Early Operative Intervention Is Associated With Better Patient Survival in Patients With Intracapsular Femur Fractures But Not Extracapsular Fractures

The purpose of this study was to determine patients' survival after undergoing an early or delayed operation. We retrospectively assessed 1849 files of patients operated for proximal femoral fracture, divided into two diagnostic groups: intracapsular (n = 640) and extracapsular (n = 1209). 1163 (63%) were treated within 48 h from hospital admission and 686 (37%) were treated > 48 h afterwards. Delayed operation in patients with intracapsular fractures was associated with a 1.8-fold excess risk for 1-year mortality (HR = 1.83, P = 0.008), while no effect was observed for patients with extracapsular fractures. Males had a higher HR for mortality in both diagnostic groups. Early surgical intervention is beneficial for intra-capsular femoral fractures; male gender and a high ASA score are associated with an increased mortality hazard risk.     

The role of microRNA profiling in prognosticating progression in Ta and T1 urinary bladder cancer

ObjectiveTo analyze microRNA profile in Ta and T1 urinary bladder cancers in combination and separately and to relate this to the risk of later developing higher-stage disease.Materials and methodsFormalin-fixed, paraffin-embedded samples of 44 Ta and 42 T1 bladder cancers representing cases with and without stage progression during follow-up were collected and microRNA expression levels were measured by microarray analysis.ResultsIn a comparison between the progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were differentially expressed. miR-10a-5p was also correlated to time to progression (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and miR-130a-3p, were differentially expressed among Ta tumors and had a fold change of more than 1.5 (P<0.038). The comparison concerning microRNA expression between the progressors and controls in category T1 cancers revealed no significant differences.ConclusionsProfiling revealed that certain microRNAs predicted the risk of developing higher-stage disease among patients with Ta cancers. Lower miR-10a-5p expression in Ta progressing tumors indicates that this microRNA could be important for later malignant potential among this group of patients.     

Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid

We report the crystal structure of the glycosylated ligand-binding (S1S2) domain of the kainate receptor subunit GluR6, in complex with the agonist domoate. The structure shows the expected overall homology with AMPA and NMDA receptor subunit structures but reveals an unexpected binding mode for the side chain of domoate, in which contact is made to the larger lobe only (lobe I). In common with the AMPA receptor subunit GluR2, the GluR6 S1S2 domain associates as a dimer, with many of the interdimer contacts being conserved. Subtle differences in these contacts provide a structural explanation for why GluR2 L483Y and GluR3 L507Y are nondesensitizing, but GluR6, which has a tyrosine at that site, is not. The structure incorporates native glycosylation, which has not previously been described for ionotropic glutamate receptors. The position of the sugars near the subunit interface rules out their direct involvement in subunit association but leaves open the possibility of indirect modulation. Finally, we observed several tetrameric assemblies that satisfy topological constraints with respect to connection to the receptor pore, and which are therefore candidates for the native quaternary structure.     

Allatostatic regulation of juvenile hormone production in vitro by the ring gland of Drosophila melanogaster

A factor(s) extracted from the third instar larval brains of the dipteran species Sarcophaga bullata and Drosophila melanogaster causes a dose-dependent reduction of juvenile hormone (JHB3) biosynthesis by isolated ring glands in vitro. In situ, this factor is presumably neuronally transmitted from the brain to ring gland. The allatostatic effect of the brain factor is reversible in vitro and may be overcome partially by the JHB3 precursor farnesoic acid. Agents which act to increase the intracellular levels of cAMP (3-isobutyl-1-methylxanthine (MIX), forskolin, 8-benzoyl cAMP) all caused the reduction of JHB3 synthesis in vitro in a reversible manner. The inhibitory effect of increased levels of cAMP was overcome by the addition of farnesoic acid to the culture medium. The dependence of JHB3 synthesis on extracellular calcium was demonstrated by incubation of ring glands in the presence of the Ca2+ channel blocker lanthanum chloride, and in Ca2(+)-free medium containing EGTA. The inclusion of farnesoic acid abolished the zero Ca2+ effect completely. However, the Ca2+ ionophore A23187 inhibited JHB3 production in medium containing Ca2+, suggesting that elevated intracellular levels of Ca2+ also suppress JHB3 production. This latter inhibition could not be reversed completely by farnesoic acid.     

Macrophage migration inhibitory factor in systemic lupus erythematosus

OBJECTIVE: To examine associations between serum macrophage migration inhibitory factor (MIF) and disease-related variables and corticosteroid use in patients with systemic lupus erythematosus (SLE). METHODS: Serum MIF concentration was measured by ELISA in 90 female patients with SLE and 279 healthy controls. Univariate and multivariate regression analyses were used to examine the associations between serum MIF concentration and disease-related indices of SLE and corticosteroid use. RESULTS: Serum MIF concentrations were positively associated with SLE disease damage (SLICC/ACR index), and indices of disease damage were greater in SLE patients with serum MIF concentrations above the normal median value. Serum MIF concentration was also observed to be significantly greater in patients with SLICC/ACR damage index (DI) scores >/= 3. Serum MIF was also positively associated with current corticosteroid dose. Significantly higher SLICC/ACR DI scores were observed in patients with values of serum MIF above the normal median, and this remained significant after adjusting for corticosteroid dose. Serum MIF concentration was also predictive of SLICC/ACR index after 3 years of followup, but this association was partly confounded by corticosteroid dose. Serum MIF was also negatively associated with serum creatinine concentration, independent of disease damage and corticosteroid dose. CONCLUSION: MIF is overexpressed in patients with SLE. While this can be partly explained by corticosteroid use, there is evidence of an association between MIF and lupus-related disease damage.     

Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes

BACKGROUND: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. AIMS: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. METHODS AND RESULTS: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. CONCLUSIONS: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation.