Search

Evaluate quantitative leakage parameters on ultrawidefield fluorescein angiography (UWF-FA) images and explore their association with Diabetic Retinopathy Severity Scale (DRSS), predominantly peripheral lesions (PPLs), visual acuity, and clinical characteristics.

There are currently no effective treatments for moderate-to-severe traumatic brain injuries (TBIs). The paracrine functions of undifferentiated neural stem cells (NSCs) are believed to play a significant role in stimulating the repair and regeneration of injured brain tissue. We therefore hypothesized that fibroblast growth factor (FGF2) enriching chondroitin sulfate glycosaminoglycan (CS-GAG) matrices can maintain the undifferentiated state of neural stem cells (NSCs) and facilitate brain tissue repair subacutely post-TBI. Rats subjected to a controlled cortical impactor (CCI) induced TBI were intraparenchymally injected with CS-GAG matrices alone or with CS-GAG matrices containing PKH26GL labeled allogeneic NSCs. Nissl staining of brain tissue 4 weeks post-TBI demonstrated the significantly enhanced (p< 0.05) tissue protection in CS-GAG treated animals when compared to TBI only control, and NSC only treated animals. CS-GAG-NSC treated animals demonstrated significantly enhanced (p< 0.05) FGF2 retention, and maintenance of PKH26GL labeled NSCs as indicated by enhanced Sox1+ and Ki67+ cell presence over other differentiated cell types. Lastly, all treatment groups and sham controls exhibited a significantly (p< 0.05) attenuated GFAP+ reactive astrocyte presence in the lesion site when compared to TBI only controls.

BACKGROUND:At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y12response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y12inhibitors in the cardiac population.OBJECTIVE:To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury.METHODS:Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion.RESULTS:One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel.CONCLUSION:A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half.

BACKGROUND:Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity.OBJECTIVE:To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy.METHODS:This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy.RESULTS:A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response.CONCLUSION:Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI.

Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up.

It is now well established that an isolated C-defect on the Si(001) surface corresponds to a dissociated water molecule with the H and OH species bonded to silicon atoms on the same side of two adjacent surface dimers. In this paper we show that there are two distinct types of such C-defects at both low temperature (∼100 K) and room temperature. These defects differ in the buckling orientation of the Si–Si dimers adjacent to the defect and/or the distribution of their localized electron spins. Changes in the buckling configuration of the bare Si–Si dimers neighboring the defect modifies the interaction between its dangling bonds and the surface and leads to significant variations in the defect charge density distributions.

There is currently considerable interest in processes associated with the modification of germanium surfaces due to their potential application in electronic components such as MOSFETs. In this work, we combine first-principles total energy and reaction path calculations to study the initial stages of the oxidation of the Ge(001) surface due to the adsorption of both atomic and molecular oxygen. The obtained results provide real insights regarding several outstanding issues in the literature, including the identification of key features observed in the experimental studies. Three new structures for oxygen adsorption on Ge(001) have been examined, at least one of which is predicted to be likely to occur. Scanning Tunnelling Microscopy (STM) images have also been simulated for comparison with the experimental data.

Quantum confinement effects on the electronic structure of thin Ge(001) slabs with one clean and one H-terminated surface are discussed based on density functional theory calculations for periodic slabs. Recent work has shown that while the geometry of the clean Ge(001) surface is reliably reproduced by relatively thin asymmetric slabs, the associated electronic structure can be quite sensitive to the number of layers in the slab. Here we show that the changes in the character and energy of the states near the Fermi energy of such slabs are related to the description of the bulk states and the width of the valence band, both of which are sensitive to the thickness of the slabs. Calculations performed for an isolated H or Cl atom adsorbed on the surface of a Ge(001) slab show that the effect of bulk electron confinement within thin slabs significantly influences the geometries, electronic structures, and relative thermodynamic stability of the single-atom adsorbates and the associated reconstructed surface. By contrast, the corresponding Si(001) surface does not exhibit any significant slab thickness dependence. We believe that these differences are a direct consequence of the nature of the states in the vicinity of the Fermi energy. Our results highlight the importance of employing an appropriate number of layers in slab calculations of the Ge(001) surface and imply that the surface electronic properties of Ge(001) slabs may be manipulated by employing a thin film technology.

Mutations in the IC138 regulatory subunit of I1 dynein alter dynein motor activity and the flagellar waveform but do not affect phototaxis.

I1 dynein, or dynein f, is a highly conserved inner arm isoform that plays a key role in the regulation of flagellar motility. To understand how the IC138 IC/LC subcomplex modulates I1 activity, we characterized the molecular lesions and motility phenotypes of several bop5 alleles. bop5-3, bop5-4, and bop5-5 are null alleles, whereas bop5-6 is an intron mutation that reduces IC138 expression. I1 dynein assembles into the axoneme, but the IC138 IC/LC subcomplex is missing. bop5 strains, like other I1 mutants, swim forward with reduced swimming velocities and display an impaired reversal response during photoshock. Unlike mutants lacking the entire I1 dynein, however, bop5 strains exhibit normal phototaxis. bop5 defects are rescued by transformation with the wild-type IC138 gene. Analysis of flagellar waveforms reveals that loss of the IC138 subcomplex reduces shear amplitude, sliding velocities, and the speed of bend propagation in vivo, consistent with the reduction in microtubule sliding velocities observed in vitro. The results indicate that the IC138 IC/LC subcomplex is necessary to generate an efficient waveform for optimal motility, but it is not essential for phototaxis. These findings have significant implications for the mechanisms by which IC/LC complexes regulate dynein motor activity independent of effects on cargo binding or complex stability.

The interaction of atomic chlorine with the Cu(110) surface is studied using density functional theory and ab initio atomistic thermodynamics. The calculated surface free energies of different Cl/Cu(110) structures as a function of chlorine chemical potential show that under ultrahigh-vacuum conditions, the c(2 × 2)-Cl structure is the most stable for coverages up to and including 1/2 ML, whereas the (2 × 3)-Cl and (1 × 4)-Cl configurations are the most stable at 2/3 and 3/4 ML coverages, respectively. It is also shown that although there are thermodynamically stable geometries for high (1 ML) coverage of Cl, these structures are only kinetically accessible. The morphology of a copper nanostructure terminated by low-index Cu surfaces in a chlorine environment has been predicted using a Wulff construction. It is found that the (111) facets dominate at low chlorine concentration, but as the chlorine concentration is increased, the (100) planes become predominant, resulting in a cubical crystal shape.

Density functional theory calculations have been performed to study the combined interaction of oxygen and chlorine with the Cu(100) surface. We found the presence of atomic chlorine increases the stability of molecular oxygen adsorption, and that the barrier required to dissociate the oxygen molecule in the presence of chlorine is three times larger than the dissociation barrier of molecular oxygen on the clean Cu(100) surface. In addition, chlorine monoxide was generated on the surface when molecular oxygen was adsorbed horizontally into a hollow site immediately adjacent to atomic chlorine. Our calculations indicate that while chlorine is easily adsorbed dissociatively on the clean Cu(100) surface, it is stable in the molecular form in the presence of atomic oxygen. The presence of chlorine leads to the production of subsurface atomic oxygen and enables an oxygen atom to go into the Cu bulk with a small activation energy barrier.

One of the fundamental requirements in the development of silicon-based molecular electronic devices is the ability to attach organic molecules to silicon surfaces to form well-defined structures that are stable and possess specific characteristics. Previous work has shown that, although norbornadiene (NBE) forms very stable structures on the Si(001) surface with its apex CH2group pointing outward from the surface, these structures cannot be resolved in scanning tunneling microscopy. In this paper, we report the results of density functional theory calculations of the interaction with the Si(001) surface of 7-trifluoroacetoxy-norbornadiene (7-TFA-NBE) in which a hydrogen atom of the apex CH2group is substituted by the trifluoroacetoxy OC(O)CF3group. This molecule is shown to form very stable structures with the trifluoroacetoxy group sitting well above the surface. Moreover, in contrast to NBE, we find that the different 7-TFA-NBE chemisorption structures should be distinguishable in high-resolution scanning tunneling microscopy experiments. This raises the exciting possibility of employing norbornadiene-based molecules with appropriately chosen functional groups to create molecular structures on Si(001) that are stable and experimentally distinguishable and yield the requisite atomic and electronic properties.

