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Julien Cottineau, Molly C Kottemann, Francis P Lach, Young-Hoon Kang, Frédéric Vély, Elissa K Deenick, Tomi Lazarov, Laure Gineau, Yi Wang, Andrea Farina, Marie Chansel, Lazaro Lorenzo, Christelle Piperoglou, Cindy S Ma, Patrick Nitschke, Aziz Belkadi, Yuval Itan, Bertrand Boisson, Fabienne Jabot-Hanin, Capucine Picard, Jacinta Bustamante, Céline Eidenschenk, Soraya Boucherit, Nathalie Aladjidi, Didier Lacombe, Pascal Barat, Waseem Qasim, Jane A Hurst, Andrew J Pollard, Holm H Uhlig, Claire Fieschi, Jean Michon, Vladimir P Bermudez, Laurent Abel, Jean-Pierre de Villartay, Frédéric Geissmann, Stuart G Tangye, Jerard Hurwitz, Eric Vivier, Jean-Laurent Casanova, Agata Smogorzewska, Emmanuelle Jouanguy
Inborn errors of DNA repair or replication underlie a variety of clinical phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed intrauterine growth retardation, chronic neutropenia, and NK cell deficiency. Four of the 5 patients also had postnatal growth retardation. The association of neutropenia and NK cell deficiency, which is unusual among primary immunodeficiencies and bone marrow failures, was due to a blockade in the bone marrow and was mildly symptomatic. We discovered compound heterozygous rare mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (GINS1, also known as PSF1) in the 5 patients...
April 17, 2017: Journal of Clinical Investigation
Alexandre G Martini, Lucie K Xa, Marie-Josée Lacombe, Alexis Blanchet-Cohen, Chantal Mercure, Benjamin Haibe-Kains, Edith C H Friesema, Anton H van den Meiracker, Kenneth W Gross, Michel Azizi, Pierre Corvol, Geneviève Nguyen, Timothy L Reudelhuber, A H Jan Danser
Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular cells of the kidney. Chronic stimulation of renin release results in a recruitment of new juxtaglomerular cells by the apparent conversion of adjacent smooth muscle cells along the afferent arterioles. Because juxtaglomerular cells rapidly dedifferentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain unclear...
April 10, 2017: Hypertension
Alison Lacombe, Brendan A Niemira, Joseph Sites, Glenn Boyd, Joshua B Gurtler, Breanna Tyrell, Melissa Fleck
The disinfecting properties of high-intensity monochromatic blue light (MBL) were investigated against Escherichia coli O157:H7, Salmonella , and nonpathogenic bacteria inoculated onto the surface of almonds. MBL was generated from an array of narrow-band 405-nm light-emitting diodes. Almonds were inoculated with higher or lower levels (8 or 5 CFU/g) of pathogenic E. coli O157:H7 and Salmonella , as well as nonpathogenic E. coli K-12 and an avirulent strain of Salmonella Typhimurium, for evaluation as potential surrogates for their respective pathogens...
November 2016: Journal of Food Protection
Michael Fraser, Veronica Y Sabelnykova, Takafumi N Yamaguchi, Lawrence E Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P Masella, Natalie S Fox, Michael Xie, Stephenie D Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A Beck, Alice Meng, Junyan Zhang, Alister D'Costa, Robert E Denroche, Haiying Kong, Shadrielle Melijah G Espiritu, Melvin L K Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J Harding, Christine P'ng, Kathleen E Houlahan, Kenneth C Chu, Bryan Lo, Francis Nguyen, Constance H Li, Ren X Sun, Richard de Borja, Christopher I Cooper, Julia F Hopkins, Shaylan K Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C Collins, Cenk Sahinalp, Mathieu Lupien, Neil E Fleshner, Housheng H He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D McPherson, Robert G Bristow, Paul C Boutros
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries...
January 19, 2017: Nature
Carmen H Logie, Ashley Lacombe-Duncan, Rachel K MacKenzie, Tonia Poteat
PURPOSE: Sexual stigma is a chronic stressor that enhances vulnerability to mental health disparities among lesbian, gay, bisexual, and queer people. Sexual stigma has also been associated with reduced uptake of safer sex practices, such as condom use, among gay and bisexual men. Scant research has examined the relationship between sexual stigma and safer sex practices among sexual minority women (SMW), including lesbian, bisexual, and queer women. METHODS: We explored associations between sexual stigma and safer sex practices among SMW...
