Enterotoxigenic and Enterohemorrhagic <i>Escherichia coli</i>: Survival and Modulation of Virulence in the Human Gastrointestinal Tract

Enterotoxigenic Escherichia coli (ETEC) and Enterohemorrhagic Escherichia coli (EHEC) are major food‐ and water‐borne pathogens that constitute a serious public health threat in low‐income and developed countries, respectively. Survival and expression of virulence genes in the human digestive tract are key features in bacterial pathogenesis, but the mechanisms behind these processes remain largely unknown due to obvious prohibition of human studies. Use of well‐controlled and multi‐parametric in vitro models can aid in addressing knowledge gaps in ETEC and EHEC pathogenesis. After a general description of the physiopathology of ETEC and EHEC infections, this chapter will give an overview of all the in vitro studies that have investigated the effect of the main physicochemical and biotic parameters of the human gut on pathogen survival and expression of virulence factors. We bring a picture of how ETEC and EHEC are able to adapt to each of the successive environments of the human gastrointestinal tract by reading many cues provided by both the host and the gut microbiota

Influence of Lipid Profiles on the Risk of Hemorrhagic Transformation after Ischemic Stroke: Systematic Review

Background: It has been suggested that low cholesterol levels might be associated with an increased risk of hemorrhagic transformation (HT) in patients with acute cerebral ischemia. We systematically reviewed the literature to determine the influence of lipid profiles on the HT risk. Methods: We searched PubMed from 1966 and EMBASE from 1980 for studies that investigated the association between lipid profiles and HT. We performed a meta-analysis (weighted mean difference method) for the comparison between presence and absence of HT (all or symptomatic) for total, low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol, and triglycerides. Results: Eight studies investigating 1,763 patients were eligible, but none was designed specifically to address this question. All studies recruited acute stroke patients selected on the presumed cause of cerebral ischemia or treatment received. The meta-analysis showed that: (i) patients with all HT had lower LDL cholesterol levels (p = 0.008) but no difference in HDL cholesterol levels (p = 0.066), total cholesterol (p = 0.129) and triglycerides (p = 0.900); (ii) patients with symptomatic HT had lower total cholesterol levels (p = 0.035) but did not differ in LDL (p = 0.056) and HDL cholesterol (p = 0.138) and triglyceride (p = 0.851) levels. Conclusion: HT is associated with baseline total and LDL cholesterol levels, but the mechanism of this association needs to be explored to identify preventive strategies

Detection of Adsorbed Chlordecone on Microplastics in Marine Sediments in Guadeloupe: A Preliminary Study

Plastic pollution in the oceans is recognized as a worldwide problem. Since the 1950s, the production of plastics has been increasing and the first reports of microplastics (particles \u3c 500 μm) in the marine environment began to appear in the 1970s. These particles represent a growing environmental problem due to their dispersion in seawater and marine organisms. Additionally, microparticles in general can adsorb pollutants that will then become bioavailable to organisms by being desorbed during digestion, which could be an important pathway for the contamination of organisms. In Guadeloupe and Martinique, an organochlorine pesticide called “chlordecone” was used from 1972 to 1993 in banana plantations and this very persistent pollutant contaminates soils, rivers, and coastal marine areas and accumulates in marine foodwebs. To examine these issues, we had two goals: 1) to assess the contamination of marine sediments by microplastics surrounding Guadeloupe; and 2) to determine the ability of microplastics to adsorb chlordecone, as has been demonstrated for other organochlorine pollutants. To do so, marine sediments were collected in triplicate from 12 sites in coral reef environments around the island. Microplastics from each sample were then enumerated by size, color and shape under a binocular microscope. The results indicate that microplastics are found in all the studied sites and that their distribution could be linked to marine currents or proximity to areas of significant human activities (port activities, agglomeration, etc.). Finally, our preliminary results indicated that chlordecone could be adsorbed onto microplastics, with a concentration ranging from 0.00036—0.00173 µg/µg of microfilter

Stroke in women — from evidence to inequalities

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke — including diabetes mellitus and atrial fibrillation — are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials — despite governmental actions highlighting the need to include both men and women in clinical trials — resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women

Cerebral microbleeds a guide to detection and interpretation

Cerebral microbleeds (CMB) are increasingly recognized neuroimaging findings, occurring with cerebrovascular disease, dementia, and normal aging. Recent years have seen substantial progress, particularly in developing newer MRI methodologies for CMB detection and applying them to population-based elderly samples. This review focuses on these recent developments and their impact on two major questions: how CMB are detected, and how they should be interpreted. There is now ample evidence that prevalence and number of detected CMB varies with MRI characteristics such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and post-processing, underlining the importance of MRI technique in interpreting studies. Recent investigations using sensitive techniques find the prevalence of CMB detected in community-dwelling elderly to be surprisingly high. We propose procedural guidelines for identifying CMB and suggest possible future approaches for elucidating the role of these common lesions as markers for, and potential contributors to, small vessel brain disease

