Access to mechanical thrombectomy for cerebral ischaemia: A population-based study in the North-of-France.

BACKGROUND AND PURPOSE: Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. METHOD: We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. RESULTS: During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. CONCLUSION: The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.

MRI for in vivo diagnosis of cerebral amyloid angiopathy: Tailoring artifacts to image hemorrhagic biomarkers.

Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature.

Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI).

AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD: Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS: Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION: In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

Blood biomarkers in the early stage of cerebral ischemia.

In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed.

Mechanism and dynamics of fatty acid photodecarboxylase.

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser x-ray sources highlighted an unusual bent shape of the oxidized flavin chromophore. We demonstrate that decarboxylation occurs directly upon reduction of the excited flavin by the fatty acid substrate. Along with flavin reoxidation by the alkyl radical intermediate, a major fraction of the cleaved carbon dioxide unexpectedly transformed in 100 nanoseconds, most likely into bicarbonate. This reaction is orders of magnitude faster than in solution. Two strictly conserved residues, R451 and C432, are essential for substrate stabilization and functional charge transfer.

Plasma levels of VLDL- + LDL-cholesterol, HDL-cholesterol, triglycerides and apoproteins B and A-I in a healthy population--influence of several risk factors.

Plasma apo B and apo A-I were determined in 477 subjects (206 males and 271 females) by laser immuno-nephelometry. Measurements of VLDL- + LDL-cholesterol, HDL-cholesterol and triglycerides were done simultaneously. VLDL- + LDL-cholesterol and apo B values were similar in males and females and increased with age. HDL-cholesterol and apo A-I values were higher in females but stable with age. Different regression curves (HDL-cholesterol vs apo A-I) were obtained in males and females and a negative correlation was found between HDL-cholesterol or apo A-I and triglycerides. Increased body weight was associated with higher values of VLDL- + LDL-cholesterol, apo B and triglycerides in both sexes but lower values of HDL-cholesterol and apo A-I essentially in males. Finally, the study provides evidence of a relationship between smoking and alcohol consumption on the one hand, and HDL-cholesterol and apo A-I on the other.

[Lipoprotein electrophoresis on acrylamide-agarose plates, with discontinuous acrylamide gradient]. / Electrophorese des lipoproteines seriques sur plaque de gel d'acrylamide-agarose, en gradient discontinu d'acrylamide.

We describe a modified lipoprotein electrophoresis on acrylamide gel. The lipoproteins, prestained with Sudan Black, are separated by running on acrylamide-agarose gels, with two different concentrations of acrylamide and a constant concentration of agarose. The sera are deposited in the first gel (2% acrylamide). Chylomicrons remain at origin and other lipoproteins run through the first gel to the second one (3% acrylamide gel). VLDL stays at the junction of both gels, LDL and HDL are separated in the 3% acrylamide gel. By this technique, we were able to detect an increase of Lp(a) and to identify the different types of hyperlipoproteinemia. After running, the plates can be treated for storage.

Epidemiology of single and multiple species of helminth infections among school children in Busia District, Kenya.

OBJECTIVE: To describe the patterns of single and multiple helminth infection in school children from Busia District, Kenya. DESIGN: A cross-sectional school survey using a randomly selected sample, forming part of an evaluation study of an ongoing deworming project. SETTING: Budalangi and Funyula divisions of Busia District, Western Province, Kenya. SUBJECTS: One thousand seven hundred and thirty eight school children aged 8-20 years randomly selected from those enrolled in standards 3-8 in 25 randomly selected primary schools. RESULTS: Overall, 91.7% of children were infected with either hookworm, Ascaris lumbricoides, Trichuris trichiura or Schistosoma mansoni. Infection prevalence of each species varied considerably among schools, being most marked for S. mansoni, where prevalence was highest in lakeshore schools. Children were typically infected with two or more species of helminth. Infection intensity of each geohelminth species was higher in school children infected with multiple species than in school children with single species infections, and intensity increased with the number of concurrent infections. CONCLUSION: Helminth infections are exceptionally common among school children in Busia district, thus confirming the good sense of the school-based approach adopted by the control programme. The study also shows that there is an association between concurrent infection and the intensity of infection, which may have consequences for nutritional and educational status.