Spontaneous intestinal perforation (SIP) occurs commonly in extremely low birth weight (ELBW) infants. Our understanding of its etiologies has improved dramatically over the last decade. Included in this comprehension is an ongoing reconciliation of the iatrogenic risk factors, the microbiology, and the histopathology. The latter shows focal perforations with necrosis of the muscularis externa and no sign of ischemic damage (typically characterized by mucosal necrosis in the preterm bowel). Associations include extreme prematurity, early postnatal steroids (EPS), early use of indomethacin (EUI), and two common pathogens (Candidaand Staphylococcus epidermis). Animal models of SIP suggest that all risk factors converge on a common collection of signaling pathways: those of nitric oxide synthases (NOS), insulin-like growth factors (IGFs), and epidermal growth factors (EGFs). Many of these factors skew trophism of the ileum (defined as thinning of the submucosa concomitant with hyperplasia of the muscosa). Global depletion of NOS is associated with disturbed intestinal motility and diminished transforming growth factor-alpha (TGF-) in the muscularis externa. This constellation of insults seems to make the distal intestine vulnerable to perforation during recovery of motility.

Spontaneous intestinal perforation (SIP) occurs commonly in extremely low birth weight (ELBW) infants. Our understanding of its etiologies has improved dramatically over the last decade. Included in this comprehension is an ongoing reconciliation of the iatrogenic risk factors, the microbiology, and the histopathology. The latter shows focal perforations with necrosis of the muscularis externa and no sign of ischemic damage (typically characterized by mucosal necrosis in the preterm bowel). Associations include extreme prematurity, early postnatal steroids (EPS), early use of indomethacin (EUI), and two common pathogens (Candida and Staphylococcus epidermis). Animal models of SIP suggest that all risk factors converge on a common collection of signaling pathways: those of nitric oxide synthases (NOS), insulin-like growth factors (IGFs), and epidermal growth factors (EGFs). Many of these factors skew trophism of the ileum (defined as thinning of the submucosa concomitant with hyperplasia of the muscosa). Global depletion of NOS is associated with disturbed intestinal motility and diminished transforming growth factor-alpha (TGF-a) in the muscularis externa. This constellation of insults seems to make the distal intestine vulnerable to perforation during recovery of motility.

Early postnatal steroids and indomethacin in combination have been shown to increase the risk of spontaneous intestinal perforation (SIP) in infants with extremely low birth weight (ELBW), but the mechanism behind this synergistic effect is unknown.

Early postnatal steroids and indomethacin in combination have been shown to increase the risk of spontaneous intestinal perforation (SIP) in infants with extremely low birth weight (ELBW), but the mechanism behind this synergistic effect is unknown. Based on literature in a variety of models suggesting that glucocorticoids and nonsteroidal antiinflammatory agents diminish complementary isoforms of nitric oxide synthase (NOS), we hypothesized that perturbations in NO metabolism contribute to SIP. Our results using newborn wild-type (WT) and endothelial NOS-knockout (eNOS KO) mice treated with dexamethasone and/or indomethacin indicate that indomethacin treatment diminishes ileal eNOS abundance; dexamethasone treatment diminishes ileal inducible NOS and neuronal NOS (nNOS); 100% of dexamethasone-treated eNOS KO mice die after 3 days; eNOS KO mice treated for 2 days with dexamethasone develop acute pyloric stenosis in association with reduced expression of pyloric nNOS; and isolated ileum from eNOS KO mice treated for 2 days with dexamethasone exhibit a significant decrease in spontaneous peristalsis, decreased circumference, and decreased capacitance for forced volume before ileal perforation compared with ileum from untreated controls. Our findings suggest that eNOS and nNOS display functional overlap in the newborn mouse gastrointestinal tract and that simultaneous reduction in the activity of both NOS isoforms may be a risk factor for neonatal ileal perforation. If this holds true in human infants, then it provides a plausible etiologic explanation for the strong temporal association between SIP and the simultaneous treatment of ELBW infants with glucocorticoids and indomethacin.

Objectives:To quantify the impact of input and output factors on emergency department (ED) process outcomes while controlling for patient‐level variables.

Background

Background:Clinical practice guidelines and computerized provider order entry (CPOE) have potential for improving clinical care. Questions remain about feasibility and effectiveness of CPOE in the emergency department (ED). However, successful implementations in other settings typically incorporate decision support functions that are lacking in many commercially available ED information systems.

