The lateral entorhinal cortex (LEC) computes and transfers olfactory information from the olfactory bulb to the hippocampus. Here we established LEC connectivity to upstream and downstream brain ...regions to understand how the LEC processes olfactory information. We report that, in layer II (LII), reelin- and calbindin-positive (RE(+) and CB(+)) neurons constitute two major excitatory cell types that are electrophysiologically distinct and differentially connected. RE(+) neurons convey information to the hippocampus, while CB(+) neurons project to the olfactory cortex and the olfactory bulb. In vivo calcium imaging revealed that RE(+) neurons responded with higher selectivity to specific odors than CB(+) neurons and GABAergic neurons. At the population level, odor discrimination was significantly better for RE(+) than CB(+) neurons, and was lowest for GABAergic neurons. Thus, we identified in LII of the LEC anatomically and functionally distinct neuronal subpopulations that engage differentially in feedforward and feedback signaling during odor processing.
Halite already deforms at surface temperatures. A valuable universal dating tool to constrain the timing of sedimentary, diagenetic, or deformational structures is still missing. The evaporite ...mineral polyhalite can be dated by the
40
Ar/
39
Ar method. On the example of the extremely deformed halite deposits of the Eastern Alps, polyhalite was tested to date early diagenetic stages of the deposits. The sedimentological investigation of the present study indicates that some of the macrostructures of polyhalite had a syn-depositional origin during the late Permian. It is supposed that polyhalite originated during reflux of brines. All samples selected for age dating represent characteristic microfabric types of euhedral to subhedral polyhalite crystals. Intact macro- and non-recrystallized looking microstructures of polyhalite can be expected to give plateau ages. However, nearly all measurements produced overdispersed data that do not define an age. The oldest age steps thus represent only minimum ages. A closer look revealed grain boundary migration, subgrain rotation recrystallization, twinning, and fluid-supported grain size increase. These recovery processes obscured the original ages and/or reflect the origin of new polyhalite in place of the original individuals. Based on these microstructures, the age data are supposed to reflect the circulation of aqueous fluids. Just extremely careful separation of individual crystals or in situ age dating under the microscope will be successful in dating polyhalite. Nevertheless, polyhalite can potentially serve to date deformational events of halite deposits due to its easy recrystallization property.
Experimental and volunteer studies have reported pulmonary vasoconstriction during transfusion of packed red blood cells (PRBCs) stored for prolonged periods. The primary aim of this study was to ...evaluate whether transfusion of PRBCs stored over 21 days (standard-issue, siPRBCs) increases pulmonary artery pressure (PAP) to a greater extent than transfusion of PRBCs stored for less then 14 days (fresh, fPRBCs) in critically ill patients following cardiac surgery. The key secondary aim was to assess whether the pulmonary vascular resistance index (PVRI) increases after transfusion of siPRBCs to a greater extent than after transfusion of fPRBCs.
The study was performed as a single-center, double-blinded, parallel-group, randomized clinical trial. Leukoreduced PRBCs were transfused while continuously measuring hemodynamic parameters. Systemic concentrations of syndecan-1 were measured to assess glycocalyx injury. After randomizing 19 patients between January 2014 and June 2016, the study was stopped due to protracted patient recruitment.
Of 19 randomized patients, 11 patients were transfused and included in statistical analyses. Eight patients were excluded prior to transfusion, 6 patients received fPRBCs (10±3 storage days), whereas 5 patients received siPRBCs (33±4 storage days). The increase in PAP (7±3 vs. 2±2 mmHg, P = 0.012) was greater during transfusion of siPRBCs than during transfusion of fPRBCs. In addition, the change in PVRI (150±89 vs. -4±37 dyn·s·cm-5·m2, P = 0.018) was greater after transfusion of siPRBCs than after transfusion of fPRBCs. The increase in PAP correlated with the change of systemic syndecan-1 concentrations at the end of transfusion (R = 0.64,P = 0.034).
Although this study is underpowered and results require verification in larger clinical trials, our findings suggest that transfusion of siPRBCs increases PAP and PVRI to a greater extent than transfusion of fPRBCs in critically ill patients following cardiac surgery. Glycocalyx injury might contribute to pulmonary vasoconstriction associated with transfusion of stored blood.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of ...life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity.
