Objectives The risk of recurrent stroke in patients with symptomatic carotid artery stenosis is highest in the first weeks after a transient ischemic attack (TIA) or minor stroke and can be reduced ...with carotid endarterectomy (CEA). The optimal timing of CEA remains a controversial issue since very urgent CEA is associated with an increased procedural risk. The aim of this study was to determine the risk of very early recurrent stroke in a population with symptomatic high grade carotid stenosis. Methods Data were analyzed on all patients with ocular TIA, TIA, or minor stroke with >70% carotid stenosis as assessed by carotid ultrasound at Sahlgrenska University Hospital during the periods 2004–2006 and 2010–2012. The two time periods were chosen to minimize selection bias and to analyze changes over time. The risk of recurrent stroke within 30 days of the referring event was assessed. Results 397 patients with symptomatic carotid stenosis were identified. The risk of recurrent stroke in the total cohort was 2.0% (CI 95% 0.6–3.4) by day 2, 4.0% (CI 95% 2.0–5.9) by day 7, and 7.5% (CI 95% 4.4–10.6) by day 30. There was no significant difference between the two time periods. Patients with minor stroke had a significantly higher risk of recurrent stroke than patients with TIA or ocular TIA as the referring event. Conclusions The data suggest that the early risk of recurrent stroke in symptomatic significant carotid stenosis is not as high as some earlier studies have shown. The risk is similar to several studies in which a modern medical treatment regime could be assumed.
Background & Aims: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis ...(UC) was performed.
Methods: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy.
Results: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 ± 5 to 20 ± 3 Ω · cm
2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 ± 1 to 36 ± 3 Ω · cm
2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 ± 0.25 to 4.76 ± 0.47 at the surface and from 7.26 ± 0.31 to 5.46 ± 0.37 in the crypts.
Conclusions: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.
GASTROENTEROLOGY 1999;116:301-309
Herein we report on the reactivity between silicon carbide, SiC, and pyrolytic carbon, PG, with the MAX phases, Ti2AlC, Ti3AlC2, Ti3SiC2 and Cr2AlC. Diffusion couples were assembled and heated to ...1300°C under a load corresponding to a uniaxial stress of ∼30MPa for 4, 10, and 30h in a vacuum hot press, at a vacuum level of less than 1Pa. The couples were then examined using optical and scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and orientation image microscopy. Based on the totality of the results – after 30h at 1300°C – it is concluded that neither Ti3SiC2 nor Cr2AlC appear to react with SiC. The former also appears not to react with PG. When heated in the vacuum of the hot press, both Ti2AlC and Ti3AlC2 dissociated to form TiC surface layers that were ≈15–20μm thick. After reaction of Ti2AlC with SiC and PG, the TiC layer was only ≈10μm thick, indirectly confirming that the dissociation of these phases in vacuum was due to the Al evaporation from the surfaces. The Ti3AlC2/SiC and Ti3AlC2/PG diffusion couples resulted in TiC layers that were ≈50μm and ≈100μm thick, respectively. The Cr2AlC/PG diffusion couple resulted in the formation of ≈10μm interfacial layer comprised of Cr3C2 and Cr7C3 at the interface between the two materials.
Herein we report on the reactivity between palladium, Pd, and the MAX phases, Ti2AlC, Ti3AlC2, Ti3SiC2 and Cr2AlC. Diffusion couples of Pd/MAX were heated to 900 °C under uniaxial stress of ∼20 MPa ...for 2, 4, and 10 h in a vacuum (<1 Pa) hot press. The diffusion couples were examined using X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. After heating to 900 °C for 10 h, the diffusion layer thicknesses in the Ti2AlC/Pd, Cr2AlC/Pd, Ti3AlC2/Pd and Ti3SiC2/Pd couples were found to be 35, 45, 105 and 410 μm, respectively. Thus, Ti2AlC is the most resistant to reaction, while Ti3SiC2 is least resistant, with Cr2AlC and Ti3AlC2, in between. In all cases, the reaction occurred by the diffusion of the A-group element into Pd, concomitant with Pd diffusion into the MAX phase. No diffusion of the M and X atoms was detected.
•The interaction between Pd with the MAX phases, Cr2AlC, Ti2AlC, Ti3AlC2 and Ti3SiC2 was studied.•The reaction occurred by the diffusion of the A-group element into Pd, concomitant with Pd diffusion into the MAX phase.•The best resistance to Pd attack follows, from best to worst, Ti2AlC, Cr2AlC, Ti3AlC2, and Ti3SiC2.
