CR TKA UHMWPE Wear Tested after Artificial Aging of the Vitamin E Treated Gliding Component by Simulating Daily Patient Activities

The wear behaviour of total knee arthroplasty (TKA) is dominated by two wear mechanisms: the abrasive wear and the delamination of the gliding components, where the second is strongly linked to aging processes and stress concentration in the material. The addition of vitamin E to the bulk material is a potential way to reduce the aging processes. This study evaluates the wear behaviour and delamination susceptibility of the gliding components of a vitamin E blended, ultra-high molecular weight polyethylene (UHMWPE) cruciate retaining (CR) total knee arthroplasty. Daily activities such as level walking, ascending and descending stairs, bending of the knee, and sitting and rising from a chair were simulated with a data set received from an instrumented knee prosthesis. After 5 million test cycles no structural failure of the gliding components was observed. The wear rate was with mg/million cycles falling within the limit of previous reports for established wear test methods

New vegetation history reconstructions suggest a biostratigraphic assignment of the lowermost Rodderberg interglacial (Germany) to MIS 11

Along with the ongoing climate crisis, research efforts increasingly focus on Pleistocene environmental archives. Interglacial periods are of special interest, as they offer crucial information about natural interactions (i.e. not influenced by human activities) between climate and ecosystems within a climatic setting comparable to the Holocene and/or climate change projections. The sedimentary infill of the Rodderberg crater, 10 km south of the city of Bonn (Germany), records several glacial-interglacial cycles in superposition, which makes it a rare and promising environmental archive. One of the most challenging targets is to establish a robust chronological framework for the Rodderberg sediment sequence. In the present study we reconstruct the vegetation history of the basal and most prominent interglacial sequence, the lowermost Rodderberg interglacial (LRI), and apply the principles of pollen biostratigraphy to estimate the depositional age. At the base of the sequence steppe tundra conditions prevailed during the cryocratic phase before the onset of the interglacial. Rising temperatures caused afforestation of the landscape with boreal forests during the protocratic phase, which subsequently were replaced by temperate forests in the mesocratic phase. The sequence continues under unstable vegetation conditions characterized by temperate forests dominated by Carpinus and Abies during the oligocratic phase. During the terminal part of the LRI, the telocratic phase, boreal to nemoboreal forests covered the landscape. Due to climatic deterioration these forests collapsed and a steppe tundra evolved again (cryocratic phase). This climate-driven glacial-interglacial cycle is followed by an interstadial with rather closed nemoboreal forest vegetation. Based on the occurrences of characteristic taxa as well as the vegetation assemblages and succession, we refrain from correlating the LRI with any of the warm stages between c. 240 and 180 ka BP, i.e. roughly corresponding to MIS 7. A correlation with the Holsteinian, which was previously physically dated to c. 340e325 ka BP, cannot unambiguously be excluded, however, the absence of Pterocarya during the LRI argues against it. Instead, the LRI has striking similarities with the Kärlich interglacial, which has been previously physically dated to c. 400 ka BP, making it chronologically equivalent to MIS 11

Cultivation of the PHB-producing cyanobacterium Synechococcus leopoliensis in a pilot-scale open system using nitrogen from waste streams

PHB-producing cyanobacteria may provide the raw material for bio-based and biodegradable plastics. To commercialize photoautotrophic PHB production, their cultivation needs to be scaled up in open systems and to reduce costs and increase sustainability, nutrients must be obtained from waste streams. Here, the feasibility of these steps was verified. Different PHB-producing cyanobacteria were compared in laboratory-scale cultivations using either water from recirculating aquaculture systems or pre-processed liquid digestate as nutrient sources. Then, Synechococcus leopoliensis was cultivated in an open thin-layer photobioreactor (18 m2, 200 L), were growth in mineral Z-medium was again compared to said waste streams. All cultivations were successful. Cultivation in mineral medium resulted in both the highest final biomass yield (6 g L−1) and productivity (0.7 g L−1 d−1). Both waste stream-based media showed lower biomass yields and productivities (2 g L−1 and 0.25–0.3 g L−1 d−1). However, due to differences in the cultivation conditions (e.g., temperature, nutrient supply), final biomass yield and productivity do not represent the performance of the cultivations adequately. Relative parameters such as nitrogen and energy conversion ratios indicate that cultivation with aquaculture water suffered from insufficient nitrogen supply to the culture, whereas the use pre-processed liquid digestate resulted in a substantial loss of nitrogen due to volatilization. All cultivations in the open system were continued in the laboratory, where cultures were starved for ten days under nutrient-depleted conditions (without nitrogen, phosphorus, or both). While PHB accumulation occurred, concentrations were comparatively low (< 1%dw). The comparison of the results suggests that PHB yields were influenced more by the initial cultivation condition than by the specific type of nutrient depletion. Thus, while the cultivation with waste streams in an open system is feasible, environmental parameters seem to influence PHB yields considerably and must be considered for the optimization of the complete process

ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability

Endothelial cell–selective adhesion molecule (ESAM) is specifically expressed at endothelial tight junctions and on platelets. To test whether ESAM is involved in leukocyte extravasation, we have generated mice carrying a disrupted ESAM gene and analyzed them in three different inflammation models. We found that recruitment of lymphocytes into inflamed skin was unaffected by the gene disruption. However, the migration of neutrophils into chemically inflamed peritoneum was inhibited by 70% at 2 h after stimulation, recovering at later time points. Analyzing neutrophil extravasation directly by intravital microscopy in the cremaster muscle revealed that leukocyte extravasation was reduced (50%) in ESAM−/− mice without affecting leukocyte rolling and adhesion. Depletion of >98% of circulating platelets did not abolish the ESAM deficiency–related inhibitory effect on neutrophil extravasation, indicating that it is only ESAM at endothelial tight junctions that is relevant for the extravasation process. Knocking down ESAM expression in endothelial cells resulted in reduced levels of activated Rho, a GTPase implicated in the destabilization of tight junctions. Indeed, vascular permeability stimulated by vascular endothelial growth factor was reduced in ESAM−/− mice. Collectively, ESAM at endothelial tight junctions participates in the migration of neutrophils through the vessel wall, possibly by influencing endothelial cell contacts

Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells

By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combina- torial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebi- otic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarci- nogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids were produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal ca- pacity. Our integrated approach demonstrates the potential of modeling for rationally formulating synbi- otics-based treatments in the future

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Correlation between contrast sensitivity and thickness of individual retinal layers studied on patients with multiple sclerosis

