, Google Scholar, and ScienceDirect, Magiran, SID, Iran Doc using keywords including Evaluation, Assessment, Estimate, Appraisement, Appraisal, Faculty Member, Professor, University, and College, as well as their MeSH equivalents, using "AND" and "OR" operators. The results of the articles about investigating factors affecting the evaluation of teachers' medical universities from the perspective of students were reviewed, summarized, and reported. RESULTS: In the initial search, 3949 articles were found, and after evaluation, finally 21 articles were included in the systematic review. Based on the findings, investigating factors affecting the evaluation of teachers' medical universities from the perspective of 130,187 students can be categorized into 6 dimensions and 53 components. These dimensions include individual and professional characteristics of the educational system, attitude within the educational system, educational programs and guides, teaching methodology, internal coherence of educational resources, and evaluation system information. CONCLUSION: The results of the articles about investigating factors affecting the evaluation of teachers' medical universities from the perspective of students were reviewed, summarized, and reported. It is necessary to pay attention to the factors affecting the evaluation of teachers in the recruitment of faculty members. Additionally, by holding practical training workshops with consideration of various dimensions that have an impact on faculty evaluation and student learning, it is possible to enhance the expertise of faculty members.

Predictive factors of occupational stress among nurses during the COVID-19 pandemic: a cross-sectional study in Kashan, Iran.

BACKGROUND: Considering the severe and sudden changes in the job conditions of nurses during the covid-19 pandemic, the increase in job tensions during this critical period and its consequences on the quantity and quality of nursing care, this study aims to investigate the job stress of nurses during the covid-19 pandemic and its predictors in Iran. METHODS: This cross-sectional study was conducted on 400 nurses in 'Kashan', Iran, who were randomly selected using stratified sampling. Data were collected using two questionnaires on occupational stress and potential related factors. The data were analyzed in SPSS version 16. RESULTS: The results showed that the occupational stress of nurses in Iran was at a medium to high level with a mean and standard deviation of 103.773 ± 15.742 (scale of 34-136). Factors such as satisfaction with physical health, quality of work life, satisfaction with the availability of facilities, sense of coherence, education level, work experience, job burnout, male gender, being native, and workplace were predictors of occupational stress and explained 23.3% of the variance in occupational stress score. The highest contribution was related to satisfaction with physical health. CONCLUSION: Considering the consequences of occupational stress for nurses, it is crucial for health and nursing authorities to take these factors into consideration in policy-making and planning.

The effect of ear acupressure on occupational cognitive failure in nurses after the COVID-19 crisis: a randomized controlled clinical trial.

BACKGROUND: In the aftermath of the COVID-19 pandemic, nurses reported varying degrees of cognitive failure. To prioritize patient safety in clinical settings, it is important and necessary to address and mitigate the symptoms of cognitive failure among nurses. AIM: This study was conducted in Iran to evaluate the impact of ear acupressure on occupational cognitive failure in nurses. METHODS: This randomized controlled clinical trial was conducted with 54 nurses who experienced cognitive failure in 2022. Sampling was performed by convenience. Fifty-six nurses who scored 40 or higher on the occupational cognitive failure questionnaire were randomly assigned to either the intervention group (28 subjects) or the sham group (28 subjects). In the intervention group, pressure was applied to the shen-men point, zero point, hippocampus, master cerebral, brain, and memory 1 and 2 of the earlobes for six weeks using Vaccaria seeds. In the sham group, a sticker without seeds was applied at the same points as in the intervention group, and no pressure was applied. Cognitive failure was assessed at the beginning of the study (T0), at the end of the intervention (sixth week of study, T1), and four weeks after the end of the intervention (tenth week of study, T2). The data were collected using contextual data questionnaires and the Occupational Cognitive Failure Questionnaire (OCFQ). The data obtained from 54 nurses (28 in the sham group and 26 in the intervention group) were analyzed by SPSS v16 using repeated-measures ANOVA. RESULTS: The two groups had no significant differences regarding background variables. The between-group analysis revealed a significant interaction effect of time and intervention on cognitive failure (F = 60.320, p < 0.001, effect size = 0.537). The cognitive failure score in the intervention group was significantly lower at the end of the intervention and one month later than that in the sham group (p < 0.001). Within-group analysis revealed a significant difference in the cognitive failure scores of the intervention group at T0, T1, and T2 (61.231 ± 14.230, 34.000 ± 14.659, and 29.808 ± 14.266, respectively; F = 52.331, p < 0.001, effect size = 0.677). However, in the sham group, the cognitive failure score exhibited a brief but significant increase at T0, T1, and T2 (54.786 ± 11.239, 56.250 ± 10.950, and 56.000 ± 11.337, respectively; F = 6.369, p = 0.006, effect size = 0.191). CONCLUSION: Auriculotherapy has shown promise in improving occupational cognitive failure in nurses. It is recommended that nurses consider incorporating auriculotherapy as a complementary treatment modality, particularly through self-treatment programs, when experiencing symptoms of cognitive impairment. TRIAL REGISTRATION NUMBER (TRN): IRCT20100211003329N10 DATE OF REGISTRATION: 04/11/2022.

