Search

BackgroundSex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women.ObjectiveTo compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women.MethodsFrom the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016–2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model.ResultsOf 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57–81) years vs 64.5 (56–75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (p<0.001), and had better collaterals on CT angiography and CT perfusion but similar ischemic core size (relative cerebral blood flow <30%: 7.6 (0–25.2) vs 11.4 (0–38) mL, p=0.22). In 65 propensity-matched pairs, despite similar discharge functional independence rates (women: 42% vs men: 48%, aOR=0.55, 95% CI 0.18 to 1.69, p=0.30), women exhibited worse 90-day functional independence rates (women: 46% vs men: 60%, aOR=0.41, 95% CI 0.16 to 1.00, p=0.05). The reduction in mRS scores from discharge to 90 days also demonstrated a significantly larger improvement in men (discharge 2.49 and 90 days 1.88, improvement 0.61) than in women (discharge 2.52 and 90 days 2.44, improvement 0.08, p=0.036).ConclusionIn a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. Further exploration of this phenomenon to identify target interventions is warranted.Trial registration numberNCT02446587.

•89% of investigated Omicron cases were symptomatic with mild symptoms.•64% of investigated Omicron cases were vaccinated with two doses.•9% and 8.3% of cases reported loss of taste and smell, respectively.•2% of investigated Omicron cases were hospitalized, none admitted to intensive care or deceased.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Présenter les recommandations de pratique clinique (RCP) de la Société française d’otorhinolaryngologie–chirurgie de la face et du cou concernant l’utilisation des AINS dans les infections ORL pédiatriques.

AbstractAdelges tsugaeAnnand (Hemiptera: Adelgidae) has caused extensive mortality of hemlocks (Tsuga(Endlicher) Carrière; Pinaceae) in the eastern United States of America and was discovered recently in Nova Scotia, Canada. We evaluated the use of a Velcro-covered racquetball as a sampling device for A. tsugaewool. Specifically, we report on improvements to an earlier design and evaluate several factors seen in routine sampling that influence the ability of the ball to trap and retain adelgid wool. Velcro was found to be critical for trapping and retaining adelgid wool on the ball during flight and landing. Wooden beads, inserted in the ball, reduced deflection during flight and bounce during landing. Higher probability of trapping wool on the ball was associated with an ascent through the crown, with increasing diameter and density of ovisacs on branch tips, and with increasing abundance of woolly twigs on the forest floor. Higher probability of retaining wool on the ball was associated with Velcro surface area and with amount and location of wool loaded on the ball. These modifications improved detection surveys for A. tsugaein general.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by progressive calcification of spinal tissues; however, the impact of calcification on pain and function is poorly understood. This study examined the association between progressive ectopic spine calcification in mice lacking equilibrative nucleoside transporter 1 (ENT1−/−), a preclinical model of DISH, and behavioral indicators of pain. Methods: A longitudinal study design was used to assess radiating pain, axial discomfort, and physical function in wild-type and ENT1−/−mice at 2, 4, and 6 months. At endpoint, spinal cords were isolated for immunohistochemical analysis of astrocytes (GFAP), microglia (IBA1), and nociceptive innervation (CGRP). Results: Increased spine calcification in ENT1−/−mice was associated with reductions in flexmaze exploration, vertical activity in an open field, and self-supporting behavior in tail suspension, suggesting flexion-induced discomfort or stiffness. Grip force during the axial stretch was also reduced in ENT1−/−mice at 6 months of age. Increased CGRP immunoreactivity was detected in the spinal cords of female and male ENT1−/−mice compared to wild-type. GFAP- and IBA1-immunoreactivity were increased in female ENT1−/−mice compared to wild-type, suggesting an increase in nociceptive innervation. Conclusion: These data suggest that ENT1−/−mice experience axial discomfort and/or stiffness and importantly that these features are detected during the early stages of spine calcification.