•Interaction of select MAX phases with pure molten sodium is reported for first time.•Samples sealed in 316 stainless steel filled with Na and heated to 750°C for 168h.•Using SEM, EDS, and XRD, we ...conclude samples did not react with Na.•For Ti3AlC2, Na appears to attack the grain boundaries, with no Na signal detected.
Herein we report on the interaction of the Mn+1AXn phases – Ti2AlC, Ti3AlC2, Ti3SiC2 and Cr2AlC – with static, pure molten sodium. The MAX phases were sealed in 316 stainless steel tubes filled with Na that, in turn, were heated to 550°C or 750°C for 168h. Based on scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) of post-exposed samples we conclude that even after exposure for 168h at 750°C, Ti2AlC, Ti3SiC2 and Cr2AlC did not react with Na. In the case of Ti3AlC2, exposure to molten Na alters both the grains and the grain boundaries, despite the fact that no Na signal was detected in the post-exposed samples. These chemical alterations were observed in TEM and manifested themselves by a change in the hardness values of the exposed surfaces.
In Alzheimer’s disease (AD) and tauopathies, tau aggregation accompanies progressive neurodegeneration. Aggregated tau appears to spread between adjacent neurons and adjacent brain regions by ...prion-like seeding. Hence, inhibitors of this seeding offer a possible route to managing tauopathies. Here, we report the 1.0 Å resolution micro-electron diffraction structure of an aggregation-prone segment of tau with the sequence SVQIVY, present in the cores of patient-derived fibrils from AD and tauopathies. This structure illuminates how distinct interfaces of the parent segment, containing the sequence VQIVYK, foster the formation of distinct structures. Peptide-based fibril-capping inhibitors designed to target the two VQIVYK interfaces blocked proteopathic seeding by patient-derived fibrils. These VQIVYK inhibitors add to a panel of tau-capping inhibitors that targets specific polymorphs of recombinant and patient-derived tau fibrils. Inhibition of seeding initiated by brain tissue extracts differed among donors with different tauopathies, suggesting that particular fibril polymorphs of tau are associated with certain tauopathies. Donors with progressive supranuclear palsy exhibited more variation in inhibitor sensitivity, suggesting that fibrils from these donors were more polymorphic and potentially vary within individual donor brains. Our results suggest that a subset of inhibitors from our panel could be specific for particular disease-associated polymorphs, whereas inhibitors that blocked seeding by extracts from all of the tauopathies tested could be used to broadly inhibit seeding by multiple disease-specific tau polymorphs. Moreover, we show that tau-capping inhibitors can be transiently expressed in HEK293 tau biosensor cells, indicating that nucleic acid–based vectors can be used for inhibitor delivery.
Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term ...treatment adherence, risk factor control, and its association to recurrent ACS and death.
We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio HR 1.19 95% confidence interval (CI) 1.00-1.40} and death HR 1.26 (95% CI 1.08-1.47) compared with an LDL-C of 1.8 mmol/L.
This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population.
The capsule polysaccharide (CPS) of Campylobacter jejuni is one of the few identified virulence determinants of this important human pathogen. Since CPS conjugate vaccines have been so effective ...against other mucosal pathogens, we evaluated this approach using CPSs from two strains of C. jejuni, 81-176 (HS23 and HS36 serotype complex) and CG8486 (HS4 serotype complex). The CPSs of 81-176 and CG8486 were independently linked to the carrier protein CRM₁₉₇ by reductive amination between an aldehyde(s), strategically created at the nonreducing end of each CPS, and accessible amines of CRM₁₉₇. In both cases, the CPS:CRM₁₉₇ ratio used was 2:1 by weight. Mass spectrometry and gel electrophoresis showed that on average, each glycoconjugate preparation contained, at least in part, two to five CPSs attached to one CRM₁₉₇. When administered subcutaneously to mice, these vaccines elicited robust immune responses and significantly reduced the disease following intranasal challenge with the homologous strains of C. jejuni. The CPS₈₁₋₁₇₆-CRM₁₉₇ vaccine also provided 100% protection against diarrhea in the New World monkey Aotus nancymaae following orogastric challenge with C. jejuni 81-176.
PDF
