Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus.

BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16-, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. METHODS: Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. RESULTS: Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. CONCLUSIONS: Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Mapping the electric field distribution of tightly focused cylindrical vector beams with gold nanorings.

In this paper gold nanorings (NRs) are applied as particularly well-suited sensing elements for mapping the radially symmetric electric fields in the high numerical aperture focus of cylindrical vector beams. The optical properties of gold nanorings are analyzed by a combination of extinction and single particle dark field spectroscopy as well as confocal photoluminescence (PL) imaging. The results are compared to numerical calculations. The in-plane components in the focus of the cylindrical vector beams are estimated through the PL intensity distributions of the NRs. The optimum overlap between the structure and excitation is visualized by a narrow centre spot in the far-field PL scan.

Transcriptomic and proteomic insight into the effects of a defined European mistletoe extract in Ewing sarcoma cells reveals cellular stress responses.

BACKGROUND: The hydrophobic triterpenes, oleanolic and betulinic acid as well as the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties. They do all occur in combination in European mistletoe (Viscum album L.). Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We have previously shown that mistletoe lectins and triterpene acids are effective against Ewing sarcoma in vitro, ex vivo and in vivo. METHODS: We recreated a total mistletoe effect (viscumTT) by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilised with cyclodextrins and analysed the effects of viscumTT and the single extracts on TC-71 Ewing sarcoma cells in vitro by transcriptomic and proteomic profiling. RESULTS: Treatment with the extracts strongly impacted Ewing sarcoma cell gene and protein expression. Apoptosis-associated and stress-activated genes were upregulated, proteasomal protein abundance enhanced and ribosomal and spliceosomal proteins downregulated. The mechanism of action of viscum, TT and viscumTT in TC-71 and MHH-ES-1 cells suggests the involvement of the unfolded protein response. While viscum and viscumTT extract treatment indicate response to oxidative stress and activation of stress-mediated MAPK signalling, TT extract treatment suggests the involvement of TLR signalling and autophagy. CONCLUSIONS: Since the combinatory extract viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic option for paediatric patients with Ewing sarcoma.

Femoral rotation in total knee arthroplasty: a comparison of patient individualized jigs with gap balancing in relation to anatomic landmarks.

PURPOSE: The purpose of our study was to compare the accuracy of the rotational position of the femoral component in total knee arthroplasty aligned with patient individualized jigs (PSJ) to a gap balancing technique (GBT). METHODS: A consecutive series of 21 osteoarthritic patients were treated with 22 cruciate-retaining total knee prostheses. During surgery, the rotation of the femoral component pinholes was recorded for all knees using PSJ and GBT and transferred to computer tomograms (CT). The rotational differences between PSJ and GBT relative to the transepicondylar axis were analysed. RESULTS: The medium rotation of the femoral component pinholes was 1.3° ± 5.1° (min = -6.3°; max = 14.4°) for PSJ and 0.1 ± 1.4° (min = -1.6°; max = 3.4°) for GBT. Outliers of more than 3° were found more frequently with PSJ in 12 cases but only in one for GBT. CONCLUSION: Based on our study, we would not recommend relying intra-operatively solely on the CT-based PSJ without the option to adjust or control femoral rotation. LEVEL OF EVIDENCE: II.

Heat-killed Staphylococcus aureus reduces atherosclerosis by inducing anti-inflammatory macrophages.

BACKGROUND: Staphylococcus aureus cell wall components can induce IL-10 responses by immune cells, which may be atheroprotective. Therefore, in this study, we investigated whether heat-killed S. aureus (HK-SA) could inhibit the development of atherosclerosis. METHODS: Atherosclerosis-susceptible LDL receptor-deficient mice were administered intraperitoneal HK-SA twice weekly and fed a Western-type diet for 6 weeks. RESULTS: HK-SA administration resulted in a 1.6-fold increase in IL-10 production by peritoneal macrophages and splenocytes, and a 12-fold increase in serum IL-10 levels. Moreover, aortic plaque ICAM-1, VCAM-1 and CCL2 expression levels were significantly downregulated by on average 40%. HK-SA-treated mice had reduced numbers of inflammatory Ly-6C(hi) monocytes as well as Th1 and Th17 cells in the circulation and spleen, respectively. Attenuated leucocyte recruitment resulted in a significant inhibition of macrophage and T cell infiltration in atherosclerotic plaques, culminating in a significant 34% reduction in the development of atherosclerosis. To determine the effects of intraperitoneal HK-SA treatment, we stimulated macrophages with HK-SA in vitro. This resulted in a significant toll-like receptor 2 (TLR2)-dependent increase in IL-10, arginase-1, iNOS, TNF-α, PD-L1, CCL22 and indoleamine 2,3-dioxygenase expression. It was found that phosphoinositide 3-kinase crucially determined the balance of pro- and anti-inflammatory gene expression. The HK-SA-induced macrophage phenotype resembled M2b-like immunoregulatory macrophages. CONCLUSIONS: We have shown that HK-SA treatment induces strong anti-inflammatory IL-10 responses by macrophages, which are largely dependent on TLR2 and PI3K, and protects against the development of atherosclerosis. Commensalism with S. aureus could thus reduce cardiovascular events.

Local delivery of the Neuregulin1 receptor ecto-domain (ecto-ErbB4) has a positive effect on regenerated nerve fiber maturation.

The Neuregulin/ErbB system plays an important role in the peripheral nervous system, under both normal and pathological conditions. We previously demonstrated that expression of soluble ecto-ErbB4, the released extracellular fragment of the ErbB4 receptor, stimulated glial cell migration in vitro. In this study we examined the possibility of manipulating this system in vivo in order to improve injured peripheral nerve regeneration. Transected rat median nerves of adult female Wistar rats were repaired with a 10-mm-long graft made by muscle-in-vein combined nerve guide previously transduced with either the adeno-associated viral (AAV) vector AAV2-LacZ or AAV2-ecto-ErbB4. Autologous nerve grafts were used as control. Both stereological and functional analyses were performed to assess nerve regeneration. Data show that delivery of soluble ecto-ErbB4 by gene transfer in the muscle-in-vein combined nerve guide has a positive effect on fiber maturation, suggesting that it could represent a potential tool for improving peripheral nerve regeneration.

Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction.

Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU, p < 0.0001) and correlated with simultaneously measured CK levels (R = 0.357, p < 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU), p < 0.0001). MNV correlated with infarct size (R = 0.705, p = 0.007) and inversely correlated with left ventricular ejection fraction (R = -0.718, p = 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU, p = 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU, p = 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia-reperfusion.

Change of gait in patients with lateral osteoarthritis of the knee after mobile-bearing unicompartmental knee arthroplasty.

PURPOSE: Patients with lateral osteoarthritis of the knee suffer not only from pain but also impaired gait and limited mobility. Common treatment options are total knee replacement and lateral unicompartmental knee arthroplasty (UKA). The domed lateral mobile-bearing Oxford Uni is a new treatment option for patients with isolated osteoarthritis of the lateral compartment of the knee joint. We used instrumented gait analysis and clinical scores to study patients before and after lateral UKA. METHODS: Nineteen patients suffering from lateral osteoarthritis underwent implantation of a mobile-bearing lateral UKA. They were examined in a gait analysis before the operation and after an average follow-up time of 7 months. Gait analysis was performed on a treadmill with six infrared cameras to identify gait characteristics (e.g. velocity, stride time, stride length, knee abduction or hip adduction). RESULTS: Mean velocity changed from 0.58 to 0.73 m/s. Significant advancements were also found in knee abduction and hip adduction. Time and length of strides improved significantly as well as the clinical scores American Knee Society Score, Oxford-12, FFb-H-OA and Devane Score. CONCLUSION: Patients with lateral osteoarthritis of the knee showed an impaired gait with an increased knee abduction and hip adduction angle. Implantation of a lateral mobile UKA can restore normal axis of the leg and improve gait and function of the knee. Instrumented gait analysis is a suitable measuring instrument to quantify and qualify the post-operative change of gait. LEVEL OF EVIDENCE: II.

