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https://www.readbyqxmd.com/read/29148806/discovery-of-tropifexor-ljn452-a-highly-potent-non-bile-acid-fxr-agonist-for-the-treatment-of-cholestatic-liver-diseases-and-nonalcoholic-steatohepatitis-nash
#1
David C Tully, Paul V Rucker, Donatella Chianelli, Jennifer Williams, Agnes Vidal, Phil B Alper, Daniel Mutnick, Badry Bursulaya, James Schmeits, Xiangdong Wu, Dingjiu Bao, Jocelyn Zoll, Young Kim, Todd Groessl, Peter McNamara, H Martin Seidel, Valentina Molteni, Bo Liu, Andrew Phimister, Sean B Joseph, Bryan Laffitte
The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and non-alcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold...
November 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29134637/ercc4-regulatory-variant-predict-grade-3-or-4-toxicities-in-patients-with-advanced-non-small-cell-lung-cancer-treated-by-platinum-based-therapy
#2
Ruoxin Zhang, Ming Jia, Yuan Xu, Danwen Qian, Mengyun Wang, Meiling Zhu, Menghong Sun, Jianhua Chang, Qingyi Wei
Platinum-based chemotherapy (PBC) in combination with the 3(rd) generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts, contributing to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in eight NER core genes with overall, gastrointestinal and hematologic toxicities...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29130570/cold-water-or-partial-body-cryotherapy-comparison-of-physiological-responses-and-recovery-following-muscle-damage
#3
Erich Hohenauer, Joseph T Costello, Rahel Stoop, Ursula M Küng, Peter Clarys, Tom Deliens, Ron Clijsen
The aim of this study was to compare i) the physiological responses following cold-water immersion (CWI) and partial-body cryotherapy (PBC) and ii) the effects on recovery following a muscle-damaging protocol (5 x 20 drop jumps). Nineteen healthy males were randomly allocated into either a CWI (10 °C for 10 min; n = 9) or a PBC (-60 °C for 30 sec, -135 °C for 2 min; n = 10) group. The physiological variables (thigh muscle oxygen saturation [SmO2 ], cutaneous vascular conductance [CVC], mean-arterial pressure [MAP] and local skin temperature) were assessed immediately prior and up to 60 min post-treatment (10 min intervals)...
November 11, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29127360/a-mouse-model-of-autoimmune-cholangitis-via-syngeneic-bile-duct-protein-immunization
#4
Wen-Tao Ma, Qing-Zhi Liu, Jing-Bo Yang, Yan-Qing Yang, Zhi-Bin Zhao, Hong-Di Ma, M Eric Gershwin, Zhe-Xiong Lian
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules, which progressively leads to cholestasis, hepatic fibrosis, cirrhosis, and eventually liver failure. Several mouse models have been used to clarify the pathogenesis of PBC and are generally considered reflective of an autoimmune cholangitis. Most models focus on issues of molecular mimicry between the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC and xenobiotic cross reactive chemicals...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122851/guidelines-on-the-management-of-abnormal-liver-blood-tests
#5
Philip N Newsome, Rob Cramb, Suzanne M Davison, John F Dillon, Mark Foulerton, Edmund M Godfrey, Richard Hall, Ulrike Harrower, Mark Hudson, Andrew Langford, Anne Mackie, Robert Mitchell-Thain, Karen Sennett, Nicholas C Sheron, Julia Verne, Martine Walmsley, Andrew Yeoman
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine...
November 9, 2017: Gut
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#6
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110188/percutaneous-balloon-compression-for-persistent-or-recurrent-trigeminal-neuralgia-after-microvascular-decompression-personal-experience-of-28-patients
#7
Wu Xu, Chengrong Jiang, Chen Yu, Weibang Liang
The objective of this study is to investigate the long-term effects of percutaneous balloon compression (PBC) for treating persistent or recurrent trigeminal neuralgia (TN) after microvascular decompression (MVD). The clinical features, surgical findings, outcomes, and complications of 28 patients underwent PBC for TN in Nanjing Drum Tower Hospital between April 2011 and March 2015 were analyzed retrospectively. All the patients had received MVD before but they did not get cured or the symptom relapsed during follow-up...
November 6, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/29110023/-modern-treatment-of-primary-biliary-cholangitis
#8
REVIEW
C P Strassburg
For nearly 30 years ursodeoxycholic acid (UDCA) represented the only pharmacological treatment option available for primary biliary cholangitis (PBC). This changed at the end of 2016 when obeticholic acid was licensed in Europe for PBC patients not responding to UDCA. Novel treatment concepts involving the modulation of nuclear receptor signaling in cholestatic and other liver diseases have led to a host of new potential options, studies and drug candidates for the treatment of PBC. The analysis of large multinational cohorts has additionally confirmed the effectiveness of UDCA in slowing PBC progression, and has led to the development of new definitions for the risk assessment of PBC patients under therapy, which will be an asset for clinical decision making...