EINLEITUNG: Multiple Sklerose (MS) ist die häufigste neuroinflammatorische und neurodegenerative Erkrankung im jungen Erwachsenenalter und führt zu vielen verschiedenen Einschränkungen für die Betroffenen. Erheblich beeinträchtigt fühlen sich Patienten, wenn das visuelle System betroffen ist, was häufig und oft im frühen Erkrankungsstadium der Fall ist. Ein Zusammenhang zwischen retinaler Degeneration, erhoben durch Messungen mit optischer Kohärenztomografie (OCT), und Kontrastempfindlichkeit (KE) konnte bereits nachgewiesen werden. Ziel dieser Arbeit ist die Überprüfung eines Zusammenhangs zwischen Degenerationen bestimmter Netzhautschichten und KE. METHODEN: Untersucht wurden sechsundfünfzig Augen von achtundzwanzig an MS erkrankten Patienten. Dabei hatten fünfundzwanzig Patienten schubförmige MS (RRMS), zwei Patienten ein klinisch isoliertes Syndrom (CIS) und ein Patient sekundär progressive MS (SPMS). Als Kontrollgruppe dienten vierzehn gesunde Probanden. Die Netzhaut wurde mittels Spectral-Domain OCT untersucht und mit einer Betasoftware des Herstellers automatisch segmentiert. Die intraretinale Segmentierung der Einzelschichten wurde manuell nachbearbeitet. In verallgemeinerten Schätzungsgleichungen (GEEs) erfolgte ein Gruppenvergleich der einzelnen Netzhautschichten von Erkrankten (MS) mit einer gesunden Kontrollgruppe (HC). Die KE wurde durch einen Functional Acuity Contrast Test (FACT) unter photopischen und mesopischen Bedingungen erhoben (KE-Tag und KE- Nacht). Die ermittelten KE-Werte wurden innerhalb der MS-Gruppe auf Korrelation zu den einzelnen Netzhautschichtdicken untersucht. ERGEBNISSE: In den GEEs zeigt sich eine signifikante Verdünnung in der MS-Kohorte im Vergleich zur gesunden Kontrollgruppe der gesamten Netzhaut (totales Makulavolumen (TMV), p < 0,001), der peripapillären Nervenfaserschicht (p-RNFL) (p = 0,001), der kombinierten Ganglienzell-/inneren plexiformen Schicht (GCIPL) (p < 0,001) und dem Komplex aus äußerem Segment (OS) der Photorezeptoren und retinalem Pigmentepithel (RPE) (p < 0,001). Bei MS- Patienten konnte eine signifikante KE-Minderung unter photopischen (p = 0,007) und mesopischen (p = 0,027) Bedingungen im Vergleich zu gesunden Kontrollen nachgewiesen werden. Die p-RNFL (p = 0,006) und GCIPL-Schicht (p = 0,008) korrelieren signifikant mit der KE bei Tagmessung. FAZIT: KE-Minderungen bei MS-Erkrankten zeigen sich signifikant im Vergleich zu Gesunden. Weiterhin korrelieren KE-Minderungen mit Schichtdickenabnahme der p-RNFL und GCIPL innerhalb der MS-Kohorte. Dies könnte vielleicht ein Hinweis auf eine Struktur-Funktionsbeziehung innerhalb der Netzhaut sein. Auf Grund des Zelluntergangs scheint das Zusammenspiel der einzelnen Netzhautschichten gestört, so dass die Netzhaut in ihrer Funktionalität eingeschränkt wird, wodurch es final zu Einschränkungen im visuellen System, vor allem beim Kontrastsehen kommt.INTRODUCTION: Multiple sclerosis (MS) is the most common inflammatory and neurodegenerative disease in young adulthood and leads to varying impairment for affected persons. Visual dysfunction is a frequent symptom in an early stage of the disease which considerably impairs patients. Previous studies based on optical coherence tomography (OCT) indicated there exists an association between retinal damage and contrast sensitivity (CS) in MS. Goal of this work is the evaluation of a correlation between degeneration of retinal layers and CS. METHODS: Fifty-six eyes of twenty-eight patients suffering from multiple sclerosis were studied. Twenty-five patients have been diagnosed with relapsing-remitting multiple sclerosis (RRMS), two patients with clinical isolated syndrome and one patient with secondary-progressive multiple sclerosis (SPMS). The control group consisted of fourteen healthy subjects. The retina was examined by spectral domain OCT and automatically segmented by using a beta software of the manufacturer. The intraretinal segmentation of the individual layers was then post-processed manually. In generalized estimating equations (GEEs) a group comparison of the different retinal layers of patients (MS) with a healthy control group (HC) was carried out. CS was measured by Functional Acuity Contrast Test (FACT) under photopic and mesopic conditions (CS-day and CS-night). The determined CS values were examined within the MS group in correlation with the individual retinal layer thickness. RESULTS: The GEEs show a significant thinning in the MS cohort compared to the healthy control group throughout the retina (total macular volume (TMV), p <0.001), the peripapillary nerve fiber layer (p-RNFL) (p = 0.001), the combined ganglion cell-/inner plexiform layer (GCIPL) (p <0.00) and the complex of the outer segment (OS) of the photoreceptors and retinal pigment epithelium (RPE) (p <0.00). In MS patients a significant reduction of CS under photopic (p = 0.007) and mesopic (p = 0.027) conditions compared to healthy controls could be detected. The p-RNFL (p = 0.006) and GCIPL layer (p = 0.008) significantly correlated with the reduction of CS-Day. DISCUSSION: MS patients show significantly reduced CS in comparison to healthy subjects. Furthermore CS reductions correlate with a decrease in layer thickness of p-RNFL and GCIPL within the MS cohort. This might be an indication of a structure-functional relationship within the retina. Due to the cell destruction the interplay between the retinal layers seems to be disturbed. So the retina is limited in functionality which ultimately leads to restrictions in the visual system, especially in CS

In-depth analysis of cost structure for electroconvulsive therapy in a performance-based hospital budget

Objective New medical guideline recommendations for the treatment of major depressive disorders and regulative changes in the payment system of the German mental health care system warrant a revision of the framework in which electroconvulsive therapies (ECT) are offered. Methods A cost structure analysis of the clinical resources essential for the ECT procedure was conducted and economically validated, exemplified at a German inpatient ECT treatment center. Results The identification of directly attributable costs to the ECT intervention presupposes an accurate assessment of personnel engagement time and material consumption as well as an inclusion of overhead costs for the operational readiness of the hospital. Conclusion The increasing importance of ECT in the clinical portfolio of therapy options demands an adequate refunding to support the expansion of this highly effective treatment. For the calculation of an appropriate reimbursement for ECT and ascertaining an acceptable contribution, a detailed knowledge of personnel costs and infrastructure settings of the respective hospitals is required