Geographic and temporal variations in pollen exposure across Europe.

BACKGROUND: The EC-funded EuroPrevall project examined the prevalence of food allergy across Europe. A well-established factor in the occurrence of food allergy is primary sensitization to pollen. OBJECTIVE: To analyse geographic and temporal variations in pollen exposure, allowing the investigation of how these variations influence the prevalence and incidence of food allergies across Europe. METHODS: Airborne pollen data for two decades (1990-2009) were obtained from 13 monitoring sites located as close as possible to the EuroPrevall survey centres. Start dates, intensity and duration of Betulaceae, Oleaceae, Poaceae and Asteraceae pollen seasons were examined. Mean, slope of the regression, probability level (P) and dominant taxa (%) were calculated. Trends were considered significant at P < 0.05. RESULTS: On a European scale, Betulaceae, in particular Betula, is the most dominant pollen exposure, two folds higher than to Poaceae, and greater than five folds higher than to Oleaceae and Asteraceae. Only in Reykjavik, Madrid and Derby was Poaceae the dominant pollen, as was Oleaceae in Thessaloniki. Weed pollen (Asteraceae) was never dominant, exposure accounted for >10% of total pollen exposure only in Siauliai (Artemisia) and Legnano (Ambrosia). Consistent trends towards changing intensity or duration of exposure were not observed, possibly with the exception of (not significant) decreased exposure to Artemisia and increased exposure to Ambrosia. CONCLUSIONS: This is the first comprehensive study quantifying exposure to the major allergenic pollen families Betulaceae, Oleaceae, Poaceae and Asteraceae across Europe. These data can now be used for studies into patterns of sensitization and allergy to pollen and foods.

An unexpected intriguing effect of Toll-like receptor regulator RP105 (CD180) on atherosclerosis formation with alterations on B-cell activation.

OBJECTIVE: In atherosclerosis, Toll-like receptors (TLRs) are traditionally linked to effects on tissue macrophages or foam cells. RP105, a structural TLR4 homolog, is an important regulator of TLR signaling. The effects of RP105 on TLR signaling vary for different leukocyte subsets known to be involved in atherosclerosis, making it unique in its role of either suppressing (in myeloid cells) or enhancing (in B cells) TLR-regulated inflammation in different cell types. We aimed to identify a role of TLR accessory molecule RP105 on circulating cells in atherosclerotic plaque formation. APPROACH AND RESULTS: Irradiated low density lipoprotein receptor deficient mice received RP105(-/-) or wild-type bone marrow. RP105(-/-) chimeras displayed a 57% reduced plaque burden. Interestingly, total and activated B-cell numbers were significantly reduced in RP105(-/-) chimeras. Activation of B1 B cells was unaltered, suggesting that RP105 deficiency only affected inflammatory B2 B cells. IgM levels were unaltered, but anti-oxidized low-density lipoprotein and anti-malondialdehyde-modified low-density lipoprotein IgG2c antibody levels were significantly lower in RP105(-/-) chimeras, confirming effects on B2 B cells rather than B1 B cells. Moreover, B-cell activating factor expression was reduced in spleens of RP105(-/-) chimeras. CONCLUSIONS: RP105 deficiency on circulating cells results in an intriguing unexpected TLR-associated mechanisms that decrease atherosclerotic lesion formation with alterations on proinflammatory B2 B cells.

High-resolution tomography study of the porosity of three restorative resin composites.