[Diagnosis of type III hyperlipoproteinemia: contribution of an air-driven ultracentrifuge associated with an original tube-slicer (author's transl]. / Diagnostic de l'hyperlipoprotéinémie de type III: apport d'une ultracentrifugeuse à turbine à air associée à un coupe-tube de conception originale.

Diagnosis of type III hyperlipoproteinemia requires preparative ultracentrifugation in order to measure the cholesterol/triglyceride molar ratio into isolated d less than 1.006 lipoproteins. The authors describe an ultracentrifugation micromethod which needs 600 microliter of serum and can be completed within three hours (Airfuge Beckman instruments). An original tube-slicer allows the separation of the d less than 1.006 lipoproteins located into top fractions. This simple micromethod might confirm diagnosis of type III in patients and would be useful for clinical laboratories.

[Bird headed dwarfism in Seckel syndrome. Nosologic difficulties]. / Le nanisme à tête d'oiseau ou syndrome de Seckel. Difficultés nosologiques.

Seckel syndrome is a clinical picture which associates four main features: intrauterine growth retardation, microcephaly often due to craniosynostosis, orofacial dysmorphology with bird headed appearance and variable mental retardation which is present after several months. Malformations of the central nervous system, limbs, and hair, may also be observed. On the basis of 78 cases reported in the literature, the authors discuss the validity of the morphological features of the syndrome. It is likely that the variability in the expressivity of each symptom explains its heterogeneity. According to the radiological abnormalities, three different forms of the syndrome have been described. Seckel syndrome is a genetic disorder with autosomal recessive inheritance. Its ethiopatogeny remains unclear. Hopefully linkage studies will allow to map the gene in order to determine the underlying abnormal protein.

[Value of the analysis of lipoproteins after myocardial infarction]. / Intérêt de l'analyse des lipoprotéines après infarctus du myocarde.

Lipid and apoprotein constituents of plasma lipoproteins were determined in survivors of myocardial infarction in relation to a control population. Compared to controls, the patients had significantly higher concentrations of total triglycerides, VLDL + LDL - cholesterol and apo-B, but lower concentrations of HLD-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apo A-I and A-II. Survivors with normal lipaemia also had perturbations in HDL and subfractions (HDL2 and HDL3). In addition, the patients exhibited a significant decrease in HDL-cholesterol to VLDL + LDL-cholesterol ratio and in apo A-I to apo-B ratio. These results demonstrate the importance of determining all lipoproteins in future biological studies to evaluate more precisely the relationship between these compounds and atherosclerosis.

Binding to nucleophosmin determines the localization of human and chicken ARF but not its impact on p53.

The ARF tumour suppressor gene encodes a small highly basic protein whose known functions are largely determined by the amino acids encoded within the first exon. In mammals, the protein incorporates additional residues specified by an alternative reading frame in the second exon of INK4a, but this arrangement does not apply to the chicken homologue. In exploring the intracellular localization of chicken p7(ARF), we found that while the FLAG- and HA-tagged versions localize in the nucleolus, in line with mammalian ARF, the GFP-tagged version is excluded from the nucleolus. Here we show that irrespective of the source or composition of the ARF fusion proteins, versions that accumulate in the nucleolus share the ability to bind to nucleophosmin (NPM). Depletion of NPM with siRNA results in the re-location and destabilization of nucleolar forms of ARF but has little effect on the location or stability of a nucleoplasmic form of ARF. Importantly, knockdown of endogenous NPM does not impair the ability of ARF to bind to MDM2 and stabilize p53. These findings support the view that nucleolar localization determines the stability of ARF but not its primary function.

Use of meiotic pachytene stage of spermatocytes for karyotypic studies in insects.

