Improved algorithm with adaptive regularization for tomographic reconstruction of gas distributions using DOAS measurements.

Differential optical absorption spectroscopy (DOAS) is notably well suited for the retrieval of UV-absorbing trace gases present in the atmosphere. We combine multi-axis DOAS observations to perform a tomographic reconstruction of the distribution of gases emitted from different sources. We use a new algorithm based on a regularized minimization approach embedding key physical aspects of the solution to constrain the inversion. In this work, we take into account that the spatial sampling of the plume being scanned by the instruments is not homogeneous. Therefore, we introduce an adaptive approach with a locally tuned regularization weight according to the uncertainty levels introduced by the sampling scheme. We tested our approach on reconstructions of simulated gas distributions and different configurations applicable to multi-axis DOAS. Finally, our approach is applied to experimental data for the retrieval of the distribution of ${\rm NO}_2$NO2 within a plume cross section emitted from a group of stacks.

Intravenous thrombolysis in wake-up stroke: real-world data from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: Data on real-world experience with intravenous thrombolysis (IV tPA) in wake-up stroke (WUS) are limited. The aim of this study was to examine the efficacy and safety of IV tPA in patients with WUS included in the Austrian Stroke Unit Registry. METHODS: Data from a large nationwide stroke unit registry including initial stroke severity, vascular risk factors, comorbidities, treatment with IV tPA, symptomatic intracerebral haemorrhage (sICH) and functional outcome were extracted and analysed. Patients with WUS were compared with patients with known-onset stroke (KOS) regarding the frequency of IV tPA treatment, neurological improvement (National Institutes of Health Stroke Scale score ≥4), sICH and 3-month functional outcome by modified Rankin Scale score using standard statistical tests. RESULTS: A total of 107 895 stroke patients entered the analysis, including 12 534 with WUS and 91 899 with KOS. Altogether, 904 (7.2%) patients with WUS received IV tPA as compared with 16 694 (18.2%) patients with KOS. Patients with WUS who received IV tPA treatment had twofold higher initial National Institutes of Health Stroke Scale score (median 8 vs. median 4) as compared with patients with KOS. There was no statistical difference in functional outcome by modified Rankin Scale score 0-1 at 3 months between patients with WUS and patients with KOS treated with IV tPA (adjusted odds ratio, 1.08; 95% confidence interval, 0.9-1.31). Also, the rate of sICH did not differ (4.1% vs. 4%, P = 0.852). CONCLUSIONS: In this large non-randomized comparison, the safety and efficacy of IV tPA in patients with WUS in the real-world setting seems to be comparable to patients with KOS.

Joint Theoretical and Experimental Study on the La Doping Process in In2O3: Phase Transition and Electrocatalytic Activity.

In2O3 and La3+-doped In2O3 nanostructures were synthesized through a facile and fast chemical route based on the microwave-assisted hydrothermal method combined with rapid thermal treatment in a microwave oven. The presence of the La3+ doping process modifies the size and morphology of the In2O3 nanostructures and also stabilizes the rhombohedral (rh) In2O3 phase with respect to the most stable cubic (bcc) polymorph. X-ray diffraction (XRD) patterns and Rietveld refinements, Raman, UV-vis, and energy dispersive X-ray (EDX) spectroscopies, transmission electron (TEM) and field-emission scanning electron (FE-SEM) microscopies, as well as PL emissions have been performed. To complement and rationalize the experimental results, first-principle calculations, based on density functional theory, are carried out to obtain the formation energies of the In2O3 and bcc- and rh-In2O3-doped phases, their geometry and electronic properties. Theoretical results are able to explain the relative stabilization of the rh-phase with respect to the bcc-phase based on the analysis geometry changes and the electronic redistribution induced by the La3+ doping process. In addition, Wulff construction is employed to match the theoretical and experimental morphologies of the cubic phase. The synthesized samples were applied for the O2 evolution reaction (OER). The La3+-doped In2O3 film presents superior electrocatalytic activity, with an onset potential lower than the undoped In2O3 film that can be associated with the increase in electron density caused by the La3+ doping process. This study provides a versatile strategy for obtaining In2O3 and La3+-doped In2O3 nanostructures for practical applications.

