Prognostic Value of Histopathological Thrombus Age in Large Vessel Occlusion-Related Stroke.

INTRODUCTION: Acute mechanical thrombectomy (MT) is the preferred treatment for large vessel occlusion-related stroke. Histopathological research on the obtained occlusive embolic thrombus may provide information regarding the aetiology and pathology of the lesion to predict prognosis and propose possible future acute ischaemic stroke therapy. METHODS: A total of 75 consecutive patients who presented to the Amphia Hospital with acute large vessel occlusion-related stroke and underwent MT were included in the study. The obtained thrombus materials were subjected to standard histopathological examination. Based on histological criteria, they were considered fresh (<1 day old) or old (>1 day old). Patients were followed for 2 years for documentation of all-cause mortality. RESULTS: Thrombi were classified as fresh in 40 patients (53%) and as older in 35 patients (47%). Univariate Cox regression analysis showed that thrombus age, National Institutes of Health Stroke Scale at hospital admission, and patient age were associated with long-term mortality (p < 0.1). Multivariable Cox hazards and Kaplan-Meier analysis demonstrated that after extensive adjustment for clinical and procedural variables, thrombus age persisted in being independently associated with higher long-term mortality (hazard ratio: 3.34; p = 0.038, log-rank p = 0.013). CONCLUSION: In this study, older thromboemboli are responsible for almost half of acute large ischaemic strokes. Moreover, the presence of an old thrombus is an independent predictor of mortality in acute large vessel occlusion-related stroke. More research is warranted regarding future therapies based on thrombus composition.

"It's completely erasure": A Qualitative Exploration of Experiences of Transgender, Nonbinary, Gender Nonconforming, and Questioning Students in Biology Courses.

Biology is the study of the diversity of life, which includes diversity in sex, gender, and sexual, romantic, and related orientations. However, a small body of literature suggests that undergraduate biology courses focus on only a narrow representation of this diversity (binary sexes, heterosexual orientations, etc.). In this study, we interviewed students with queer genders to understand the messages about sex, gender, and orientation they encountered in biology and the impact of these messages on them. We found five overarching themes in these interviews. Students described two narratives about sex, gender, and orientation in their biology classes that made biology implicitly exclusionary. These narratives harmed students by impacting their sense of belonging, career preparation, and interest in biology content. However, students employed a range of resilience strategies to resist these harms. Finally, students described the currently unrealized potential for biology and biology courses to validate queer identities by representing the diversity in sex and orientation in biology. We provide teaching suggestions derived from student interviews for making biology more queer-inclusive.

Revealing the queer-spectrum in STEM through robust demographic data collection in undergraduate engineering and computer science courses at four institutions.

Queer identities are often ignored in diversity initiatives, yet there is a growing body of research that describes notable heterosexist and gender-normative expectations in STEM that lead to unsupportive and discriminatory environments and to the lower persistence of queer individuals. Research on the experiences of queer-spectrum individuals is limited by current demographic practices. In surveys that are queer-inclusive there is no consensus on best practices, and individuals with queer genders and queer sexual, romantic, and related orientations are often lumped together in a general category (e.g. LGBTQ+). We developed two queer-inclusive demographics questions and administered them as part of a larger study in undergraduate engineering and computer science classes (n = 3698), to determine which of three survey types for gender (conventional, queered, open-ended) provided the most robust data and compared responses to national data to determine if students with queer genders and/or queer sexual, romantic, and related orientations were underrepresented in engineering and computer science programs. The gender survey with queer-identity options provided the most robust data, as measured by higher response rates and relatively high rates of disclosing queer identities. The conventional survey (male, female, other) had significantly fewer students disclose queer identities, and the open-ended survey had a significantly higher non-response rate. Allowing for multiple responses on the survey was important: 78% of those with queer gender identities and 9% of those with queer sexual, romantic and related orientations selected multiple identities within the same survey question. Queer students in our study were underrepresented relative to national data. Students who disclosed queer gender identities were 7/100ths of the expected number, and those with queer orientations were under-represented by one-quarter. Further work developing a research-based queered demographics instrument is needed for larger-scale changes in demographics practices, which will help others identify and address barriers that queer-spectrum individuals face in STEM.

No evidence for cerebellar abnormality in adults with developmental dyslexia.

Developmental dyslexia is commonly believed to result from a deficiency in the recognition and processing of speech sounds. According to the cerebellar deficit hypothesis, this phonological deficit is caused by deficient cerebellar function. In the current study, 26 adults with developmental dyslexia and 25 non-dyslexic participants underwent testing of reading-related skills, cerebellar functions, and MRI scanning of the brain. Anatomical assessment of the cerebellum was conducted with voxel-based morphometry. Behavioural evidence, that was indicative of impaired cerebellar function, was found to co-occur with reading impairments in the dyslexic subjects, but a causal relation between the two was not observed. No differences in local grey matter volume, nor in structure-function relationships within the cerebellum were found between the two groups. Possibly, the observed behavioural pattern is due to aberrant white matter connectivity. In conclusion, no support for the cerebellar deficit hypothesis or the presence of anatomical differences of the cerebellum in adults with developmental dyslexia was found.

Etiology of language network changes during recovery of aphasia after stroke.

