175 research outputs found
First metatarsophalangeal hemiarthroplasty for hallux rigidus
There is a paucity of objective information in the literature about first metatarsophalangeal (MTP) hemiarthroplasty. The authors postulate that it is a reasonable treatment option for severe hallux rigidus in selected patients. Twenty-two elective first MTP hemiarthroplasties were performed on 20 patients that met the inclusion criteria. Pre- and postoperative evaluations were done using the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score, visual analogue scale (VAS) pain score, range of motion (ROM) measurements, and radiographs. Average ROM and dorsiflexion improved by 15° and 8°, respectively. VAS pain scores improved from 5 to 2.5 after six weeks. Painless ambulation occurred after six weeks, with maximum improvement by six months. After 24 months, two patients had pain at the surgical site interfering with function, leading to an unsatisfactory result that required conversion to arthrodesis. First MTP hemiarthroplasty for severe hallux rigidus can be considered an alternative to fusion in properly selected patients who wish to maintain a functional range of motion
Resident Cardiac Immune Cells and Expression of the Ectonucleotidase Enzymes CD39 and CD73 after Ischemic Injury
BACKGROUND: The ectoenzymes CD39 and CD73 are expressed by a broad range of immune cells and promote the extracellular degradation of nucleotides to anti-inflammatory adenosine. This study explored the abundance of CD73 and CD39 on circulating and resident cardiac leukocytes and coronary endothelial cells under control conditions and in response to inflammation following myocardial ischemia and reperfusion (I/R). METHODS AND RESULTS: A method was elaborated to permit FACS analysis of non-myocardial cells (resident leukocytes, coronary endothelium and CD31(-) CD45(-) cells) of the unstressed heart. Under control conditions the murine heart contained 2.3 × 10(3) resident leukocytes/mg tissue, the most prominent fraction being antigen-presenting mononuclear cells (CD11b(+) CD11c(+) F4/80(+) MHCII(+)) followed by B-cells, monocytes and T-cells. CD73 was highly expressed on circulating and resident cardiac lymphoid cells with little expression on myeloid cells, while the opposite was true for CD39. Cardiomyocytes and erythrocytes do not measurably express CD39/CD73 and CD39 dominates on coronary endothelium. Three days after I/R, CD73 was significantly upregulated on invading granulocytes (2.8-fold) and T-cells (1.5-fold). Compared with coronary endothelial cells, CD73 associated with leukocytes comprised 2/3 of the total cardiac CD73. CONCLUSION: Our study suggests that extracellular ATP formed during I/R is preferentially degraded by CD39 present on myeloid cells, while the formation of immunosuppressive adenosine is mainly catalysed by CD73 present on granulocytes and lymphoid cells. Upregulated CD73 on granulocytes and T-cells infiltrating the injured heart is consistent with the existence of an autocrine adenosinergic loop which may promote the healing process
Juvenile obesity and its association with utilisation and costs of pharmaceuticals - results from the KiGGS study
<p>Abstract</p> <p>Background</p> <p>According to a national reference, 15% of German children and adolescents are overweight (including obese) and 6.3% are obese. An earlier study analysed the impact of childhood overweight and obesity on different components of direct medical costs (physician, hospital and therapists). To complement the existing literature for Germany, this study aims to explore the association of body mass index (BMI) with utilisation of pharmaceuticals and related costs in German children and adolescents.</p> <p>Methods</p> <p>Based on data from 14, 836 respondents aged 3-17 years in the German Interview and Examination Survey for Children and Adolescents (KiGGS), drug intake and associated costs were estimated using a bottom-up approach. To investigate the association of BMI with utilisation and costs, univariate analyses and multivariate generalised mixed models were conducted.</p> <p>Results</p> <p>There was no significant difference between BMI groups regarding the probability of drug utilisation. However, the number of pharmaceuticals used was significantly higher (14%) for obese children than for normal weight children. Furthermore, there was a trend for more physician-prescribed medication in obese children and adolescents. Among children with pharmaceutical intake, estimated costs were 24% higher for obese children compared with the normal weight group.</p> <p>Conclusions</p> <p>This is the first study to estimate excess drug costs for obesity based on a representative cross-sectional sample of the child and adolescent population in Germany. The results suggest that obese children should be classified as a priority group for prevention. This study complements the existing literature and provides important information concerning the relevance of childhood obesity as a health problem.</p
Heterologous Expression and Maturation of an NADP-Dependent [NiFe]-Hydrogenase: A Key Enzyme in Biofuel Production
