The Effect of Residential Aged Care Size,Ownership Model,and Multichain Affiliation on Resident Comfort and Symptom Management at the End of Life

Context

In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a residential aged care (RAC) facility.

A multivariate hypothesis testing framework for tissue clustering and classification of DTI data

The primary aim of this work is to propose and investigate the effectiveness of a novel unsupervised tissue clustering and classification algorithm for diffusion tensor MRI (DTI) data. The proposed algorithm utilizes information about the degree of homogeneity of the distribution of diffusion tensors within voxels. We adapt frameworks proposed by Hext and Snedecor, where the null hypothesis of diffusion tensors belonging to the same distribution is assessed by an F‐test. Tissue type is classified according to one of the four possible diffusion models, the assignment of which is determined by a parsimonious model selection framework based on Schwarz Criterion. Both numerical phantoms and diffusion‐weighted imaging (DWI) data obtained from excised rat and pig spinal cords are used to test and validate these tissue clustering and classification approaches. The unsupervised clustering method effectively identifies distinct regions of interest (ROIs) in phantoms and real experimental DTI data. Copyright © 2009 John Wiley & Sons, Ltd.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willebrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.     

Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore

Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 A in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids.     

Toll-like receptors and their ligands control mesenchymal stem cell functions.

Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency.     

Evaluation of the Glasgow coma scale score in critically Ill infectious disease patients

Summary In this prospective study the Glasgow Coma Scale (GCS) score was evaluated in 107 critically ill infectious disease (ID) patients admitted to the Intensive Care Unit (ICU) during a 1-year period. Patients were separated into two groups: those affected by central nervous system (CNS) infections and those affected by infections other than of the CNS. There were no apparent differences in the first ICU day GCS score values between the two groups (11±4 vs. 11±4, p=0.5318). Univariate logistic regression analysis confirmed a significant relationship between the first ICU day GCS score and the subsequent ICU mortality in the group of patients with CNS infections (r=0.3152, p=0.0015) but not in the group with infections not affecting the CNS (r=0.0919, p=0.1106). Our preliminary results suggest that the prognostic value of the GCS score is valid only in patients with CNS infections but not in other ID patients.

---

Evaluierung der Glasgow Coma Skala bei schwerkranken Patienten mit Infektionen

Zusammenfassung Die Glasgow Coma Scale (GCS) wurde bei 107 schwerkranken Patienten mit Infektionen im Rahmen einer prospektiven Studie evaluiert. Es handelte sich um Patienten, die während eines Jahres in der Intensivpflegestation behandelt wurde. Sie wurden nach dem Vorliegen oder nicht Vorliegen einer Infektion des Zentralnervensystems in zwei Gruppen eingeteilt. In den GCS-Scores am ersten Tag der Intensivpflegebehandlung wiesen die beiden Gruppen keine Unterschiede auf (11±4 und 11±4; p=0,5318). Die logistische Regressionsanalyse für eine Variable deckte eine signifikante Beziehung zwischen dem GCS Punktewert am ersten Tag und der folgenden Sterberate bei Patienten mit ZNS-Infektionen auf (r=0,3152; p=0,0015). Bei Patienten, deren Infektion das ZNS nicht betraf, war eine derartige Beziehung nicht zu erkennen (r=0,0919; p=0,1106). Diese vorläufigen Ergebnisse lassen darauf schließen, daß der Glasgow Coma Score nur bei Patienten mit ZNS-Infektionen eine valide Funktion hat, nicht aber bei Patienten mit anderen Infektionen.

     

Inkjet printing and UV-LED curing of photochromic dyes for functional and smart textile applications

Health concerns as a result of harmful UV-rays drive the development of UV-sensors of different kinds. In this research, a UV-responsive smart textile is produced by inkjet printing and UV-LED curing of a specifically designed photochromic ink on PET fabric. This paper focuses on tuning and characterizing the colour performance of a photochromic dye embedded in a UV-curable ink resin. The influence of industrial fabrication parameters on the crosslinking density of the UV-resin and hence on the colour kinetics is investigated. A lower crosslinking density of the UV-resin increases the kinetic switching speed of the photochromic dye molecules upon isomerization. By introducing an extended kinetic model, which defines rate constants k_colouration, k_decay and k_{decolouration}, the colour performance of photochromic textiles can be predicted. Fabrication parameters present a flexible and fast alternative to polymer conjugation to control kinetics of photochromic dyes in a resin. In particular, industrial fabrication parameters during printing and curing of the photochromic ink are used to set the colour yield, colouration/decolouration rates and the durability, which are important characteristics towards the development of a UV-sensor for smart textile applications.

Tuned performance of an inkjet-printed and UV-LED cured smart textile UV-sensor based on a photochromic dye using fabrication parameters.