OBJECTIVES: The aim of this study was to analyze the porosity of three photopolymerizable resin composites: one high-viscous resin composite (Filtek™ P60®, 3 M™ ESPE™), one moderate-viscosity resin composite (Grandio®, VOCO™), and one low-viscous resin composite (Filtek™ Supreme XTE®, 3 M™ ESPE™). MATERIALS AND METHODS: A total of 36 cylindrical samples with a height of 2 mm and a diameter of 2 mm were prepared using PTFE molds. Eighteen cylinders were prepared by two incremental applications of 1 mm into the molds, then polymerized (group 1). For the other 18 samples (group 2), the first increment was polymerized before the second addition was made. The average porosity percentage and the average porosity volume were evaluated by high-resolution tomography (Nanotom M® - Phoenix X-Ray(TM), Wunstorf, Germany). The impact of incremental applications in terms of porosity was also evaluated. RESULTS: Irrespective of the protocol used, the low viscous material presented an average porosity percentage and an average porosity volume significantly greater than those of the other materials. Incremental application (group 2 samples) led to an increase in the average porosity percentage and volume irrespective of the material compared to the group 1 samples. CONCLUSIONS: High-resolution tomography appeared to be a particularly suitable tool for studying the porosity of resin composites. The viscosity and the handling of these materials seemed to be influential factors on their porosity. CLINICAL RELEVANCE: The presence of porosities in dental resin composites remains an objective reality, especially with low-viscous resin composites. Since the intrinsic porosity of the materials can be neither controlled nor modified by the operator, rigorous and iterative clinical protocols still remain the best way to limit inclusion of porosities in the resin composites.

Cardiac delivery of modified mRNA using lipid nanoparticles: Cellular targets and biodistribution after intramyocardial administration.

Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac tissue impairment. Modified messenger RNA (modRNA) presents compelling properties that could allow new therapeutic strategies to tackle the underlying molecular pathways that ultimately lead to development of chronic heart failure. However, clinical application of modRNA for the heart is challenged by the lack of effective and safe delivery systems. Lipid nanoparticles (LNPs) represent a well characterized class of RNA delivery systems, which were recently approved for clinical usage in mRNA-based COVID-19 vaccines. In this study, we evaluated the potential of LNPs for cardiac delivery of modRNA. We tested how variations in C12-200 modRNA-LNP composition affect transfection levels and biodistribution after intramyocardial administration in both healthy and myocardial-infarcted mice, and determined the targeted cardiac cell types. Our data revealed that LNP-mediated modRNA delivery outperforms the current state of the art (modRNA in citrate buffer) upon intramyocardial administration in mice, with only minor differences among the formulations tested. Furthermore, we determined both in vitro and in vivo that the cardiac cells targeted by modRNA-LNPs include fibroblasts, endothelial cells and epicardial cells, suggesting that these cell types could represent targets for therapeutic interference with these LNP formulations. These outcomes may serve as a starting point for LNP development specifically for therapeutic mRNA cardiac delivery applications.

Airborne olive pollen counts are not representative of exposure to the major olive allergen Ole e 1.

Pollen is routinely monitored, but it is unknown whether pollen counts represent allergen exposure. We therefore simultaneously determined olive pollen and Ole e 1 in ambient air in Córdoba, Spain, and Évora, Portugal, using Hirst-type traps for pollen and high-volume cascade impactors for allergen. Pollen from different days released 12-fold different amounts of Ole e 1 per pollen (both locations P < 0.001). Average allergen release from pollen (pollen potency) was much higher in Córdoba (3.9 pg Ole e 1/pollen) than in Évora (0.8 pg Ole e 1/pollen, P = 0.004). Indeed, yearly olive pollen counts in Córdoba were 2.4 times higher than in Évora, but Ole e 1 concentrations were 7.6 times higher. When modeling the origin of the pollen, >40% of Ole e 1 exposure in Évora was explained by high-potency pollen originating from the south of Spain. Thus, olive pollen can vary substantially in allergen release, even though they are morphologically identical.

Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of toll-like receptors.

BACKGROUND: After myocardial infarction (MI), the inflammatory response is indispensable for initiating reparatory processes. However, the intensity and duration of the inflammation cause additional damage to the already injured myocardium. Treatment with mesenchymal stem cells (MSC) upon MI positively affects cardiac function. This happens likely via a paracrine mechanism. As MSC are potent modulators of the immune system, this could influence this postinfarct immune response. Since MSC express toll-like receptors (TLR), danger signal (DAMP) produced after MI could influence their immunomodulatory properties. SCOPE OF REVIEW: Not much is known about the direct immunomodulatory efficiency of MSC when injected in a strong inflammatory environment. This review focuses first on the interactions between MSC and the immune system. Subsequently, an overview is provided of the effects of DAMP-associated TLR activation on MSC and their immunomodulative properties after myocardial infarction. MAJOR CONCLUSIONS: MSC can strongly influence most cell types of the immune system. TLR signaling can increase and decrease this immunomodulatory potential, depending on the available ligands. Although reports are inconsistent, TLR3 activation may boost immunomodulation by MSC, while TLR4 activation suppresses it. GENERAL SIGNIFICANCE: Elucidating the effects of TLR activation on MSC could identify new preconditioning strategies which might improve their immunomodulative properties.

[Metal ion concentrations in patients with metal-metal bearings in prostheses]. / Metallkonzentrationen bei Patienten mit Metall-Metall-Gleitpaarungs-Prothese.

Increased wear leads to elevated systemic and local metal ion concentrations for patients treated with metal-on-metal bearings. The local metal ion content in the close environment of the joint replacement (e.g. joint aspirate or tissue) is several times higher compared to the systemic metal content (e.g. in blood or serum). As a result of increased metal ion levels, local and systemic effects, such as osteolysis, pseudotumors, sensitization or in rare cases toxicity may occur. Although the definition of a specific threshold to define clinical problems is difficult due to a lack of sensitivity, the systemic metal concentration is frequently measured clinically. Currently a threshold for cobalt and chromium between 4 µg/l and 7 µg/l is under debate. Very high levels (≥ 20 µg/l) or a steady increase over time should be a warning sign; however, metal ion levels should not be interpreted as a single diagnostic tool but rather in the entire context of the clinical, radiological and cross-sectional imaging, metal artefact reduction sequence (MARS) magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) findings.

Teledentistry and management protocol in a pediatric dental department during the first COVID-19 lockdown.

BACKGROUND: During the first COVID-19 lockdown, from March 12 to May 15, 2020, private dental practices in France and in many other countries remained closed. Dental emergencies were therefore partly redirected to hospital dental departments. The aim of this article is to describe the modalities of remote management of emergencies during this period, by the pediatric dentistry department of Nancy University Hospital (France), via an oral telemedicine protocol. PATIENTS AND METHODS: All parents of children in difficulty were invited to contact the department by phone. Initial triage was managed by externs, interns, or dental practitioners following a management protocol specifically adapted to pediatric dentistry for this context. Depending on the situation (type of complaint, geographical location of the patients, possibility of travel, availability of digital equipment, etc.), an oral telemedicine solution was proposed using the Covotem® software (Maincare Society, Canejan, France) via the Pulsy platform (public interest grouping validated by the Grand Est Regional Agency for Health) and possibly using an intraoral photographic protocol suggested by the team. RESULTS: During this period, 176 patients used the pediatric dental department, 40 of whom were managed via oral telemedicine. Of these children, 57% (23/40) required an appointment in the department during the lockdown, 30% (12/40) did not require follow-up, and 13% (5/40) required a post-lockdown appointment. This teledentistry protocol resulted in a diagnosis in most cases (93%). CONCLUSION: Patient management through oral telemedicine appears to be an effective tool for planning and organizing oral healthcare. It should be more widely considered in dentistry in the current context of pressure in medical emergencies, significant medical needs, and medical desertification.