Microglia Modulate Cortical Spreading Depolarizations After Ischemic Stroke: A Narrative Review.

Cortical spreading depolarizations (CSDs) are characterized by waves of diminished electroencephalography activity that propagate across the cortex with subsequent loss of ionic homeostasis. CSDs have been found in many pathological conditions, including migraine, traumatic brain injury, and ischemic stroke. Because of CSD-associated ionic and metabolic disturbances at the peri-infarct area after ischemic stroke, it is thought that CSDs exacerbate tissue infarction and worsen clinical outcomes. Microglia, the main innate immune cells in the brain, are among the first responders to brain tissue damage. Recent studies demonstrated that microglia play a critical role in CSD initiation and propagation. In this article, we discuss the significance of CSD in the setting of ischemic stroke and how microglia may modulate peri-infarct CSDs, also known as iso-electric depolarizations. Finally, we discuss the significance of microglial Ca2+ and how it might be used as a potential therapeutic target for patients with ischemic stroke.

Microglial Calcium Waves During the Hyperacute Phase of Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic injury triggers multiple pathological responses in the brain tissue, including spreading depolarizations across the cerebral cortex (cortical spreading depolarizations [CSD]). Microglia have been recently shown to play a significant role in the propagation of CSD. However, the intracellular responses of myeloid cells during ischemic stroke have not been investigated. METHODS: We have studied intracellular calcium activity in cortical microglia in the stroke model of the middle cerebral artery occlusion, using the murine Polr2a-based and Cre-dependent GCaMP5 and tdTomato reporter (PC::G5-tdT). High-speed 2-photon microscopy through cranial windows was employed to record signals from genetically encoded indicators of calcium. Inflammatory stimuli and pharmacological inhibition were used to modulate microglial calcium responses in the somatosensory cortex. RESULTS: In vivo imaging revealed periodical calcium activity in microglia during the hyperacute phase of ischemic stroke. This activity was more frequent during the first 6 hours after occlusion, but the amplitudes of calcium transients became larger at later time points. Consistent with CSD nature of these events, we reproducibly triggered comparable calcium transients with microinjections of potassium chloride (KCl) into adjacent cortical areas. Furthermore, lipopolysaccharide-induced peripheral inflammation, mimicking sterile inflammation during ischemic stroke, produced significantly greater microglial calcium transients during CSD. Finally, in vivo pharmacological analysis with CRAC (calcium release-activated channel) inhibitor CM-EX-137 demonstrated that CSD-associated microglial calcium transients after KCl microinjections are mediated at least in part by the CRAC mechanism. CONCLUSIONS: Our findings demonstrate that microglia participate in ischemic brain injury via previously undetected mechanisms, which may provide new avenues for therapeutic interventions.

Arteriovenous malformation presenting with epilepsy: a multimodal approach to diagnosis and treatment.

