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Most pesticide research has focussed on risk to managed honeybees, but other managed and wild bees are also exposed to pesticides. Critically, we know little about the magnitude and sources of risk to honeybees compared with other bees during crop pollination.To compare pesticide exposure and risk across wild and managed bees, we sampled the main bee groups present during bloom in 20 apple orchards, including managed honeybees (Apis mellifera), managed bumblebee workers (Bombus impatiens), wild mining bees (Andrena spp. and Andrena [Melandrena] spp.), bumblebee foundress queens (Bombus impatiens) and eastern carpenter bees (Xylocopa virginica). We screened all bees for 92 pesticides and computed a Risk Quotient using available toxicity data (honeybee LD50s), adjusting for differences in toxicity known to scale with body mass. To gain insight into exposure origin, we compared residues in bees to those in focal orchard apple and dandelion flowers.Nearly all bee samples contained pesticides (95%), with the average contamination level ranging from 7.1 ± 2.8 parts per billion (ppb) in B. impatiens workers to 388.4 ± 146.2 ppb in Andrena. Exposure profiles were similar for all bees except A. mellifera, whose unique exposure profile included high levels of the neonicotinoid insecticide thiamethoxam.All bee groups except wild B. impatiens queens had at least one sample exceeding a US Environmental Protection Agency or European Food Safety Authority exposure level of concern. Apis mellifera experienced significantly greater risk than other bee groups, with 63% and 81% of samples exceeding an acute or chronic exposure level of concern, respectively. Risk to honeybees was driven primarily by high thiamethoxam levels not found in focal orchard flowers and likely originating outside the orchard.Synthesis and applications: We find that pesticide exposure and risk differ between honeybees and other managed and wild bees during apple pollination. Furthermore, pesticide exposure is a landscape‐scale phenomenon and therefore measures to reduce exposure must consider the surroundings beyond focal farms. Limiting orchard sprays, while reducing on‐farm exposures, will not protect far‐foraging bees from off‐farm exposures such as thiamethoxam, which we hypothesize is coming from nearby seed‐treated corn fields planted during apple bloom. [ABSTRACT FROM AUTHOR]

Summary: Epiphytic microbes frequently affect plant phenotype and fitness, but their effects depend on microbe abundance and community composition. Filtering by plant traits and deterministic dispersal‐mediated processes can affect microbiome assembly, yet their relative contribution to predictable variation in microbiome is poorly understood.We compared the effects of host‐plant filtering and dispersal on nectar microbiome presence, abundance, and composition. We inoculated representative bacteria and yeast into 30 plants across four phenotypically distinct cultivars of Epilobium canum. We compared the growth of inoculated communities to openly visited flowers from a subset of the same plants.There was clear evidence of host selection when we inoculated flowers with synthetic communities. However, plants with the highest microbial densities when inoculated did not have the highest microbial densities when openly visited. Instead, plants predictably varied in the presence of bacteria, which was correlated with pollen receipt and floral traits, suggesting a role for deterministic dispersal.These findings suggest that host filtering could drive plant microbiome assembly in tissues where species pools are large and dispersal is high. However, deterministic differences in microbial dispersal to hosts may be equally or more important when microbes rely on an animal vector, dispersal is low, or arrival order is important. [ABSTRACT FROM AUTHOR]

Floral nectar is frequently colonised by microbes. However, nectar microbial communities are typically species‐poor and dominated by few cosmopolitan genera. One hypothesis is that nectar constituents may act as environmental filters. We tested how five non‐sugar nectar compounds as well as elevated sugar impacted the growth of 12 fungal and bacterial species isolated from nectar, pollinators, and the environment. We hypothesised that nectar isolated microbes would have the least growth suppression. Additionally, to test if nectar compounds could affect the outcome of competition between microbes, we grew a subset of microbes in co‐culture across a subset of treatments. We found that some compounds such as H2O2 suppressed microbial growth across many but not all microbes tested. Other compounds were more specialised in the microbes they impacted. As hypothesised, the nectar specialist yeast Metschnikowia reukaufii was unaffected by most nectar compounds assayed. However, many non‐nectar specialist microbes remained unaffected by nectar compounds thought to reduce microbial growth. Our results show that nectar chemistry can influence microbial communities but that microbe‐specific responses to nectar compounds are common. Nectar chemistry also affected the outcome of species interactions among microbial taxa, suggesting that non‐sugar compounds can affect microbial community assembly in flowers. [ABSTRACT FROM AUTHOR]

Hydrogen is a promising fuel to decarbonize aviation, but macroeconomic studies are currently missing. Computable general equilibrium (CGE) models are suitable to conduct macroeconomic analyses and are frequently employed in hydrogen and aviation research. The main objective of this paper is to investigate existing CGE studies related to (a) hydrogen and (b) aviation to derive a macroeconomic research agenda for hydrogen-powered aviation. Therefore, the well-established method of systematic literature review is conducted. First, we provide an overview of 18 hydrogen-related and 27 aviation-related CGE studies and analyze the literature with respect to appropriate categories. Second, we highlight key insights and identify research gaps for both the hydrogen- and aviation-related CGE literature. Our findings comprise, inter alia, hydrogen's current lack of cost competitiveness and the macroeconomic relevance of air transportation. Research gaps include, among others, a stronger focus on sustainable hydrogen and a more holistic perspective on the air transportation system. Third, we derive implications for macroeconomic research on hydrogen-powered aviation, including (I) the consideration of existing modeling approaches, (II) the utilization of interdisciplinary data and scenarios, (III) geographical suitability, (IV) the application of diverse policy tools and (V) a holistic perspective. Our work contributes a meaningful foundation for macroeconomic studies on hydrogen-powered aviation. Moreover, we recommend policymakers to address the macroeconomic perspectives of hydrogen use in air transportation. [ABSTRACT FROM AUTHOR]

