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https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#1
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808688/adaptive-mistranslation-accelerates-the-evolution-of-fluconazole-resistance-and-induces-major-genomic-and-gene-expression-alterations-in-candida-albicans
#2
Tobias Weil, Rodrigo Santamaría, Wanseon Lee, Johan Rung, Noemi Tocci, Darren Abbey, Ana R Bezerra, Laura Carreto, Gabriela R Moura, Mónica Bayés, Ivo G Gut, Attila Csikasz-Nagy, Duccio Cavalieri, Judith Berman, Manuel A S Santos
Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole...
July 2017: MSphere
https://www.readbyqxmd.com/read/28807091/rapid-and-sensitive-determination-of-13-components-in-a-traditional-chinese-medicine-formula-of-da-huang-gan-cao-decoction-by-high-performance-liquid-chromatography-coupled-with-triple-quadrupole-mass-spectrometry
#3
Jialin Qu, Nan Xiao, Hua Sui, Lina Liang, Jing Chen, Weiling Li, Dong Shang
Da-Huang-Gan-Cao decoction (DHGCD), which is a classic formula in traditional Chinese medicine, has been clinically used for the treatment of vomiting, constipation, pancreatitis, and cholelithiasis in China and Japan. In this study, a rapid and validated method using HPLC coupled with triple quadrupole MS was developed for the simultaneous determination of 13 components in DHGCD. Separation was performed on an XBridge BEH C18 column (50 × 2.1 mm, 2.5 μm) with a gradient elution of acetonitrile and 0.1% formic acid in water...
June 15, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28802560/traumatic-brain-injuries-during-development-disrupt-dopaminergic-signaling
#4
Kate Karelina, Kristopher R Gaier, Zachary M Weil
Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI on dopaminergic dysfunction and its relationship with substance abuse have not been investigated. In order to determine the effect of juvenile brain injury on dopaminergic signaling, female mice were injured at 21days of age and then beginning seven weeks later were assessed for behavioral sensitization to amphetamine, a drug that increases synaptic dopamine availability...
August 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28801466/statewide-payment-and-delivery-reform-do-states-have-what-it-takes
#5
Judy Feder, Alan R Weil, Robert Berenson, Rachel Dolan, Nicole Lallemand, Emily Hayes
States' role in payment as well as coverage will be subject to debate as the administration and the Congress decide how to address the Affordable Care Act (ACA) and otherwise reshape the nation's health policies. Acting as stewards of health care for the entire state population and stimulated by concern about rising costs and federal support under the ACA, the elected and administrative leaders of some states have been using their political influence and authority to improve their state's overall systems of care regardless of who pays the bill...
August 11, 2017: Journal of Health Politics, Policy and Law
https://www.readbyqxmd.com/read/28799806/elevated-serum-level-of-ca125-is-a-biomarker-that-can-be-used-to-alter-prognosis-determined-by-brca-mutation-and-family-history-in-ovarian-cancer
#6
Weiling Liu, Zhizhong Wang, Jie Ma, Yangyang Hou, Jiuzhou Zhao, Bing Dong, Shichun Tu, Li Wang, Yongjun Guo
AIMS: In this study, we determined whether serum tumor markers (STMs), including CA125, are associated with BRCA mutation status and if they can be used prognostically in sporadic ovarian cancer (SOC) and familial ovarian cancer (FOC). METHODS: BRCA gene mutations were screened using next-generation sequencing (NGS) in 31 FOC and 66 SOC patients enrolled between 2013 and 2014. The serum levels of STM CEA, CA125, CA199, and HE4 were also measured in these patients to determine the prognostic potential of these markers and their association with BRCA mutations...
August 11, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28799301/rickettsial-infections-in-goa-not-just-scrub-typhus
#7
Kedareshwar Narvencar, Gurleen Kaur, Savio Rodrigues
BACKGROUND AND OBJECTIVE: Rickettsial infections are an important cause of undifferentiated febrile illness in tropics. While scrub typhus was reported from Goa, other rickettsial infections have not been reported earlier. The present study was planned to identify pattern of rickettsial infections in Goa. MATERIALS AND METHODS: All patients presenting with undiagnosed acute febrile illness were recruited over a two-year period. Other causes of febrile illness were ruled out by appropriate tests...
