tbuckley/cabot-search huggingface dataset:
PTU-262 Effects of bovine lactoferrin in an<i>in vitro</i>human gut model of c. difficile infection
Authors: TM Monaghan, C Chilton, G Crowther, K Spiewak, M Brindell, G Singh, M Wilcox
Journal: Gut (2015)

<h3>Introduction</h3> <i>C. difficile</i>infection (CDI) is a global health care problem. Recurring infections and increasing antibiotic resistance have complicated treatment of CDI. There is now, therefore, an urgent need for the development of novel non-antibiotic-based therapeutic and preventative strategies. Recent evidence suggests that the availability of iron may be important for <i>C. difficile</i>growth. Lactoferrin, a multifunctional iron-binding glycoprotein, exhibits bacteriostatic activity due to its ability to sequester iron, thereby depriving potential pathogens of this essential nutrient. The aim of this research is to evaluate the comparative effects of iron-depleted (1% saturated) bovine apolactoferrin (apo-bLf) and iron-saturated (84% saturated) bovine hololactoferrin (holo-bLf) in a human <i><i>in vitro</i></i>gut model predictive of CDI. <h3>Method</h3> Two parallel triple-stage chemostat gut models designed to facilitate the formation of intestinal biofilms were primed with human faecal emulsions and spiked with <i>C. difficile</i>spores (∼10<sup>7 </sup>cfu/ml, PCR ribotype 027). Bacterial populations were allowed to equilibrate before simulated CDI was induced by instillation of Clindamycin (33.9 mg/L, four times daily for 7 days). Samples were collected for determination of microflora populations, <i>C. difficile</i>vegetative cells and spores, cytotoxin titres, short chain fatty acids, bile acids, lactoferrin, iron and% iron saturation of Lf at multiple time points. <h3>Results</h3> Preliminary analyses indicate that there were no differences in biofilm formation in the two models. Both apo- and holo-bLf appeared to have little effect on microflora populations or <i>C. difficile</i>during control periods pre-antimicrobial instillation. Two major differences were observed in <i>C. difficile</i>populations post-antibiotic: germination was seen 6 days post-Clindamycin instillation in the apo-bLF model, but not until 15 days post clindamycin in the holo-bLf model; no toxin was detected in the holo-bLf model for the duration of the experiment whereas toxin was rapidly detected in the apo-bLf model (1 day post germination). <h3>Conclusion</h3> In conclusion, we have shown for the first time that disrupting iron homoeostasis has major effects on <i>C. difficile </i>growth and development in a human gut model. As the clinical effects of <i>C. difficile</i>infection are mediated through toxin production, it may be that iron toxicity (rather than iron deprivation) has the greater potential as a novel preventative or treatment strategy. <h3>Disclosure of interest</h3> T. Monaghan: None Declared, C. Chilton: None Declared, G. Crowther: None Declared, K. Spiewak: None Declared, M. Brindell: None Declared, G. Singh: None Declared, M. Wilcox Grant/ Research Support from: Multiple therapeutic and diagnostic companies, Consultant for: Multiple therapeutic and diagnostic companies.
Supplements such as fish oils improve antidepressant effectiveness, review finds
Authors: Susan Mayor
Journal: BMJ (2016)

Taking nutritional supplements such as omega 3 fish oils significantly improves the effectiveness of antidepressants in people being treated for clinical depression, a systematic review has shown.1

Researchers systematically searched for clinical trials that used adjunctive nutrients for depression published before December 2015. They included 40 studies with a length of at least 21 days and a sample size of at least 10 per arm (mean sample size 63).

The review included nine …
The shelterin complex and hematopoiesis
Authors: Morgan Jones, Kamlesh Bisht, Sharon A. Savage, Jayakrishnan Nandakumar, Catherine E. Keegan, Ivan Maillard
Journal: Journal of Clinical Investigation (2016)