Background and aims: This experimental study assesses the influence of different gases and insufflation pressures on the portal, central-venous and peripheral-arterial pH during experimental laparoscopy. Methods: Firstly, 36 male WAG/Rij rats were randomized into six groups (n = 6) spontaneously breathing during anaesthesia: laparoscopy using carbon dioxide or helium at 6 and 12 mmHg, gasless laparoscopy and laparotomy. 45 and 90 min after setup, blood was sampled from the portal vein, vena cava and the common femoral artery with immediate blood gas analysis. Secondly, 12 animals were mechanically ventilated at physiological arterial pH during 90 min of laparotomy (n = 6) or carbon dioxide laparoscopy at 12 mmHg (n = 6) with respective blood gas analyses. Results: Over time, in spontaneously breathing rats, carbon dioxide laparoscopy caused significant insufflation pressure-dependent portal acidosis (pH at 6 mmHg, 6.99 [6.95–7.04] at 45 min and 6.95 [6.94–6.96] at 90 min, pH at 12 mmHg, 6.89 [6.82–6.90] at 45 min and 6.84 [6.81–6.87] at 90 min; p < 0.05) compared to laparotomy (portal pH 7.29 [7.23–7.30] at 45 min and 7.29 [7.20–7.30] at 90 min; p > 0.05). Central-venous and peripheral-arterial acidosis was significant but less severely reduced during carbon dioxide laparoscopy. Laparotomy, helium laparoscopy and gasless laparoscopy showed no comparable acidosis in all vessels. Portal and central-venous acidosis during carbon dioxide laparoscopy at 12 mmHg was not reversible by mechanical hyperventilation maintaining a physiological arterial pH (pH portal 6.85 [6.84–6.90] (p = 0.004), central-venous 6.93 [6.90–6.99] (p = 0.004), peripheral-arterial 7.29 [7.29–7.31] (p = 0.220) at 90 min; Wilcoxon–Mann–Whitney test). Conclusion: Carbon dioxide laparoscopy led to insufflation pressure-dependent severe portal and less severe central-venous acidosis not reversible by mechanical hyperventilation. [ABSTRACT FROM AUTHOR]

TV series such as “House MD”, “Grey´s Anatomy” or “Emergency Room” are well perceived by medical students. Seminars featuring medical TV series such as “House MD” might serve as door-opener to attract medical students to learn more about rare diseases. The TV series “House MD” is troublesome for the main character Dr. House is an excellent diagnostician but at the same time a rather misanthropic person. Therefore, lecturing medicine with the help of “House MD” requires constant evaluation. From 2008 to 2016 we are using the well-known TV series “House MD” continuously to attract medical students and teach them about rare diseases as well as diagnostic strategies. We collected from 213 students a detailed questionnaire assessing their learning experience. 76.6% of our students (n = 157) reported to watching medical dramas on a regular basis. The Dr. House seminar was compared to traditional seminars and our students reported an improved learning effect (69.9%), better concentration (89.7%), higher motivation to participate (88.7%), and more fun (86.7%) (all p<0.001). The students see Dr. House’s behavior quite critically. Likert assessment on a 5-point scale identified strong disagreement with Dr. House´s interpersonal skills in dealing with his colleagues (median = 1) and patients (median = 1). At the same time, the students strongly agreed with his outstanding diagnostic (median = 5) and therapeutic capabilities (median = 4). Medical students visiting a Dr. House teaching seminar are highly motivated to learn more about rare diseases. They were positively influenced by TV series such as Dr. House to improve their diagnostic and clinical skills. At the same time, they are critical enough not to see Dr. House as a role model for their own personality. Well performed medical TV shows such as Dr. House can successfully be used in an educational setting to motivate medical students to come into seminars to learn more about rare diseases. [ABSTRACT FROM AUTHOR]

Background & Aims Infectious hepatitis C virus (HCV) particles bind to host lipoproteins such as low-density lipoproteins ( LDLs). Low-density lipoprotein receptors (LDLR) have been termed candidate receptors for HCV- LDL complexes. Functional host genetic single nucleotide polymorphisms ( SNPs) in the apolipoprotein E ( APOE) gene encoding apolipoprotein E (apoE) - a major structural LDL component and natural ligand of LDLR - likely influence the course of HCV infection. We investigated the prevalence of APOE SNPs in two large and independent cohorts of patients with chronic HCV infection compared to respective controls. Methods We genotyped 996 chronically HCV-infected patients; 179 patients with spontaneous HCV clearance; 283 individuals with non- HCV-associated liver disease; and 2 234 healthy controls. Results APOE genotype proportions in patients with persistent HCV infection significantly differed from healthy controls ( P = 0.007) primarily because of a substantial under-representation of APOE4 alleles in chronically HCV-infected patients (10.2%) compared to 13.0% in healthy controls ( P = 0.001). The distribution of APOE4 allele positive genotypes (ε2ε4, ε3ε4, ε4ε4) also significantly differed between chronically HCV-infected patients and healthy controls (1.4%, 17%, 1% vs. 2.4%, 20.5%, 1.7%; P = 0.001), suggesting a protective effect of the APOE4 allele in HCV infection. This was confirmed by a significant over-representation of the APOE4 allele in patients with spontaneous HCV clearance (17.6%; P = 0.00008). The APOE4 allele distribution in patients with non- HCV-associated liver disease (14.0%) was very similar to healthy controls and also differed from chronically HCV-infected patients ( P = 0.012), suggesting HCV specificity. Conclusions Our findings suggest that the APOE4 allele may confer a protective effect in the course of HCV infection. [ABSTRACT FROM AUTHOR]

