Irinotecan Upregulates Fibroblast Growth Factor Receptor 3 Expression in Colorectal Cancer Cells, Which Mitigates Irinotecan-Induced Apoptosis.

BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed. RESULTS: IRI exposure induced expression of FGFR3 as well as its ligands FGF8 and FGF18 both in cell cultures and in xenograft tumors. As overexpression of FGFR3 mitigated IRI-induced apoptosis in CRC cell models, this suggests that the drug itself activated a survival response. On the cellular level, the antiapoptotic protein bcl-xl was upregulated and caspase 3 activation was inhibited. Targeting FGFR3 signaling using a dominant-negative receptor mutant sensitized cells for IRI. In addition, the FGFR inhibitor PD173074 acted synergistically with the chemotherapeutic drug and significantly enhanced IRI-induced caspase 3 activity in vitro. In vivo, PD173074 strongly inhibited growth of IRI-treated tumors. CONCLUSION: Together, our results indicate that targeting FGFR3 can be a promising strategy to enhance IRI response in CRC patients.

[Cardiovascular assessment and management before non-cardiac surgery]. / Kardiologische Abklärung und Behandlung vor chirurgischen Eingriffen.

The preoperative cardiovascular risk management accounts for patient-related risk factors, the circumstances leading to the surgical procedure, and the risk of the operation. While urgent operations should not be delayed for cardiac testing, an elective surgical intervention should be postponed in unstable cardiac conditions. In stable cardiac situations, prophylactic coronary interventions to reduce the risk of perioperative complications are rarely indicated. Therefore, in most cases, the planned operation can be performed without previous cardiac stress testing or coronary angiography. Preoperative imaging stress testing is recommended for patients with poor functional capacities that are at high cardiovascular risk prior to a high-risk operation. According to the literature, preoperative prophylactic administration of betablockers and aspirin is controversial. Preoperative discontinuation of dual anti-platelet therapy within six months following drug-eluting stent implantation is not recommended.

Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial.

BACKGROUND: Urinary tract infections (UTIs) are common drivers of antibiotic use. The minimal effective duration of antibiotic therapy for UTIs is unknown, but any reduction is important to diminish selection pressure for antibiotic resistance, costs, and drug-related side-effects. The aim of this study was to investigate whether an algorithm based on procalcitonin (PCT) and quantitative pyuria reduces antibiotic exposure. METHODS: From April 2012 to March 2014, we conducted a factorial design randomized controlled open-label trial. Immunocompetent adults with community-acquired non-catheter-related UTI were enrolled in the emergency department of a tertiary-care 600-bed hospital in northwestern Switzerland. Clinical presentation was used to guide initiation and duration of antibiotic therapy according to current guidelines (control group) or with a PCT-pyuria-based algorithm (PCT-pyuria group). The primary endpoint was overall antibiotic exposure within 90 days. Secondary endpoints included duration of the initial antibiotic therapy, persistent infection 7 days after end of therapy and 30 days after enrollment, recurrence and rehospitalizations within 90 days. RESULTS: Overall, 394 patients were screened, 228 met predefined exclusion criteria, 30 declined to participate, and 11 were not eligible. Of these, 125 (76% women) were enrolled in the intention-to-treat (ITT) analysis and 96 patients with microbiologically confirmed UTI constituted the per protocol group; 84 of 125 (67%) patients had a febrile UTI, 28 (22%) had bacteremia, 5 (4%) died, and 3 (2%) were lost to follow-up. Overall antibiotic exposure within 90 days was shorter in the PCT-pyuria group than in the control group (median 7.0 [IQR, 5.0-14.0] vs. 10.0 [IQR, 7.0-16.0] days, P = 0.011) in the ITT analysis. Mortality, rates of persistent infections, recurrences, and rehospitalizations were not different. CONCLUSIONS: A PCT-pyuria-based algorithm reduced antibiotic exposure by 30% when compared to current guidelines without apparent negative effects on clinical outcomes.