Arteriovenous malformation (AVM) presenting with epilepsy significantly impacts patient quality of life, and it should be considered very much a seizure disorder. Although hemorrhage prevention is the primary treatment aim of AVM surgery, seizure control should also be at the forefront of therapeutic management. Several hemodynamic and morphological characteristics of AVM have been identified to be associated with seizure presentation. This includes increased AVM flow, presence of long pial draining vein, venous outflow obstruction, and frontotemporal location, among other aspects. With the advent of high-throughput image processing and quantification methods, new radiographic attributes of AVM-related epilepsy have been identified. With respect to therapy, several treatment approaches are available, including conservative management or interventional modalities; this includes microsurgery, radiosurgery, and embolization or a combination thereof. Many studies, especially in the domain of microsurgery and radiosurgery, evaluate both techniques with respect to seizure outcomes. The advantage of microsurgery lies in superior AVM obliteration rates and swift seizure response. In addition, by incorporating electrophysiological monitoring during AVM resection, adjacent or even remote epileptogenic foci can be identified, leading to extended lesionectomy and improved seizure control. Radiosurgery, despite resulting in reduced AVM obliteration and prolonged time to seizure freedom, avoids the risks of surgery altogether and may provide seizure control through various antiepileptic mechanisms. Embolization continues to be used as an adjuvant for both microsurgery and radiosurgery. In this study, the authors review the latest imaging techniques in characterizing AVM-related epilepsy, in addition to reviewing each treatment modality.

Psychometric evaluation of the Persian version of the Doloplus-2 (P-Doloplus-2) scale in elderly with dementia

Background/aim: A scale for behavioural pain assessment is useful for the detection and determination of pain in the elderly with dementia. This study aimed to translate and evaluate the psychometric properties of Doloplus-2 in the elderly with dementia in Iran. Materials and methods: In this methodological study, after translation and evaluating the face and content validity of Doloplus-2, 100 elderly people were selected by the convenience sampling method in Kashan, 2018­2019. Exploratory factor analysis, convergent validity, and known-groups comparison were applied to determine construct validity. Reliability was also assessed through internal consistency, equivalence, and stability methods were used. The ceiling and floor effects were also examined. Data were analyzed using the SPSS-v16 and via Mann-Whitney U test, Cronbach's alpha, Spearman-Brown, and intraclass correlation coefficient (ICC). Results: The scale's content validity index was 0.95%, and the item impact of each item was above 1.5. Factor analysis identified 2 "social- functional" and "conventional subjective-objective" factors in scale that altogether were able to explain 76% of the total variance. The results revealed that P-Doloplus-2 could discriminate between the 2 groups of elderly with and without known chronic painful diseases (P < 0.0001). There was a significant positive correlation between P-Doloplus-2 and PACSLAC-II-IR scores (r = 0.878, P < 0.0001). Cronbach's alpha, ICC, and standard error of measurement for the scale were 0.950, 0.864, and ± 1.759, respectively. The frequency of minimum and maximum possible score of scale was less than 15%. Conclusion: The Persian version of Doloplus-2 can be considered as a valid and reliable scale for pain assessment in the elderly with dementia.

Clinical utility of arterial spin labeling imaging in disorders of the nervous system.

Neuroimaging is an indispensable tool in the workup and management of patients with neurological disorders. Arterial spin labeling (ASL) is an imaging modality that permits the examination of blood flow and perfusion without the need for contrast injection. Noninvasive in nature, ASL provides a feasible alternative to existing vascular imaging techniques, including angiography and perfusion imaging. While promising, ASL has yet to be fully incorporated into the diagnosis and management of neurological disorders. This article presents a review of the most recent literature on ASL, with a special focus on its use in moyamoya disease, brain neoplasms, seizures, and migraines and a commentary on recent advances in ASL that make the imaging technique more attractive as a clinically useful tool.

Social Health and Related Factors in Nurses: A Systematic Review and Meta-Analysis.

Background: The present study was conducted to evaluate the level of social health and related factors in nurses. Materials and Methods: This systematic review and meta-analysis were done based on searching English and Persian articles published in PubMed, Scopus, Web of Science, Science Direct databases, Google Scholar, Scientific Information Database, Iranmedex, and Magiran from inception to January 2022. The mean (SD) of nurses' social health scores, their various dimensions, and related factors were extracted from the retrieved articles. Data analysis was performed using Review Manager software, and p < 0.05 was considered significant. Results: A total of 36 studies were reviewed for systematic review and 34 studies for meta-analysis. The total mean (SD) of social health in 9281 nurses was 57.13 (6.82) (on a scale of 0-100) with a 95% confidence interval of 50.31-63.95. Social health of nurses showed a statistically significant relationship with some demographic-personal factors and occupational-organizational factors. Conclusions: The level of nurses' social health was moderate which needs to be improved. To improve the performance of professional roles and the nursing care quality, it is necessary for healthcare system managers, especially nursing managers, to consider individual and organizational factors affecting nurses' social health in planning and decision making and try to increase nurses' social health. Some of the limitations of this study were that only reviewing quantitative cross-sectional studies and couldn't combine words when searching in Iranian databases.