Uncivil behavior by a faculty member or student can threaten a classroom environment and make it less conducive to learning. The aim of this study was to explore faculty behaviors that dental faculty and students perceive to be uncivil when exhibited in the classroom and clinic. In 2015, all faculty, administrators, and students at a single academic dental institution were invited to participate in an electronic survey that used a five‐point Likert scale for respondents to indicate their agreement that 33 faculty behaviors were uncivil. Response rates were 49% for faculty and 59% for students. Significant differences were found between student and faculty responses on 22 of the 33 behavioral items. None of the three category composite scores differed significantly for students compared to faculty respondents. The category composite scores were not significantly associated with gender, ethnicity, or age for faculty or students. Overall, this study found significant differences between students and faculty about perceived uncivil faculty behaviors, though not for categories of behaviors.

Le marché des capteurs, classiquement fondé sur l'usage de matériaux inorganiques, s'ouvre désormais de plus en plus largement à des systèmes utilisant des matériaux organiques comme éléments actifs. Cet essor est à mettre en relation avec la diversité chimique des matières plastiques et les nouvelles possibilités de détection associées à l'exploitation des propriétés spécifiques en résultant. Des recherches intensives sont ainsi menées afin de développer le potentiel important des matériaux polymères dans le secteur de la détection et de la mesure. Des exemples issus aussi bien de la recherche que des applications commerciales, et couvrant les principaux domaines d'utilisation sont présentés ici avec les différentes approches pouvant être mises à profit pour les mesures. Des applications très variées sont abordées telles que la détection de composés volatils (solvants, arômes, vapeur d'eau...), les électrodes ou encore les capteurs de force ou de température.

Background:Stroke is a leading cause of death and disability. Early presentation allows clinicians to use tPA for acute stroke therapy to improve outcomes. However, healthcare disparities among different racial/ethnic and gender groups remain a limitation for uniform access to acute stroke therapy. We investigated if such gender and racial disparity exist in tPA administration at a large community comprehensive stroke center (CSC).Methods:Retrospective analysis of a prospective cohort of patients was conducted of patient with acute stroke symptoms who presented to a CSC between May 2018 and May 2022. Demographics, time from last known normal (LKN), rate of tPA administration and door to needle time (DTN) was calculated. Univariate analysis between groups was performed using one-way ANOVA for mean, Kruskal-Wallis test for median and p-value &lt;0.05 was considered significant.Results:Total number of patients presenting to our CSC during the study period with stroke like symptoms was 3901. Of this index cohort, 401 (10.2%) were administered tPA - 207 (51.6%) women and 194 (48.3%) men. Women were significantly older [67.5 ± 15.1 years compared to men, 62.6 ± 13.3 years (p=0.027)]. Average time of LKN to arrival was 124 ± 3.8 min for women and 130 ± 4.9 min for men (p=0.298). Black women’s DTN was longer compared to white women (50.9 ± 3.15 min v. 41.5 ± 2.07 min, p=0. 0103). However, proportion of Black women receiving tPA did not differ from white women [87/770 (11.3%) v. 113/1041 (10.9%), p=0.824]. Race disparity was noted among Black men compared to white men for tPA administration [64/798 (8.0%) v 119/1226 (9.7%), p=0.018]. No gender or racial disparity was noted among tPA recipients regarding mRS at discharge [white men v. white women v. Black men v. Black women - 2 (IQR 1,4) v. 3 (IQR 1,4) v. 3 (IQR 1,4) v. 3 (IQR 1,4), p=0.211].Conclusions:At a large volume, urban, non-academic comprehensive stroke center, overall gender, or racial factors were similar for discharge outcome. However, a delay in tPA administration among Black women and lower incidence of tPA administration in Black men compared to their respective white counterparts need to be validated in larger registries.

La mémorisation d’événements douloureux par les enfants peut entraîner à court et moyen termes une sensibilisation à la douleur suivante, une anxiété, et à plus long terme une phobie ou un évitement des soins. Dès la période néonatale, les facultés de mémorisation implicites, inconscientes, sont actives. Cet article propose une revue de la littérature sur cette question (d’un point de vue médical, neuroscientifique et psychologique), et en souligne les conséquences pour la prise en charge clinique. Nous formulons des recommandations spécifiques adressées aux professionnels pour éviter les conséquences néfastes des douleurs mémorisées, en tenant compte des recherches connues autour de la douleur de l’enfant et sa mémorisation, particulièrement en lien avec la douleur provoquée par les soins. Children’s memories of painful experiences can have consequences for their reaction to their acceptance of later health care interventions. This review surveys research on children’s memory for pain (medical, neuroscientific and psychological point of view), and underlined implications for clinical practice. Specific recommendations to prevent the adverse consequences of memorized pain are offered to clinicians, providing care with reference to current research on pediatric pain and memory, especially in procedural pain.