Psychotropic drug treatment, clinical characteristics and cognitive processing speed in patients with schizophrenia: results from the ELAN study.

INTRODUCTION: Psychotropic drug combinations (PDC) are common in the treatment of patients with schizophrenia but there is little research regarding the effects of PDC on cognition. OBJECTIVE: The aim of this study was to analyse the effects of antipsychotic monotherapy and various types of PDC on cognitive processing speed (CPS). METHODS: ELAN is a 24-month multi-site prospective observational controlled trial following up 374 patients with schizophrenia under routine treatment conditions following discharge from inpatient treatment. The propensity score method, multinomial logistic regression analyses and mixed effects regression models were used. RESULTS: CPS correlated significantly with PANSS and GAF scores and improved over time in the monotherapy group. Negative effects of some PDC (antipsychotics + tranquilizers/antipsychotics+at least 2 other psychopharmacological subclasses, sedative/anticholinergic drugs/high adjusted antipsychotic dose) lost significance after controlling for clinical characteristics. DISCUSSION: Indications for PDC should be examined with care although, in the present study, effects on cognition were small.

A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells.

The European mistletoe Viscum album L. is a plant used for remedies in cancer treatment. The benefit of commonly used aqueous extracts is controversial but the plant contains water insoluble triterpene acids providing interesting anticancer properties. Triterpene extracts (TE) from plants and single triterpenoids such as oleanolic acid (OA) or betulinic acid (BA) are known for their cytotoxic effects on cancer cell lines in vitro. We report here cytotoxic effects of a novel OA-rich triterpene extract from mistletoe (V. album L., Santalaceae) solubilized by 2-hydroxypropyl-ß-cyclodextrin (2-HP-ß-CD) on B16.F10 mouse melanoma cells. The 2-HP-ß-CD solubilized triterpene extract (STE) was highly cytotoxic by causing DNA fragmentation, followed by loss of membrane integrity and intracellular adenosine-5'-triphosphate (ATP). Blocking the caspase machinery by inhibitors aborted DNA fragmentation and delayed the cytotoxic effects but did not prevent cell death. The solubilization by 2-HP-ß-CD allows a solvent-free application of triterpene extracts in the in vitro setting. These findings suggest the use of STE from mistletoe as a solvent-free anticancer drug for preclinical animal experiments and clinical trials.

Extended sagittal saw cut significantly reduces fracture load in cementless unicompartmental knee arthroplasty compared to cemented tibia plateaus: an experimental cadaver study.

PURPOSE: Periprosthetic tibial plateau fractures represent a rare but serious complication in unicompartmental knee arthroplasty and are associated with extended sagittal tibial bone cuts. These can occur during the surgery, weaken the posterior cortex of the tibia and are associated with periprosthetic tibial plateau fractures. Although excellent long-term results have been reported with cemented unicompartmental knee arthroplasty, there is high interest in cementless fixation. The aim of the study was to compare fracture loads of cementless and cemented unicompartmental knee arthroplasty. METHODS: Tibial components of the Oxford Uni were implanted in six paired fresh-frozen tibiae with a defined extended saw cut (10°) at the dorsal cortex of each specimen. In one set, surgery was performed with cement fixation, and in the other, cementless components were implanted. Vertical loads were then applied under standardised conditions to fracture the specimens. RESULTS: Median loads of 3.7 (0.7-6.9) kN led to fractures in the cemented group, whereas cementless fixated tibiae fractured with a median load of 1.6 (0.2-4.3) kN (P = 0.02). CONCLUSION: The loading capacity in tibiae with cementless components is significantly less compared to cemented fixation. The results show that in case of an extended sagittal bone cut patients especially those with poor bone quality who are treated with a cementless unicompartmental knee arthroplasty are at higher risk for periprosthetic tibial fractures.