Prognosis of implants and abutment teeth under combined tooth-implant-supported and solely implant-supported double-crown-retained removable dental prostheses.

OBJECTIVE: Objective of this study was to evaluate the incidence of complications in dental implants and abutment teeth used for combined tooth-implant- and solely implant-supported double crown-retained removable dental prostheses (RDPs). MATERIAL AND METHODS: Patients were selected from a prospective clinical study. Seventy-three RDPs retained by 234 implants and 107 abutment teeth were placed in 39 men and 22 women with a mean age of 65 years. Forty-five RDPs were located in the maxilla and 28 in the mandible. Thirty-four RDPs were solely implant-supported and 39 were combined tooth-implant-supported. Kaplan-Meier analysis was used to estimate success defined as survival without severe abutment-related complications, and Cox regression was used to isolate the most relevant prognostic risk factors. RESULTS: After a median observation period of 2.7 years for the RDPs, six implants failed and eleven implants were diagnosed with peri-implantitis. Four abutment teeth were extracted, and three abutment teeth showed severe complications requiring extended interventions. For both abutment teeth and implants, Kaplan-Meier analyses revealed a 5-year probability of success of 85% for solely implant-supported RDPs and 92% for combined tooth-implant-supported RDPs. Multiple Cox regression identified RDP location (P = 0.01), age (P = 0.01), and gender (P = 0.04) as prognostic risk factors for severe implant-related complications. Solely implant-supported RPDs showed a poorer prognosis, but the risk difference did not reach statistical significance. CONCLUSIONS: Preliminary data suggest that the combination of teeth and implants to support double crown-retained RDPs may result in a prognostic advantage. The present findings should be validated in independent studies.

Early loading of implants with fixed dental prostheses in edentulous mandibles: 7.2-year clinical results from a prospective study.

PURPOSE: The purpose of this prospective follow-up study was to evaluate survival and success of early-loaded implants placed in the edentulous mandible and the survival of the fixed dental prostheses (FDPs) after in mean 7.2 years. MATERIALS AND METHODS: Thirty-seven patients (mean age 64.5 years, 18.9% male) received 185 implants in the intraforaminal area of the edentulous mandible (five implants per patient). Within 2 weeks, all implants were early loaded with fixed dental prostheses. The patients were recalled once a year for clinical and radiographic examinations. The 17 patients (79 implants) attending the recall in 2012 were additionally asked for their satisfaction of functional and aesthetic aspects. RESULTS: During a mean observation time of 7.2 years, 20 implants were lost in 11 patients, resulting in implant survival of 89.2%. Eight of all implants (4.3%) had too much marginal bone loss to satisfy the criteria of success. A total of 19 prosthetic complications and aftercare measurements had to be performed between in mean 4.5 to 7.2 years of observation. The survival of the original FDPs decreased to 83.8%. Of the 17 patients attending the recall in 2012, a total 59.5% had a satisfactory oral hygiene. According to the criteria of Albrektsson, the success rate for the remaining 79 implants was 89.9% after in mean 11.7 years. Patient satisfaction for assessment of functional and aesthetic aspects was in median 9 and 8 on the numeric rating scales. CONCLUSION: Long-term observation of in mean 7.2 years showed satisfactory results for both implant and superstructure survival. Prosthetic complications were easy to repair in most cases, but patients' ability for oral hygiene was reduced after the longer observation period. Especially in elderly patients, their attitudes and manual skills should be considered when planning the design of a new superstructure.

Survival of double-crown-retained dentures either tooth-implant or solely implant-supported: an 8-year retrospective study.