August 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28797075/arginine-metabolic-endotypes-related-to-asthma-severity
#8
Weiling Xu, Suzy A A Comhair, Allison J Janocha, Abigail Lara, Lori A Mavrakis, Carole D Bennett, Satish C Kalhan, Serpil C Erzurum
AIMS: Arginine metabolism via inducible nitric oxide synthase (iNOS) and arginase 2 (ARG2) is higher in asthmatics than in healthy individuals. We hypothesized that a sub-phenotype of asthma might be defined by the magnitude of arginine metabolism categorized on the basis of high and low fraction of exhaled nitric oxide (FENO). METHODS: To test this hypothesis, asthmatics (n = 52) were compared to healthy controls (n = 51) for levels of FENO, serum arginase activity, and airway epithelial expression of iNOS and ARG2 proteins, in relation to clinical parameters of asthma inflammation and airway reactivity...
2017: PloS One
https://www.readbyqxmd.com/read/28793347/a-study-on-real-time-low-quality-content-detection-on-twitter-from-the-users-perspective
#9
Weiling Chen, Chai Kiat Yeo, Chiew Tong Lau, Bu Sung Lee
Detection techniques of malicious content such as spam and phishing on Online Social Networks (OSN) are common with little attention paid to other types of low-quality content which actually impacts users' content browsing experience most. The aim of our work is to detect low-quality content from the users' perspective in real time. To define low-quality content comprehensibly, Expectation Maximization (EM) algorithm is first used to coarsely classify low-quality tweets into four categories. Based on this preliminary study, a survey is carefully designed to gather users' opinions on different categories of low-quality content...
2017: PloS One
https://www.readbyqxmd.com/read/28791541/cancer-counseling-of-low-income-limited-english-proficient-latina-women-using-medical-interpreters-implications-for-shared-decision-making
#10
Daniella Kamara, Jon Weil, Janey Youngblom, Claudia Guerra, Galen Joseph
In cancer genetic counseling (CGC), communication across language and culture challenges the model of practice based on shared decision-making. To date, little research has examined the decision-making process of low-income, limited English proficiency (LEP) patients in CGC. This study identified communication patterns in CGC sessions with this population and assessed how these patterns facilitate or inhibit the decision-making process during the sessions. We analyzed 24 audio recordings of CGC sessions conducted in Spanish via telephone interpreters at two public hospitals...
August 9, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28782088/reconstitution-of-a-ligand-binding-competent-murine-nkp30-receptor
#11
Stefanie Memmer, Sandra Weil, Joachim Koch
The activating natural cytotoxicity receptors on natural killer (NK) cells play a fundamental role in immunosurveillance of infections and cancer. Phylogenetic analyses showed that NKp30 is highly conserved in almost all jawed vertebrates and thus, represents one of the most ancient NK cell receptors. However, in contrast to other higher vertebrates, NKp30 is only a pseudogene in mouse, which contains two premature stop codons. To decipher the evolutionary role and biological function of NKp30 in mouse, we removed these premature stop codons and expressed the putative mouse NKp30 (mNKp30) protein as soluble Fc fusion construct and as full-length receptor on A5-GFP reporter cells...
August 7, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28768202/dual-rna-processing-roles-of-pat1b-via-cytoplasmic-lsm1-7-and-nuclear-lsm2-8-complexes
#12
Caroline Vindry, Aline Marnef, Helen Broomhead, Laure Twyffels, Sevim Ozgur, Georg Stoecklin, Miriam Llorian, Christopher W Smith, Juan Mata, Dominique Weil, Nancy Standart
Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5' to 3' mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28764157/seroepidemiology-of-spotted-fever-rickettsiosis-in-uttar-pradesh-a-prospective-study
#13
Chandra Dev Pati Tripathi, Mastan Singh, Jyotsna Agarwal, Chandra Kanta, Virendra Atam
INTRODUCTION: Spotted Fever Rickettsiosis (SFR), an acute febrile illness caused by Rickettsia rickettsii, R. conorii and R. akari which is associated with considerable morbidity and mortality. SFR is one of the most covert emerging infections of the present time which is prevalent in various parts of India as shown by the increase in the number of clinically diagnosed patients in various states except Uttar Pradesh. AIM: To diagnose SFR in clinically suspected patients using serological tests and recognition of common epidemiologic situations and clinical manifestations of SFR in the state of Uttar Pradesh...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28758712/spatiotemporally-controlled-release-of-rho-inhibiting-c3-toxin-from-a-protein-dna-hybrid-hydrogel-for-targeted-inhibition-of-osteoclast-formation-and-activity
#14
Jasmina Gačanin, Anna Kovtun, Stephan Fischer, Victoria Schwager, Johanna Quambusch, Seah Ling Kuan, Weina Liu, Felix Boldt, Chuang Li, Zhongqiang Yang, Dongsheng Liu, Yuzhou Wu, Tanja Weil, Holger Barth, Anita Ignatius
In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks...
