Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its’ known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients’ outcome.     

Effect of Bacterial Infection on Ghrelin Receptor Regulation in Periodontal Cells and Tissues

The effect of bacterial infection on the expression of growth hormone secretagogue receptor (GHS-R) was investigated in periodontal cells and tissues, and the actions of ghrelin were evaluated. GHS-R was assessed in periodontal tissues of rats with and without periodontitis. Human gingival fibroblasts (HGFs) were exposed to Fusobacterium nucleatum in the presence and absence of ghrelin. GHS-R expression was determined by real-time PCR and immunocytochemistry. Furthermore, wound healing, cell viability, proliferation, and migration were evaluated. GHS-R expression was significantly higher at periodontitis sites as compared to healthy sites in rat tissues. F. nucleatum significantly increased the GHS-R expression and protein level in HGFs. Moreover, ghrelin significantly abrogated the stimulatory effects of F. nucleatum on CCL2 and IL-6 expressions in HGFs and did not affect cell viability and proliferation significantly. Ghrelin stimulated while F. nucleatum decreased wound closure, probably due to reduced cell migration. Our results show original evidence that bacterial infection upregulates GHS-R in rat periodontal tissues and HGFs. Moreover, our study shows that ghrelin inhibited the proinflammatory actions of F. nucleatum on HGFs without interfering with cell viability and proliferation, suggesting that ghrelin and its receptor may act as a protective molecule during bacterial infection on periodontal cells.     

On the decomposition behaviour of Al-4.5 at% Zn-2 to 3 at% Mg alloys during continuous heating

The decomposition processes taking place in the Al-4.5 at % Zn-2 to 3 at % Mg alloys were studied during continuous heating by means of electrical resistivity, XSAS and DSC measurements and by TEM investigations. It was found that the room temperature pre-ageing has no significant influence on the processes taking place above 230° C. Several temperature ranges were determined in which the decomposition of the solid solution and/or the transformation of the different particles of the second phases take place by different mechanisms.     

2099 Aluminum-Lithium with Key-Locked Inserts for Aerospace Applications

The purpose of this study was to determine the acceptability of nonpenetrating, key-locked inserts in 2099 aluminum-lithium. The tests conducted to make this assessment were: (1) microscopic examination for thread damage and delaminations after key installation, (2) pull-out load at 21 °C (70 °F) and −179 °C (−290 °F), and (3) mechanical cycling tests at room temperature and −179 °C (−290 °F). The test results indicated that for the three sizes evaluated, key-locked inserts in 2099-T6 and 2099-T8 were acceptable and although delaminations did occur on some T6 temper specimens, it was only as a failure mode at ultimate load and such behavior was judged to be acceptable.     

Structural Insight into the Complex of Ferredoxin and [FeFe] Hydrogenase from Chlamydomonas reinhardtii

The transfer of photosynthetic electrons by the ferredoxin PetF to the [FeFe] hydrogenase HydA1 in the microalga Chlamydomonas reinhardtii is a key step in hydrogen production. Electron delivery requires a specific interaction between PetF and HydA1. However, because of the transient nature of the electron‐transfer complex, a crystal structure remains elusive. Therefore, we performed protein–protein docking based on new experimental data from a solution NMR spectroscopy investigation of native and gallium‐substituted PetF. This provides valuable information about residues crucial for complex formation and electron transfer. The derived complex model might help to pinpoint residue substitution targets for improved hydrogen production.     

Wrapping of Web Sources with restricted Query Interfaces by Query Tunneling

Information sources in the World Wide Web usually offer two different schemes to their users, an Interface Schema which the user can query and a Result Schema which the user can browse. Often the Interface Schema is more restricted than the Result Schema, moreover many sources offer keyword-search interfaces only. Thus query capabilities of such sources are very small and a useful integration into a mediator-based information system using query capabilities is almost impossible. We propose the Query Tunnelling architecture for the wrapping of these restricted web sources. Wrapping of sources by Query Tunneling hides restrictive query interfaces and makes such sources fully queryable based on their result schema. The process of Query Tunneling is divided into two main steps, Query Relaxation to make a higher order query suitable to a restricted interface and Result Restriction in order to filter the results using the original query.     

10 years' neuroblastoma screening in Europe: preliminary results of a clinical and biological review from the Study Group for Evaluation of Neuroblastoma Screening in Europe (SENSE)

Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.     

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4–5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies.