bluuebunny/crossref_metadata_2025_split huggingface dataset:
FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis
Authors: Verbeke Len , Mannaerts Inge , Schierwagen Robert , Govaere Olivier , Klein Sabine , Vander Elst Ingrid , Windmolders Petra , Farre Ricard , Wenes Mathias , Mazzone Massimiliano , Nevens Frederik , van Grunsven Leo A. , Trebicka Jonel , Laleman Wim 
Published: September 2016

AbstractHepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis.
Molecular basis of a novel renal amyloidosis due to N184K gelsolin variant
Authors: Bonì Francesco , Milani Mario , Porcari Riccardo , Barbiroli Alberto , Ricagno Stefano , de Rosa Matteo 
Published: September 2016

AbstractMutations in gelsolin are responsible for a systemic amyloidosis first described in 1969. Until recently, the disease was associated with two substitutions of the same residue, leading to the loss of the calcium binding site. Novel interest arose in 2014 when the N184K variant of the protein was identified as the etiological agent of a novel kidney-localized amyloidosis. Here we provide a first rationale for N184K pathogenicity. We show that the mutation induces a destabilization of gelsolin second domain, without compromising its calcium binding capacity. X-ray data combined with molecular dynamics simulations demonstrates that the primary source of the destabilization is a loss of connectivity in proximity of the metal. Such rearrangement of the H-bond network does not have a major impact on the overall fold of the domain, nevertheless, it increases the flexibility of a stretch of the protein, which is consequently processed by furin protease. Overall our data suggest that the N184K variant is subjected to the same aberrant proteolytic events responsible for the formation of amyloidogenic fragments in the previously characterized mutants. At the same time our data suggest that a broader number of mutations, unrelated to the metal binding site, can lead to a pathogenic phenotype.
Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice
Authors: Leite Nayara Carvalho , de Paula Flávia , Borck Patrícia Cristine , Vettorazzi Jean Franciesco , Branco Renato Chaves Souto , Lubaczeuski Camila , Boschero Antonio Carlos , Zoppi Claudio Cesar , Carneiro Everardo Magalhães 
Published: September 2016

AbstractPancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.
Lateral photovoltaic effect in flexible free-standing reduced graphene oxide film for self-powered position-sensitive detection
Authors: Moon In Kyu , Ki Bugeun , Yoon Seonno , Choi Jongwan , Oh Jungwoo 
Published: September 2016

AbstractLightweight, simple and flexible self-powered photodetectors are urgently required for the development and application of advanced optical systems for the future of wearable electronic technology. Here, using a low-temperature reduction process, we report a chemical approach for producing freestanding monolithic reduced graphene oxide papers with different gradients of the carbon/oxygen concentration ratio. We also demonstrate a novel type of freestanding monolithic reduced graphene oxide self-powered photodetector based on a symmetrical metal–semiconductor–metal structure. Upon illumination by a 633-nm continuous wave laser, the lateral photovoltage is observed to vary linfearly with the laser position between two electrodes on the reduced graphene oxide surface. This result may suggest that the lateral photovoltaic effect in the reduced graphene oxide film originates from the built-in electric field by the combination of both the photothermal electric effect and the gradient of the oxygen-to-carbon composition. These results represent substantial progress toward novel, chemically synthesized graphene-based photosensors and suggest one-step integration of graphene-based optoelectronics in the future.
Eukaryotic pathways targeted by the type III secretion system effector protein, BipC, involved in the intracellular lifecycle of Burkholderia pseudomallei
Authors: Kang Wen-Tyng , Vellasamy Kumutha Malar , Vadivelu Jamuna 
Published: September 2016

AbstractBurkholderia pseudomallei, the etiological agent for melioidosis, is known to secrete a type III secretion system (TTSS) protein into the host’s internal milieu. One of the TTSS effector protein, BipC, has been shown to play an important role in the B. pseudomallei pathogenesis. To identify the host response profile that was directly or indirectly regulated by this protein, genome-wide transcriptome approach was used to examine the gene expression profiles of infected mice. The transcriptome analysis of the liver and spleen revealed that a total of approximately 1,000 genes were transcriptionally affected by BipC. Genes involved in bacterial invasion, regulation of actin cytoskeleton, and MAPK signalling pathway were over-expressed and may be specifically regulated by BipC in vivo. These results suggest that BipC mainly targets pathways related to the cellular processes which could modulate the cellular trafficking processes. The host transcriptional response exhibited remarkable differences with and without the presence of the BipC protein. Overall, the detailed picture of this study provides new insights that BipC may have evolved to efficiently manipulate host-cell pathways which is crucial in the intracellular lifecycle of B. pseudomallei.
Redox-dependent Regulation of Gluconeogenesis by a Novel Mechanism Mediated by a Peroxidatic Cysteine of Peroxiredoxin
Authors: Irokawa Hayato , Tachibana Tsuyoshi , Watanabe Toshihiko , Matsuyama Yuka , Motohashi Hozumi , Ogasawara Ayako , Iwai Kenta , Naganuma Akira , Kuge Shusuke 
Published: September 2016