In a recently published article Sleep et al. (2009) suggested that 30-yr declines in Canada warbler (1975–2005) based on Breeding Bird Survey (BBS) data could be attributed to 30-yr declines in spruce budworm through a series of analyses based principally on correlations. We demonstrate that the relationship does not hold when a longer-term data set (1968–2008) is used for the analysis. Sleep et al. (2009) also demonstrated a positive relationship between correlations of Canada warbler abundance and time and spruce budworm defoliation and time using provincial data sets. We examined the underlying BBS data and found that there were insufficient observations of Canada warbler in the western provinces (Alberta and Manitoba) to support the conclusion because most Canada warbler observations occurred far (>100?km) from any budworm defoliation. As well, we used a density-dependent stochastic population growth model as proposed by Sleep et al. (2009) and found only 2 significant relationships (Nova Scotia, Alberta) between Canada warbler population growth rate and budworm defoliation at the provincial scale. We conclude that little analytical evidence exists to support the idea that Canada warbler decline is a function of spruce budworm decline. © 2011 The Wildlife Society.

To provide a brief overview on trends in common substances of abuse in adolescents, a summary of tools to evaluate adolescent substance abuse in an outpatient setting, and an update of outpatient and inpatient treatment options.

ABSTRACTIn the absence of a specific diagnosis based on serology, chronic Q fever is inevitably fatal. However, diagnosis is often delayed because the test is not widely available. To shorten the diagnostic delay, we adapted a nested-PCR assay with serum as a template and the LightCycler as a thermal cycler, termed LCN-PCR. We retrospectively and prospectively applied this method to samples from 48 patients diagnosed with Q fever endocarditis or vascular infection and to samples from 100 controls with endocarditis caused by other microorganisms. We also prospectively applied this technique to samples from 30 patients treated for a Q fever endocarditis and to samples from 13 patients with a convalescent acute Q fever with ambiguous immunoglobulin G (IgG) phase I titer. LCN-PCR had a specificity of 100%. It was positive only in samples from patients with evolutive Q fever, as none of the samples from patients with a treated chronic Q fever or with a convalescent acute Q fever presented positive results. When performed prospectively on recently stored sera, the sensitivity of LCN-PCR is 64% (7 of 11 samples; P= 0.004), but the efficiency of LCN-PCR was dramatically altered by the storage of specimens at -20°C. High IgG phase I titers decreased the sensitivity of LCN-PCR. A significant difference was observed among LCN-PCR results for sera with IgG phase I titers of =1:25,600 compared to sera with IgG phase I titers of <1:25,600 (0 of 15 samples versus 13 of 33 samples; P= 0.004). In patient samples with titers below 1:25,600 tested prospectively, sensitivity was 100% (7 of 7). The LCN-PCR assay may be helpful in establishing an early diagnosis of chronic Q fever.

The effects of the processing parameters on the weld-line mechanical properties of polystyrene (PS) and polycarbonate (PC) were investigated. PS was very sensitive to the presence of a weld line, showing property reductions of up to 70%. However, this sensitivity was mainly connected to the surface notch at the weld line. When this notch was removed, behavior close to that of unwelded specimens was obtained. The injection temperature was the main processing parameter because it affected the macromolecular diffusion speed and, therefore, influenced the weld quality. A direct relationship between the distance of molecular diffusion and the fracture mechanism was established. PC had a low weld-line sensitivity, despite being an amorphous polymer like PS. The difference between these materials was connected to the different sizes of the surface defects and to the different entanglement densities, which influenced the relaxation time and the global behavior (brittle–ductile). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 644–650, 2004

The effect of processing conditions on the mechanical properties of a weldline in short glass fibre reinforced polypropylene was investigated. It appears that the presence of a weldline has a deleterious effect on the tensile properties, with a serious loss of strength and rigidity. The optimisation of the process parameters through a Taguchi methodology showed some improvement, the properties remaining however quite distant from those of specimens without weldline. The analysis of the fibre arrangement around the weldline gave clues to explain this situation. In the vicinity of the weldline, the typical skin-core structure was deeply disrupted with a skin layer almost non-existent. Therefore, most of the fibres were oriented perpendicularly to the direction of loading, resulting in poor load transfer. Calculations showed that the strength was almost reduced to the transverse resistance of a unidirectional composite because of the very specific orientation of the fibres around the weldline. The generation of a back-flow in the melt, thanks to a differential gate solidification, brought some reorientation of the fibres and some increase in the properties.