November 6, 2017: Der Internist
https://www.readbyqxmd.com/read/29109567/design-implementation-and-outcomes-of-a-three-week-pharmacy-bridging-course
#9
Jacqueline E McLaughlin, Julia Khanova, Adam Persky, Nathaniel Hathaway, Wendy Cox
Objective. To evaluate the design, implementation, and outcomes of a three-week pharmacy bridging course (PBC) covering five math and science areas for first-year doctor of pharmacy students in fall 2015. Methods. Each topic was taught as a separate module. All five modules used pre- and post-module assessments to measure student knowledge and confidence. Course grades for subsequent first-year courses (PY1) were collected to examine relationships between PBC and PY1 courses. Results. Scores on the post-knowledge assessments increased for all five subject areas compared to scores on pre-PBC knowledge assessments...
September 2017: American Journal of Pharmaceutical Education
https://www.readbyqxmd.com/read/29105026/metastatic-non-small-cell-lung-carcinoma-a-mimic-of-primary-breast-carcinoma-case-series-and-literature-review
#10
Rola H Ali, Catalin Taraboanta, Tareq Mohammad, Malcolm M Hayes, Diana N Ionescu
Metastatic tumors to the breast are rare but constitute a major diagnostic dilemma. Of these, non-mammary carcinomatous metastases to the breast are particularly challenging and, without a clinical history, may be extremely difficult to distinguish from primary breast carcinoma (PBC). We specifically studied metastatic tumors of pulmonary origin, as the lung is one of the major primary sites for carcinomatous metastasis to breast. Sixteen metastatic lung tumors to the breast were identified in our archives between 1996 and 2017 including 12 non-small cell lung carcinomas (NSCLC), one large-cell neuroendocrine, one atypical carcinoid, and two small-cell carcinomas...
November 5, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29104604/entrepreneurship-education-revisited-perceived-entrepreneurial-role-models-increase-perceived-behavioural-control
#11
Katharina Fellnhofer
Relying on Bandura's (1986) social learning theory, Ajzen's (1988) theory of planned behaviour (TPB), and Dyer's (1994) model of entrepreneurial careers, this study aims to highlight the potential of entrepreneurial role models to entrepreneurship education. The results suggest that entrepreneurial courses would greatly benefit from real-life experiences, either positive or negative. The results of regression analysis based on 426 individuals, primarily from Austria, Finland, and Greece, show that role models increase learners' entrepreneurial perceived behaviour control (PBC) by increasing their self-efficacy...
2017: Int J Learn Chang
https://www.readbyqxmd.com/read/29093628/evidence-from-a-familial-case-suggests-maternal-inheritance-of-primary-biliary-cholangitis
#12
Saeam Shin, In Ho Moh, Young Sik Woo, Sung Won Jung, Jin Bae Kim, Ji Won Park, Ki Tae Suk, Hyoung Su Kim, Mineui Hong, Sang Hoon Park, Myung Seok Lee
Primary biliary cholangitis (PBC) is an idiopathic autoimmune liver disease characterized by chronic cholestasis and destruction of the intrahepatic bile ducts. Similar to other autoimmune diseases, the pathogenesis of PBC is considered to be a complex etiologic phenomenon involving the interaction of genetic and environmental factors. Although a number of common variants associated with PBC have been reported from genome-wide association studies, a precise genetic mechanism underlying PBC has yet to be identified...
October 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29090437/characterization-of-modified-biochars-prepared-at-low-pyrolysis-temperature-as-an-efficient-adsorbent-for-atrazine-removal
#13
Lulu Zhao, Fan Yang, Qun Jiang, Moran Zhu, Zhao Jiang, Yi Tang, Ying Zhang
In this study, biochars (BC, ZnBC, and PBC) produced from wheat straw at relatively lower pyrolysis are successfully fabricated using different pretreatment techniques (without and with ZnCl2 or H3PO4). The specific surface area (SSA), elemental analysis, and Fourier transform infrared spectra (FTIR) are used to analyze physicochemical properties of unmodified and modified biochars. ZnBC and PBC show higher specific surface area and more micropore structure than pure BC. Kinetic models (pseudo-first order, pseudo-second order, and intra-particle diffusion) as well as isotherm models (Langmuir and Freundlich) are applied to analyze adsorption behavior...