Mammalian chromosomes terminate in stretches of repetitive telomeric DNA that act as buffers to avoid loss of essential genetic information during end-replication. A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. Telomere erosion contributes to human diseases ranging from BM failure to premature aging syndromes and cancer. The role of shelterin telomere protection is less understood. Mutations in genes encoding the shelterin proteins TRF1-interacting nuclear factor 2 (TIN2) and adrenocortical dysplasia homolog (ACD) were identified in dyskeratosis congenita, a syndrome characterized by somatic stem cell dysfunction in multiple organs leading to BM failure and other pleiotropic manifestations. Here, we introduce the biochemical features and in vivo effects of individual shelterin proteins, discuss shelterin functions in hematopoiesis, and review emerging knowledge implicating the shelterin complex in hematological disorders.
Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction
Authors: Sonja B. Riemenschneider, Donald J. Mattia, Jacqueline S. Wendel, Jeremy A. Schaefer, Lei Ye, Pilar A. Guzman, Robert T. Tranquillo
Journal: Biomaterials (2016)
Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences
Authors: G David Poznik, Yali Xue, Fernando L Mendez, Thomas F Willems, Andrea Massaia, Melissa A Wilson Sayres, Qasim Ayub, Shane A McCarthy, Apurva Narechania, Seva Kashin, Yuan Chen, Ruby Banerjee, Juan L Rodriguez-Flores, Maria Cerezo, Haojing Shao, Melissa Gymrek, Ankit Malhotra, Sandra Louzada, Rob Desalle, Graham R S Ritchie, Eliza Cerveira, Tomas W Fitzgerald, Erik Garrison, Anthony Marcketta, David Mittelman, Mallory Romanovitch, Chengsheng Zhang, Xiangqun Zheng-Bradley, Gonçalo R Abecasis, Steven A McCarroll, Paul Flicek, Peter A Underhill, Lachlan Coin, Daniel R Zerbino, Fengtang Yang, Charles Lee, Laura Clarke, Adam Auton, Yaniv Erlich, Robert E Handsaker, Carlos D Bustamante, Chris Tyler-Smith
Journal: Nature Genetics (2016)
446P Afatinib (A) versus chemotherapy (CT) for EGFR mutation-positive NSCLC patients (pts) aged ≥65 years: Subgroup analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6)
Authors: Y.-L. Wu, L.V. Sequist, S.L. Geater, S. Orlov, K.H. Lee, C.-M. Tsai, T. Kato, K. Kiura, C.H. Barrios, M. Schuler, V. Hirsh, N. Yamamoto, K. O'Byrne, T. Mok, D. Massey, A. Märten, J.C.-H. Yang
Journal: Annals of Oncology (2015)
Prevalence, distribution and risk of sessile serrated adenomas/polyps at a center with a high adenoma detection rate and experienced pathologists
Authors: Joep IJspeert, Koos de Wit, Manon van der Vlugt, Barbara Bastiaansen, Paul Fockens, Evelien Dekker
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Sessile serrated adenomas/polyps (SSA/Ps) are the precursors of 15 % – 30 % of colorectal cancers (CRC). We aimed to determine the prevalence and distribution of SSA/Ps and to evaluate the association between SSA/Ps and the risk of synchronous advanced neoplasia at a high quality colonoscopy center. <b>Methods:</b> Data from all colonoscopies performed within one dedicated colonoscopy center between 2011 and 2015 were prospectively retrieved using an automated reporting system. All lesions were assessed by an experienced gastrointestinal pathologist. Multiple logistic regression was used to evaluate influence of age, gender, and colonoscopy indication on prevalence of SSA/Ps, and to assess the association between SSA/Ps and synchronous advanced neoplasia. <b>Results:</b> In total 4251 histologically confirmed polyps were resected in 3364 patients; 399 polyps were SSA/Ps (9.4 %). The prevalence of SSA/Ps was 8.2 % overall, increasing to 9.0 % for individuals older than 50 years. SSA/P detection rate varied between 2.5 % and 13.6 % among endoscopists. Increased SSA/P prevalence was associated with colonoscopy indications "familial CRC risk" (odds ratio [OR] 1.52, 95 % confidence interval [95 %CI] 1.05 – 2.22; <i>P</i> = 0.03) and "surveillance" (OR 1.73, 95 %CI 1.20 – 2.49; <i>P</i> < 0.01), when compared with the indication "symptoms." The presence of synchronous advanced neoplasia was associated with SSA/Ps overall (OR 1.71, 95 %CI 1.25 – 2.34; <i>P</i> = 0.001), as well as with high risk SSA/Ps (defined as ≥ 10 mm and/or with dysplasia) (OR 2.70, 95 %CI 1.56 – 4.67; <i>P</i> < 0.001) <b>Conclusion:</b> SSA/Ps are more common than previously reported and are associated with the presence of synchronous advanced neoplasia. Endoscopists should be assiduous in identifying SSA/Ps in daily practice and should carefully look for synchronous advanced neoplasia when an SSA/P has been recognized. Results from this study can guide detection standards in general colonoscopy practice adapted to the type of patient that may predominate in an individual department.
Hormonal Status of Breast Cancer. I. Theoretical Basis for the Analysis of Steroid Profile&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: M Kodama, T Kodama
Journal: JNCI Journal of the National Cancer Institute (1975)