Background: Little is known about the characteristics of patients seeking help from dedicated centers for undiagnosed and rare diseases. However, information about their demographics, symptoms, prior diagnoses and medical specialty is crucial to optimize these centers' processes and infrastructure.Methods: Using a questionnaire, structured information from 522 adult patients contacting a center for undiagnosed and rare diseases was obtained. The information included basic sociodemographic data (age, gender, insurance status), previous hospital admissions, primary symptoms of complaint and previously determined diagnosis.Results: The majority of patients completing the questionnaire were female, 300 (57 %) vs. 222 men (43 %). The median age was 52 years (range 18-92). More than half, 309 (59 %), of our patients had never been admitted to a university hospital. Common diagnoses included other soft tissue disorders, not classified elsewhere (ICD M79, n = 63, 15.3 %), somatoform disorders (ICD F45, n = 51, 12.3 %) and other polyneuropathies (ICD G62, n=36, 8.7 %). The most frequent symptoms were general weakness (n = 180, 36.6 %) followed by arthralgia (n = 124, 25.2 %) and abdominal discomfort (n = 113, 23.0 %). The majority of patients had either internal medicine (81.3 %) and/or neurologic (37.6 %) health problems.Conclusions: Pain-associated diagnoses and the typical "unexplained" medical conditions (chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome) are frequent among people contacting a center dedicated to undiagnosed diseases. The chief symptoms are mostly unspecific. An interdisciplinary organizational approach involving mainly internal medicine, neurology and psychiatry/psychosomatic care is needed. [ABSTRACT FROM AUTHOR]

Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N. meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post-infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity-associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction-based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21WAF1/CIP1 and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis-infected cells. Moreover, an increase in p21WAF1/CIP1 expression was found to be p53 independent. Genetic ablation of p21WAF1/CIP1 and cyclin G2 abrogated N. meningitidis-induced S phase accumulation. Finally, by measuring the levels of the biomarker 8-hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells. [ABSTRACT FROM AUTHOR]

In the present study, an active site titration method is demonstrated, to determine the amount of active enzyme (β-galactosidase), immobilized on a support. Two types of supports were investigated, viz. amino acrylic resin and a mixed matrix membrane. Furthermore, 2′,4′-dinitrophenyl 2-deoxy-2-fluoro-β- d -galactopyranoside was used as an inhibitor for the active site titration of immobilized β-galactosidase obtained from Kluyveromyces lactis . Using the active site titration, approximately 8.3 mg of active enzyme was found on 1 g of dried commercially available SPRIN imibond, which is an amino acrylic resin with covalently bound β-galactosidase obtained from K. lactis . However, this method, in its present form, was not effective on the mixed matrix membranes due to the irreversible partial adsorption of the leaving group (2′,4′-dinitrophenolate) by the membrane. This observation implied that it is important to investigate interactions between the support and the used inhibitor and leaving group. [ABSTRACT FROM AUTHOR]

The hydrogen (H2) momentum affects the aviation sector. However, a macroeconomic consideration is currently missing. To address this research gap, the paper derives a methodology for evaluating macroeconomic effects of H2 in aviation and applies this approach to Germany. Three goals are addressed: (1) Construction of a German macroeconomic database. (2) Translation of H2 supply chains to the system of national accounts. (3) Implementation of H2-powered aviation into the macroeconomic data framework. The article presents an economy-wide database for analyzing H2-powered aviation. Subsequently, the paper highlights three H2 supply pathways, provides an exemplary techno-economic cost break-down for ten H2 components and translates them into the data framework. Eight relevant macroeconomic sectors for H2-powered aviation are identified and quantified. Overall, the paper contributes on a suitable foundation to apply the macroeconomic dataset and to conduct macroeconomic analyses on H2-powered aviation. Finally, the article highlights further research potential on job effects related to future H2 demand. • The hydrogen momentum affects the aviation sector, but a macroeconomic perspective is currently lacking. • This article derives a methodology for evaluating the macroeconomic effects of hydrogen use in aviation and applies this approach to an economy-wide dataset for Germany. • The study investigates three hydrogen supply pathways, provides an exemplary cost break-down for ten hydrogen components and translates them into a national data framework. • Eight macroeconomic sectors relevant for hydrogen-powered aviation are identified and quantified by assigning the respective techno-economic cost components. • The article highlights meaningful research potential on macroeconomic analyses of hydrogen-powered aviation and employment effects related to future hydrogen demands. [ABSTRACT FROM AUTHOR]