Hydrogen gas is a major biofuel and is metabolized by a wide range of microorganisms. Microbial hydrogen production is catalyzed by hydrogenase, an extremely complex, air-sensitive enzyme that utilizes a binuclear nickel-iron [NiFe] catalytic site. Production and engineering of recombinant [NiFe]-hydrogenases in a genetically-tractable organism, as with metalloprotein complexes in general, has met with limited success due to the elaborate maturation process that is required, primarily in the absence of oxygen, to assemble the catalytic center and functional enzyme. We report here the successful production in Escherichia coli of the recombinant form of a cytoplasmic, NADP-dependent hydrogenase from Pyrococcus furiosus, an anaerobic hyperthermophile. This was achieved using novel expression vectors for the co-expression of thirteen P. furiosus genes (four structural genes encoding the hydrogenase and nine encoding maturation proteins). Remarkably, the native E. coli maturation machinery will also generate a functional hydrogenase when provided with only the genes encoding the hydrogenase subunits and a single protease from P. furiosus. Another novel feature is that their expression was induced by anaerobic conditions, whereby E. coli was grown aerobically and production of recombinant hydrogenase was achieved by simply changing the gas feed from air to an inert gas (N2). The recombinant enzyme was purified and shown to be functionally similar to the native enzyme purified from P. furiosus. The methodology to generate this key hydrogen-producing enzyme has dramatic implications for the production of hydrogen and NADPH as vehicles for energy storage and transport, for engineering hydrogenase to optimize production and catalysis, as well as for the general production of complex, oxygen-sensitive metalloproteins
Combinations of Host Biomarkers Predict Mortality among Ugandan Children with Severe Malaria: A Retrospective Case-Control Study
Background: Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. Methodology/Findings: Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1-99.9) sensitivity and 88.8% (79.7-94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). Conclusions: We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria
Purinergic signalling and immune cells
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells
A palaeoenvironmental reconstruction of the Middle Jurassic of Sardinia (Italy) based on integrated palaeobotanical, palynological and lithofacies data assessment
During the Jurassic, Sardinia was close to continental Europe. Emerged lands started from a single island forming in time a progressively sinking archipelago. This complex palaeogeographic situation gave origin to a diverse landscape with a variety of habitats. Collection- and literature-based palaeobotanical, palynological and lithofacies studies were carried out on the Genna Selole Formation for palaeoenvironmental interpretations. They evidence a generally warm and humid climate, affected occasionally by drier periods. Several distinct ecosystems can be discerned in this climate, including alluvial fans with braided streams (Laconi-Gadoni lithofacies), paralic swamps and coasts (Nurri-Escalaplano lithofacies), and lagoons and shallow marine environments (Ussassai-Perdasdefogu lithofacies). The non-marine environments were covered by extensive lowland and a reduced coastal and tidally influenced environment. Both the river and the upland/hinterland environments are of limited impact for the reconstruction. The difference between the composition of the palynological and palaeobotanical associations evidence the discrepancies obtained using only one of those proxies. The macroremains reflect the local palaeoenvironments better, although subjected to a transport bias (e.g. missing upland elements and delicate organs), whereas the palynomorphs permit to reconstruct the regional palaeoclimate. Considering that the flora of Sardinia is the southernmost of all Middle Jurassic European floras, this multidisciplinary study increases our understanding of the terrestrial environments during that period of time
Search for anomalous production of di-lepton events with missing transverse momentum in e(+)e(-) collisions at root s = 161 and 172 GeV
Events containing a pair of charged leptons and significant missing transverse momentum are selected from a data sample corresponding to a total integrated luminosity of 20.6 pb^-1 at centre-of-mass energies of 161 GeV and 172 GeV. The observed number of events, four at 161 GeV and nine at 172 GeV, is consistent with the number expected from Standard Model processes, predominantly arising from W+W- production with each W decaying leptonically. This topology is also an experimental signature for the pair production of new particles that decay to a charged lepton accompanied by one or more invisible particles. Further event selection criteria are described that optimise the sensitivity to particular new physics channels. No evidence for new phenomena is observed and limits on the production of scalar charged lepton pairs and other new particles are presented
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