PURPOSE: To compare survival and incidence of complications for solely implant-supported double-crown-retained dentures (DCRDs) and combined tooth-implant-supported DCRDs for restoration of a complete jaw. MATERIALS AND METHODS: Patients were consecutively admitted to treatment at the Department of Prosthodontics, University of Heidelberg, during a time period from 2003 to 2011. Schedule and unscheduled visits were recorded on standardized documentation forms. Age, gender, location of implants, number of abutment teeth, jaw, and antagonist were assessed as possible factors affecting the number of complications per patient. RESULTS: Fifty-five patients with 66 DCRDs on 209 implants and 102 teeth were included. Of these, 30 dentures on 129 implants were solely implant-supported whereas the other 36 were combined tooth-implant-supported. During an observation period of up to 8.3 years (mean 3.4 years; SD 1.9) superstructure survival was 93.3% for the solely implant-supported DCRDs and 100% for the combined tooth-implant-supported DCRDs. Survival without major complications was 86.7% and 83.3%, respectively. Gender and location of both superstructure and implants were statistically associated with a greater number of complications. CONCLUSION: Within the limitations of this exploratory retrospective study, not only solely implant-supported DCRDs but also superstructures combining remaining teeth and implants within DCRDs might be a reliable treatment option for elderly patients. Prospective randomized clinical trials are needed to confirm this, however.

Mycophilic or mycophobic? Legislation and guidelines on wild mushroom commerce reveal different consumption behaviour in European countries.

Mycophiles forage for and pick vast quantities of a wide variety of wild mushroom species. As a result, mushroom intoxications are comparatively frequent in such countries with mycophiles. Thus, national governments are forced to release guidelines or enact legislation in order to ensure the safe commerce of wild mushrooms due to food safety concerns. It is in these guidelines and laws that one can observe whether a country is indeed mycophobic or mycophilic. Furthermore, these laws and guidelines provide valuable information on mushroom preferences and on the consumption habits of each country. As such we were interested in the questions as to whether mushroom consumption behaviour was different within Europe, and if it was possible to discover the typical or distinctive culinary preferences of Slavic or Romanic speaking people, people from special geographical regions or from different zones. This work is based on the analysis of edible mushroom lists available in specific guidelines or legislation related to the consumption and commerce of mushrooms in 27 European countries. The overall diversity of edible mushrooms authorised to be commercialised in Europe is very high. However, only 60 out of a total 268 fungal species can be cultivated. This highlights the importance of guidelines or legislation for the safe commerce of wild mushrooms. The species richness and composition of the mushrooms listed for commerce is very heterogeneous within Europe. The consumption behaviour is not only language-family-related, but is strongly influenced by geographical location and neighbouring countries. Indicator species were detected for different European regions; most of them are widespread fungi, and thus prove culture-specific preferences for these mushrooms. Our results highlight tradition and external input such as trade and cultural exchange as strong factors shaping mushroom consumption behaviour.

Procalcitonin, pyuria and proadrenomedullin in the management of urinary tract infections--'triple p in uti': study protocol for a randomized controlled trial.

BACKGROUND: Urinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions. METHODS AND DESIGN: This randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent. For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines. The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions. DISCUSSION: This trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability. TRIAL REGISTRATION NUMBER: ISRCTN13663741.

Short-term complications of implant-supported and combined tooth-implant-supported fixed dental prostheses.

OBJECTIVE: The objective of this clinical study was to evaluate survival and incidence of complications for metal-ceramic and all-ceramic implant-supported fixed dental prostheses (FDPs) and tooth-implant-supported FDPs. MATERIAL AND METHODS: One-hundred and sixty-six FDPs placed in 132 patients from a prospective study were selected for this retrospective analysis. Included were 91 conventional implant-supported FDPs with implant support on both extremities, 27 implant-supported cantilever FDPs, and 48 tooth-implant-supported FDPs. All restorations were veneered with ceramic. Twenty-six FDPs had a zirconia framework and 140 had a metal framework. Kaplan-Meier analysis was performed to estimate FDP success defined as complication-free survival and the Cox regression model was used to isolate risk factors for the most frequent complications. RESULTS: Within a median follow-up of 1 year and 2 months, three failures were caused by a failed implant (n = 2) and by extended chipping of the veneer (n = 1). In contrast with this low incidence of failure was a high incidence of complications including chipping (n = 29), loss of retention (n = 35), and abutment fractures (n = 2). Multivariate survival analysis revealed a significantly greater incidence of chipping for males and a tendency to increased incidence of chipping for zirconia-based FDPs. The incidence of loss of retention tended to be less for tooth-implant-supported FDPs, for which semi-permanent cement was the only significant risk factor, with a hazard ratio of almost 5. CONCLUSIONS: As chipping of the ceramic veneer was the most frequent complication leading to substantial aftercare, improvements of ceramic veneers are desirable for zirconia-based and metal-based FDPs.

Clinical success rates for polyether crown impressions when mixed dynamically and statically.

The purpose of this study is to compare success rates of dual-viscosity impressions for two types of mixing techniques of the polyether elastomeric impression material. Additionally, influencing parameters on the success rates should be evaluated. The expectation was that there would be no difference between the success rates for the two mixing techniques. Two centres enrolled 290 subjects (727 teeth) into the trial. Patients were randomized for the two types of mixing techniques. One step, dual-viscosity impressions were made with either statically mixed Impregum Soft tray material (SAM) or dynamically mixed Impregum Penta H DuoSoft (DMM). Low viscosity Impregum Garant L DuoSoft was used for both groups. Gingival displacement involved the use of two braided cords. Full-arch trays were used exclusively. Both critical defects and operator errors were assessed for the first impression taken by trained dentists. The primary outcome was impression success. For comparison of the two mixing techniques, the odds ratio for success and the corresponding one-sided 95% confidence interval was calculated by a logistic regression model. To account for the dependence between several teeth within one patient, the method of general estimating equations was used. The overall impression success rate was 35.4%. Both mixing techniques showed equal success rates indicated by an OR of 1.0 and a lower limit of the one-sided 95% confidence interval of 0.71. Using this result to develop the corresponding interval for the difference, it could be shown that the success rate using SAM was at most 8.2% lower than that when using DMM with a probability of 95%. Multivariate logistic regression analysis of other potential influencing factors showed position of finish line (p = 0.008, supra compared to mixed), blood coagulation disorder (p = 0.021) and the level of training of the clinician (student vs dentist, p=0.008) to have an independent influence on the success rate. Dynamic mechanical mixing and the new static mixing of polyether tray material showed nearly equal success rates in the study even though success rates were comparatively low (DMM, 35.3%; SAM, 35.4%).

Survival and chipping of zirconia-based and metal-ceramic implant-supported single crowns.

PURPOSE: The objective of this retrospective study was to compare the incidence of chipping of implant-supported, all-ceramic, and metal-ceramic single crowns. MATERIAL AND METHODS: One hundred fifty-three patients (51.7% male, mean age 55.0 years) received 232 cemented implant-supported single crowns. One hundred and seventy-nine crowns had a metal framework (gold alloy) and 53 crowns were all-ceramic (zirconia framework and glass-ceramic veneer material). Age, gender, kind of cementation, and location of the restorations were assessed as possible factors affecting chipping. RESULTS: During the observation period of up to 5.8 years (mean 2.1 years; standard deviation 1.4), a total of 13 (24.5%) all-ceramic and 17 (9.5%) metal-ceramic crowns suffered from chipping, a difference that was statistically significant. A total of ten single crowns had to be remade resulting in survival of 86.8% (all-ceramic) and 98.3% (metal-ceramic). The other possible factors did not have a significant effect on the chipping. CONCLUSION: Chipping was found to be more frequent for all-ceramic implant-supported single crowns. If the reasons for the vulnerability of all-ceramic crowns remain unknown, implants with all-ceramic single crowns should generally be recommended with care.

Retrospective comparison of semipermanent and permanent cementation of implant-supported single crowns and FDPs with regard to the incidence of survival and complications.

