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Objective: Despite advances in hematopoietic stem cell transplantation (HSCT), a considerable number of pediatric HSCT patients develops post-transplant complications requiring admission to the pediatric intensive care unit (PICU). The objective of this study was to evaluate clinical findings, PICU supportive therapy and outcome as well as predictive factors for 6-months survival after discharge of HSCT patients from PICU. Study design: This retrospective single-center analysis investigated patient characteristics, microbiological findings, reasons for admission and death of 54 cases accounting for 94 admissions to the PICU of the University Children's Hospital Tuebingen from 2002 to 2017. We compared clinical characteristics between children with and without 6-months survival after discharge from PICU following HSCT. Finally, we assessed the potential prognostic value of the oncological Pediatric Risk of Mortality Score (O-PRISM), the Pediatric Sequential Organ Failure Assessment Score (pSOFA) and the pRIFLE Criteria for Acute Kidney Injury for 6-months survival using Generalized Estimating Equations (GEE) and Receiver Operating Characteristic curves. Results: Respiratory insufficiency, gastroenterological problems and sepsis were the most common reasons for PICU admission. Out of 54 patients, 38 (70%) died during or after their last PICU admission, 30% survived for at least six months. When considering only first PICU admissions, we could not determine prognostic factors for 6-months mortality. In contrast, under consideration of all PICU admissions in the GEE model, ventilation (p=0.03) and dialysis (p=0.007) were prognostic factors for 6-months mortality. Furthermore, pSOFA (p=0.04) and O-PRISM (p=0.02) were independent risk factors for 6-months mortality considering all PICU admissions. Conclusion: Admission of HSCT patients to PICU is still associated with poor outcome and 69% of patients died within 6 months. Need for respiratory support and dialysis are associated with poor outcome. Prediction of 6-months survival is difficult, especially during a first PICU admission. However, on subsequent PICU admissions pSOFA and O-PRISM scores might be useful to predict mortality. These scores should be prospectively evaluated in further studies to verify whether they can identify pediatric HSCT recipients profiting most from transferal to the PICU. [ABSTRACT FROM AUTHOR]

The regulation of renal function by extracellular nucleotides encompasses alterations in glomerular hemodynamics, microvascular function, tubuloglomerular feedback, tubular transport, cell growth or apoptosis, and transport of water and solutes in the medullary collecting duct. Nearly all cells can release ATP or other nucleotides that are then rapidly hydrolyzed in the extracellular milieu. However, little information is available on the cellular expression of ectoenzymes that hydrolyze extracellular nucleotides within the kidney. Nucleoside triphosphate diphosphohydrolases (NTPDases) are plasma membrane-bound ectonucleotidases. NTPDase1 has identity with CD39, a B lymphocyte activation marker, and hydrolyzes extracellular ATP and ADP to AMP within the vasculature, whereas NTPDase2/CD39L(ike)1 preferentially converts ATP to ADP outside of blood vessels. Using immunohistochemical and in situ hybridization approaches, we localized the protein and mRNA of NTPDase1 and 2 in murine renal tissues. In the renal cortex, NTPDase1 is expressed by vascular smooth muscle cells and endothelium in interlobular arteries, afferent glomerular arterioles, and peritubular capillaries. In the inner medulla, NTPDase1 is expressed in ascending thin limbs of Henle's loop, ducts of Bellini, and in the pelvic wall. In contrast, NTPDase2 is expressed in Bowman's capsule, glomerular arterioles, adventitia of blood vessels, and pelvic wall. Thus the distribution patterns of NTPDases have parallels to the known distribution of P2 receptors within the kidney. NTPDases may modulate regulatory effects of ATP and degradation products within the vasculature and other sites and thereby potentially influence physiological as well as multiple pathological events in the kidney. ectonucleotidases; CD39; ATP; immunohistochemistry; in situ hybridization

Purpose: To study immunogenic properties of human embryonic stem cell–derived retinal pigment epithelium (hESC‐RPE) and to evaluate subretinal xenotransplantation of hESC‐RPE on porous polyethylene terephthalate (PET) in rabbits. Methods: Human ESC‐RPE cells were characterized by morphology, transepithelial electrical resistance (TER), protein expression and photoreceptor outer segment phagocytosis in vitro. Expression of major histocompatibility complex (MHC) proteins was assessed in conventionally or xeno‐free produced hESC‐RPE ± interferon‐gamma (IFN‐γ) stimulation (n = 1). Xeno‐free hESC‐RPE on PET with TER < 200 Ω·cm2 > or PET alone were transplanted into 18 rabbits with short‐term triamcinolone ± extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4 weeks, the eyes were processed for histology and transmission electron microscopy. Results: Upon in vitro IFN‐γ stimulation, xeno‐free hESC‐RPE expressed lower level of MHC‐II proteins compared to the conventional cells. Outer nuclear layer (ONL) atrophy was observed over the graft in most cases 4 weeks post‐transplantation. In 3/4 animals with high TER hESC‐RPE, but only in 1/3 animals with low TER hESC‐RPE, ONL atrophy was observed already within 1 week. Retinal cell infiltrations were more frequent in animals with high TER hESC‐RPE. However, the difference was not statistically significant. In three animals, preservation of ONL was observed. Weekly intravitreal tacrolimus did not affect ONL preservation. In all animals, hESC‐RPE cells survived for 4 weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC‐RPE (n = 1). Conclusions: Xenografted xeno‐free hESC‐RPE monolayers can survive and retain some functionality for 4 weeks following short‐term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC‐RPE xenografts in rabbits should be addressed especially toward the roles of hESC‐RPE maturation stage and extended intravitreal immunosuppression. [ABSTRACT FROM AUTHOR]