Trauma in the adult mammalian central nervous system (CNS) results in devastating clinical consequences due to the failure of injured axons to spontaneously regenerate. This regenerative failure can be attributed to both a lack of positive cues and to the presence of inhibitory cues that actively prevent regeneration. Substantial progress has been made in elucidating the molecular identity of negative cues present at the CNS injury site following injury. In the past several years, multiple myelin-associated inhibitors including Nogo, Myelin-associated glycoprotein and Oligodendrocyte-myelin glycoprotein have been characterized. Furthermore a neuronal receptor complex and several intracellular substrates leading to outgrowth inhibition have been identified. Rapid progress has also been made in identifying the role of neurotrophins and other positive cues in promoting axonal regrowth. The most recent advances in our understanding of positive stimuli for axon regeneration come from transplantation studies at the CNS lesion site. A number of artificial substrates, tissues, and cells including fetal cells, neural stem cells, Schwann cells and olfactory-ensheathing cells have been tested in animal models of CNS injury. Based on our expanded knowledge of inhibitory influences and on the positive characteristics of various transplants, a number of interventions have been tested to promote recovery in models of CNS trauma. These advances represent the first steps in developing a viable therapy to promote axon regeneration following CNS trauma.

Rickettsia typhiand R. felisare flea-transmitted human pathogenic rickettsial species. To investigate the distributional dynamics of these rickettsiae we designed a micro-immunofluorescence assay (MIF) using species-specific monoclonal antibodies (MAbs) applied to flea cryosections. Our assay was performed in less than 3 h and its applicability was demonstrated by the detection of R. typhiin 50 artificially infected human body lice but in none of 50 uninfected lice. With MIF, we identified 31 positive among 32 fleas proven with PCR to be naturally infected with R. felis; and 7 positive among 32 fleas proven with PCR to be naturally infected with R. typhi. No cross-detection was observed with both MAbs. Fresh R. felis-infected fleas were significantly more MIF-positive than long conserved R. typhi-infected fleas (3132 vs. 732, P< 0.01 ). This discrepancy may be linked to degradation of antigens by long-term freezing. For R. typhi-infected fleas, our assay was significantly more efficient when applied to fleas in early stages of infection (less than 15 days) by comparison with fleas frozen more than 20 days after infection (715 vs. 017, P 0.01 ). This difference may be related to an antigenic modification caused by selection pressure in the vector and host process. The sensitivity of the described method did not exceed 47 (715) for R. typhibut, in contrast, was 97 for R. felis. Thus, our method appears to be useful for surveillance in R. felisinfections, but requires further studies for the detection of R. typhi.

Cardiac valve pathology was evaluated in 15 patients with confirmed diagnosis of Bartonella endocarditis. Ten were infected by Bartonella quintana and 5 by Bartonella henselae. Histologic features of these cases, including fibrosis, calcification, vegetation, pattern of inflammation, and vascularization, were compared with those of valves from 25 cases of non-Bartonella endocarditis as controls using a computerized quantitative image analysis. Pathologic and immunohistologic testing for localization of Bartonella species in resected valves included Warthin-Starry stain and polyclonal antibody-based immunodetection. Compared with other cases of infective endocarditis, cases of Bartonella endocarditis are more fibrotic and calcified, less vascularized, with less extensive vegetation and chronic inflammation. These pathologic changes are suggestive of a prolonged infection. Warthin-Starry stain and immunohistologic testing demonstrated the presence of the organism, respectively, in 11 and 10 of the 13 tested valves. Results of both staining methods showed microorganisms in extracellular locations and in regions unaccompanied by inflammation. Pathology and immunohistology may contribute to the etiologic diagnosis of Bartonella endocarditis when serology and molecular techniques are not available.