AbstractPeroxiredoxin is an abundant peroxidase, but its non-peroxidase function is also important. In this study, we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. The physical interactions between Pyk1 and Tsa1 were augmented during the shift from glycolysis to gluconeogenesis. Intriguingly, a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions. These interactions are enhanced by exogenous H2O2 and by endogenous reactive oxygen species, which is increased during gluconeogenesis. Only the peroxidatic cysteine, but no other catalytic cysteine of Tsa1, is required for efficient growth during the metabolic shift to obtain maximum yeast growth (biomass). This Tsa1 function is separable from the peroxidase function as an antioxidant. This is the first report to demonstrate that peroxiredoxin has a novel nonperoxidase function as a redox-dependent target modulator and that pyruvate kinase is modulated via an alternative mechanism.
Rare variants in BRCA2 and CHEK2 are associated with the risk of urinary tract cancers
Authors: Ge Yuqiu , Wang Yunyan , Shao Wei , Jin Jing , Du Mulong , Ma Gaoxiang , Chu Haiyan , Wang Meilin , Zhang Zhengdong 
Published: September 2016

AbstractPrevious studies have shown that two rare variants, rs11571833 in BRCA2 and rs17879961 in CHEK2 were associated with lung cancer. However, the associations between these two variants and urinary tract cancers risk remain largely unexplored. We applied imputation of three genome-wide association studies published in the database of Genotypes and Phenotypes (dbGaP). Unconditional logistic regression analysis and meta-analysis were performed to assess the association between these two variants and the risk of urinary tract cancers. Our results showed that rs11571833[T] had an effect on urinary tract cancers predisposition (ORmeta = 1.45, Pmeta = 0.013), especially associated with increased the risk of bladder cancer (ORmeta = 1.60, Pmeta = 0.010). Moreover, rs17879961[C] had a protective effect on the urinary tract cancers (ORmeta = 0.67, Pmeta = 1.0 × 10−3) and was mostly associated with a lower incidence of renal cell carcinoma (ORmeta = 0.51, Pmeta = 2.0 × 10−3). Together, our study indicates that BRCA2 and CHEK2 play an important role in the genetic susceptibility to urinary tract cancers.
Meta-analysis of associations between DLG5 R30Q and P1371Q polymorphisms and susceptibility to inflammatory bowel disease
Authors: Li Yunhai , Chen Ping , Sun Jiazheng , Huang Jing , Tie Hongtao , Li Liangliang , Li Hongzhong , Ren Guosheng 
Published: September 2016

AbstractGrowing evidence from recent studies has demonstrated an association between inflammatory bowel disease (IBD) susceptibility and two polymorphisms of DLG5 R30Q (rs1248696) and P1371Q (rs2289310), but the results remain controversial. We conducted a meta-analysis including a total of 22 studies with 10,878 IBD patients and 7917 healthy controls for R30Q and 5277 IBD cases and 4367 controls for P1371Q in order to systematically assess their association with the disease. The results indicated that R30Q was significantly associated with reduced susceptibility to IBD in Europeans by allelic and dominant comparisons, but not in overall population. No significant association was found between R30Q and Crohn’s disease (CD) or ulcerative colitis (UC). P1371Q was associated with increased risk of IBD in Europeans and Americans. On the contrary, a decreased risk of IBD was observed in Asian population for P1371Q. In disease subgroup analysis, we found that P1371Q was also significantly associated with CD, but this relationship was not present for UC. In conclusion, our results strongly suggest that the both polymorphisms of DLG5 are correlated with IBD susceptibility in an ethnic-specific manner. Additional well-designed studies with large and diverse cohorts are needed to further strengthen our findings.
Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile
Authors: Gooyit Major , Janda Kim D. 
Published: September 2016

AbstractProlonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species) and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents.
Autophagy-related proteins are functionally active in human spermatozoa and may be involved in the regulation of cell survival and motility
Authors: Aparicio I. M. , Espino J. , Bejarano I. , Gallardo-Soler A. , Campo M. L. , Salido G. M. , Pariente J. A. , Peña F. J. , Tapia J. A. 
Published: September 2016