Background Pattern recognition receptors ( PRRs) orchestrate the innate immune defence in human biliary epithelial cells ( BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. Aims We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. Methods We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis ( PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT- PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-κB activation assays and ELISA for secreted IL-8 and tumour necrosis factor ( TNF)-α. Results Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/ IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-γ and TNF-α in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-α inhibition partly restored protective innate immune tolerance, endogenous TNF-α secretion probably contributed to inappropriate endotoxin responses in BECs. Conclusion Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis. [ABSTRACT FROM AUTHOR]

Abstract: Low-density lipoprotein receptor (LDLR) is involved in the entry of hepatitis C virus (HCV) in host cells. We investigated whether three single-nucleotide alterations within LDLR might be associated with the course of hepatitis C infection and response to antiviral therapy. We enrolled 651 individuals with chronic HCV infection who had received interferon-based combination therapy, 174 individuals with self-limited HCV infection, and 516 healthy controls. LDLR c.1171G>A, c.1413G>A, and c.*52G>A genotyping was performed by real-time PCR-based assays. HCV genotype 1-infected individuals who were homozygous for 3′UTR c.*52G were at increased risk for virologic non-response to antiviral therapy compared to virologic responders (66.3% vs. 51.0%, p = 0.001). Furthermore, compared to healthy controls, self-limited HCV genotype 1 infection was significantly associated with c.1171A (15.1% vs. 6.6%, p = 0.006) and negatively associated with c.1413G>A heterozygosity (33.0% vs. 46.1%, p = 0.023). The data indicate that LDLR alterations are correlated with response to interferon-based combination therapy and with self-limitation of HCV 1 infection. [Copyright &y& Elsevier]

Signaling pathways based on the reversible phosphorylation of proteins control most aspects of cellular life in higher organisms. Extracellular stimuli can induce growth, differentiation, survival and the stress response through a number of highly conserved signaling pathways. We discuss how the intensity and duration of signals may have dramatic consequences on the way cells respond to stimuli. Picking the central Ras-Raf-MEK-ERK signal cascade, we developed a mathematical model of how stimuli induce different signal patterns and thereby different cellular responses, depending on cell type and the ratio between B-Raf and C-Raf. Based on biochemical data for activation and dephosphorylation, as well as the differential equations of our model, we suggest a different signaling pattern and response result for B-Raf (strong activation, sustained signal) and C-Raf (steep activation, transient signal). We further support the significance of such differential modulatory signaling by showing different Raf isoform expression in various cell lines and experimental testing of the predicted kinase activities in B-Raf, C-Raf and mutated versions. [ABSTRACT FROM AUTHOR]

Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4bp insertion/deletion) and the 3′-UTR (1188-A/C), which have been reported to influence IL-12 synthesis, are associated with the outcome of HCV infection.We analyzed 186 individuals with spontaneous HCV clearance, 501 chronically HCV infected patients, and 217 healthy controls. IL12B 3′-UTR and promoter genotyping was performed by Taqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA-amplification, respectively.The proportion of IL12B promoter and 3′-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype 1-infected patients with high baseline viremia carrying the IL12B 3′-UTR 1188-C-allele showed significantly higher sustained virologic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates (24.2% vs. 12% vs. zero % for A/A, A/C and C/C).IL12B 3′-UTR 1188-C-allele carriers appear to be capable of responding more efficiently to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be demonstrated. [Copyright &y& Elsevier]

While Botrytis cinerea causes gray mold on many plants, its close relative, Botrytis fabae, is host-specifically infecting predominantly faba bean plants. To explore the basis for its narrow host range, a gapless genome sequence of B. fabae strain G12 (BfabG12) was generated. The BfabG12 genome encompasses 45.0 Mb, with 16 chromosomal telomere-to-telomere contigs that show high synteny and sequence similarity to the corresponding B. cinerea B05.10 (BcB0510) chromosomes. Compared to BcB0510, it is 6% larger, due to many AT-rich regions containing remnants of transposable elements, but encodes fewer genes (11,420 vs. 11,707), due to losses of chromosomal segments with up to 20 genes. The coding capacity of BfabG12 is further reduced by nearly 400 genes that had been inactivated by mutations leading to truncations compared to their BcB0510 orthologues. Several species-specific gene clusters for secondary metabolite biosynthesis with stage-specific expression were identified. Comparison of the proteins secreted during infection revealed high similarities, including 17 phytotoxic proteins that were detected in both species. Our data indicate that evolution of the host-specific B. fabae occurred from an ancestral pathogen with wide host range similar to B. cinerea and was accompanied by losses and degeneration of genes, thereby reducing its pathogenic flexibility. [ABSTRACT FROM AUTHOR]

The present paper reports on the development of a biodegradable overmolded orthopedic implant: a metal bone fixing screw, which has been overmolded with a functionalized thin layer of biodegradable polymer to enhance cell adhesion during the healing process. The main challenges were to integrate precise, high-throughput and repeatable solutions to achieve a thin, defect-free structured polymer layer and to ensure a high and consistent implant quality. The work carried out entailed determining proper materials (Purasorb PDLG 5010) for the biodegradable overmolding layer and its economical substitute (NaKu PLA 100HF) to be used during initial tool and process development, designing the surface structure of the overmolded polymer layer, development of injection molding tools, as well as feeding and handling procedures. The injection overmolding process of Purasorb PDLG 5010 polymer was controlled, and the process parameters were optimized. In particular, the dominant process parameters for the overmolding, namely injection pressure, barrel temperature and mold temperature, were experimentally examined using a circumscribed three-factor central composite design and two quality marks; overmolding roughness and mass of polymer. The analysis of the experimental results shows that the mass of the overmolding is not feasible for use as the quality mark. However, the optimal parameters for the overmolding of a metallic implant screw with a thin, micro-structured polymer layer with a predefined roughness of the surface texture have been identified successfully. [ABSTRACT FROM AUTHOR]

no abstract available [ABSTRACT FROM AUTHOR]