Coleopterans represent by far the largest animal group, with more than 300,000 identified species. Only little progress in their chromosome analysis has been accomplished during recent decades, compared with that made in vertebrate cytogenetics. Both the small size of their genome and the difficulty of obtaining mitotic cells with nice chromosomes have limited the application of conventional techniques, such as chromosome banding. A method for obtaining chromosome banding on well-spread bivalents from the pachytene stage of the meiotic prophase, the most frequent stage in young imagines, is described. It makes possible the identification of all bivalents and the establishment of the karyotype with greater ease and accuracy than with mitotic cells. In addition, it gives some insight into chromosome organization at a stage when autosomes are assumed to undergo an intense transcriptional activity. The results of the technique, which was successfully applied to many species, are described here in two of them, Cetonia aurata and Adesmia montana as examples.

Cytogenetic repartition of chicken CR1 sequences evidenced by PRINS in Galliformes and some other birds.

Chicken repeat 1 (CR1) belongs to the non-long repeat class of retrotransposons. Nearly 100000 repeats interspersed in the chicken genome are subdivided into at least six distinct subfamilies, each 300 bp long and all sharing substantial sequence similarity. CR1-like elements were found in genomes from invertebrates to mammals, suggesting their importance for genome structure and/or function. Moreover, numerous data support the hypothesis of their implication in regulation of gene expression. So, the chromosomal distribution of these CR1 sequences in vertebrates is of great interest to improve our knowledge about the genome structure, function and evolution. A comparison of the cytogenetic distribution of CR1 sequences was performed by PRINS using consensus chicken primers on the chromosomes of chicken and species of several bird orders: Galliformes, Anseriformes, Passeriformes and Falconiformes. The study revealed that CR1 repeats are spread over nearly all chicken chromosomes with a higher density on the macrochromosomes and in particular with hot spots on subtelomeric regions of chromosome 1, 2, 3q, 4q, 5q. Their distribution on the macrochromosomes forms a kind of banding pattern, which was not systematically matched with R- or G-banding. This banding pattern appears to be conserved on the chromosomes of the Galliformes studied, irrespective of their karyotypes, rearranged or not. CR1 primers also show similar signals on the chromosomes of birds phylogenetically more distant (Anseriformes, Passeriformes and Falconiformes). This fact confirms the importance of these sequences at the large scale of bird evolution and in the chromosomal structure. The location of CR1 sequences, and in particular of the hot spots, mainly within the richest CG areas are in conformity with the data on an epigenetic role of these highly conserved sequences.

Subcellular trafficking of growth hormone receptor and Jak2 under ligand exposure.

In CHO cells, growth hormone stimulation induces a rapid degradation of mature and precursor forms of its receptor, but does not affect Jak2 concentration. Confocal analysis of the receptor and of specific markers for subcellular localization shows that ligand exposure induced the disappearance of cell surface receptors, while some receptors seem to be sequestered in the endoplasmic reticulum (ER) and in the Golgi apparatus. Using a tagged version of Jak2 (HA-Jak2) and double immuno-fluorescence analysis with anti-HA and anti-Stat5 antibodies, we demonstrate that ligand stimulation induces Stat5 nuclear accumulation while Jak2 remains localized in the cytoplasm. Immunoblots of nuclear extracts confirm the Jak2 nuclear exclusion.

[Platelet aggregation and platelet and plasma fatty acid levels in the child with migraine. Apropos of 40 case reports]. / Etude de l'agrégation plaquettaire et dosage des acides gras plaquettaires et plasmatiques chez l'enfant migraineux. A propos de 40 observations.

The authors have studied platelet aggregability in the presence of ADP and collagen in a population of 40 migrainous children between migraine attacks. They completed their investigations by a qualitative dosage in platelets and in plasma of fatty acids, precursors of prostaglandins, which are well known for their importance in platelet aggregation and vasculomotor reactions. This study was made in comparison with an equal number of controls chosen from the same age-groups. The authors didn't find the hyperaggregability observed by other authors in grown-up populations. They noticed a light-but statistically significant-diminution of linoleic acid in the platelets and in the plasma. A study based on observations does not entirely confirm for certain an alimentary origin.