Gas-liquid chromatography was applied to the analysis of urinary steroids of women. In the statistical analysis, quantitation of all steroid excretions and ratios among them were transformed to give a normal frequency distribution. The influence of the host's age and the menstrual cycle on 24 hours' excretion was investigated for each of 14 identified neutral steroids, of which four in our fraction 2 (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetriol) were menstruation dependent. The 14 neutral steroid excretions were generally correlated with one another within the host, and the use of a steroid ratio rather than quantitation of steroid excretion was often more sensitive in the characterization of the hormonal status.
Reducible self-assembling cationic polypeptide-based micelles mediate co-delivery of doxorubicin and microRNA-34a for androgen-independent prostate cancer therapy
Authors: Chong Yao, Jiyong Liu, Xin Wu, Zongguang Tai, Yuan Gao, Quangang Zhu, Jiafei Li, Lijuan Zhang, Chuling Hu, Fenfen Gu, Jing Gao, Shen Gao
Journal: Journal of Controlled Release (2016)
IRON AND HYPOXIA LINK: DOWNREGULATION OF LUCIFERASE ACTIVITY OF HEPCIDIN PROMOTER BY HYPOXIC SERA IN HUH-7 CELLS
Authors: F Greni, G Ravasi, S Pelucchi, L Silvestri, M Cappellini, D Barisani, C Camaschella, A Piperno
Journal: American Journal of Hematology (2013)
NICE approves innovative treatment for moderate to severe heart failure
Authors: Jacqui Wise
Journal: BMJ (2016)

Doctors have a new treatment option for patients whose heart failure is not controlled by angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, after the National Institute for Health and Care Excellence (NICE) approved sacubitril valsartan (Entresto).1

Sacubitril valsartan is a novel treatment that includes both an angiotensin receptor neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (valsartan). Sacubitril works by restricting the action of neprilysin, a substance that prevents the dilation of blood vessels.

The guidance from NICE said that sacubitril valsartan is recommended for people with moderate …
Synergy made simple: What does it mean and how valid are claims for synergy between antitumor agents?
Authors: A. Ocana, C. Yeung, I. Tannock
Journal: Journal of Clinical Oncology (2010)

6082 Background: Clinical trials evaluating drug combinations are often stimulated by claims that the agents are synergistic in preclinical models. Overuse or misuse of the term synergy could lead to evaluation of nonrational drug combinations and to poorly-designed clinical studies. Here we identified reports of clinical trials that contained the term “synergy” and reviewed the preclinical data used to justify evaluation of a drug combination. Methods: We reviewed MEDLINE using the terms “synergy and cancer” with the limits of “human” and “clinical trials” to select 96 articles published between 2003 and 2009. Eligible studies were those that referred to synergy in preclinical studies to justify the drug combination evaluated. We then reviewed the cited preclinical studies to evaluate whether claims for synergy were justified. Descriptive statistics and Fisher's exact test were used to summarize the characteristics and possible associations. Results: Thirty-four clinical articles met eligibility criteria and 57 preclinical articles were cited in them. Most of the clinical studies were phase I trials (n = 18; 53%) and 15 were phase II studies (44%). The primary endpoints were toxicity evaluated by the MTD in 53% (n = 18) followed by response rate in 32% (n = 11). Clinical activity was identified in 8 phase II studies. Cell lines in culture provided the most frequent model used in preclinical studies (53%; n = 30), followed by animal studies alone in 26% (n = 15); others used a combination of models. Appropriate methods to evaluate synergy (isobologram analysis, median effect or both) were used in 18 articles (32%) but 39 articles did not used these methods. A trend to a positive association was identified between using an appropriate method to evaluate synergy and positive results observed in phase II trials (p = 0.07). Conclusions: Synergy is frequently cited in phase I and II studies to justify evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy have been used in most preclinical articles. There was a trend toward a positive association between use of an appropriate method to support a claim for synergy and positive results of the clinical studies. No significant financial relationships to disclose.
TCTAP A-153 Efficacy Analysis of Transcatheter Closure of Coronary Artery Fistulas in 70 Cases - Single Center Experience
Authors: Wang Qian, Wu Hong, Xu Rong-Liang, Zheng Xing, Qin Yong-Wen, Zhao Xian-Xian
Journal: Journal of the American College of Cardiology (2016)
Soundings: Bill and Bob
Authors: Trisha Greenhalgh
Journal: BMJ (2002)

We had been asleep for more than an hour when the phone rang. Assuming a wrong number, we ignored it. Fifteen minutes later the bedroom filled with slowly strobing blue light and there was a loud rap-rap at the door. I pulled on a dressing gown and went down to face the policeman.