During the recent decades, powder injection molding has achieved a significant position as a manufacturing technique for high value-add products. For further progress, the improved dimensional accuracy of the sintered parts is of considerable importance. Investigations into meeting this demand through an enhanced process conduct comprising an additional compression step after cavity filling were performed. To achieve improved cavity filling and investigate influencing parameters, a demonstrator design was developed which enabled the generation of thin membranes by controlled piston movements. The combined injection and embossing process reached replication accuracies of ±0.15 to ±0.4%. An interaction between membrane quality and the compression parameters could be asserted. Moreover, the additional compaction step allowed for reduction of the minimum membrane values to about half of the thicknesses feasible by unmodified PIM processes. [ABSTRACT FROM AUTHOR]

A novel aryl boronate salt is synthesized and successfully applied as catalyst for the aldol reaction of aldehydes (I) with acetone. [ABSTRACT FROM AUTHOR]

Although offering distinctive economic benefits the mass fabrication of carrier devices incorporating membranes as quasi-monolithic devices reveals strong technological challenges. Powder injection molding would be an effective process for this purpose, however, manufacturing parts of considerable wall thickness variations and to meet strong precision demands remains problematic. To evaluate novel ways of process conducts as well as to determine influencing parameters a demonstrator design had been developed which enabled the generation of thin membranes by controlled piston movement. Suitable lay-out of the runner system had been determined with the help of simulation calculations. The combined injection + embossing process conduct enabled to reduce minimum membrane thickness to about a half. Investigation of parameter influence showed that embossing force and gap width before injection have an ameliorative effect on membrane quality whereas the embossing delay time had no significant impact. [ABSTRACT FROM AUTHOR]

The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls. Results are correlated with clinical records. suPAR concentrations were elevated in patients with PSC compared to patients with IBD only and to healthy controls (p < 0.001). Elevated suPAR levels were associated with the presence of liver cirrhosis (p < 0.001) and signs of portal hypertension (p < 0.001). suPAR revealed a high accuracy for the discrimination of the presence of liver cirrhosis comparable to previously validated noninvasive fibrosis markers (area under the curve (AUC) 0.802 (95%CI: 0.702–0.902)). Further, we demonstrated that suPAR levels may indicate the presence of acute cholangitis episodes (p < 0.001). Finally, despite the high proportion of PSC patients with IBD, presence of IBD and its disease activity did not influence circulating suPAR levels. suPAR represents a previously unrecognized biomarker for diagnosis and liver cirrhosis detection in patients with PSC. However, it does not appear to be confounded by intestinal inflammation in the context of IBD. [ABSTRACT FROM AUTHOR]

Variation in dispersal ability among taxa affects community assembly and biodiversity maintenance within metacommunities. Although fungi and bacteria frequently coexist, their relative dispersal abilities are poorly understood. Nectar-inhabiting microbial communities affect plant reproduction and pollinator behavior, and are excellent models for studying dispersal of bacteria and fungi in a metacommunity framework. Here, we assay dispersal ability of common nectar bacteria and fungi in an insect-based dispersal experiment. We then compare these results with the incidence and abundance of culturable flower-inhabiting bacteria and fungi within naturally occurring flowers across two coflowering communities in California across two flowering seasons. Our microbial dispersal experiment demonstrates that bacteria disperse via thrips among artificial habitat patches more readily than fungi. In the field, incidence and abundance of culturable bacteria and fungi were positively correlated, but bacteria were much more widespread. These patterns suggest shared dispersal routes or habitat requirements among culturable bacteria and fungi, but differences in dispersal or colonization frequency by thrips, common flower visitors. The finding that culturable bacteria are more common among nectar sampled here, in part due to superior thrips-mediated dispersal, may have relevance for microbial life history, community assembly of microbes, and plant–pollinator interactions. [ABSTRACT FROM AUTHOR]

Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. NCT02669680 Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies. [Display omitted] • G-CSF was expected to be a novel therapy for acute-on-chronic liver failure. • In this first multicenter, randomized phase II trial, G-CSF did not improve patient survival. • G-CSF was unable to reduce the rate of complications and did not improve organ function. [ABSTRACT FROM AUTHOR]

Purpose: Several retrospective analyses have suggested that obese men with prostate cancer treated with external beam radiotherapy (EBRT) have outcomes inferior to those of normal-weight men. However, a recently presented analysis for the first time challenged this association between body mass index (BMI) and treatment failure. It is therefore important to provide further data on this issue. Methods and Materials: This was a retrospective analysis of 564 men treated with risk-adapted conformal EBRT at a single institution. Low-risk patients received EBRT alone, and the other patients received EBRT plus endocrine treatment. In addition, high-risk patients were treated to higher EBRT doses (74 Gy). A rectal balloon catheter for internal immobilization, which can be identified on portal images, was used in 261 patients (46%). Thus, localization did not rely on bony landmarks alone in these cases. Results: The median BMI was 26, and 15% of patients had BMI ≥30. Neither univariate nor multivariate analyses detected any significant impact of BMI on biochemical relapse, prostate cancer–specific survival, or overall survival. The 5-year biochemical relapse rate was 21% and prostate cancerspecific survival 96%. Conclusions: The present analysis of a large cohort of consecutively treated patients suggests that efforts to reduce prostate movement and geographic miss might result in comparable outcomes in obese and normal-weight patients. [ABSTRACT FROM AUTHOR]