July 31, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28741328/-short-term-results-of-weils-osteotomy-in-patients-with-propulsive-metatarsalgia
#15
J C Hernández-Martínez, J Vázquez-Escamilla, M Coronado-Puente
INTRODUCTION: Metatarsalgia is the most common reason for consultation in orthopedic pathology of the foot. The key to its treatment lies in the correct determination of the symptoms, which are biological, morphological and mechanical alterations responsible for pain. Weil´s osteotomy is commonly used for multiple forefoot pathologies, including metatarsalgias. MATERIAL AND METHODS: We included patients with first-line failure syndrome and associated mechanical metatarsalgia-producing deformities...
January 2017: Acta Ortopédica Mexicana
https://www.readbyqxmd.com/read/28738706/relationship-between-premature-brain-injury-and-multiple-biomarkers-in-cord-blood-and-amniotic-fluid
#16
Hongyan Lu, Weiling Huang, Xiaoqing Chen, Qiuxia Wang, Qiang Zhang, Ming Chang
PURPOSE: To investigate the relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid, identify potential biomarkers for early monitoring of premature brain injury. METHODS: 130 cases of singleton premature infants with gestational age less than 34 weeks were evaluated. Based on brain imaging examination, all cases were divided into brain injury group and no brain injury group. Eleven biomarkers in cord blood and amniotic fluid were measured...
July 24, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28738529/nitrogen-functionalization-biochars-derived-from-wheat-straws-via-molten-salt-synthesis-an-efficient-adsorbent-for-atrazine-removal
#17
Fan Yang, Lili Sun, Weiling Xie, Qun Jiang, Yan Gao, Wei Zhang, Ying Zhang
N-doped porous carbon sheets (NPCS) resulted from wheat straws are fabricated through using molten salts via the carbonization-functionalization progress, which show unique hierarchical structure, large pore volume and high surface area with affluent micropores. Results indicate that there exist many hierarchical pores consisting of the single carbon sheet with ultrathin nature, owing to the template role of molten salt mixtures at high temperature. Such superior structure can bring about desired performance of adsorption capacity of 82...
July 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28735363/routine-follow-up-radiographs-for-distal-radius-fractures-are-seldom-clinically-substantiated
#18
N L Weil, M El Moumni, S M Rubinstein, P Krijnen, M F Termaat, I B Schipper
INTRODUCTION: The value of routine radiographs during follow-up after distal radius fractures is unclear. The aim of this study was to evaluate whether routine radiographs performed during the follow-up period in patients with a distal radius fracture influenced clinical decision making. METHODS: This retrospective cohort study included patients aged ≥18 years who were treated for a distal radius fracture at four hospitals in The Netherlands in 2012. Demographic and clinical and radiographic characteristics were collected from medical records...
July 22, 2017: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/28730418/total-and-free-cortisol-levels-during-1-%C3%AE-g-25-%C3%AE-g-and-250-%C3%AE-g-cosyntropin-stimulation-tests-compared-to-insulin-tolerance-test-results-of-a-randomized-prospective-pilot-study
#19
Seenia Peechakara, James Bena, Nigel J Clarke, Michael J McPhaul, Richard E Reitz, Robert J Weil, Pablo Recinos, Laurence Kennedy, Amir H Hamrahian
PURPOSE: The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. METHOD: The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12)...
July 20, 2017: Endocrine
https://www.readbyqxmd.com/read/28727974/autoamputation-of-the-appendix-presenting-as-a-calcified-abdominal-mass-following-necrotizing-enterocolitis
#20
Brent R Weil, Alyaa Al-Ibraheemi, Sara O Vargas, Shawn J Rangel
Autoamputation of the appendix has previously been reported in the literature, but it is likely an unusual event. We report a 2-year-old male child who had previously undergone laparotomy and bowel resection for necrotizing enterocolitis. Two years later a calcified intra-abdominal mass was identified on abdominal radiography and ultrasonography. Eventual laparotomy revealed a densely calcified mass within the transverse mesocolon. The mass was uneventfully resected. Pathologic evaluation showed appendiceal tissue, consistent with prior autoamputation of the vermiform appendix...
July 2017: Pediatric and Developmental Pathology
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