AbstractMacroautophagy (hereafter autophagy) is an evolutionarily highly conserved cellular process that participates in the maintenance of intracellular homeostasis through the degradation of most long-lived proteins and entire organelles. Autophagy participates in some reproductive events; however, there are not reports regarding the role of autophagy in the regulation of sperm physiology. Hence, the aim of this study was to investigate whether autophagy-related proteins are present and functionally active in human spermatozoa. Proteins related to autophagy/mitophagy process (LC3, Atg5, Atg16, Beclin 1, p62, m-TOR, AMPKα 1/2 and PINK1) were present in human spermatozoa. LC3 colocalized with p62 in the middle piece of the spermatozoa. Autophagy activation induced a significant increase in motility and a decrease in PINK1, TOM20 expression and caspase 3/7 activation. In contrast, autophagy inhibition resulted in decreased motility, viability, ATP and intracellular calcium concentration whereas PINK1, TOM20 expression, AMPK phosphorylation and caspase 3/7 activation were significantly increased. In conclusion our results show that autophagy related proteins and upstream regulators are present and functional in human spermatozoa. Modification of mitochondrial proteins expression after autophagy activation/inhibition may be indicating that a specialized form of autophagy named mitophagy may be regulating sperm function such as motility and viability and may be cooperating with apoptosis.
The Palin Parent Rating Scales: Parents' Perspectives of Childhood Stuttering and Its Impact
Authors: Millard Sharon K. , Davis Stephen 
Published: September 2016

Purpose
The goal of this study is to explore the psychometric properties of the Parent Rating Scales–V1 (S. K. Millard, S. Edwards, & F. M. Cook, 2009), an assessment tool for parents of children who stutter, and to refine the measure accordingly.

Method
We included 259 scales completed prior to therapy. An exploratory factor analysis determined the test constructs and identified the items that had greatest loadings on those factors. Items that did not load on the factors were removed, and normative scores calculated.

Results
The resulting 19-item questionnaire measures three factors: (a) the impact of stuttering on the child; (b) the severity of stuttering and its impact on the parents; and (c) the parents' knowledge about stuttering and confidence in managing it. Reliability was demonstrated, norms established, and an automated online version constructed.

Conclusions
The Palin Parent Rating Scale is a valid and reliable tool, providing a method of exploring parents' perceptions of stuttering, the impact it has on the child and themselves, and the parents' knowledge of and confidence in managing the stuttering. This is an important addition to the existing range of assessments that may be used to evaluate stuttering in children up to age 14;6 (years;months) and allows the wider targets of parent-led therapy programs to be evaluated.
Load‐insensitive active quasi‐circulator for continuous‐wave Doppler ultrasound applications
Authors: Santini T.R.S. , Ibrahim T.S. , Maciel C.D. 
Published: September 2016

Circulators are often used in RF systems; however, their size, cost, and weight increase greatly at lower frequencies (<300 MHz). The development of a load‐insensitive active quasi‐circulator is presented as an alternative for the traditional circulators to be used in low‐frequency systems such as Doppler ultrasound. Major challenges to these active devices are limited power and low isolation between non‐consecutive ports. The use of current‐feedback operational amplifiers allowed higher‐power delivery to the load. Simulations using Monte Carlo method showed an isolation >19 dB for 20% of variation of the load impedance. The circuit was implemented and tested with an ultrasound probe in a water tank. The results show that the circuit was able to send and receive signals simultaneously from a single ultrasound transducer element.
Single‐stage QR AC–DC converter based on buck–boost and flyback circuits
Authors: Wang Yijie , Zhang Shu , Guan Yueshi , Liu Xiaosheng , Xu Dianguo 
Published: September 2016

In this study, a single‐stage quasi‐resonant (QR) AC–DC converter based on buck–boost and flyback circuits is proposed. The forestage buck–boost circuit works in discontinuous conduction mode to achieve a high‐input power factor (PF), and the backstage flyback converter, working in QR mode, is responsible for energy transfer. The QR switch mode can improve the efficiency of the converter by decreasing the switch turn‐on losses. The single‐stage topology can reduce the cost and raise the reliability of the system. The detailed design process is described in this study, and a 50 W prototype was developed that has a maximum PF higher than 0.99 and a maximum efficiency of 90.91% in nominal working conditions.
Wie bewerten und akzeptieren Patienten die Betreuung durch Medizinische Fachangestellte in der Hausarztpraxis? Ergebnisse einer Patienten-Befragung in der HzV in Baden-Württemberg
Authors: Mergenthal K. , Güthlin C. , Beyer M. , Gerlach F. , Siebenhofer A. 
Published: September 2016

