Epidemiology of ischaemic stroke subtypes: do differences in epidemiology provide evidence for a distinct lacunar arterial pathology?

Background Lacunar ischaemic stroke accounts for around one quarter of all strokes, and is presumed to result from the occlusion of a single perforating artery supplying the deep subcortical areas of the brain. The underlying arterial pathology is poorly understood, but is thought to differ from the atherothrombotic processes that occlude larger intra- and extracranial arteries causing most other ischaemic stroke subtypes. Progress in understanding the aetiology of lacunar stroke has been limited by the lack of informative autopsy studies, and the difficulties in studying small blood vessels using brain imaging. One alternative approach is to compare the epidemiology of ischaemic stroke subtypes, since differences in the epidemiology may reflect and inform about different underlying pathologies. Methods I performed two systematic literature reviews to identify studies presenting data on (1) the risk factors for, and (2) the outcome of, different ischaemic stroke subtypes. I extracted relevant data from included studies and performed a series of meta-analyses comparing risk factor profiles, and risks of death, recurrent stroke and myocardial infarction (MI) in patients with lacunar versus non-lacunar ischaemic stroke. To address some of the unanswered questions and controversies surrounding the causes of ischaemic stroke we set up the Edinburgh Stroke Study (ESS), which I co-ordinated. We recruited patients with stroke and transient ischaemic attack seen at our hospital between 2002 and 2005, and followed them for 1-4 years for death, recurrent stroke and MI. To overcome the methodological limitations of the studies included in my reviews and of my meta-analyses, I carried out a large collaborative individual patient data analysis in which I combined data from five stroke registries - including the ESS - that had used similar robust methodology, and performed a series of analyses comparing the risk factor profiles of patients with lacunar versus nonlacunar ischaemic stroke. In an updated meta-analysis, I combined this data with existing published studies that had used an unbiased method of classifying ischaemic stroke subtypes. Using the ESS data, I compared the risks of recurrent stroke and MI, and patterns of recurrent stroke subtypes in patients with lacunar versus nonlacunar stroke. Results In my systematic review of risk factors I found evidence of classification bias in many studies, where systematic error was introduced through the use of classification methods that included risk factors in the definitions of stroke subtypes. This led to overestimation of some risk factor-stroke subtype associations and, in particular, to apparently stronger associations between hypertension and diabetes and lacunar compared with non-lacunar ischaemic stroke. When I included only unbiased studies, I found a significantly reduced prevalence of atrial fibrillation (AF) and severe carotid stenosis and a trend towards a reduced prevalence of ischaemic heart disease (IHD) in lacunar patients. I found a very slight excess of hypertension among lacunar patients, but no difference in the prevalence of diabetes, or any other risk factor studied. In my collaborative individual patient data analysis, I confirmed a significantly lower prevalence of severe carotid stenosis, AF and previous IHD in patients with lacunar ischaemic stroke, but found no difference in the prevalence of hypertension, diabetes, or any other risk factor studied, even after adjusting for confounding factors. These results were largely confirmed in my updated metaanalysis, although there was a slight excess of hypertension among lacunar compared with non-lacunar ischaemic strokes. In my systematic review of outcome after lacunar versus non-lacunar ischaemic stroke, I found a lower risk of death following lacunar compared with non-lacunar stroke which attenuated but persisted long-term; a higher recurrent stroke risk in non-lacunar patients during the first month only; and limited data on recurrent stroke subtypes suggesting that ischaemic stroke subtypes may breed true to type. Data on MI risk were extremely sparse. My analyses of data from the ESS showed no difference overall in risk of recurrent stroke between patients with lacunar versus non-lacunar ischaemic stroke, but some evidence for a lower very early recurrence risk among lacunar patients. There was evidence that recurrent stroke subtypes breed true, since patients with a lacunar stroke at baseline were much more likely to have a lacunar than a non-lacunar recurrence. We identified five times as many MI events following stroke than have been previously reported in the published literature, and found a non-significantly reduced risk of MI in patients with lacunar compared with non-lacunar ischaemic stroke. Conclusions My comparisons of the epidemiology of lacunar versus non-lacunar ischaemic stroke subtypes revealed differences in the risk factor profiles and risks of recurrent stroke and myocardial infarction which suggest that a distinct, nonatherothrombotic arteriopathy underlies many lacunar ischaemic strokes. My analyses of recurrent stroke subtype patterns suggest that recurrent ischaemic strokes subtypes tend to breed true, providing further support for a distinct lacunar arteriopathy. Contrary to widespread belief, hypertension and diabetes do not appear to be more important in the aetiology of lacunar stroke than in other types of ischaemic stroke. These findings support other lines of evidence for a distinct lacunar arteriopathy, and highlight the need for further research into the aetiology of lacunar ischaemic stroke

Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

Effect of lifelong overexpression of HSP70 in skeletal muscle on age‐related oxidative stress and adaptation after nondamaging contractile activity

[EN] Skeletal muscle aging is characterized by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe injury. The ability of muscles of old mice to produce heat shock proteins (HSPs) in response to stress is severely diminished. Studies in our laboratory using HSP70 overexpressor mice demonstrated that lifelong overexpression of HSP70 in skeletal muscle provided protection against damage and facilitated successful recovery after damage in muscles of old mice. The mechanisms by which HSP70 provides this protection are unclear. Aging is associated with the accumulation of oxidation products, and it has been proposed that this may play a major role in age-related muscle dysfunction. Muscles of old wild-type (WT) mice demonstrated increased lipid peroxidation, decreased glutathione content, increased catalase and superoxide dismutase (SOD) activities, and an inability to activate nuclear factor (NF)- B after contractions in comparison with adult WT mice. In contrast, levels of lipid peroxidation, glutathione content, and the activities of catalase and SOD in muscles of old HSP70 overexpressor mice were similar to adult mice and these muscles also maintained the ability to activate NF- B after contractions. These data provide an explanation for the preservation of muscle function in old HSP70 overexpressor mice.—Broome, C. S., Kayani, A. C., Palomero, J., Dillmann, W. H., Mestril, R., Jackson, M. J., McArdle, A. Effect of lifelong overexpression of HSP70 in skeletal muscle on age-related oxidative stress and adaptation after nondamaging contractile activity

Associations of clinical stroke misclassification (‘clinical-imaging dissociation’) in acute ischemic stroke

Background: Up to 20% of lacunar infarcts are misdiagnosed as cortical infarcts clinically and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this ‘clinical-imaging dissociation’. Methods: Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts, proximity to cortex for small subcortical infarcts. We examined factors associated with clinical-imaging dissociation. Results: 137 patients with a mild cortical or lacunar syndrome had an acute ischaemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61 to 130.1), left hemisphere location (OR 8.95, 95% CI 1.23 to 64.99) and diabetes (OR 17.1, 95% CI 1.49 to 196.16) predicted clinical-imaging dissociation. On multivariate analysis of all 137 patients, clinical-imaging dissociation was associated with diabetes (OR 7.12, 95% CI 1.86 to 27.2). Conclusions: Clinical-imaging dissociation occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimised in research by verification with high sensitivity imaging

Gender and class in Britain and France

This article examines the treatment of women's oppression in feminist theory, focusing on the engagement of second wave feminists with the concept of class and its relation to gender. This examination is carried out with reference to British and French feminisms, identifying the main trends and shifts that have developed over the last 35 years and noting that while these are undoubtedly influenced by a particular national context they are also shaped by increasing European integration and social, political and cultural exchanges at a global level. The authors find evidence of a number of similarities in the questions that feminist theorists have asked in Britain and France but also demonstrate that there are significant differences. They conclude that areas of convergent theoretical interests will extend along with cross-border flows of peoples and information

An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor

Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology

Análise das limitações para inserção dos homens nos serviços de saúde: revisão de literatura: Analysis of limitations for the insertion of men in health services: literature review

Objetivo: O presente estudo objetiva descrever, por meio da literatura, as limitações para inserção dos homens nos serviços de saúde, à luz da política de atenção integral à saúde do homem. Metodologia: O método de construção dessa pesquisa foi o de revisão integrada, aliada à pesquisa bibliográfica, revisão de literatura, com métodos dedutivos, análises descritivas de natureza qualitativa. Os resultados foram obtidos com a coleta de dados por meio de artigos científicos, teses, dissertações e livros divulgados publicados em periódicos indexados nas bases de dados do SCIELOme LILACS entre os meses de novembro de 2021 a abril de 2022. Resultados: No total, houve 35 menções às barreiras limitantes para o processo de inserção dos homens aos serviços de saúde. Destas, três (3) estão ligadas a limitações da própria instituição de saúde ou a gestão e duas (2) estão ligadas a limitações intrínsecas do indivíduo. As barreias mais mencionadas neste trabalho foram as limitações do próprio indivíduo (n=10), entraves importantes na implantação do processo de cuidado, seguido do despreparo da Unidades Básicas de Saúde para atender o público masculino (n=9) e das ações em saúde não centralizadas no público masculino (n=7). Conclusão: As barreiras mais limitantes para o acesso dos homens aos serviços de saúde foram, em sequência: 1) limitações do próprio indivíduo; 2) despreparo da Unidades Básicas de Saúde para atender o público masculino; 3) ações em saúde não centralizadas no pú­blico masculino; 4) falta de capacitação profissional; e 5) procura tardia ao serviço de saúde. As limitações encontradas neste trabalho são indicadores importantes no aumento da taxa de adoecimento da população masculina