Aims
The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact.
Methods
IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (
n
= 396).
Results
A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control.
Conclusion
Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.
Pathogen inactivation techniques for blood products have been implemented to optimize clinically safe blood components supply. The INTERCEPT system uses amotosalen together with ultraviolet light ...wavelength A (UVA) irradiation. Irradiation-induced inactivation of nucleic acids may actually be accompanied by modifications of chemically reactive polyunsaturated fatty acids known to be important mediators of platelet functions. Thus, here, we investigated eicosanoids and the related fatty acids released upon treatment and during storage of platelet concentrates for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation, and clot firmness hardly differed between the two treatment groups. In contrast to gamma irradiation, here, we demonstrated that INTERCEPT treatment immediately caused new formation of trans-arachidonic acid isoforms, while 11-hydroxyeicosatetraenoic acid (11-HETE) and 15-HETE were increased and two hydroperoxyoctadecadienoic acid (HpODE) isoforms decreased. During further storage, these alterations remained stable, while the release of 12-lipoxygenase (12-LOX) products such as 12-HETE and 12-hydroxyeicosapentaenoic acid (12-HEPE) was further attenuated. In vitro synthesis of trans-arachidonic acid isoforms suggested that thiol radicals formed by UVA treatment may be responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is reasonable to assume that UVA-induced molecules may have specific biological effects which need to be further investigated.
Background
The latest technical innovation for granulocyte (PMN) collections is the fully automated Spectra Optia (Optia) device (TerumoBCT). In a retrospective investigation we evaluated the impact ...of the technical automation on the product quality in a routine working field.
Study Design and Methods
A total of 71 granulocyte collections (GCs) were collected from either routine random blood donors, mobilized with prednisolone (P; two females/23 males; median age, 42 years; range, 25‐63 years), or family donors (three females/12 males; median age, 29 years; range, 21‐59 years) who were mobilized with recombinant human granulocyte–colony‐stimulating factor (rHuG‐CSF) at a dose of 5 μg/kg body weight. All collections were performed with the Optia device. Fifty‐nine concentrates (GTX) produced with the Cobe Spectra (Cobe; TerumoBCT) served as a historical control.
Results
In total a mean of 452 ± 60 mL with a mean purity of 83 ± 9.6% PMNs was collected with the Optia. Compared with the Cobe collections (298 ± 52 mL), the product volumes in general as well as the absolute PMN yield in P‐mobilized products were significantly higher with the Optia: PMN count, 1.9 × 1010 ± 0.49 × 1010 versus 1.5 × 1010 ± 0.85 × 1010, respectively (p < 0.05), due to higher white blood cell (WBC) yields. rHuG‐CSF–mobilized products showed no significant differences in the absolute WBC (7.2 ± 3.0/Optia vs. 7.0 ± 2.1/Cobe) and PMN (5.9 ± 2.6/Optia vs. 5.7 ± 1.9/Cobe) yield. The PMN purity was equal in both devices (mean, 83%) although it was slightly lower in the rHuG‐CSF group (82 ± 9.2%) than in the P group (84 ± 6.2%). In none of the procedures were side effects recorded.
Conclusion
GC with the fully automated Optia device is safe for donors, is not inferior to its forerunner Cobe Spectra, produces GTX of a high quality, and requires less manpower than the Cobe Spectra.
Ultrasound transducers can be modelled from scratch in software. Simulations employ these models to investigate the influences of materials and shapes of transducer structures on the resonance ...behaviour. However, there is a lack of publicly available code implementations for such models. In addition, printed transducers place special demands on the design. For example, printing processes always require substrate materials that can affect resonances. To support rapid prototyping, we provided an equivalent circuit model based on the model suggested by Mason. We employed transmission line theory to account for impedance loads from auxiliary structures (e.g. electrodes or substrate). We evaluated our model on 6 printed transducer samples and found mean differences in resonant frequencies of 3.63±2.5MHz. Moreover, we demonstrated the usage of this model in the design process of printed transducers. We made all our code available as open-source software via: https://github.com/luuleitner/xMason.