Background: The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress, however it is unclear whether HCV induces chronic ER stress, and if so whether adaptation mechanisms are initiated. We wanted to characterize the kinetics of HCV-induced ER stress during infection and assess adaptation mechanisms and their significance. Methods and Findings: The HuH7.5.1 cellular system and HCV-transgenic (HCV-Tg) mice were used to characterize HCVinduced ER stress/UPR pathway activation and adaptation. HCV induced a wave of acute ER stress peaking 2-5 days postinfection, which rapidly subsided thereafter. UPR pathways were activated including IRE1 and EIF2α phosphorylation, ATF6 cleavage and XBP-1 splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4 were upregulated. CHOP, a UPR regulated protein was activated and translocated to the nucleus. Remarkably, UPR activity did not return to baseline but remained elevated for up to 14 days post infection suggesting that chronic ER stress is induced. At this time, cells adapted to ER stress and were less responsive to further drug-induced ER stress. Similar results were obtained in HCVTg mice. Suppression of HCV by Interferon-α 2a treatment, restored UPR responsiveness to ER stress tolerant cells. Conclusions: Our study shows, for the first time, that HCV induces adaptation to chronic ER stress which was reversed upon viral suppression. These finding represent a novel viral mechanism to manipulate cellular response pathways. [ABSTRACT FROM AUTHOR]

Recently CC chemokine receptor 5 (CCR5) related immune mechanisms and a functional mutation of the CCR5 gene have been implicated in hepatitis C virus (HCV) infection in a cohort of predominantly hemophiliac patients. The present study investigated the frequency and clinical consequences of the CCR5 Δ32 mutation in two genetically homogeneous populations of HCV infected patients with a different risk profile for infection. Genomic DNA samples from 333 German patients with chronic HCV infection were screened by PCR for the presence of the CCR5 Δ32 polymorphism. In-hospital patients admitted for other diseases than viral hepatitis but with a comparable risk for HCV exposure were used as control population (n=125). Allele frequencies of CCR5 Δ32 polymorphism did not differ significantly between the two groups (7.6% and 9.5%, respectively) and control subjects (10.4%), and did not deviate from Hardy-Weinberg equilibrium in any group. Furthermore, there were no major differences between patients with respect to HCV genotypes, viral loads, liver enzymes, or fibrosis scores in relation to the presence or absence of the heterozygous CCR5 Δ32 mutation. Differences in inflammatory scores in liver biopsy samples and response to antiviral therapy in CCR5 Δ32 heterozygotes in one cohort could neither be reproduced in the other group of patients nor when both cohorts were pooled. These results argue against a strong effect of the CCR5 Δ32 deletion regarding these phenotypes. In conclusion, we found no increased frequency of the CCR5 Δ32 polymorphism in two independent cohorts of patients with HCV infection but without hemophilia as the main risk factor for infection. As the major difference to investigations demonstrating an association between CCR5 Δ32 and HCV infection is the selection of cases and controls, our study emphasizes the importance of epidemiological criteria for association studies of HCV infection. [ABSTRACT FROM AUTHOR]

African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host's circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia. [ABSTRACT FROM AUTHOR]

Background: The increasing popularity and availability of tablet computers raises questions regarding clinical scenarios. This pilot study examined the patient's satisfaction when using a tablet-based digital questionnaire as a tool for obtaining medical history in an emergency department and to what extent gender, age, technical competence and mother tongue influence the user satisfaction. Patients were asked to complete three consecutive questionnaires: The first questionnaire collected basic epidemiological data to measure past digital usage behaviour, the second questionnaire collected the patient's medical history, and the third questionnaire assessed the overall perceived user satisfaction when using the tablet-based survey application for medical anamnesis.Results: Of 111 consenting patients, 86 completed all three questionnaires. In summary, the user evaluation was positive with 97.7% (n = 84) of the patients stating that they had no major difficulties using the digital questionnaire. Only 8.1% (n = 7) of patients reported a preference to fill out a paper-and-pen version on the next visit instead, while 98.8% (n = 85) stated that they would feel confident filling out a digital questionnaire on the next visit. The variables gender, age, mother tongue and/or technical competence did not exert a statistically significant influence towards the defined scales usability, content and overall impression.Conclusion: In conclusion, self-administered tablet-based questionnaires are widely accepted tools for collecting medical information in the emergency room across all ages and genders, regardless of technical competence. [ABSTRACT FROM AUTHOR]