Familial hypercholesterolaemia in patients with ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Identification of patients with familial hypercholesterolaemia (FH) is a prerequisite for the appropriate management of their excess cardiovascular risk. It is currently unknown how many patients with acute ischaemic stroke or transient ischaemic attack (TIA) are affected by FH and whether systematic screening for FH is warranted in these patients. METHODS: The prevalence of a clinical diagnosis of FH was estimated in a large representative series of patients with acute ischaemic stroke or TIA (ABCD2 score ≥ 3) using the Dutch Lipid Clinic Network Algorithm (DLCNA; possible FH ≥3, probable/definite FH ≥6). RESULTS: Out of 1054 patients included in the present analysis, 14 had probable/definite FH (1.3%; 95% confidence interval 0.6-2.0) and 107 possible FH (10.2%; 8.4-12.0) corresponding to an overall prevalence of potential FH of 11.5%. Prevalences were even higher in patients with stroke/TIA manifestation before age 55 in men or 60 in women (3.1%, 0.6-5.6; and 13.1%, 8.3-17.9) and those with a prior history of cardiovascular disease (2.6%, 0.9-4.3; and 15.1%, 11.3-18.9). Of note, in two-thirds of our patients with probable/definite and possible FH, stroke or TIA was the initial clinical disease manifestation. CONCLUSIONS: The frequency of potential FH, based on clinical criteria, in patients with acute ischaemic stroke or TIA was 11.5% and that of probable/definite FH (1.3%) was similar to recently reported counts for patients with acute coronary syndrome (1.6%). FH screening using the DLCNA is feasible in clinical routine and should be considered as part of the usual diagnostic work-up.

Effect of Mercaptosuccinic Acid Stabilizer Agent on the Optical Properties of Colloidal CdTe Quantum Dots.

In the present work, we report on the positive effect of mercaptosuccinic acid (MSA) stabilizer agent on the optical features of colloidal CdTe quantum dots (QDs). With this aim, we performed some spectroscopic measurements such as steady-state absorption and fluorescence, fluorescence quantum yield and time-resolved photoluminescence for five MSA-capped CdTe QD samples with different synthesis times. The first general aspect to highlight is that the QDs' average size increased with synthesis time (from 30 to 150 min) while the size dispersion decreased due to the Ostwald ripening mechanism. Second, comparing the optical properties of CdTe QDs obtained from the same synthesis route, we show that MSA stabilizer agent enhanced the optical properties of CdTe QDs as compared with other widely used stabilizer agents such as GSH and TGA. We ascribe this outcome to reduction of the number of surface defects of the CdTe QDs because the MSA stabilizer agent decreases the growth rate of nanocrystals, causing an improvement in their surface quality. In the light of Fermi's golden rule, we observed that for longer synthesis time the optical properties of CdTe QDs increases due to the enhancement of the direct radiative recombination rate of electrons and holes and decrease in the decay rate for core states. Finally, we investigated the pH-dependent fluorescence and demonstrated the similar behaviour in acidic range between MSA-capped CdTe and mercaptocarboxylates-capped CdTe.

Heritable symbionts in a world of varying temperature.

