Structural changes of cellulose dissolved in molten salt hydrates

The behavior of cellulose in molten salt hydrates, e. g., LiClO₄*3 H₂O, ZnCl₂*4 H₂O, LiCl*5 H₂O and mixtures of thiocyanates was investigated. Melts, which give rise to a swelling or dissolution of the cellulose were the focus of interest. The melt composition and species, the water amount and the structure of the coordination sphere of the cation of the molten salt hydrate as well as the acidity influence the solubility of the cellulose in molten salt systems. The interactions between cellulose and species of the melts were determined by solution state ¹³C NMR measurements at temperatures between 65°C and 140°C. Each regenerated cellulose showed other but specific properties which were characterized by wide angle X‐ray Scattering (WAXS), solid‐state NMR (¹³C CP/MAS NMR), molecular weight distribution, surface‐area determinations and scanning electron microscopy (SEM).     

Investigation of poly(arylene vinylene)s, 41. Synthesis of soluble dialkoxy-substituted poly(phenylene alkenylidene)s by applying the Horner-reaction for condensation polymerization

Soluble poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-1,2-ethenylene] (MEH-PPV) and its alternating copolymer poly[2,5-dimethoxy-1,4-phenylene-1,2-ethenylene-2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-1,2-ethenylene] (M3EH-PPV) were successfully synthesized by condensation polymerization of substituted terephthalaldehydes with substituted xylylene bisphosphonates via the Horner reaction. This polycondensation method was also applied to the synthesis of the analogous poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-1,3-butadiene-1,4-diyl] (MEH-PPB), which contains a 1,3-butadiene instead of a vinylene unit. The optical data of MEH-PPV and M3EH-PPV (solid film, abs. λ_max 484 nm, em. λ_max 589 nm) are consistent with those previously reported for MEH-PPV from the dehydrohalogenation route. In comparison to MEH-PPV, the longer alkenylene sequence of MEH-PPB exhibits a slight red shift in its absorption and fluorescence spectra (abs. λ_max 502 nm, em. λ_max 604 nm). All three polyphenylene alkenylidenes (MEH-PPV, M3EH-PPV, and MEH-PPB) are completely soluble in common solvents. They are well-defined conjugated polymers of high molecular weight (M_w > 20 000) and possess all-trans structure. Optical quality solid films are easily prepared from these polymers by solution processing. Blends with phenyl-substituted PPV derivatives can also be prepared in this way. This combination of properties is highly desirable for many light-emitting, nonlinear optical, and photoelectrical applications.     

Clinical benefit of left atrial appendage closure in octogenarians

OBJECTIVESWhether left atrial appendage closure (LAAC) in octogenarians yield similar net clinical benefit compared to younger patients, was the purpose of the present study.METHODSTwo real-world LAAC registries, enrolling 744 consecutive Amplatzer and Watchman patients from 2009 to 2018, were retrospectively analyzed.RESULTSAll events are reported per 100 patient-years. Two hundred and sixty one octogenarians and 483 non-octogenarians with a mean follow-up of 1.7 ± 1.3 and 2.3 ± 1.6 years, and a total of 1,502 patient-years were included. Octogenarians had a higher risk for stroke (CHA₂DS₂-VASc score: 5.2 ± 1.2 vs. 4.3 ± 1.7, P < 0.0001) and bleeding (HAS-BLED score: 3.3 ± 0.8 vs. 3.1 ± 1.1, P = 0.001). The combined safety endpoint of major periprocedural complications and major bleeding events at follow-up was comparable (30/446, 6.7% vs. 47/1056, 4.4%; hazard ratio [HR] = 1.2; 95% confidence interval [CI]: 0.73−1.98;P = 0.48) between the groups. The efficacy endpoint of all-cause stroke, systemic embolism, and cardiovascular/unexplained death occurred more often in octogenarians (61/446, 13.7% vs. 80/1056, 7.6%; HR = 7.0; 95% CI: 4.53−10.93;P < 0.0001). Overall, octogenarians had a lower net clinical benefit, i.e., the composite of all above mentioned hazards, from LAAC compared to younger patients (82/446, 18.4% vs. 116/1056, 11.0%; HR = 4.6; 95% CI: 3.11−7.0;P < 0.0001). Compared to the anticipated stroke rate, the observed rate decreased by 41% in octogenarians and 53% in non-octogenarians. The observed bleeding rate was reduced by 10% octogenarians and 41% non-octogenarians. CONCLUSIONSLAAC can be performed with similar safety in octogenarians as compared to younger patients. On the long-term, it both reduces stroke and bleeding events, although to a lesser extent than in non-octogenarians.