PURPOSE: To retrospectively compare the fixation modalities semipermanent and permanent for all cemented single crowns and Fixed Dental Prostheses (FDPs) placed at the Department of Prosthodontics in the years 2002 to 2010 with regard to the incidence of survival and complications. MATERIALS AND METHODS: Two hundred forty-one patients (48.5% male, mean age 57.3 years) received 166 FDPs and 232 single crowns. A total of 50.6% of the FDPs and 54.7% of the single crowns were fixed using semipermanent cements. Aside from fixation, age, gender, type, location, and material of the suprastructures were assessed as possible factors affecting complications, namely de-cementation, chipping, framework, or abutment fracture. RESULTS: During an observation period of up to 6.6 years (mean 2.24 years; standard deviation 1.38), the survival rates were 96.4% and 100% for FDPs (semipermanent/permanent cementation), and 98.4% and 92.4% for single crowns (semipermanent/permanent). The success rates achieved, counting every complication, for the FDPs were 61.9% and 70.7% (semipermanent/permanent) and for single crowns were 75.6% and 77.1% (semipermanent/permanent). The cement used had a significant effect on loss of retention of the FDPs (p = .006), but no significant effect on the retention of the single crowns. Cementation procedure exhibited no significant impact on chipping for both FDPs and single crowns. The frequency of framework or abutment fractures was too low for further statistical analyses. CONCLUSION: Both semipermanent and permanent cementation of FDPs and single crowns resulted in high survival rates. Within the limitations of the study design, because of the amount of chairside aftercare required, implant-borne FDPs could be recommended for permanent cementation.

Influence of bone augmentation procedures on the short-term prognosis of simultaneously placed implants.

OBJECTIVES: The purpose of this study was to investigate the effect of simultaneous bone-augmentation procedures, and their combination, on the survival of dental implants and on the incidence of complications. MATERIAL AND METHODS: Within a retrospective analysis, 958 implants placed in 404 patients (mean age 58.18) were selected from a prospective clinical study. In 304 cases of reduced bone width, bone spreading (n = 217) with hand osteotomes, or bone splitting (n = 15), or guided bone regeneration (n = 72) combined with autogenous bone grafts were also performed. Eighty-eight implants were placed in combination with simultaneous internal sinus floor elevation without using graft material. For 194 additional implants, several augmentation procedures were combined because of extensive bone deficits. Three-hundred and seventy-two conventionally placed implants served as controls. Implant failures and complications were recorded after a mean observation period of 2.1 years (maximum 6.9 years). RESULTS: Seventeen failures and nine additional implant-related complications were observed. After 4 years, Kaplan-Meier curves revealed a probability of survival without complication of 97.5% for conventionally placed implants, and 95.8% for implants placed in combination with a single augmentation technique. If several augmentation techniques were combined, success decreased to 94.1%. Complication-free survival differences between combined augmentation techniques and conventionally placed implants were significant (P = 0.004). Age, gender, and location showed no effect on implant survival. CONCLUSIONS: It can be concluded that simultaneous bone-augmentation techniques slightly reduce short-term prognosis for dental implants. This effect was more pronounced when advanced defects required the combination of several augmentation procedures.

Efficient prosthodontic treatment in a young patient with long-standing bulimia nervosa: A clinical report.

Time-saving, efficient dental treatment is essential for patients in poor dental condition. This clinical report describes a systematic technique for restoration of the visibly-destroyed dentition of a long-term bulimia nervosa patient, including occlusal vertical dimension increase, with composite resin core foundations and prosthetic rehabilitation with ceramic crowns, in only a few treatment sessions. The efficiency of this procedure is gained from composite resin core restorations that establish the new occlusal vertical dimension (OVD) and replace and form the foundation for the subsequent crown preparation.

Early loading of implants with fixed dental prostheses in edentulous mandibles: 4.5-year clinical results from a prospective study.

