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Minimal pairs therapy

Sarah Elizabeth Skerratt, Mark D Andrews, Sharan K Bagal, James Bilsland, David Brown, Peter J Bungay, Susan Cole, Karl R Gibson, Russell Jones, Inaki Morao, Angus Nedderman, Kiyoyuki Omoto, Colin Robinson, Thomas Ryckmans, Kimberly Skinner, Paul Anthony Stupple, Gareth Waldron
The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially "druggable" point of intervention...
October 21, 2016: Journal of Medicinal Chemistry
Karolien Verhoeven, Stéphanie Peeters, Katrien Erven, Hilde Janssen, Isabelle Kindts, Erik Van Limbergen, Annouschka Laenen, Saskia Petillion, Caroline Weltens
PURPOSE: The purpose of this article is to compare isotropic and anisotropic margin expansion with regard to the size of the clinical target volume boost (CTVboost) and the interobserver variability (IOV). METHODS AND MATERIALS: Lumpectomy cavities marked with 3 or more surgical clips were delineated by 6 radiation oncologists who specialized in breast radiation therapy. CTVboost anisotropic was created by manually expanding the tumor bed with an anisotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the surgical free margins in 6 directions (anteroposterior, craniocaudal, and superoinferior)...
March 19, 2016: Practical Radiation Oncology
D Vinayagam, S Bampoe, B Thilaganathan, A Khalil
BACKGROUND: Intraoperative haemodynamic monitoring is carried out in high-risk surgical patients, often using invasive methods, including pulmonary artery catheterisation. Early goal-directed therapy in high-risk surgical patients reduces tissue hypoxia, organ failure and improves outcomes. Significant maternal morbidity arises as a result of perioperative haemorrhage. At present, heart rate and brachial blood pressure are used as proxy markers to aid in fluid resuscitation, however, we know that these exhibit minimal change during early stages of shock, and are poor indicators of the adequacy of therapeutic intervention...
August 2016: Journal of Maternal-fetal & Neonatal Medicine
Kenneth K Mugwanya, Craig W Hendrix, Nelly R Mugo, Mark Marzinke, Elly T Katabira, Kenneth Ngure, Nulu B Semiyaga, Grace John-Stewart, Timothy R Muwonge, Gabriel Muthuri, Andy Stergachis, Connie L Celum, Jared M Baeten
BACKGROUND: As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women. METHODS AND FINDINGS: We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials...
September 2016: PLoS Medicine
Simone Weber, Torsten Haferlach, Tamara Alpermann, Karolína Perglerová, Susanne Schnittger, Claudia Haferlach, Wolfgang Kern
High BAALC gene expression has been associated with poor prognosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and has been suggested as a suitable marker for assessing minimal residual disease (MRD). The purpose of this study was to substantiate these findings by the analysis of a large data set of 632 diagnostic and follow-up samples in 142 intensively treated CN-AML patients. Paired diagnostic/relapse samples of 35 patients revealed stable high BAALC expression in 89%, irrespective of a high proportion of clonal evolution found in 49% of these cases...
September 23, 2016: British Journal of Haematology
Chanida Vinayanuwattikun, Florence Le Calvez-Kelm, Behnoush Abedi-Ardekani, David Zaridze, Anush Mukeria, Catherine Voegele, Maxime Vallée, Dewajani Purnomosari, Nathalie Forey, Geoffroy Durand, Graham Byrnes, James Mckay, Paul Brennan, Ghislaine Scelo
To examine the diversity of somatic alterations and clonal evolution according to aggressiveness of disease, nineteen tumor-blood pairs of 'formerly bronchiolo-alveolar carcinoma (BAC)' which had been reclassified into preinvasive lesion (adenocarcinoma in situ; AIS), focal invasive lesion (minimally invasive adenocarcinoma; MIA), and invasive lesion (lepidic predominant adenocarcinoma; LPA and non-lepidic predominant adenocarcinoma; non-LPA) according to IASLC/ATS/ERS 2011 classification were explored by whole exome sequencing...
2016: Scientific Reports
Reena Khanna, Sigrid A Nelson, Brian G Feagan, Geert D'Haens, William J Sandborn, G Y Zou, John K MacDonald, Claire E Parker, Vipul Jairath, Barrett G Levesque
BACKGROUND: Endoscopic assessment of mucosal disease activity is widely used to determine eligibility and response to therapy in clinical trials of treatment for Crohn's disease. However, the operating properties of the currently available endoscopic indices remain unclear. OBJECTIVES: A systematic review was undertaken to evaluate the development and operating characteristics of the Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Scale for Crohn's Disease (SES-CD)...
2016: Cochrane Database of Systematic Reviews
Angel Chao, Ren-Chin Wu, Shih-Ming Jung, Yun-Shien Lee, Shu-Jen Chen, Yen-Lung Lu, Chia-Lung Tsai, Chiao-Yun Lin, Yun-Hsin Tang, Ming-Yu Chen, Huei-Jean Huang, Hung-Hsueh Chou, Kuan-Gen Huang, Ting-Chang Chang, Tzu-Hao Wang, Chyong-Huey Lai
OBJECTIVES: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas. METHODS: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays...
October 2016: Gynecologic Oncology
Alastair J Hutchison, Rosamund J Wilson, Svetlana Garafola, JBrian Copley
Despite 10 years of postmarketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium-like accumulation and toxicity persist. Here we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5-year observational database study (SPD405-404; identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys...