He read out my full name and I confirmed my identity. He spoke into a walkie-talkie. “Located the next of kin, Sarge, over.” At my kitchen table, he introduced himself as Trevor, our family liaison officer. “Your uncle,” he said, “has been reported missing. The police are out combing the streets. We need a full description and a recent photograph.”

Uncle Bob had always been incorrigible. Large, bewhiskered, and irrepressibly gregarious, he had appeared periodically throughout my childhood with his pockets stuffed with forbidden lollipops. His love life had been colourful but unenduring, and following a series of cerebral infarcts, he had transferred his attentions to the nurses at a home for elderly mentally infirm people.

We had no pictures of him. In his striped pyjama top and long grey mac, Uncle Bob would be indistinguishable from the thousands of half-cut tramps on London's streets.

My husband joined the search, leaving me pacing the kitchen and trying not to think of inquests and funerals. Uncle Bob had taken his insulin but no food, hence (apparently) the heavy turnout of foot police, sniffer dogs, and—as the search wore on—a helicopter with heat seeking equipment.

Later, I remembered Uncle Bob's passport and took it round to the home, where the lounge had been turned into an incident room and 20 rain soaked officers were temporarily regrouped around a large-scale map. Some of the residents had awoken and placed themselves in their usual chairs. “It's very exciting, isn't it?” said one lady.

Suddenly Trevor's walkie-talkie crackled. The game was over. Uncle Bob had been found by a panda car, curled up by a statue of a naked lady—hypothermic, normoglycaemic, and refusing hospital admission. He had, he claimed, received a message about an impending Iraqi invasion, and had gone off in search of the secret agents.

The nurses and I hugged one another and the traditional cup of tea was offered all round. “Thanks,” said Trevor, “but we've just been redrafted. There's an 80 year old lady on the run from a care home in Walthamstow.”
TCTAP C-226 Which Stent Should I Implant This Time? - Additional Role of Optical Frequency Domain Imaging in the Treatment of In-Stent-Restenosis
Authors: Hiu Lam Chan, Kin Lam Tsui, Dick Chi Yeung Cheung, Kwok Leung Wu, Joe Kin-Tong Lee, Kwok Keung Chan
Journal: Journal of the American College of Cardiology (2016)
Functional Properties of Dendritic Gap Junctions in Cerebellar Golgi Cells
Authors: Miklos Szoboszlay, Andrea Lőrincz, Frederic Lanore, Koen Vervaeke, R. Angus Silver, Zoltan Nusser
Journal: Neuron (2016)

The strength and variability of electrical synaptic connections between GABAergic interneurons are key determinants of spike synchrony within neuronal networks. However, little is known about how electrical coupling strength is determined due to the inaccessibility of gap junctions on the dendritic tree. We investigated the properties of gap junctions in cerebellar interneurons by combining paired somato-somatic and somato-dendritic recordings, anatomical reconstructions, immunohistochemistry, electron microscopy, and modeling. By fitting detailed compartmental models of Golgi cells to their somato-dendritic voltage responses, we determined their passive electrical properties and the mean gap junction conductance (0.9 nS). Connexin36 immunofluorescence and freeze-fracture replica immunogold labeling revealed a large variability in gap junction size and that only 18% of the 340 channels are open in each plaque. Our results establish that the number of gap junctions per connection is the main determinant of both the strength and variability in electrical coupling between Golgi cells.
METB-01METABOLIC REPROGRAMMING DURING RESISTANCE TO ANTI-ANGIOGENIC THERAPY
Authors: Ruby Kuang, Smita Mascharak, Arman Jahangiri, Brandon Imber, Michael De Lay, Brandyn Castro, Maxim Sidrov, Liane Miller, Garima Yagnik, Manish Aghi
Journal: Neuro-Oncology (2015)