October 31, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29080526/adsorption-of-heavy-metals-from-aqueous-solution-by-uv-mutant-bacillus-subtilis-loaded-on-biochars-derived-from-different-stock-materials
#14
Ting Wang, Hongwen Sun, Xinhao Ren, Bing Li, Hongjun Mao
Two kinds of biochars, one derived from corn straw (CBC) and one from pig manure (PBC), were used as the carriers of a bacterium (B38) to adsorb heavy metals in solution. CBC exhibited high affinity to Hg(II), while PBC showed large adsorption capacity of Pb(II). After loading with B38, the sorption capacity of the co-sorbents were enhanced for Pb(II), but weakened for Hg(II). In a binary system, the overall adsorption capacity to Hg-Pb (CBC+B38, 136.7mg/g; PBC+B38, 181.3mg/g) on co-sorbents was equal to the sum of the single-component values for Hg(II) and Pb(II)...
October 25, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29079982/effect-of-peanut-shell-and-wheat-straw-biochar-on-the-availability-of-cd-and-pb-in-a-soil-rice-oryza-sativa-l-system
#15
Chao Xu, Hao-Xiang Chen, Qian Xiang, Han-Hua Zhu, Shuai Wang, Qi-Hong Zhu, Dao-You Huang, Yang-Zhu Zhang
Soil amendments, such as biochar, have been used to enhance the immobilization of heavy metals in contaminated soil. A pot experiment was conducted to immobilize the available cadmium (Cd) and lead (Pb) in soil using peanut shell biochar (PBC) and wheat straw biochar (WBC), and to observe the accumulation of these heavy metals in rice (Oryza sativa L.). The application of PBC and WBC led to significantly higher pH, soil organic carbon (SOC), and cation exchange capacity (CEC) in paddy soil, while the content of MgCl2-extractable Cd and Pb was lower than that of untreated soil...
October 27, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29077518/moderating-effects-of-sexual-orientation-and-gender-characteristic-on-condom-use-intentions-among-boys-senior-high-school-students-in-taiwan-an-exploration-based-on-the-theory-of-planned-behavior
#16
Chien-Mu Cheng, Jiun-Hau Huang
This study examined condom use intentions among adolescent boys in relation to the constructs of the Theory of Planned Behavior (TPB): attitude toward the behavior (ATB), subjective norm (SN), and perceived behavioral control (PBC). The potential moderating effects of sexual orientation and gender characteristic (masculine/feminine) were also explored. Anonymous survey data were collected from 929 students enrolled in a boys' senior high school in Taiwan (response rate: 89.9%). Multivariate logistic regression analyses found higher condom use intentions linked to more positive ATB (adjusted odds ratio [AOR] = 8...
October 27, 2017: Journal of Sex Research
https://www.readbyqxmd.com/read/29066370/factors-associated-with-prevalence-and-treatment-of-primary-biliary-cholangitis-in-united-states-health-systems
#17
Mei Lu, Jia Li, Irina V Haller, Robert J Romanelli, Jeffrey J VanWormer, Carla V Rodriguez, Marsha A Raebel, Joseph A Boscarino, Mark A Schmidt, Yihe G Daida, Amandeep Sahota, Jennifer Vincent, Christopher L Bowlus, Keith Lindor, Loralee B Rupp, Stuart C Gordon
BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) consortium, from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD consortium database, from 2003 through 2014...
October 21, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29063616/genetic-association-studies-and-the-risk-factors-for-developing-the-immuno-bile-logic-disease-pbc
#18
Evaggelia Liaskou, Gideon M Hirschfield
No abstract text is available yet for this article.
October 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29057955/investigation-of-melts-of-polybutylcarbosilane-dendrimers-by-1-h-nmr-spectroscopy
#19
Vladimir V Matveev, Denis A Markelov, Sergey V Dvinskikh, Andrei N Shishkin, Konstantin V Tyutyukin, Anastasia V Penkova, Elena A Tatarinova, Galina M Ignat'eva, Sergey A Milenin
Melts of polybutylcarbosilane (PBC) dendrimers from third (G3) up to sixth (G6) generations are investigated by (1)H NMR spectroscopy in a wide temperature range up to 493 K. At room temperature, NMR spectra of G3-G5 dendrimers exhibit resolved, solution-like spectra ("liquid" phase). In contrast, the spectrum of the G6 dendrimer is characterized by a single unresolved broad line at whole temperature range, which supports the presence of an anomalous phase state of G6 at temperatures higher than glass transition temperature...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29057387/toward-solving-the-etiological-mystery-of-primary-biliary-cholangitis
#20
Atsushi Tanakaa, Patrick Sc Leung, Howard A Young, M Eric Gershwin
Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature AMA autoantibody, female predominance and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens, recognized by AMA, have served as an immunologic platform to identify the earliest events involved in loss of tolerance. Despite the relative high concordance rate in identical twins, genome wide association studies have not proven clinically useful and have led to suggestions of epigenetic events...
June 2017: Hepatol Commun
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