Zusammenfassung
Hintergrund: Modelle zur Delegation hausärztlicher Tätigkeiten an nichtärztliches Personal wurden in den letzten Jahren erprobt, im hausärztlichen Setting implementiert und fanden zum Teil Einzug in den Leistungskatalog der gesetzlichen Krankenkassen.
Ziel: Wie wurde das veränderte Tätigkeitsspektrum von den Patienten wahrgenommen und akzeptiert?
Methode: Zwischen Oktober 2014 und Januar 2015 fand eine schriftlichen Befragung unter chronisch erkrankten HzV-Versicherten (≥ 65 Jahren) zur Betreuung durch Medizinische Fachangestellte (MFA) (mit oder ohne Zusatzqualifikation zur „Versorgungsassistentin in der Hausarztpraxis“ (VERAH) statt. Mittels eines selbst entwickelten Befragungsinstruments (auf Basis einer früheren Datenerhebung) wurden Aspekte der Versorgungsunterstützung und Betreuung durch MFA erhoben.
Ergebnisse: 77 Praxen nahmen teil und befragten insgesamt 1 266 Patienten. Die befragten Patienten gaben an, dass die MFA in vielen Aspekten der Betreuung eine Rolle spielen. Dabei gaben mehr als die Hälfte der Patienten an, dass MFA einen Teil der Hausbesuche oder Praxiskontakte übernehmen kann. Organisatorische Leistungen, Betreuungs- und Unterstützungsleistungen durch MFA bewerteten die Teilnehmer allgemein als fast ausnahmslos sehr gut. Bei konkreten Beratungsleistungen waren die Ergebnisse heterogener. Während Beratungen zu Impfschutz, zur Inanspruchnahme von Vorsorgeleistungen, Arztkontrollen und Einnahmetreue von Tabletten offenbar bei Patienten „ankamen“, war dies bei konkreten Beratungen zum Lebensstil offenbar weitaus seltener der Fall. Viele Patienten sahen in den MFA eine zusätzliche kompetente Vertrauensperson und konnten sich vorstellen, dass MFA weitere delegierbare Leistungen übernehmen.
Schlussfolgerung: Viele an MFA delegierte Aspekte der Versorgung scheinen bei den Patienten – zumindest in der HzV – angekommen und akzeptiert zu sein. Potenzial für weitere delegierbare Leistungen könnten in der Übernahme von Hausbesuchen und beim Case Management im Sinne einer strukturierten Einzelfallbetreuung für Patienten mit besonderem Betreuungsbedarf bestehen. Dies müsste in weiteren Studien ausführlicher (u. a. auch qualitativ) untersucht werden.
Polypharmazie in der nachstationären Versorgung: Eine Analyse mit Daten der AOK Sachsen-Anhalt
Authors: Tetzlaff F. , Singer A. , Swart E. , Robra B.-P. , Herrmann M. 
Published: September 2016

Zusammenfassung
Hintergrund und Ziel der Studie: In Folge eines zunehmend alternden und multimorbiden Patientenklientels erhöht sich das Risiko einer Polypharmakotherapie. Ziel der Studie ist, Prävalenz und Determinanten der Polypharmazie im Übergang von der stationären zur ambulanten Versorgung zu analysieren. Dabei wird insbesondere der Zusammenhang zwischen Multimorbidität und der Zahl der an der Behandlung beteiligten Ärzte auf das Risiko einer Polypharmakotherapie und die Verordnung potenziell inadäquater Medikationen (PIM) untersucht.
Methodik: Die Basis der Analysen bilden stationäre und ambulante Versorgungsdaten der AOK Sachsen-Anhalt des dritten Quartals 2009. Einbezogen werden Personen ab dem 60ten Lebensjahr, die innerhalb dieses Zeitraumes aus der stationären Behandlung entlassen wurden und mindestens ein Rezept in der Apotheke einlösten (N=21 041). Nach der Prävalenzanalyse der Polypharmazie, in einem Zeitraum von bis zu 30 Tagen nach Entlassung, wird eine multivariate binär logistische Regression zur Ermittlung von Determinanten der Polypharmazie und der Verordnung von PIM durchgeführt. Zusätzlich wird die Interaktion zwischen der Anzahl der Erkrankungen und der Anzahl der an der Behandlung beteiligten Ärzte betrachtet.
Ergebnisse: Das Polypharmazierisiko ist signifikant mit der Anzahl der Erkrankungen assoziiert. Darüber hinaus besitzt die Anzahl der behandelnden Ärzte einen von der Anzahl der Erkrankungen unabhängigen Effekt auf das Risiko einer Polypharmazie. Zudem zeigt sich für Frauen, dass das Polypharmazierisiko gerade bei hoher Morbiditätslast mit steigender Anzahl der Behandler überproportional zunimmt. Eine vorliegende Polypharmakotherapie und die Anzahl der beteiligten Ärzte stellen sich zudem als Determinanten des Risikos einer PIM heraus.
Schlussfolgerung: Die Ergebnisse sprechen dafür, dass Polypharmazie nicht allein aus einer hohen Morbiditätslast resultiert. Vielmehr signalisiert der deutliche Effekt der Behandler ein ungelöstes Kommunikations- und Koordinationsproblem in der nachstationären Medikamententherapie und zeigt die Notwendigkeit eines zentralen Medikamentenmonitorings.