AIM: The purpose of this study was to evaluate the survival and success of early-loaded implants placed in the intraforaminal area of the edentulous mandible, and the survival of the implant-supported fixed dental prostheses (FDP). MATERIAL AND METHODS: Thirty-seven patients (18.9% male, mean age 64.5 years) with edentulous lower jaws were treated with implant-supported FDPs in the mandible. One hundred and eighty-five screw-type implants were placed in the intraforaminal area of the symphysis (five implants per patient). Immediately after implant placement, a framework was fabricated and the FDP was manufactured on the framework. Within 2 weeks, the implants were rigidly connected and loaded with the implant-retained FDP. RESULTS: During the 1-8-year observation period (mean 4.5 years), a total of 32 implant-retained complications occurred. Nineteen implants were lost in 10 patients, resulting in a cumulative survival of 89.7%. Nine implants in five patients did not osseointegrate. Although these implants were not removed, because stability within the connective tissue was acceptable and inflammation was absent, they were recorded as unsuccessful. Consequently, the cumulative success declined to 84.9%. Four implants in three patients had clinical signs of periimplantitis (2.2% of all implants). Denture-related complications included one complete failure, when one FDP had to be removed after the last of five implants had been replaced. Furthermore, 10 fractures of the framework occurred in six patients, three FDPs had to be adapted or modified, and the facing of the FDP had to be repaired 16 times in 11 patients. CONCLUSION: Although one-stage early-loaded implants functioned well for most patients with edentulous mandibles, immediate loading is associated with a larger number of implant-related complications than in other studies investigating delayed loading. Because of the substantial prosthetic complications and aftercare, this procedure cannot be generally recommended.

Dopaminergic signals in primary motor cortex.

Brainstem monoamine areas such as the ventral tegmental area (VTA) send dopaminergic projections to the cerebral cortex that are widely distributed across different cortical regions. Whereas the projection to prefrontal areas (PFC) has been studied in detail, little is known about dopaminergic projections to primary motor cortex (M1). These projections have been anatomically characterized in rat and primate M1. Primates have even denser dopaminergic projections to M1 than rats. The physiological role, the effects of dopaminergic input on the activity of M1 circuits, and the behavioral function of this projection are unknown. This review explores the existing anatomical, electrophysiological and behavioral evidence on dopaminergic projections to M1 and speculates about its functional role. The projection may explain basic features of motor learning and memory phenomena. It is of clinical interest because of its potential for augmenting motor recovery after a brain lesion as well as for understanding the symptomatology of patients with Parkinson's disease. Therefore, targeted investigations are necessary.

Optimising lifestyle interventions: identification of health behaviour patterns by cluster analysis in a German 50+ survey.

BACKGROUND: Many prevention and intervention measures are still targeting isolated behaviours such as tobacco use or physical inactivity. Cluster analysis enables the aggregation of single health behaviours in order to identify distinctive behaviour patterns. The purpose of this study was to group a sample of the over-50 population into clusters that exhibit specific health behaviour patterns regarding regular tobacco use, excessive alcohol consumption, unhealthy diet and physical inactivity. METHODS: From the total population of the federal state of Baden-Wuerttemberg, Germany, 982 men and 1020 women aged 50-70 were randomly selected. Subjects were asked by trained interviewers in computer-assisted telephone interviews (CATI) about health behaviour and sociodemographic characteristics. Cluster analysis was conducted to identify distinct health behaviour patterns. Multinomial logistic regression was used to characterize clusters by specific social attributes. RESULTS: Five homogeneous health behaviour clusters were identified: 'No Risk Behaviours' (25.3%), 'Physically Inactives' (21.1%), 'Fruit and Vegetable Avoiders' (18.2%), 'Smokers with Risk Behaviours' (12.7%) and 'Drinkers with Risk Behaviours' (22.7%). Whereas the first cluster is the ideal in terms of risk and prevention, the latter two groups include regular users of tobacco and excessive consumers of alcohol, who also engage in other risk behaviours like inactivity and maintaining an unhealthy diet. These two risk groups also exhibit specific sociodemographic attributes (male, living alone, social class affiliation). CONCLUSION: Unhealthy behaviours evidently occur in typical combinations. An awareness of this clustering enables prevention and intervention measures to be planned so that multiple behaviours can be modified simultaneously.