The human gene encoding alpha1-antitrypsin (alpha1AT, gene symbol PI) resides in a cluster of serine protease inhibitor (serpin) genes on chromosome 14q32.1. alpha1AT is highly expressed in the liver and in cultured hepatoma cells. We recently reported the chromatin structure of a >100 kb region around the gene, as defined by DNase I-hypersensitive sites (DHSs) and matrix-attachment regions, in expressing and non-expressing cells. Transfer of human chromosome 14 by microcell fusion from non-expressing fibroblasts to rat hepatoma cells resulted in activation of alpha1AT transcription and chromatin reorganization of the entire region. In the present study, we stably introduced cosmids containing alpha1AT with various amounts of flanking sequence and a linked neo selectable marker into rat hepatoma cells. All single-copy transfectants with >14 kb of 5' flanking sequence expressed wild-type levels of alpha1AT mRNA in a position-independent manner. In contrast, expression of transgenes containing only approximately 1.5-4 kb of flanking sequence was highly variable. Long-term culture of transfectant clones in the absence of selection resulted in gradual loss of neo expression, but expression of the linked alpha1AT gene remained constant. DHS mapping of cosmid transgenes integrated at ectopic sites revealed a hepatoma-specific chromatin structure in each transfectant clone. The implications of these findings are discussed.

To determine the phylogenetic position of two new rickettsial strains isolated from ticks in China, 16S ribosomal DNA, gltA, and ompA (apart from the tandem repeat units) genes were amplified by PCR and sequenced. The phylogenetic relationships between these strains and other rickettsiae were inferred from the comparison of sequences of the three genes by the parsimony, neighbor-joining, and maximum-likelihood methods. The results demonstrated that the 054 strain, a rickettsia pathogenic in humans, and the HL-93 strain were related and clustered together with Rickettsia japonica. Significant statistical bootstrap values (100 and 92%) supported the nodes in this cluster. Based on previous genotypic and antigenic data and the phylogenetic analysis presented here, the 054 and HL-93 strains should be considered as new species, and we formally propose that they be named "Rickettsia heilongjiangii" and "Rickettsia hulinii," respectively.

ABSTRACTTo determine the phylogenetic position of two new rickettsial strains isolated from ticks in China, 16S ribosomal DNA,gltA, and ompA(apart from the tandem repeat units) genes were amplified by PCR and sequenced. The phylogenetic relationships between these strains and other rickettsiae were inferred from the comparison of sequences of the three genes by the parsimony, neighbor-joining, and maximum-likelihood methods. The results demonstrated that the 054 strain, a rickettsia pathogenic in humans, and the HL-93 strain were related and clustered together withRickettsia japonica. Significant statistical bootstrap values (100 and 92%) supported the nodes in this cluster. Based on previous genotypic and antigenic data and the phylogenetic analysis presented here, the 054 and HL-93 strains should be considered as new species, and we formally propose that they be named “Rickettsia heilongjiangii” and “Rickettsia hulinii,” respectively.

The human gene encoding alpha1-antitrypsin (alpha1AT, gene symbol PI ) is highly expressed in the liver and in cultured hepatoma cells and, to a lesser extent, in macrophages, where transcription originates from a separate upstream promoter. alpha1AT maps to a region of human chromosome 14q32.1 that includes a related serine protease inhibitor (serpin) gene that encodes corticosteroid-binding globulin (CBG). We recently reported the chromatin organization of this approximately 130 kb region, as defined by DNase I hypersensitive sites (DHSs) and matrix-attachment regions, in expressing and non-expressing cells. Furthermore, we demonstrated that transfer of human chromosome 14 from non-expressing fibroblasts to rat hepatoma cells resulted in activation of both alpha1AT and CBG transcription and gene activation was accompanied by long range chromatin reorganization of the entire region. In this study, we transferred human chromosome 14 from fibroblasts to mouse macrophages and documented activation of alpha1AT but not CBG gene expression. RT-PCR experiments indicated that transcription of the human alpha1AT gene in the microcell hybrids initiated at the macrophage promoter. Furthermore, DHS mapping experiments revealed a distinctive chromatin configuration of the locus that resembled the structure found in human macrophage-like cell lines, with many DHSs around alpha1AT but few in CBG. Thus, mouse macrophage cell lines will provide a useful cell type to study the effects of targeted modifications of the human alpha1AT-CBG locus on the regulation of cell-specific gene activity and chromatin structure.