Heritable microbes represent an important component of the biology, ecology and evolution of many plants, animals and fungi, acting as both parasites and partners. In this review, we examine how heritable symbiont-host interactions may alter host thermal tolerance, and how the dynamics of these interactions may more generally be altered by thermal environment. Obligate symbionts, those required by their host, are considered to represent a thermally sensitive weak point for their host, associated with accumulation of deleterious mutations. As such, these symbionts may represent an important determinant of host thermal envelope and spatial distribution. We then examine the varied relationship between thermal environment and the frequency of facultative symbionts that provide ecologically contingent benefits or act as parasites. We note that some facultative symbionts directly alter host thermotolerance. We outline how thermal environment will alter the benefits/costs of infection more widely, and additionally modulate vertical transmission efficiency. Multiple patterns are observed, with symbionts being cold sensitive in some species and heat sensitive in others, with varying and non-coincident thresholds at which phenotype and transmission are ablated. Nevertheless, it is clear that studies aiming to predict ecological and evolutionary dynamics of symbiont-host interactions need to examine the interaction across a range of thermal environments. Finally, we discuss the importance of thermal sensitivity in predicting the success/failure of symbionts to spread into novel species following natural/engineered introduction.

Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population.

OBJECTIVES: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population. SUBJECTS AND METHODS: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms. RESULTS: A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry. CONCLUSIONS: The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population.

Neuromyelitis optica: association with paroxysmal painful tonic spasms. / Neuromielitis óptica: asociación con espasmos tónicos paroxísticos dolorosos.

INTRODUCTION: Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. PATIENTS AND METHODS: We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. RESULTS: Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. CONCLUSIONS: PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results.

Triple-negative breast carcinoma: heterogeneity in immunophenotypes and pharmacokinetic behavior.

OBJECTIVES: To evaluate the morphokinetic, pharmacokinetic, and diffusion characteristics of triple-negative breast cancers on magnetic resonance (MR) imaging and to analyze whether there is a relation between these parameters and the time to progression. MATERIAL AND METHODS: This was a retrospective observational study of a consecutive series of 100 patients with histologically confirmed triple-negative breast cancer studied at our center between January 2005 and December 2010. We reviewed the findings on MR locoregional extension studies, the histological findings, and the follow-up of patients until August 2014. RESULTS: The most common MR findings for these tumors were a rounded mass (47.3%), well-defined borders (53.7%), ring enhancement (46.2%), type 3 curves (50.5%), hyperintensity within the tumor on T2-weighted sequences, high ADC values (1.04 × 10(-3) mm2/s), and increased capillary permeability (Kep) (0.94 min(-1)). No significant association was observed between the morphokinetic or pharmacokinetic characteristics and the time to progression. The in situ component in the surgical specimens was high, although its expression was low. During follow-up, 25% of patients had metastases, with a predilection for the visceral organs, and survival was low. CONCLUSION: Tumors with the triple-negative phenotype mostly presented in MR as rounded tumors with well-defined borders and ring enhancement. We found no significant association between the morphokinetic or pharmacokinetic characteristics and the time to progression.

A facultative endosymbiont in aphids can provide diverse ecological benefits.

Ecologically important traits of insects are often affected by facultative bacterial endosymbionts. This is best studied in the pea aphid Acyrthosiphon pisum, which is frequently infected by one or more of eight facultative symbiont species. Many of these symbiont species have been shown to provide one ecological benefit, but we have little understanding of the range of effects that a single strain can have. Here, we describe the phenotypes conferred by three strains of the recently discovered bacterium known as X-type (Enterobacteriaceae), each in their original aphid genotype which also carries a Spiroplasma symbiont. All comparisons are made between aphids that are coinfected with Spiroplasma and X-type and aphids of the same genotype that harbour only Spiroplasma. We show that in all cases, infection with X-type protects aphids from the lethal fungal pathogen Pandora neoaphidis, and in two cases, resistance to the parasitoid Aphidius ervi also increases. X-type can additionally affect aphid stress responses--the presence of X-type increased reproduction after the aphids were heat-stressed. Two of the three strains of X-type are able to provide all of these benefits. Under benign conditions, the aphids tended to suffer from reduced fecundity when harbouring X-type, a mechanism that might maintain intermediate frequencies in field populations. These findings highlight that a single strain of a facultative endosymbiont has the potential to provide diverse benefits to its aphid host.

Protection against a fungal pathogen conferred by the aphid facultative endosymbionts Rickettsia and Spiroplasma is expressed in multiple host genotypes and species and is not influenced by co-infection with another symbiont.