As the most frequent arrhythmia, atrial fibrillation (AF) is associated with an increased risk of cognitive decline, stroke, disability, and mortality. The prevalence of AF is 2% in the general population and roses steadily with age, 3.7%−4.2% of subjects are aged above 60 years and up to 17% are octogenarians (age ≥ 80 years).^[1] Stroke risk from AF increases exponentially with age and is estimated at 23.9% per year in patients aged 80 years and older.^[2] Additionally, patients ≥ 80 years with AF, who are treated with oral anticoagulation (OAC), have a higher incidence of hemorrhagic events than younger patients.^[3] Therefore, octogenarians with AF are at highest risk for both thromboembolic and bleeding events. OAC is the standard of care for stroke risk. However, clinical evidence shows underuse of OAC in the elderly, who would have the highest benefit regarding ischemic stroke risk. This is mainly due to concerns about bleeding or prior bleedings. Factors of comorbidity, like impaired cognition, nonadherence, history of falls or bleedings, renal dysfunction, as well as concomitant drugs are reasons for leaving a substantial fraction of patients without stroke protection by OAC.^[4] Left atrial appendage closure (LAAC) is recommended as an alternative strategy for stroke prevention in AF patients who are not suitable for long-term treatment with OAC.^[5,6] Therefore, LAAC might be an attractive option for elderly AF patients. Several studies reported similar feasibility and safety of LAAC in subjects aged > 75 years compared to younger patients. ^[7–11] Furthermore, those studies showed favorable early clinical outcomes with regard to stroke and bleeding protection. Whether elderly patients have persistent long-term effects of LAAC has not been studied yet. Therefore, the subject of the present study was to compare the clinical benefit of LAAC in octogenarians with non-octogenarians based on the results of two real-world registries.     

Persistent efficacy of topical eprinomectin against nematode parasites in cattle

Six studies were conducted to evaluate the persistent efficacy of eprinomectin pour-on against experimental challenges with infective nematode larvae in calves. In each study, calves were randomly assigned to one untreated group and up to four test groups, which were treated with eprinomectin at 500 μg/kg body weight at weekly intervals before single bolus challenge. The calves were necropsied approximately 4 weeks after challenge infection for nematode recovery. Eprinomectin pour-on provided ≥90% efficacy against challenge with Haemonchus placei, Trichostrongylus axei and T. colubriformis at 21 days after treatment and against Cooperia oncophora, C. punctata, C. surnabada, Dictyocaulus viviparus, Nematodirus helvetianus, Oesophagostomum radiatum and Ostertagia ostertagi at 28 days after treatment. Received: 14 April 2000 / Accepted: 18 May 2000     

Principal intestinal parasites of dogs in Tirana,Albania

From 2004 to 2009, the digestive tracts of 111 dogs from suburban areas around Tirana, Albania, were examined for intestinal helminths. In addition, rectal faecal samples of all dogs were examined for protozoan infections and 48 faecal samples from dogs >6 months of age were processed with the Baermann technique to test for the excretion of lungworm larvae. The heart and pulmonary arteries of 30 dogs >6 months of age also were examined for nematode parasites. The intestinal parasite fauna of the dogs included three protozoan species (Cystoisospora canis, Cystoisospora ohioensis/burrowsi, Sarcocystis spp.), three cestode species (Dipylidium caninum, Taenia hydatigena, Echinococcus granulosus), five nematode species (Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, Toxascaris leonina, Trichuris vulpis) and one acanthocephalan (Centrorhynchus buteonis). Rates of infection were: 15.3% for C. canis, 31.5% for C. ohioensis/burrowsi, 1.8% for Sarcocystis spp., 65.8% for D. caninum, 16.2% for T. hydatigena, 2.7% for E. granulosus (genotype G1), 13.5% for A. caninum, 64.9% for U. stenocephala, 75.7% for T. canis, 0.9% for T. leonina, 21.6% for T. vulpis and 0.9% for C. buteonis. Up to six species of gastrointestinal parasites were found per dog. The 63 ≤6-month-old dogs harboured significantly (p < 0.001) fewer gastrointestinal parasite species concurrently (mean 2.65 ± 1.25 species per animal) than the 48 older animals (mean 3.77 ± 1.45 species per animal). Dogs >6 months of age harboured significantly (p < 0.05) more D. caninum, T. hydatigena, A. caninum, U. stenocephala and T. vulpis compared to younger dogs. Conversely, the younger dogs harboured significantly (p < 0.001) more T. canis than the older ones. There was no difference in the male and female dogs’ counts of individual intestinal helminth species apart from T. hydatigena in dogs >6 months of age: Male dogs harboured significantly (p < 0.05) more tapeworms than female dogs. Based on faecal examination, there was no indication for lungworm infection; however, two adult heartworms (Dirofilaria immitis) were found in the right ventricle of one dog.     