Translation and Psychometric Evaluation of the Comfort Questionnaire in a Sample of Iranian Nurses: A Methodological Study.

Background and Purpose: This study was conducted to translate the Nurses' Comfort Questionnaire (NCQ) into Persian and examine its psychometric properties. Methods: In this methodological study, after translation, and face and content validity of the instrument, 300 nurses were randomly selected from the various hospitals in Kashan, during 2022. The construct validity and reliability of the instrument were examined. Results: The extracted five factors in exploratory factor analysis were able to explain 35.7% of the total variance of the questionnaire score. Coefficient α, intraclass correlation coefficient, standard error of measurement, and the smallest measurable change of the psychometric of NCQ (P-NCQ) were calculated as .872, .899, ±4.284, and 5.737, respectively. Conclusions: The P-NCQ has 30 items in five subscales and can be used as a valid and reliable instrument to measure the comfort of nurses.

The effects of auriculotherapy on depression among elderly people: A randomized controlled clinical trial.

BACKGROUND: Given the high prevalence of depression in elderly people, appropriate interventions are essential. This study aimed to assess the effects of auriculotherapy on depression among elderly people. METHODS: This randomized controlled clinical trial was conducted in 2021. Fifty-two elderly were conveniently selected and randomly allocated to the sham (n = 26) and intervention (n = 26) groups through block randomization. The intervention group was subjected to four weeks of auriculotherapy at the Shen-Men, zero, heart, antidepressant, and master cerebral points using Vaccaria seeds fixed with adhesive tape. In the sham group, adhesive tapes were attached to the points with neither seeds nor compression. The elderly and data collector were blinded. The 15-item Geriatric Depression Scale was used to assess depression before, immediately after, and four weeks after the intervention (T1-T3). The statistical methods used were repeated measures analysis of variance and covariance. RESULTS: Groups significantly differed concerning participants' gender, education, and employment (p < 0.05). After adjusting for confounding effects, the time-group interaction significantly affected the mean depression score (p < 0.0001, effect size = 0.54). There was no significant difference between the depression score in the sham and intervention groups at T1 (9.6 ± 2.5 vs 9.5 ± 2.5, p = 0.263); however, this difference was found to be significant at T2 (8.6 ± 2 vs 4.2 ± 1.2, p < 0.0001, effect size = 0.68) and T3 (9.3 ± 2.3 vs 4.3 ± 1.3, p < 0.0001, effect size = 0.65). Within-group analysis revealed significant differences in the depression scores of the intervention group at T1 compared with those at T2 and T3 (p < 0.05). In contrast, the mean depression score in the sham group at T2 was significantly lower than that at T1 (p = 0.003) and greater than that at T3 (p = 0.049). CONCLUSIONS: Auriculotherapy alleviates depression and can be used as a complementary therapy for elderly people with depression.

Focused Ultrasound Impels the Delivery and Penetration of Model Therapeutics into Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular neoplasms in the brain that can cause debilitating symptoms. Current treatments pose significant risks to some patients, motivating the development of new nonsurgical options. We recently discovered that focused ultrasound-mediated blood-brain barrier opening (FUS) arrests CCM formation and growth. Here, we build on this discovery and assess the ability of FUS to deliver model therapeutics into CCMs. METHODS: Quantitative T1 mapping MRI sequences were used with 1 kDa (MultiHance; MH) and 17 kDa (GadoSpin D; GDS) contrast agents to assess the FUS-mediated delivery and penetration of model small molecule drugs and biologics, respectively, into CCMs of Krit1 mutant mice. RESULTS: FUS elevated the rate of MH delivery to both the lesion core (4.6-fold) and perilesional space (6.7-fold). Total MH delivery more than doubled in the lesion core and tripled in the perilesional space when FUS was applied immediately prior to MH injection. For the model biologic drug (i.e. GDS), FUS was of greater relative benefit, resulting in 21.7-fold and 3.8-fold delivery increases to the intralesional and perilesional spaces, respectively. CONCLUSIONS: FUS is capable of impelling the delivery and penetration of therapeutics into the complex and disorganized CCM microenvironment. Benefits to small molecule drug delivery are more evident in the perilesional space, while benefits to biologic delivery are more evident in CCM cores. These findings, when combined with ability of FUS alone to control CCMs, highlight the potential of FUS to serve as a powerful non-invasive therapeutic platform for CCM.