Many insects harbour facultative endosymbiotic bacteria, often more than one type at a time. These symbionts can have major effects on their hosts' biology, which may be modulated by the presence of other symbiont species and by the host's genetic background. We investigated these effects by transferring two sets of facultative endosymbionts (one Hamiltonella and Rickettsia, the other Hamiltonella and Spiroplasma) from naturally double-infected pea aphid hosts into five novel host genotypes of two aphid species. The symbionts were transferred either together or separately. We then measured aphid fecundity and susceptibility to an entomopathogenic fungus. The pathogen-protective phenotype conferred by the symbionts Rickettsia and Spiroplasma varied among host genotypes, but was not influenced by co-infection with Hamiltonella. Fecundity varied across single and double infections and between symbiont types, aphid genotypes and species. Some host genotypes benefit from harbouring more than one symbiont type.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Earliest innate immune responses require macrophage RelA during pneumococcal pneumonia.

NF-κB regulates cytokine expression to initiate and control the innate immune response to lung infections. The NF-κB protein RelA is critical for pulmonary host defense during Streptococcus pneumoniae pneumonia, but the cell-specific roles of this transcription factor remain to be determined. We hypothesized that RelA in alveolar macrophages contributes to cytokine expression and host defense during pneumococcal pneumonia. To test this hypothesis, we compared mice lacking RelA exclusively in myeloid cells (RelA(Δ/Δ)) with littermate controls (RelA(F/F)). Alveolar macrophages from RelA(Δ/Δ) mice expressed no full-length RelA, demonstrating effective targeting. Alveolar macrophages from RelA(Δ/Δ) mice exhibited reduced, albeit detectable, proinflammatory cytokine responses to S. pneumoniae, compared with alveolar macrophages from RelA(F/F) mice. Concentrations of these cytokines in lung homogenates were diminished early after infection, indicating a significant contribution of macrophage RelA to the initial expression of cytokines in the lungs. However, the cytokine content in infected lungs was equivalent by 15 hours. Neutrophil recruitment during S. pneumoniae pneumonia reflected a delayed onset in RelA(Δ/Δ) mice, followed by similar rates of accumulation. Bacterial clearance was eventually effective in both genotypes, but began later in RelA(Δ/Δ) mice. Thus, during pneumococcal pneumonia, only the earliest induction of the cytokines measured depended on transcription by RelA in myeloid cells, and this transcriptional activity contributed to effective immunity.

Effects of bacterial secondary symbionts on host plant use in pea aphids.

Aphids possess several facultative bacterial symbionts that have important effects on their hosts' biology. These have been most closely studied in the pea aphid (Acyrthosiphon pisum), a species that feeds on multiple host plants. Whether secondary symbionts influence host plant utilization is unclear. We report the fitness consequences of introducing different strains of the symbiont Hamiltonella defensa into three aphid clones collected on Lathyrus pratensis that naturally lack symbionts, and of removing symbionts from 20 natural aphid-bacterial associations. Infection decreased fitness on Lathyrus but not on Vicia faba, a plant on which most pea aphids readily feed. This may explain the unusually low prevalence of symbionts in aphids collected on Lathyrus. There was no effect of presence of symbiont on performance of the aphids on the host plants of the clones from which the H. defensa strains were isolated. Removing the symbiont from natural aphid-bacterial associations led to an average approximate 20 per cent reduction in fecundity, both on the natural host plant and on V. faba, suggesting general rather than plant-species-specific effects of the symbiont. Throughout, we find significant genetic variation among aphid clones. The results provide no evidence that secondary symbionts have a major direct role in facilitating aphid utilization of particular host plant species.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register.