December 2016: LGBT Health
James P B O'Connor, Eric O Aboagye, Judith E Adams, Hugo J W L Aerts, Sally F Barrington, Ambros J Beer, Ronald Boellaard, Sarah E Bohndiek, Michael Brady, Gina Brown, David L Buckley, Thomas L Chenevert, Laurence P Clarke, Sandra Collette, Gary J Cook, Nandita M deSouza, John C Dickson, Caroline Dive, Jeffrey L Evelhoch, Corinne Faivre-Finn, Ferdia A Gallagher, Fiona J Gilbert, Robert J Gillies, Vicky Goh, John R Griffiths, Ashley M Groves, Steve Halligan, Adrian L Harris, David J Hawkes, Otto S Hoekstra, Erich P Huang, Brian F Hutton, Edward F Jackson, Gordon C Jayson, Andrew Jones, Dow-Mu Koh, Denis Lacombe, Philippe Lambin, Nathalie Lassau, Martin O Leach, Ting-Yim Lee, Edward L Leen, Jason S Lewis, Yan Liu, Mark F Lythgoe, Prakash Manoharan, Ross J Maxwell, Kenneth A Miles, Bruno Morgan, Steve Morris, Tony Ng, Anwar R Padhani, Geoff J M Parker, Mike Partridge, Arvind P Pathak, Andrew C Peet, Shonit Punwani, Andrew R Reynolds, Simon P Robinson, Lalitha K Shankar, Ricky A Sharma, Dmitry Soloviev, Sigrid Stroobants, Daniel C Sullivan, Stuart A Taylor, Paul S Tofts, Gillian M Tozer, Marcel van Herk, Simon Walker-Samuel, James Wason, Kaye J Williams, Paul Workman, Thomas E Yankeelov, Kevin M Brindle, Lisa M McShane, Alan Jackson, John C Waterton
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification...
March 2017: Nature Reviews. Clinical Oncology
Patrick Ingiliz, Thomas C Martin, Alison Rodger, Hans-Jürgen Stellbrink, Stefan Mauss, Christoph Boesecke, Mattias Mandorfer, Julie Bottero, Axel Baumgarten, Sanjay Bhagani, Karine Lacombe, Mark Nelson, Jürgen K Rockstroh
BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014...
February 2017: Journal of Hepatology
M R Trusheim, A A Shrier, Z Antonijevic, R A Beckman, R K Campbell, C Chen, K T Flaherty, J Loewy, D Lacombe, S Madhavan, H P Selker, L J Esserman
Adaptive, seamless, multisponsor, multitherapy clinical trial designs executed as large scale platforms, could create superior evidence more efficiently than single-sponsor, single-drug trials. These trial PIPELINEs also could diminish barriers to trial participation, increase the representation of real-world populations, and create systematic evidence development for learning throughout a therapeutic life cycle, to continually refine its use. Comparable evidence could arise from multiarm design, shared comparator arms, and standardized endpoints-aiding sponsors in demonstrating the distinct value of their innovative medicines; facilitating providers and patients in selecting the most appropriate treatments; assisting regulators in efficacy and safety determinations; helping payers make coverage and reimbursement decisions; and spurring scientists with translational insights...
December 2016: Clinical Pharmacology and Therapeutics
D Salmon, C Gilbert, E Rosenthal, P Miailhes, J Chas, K Lacombe, I Poizot-Martin, A Gervais, P Sogni, L Wittkop Pour la Cohorte
No abstract text is available yet for this article.
June 2016: Médecine et Maladies Infectieuses
G Mellon, H Cordel, S Diamantis, K Lacombe, O Pajot, A Crémieux
No abstract text is available yet for this article.
June 2016: Médecine et Maladies Infectieuses
A Boyd, L Piroth, S Maylin, M Maynard-Muet, F Lebossé, C Bouix, C Lascoux-Combe, N Mahjoub, P-M Girard, C Delaugerre, F Carrat, K Lacombe, P Miailhes
In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status...