Prevalence of Clinical and Neuroimaging Markers in Cerebral Amyloid Angiopathy: A Systematic Review and Meta-Analysis

BACKGROUND: Limited data exist regarding the prevalence of clinical and neuroimaging manifestations among patients diagnosed with cerebral amyloid angiopathy (CAA). We sought to determine the prevalence of clinical phenotypes and radiological markers in patients with CAA. METHODS: Systematic review and meta-analysis of studies including patients with CAA was conducted to primarily assess the prevalence of clinical phenotypes and neuroimaging markers as available in the included studies. Sensitivity analyses were performed based on the (1) retrospective or prospective study design and (2) probable or unspecified CAA status. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using the Cochran Q and I2 statistics. RESULTS: We identified 12 prospective and 34 retrospective studies including 7159 patients with CAA. The pooled prevalence rates were cerebral microbleeds (52% [95% CI, 43%-60%]; I2=93%), cortical superficial siderosis (49% [95% CI, 38%-59%]; I2=95%), dementia or mild cognitive impairment (50% [95% CI, 35%-65%]; I2=97%), intracerebral hemorrhage (ICH; 44% [95% CI, 27%-61%]; I2=98%), transient focal neurological episodes (48%; 10 studies [95% CI, 29%-67%]; I2=97%), lacunar infarcts (30% [95% CI, 25%-36%]; I2=78%), high grades of perivascular spaces located in centrum semiovale (56% [95% CI, 44%-67%]; I2=88%) and basal ganglia (21% [95% CI, 2%-51%]; I2=98%), and white matter hyperintensities with moderate or severe Fazekas score (53% [95% CI, 40%-65%]; I2=91%). The only neuroimaging marker that was associated with higher odds of recurrent ICH was cortical superficial siderosis (odds ratio, 1.57 [95% CI, 1.01-2.46]; I2=47%). Sensitivity analyses demonstrated a higher prevalence of ICH (53% versus 16%; P=0.03) and transient focal neurological episodes (57% versus 17%; P=0.03) among retrospective studies compared with prospective studies. No difference was documented between the prevalence rates based on the CAA status. CONCLUSIONS: Approximately one-half of hospital-based cohort of CAA patients was observed to have cerebral microbleeds, cortical superficial siderosis, mild cognitive impairment, dementia, ICH, or transient focal neurological episodes. Cortical superficial siderosis was the only neuroimaging marker that was associated with higher odds of ICH recurrence. Future population-based studies among well-defined CAA cohorts are warranted to corroborate our findings

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage with cerebral amyloid angiopathy: model development and diagnostic test accuracy study

BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.METHODS: We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.FINDINGS: Among 110 adults (median age 83 years [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86-0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78-100).INTERPRETATION: The CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.FUNDING: UK Medical Research Council, The Stroke Association, and The Wellcome Trust.</p

ESO Guideline on Covert Cerebral Small Vessel Disease

'Covert' cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.Peer reviewe

Women in the European Stroke Organisation: One, two, many… – A Top Down and Bottom Up approach

Background: An increasing proportion of physicians are women, yet they still face challenges with career advancement. In 2014, the European Stroke Organisation established the goal of increasing the number and participation of women within the society using a Top Down and Bottom Up approach. The ‘Women’s Initiative for Stroke in Europe’ was created the same year by a group of women active within the organisation. We aimed to assess the current status of women in European Stroke Organisation, and to explore the change in sex differences after the introduction of focused approaches to address disparities in 2014. Methods: Using organisational records, we collected data on sex differences in core activities from 2008 up to 2017 including membership, participation in conferences, courses and in the official journal of the society, and positions of seniority and leadership. We estimated sex distribution differences in each of the activities from 2014 to date. Results: In 2017, the proportion of female members was 40%, while 24% of fellows, 22% of the executive board and 19% of the editorial board in the official journal of the society were women. From 2014 to 2017, there was a significant increase in the proportion of female members (p 1⁄4 0.0002) and in women participating in the annual conference as faculty (p 1⁄4 0.001). There was no significant change in the sex distribution among the faculty members in junior edu- cational activities (27%) or fellows. Interpretation: In 2017, the proportion of women holding positions of seniority and leadership is still significantly lower to the proportion of women attending educational activities. Transparent data on sex distribution will assist implementing tailored programmes to achieve progress against sex-based barriers