BACKGROUND: We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke - MOnitoring STudy (SITS-MOST) and - International Stroke Thrombolysis Register (SITS-ISTR). METHODS: We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. RESULTS: Compared to the non-Austrian cohort (n=15153), the Austrian cohort (n=896) was slightly older [median, interquartile range (IQR): 70, 60-77 years vs. 69, 60-76 years, P=0.05] and included more women (44.6% vs. 41.0%, P=0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105-160 min vs. 145, 115-170 min, P<0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P=0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P=0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P=0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71-0.92, P=0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01-1.03; P=0.005) for each 10-min increase in OTT. CONCLUSIONS: The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

Broadband NIR emission in sol-gel Er(3+)-activated SiO2-Ta2O5 glass ceramic planar and channel waveguides for optical application.

An Er(3+)-doped SiO2:Ta2O5 optical channel waveguide and nanocomposite were prepared by the sol-gel route at a Si:Ta 50:50 molar ratio. Channels with an excellent surface profile were easily and quickly fabricated by focusing a femtosecond laser onto the surface of multilayered films deposited on SiO2/Si substrates. In parallel, the same sol used to prepare the film was annealed at 900, 1000, and 1100 degrees C for 2 h, to get the nanocomposite materials. A broadband NIR emission around 1538 nm, assigned to the 4I13/2 --> 4I15/2 transition of the Er3+ ions was observed in the nanocomposites of amorphous SiO2 containing dispersed Ta2O5 nanocrystals. The 4I13/2 lifetime and emission bandwidth depend on the annealing temperature. In conclusion, Er(3+)-doped SiO2:Ta2O5 channel waveguides and nanocomposites are promising materials for photonic applications.

Polymorphisms in the coagulation factor VII gene and risk of primary intracerebral hemorrhage.

Data concerning genetic factors that may influence the risk of primary intracerebral hemorrhage (PICH) are scarce. One previous study, indicated that the carriers of the (-323)Ins allele of the coagulation factor VII (FVII) have an increased risk of PICH. Another recent study, tested the effect of apolipoprotein E. We analyzed, whether the (-401)G --> T polymorphism, which is in linkage disequilibrium (LD) with the 10-bp Ins/Del polymorphism at position (-323), or the (-402)G --> A polymorphisms of the FVII gene are associated with an increased risk for PICH. We performed a small case-control study in 85 patients with PICH and in 85 healthy control subjects. To each patient a control was individually matched for age, gender, and hypertension. We did not find any significant differences in allele frequencies for the A allele of the FVII (-402)G --> A polymorphism (0.25 vs. 0.25; P = 0.900, OR = 1, ns.) nor for the T Allele of the FVII (-401)G --> T polymorphism (0.09 vs. 0.12; P = 0.480, OR = 1.38, ns.). The analysis of haplotype distributions did not reveal significant differences. Our results do not support the hypothesis that the investigated polymorphisms in the FVII gene are significantly associated with the risk for PICH.

Prior therapy with antiplatelet agents is not associated with outcome in patients with acute ischemic stroke/TIA.

BACKGROUND AND PURPOSE: It is unclear whether prior therapy with antiplatelet agents (APA) is associated with a better outcome in patients with acute ischemic cerebrovascular events. METHODS: Within a multi-center cross-sectional study, nested in a cohort we analyzed the relation between prior therapy with APA and stroke severity in 1643 patients with acute ischemic stroke or TIA. Clinical severity of the vascular event was evaluated by the National Institutes of Health Stroke Scale on admission (NIHSS1) and after 1 week (NIHSS2). By means of analysis of variance we analyzed a possible association of APA with stroke severity and interactions regarding stroke severity between APA and other clinical measures. RESULTS: 475 patients (29 %) received aspirin prior to the cerebrovascular event, 51 patients (3 %) ticlopidine or clopidogrel and 26 patients (1.6%) aspirin combined with extended release dipyridamole. 66% (1091) of patients did not take any antiplatelet medication. Neither the NIHSS1 nor the NIHSS2 nor the change of stroke severity between these time points (NIHSS1- NIHSS2) was associated with prior APA medication. We did not find significant interactions between APA use and clinical measures regarding stroke severity. CONCLUSIONS: Our results do not indicate that prior therapy with APA is associated with a better outcome in acute ischemic cerebrovascular events. There were no interactions found with other features that were associated with stroke severity.