Disease and cannibalism are two strongly density-dependent processes that can suppress predator populations. Here we show that California populations of the omnivorous predatory bug Geocoris pallens are subject to infection by a pathogen, as yet unidentified, that elicits elevated expression of cannibalism. Laboratory experiments showed that the pathogen is moderately virulent, causing flattened abdomens, elevated nymphal mortality, delayed development, and reduced body size of adult females. Infection furthermore increases the expression of cannibalism. Field populations of Geocoris spp. declined strongly in association with sharp increases in the expression of egg cannibalism by adult G. pallens. Increased cannibalism was accompanied by a strongly bimodal distribution of cannibalism expression, with some females (putatively uninfected) expressing little cannibalism and others (putatively infected) consuming most or all of the eggs present. Highly cannibalistic females did not increase their consumption of Ephestia cautella moth eggs, suggesting that the high cannibalism phenotype reflected a specific loss of restraint against eating conspecifics. Highly cannibalistic females also often exhibited reduced egg laying, consistent with a virulent pathogen; less frequently, more cannibalistic females exhibited elevated egg laying, suggesting that cannibalism might also facilitate recycling of nutrients in eggs. Elevated cannibalism was not correlated with reduced prey availability or elevated field densities of G. pallens. Geocoris pallens population crashes appear to reflect the combined consequences of direct virulence—adverse pathogen effects on the infected host's physiology—and indirect virulence—mortality of both infected and uninfected individuals due to elevated cannibalism expression by infected individuals. [ABSTRACT FROM AUTHOR]

Background: Foodborne botulism is a life-threatening, rapidly progressive disease. It has an incidence of less than 10 cases per year in Germany and mostly affects several previously healthy people at the same time. The only specific treatment is the administration of botulism antitoxin. According to the German guidelines administration of antitoxin is recommended only in the first 24 hours after oral ingestion of the toxin.Case Presentation: A 47-year-old white woman and her 51-year-old white husband presented with paralysis of multiple cranial nerves and rapidly descending paralysis approximately 72 hours after ingestion of home-canned beans. The disease was complicated by autonomic changes like hypertension, febrile temperatures, and a paralytic ileus. The diagnosis was confirmed by identification of botulinum neurotoxin type A in the serum of the woman. In accordance with the German guidelines, antitoxin was not given due to the prolonged time interval at diagnosis. Both patients had a long intensive care unit course requiring ventilation for approximately 5 months. Finally they recovered completely.Conclusions: A full recovery from foodborne botulism is possible even in patients with intensive care lasting several months. There are only case reports indicating that administration of antitoxin may shorten the course of the disease, even if given later than 24 hours after intoxication. Due to the rarity of the disease and its rapid course there are no randomized controlled trials. Thus, evidence of the superiority of this treatment is lacking. However, the prevailing view according to the German guidelines to administer antitoxin only within 24 hours after ingestion of the toxin should be questioned in the case of progression of the disease with proof of remaining toxin in the blood. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 30-year old male received transplantation of liver, pancreas, kidney, small bowel and right hemicolon for short bowel syndrome after multiple enteral resections due to Crohn‘s disease. It discussed the infections with zoonotic hepatitis E virus (HEV) that have been increasingly in industrialized countries; and mentions treatment guidelines, the initiation of ribavirin (RBV) monotherap.

isolation of two new indole alkaloids (I) and (II) and confirmation of their structure by independent synthesis [ABSTRACT FROM AUTHOR]

The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA. [ABSTRACT FROM AUTHOR]

Background and Aims: C/EBP homologous protein (CHOP) plays pro-apoptotic roles in the integrated stress response. Recently, a tumor suppressive role for CHOP was demonstrated in lung cancer via regulation of tumor metabolism. To explore the role of CHOP in hepatocarcinogenesis, we induced hepatocellular carcinoma (HCC) in wild type (wt) and CHOP knockout (KO) mice using the carcinogen N-diethylnitrosamine (DEN). Results: Analysis of tumor development showed reduced tumor load, with markedly smaller tumor nodules in the CHOP KO animals, suggesting oncogenic roles of CHOP in carcinogen-induced HCC. In wt tumors, CHOP was exclusively expressed in tumor tissue, with minimal expression in normal parenchyma. Analysis of human adenocarcinomas of various origins demonstrated scattered expression of CHOP in the tumors, pointing to relevance in human pathology. Characterization of pathways that may contribute to preferential expression of CHOP in the tumor identified ATF6 as a potential candidate. ATF6, a key member of the endoplasmic reticulum stress signaling machinery, exhibited a similar pattern of expression as CHOP and strong activation in wt but not CHOP KO tumors. Because HCC is induced by chronic inflammation, we assessed whether CHOP deficiency affects tumor-immune system crosstalk. We found that the number of macrophages and levels of IFNγ and CCL4 mRNA were markedly reduced in tumors from CHOP KO relative to wt mice, suggesting a role for CHOP in modulating tumor microenvironment and macrophage recruitment to the tumor. Conclusion: Our data highlights a role for CHOP as a positive regulator of carcinogen-induced HCC progression through a complex mechanism that involves the immune system and modulation of stress signaling pathways. [ABSTRACT FROM AUTHOR]