Exploring the dynamics of adult Axin2 cell lineage integration into dentate gyrus granule neurons.

The Wnt pathway plays critical roles in neurogenesis. The expression of Axin2 is induced by Wnt/ß-catenin signaling, making this gene a reliable indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with the Axin2-CreERT2 allele to follow the fate of Axin2+ lineage in the adult hippocampal formation. We found Axin2 expressed in astrocytes, neurons and endothelial cells, as well as in the choroid plexus epithelia. Simultaneously with the induction of Axin2 fate mapping by tamoxifen, we marked the dividing cells with 5-ethynyl-2'-deoxyuridine (EdU). Tamoxifen induction led to a significant increase in labeled dentate gyrus granule cells three months later. However, none of these neurons showed any EdU signal. Conversely, six months after the pulse-chase labeling with tamoxifen/EdU, we identified granule neurons that were positive for both EdU and tdTomato lineage tracer in each animal. Our data indicates that Axin2 is expressed at multiple stages of adult granule neuron differentiation. Furthermore, these findings suggest that the integration process of adult-born neurons from specific cell lineages may require more time than previously thought.

Focused Ultrasound Blood-Brain Barrier Opening Arrests the Growth and Formation of Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCM) are vascular lesions within the central nervous system, consisting of dilated and hemorrhage-prone capillaries. CCMs can cause debilitating neurological symptoms, and surgical excision or stereotactic radiosurgery are the only current treatment options. Meanwhile, transient blood-brain barrier opening (BBBO) with focused ultrasound (FUS) and microbubbles is now understood to exert potentially beneficial bioeffects, such as stimulation of neurogenesis and clearance of amyloid-ß. Here, we tested whether FUS BBBO could be deployed therapeutically to control CCM formation and progression in a clinically-representative murine model. METHODS: CCMs were induced in mice by postnatal, endothelial-specific Krit1 ablation. FUS was applied for BBBO with fixed peak-negative pressures (PNPs; 0.2-0.6 MPa) or passive cavitation detection-modulated PNPs. Magnetic resonance imaging (MRI) was used to target FUS treatments, evaluate safety, and measure longitudinal changes in CCM growth after BBBO. RESULTS: FUS BBBO elicited gadolinium accumulation primarily at the perilesional boundaries of CCMs, rather than lesion cores. Passive cavitation detection and gadolinium contrast enhancement were comparable in CCM and wild-type mice, indicating that Krit1 ablation does not confer differential sensitivity to FUS BBBO. Acutely, CCMs exposed to FUS BBBO remained structurally stable, with no signs of hemorrhage. Longitudinal MRI revealed that FUS BBBO halted the growth of 94% of CCMs treated in the study. At 1 month, FUS BBBO-treated lesions lost, on average, 9% of their pre-sonication volume. In contrast, non-sonicated control lesions grew to 670% of their initial volume. Lesion control with FUS BBBO was accompanied by a marked reduction in the area and mesenchymal appearance of Krit mutant endothelium. Strikingly, in mice receiving multiple BBBO treatments with fixed PNPs, de novo CCM formation was significantly reduced by 81%. Mock treatment plans on MRIs of patients with surgically inaccessible lesions revealed their lesions are amenable to FUS BBBO with current clinical technology. CONCLUSIONS: Our results establish FUS BBBO as a novel, non-invasive modality that can safely arrest murine CCM growth and prevent their de novo formation. As an incisionless, MR image-guided therapy with the ability to target eloquent brain locations, FUS BBBO offers an unparalleled potential to revolutionize the therapeutic experience and enhance the accessibility of treatments for CCM patients.