August 3, 2016: Journal of Viral Hepatitis
Yudai Izumi, Kentaro Fujii, Frank Wien, Chantal Houée-Lévin, Sandrine Lacombe, Daniela Salado-Leza, Erika Porcel, Rawand Masoud, Satoshi Yamamoto, Matthieu Réfrégiers, Marie-Anne Hervé du Penhoat, Akinari Yokoya
Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of α-helix structure and a decrease of β-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new α-helix structures at 310 K. We propose the structural transition from β-strand and turn structures to an α-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response...
July 12, 2016: Biophysical Journal
L Michel, C Lions, M Winnock, J-P Lang, M-A Loko, E Rosenthal, B Marchou, M-A Valantin, P Morlat, P Roux, P Sogni, B Spire, I Poizot-Martin, K Lacombe, C Lascoux-Combe, C Duvivier, D Neau, F Dabis, D Salmon-Ceron, M P Carrieri
OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5...
May 17, 2016: HIV Medicine
Thomas Schlathölter, Pierre Eustache, Erika Porcel, Daniela Salado, Lenka Stefancikova, Olivier Tillement, Francois Lux, Pierre Mowat, Aleksandra K Biegun, Marc-Jan van Goethem, Hynd Remita, Sandrine Lacombe
The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe...
2016: International Journal of Nanomedicine
Denise D Correa, Jaya Satagopan, Kenneth Cheung, Arshi K Arora, Maria Kryza-Lacombe, Youming Xu, Sasan Karimi, John Lyo, Lisa M DeAngelis, Irene Orlow
BACKGROUND: Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors...
October 2016: Neuro-oncology
Anne-Laurence Tomi, Jérémie Sellam, Karine Lacombe, Soraya Fellahi, Manuela Sebire, Caroline Rey-Jouvin, Anne Miquel, Jean-Philippe Bastard, Emmanuel Maheu, Ida K Haugen, David T Felson, Jacqueline Capeau, Pierre-Marie Girard, Francis Berenbaum, Jean-Luc Meynard
OBJECTIVE: To determine radiographic hand osteoarthritis (HOA) prevalence in patients with HIV-1 infection in comparison with the general population and to address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV-1 infection. PATIENTS: Patients with HIV-1 infection and MetS (International Diabetes Federation, IDF criteria) aged 45-65 years were matched by age and gender to HIV-1-infected subjects without MetS and underwent hand radiographs...
December 2016: Annals of the Rheumatic Diseases
C Popadiuk, C L Gauvreau, M Bhavsar, C Nadeau, K Asakawa, W M Flanagan, M C Wolfson, A J Coldman, S Memon, N Fitzgerald, J Lacombe, A B Miller
BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals...
February 2016: Current Oncology
Constance Auvynet, Camille Baudesson de Chanville, Patricia Hermand, Karim Dorgham, Christophe Piesse, Charlotte Pouchy, Ludovic Carlier, Lucie Poupel, Sandrine Barthélémy, Virginie Felouzis, Claire Lacombe, Sandrine Sagan, Benoit Salomon, Philippe Deterre, Florian Sennlaub, Christophe Combadière
CC chemokine receptor type 2 (CCR2) is a key molecule in inflammatory diseases and is an obvious drug target for the treatment of inflammation. A number of nonpeptidic, competitive CCR2 antagonists have been developed, but none has yet been approved for clinical use. Our aim was to identify a short peptide that showed allosteric antagonism against human and mouse CCR2. On the basis of sequence analysis and 3-dimensional modeling, we identified an original 7-d-amino acid peptidic CCR2 inhibitor that we have called extracellular loop 1 inverso (ECL1i), d(LGTFLKC)...
June 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jason Lacombe, Benjamin J Cairns, Jane Green, Gillian K Reeves, Valerie Beral, Miranda Eg Armstrong
Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day-case or overnight admissions with a mean follow-up of 11 years per woman...
August 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
F Lacombe, E Bernal, D Bloxham, S Couzens, M G D Porta, U Johansson, W Kern, M Macey, T Matthes, R Morilla, A Paiva, C Palacio, F Preijers, R Ratei, S Siitonen, K Allou, A Porwit, M C Béné
No abstract text is available yet for this article.
August 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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