Background & Aims: The liver is a major site of drug metabolism and elimination and as such is susceptible to drug toxicity. Drug induced liver injury is a leading cause of acute liver injury, of which acetaminophen (APAP) is the most frequent causative agent. APAP toxicity is initiated by its toxic metabolite NAPQI. However, downstream mechanisms underlying APAP induced cell death are still unclear. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have recently emerged as major regulators of metabolic homeostasis. UPR regulation of the transcription repressor CHOP promotes cell death. We analyzed the role of UPR and CHOP in mediating APAP hepatotoxicity. Methods: A toxic dose of APAP was orally administered to wild type (wt) and CHOP knockout (KO) mice and damage mechanisms were assessed. Results: CHOP KO mice were protected from APAP induced damage and exhibited decreased liver necrosis and increased survival. APAP metabolism in CHOP KO mice was undisturbed and glutathione was depleted at similar kinetics to wt. ER stress and UPR activation were overtly seen 12h following APAP administration, a time that coincided with strong upregulation of CHOP. Remarkably, CHOP KO but not wt mice exhibited hepatocyte proliferation at sites of necrosis. In vitro, large T immortalized CHOP KO hepatocytes were protected from APAP toxicity in comparison to wt control cells. Conclusions: CHOP upregulation during APAP induced liver injury compromises hepatocyte survival in various mechanisms, in part by curtailing the regeneration phase following liver damage. Thus, CHOP plays a pro-damage role in response to APAP intoxication. [Copyright &y& Elsevier]

Background/Aims: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. Methods: The CHI3L1 −131G→C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n =440) by 5′-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 −131G→C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. Results: CHI3L1 −131G→C genotype was strongly associated with the stage of liver fibrosis in the screening (n =265, P =0.001) and validation cohort (n =175, P =0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P =0.002). Conclusions: The CHI3L1 promoter polymorphism −131G→C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. [Copyright &y& Elsevier]

Background/Aims: Intercross studies in inbred mice susceptible or resistant to liver fibrosis revealed complement factor 5 as a quantitative trait gene associated with the development of fibrosis. In 277 patients with hepatitis C, two C5 SNPs, rs17611 and rs2300929, have been associated with advanced fibrosis. Methods: We investigated the association of these C5 SNPs with advanced fibrosis in 1435 HCV infected patients and in 1003 patients with other liver diseases. We performed genotyping with melting curve analysis using fluorescence resonance energy transfer probes in the LightCycler. Results: The defined high-risk genotypes (AA and TT) and alleles (A and T) were not associated with advanced fibrosis in HCV patients when Chi square testing and logistic regression analysis were applied (rs17611A 0.45 in F0-1 vs. 0.43 in F2-4, P =0.31; rs2300929T 0.91 F0-1 and 0.91 in F2-4, P =0.82). In the group of patients with liver diseases other than HCV we neither found an association of the C5 SNPs with advanced fibrosis nor an overrepresentation of the SNPs in patients with cirrhosis. Conclusions: We found no evidence that these C5 SNPs are genetic risk factors for the development of advanced fibrosis in chronic HCV infection or other chronic liver diseases. [Copyright &y& Elsevier]

Members of the guanine exchange factor (GEF) family of scaffold proteins are involved in the integration of signal flow down-stream of many receptors in adaptive immunity. However, the full complement of GEFs that function downstream of Toll-like receptors (TLRs) requires further identification and functional understanding. By systematically integrating expression profiles from immune and epithelial cells with functional studies, we demonstrate that protein kinase A anchoring protein 13 (AKAP13), a scaffold protein with GEF activity, is an activator of NF-κB downstream of TLR2 signaling. Stimulation of the human macrophage cell line THP-1 and epithelial cells with a TLR2 ligand caused a significant up-regulation in AKAP13 mRNA, corresponding to an increase in protein expression. Analysis of TLR2 reporter cell lines deficient in AKAP13 expression revealed significantly reduced NF-κB activation and reduced secretion of interleukin-8 and MCP-1 in response to specific ligand stimulation. Furthermore, NF-κB activation was partially inhibited by a GEF-deficient AKAP13 mutant. AKAP13 was also involved in phosphorylation of JNK but not of extracellular signal-regulated kinase ERK1 and -2 following ligand stimulation. Together, our results suggest that AKAP13 plays a role in TLR2-mediated NF-κB activation and suggest that GEF-containing scaffold proteins may confer specificity to innate immune responses downstream of TLRs. [ABSTRACT FROM AUTHOR]

Background/Aims: The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein β3 subunit (GNB3) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. Methods: We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. Results: Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients (P=0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI=1.4–16.5; P=0.011). Conclusions: The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients. [Copyright &y& Elsevier]

A process for the development, characterization and correlation of composite materials for 3D printing is presented, alongside the processing of a polymer-ceramic functional composite using fused deposition modeling (FDM). The composite was developed using acrylonitrile butadiene styrene (ABS) as the matrix material filled with barium titanate (BT) micro-powder up to 35 vol % (74.2 wt %). The ABS-BT composites exhibited a shear thinning behavior with increasing ceramic content. The composite was 3D printed into structural and functional test samples using FDM by adapting and optimizing the print parameters. Structural characterization revealed increasingly brittle behavior at higher filler ratios, with the ultimate tensile strength falling from 25.5 MPa for pure ABS to 13.7 MPa for the ABS-35 vol % BT composite. Four-point flexural tests showed a similar decrease in flexural strength with increasing ceramic content. Functional characterization revealed an increase in the relative permittivity at 200 kHz from 3.08 for pure ABS to 11.5 for the composite with 35 vol % BT. These results were correlated with the Maxwell-Garnett and Jayasundere-Smith effective medium models. The process described in this work can be used for other 3D printing processes and provides a framework for the rapid prototyping of functional composites into functional parts with reliable properties. The ABS-BT composite shows promise as a functional dielectric material, with potential applications as capacitors and light-weight passive antennas. [ABSTRACT FROM AUTHOR]