Clinical trials revealed limited response duration of glioblastomas to VEGF-neutralizing antibody bevacizumab. Thriving in the harsh microenvironment created by anti-angiogenic therapy requires that tumors metabolically adapt to decreased nutrients. We investigated the hypothesis that metabolic reprogramming occurs during the evolution of anti-angiogenic therapy resistance. Bevacizumab treatment lowered glucose levels 3-fold in U87 xenografts (P  0.05). HSP60 was the only assessed mitochondrial enzyme with less expression in U87-BevR versus U87-BevS xenografts (P   0.05). We found bevacizumab resistance to be associated with greater GLUT3-mediated uptake of the reduced glucose levels, impaired mitochondrial health, and greater lipid production. Treatments targeting these potential points of weakness in resistant tumors should be developed and considered for use alongside anti-angiogenic therapy in glioblastoma.
Erratum: Corrigendum: Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss
Authors: Yunjong Lee, Senthilkumar S Karuppagounder, Joo-Ho Shin, Yun-Il Lee, Han Seok Ko, Debbie Swing, Haisong Jiang, Sung-Ung Kang, Byoung Dae Lee, Ho Chul Kang, Donghoon Kim, Lino Tessarollo, Valina L Dawson, Ted M Dawson
Journal: Nature Neuroscience (2015)
Mechanical Thrombectomy and Functional Outcomes After Stroke
Authors: Filipe Brogueira Rodrigues, Peter Langhorne, João Costa
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Early PK-Analysis Predicts Molecular Response In Patients With Early Chronic Phase Chronic Myelogenous Leukemia (CML-CP) Treated With Frontline Nilotinib
Authors: Dominik Wolf, Jorn Skavland, Christoph Seger, Sieghart Sopper, Wiktor-Wieslaw Jedrzejczak, Dubravka Sertic, Jaroslava Voglova, Satu Mustjoki, Leif Stenke, Augustin Ferrant, Richard Greil, Alois Lang, Josef Thaler, Werner Linkesch, Antica Duletić-Načinović, Andrzej Hellmann, Georgi G. Mihaylov, Tobias Gedde-Dahl, Henrik Hjorth-Hansen, Waleed Majeed, Jesper Stentoft, Gregor Verhoef, Jan Van Droogenbroeck, Ute Mark, Jens Haenig, Nidas Jurjonas, Frank Giles, Andreas Hochhaus, Kimmo Porkka, Gert J. Ossenkoppele, Bjorn T. Gjertsen
Journal: Blood (2013)
The relationship and effects of golf on physical and mental health: a scoping review protocol
Authors: A Murray, L Daines, D Archibald, R Hawkes, L Grant, N Mutrie
Journal: British Journal of Sports Medicine (2016)

Introduction Golf is a sport played in 206 countries worldwide by over 50 million people. It is possible that participation in golf, which is a form of physical activity, may be associated with effects on longevity, the cardiovascular, metabolic and musculoskeletal systems, as well as on mental health and well-being. We outline our scoping review protocol to examine the relationships and effects of golf on physical and mental health. Methods and analysis Best practice methodological frameworks suggested by Arksey and O'Malley, Levac et al and the Joanna Briggs Institute will serve as our guide, providing clarity and rigour. A scoping review provides a framework to (1) map the key concepts and evidence, (2) summarise and disseminate existing research findings to practitioners and policymakers and (3) identify gaps in the existing research. A three-step search strategy will identify reviews as well as original research, published and grey literature. An initial search will identify suitable search terms, followed by a search using keyword and index terms. Two reviewers will independently screen identified studies for final inclusion. Dissemination We will map key concepts and evidence, and disseminate existing research findings to practitioners and policymakers through peer-reviewed and non-peer reviewed publications, conferences and in-person communications. We will identify priorities for further study. This method may prove useful to examine the relationships and effects of other sports on health.
Perspectives on Margins in DCIS: Pathology
Authors: Susan Lester
Journal: Journal of the National Comprehensive Cancer Network (2010)

All breast carcinomas must originate within the ductal/lobular system as carcinoma in situ, but only a subset of these lesions progress to invasive carcinoma. Although pathologic evaluation of the extent of ductal carcinoma in situ (DCIS), the distance to margins, and the degree of margin involvement provides an estimation of the likelihood of residual disease, the amount of disease in the remaining breast cannot be predicted with certainty. Factors other than residual disease may be more important in determining whether patients with DCIS survive or succumb to breast cancer, including biologically new ipsilateral cancers, contralateral cancers, and the degree of resistance of the normal stroma to invasion.