An atmospheric pressure (AP) infrared (IR) laser ionization technique, implemented on a quadrupole ion trap mass spectrometer, was used to analyze underivatized, N‐linked oligosaccharides in solution. Experiments were conducted on an atmospheric pressure infrared ionization from solution (AP‐IRIS) ion source which differed from previous AP IR matrix‐assisted laser desorption/ionization (MALDI) interfaces in that the ion source operated in the absence of an extraction electric field with a higher power 2.94 µm IR laser. The general term ‘IRIS’ is used as the mechanism of ionization differs from that of MALDI, and is yet to be fully elucidated. The AP‐IRIS ion source demonstrated femtomole‐level sensitivity for branched oligosaccharides. AP‐IRIS showed ∼ 16 times improved sensitivity for oligomannose‐6 and the core‐fucosylated glycan M3N2F over optimal results obtainable on a AP UV‐MALDI with a 2,4,6‐trihydroxyacetophenone matrix. Comparison between IR and UV cases also showed less fragmentation in the IR spectrum for a glycan with a conserved trimannosyl core, core‐substituted with fucose. A mixture of complex, high‐mannose and sialylated glycans resulted in positive ion mass spectra with molecular ion peaks for each sugar. Tandem mass spectrometry of the sodiated molecular ions in a mixture of glycans revealed primarily glycosidic (B, Y) cleavages. The reported results show the practical utility of AP‐IRIS while the ionization mechanism is still under investigation. Copyright © 2004 John Wiley & Sons, Ltd.

Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1µg/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.

Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1g/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.

We have previously hypothesized that IGF-I is a mediator of dexamethasone (DEX) effect in the newborn mouse ileum—a model designed to mimic the precocious mucosal maturation associated with spontaneous ileal perforations in extremely premature neonates. We have further investigated this hypothesis using in vivoand in vitromodels of accelerated epithelial migration (a transient property, temporally associated with mucosal maturation). These experiments include a steroid-treatment model comparing IGF-I immunolocalization with bromo-deoxyuridine (BrdU)-pulse-labeling, as a means of assessing epithelial cell migration, within the ileum of newborn mice that received either daily intraperitoneal injections of DEX (1 g/gm) or vehicle. Likewise, a transgenic newborn mouse model was used to compare the effect of IGF-I overexpression upon the clearance of BrdU-pulse-labeled epithelial cells traveling up the villus during the same time period. For our in vitromodel, rat ileal epithelial cells (IEC-18) were cultured to confluence in serum-free media then treated with DEX, a stable IGF-I agonist, or nothing before being subjected to linear scarification. Serial photomicrographs of migrating cells were taken over time and the average speed was determined for each treatment condition. Our data demonstrate that IGF-I accelerates ileal epithelial cell migration in every model. However, DEX was only associated with accelerated epithelial cell migration in models where IGF-I (or a synthetic agonist) was highly abundant. In contrast, DEX by itself slowed migration speed in cell culture. These findings suggest that IGF-I may be a mediator of steroid effect during precocious maturation of the ileal mucosa.

We have previously hypothesized that IGF-I is a mediator of dexamethasone (DEX) effect in the newborn mouse ileum—a model designed to mimic the precocious mucosal maturation associated with spontaneous ileal perforations in extremely premature neonates. We have further investigated this hypothesis using in vivo and in vitro models of accelerated epithelial migration (a transient property, temporally associated with mucosal maturation). These experiments include a steroid-treatment model comparing IGF-I immunolocalization with bromo-deoxyuridine (BrdU)-pulse-labeling, as a means of assessing epithelial cell migration, within the ileum of newborn mice that received either daily intraperitoneal injections of DEX (1 µg/gm) or vehicle. Likewise, a transgenic newborn mouse model was used to compare the effect of IGF-I overexpression upon the clearance of BrdU-pulse-labeled epithelial cells traveling up the villus during the same time period. For our in vitro model, rat ileal epithelial cells (IEC-18) were cultured to confluence in serum-free media then treated with DEX, a stable IGF-I agonist, or nothing before being subjected to linear scarification. Serial photomicrographs of migrating cells were taken over time and the average speed was determined for each treatment condition. Our data demonstrate that IGF-I accelerates ileal epithelial cell migration in every model. However, DEX was only associated with accelerated epithelial cell migration in models where IGF-I (or a synthetic agonist) was highly abundant. In contrast, DEX by itself slowed migration speed in cell culture. These findings suggest that IGF-I may be a mediator of steroid effect during precocious maturation of the ileal mucosa.