Knowledge of spatiotemporal patterns of language network changes may help in predicting outcome in aphasic stroke patients. Here we assessed language function and performed functional MRI four times during one year to measure language network activation and cerebrovascular reactivity (with breath-holding) in twelve left-hemispheric stroke patients, of whom two dropped out before the final measurement, and eight age-matched controls. Language outcome was related to increase of activation in left and right posterior inferior temporal gyrus over the first year, while activation increase in right inferior frontal gyrus was inversely correlated to language recovery. Outcome prediction improved by addition of early language-induced activation of the left posterior inferior temporal gyrus to a regression model with baseline language performance as first predictor. Variations in language-induced activation in right inferior frontal gyrus were primarily related to differences in vascular reactivity. Furthermore, several language-activation changes could not be linked to alterations in language proficiency nor vascular reactivity, and were assumed to be caused by unspecified intersession variability. In conclusion, early functional neuroimaging improves outcome prediction of aphasia after stroke. Controlling for cerebrovascular reactivity and unspecified intersession variability may result in more accurate assessment of the relationship between activation pattern shifts and function after stroke.

Increase in sensorimotor cortex response to somatosensory stimulation over subacute poststroke period correlates with motor recovery in hemiparetic patients.

BACKGROUND: . Somatosensory input to the motor cortex may play a critical role in motor relearning after hemiparetic stroke. OBJECTIVE: . The authors tested the hypothesis that motor recovery after hemiparetic stroke relates to changes in responsiveness of the sensorimotor cortex (SMC) to somatosensory input. METHODS: . A total of 10 hemiparetic stroke patients underwent serial functional magnetic resonance imaging (fMRI) during tactile stimulation and testing of sensorimotor function over 1 year-at early subacute, late subacute, and chronic poststroke time points. RESULTS: . Over the subacute poststroke period, increased responsiveness of the ipsilesional SMC to tactile stimulation of a stroke-affected digit correlated strongly with concurrent gains in motor function. Increased responsiveness of the ipsilesional and contralesional SMC over the subacute period also correlated strongly with motor recovery experienced over the first year poststroke. CONCLUSIONS: . These findings suggest that increased responsiveness of the SMC to somatosensory stimulation over the subacute poststroke period may contribute to motor recovery.

Contribution of the left and right inferior frontal gyrus in recovery from aphasia. A functional MRI study in stroke patients with preserved hemodynamic responsiveness.

The relative contribution of dominant and non-dominant language networks to recovery from aphasia is a matter of debate. We assessed with functional magnetic resonance imaging (fMRI) to what extent the left and right hemispheres are associated with recovery from aphasia after stroke. fMRI with three language tasks was performed in 13 aphasic stroke patients and in 13 healthy subjects. Severity of aphasia was examined within 2 months after stroke and after at least 1 year. Recovery of naming ability and scores on the Token Test were correlated with data from fMRI in the chronic phase. A breath-hold paradigm was used to investigate hemodynamic responsiveness. Overall language performance in the chronic phase correlated with higher relative activation of left compared to right perisylvian areas. Recovery of naming ability was positively correlated with activation in the left inferior frontal gyrus (IFG) for semantic decision and verb generation. Recovery on the Token Test was positively correlated with activation in both left and right IFG during semantic decision and verb generation. Hemodynamic response to the breath-hold task was similar in patients and controls. Our study suggests that in the chronic stage after stroke left IFG activity is associated with improvement of picture naming and sentence comprehension, whereas activity in the right IFG may reflect up-regulation of non-linguistic cognitive processing. Altered hemodynamic responsiveness seems an unlikely confounder in the interpretations of fMRI results.

Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma.

Esophageal adenocarcinoma (EA) is characterized by a poor prognosis making the identification of clinically targetable proteins essential for improving patient outcome. We report the involvement of multiple alterations of the MET pathway in EA development and progression. Microarray analysis of Barrett's metaplasia, dysplasia, and EA revealed overexpression of the MET oncogene in EAs but only those with MET gene amplification. STS-amplification mapping revealed that the boundary of the MET amplicon in these EAs is defined by fragile site FRA7G. We also identified an amplicon at 11p13 that resulted in amplification and overexpression of CD44, a gene involved in MET autophosphorylation upon HGF stimulation. Tissue microarrays with phospho-MET-specific antibodies demonstrated a uniformly high abundance of MET activation in primary EA and cells metastatic to lymph nodes but to a lesser extent in a subset of metaplastic and dysplastic Barrett's samples. Increased expression of multiple genes in the MET pathway associated with invasive growth, for example, many MMPs and osteopontin, also was found in EAs. Treatment of EA-derived cell lines with geldanamycin, an inhibitor for tyrosine kinases including MET receptor kinase, reduced cell migration and induced EA cell apoptosis. The data indicate that upregulation of the MET pathway may contribute to the poor outcome of EA patients and that therapeutic agents targeting this pathway may help improve patient survival.

Common fragile sites.

Aphidicolin-induced common fragile sites are site-specific gaps or breaks seen on metaphase chromosomes after partial inhibition of DNA synthesis. These fragile sites were first recognized during the early studies of the fragile X syndrome and are induced by the same conditions of folate or thymidylate stress used to induce the fragile X site. Common fragile sites are normally stable in cultured human cells. However, following induction with replication inhibitors, they display a number of characteristics of unstable and highly recombinogenic DNA. From the many studies that have cloned and characterized fragile sites, it is now known that these sites extend over large regions, are associated with genes, exhibit late or delayed replication, and contain regions of high flexibility but are otherwise unremarkable in sequence. Studies showing that fragile sites and their associated genes are frequently deleted or rearranged in cancer cells have clearly demonstrated their importance in genome instability in tumorigenesis. Yet until recently, very little was known about the molecular mechanisms involved in their stability. Recent findings showing that the key checkpoint genes ATR and BRCA1 are critical for genome stability at fragile sites have shed new light on these mechanisms and on the biological significance of common fragile sites.