Dynamics of Adult Axin2 Cell Lineage Integration in Granule Neurons of the Dentate Gyrus.

The Wnt pathway plays critical roles in neurogenesis. The expression of Axin2 is induced by Wnt/ß-catenin signaling, making this gene a sensitive indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with the Axin2-CreERT2 allele to follow the fate of Axin2 -positive cells in the adult hippocampal formation. We found Axin2 expressed in astrocytes, neurons and endothelial cells, as well as in the choroid plexus epithelia. Simultaneously with tamoxifen induction of Axin2 fate mapping, the dividing cells were marked with 5-ethynyl-2'-deoxyuridine (EdU). Tamoxifen induction resulted in significant increase of dentate gyrus granule cells three months later; however, none of these neurons contained EdU signal. Conversely, six months after the tamoxifen/EdU pulse-chase labeling, EdU-positive granule neurons were identified in each animal. Our data imply that Axin2 is expressed at several different stages of adult granule neuron differentiation and suggest that the process of integration of the adult-born neurons from certain cell lineages may take longer than previously thought.

Preclinical models of middle cerebral artery occlusion: new imaging approaches to a classic technique.

Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a "gold standard" in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease.

Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction.

Background-: Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion. Methods-: Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood-brain barrier, on efficacy of delivery of mitochondria. Results-: Following intra-arterial delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase cell viability. Additional of focused ultrasound leads to improved blood brain barrier opening without hemorrhagic complications. Conclusions-: Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.

Biomarkers Predictive of Long-Term Outcome After Ischemic Stroke: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: The goal of this study was to systematically review the usefulness of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome. METHODS: A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2018. All studies assessing long-term functional outcome (defined as ≥30 days) after IS with respect to serum biomarkers were included. Data were extracted and pooled using a meta-analysis of odds ratios. RESULTS: Of the 2928 articles in the original literature search, 183 studies were selected. A total of 127 serum biomarkers were included. Biomarkers were grouped into several categories: inflammatory (n = 32), peptide/enzymatic (n = 30), oxidative/metabolic (n = 28), hormone/steroid based (n = 23), and hematologic/vascular (n = 14). The most commonly studied biomarkers in each category were found to be CRP, S100ß, albumin, copeptin, and D-dimer. With the exception of S100ß, all were found to be statistically associated with >30-day outcome after ischemic stroke. CONCLUSIONS: Serum-based biomarkers have the potential to predict functional outcome in patients with IS. This meta-analysis has identified C-reactive protein, albumin, copeptin, and D-dimer to be significantly associated with long-term outcome after IS. These biomarkers have the potential to serve as a platform for prognosticating stroke outcomes after 30 days. These serum biomarkers, some of which are routinely ordered, can be combined with imaging biomarkers and used in artificial intelligence algorithms to provide refined predictive outcomes after injury. These tools will assist physicians in providing guidance to families regarding long-term independence of patients.

Translation and Psychometric Evaluation of the Mahoney Pain Scale Among Iranian Elderly With Dementia: A Methodological Study.

Valid and reliable measurement tools are necessary for pain assessment among the elderly with dementia. This study aimed to translate the Mahoney Pain Scale (MPS) into Persian and evaluate its psychometric properties among Iranian elderly with dementia. In this methodological study, after translating and assessing the face and content validity of MPS, 100 elderly with dementia were selected via convenience sampling from nursing homes and clinics in Kashan in 2018-19; then, MPS was completed for them both at rest and during a movement pain protocol. MPS was assessed by exploratory factor analysis, known-group comparison, convergent validity, internal consistency, equivalence, and stability. The factor analysis revealed a one-factor structure, which explained 57.11% of the total variance. The Persian MPS differentiated patients with and without known painful conditions, as well as pain at rest and during the movement pain protocol (p < .0001). There was a significant positive correlation between the scores of MPS and PACSLAC-II (r = .87, p < .0001). The Cronbach's α, intraclass correlation coefficient and standard error of measurement of MPS were .91, .79, and ±1.37, respectively. As a valid and reliable tool, the Persian MPS can be used for pain assessment among Iranian elderly with dementia.