Background:The burden of acute stroke alerts on hospital resources and staff have grown with expanding treatment timelines. The purpose of this project is to develop a nurse activated acute stroke process to accurately capture ischemic and hemorrhage stroke amendable for acute treatment with a two level activation model for 0-4 hours (level 1) and 4-24 hours (level 2) from last known well.Methods:Prospective quality improvement data abstracted on patients in a five-hospital regional telestroke network from October 2020 thru June 2021 with the current single level 24-hour stroke symptom protocol. We retrospectively applied our proposed two level activation model to our data to look for accuracy in stroke diagnosis, proportion of stroke mimics, missed stroke interventions, including intracerebral hemorrhage (ICH), and telestroke provider time spent. We used standard error of mean (SEM) to measure discrepancy of process.Results:A total of 340 stroke activation were captured. Of those, 54% (183/340) were discharged without a stroke diagnosis, 27% (93/340) ischemic, 14% (48/340) transient ischemic attack, 4% (13/340) ICH, 1% (3/340) subarachnoid hemorrhage, and 34% (117/340) arrived in the level 2 window. We excluded 5 ICH patients due to arriving comatose necessitating emergent imaging outside of stroke alert process. Comparing single activation versus two level activation resulted in a reduction of stroke alerts (117 versus 21), telestroke provider time (2501 minutes versus 713 minutes), increase in accurate stroke diagnosis (46% versus 76%), decrease in stroke mimics (54% versus 29%), with 1 missed ICH and 1 missed thrombectomy (5%). The single activation showed a mean 11.11% and SEM of 0.023 compared to the two level activation mean 1.99% and SEM of 0.006.Conclusion:Two level stroke activation process was validated to reduce stroke mimics, improve accurate stroke diagnoses, maximize resources utilization, and capture 95% of all ischemic strokes with large vessel occlusions, therefore the new process will be implemented within our large telestroke system following staff education.

Introduction:Symptomatic intracerebral hemorrhage (sICH) is the primary bad outcome monitored post-alteplase (tPA) administration for treatment of acute ischemic stroke (AIS). Risk of sICH ranges from 2-7% based on patient population. However, little is reported on sICH with the use of telestroke, particularly in the rural setting. We evaluated rates of sICH after tPA administration for our telestroke process in a rural Texas spoke-hub system.Methods:Patient data was prospectively collected from 6/2018 (start of telestroke system) to 5/2021, including age, sex, race/ethnicity, tPA administration, door-to-needle times and sICH. Patients were included if >18 years old and underwent tPA administration at the hub or telemedicine spoke site in a rural Texas healthcare system. Six spokes and one hub were included in this study. Documented sICH was retrospectively abstracted from the database with the primary outcome comparing sICH rate between the hub and spokes. Statistical analysis was conducted by chi-square analysis.Results:A total of 160 patients received tPA at the hub and 239 at the spokes. Four patients suffered sICH at the hub and five at spokes (2.5% v 2.1%, p=0.793). Rates of tPA administration were not significantly different. Demographic comparison between spoke and hub were significantly different. Notably, there was a higher proportion of male and non-white patients at the hub compared to spoke sites, adding to the variation in populations. Patients were older at spoke sites.Conclusion:There was no difference in rates of tPA administration and rate of sICH between hub and spokes in a rural Texas telemedicine program. Rate of sICH in this setting was similar to rate reported in the literature. Furthermore, though there was a statistically significant difference between the populations studied, the likelihood of sICH remained similar. These findings further support the safety of telemedicine use for acute stroke care and tPA administration.

Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1−/−) exhibit progressive ectopic calcification of spinal tissues—a phenotype resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Our objective was to investigate potential calcification of orofacial tissues in ENT1−/−mice. Heads of wild-type mice and ENT1−/−mice from 3 to 17 months were evaluated using microcomputed tomography (μCT). Some heads were decalcified and processed for histological assessment. Other heads were examined using energy dispersive X-ray spectroscopy and micro X-ray diffraction. Using μCT, ENT1−/−mice showed extensive radiopaque lesions within the mandibular symphysis, the severity of which increased with advancing age. Histologically, at 6 months these ectopic radiopacities were found to correspond to acellular, amorphous, eosinophilic material, with no evidence of inflammatory cells. Because lesions were localised to the symphysis, we identified early pathological changes at 3 months and observed that lesions initiated specifically within the fibrocartilage pad. Energy-dispersive X-ray spectroscopy of ectopic lesions revealed large amounts of calcium and phosphorous in a molar ratio of ~1.59, and X-ray diffraction profiles matched that of calcium-deficient hydroxyapatite. This is the first characterisation of ectopic calcifications within the mandibular symphysis of ENT1−/−mice, indicating a role for ENT1 and adenosine metabolism in regulating calcification of fibrocartilaginous tissues. Moreover, these murine lesions resemble areas of dystrophic calcification in the spinal tissues of humans with DISH. Importantly, ectopic calcifications develop in a reproducible temporal pattern within a well-defined anatomical region and, thus, provide a model for determining the cellular and molecular pathways underlying ectopic calcification in DISH and related disorders.

Les complications infectieuses des anévrysmes de l’aorte abdominale sont rares (<5 % des complications). Une infection focalisée de la paroi aortique peut rapidement entraîner une augmentation de taille de cette dernière. Cependant, elles demeurent une cause rare d’anévrysme de l’aorte abdominale (AAA). Les AAA athéromateux préexistants peuvent également être infectés secondairement. Les micro-organismes responsables appartiennent en majorité à la flore endogène du patient et sont plus rarement liés aux soins. Nous rapportons les agents pathogènes responsables d’infection aortique identifiés sur une période de 5 ans au CHU de Marseille.

Matrix-attachment regions (MARs) are DNA elements that are defined by their abilities to bind to isolated nuclear matrices in vitro. The DNA sequences of different matrix-binding elements vary widely. The locations of some MARs at the ends of chromatin loops suggest that they may represent boundaries of individual chromatin domains. As such, MARs may play important roles in regulating transcription and chromatin structure. As a first step towards assessing the roles of MARs in these processes, we assayed DNA sequences from the human serine protease inhibitor (serpin) gene cluster at 14q32.1 for matrix-binding activity in vitro. This approximately 150 kb region contains the cell-specific genes encoding alpha1-anti-trypsin (alpha1AT) and corticosteroid-binding globulin (CBG), as well as an antitrypsin-related sequence termed ATR. A DNase I-hypersensitive site (DHS) map of the locus has recently been described. We report here that the alpha1AT-ATR-CBG region contains five distinct MARs. There is a strong matrix-binding element approximately 16 kb upstream of alpha1AT; three MARs are between ATR and CBG and one MAR is within the CBG gene itself. These MARs were matrix-associated in all cell types examined. DNA sequencing indicated that the serpin MARs contained predominantly repetitive DNA, although the types of DNA repeats differed among the MARs.

The relative efficiency of microcell-mediated chromosome transfer vs. somatic cell hybridization has been determined. The prolonged mitotic arrest generally used to micronucleate donor cells also reduced the fusion efficiency to 1/10th-1/5th of that in whole cell hybridizations. Here we report an alternative micronucleation protocol, involving sequential treatment of the donor cells with Colcemid and cytochalasin B, which yielded micronucleated cells that hybridized with the same efficiency as whole cells. The enucleation, purification, and fusion steps of the microcell procedure have also been refined. By using these modifications the practical yield of microcell hybrid clones can be increased 50- to 100-fold.

Serum albumin gene expression is generally extinguished in hepatoma x fibroblast hybrids. To define the genetic basis of this phenomenon, we screened a panel of hepatoma hybrids retaining different fibroblast chromosomes for albumin production by immunofluorescence. We report that albumin extinction in these clones was strictly correlated with the retention of mouse chromosome 1. Furthermore, albumin was systematically reexpressed in chromosome 1 segregants. These data define a tissue-specific extinguisher locus (Tse-2) that affects albumin gene expression in trans. Two other liver genes, those encoding liver alcohol dehydrogenase and liv-10, were coordinately extinguished with albumin in monochromosomal hybrids that specifically retained mouse chromosome 1.