Influence of various fatty acids on the activity of protein phosphatase type 2C and apoptosis of endothelial cells and macrophages.

In previous work we have demonstrated that protein phosphatase type 2C (PP2C) alpha and beta can be activated by mono-unsaturated fatty acids (MUFAs) leading to apoptosis of cultured endothelial cells. In the present paper we could show that saturated fatty acids (SFAs) did not activate PP2C and did not cause apoptosis both in endothelial cells and macrophages. However, long-chain SFAs (>16 C-atoms) were capable of inhibiting both, activation of PP2C as well as apoptosis of human umbilical vein endothelial cells (HUVECs) and macrophages caused by oleic acid. Interestingly, docosahexaenoic acid (DHA) known to protect arterial vessels against the progression of atherosclerosis caused apoptosis of HUVECs at high concentrations (200-400microM) but inhibited the apoptotic damage of HUVECs at a low, physiologically relevant concentration range (1-10microM). In contrast, oleic acid did not protect HUVECs against damage even at low concentrations (1-25microM). It is supposed that an unbalanced and chronically increased level of MUFAs in blood has an atherosclerotic potential. Furthermore, PP2C activated by MUFAs appears as a new target for drugs to prevent or treat atherosclerosis.

Temozolomide preferentially depletes cancer stem cells in glioblastoma.

The prognosis of patients suffering from glioblastoma (GBM) is dismal despite multimodal therapy. Although chemotherapy with temozolomide may contain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells (CSC) maintaining these tumors persist. We have therefore investigated the effect of temozolomide on CD133(+) and CD133(-) GBM CSC lines. Although differentiated tumor cells constituting the bulk of all tumor cells were resistant to the cytotoxic effects of the substance, temozolomide induced a dose- and time-dependent decline of the stem cell subpopulation. Incubation with sublethal concentrations of temozolomide for 2 days completely depleted clonogenic tumor cells in vitro and substantially reduced tumorigenicity in vivo. In O(6)-methylguanine-DNA-methyltransferase (MGMT)-expressing CSC lines, this effect occurred at 10-fold higher doses compared with MGMT-negative CSC lines. Thus, temozolomide concentrations that are reached in patients were only sufficient to completely eliminate CSC in vitro from MGMT-negative but not from MGMT-positive tumors. Accordingly, our data strongly suggest that optimized temozolomide-based chemotherapeutic protocols might substantially improve the elimination of GBM stem cells and consequently prolong the survival of patients.

All-ceramic inlay-retained fixed partial dentures: preliminary results from a clinical study.

OBJECTIVES: The objective of this study was to evaluate the clinical performance of zirconia-based all-ceramic fixed partial dentures anchored by inlays. METHODS: A total of thirty FPDs, manufactured using a zirconia frame and veneered with press ceramic, were anchored by use of inlay retainers. All FPDs were designed to replace one missing molar and were adhesively luted by use of one of two different resin cements. Documentation included failures and other complications, plaque accumulation, and aesthetic and functional performance. Statistical analysis was performed using a cox-regression model. RESULTS: During the 12 months observation period a total of thirteen clinically relevant complications occurred-four delaminations of the veneer and six decementations. Three FPDs had to be replaced because of a fracture of the framework. The cement chosen, the location, and the design of the retainer had no statistically significant effect on the occurrence of complications. During the observation period, accumulation of plaque on the abutment teeth was not significantly greater than on reference teeth. Postoperative sensitivity did not differ significantly between the different luting cement groups. The aesthetic and functional performance of the FPDs was acceptable. CONCLUSIONS: Improved adhesion between resin cement and inlay retainer is desirable before general recommendation of all-ceramic inlay-retained FPDs. Use of different luting cements seems to have no effect on the occurrence of complications.