Sialidase gene transfection enhances epidermal growth factor receptor activity in an epidermoid carcinoma cell line, A431.

Glycosphingolipids expressed in cancer cells have been implicated in the modulation of tumor cell growth through their interaction with transmembrane signaling molecules such as growth factor receptors. For glycosphingolipids to interact with growth factor receptors, the presence of sialic acid seems to be essential. Stable transfection of a gene encoding a soluble Mr 42,000 sialidase into a human epidermoid carcinoma cell line (A431) provided an approach by which the level of terminal lipid-bound sialic acid on the cell surface could be altered. In the sialidase-positive clones, the level of ganglioside GM3 was diminished, and little change was observed in protein sialylation. Sialidase-transfected cells grew faster than control cells. Sialidase expression did not modify the binding of epidermal growth factor (EGF) to its receptor but enhanced EGF receptor (EGFR) tyrosine autophosphorylation as compared to that of parental cells or cells transfected with the vector (pcDNA3) alone. Moreover, the phosphorylation of the EGFR, as well as other protein substrates, was observed at low EGF concentrations, suggesting an increase in the receptor kinase sensitivity. These data provided evidence that changes in ganglioside expression in cancer cells by appropriate gene transfection can dramatically affect EGFR kinase activity. Hence, the modulation of ganglioside expression may represent an approach to alter tumor cell growth.

Small-vessel occlusion versus large-artery atherosclerotic strokes in diabetics: Patient characteristics, outcomes, and predictors of stroke mechanism.

INTRODUCTION: Diabetes mellitus exerts a detrimental effect on cerebral vasculature affecting both macrovasculature and microvasculature. However, although ischaemic stroke is typically included among macrovascular diabetic complications, it is frequently omitted from microvascular diabetic complications. We aimed to compare the proportion of large-artery atherosclerotic and small-vessel occlusion strokes among diabetic stroke patients, explore their differences and outcomes, and assess potential mechanisms which may determine why some diabetic patients suffer large-artery atherosclerotic stroke whereas others suffer small-vessel occlusion stroke. METHODS: We pooled data of diabetic patients from four prospective ischaemic stroke registries (Acute Stroke Registry and Analysis of Lausanne (ASTRAL), Athens, Austrian, and Helsinki Stroke Thrombolysis Registries). Stroke severity and prognosis were assessed with National Institutes of Health Stroke Scale (NIHSS) and ASTRAL scores, respectively; functional outcome with three-month modified Rankin score (0-2 considered as favourable outcome). Logistic-regression analysis identified independent predictors of large-artery atherosclerotic stroke. RESULTS: Among 5412 patients, 1069 (19.8%) were diabetics; of them, 232 (21.7%) had large-artery atherosclerotic and 205 (19.2%) small-vessel occlusion strokes. Large-artery atherosclerotic stroke had higher severity than small-vessel occlusion stroke (median NIHSS: 6 vs. 3, p < 0.001), worse prognosis (median ASTRAL score: 23 vs. 19, p < 0.001), and worse three-month outcome (60.3% vs. 83.4% with favourable outcome, p < 0.001). In logistic-regression analysis, peripheral artery disease (odds ratio: 4.013, 95% confidence interval: 1.667-9.665, p < 0.01) and smoking (odds ratio: 1.706, 95% confidence interval: 1.087-2.675, p < 0.05) were independently associated with large-artery atherosclerotic strokes. CONCLUSION: In the diabetic stroke population, small-vessel occlusion and large-artery atherosclerotic strokes occur with similar frequency. Large-artery atherosclerotic strokes are more severe and have worse outcome than small-vessel occlusion strokes. The presence of peripheral artery disease and smoking independently predicted large-artery atherosclerotic stroke.