Somatic cell hybrids formed by fusing hepatoma cells with fibroblasts generally fail to express liver functions, a phenomenon termed extinction. Previous studies demonstrated that extinction of the genes encoding tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and argininosuccinate synthetase is mediated by a specific genetic locus (TSE1) that maps to mouse chromosome 11 and human chromosome 17. In this report, we show that full repression of these genes requires a genetic factor in addition to TSE1. This conclusion is based on the observation that residual gene activity was apparent in monochromosomal hybrids retaining human TSE1 but not in complex hybrids retaining many fibroblast chromosomes. Furthermore, TSE1-repressed genes were hormone inducible, whereas fully extinguished genes were not. Analysis of hybrid segregants indicated that genetic loci required for the complete repression phenotype were distinct from TSE1.

A double-blind crossover design was used to evaluate the effect of two different formulations of prazepam, on motor and cognitive functions and subjective symptoms. Ten healthy male volunteers received 20 mg of prazepam both in tablet and liquid (as drops) formulation, separated by a 1 week interval. All subjects completed a battery of 9 performance tests 2·25 h and 4·75 h after drug intake (corresponding to the times of peak plasma concentration). They also rated themselves on eight visual analogue scales before, 2 h, 4·5 h and 8 h following drug intake. A significant difference between liquid drops and tablets was demonstrated in 4 of the 9 performance tests and 2 of the 8 items of the self rating scales. These results suggest that a single dose of prazepam administered in liquid drop form exhibits greater sedative properties than the same dose administered as tablets in healthy volunteers, probably as a result of more rapid absorption.

The carcinogenetic risk assessment of veterinary drugs has to be envisaged as part of food toxicology. The authors review the recent discoveries which have proved significant for the toxicologist.Tumours arise from an inherited transformation of normal cells through genotoxic, perigenetic and epigenetic processes. Genotoxic mechanisms are best understood and have led to the development of short-term reference tests. The biochemistry of DNA alterations is being unravelled and permits quantitative estimation of carcinogenetic potencies.Work on the role of oncogenes is providing new clues to the understanding the mechanisms of chemical carcinogenesis.Perigenetic processes deal mainly with DNA repair systems and emphasize the complexity of human genome dynamics.Experimental findings about epigenetic mechanisms are still inconclusive as to their practical implications.Abnormal expression of HLA-antigens at the surface of neoplastic' cells has been reported, but its significance is still unknown.In conclusion, the main source of progress in toxicology undoubtedly comes from molecular biology, but experimental results must be interpreted with caution if practical issues are to be derived from them.

Sprague-Dawley male rats were given normal diets (UAR A 03) containing various amounts of gum arabic, sucrose and lignin for eight consecutive weeks. The caloric values of the diets were derived by utilizing the indirect method comparing the slopes from food consumption and weight gain curves. While the data obtained from sucrose diets showed that these diets caused a clear incremental effect on energy production with respect to both test animals and controls, and data from lignin diets were found to produce a negative effect on energy yields, gum arabic diets produced results indicating that at certain levels of intake, gum arabic may contribute energy values slightly superior to those of lignin (0 cal-g), possibly between zero and 1 cal/g. However, it was not found possible to attribute a clear-cut quantitative caloric value to this additive from data obtained in this study.

The photosensitivity of bromodeoxyuridine (BrdU)-substituted cells is known to be markedly enhanced by the fluorochrome Hoechst 33258. Since the incorporation of BrdU into nucleic acids depends upon its prior phosphorylation via thymidine kinase (TK; EC 2.7.1.21), cells deficient in TK activity are refractory to photoinduced killing. These observations suggested that combined treatment with BrdU, Hoechst 33258, and visible light would constitute an efficient selective strategy for the recovery of TK- mutant cells. In this report we describe a single-step selection protocol which reduced the survival of TK+ cells by a factor of 105 without affecting the viability of TK- mutants. This procedure was used to isolate H4IIEC3-derived rat hepatoma cells deficient in TK activity. The properties of several TK- hepatoma clones are discussed.