The standard treatment of many tumor entities comprises fractionated radiation therapy which applies ionizing radiation to the tumor-bearing target volume. Ionizing radiation causes double-strand breaks in the DNA backbone that result in cell death if the number of DNA double-strand breaks exceeds the DNA repair capacity of the tumor cell. Ionizing radiation reportedly does not only act on the DNA in the nucleus but also on the plasma membrane. In particular, ionizing radiation-induced modifications of ion channels and transporters have been reported. Importantly, these altered transports seem to contribute to the survival of the irradiated tumor cells. The present review article summarizes our current knowledge on the underlying mechanisms and introduces strategies to radiosensitize tumor cells by targeting plasma membrane ion transports. [ABSTRACT FROM AUTHOR]

Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL ( N = 6, 5m/1f, mean age 56 ± 11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD < 5%). After a single Rheopheresis treatment, flow-mediated vasodilatation improved significantly (from 3.9 ± 3.6% to 7.2 ± 2.4%, P = 0.05, mean ± SD, two-sided paired T-test). This was paralleled by a reduction in fibrinogen (364 ± 216 mg/dL to 142 ± 96 mg/dL, P = 0.03), total cholesterol (228 ± 23 to 98 ± 10, P < 0.0001) and LDL cholesterol levels (153 ± 8 mg/dL to 83 ± 23 mg/dL, P < 0.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL. [ABSTRACT FROM AUTHOR]

Three qualities of New Caledonian sandalwood oil were analyzed using GC and GC/MS. Eighty-four constituents were identified: 10 monoterpenes, 72 sesquiterpenes and two others. In addition β-bisabolol/epi-β-bisabolol isomers were isolated and characterized via chiral GC chromatography. Our results indicate that New Caledonian sandalwood oil is much closer related to East Indian sandalwood oil than its Western Australian counterpart. [ABSTRACT FROM AUTHOR]

Six stereoisomers of nor-helifolen-12-al and four isomers of acoren-11-ol (-acorenol, epi-α -acorenol, β -acorenol, epi-β -acorenol) were identified for the first time in Australian sandalwood oil. [ABSTRACT FROM AUTHOR]

This paper describes the concept and control of a 3d virtual character system with facial expressions and gesturesas a conversational user interface with narrative expressiveness for the hearing impaired. The gestures and facialexpressions are based on morphing techniques. The system allows the generation of sign language and mouthmotion in real time from text at the level of lip reading quality. The concept of Narrative Extended Speech Acts(NESA) is introduced, based on Interactive Storytelling techniques and the concepts of Narrative Conflict andSuspense Progression. We define a choice of annotation tags to be used with NESAs. We use the NESAs to classifyconversation fragments and to enhance computer generated sign language. We note, how the sign language gesturesare generated and show the possibilities for editing sign language gestures. Furthermore, we give details onhow the NESAs are mapped to gestures. We show the possibilities of controlling the virtual character's behaviourand gestures in a human-oriented way and provide an outlook on future work. Categories and Subject Descriptors (according to ACM CCS): 1.3.6 [Computer Graphics]: Methodology and Techniques [ABSTRACT FROM AUTHOR]

Describes the total synthesis of tricyclic azaspirane derivatives of tyrosine. Union of an amino alcohol and a carboxylic acid; Iodobenzene diacetate oxidation/acetylation of oxazoline; Conversion of dienone to cyclohexanone; Applications of oxidative cyclizations of oxazolines.

Background. Reduction of pathological autoantibodies and circulating immune complexes can be useful in the treatment of autoimmune disease. Plasmapheresis has been shown to reduce autoantibody levels in systemic lupus erythematosus (SLE), but its effect on patients' outcome was not better compared with conventional immunosuppression in the past. [ABSTRACT FROM PUBLISHER]

Introduces oxidative transformations of phenolic and indolic oxazolines. Development of techniques applicable to indolic systems; Challenges in performing oxidative cyclization of phenolic amides to a spirolactam; Details on the oxidation of phenolic oxazolines; Creation of novel heterocyclic systems.

Immunoadsorption onto staphylococcal protein A is a newly developed semiselective extracorporeal adsorption technique for immunoglobulins applied in patients suffering from severe autoimmune disease. Its effect on the humoral and cellular immune system was investigated using standard immunological assays. The elimination capacity for total IgG and IgG subclasses 1, 2, and 4 was more than 90% but for subclass IgG3 varied between 30 and 90%. Autoantibodies, e.g., anti-dsDNA, anti-glomerular basement membrane (anti-GBM), anti-cardiolipin, and anti-human leukocyte antigen (anti-HLA) antibodies, were eliminated in comparable amounts. The affinity of protein A for circulating immune complexes (CIC) was 300 times greater than for soluble IgG. HLA-II expression on monocytes and T lymphocytes was reduced over time during repeated IAs (IA). The number of activated T lymphocytes declined while the percentage of naive T cells increased. A diminished CD4/CD8 ratio normalized during IA treatment. These results indicate that IA actively modulates the humoral as well as the cellular immune system in addition to its immunoglobulin reducing effect. [ABSTRACT FROM AUTHOR]

Examines the characterization of rat ecto-adenosine triphosphatase and ecto-adenosine triphosphate (ATP) diphosphohydrolase after heterologous expression in cells. Comparison of molecular and functional properties; Discussion of the extracellular hydrolysis of ATP; Termination of the physiological action of nucleotides released from cells.

An approach for authoring virtual environments within the virtual environments themselves is presented, integrating a database containing arbitrary components that are used to construct the 3D scene. The issues important to a seamless integration of the database, such as multimedia data storage and database linkage are discussed, with the focus on the human-computer interaction component. A concept for a 3D database interface is described for query, presentation and usage of query results in the virtual environment. Finally, an implementation of the concept using VRML and Java is presented. [ABSTRACT FROM AUTHOR]