Mannan-binding-lectin-associated serine proteases, characteristics and disease associations

Mannan-binding lectin (MBL)-associated serine proteases (MASPs) circulate in plasma as zymogens in complexes with MBL and with L- and H-ficolin. Upon binding of MBL or ficolin to pathogen-associated molecular patterns, the MASPs are activated. MASP-2 can now cleave C4 and C2 to generate the C3 convertase, C4bC2b. The functions of the other two MASPs, MASP-1 and MASP-3 have not been elucidated. MASP-1 can cleave C2, and with low efficiency also C3, and may serve a function through direct C3 activation. No natural substrate for MASP-3 has been identified. MBL deficiency, occurring at a frequency of about 10%, is the most common congenital immunodeficiency and is associated with susceptibility to infections and autoimmune disorders. Inherited MASP-2 deficiency has been described as the result of a mutation causing the exchange of aspartic acid with a glycine at position 105, a position in the first domain, CUB1, involved in calcium binding. This mutation abolishes the binding to MBL and ficolins, and deprives MASP-2 of functional activity. The index case suffered from recurrent severe infections and autoimmune reactions. The gene frequency of the mutation among Caucasians is 3.6%. It is not found in Chinese, who present a different mutation also associated with MASP-2 deficiency.     

A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential

In this report, we identify in the bone marrow (BM) of normal mice a subpopulation of B220+ CD117+ CD19- NK1.1- cells with potent lymphoid and myeloid developmental potential. These cells represent 0.1-0.2% of nucleated BM cells. By limiting dilution analysis in the presence of the appropriate combination of stromal cells and cytokines, 1 in 5-10 sorted cells formed B cells, 1 in 10-15 formed T cells and 1 in 5-10 generated macrophages. When cultured on a mixture of OP9 stroma and OP9 stromal cells expressing the Notch ligand Delta-like-1, single cells generated both T and B cells. Following intravenous infusion, freshly sorted cells transiently reconstituted both the T and B cell progenitor compartments, generating cohorts of mature T and B lymphocytes. The relationship between B220+ CD117+ CD19- NK1.1- cells of wild-type mice and other multi-lineage BM progenitors is discussed.     

VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart

The strength of the heart beat can accommodate in seconds to changes in blood pressure or flow. The mechanism for such homeostatic adaptation is unknown. We sought the cause of poor contractility in the heart of the embryonic zebrafish with the mutation dead beat. We find through cloning that this is due to a mutation in the phospholipase C gamma1 (plcgamma1) gene. In mutant embryos, contractile function can be restored by PLCgamma1 expression directed selectively to cardiac myocytes. In other situations, PLCgamma1 is known to transduce the signal from vascular endothelial growth factor (VEGF), and we show here that abrogation of VEGF also interferes with cardiac contractility. Somewhat unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same system functions in the rat. Blockage of VEGF-PLCgamma1 signaling decreases calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a positive inotropic effect on cardiomyocytes by increasing calcium transients. Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility.     

Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is a gestational neoplasm derived from the extravillous (intermediate) trophoblast of the implantation site. PSTT is characterized by a highly invasive phenotype, but the molecular mechanisms are poorly understood. In this report, we demonstrate that PSTTs expressed the activated (phosphorylated) form of mitogen-activated protein kinase (MAPK) in 84% of cases, whereas the normal extravillous trophoblastic cells did not. To characterize the role of MAPK activation in PSTT, we established the first PSTT cell culture, IST-2, from a surgically resected PSTT. IST-2 cells expressed HLA-G and Mel-CAM but not E-cadherin, an immunophenotype characteristic of PSTT. IST-2 cells were highly motile and invasive in culture as compared to choriocarcinoma JEG-3 cells and normal extravillous trophoblastic cells. Based on wound assay, time-lapse videomicroscopy for cell tracking, and invasion chamber assays, we found that the motility and invasion of IST-2 cells were significantly reduced (P<0.01) after treatment with the MEK inhibitors CI-1040 and PD 59089, which prevent activation of MAPK. In contrast, neither compound had any effect on normal extravillous trophoblastic cells or JEG-3 cells. In conclusion, our findings demonstrate a functional role of MAPK activation in the motility and invasion of PSTT.     

High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors

Combining cell surface phenotyping with functional analysis, human CD8+ T cells have been divided into several subsets which are being studied extensively in diverse physiological situations, such as viral infection, cancer and ageing. In particular, so-called terminally differentiated effector cells possess a CD45RA+ CCR7- CD27- CD28- phenotype, contain perforin and, in different models, have been shown to exert direct ex vivo killing and to release interleukins upon both antigen-nonspecific and -specific stimulation. Using HLA class I multimers, we have identified a high frequency of peripheral CD8+ T cells that recognize a peptide derived from the self protein cytokeratin 18 presented by the HLA-A*0201 molecule. These cells can be detected in approximately 15% of the HLA-A2-positive healthy donors tested. A detailed analysis revealed that they must have divided extensively in vivo, have an effector cell phenotype and express various natural killer cell-associated receptors. Interestingly, however, they remained unresponsive to antigen-specific stimulation in vitro in terms of cytotoxicity and cytokine secretion. Thus, cytokeratin 18-specific cells constitute a frequently encountered, new CD8+ T lymphocyte subpopulation without classical effector status and with so far unknown function.