Plerixafor in combination with granulocyte‐colony stimulating factor (G‐CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. ...The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G‐CSF alone or chemotherapy and G‐CSF in patients at risk for mobilization failure. Eighty‐five patients mobilized with G‐CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 106 CD34+ cells/kg for a single or ≥5 × 106 CD34+ cells/kg for a double transplantation and potential differences between G‐CSF and chemotherapy‐based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34+ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9‐fold increase in CD34+ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 106 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19+ and natural killer cells were collected after G‐CSF. Fifty‐two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G‐CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.
Abstract The evaluation of postural stability using posturography could be both a valuable functional diagnostic and treatment outcome monitoring tool in rehabilitation practice of patients with ...chronic low back pain (cLBP). No evidence, however, seems to exist, whether or not such posturographic measures are reliable in these patients and therefore clinically and scientifically useful. The aims of this study were manifold and aimed at investigating (1) differences of posturographic measures between cLBP patients and healthy controls (HCs), (2) short- (intrasession-) and long-term (intersession-) reliability of these measurements, and (3) the relationship between both pain intensity and test-related feelings and significant learning effects of the posturographic measures in cLBP. A total of 32 cLBP patients and 19 non-sportive HCs completed (1) comprehensive clinical examination, (2) quantitative posturographic testing (SMART EquiTest, Neurocom International, Clackamas, Oregon) that included all the sensory organisation test (SOT), the motor control test (MCT) and the adaptation test (ADT) and (3) psychological ratings of pain as well as posturographic test related personal feelings and fear associated beliefs. Of these, 22 cLBP patients who received no therapy repeated all measurements and examinations on a second day, 2–3 weeks later. Results revealed significant differences between cLBP patients and HCs in the more demanding postural test conditions of the SOT and the SOT composite score only. Intra-session reliability testing demonstrated significant improvements of the SOT and ADT measures for both HCs and cLBP patients. Results of long-term reliability testing showed significant improvements of the more challenging SOT conditions and SOT composite score. VAS ratings of pain, feelings and fear associated beliefs were not associated with such longitudinal changes. Conclusion Our findings suggest that the significant learning effects observed for the SOT conditions may limit the clinical application of SMART EquiTest postural stability measures for cLBP patients in rehabilitation everyday practice. Further development in software processing will be necessary to identify new postural parameters that are less prone to learning effects.
Pyranose 2-oxidase (P2Ox) is a 270 kDa homotetramer localized preferentially in the hyphal periplasmic space of lignocellulolytic fungi and has a proposed role in lignocellulose degradation to ...produce the essential co-substrate, hydrogen peroxide, for lignin peroxidases. P2Ox oxidizes
d-glucose and other aldopyranoses regioselectively at C2 to the corresponding 2-keto sugars; however, for some substrates, the enzyme also displays specificity for oxidation at C3. The crystal structure of P2Ox from
Trametes multicolor has been determined using single anomalous dispersion with mercury as anomalous scatterer. The model was refined at 1.8
Å resolution to
R and
R
free values of 0.134 and 0.171, respectively. The overall fold of the P2Ox subunit resembles that of members of the glucose–methanol–choline family of long-chain oxidoreductases, featuring a flavin-binding Rossmann domain of class α/β and a substrate-binding subdomain with a six-stranded central β sheet and three α helices. The homotetramer buries a large internal cavity of roughly 15,000
Å
3, from which the four active sites are accessible. Four solvent channels lead from the surface into the cavity through which substrate must enter before accessing the active site. The present structure shows an acetate molecule bound in the active site with the carboxylate group positioned immediately below the flavin N5 atom, and with one carboxylate oxygen atom interacting with the catalytic residues His548 and Asn593. The entrance to the active site is blocked by a loop (residues 452 to 461) with excellent electron density but elevated temperature factors. We predict that this loop is dynamic and opens to allow substrate entry and exit.
In silico docking of
d-glucose in the P2Ox active site shows that with the active-site loop in the closed conformation, monosaccharides cannot be accommodated; however, after removing the loop from the model, a tentative set of protein–substrate interactions for β-
d-glucose have been outlined.
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