August 1, 2016: Nephrology
Ilias Lazarou, Stephen Kelly, Frances Humby, Maria Di Cicco, Lu Zou, Vidalba Rocher-Ros, Rebecca Eve Hands, Nora Ng, Arti Mahto, Costantino Pitzalis
OBJECTIVES: Ultrasound-guided synovial biopsy (UGSB) is a minimally-invasive procedure capable of retrieving good quality tissue from small and large joints. The use of UGSB in prospective clinical trials poses a dilemma as to whether biopsied joints may be later included in core data sets for clinical or imagining response, as the procedure itself may alter disease activity assessment. In this study, we examine the impact of UGSB of the wrist on subsequent clinical and ultrasound (US) assessments in a cohort of rheumatoid arthritis (RA) patients prior to initiation of anti-TNF-alpha therapy...
September 2016: Clinical and Experimental Rheumatology
Euson Yeung, Kulamakan Kulasagarem, Nicole Woods, Adam Dubrowski, Brian Hodges, Heather Carnahan
BACKGROUND: The validity of high-stakes decisions derived from assessment results is of primary concern to candidates and certifying institutions in the health professions. In the field of orthopaedic manual physical therapy (OMPT), there is a dearth of documented validity evidence to support the certification process particularly for short-answer tests. To address this need, we examined the internal structure of the Case History Assessment Tool (CHAT); this is a new assessment rubric developed to appraise written responses to a short-answer test of clinical reasoning in post-graduate OMPT certification in Canada...
2016: BMC Medical Education
Bartlomiej Pycinski, Joanna Czajkowska, Pawel Badura, Jan Juszczyk, Ewa Pietka
PURPOSE: A growing number of medical applications, including minimal invasive surgery, depends on multi-modal or multi-sensors data processing. Fast and accurate 3D scene analysis, comprising data registration, seems to be crucial for the development of computer aided diagnosis and therapy. The advancement of surface tracking system based on optical trackers already plays an important role in surgical procedures planning. However, new modalities, like the time-of-flight (ToF) sensors, widely explored in non-medical fields are powerful and have the potential to become a part of computer aided surgery set-up...
2016: PloS One
E Kuhn, A Potthoff, H Dirks, R Borgmann, S Esser, N Scherbaum, N H Brockmeyer, A Skaletz-Rorowski
BACKGROUND: Incidence and prevalence of HIV are continuously high in German men, who have sex with men (MSM). Different transmission risk minimizing strategies have been observed. The viral load strategy rates patients unlikely to be sexually infectious if their viral load under effective therapy is stably suppressed during 6 months and no other sexually transmitted infections are present. OBJECTIVES: We aim to objectify the current popularity of the viral load strategy, the adherence to basic conditions and its impact on risk behaviour and serocommunication...
September 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Vernissia Tam, James D Luketich, Daniel G Winger, Inderpal S Sarkaria, Ryan M Levy, Neil A Christie, Omar Awais, Manisha R Shende, Katie S Nason
BACKGROUND: Postoperative infection increases cancer recurrence and worsens survival in colorectal cancer, but the relationship for esophagogastric adenocarcinoma after esophagectomy is not well defined. We aimed to determine whether recurrence and survival after minimally invasive esophagectomy for esophagogastric adenocarcinoma were influenced by postoperative infection using propensity-matched analysis. METHODS: We abstracted data for 810 patients (1997-2010) and defined exposure as at least 1 in-hospital or 30-day infectious complication (n = 206 [25%])...
June 25, 2016: Annals of Thoracic Surgery
Michael R Pinsky, Hyung Kook Kim, Sven Zenker, Lauren Johnson, Sanjeev Shroff
OBJECTIVE: To define the differential effect of site-specific ventricular counterpacing efficacy during cardiac resynchronization therapy (CRT) to identify the most informative imaging views to quantify it. Cross-sectional and long-axis views commonly are used to assess left ventricular (LV) contractility. DESIGN: The effects of LV apical (LVa) and free-wall (LVfw) pacing during CRT on long- and short-axis contraction, cardiac output, and stroke work were assessed in an open-chested acute canine model to determine whether LVa and LVfw would induce earlier apical than basilar LV radial contraction and earlier free-wall than septal contraction, respectively...
June 2016: Journal of Cardiothoracic and Vascular Anesthesia
Suijing Wu, Ling Xu, Xin Huang, Suxia Geng, Yan Xu, Shaohua Chen, Lijian Yang, Xiuli Wu, Janyu Weng, Xin DU, Yangqiu Li
Currently, arsenic trioxide therapy is widely used for the treatment of acute promyelocytic leukemia (APL), relapsed and refractory adult T-cell leukemia/lymphoma and myelodysplastic syndrome. Regarding the broad antitumor activity of arsenic, certain studies have been undertaken to test its efficacy in treating acute T-cell lymphoblastic leukemia (T-ALL) cell lines and patients; however, to the best of our knowledge, no reports document that arsenic is able to induce the remission of T-ALL patients. The present study reports the case of young male patient diagnosed with T-ALL, with no significant response to common chemotherapy regimens, who finally achieved complete remission without minimal residual disease (as detected by flow cytometry) due to arsenic treatment...
June 2016: Oncology Letters
Mohammed Zuhaib, Krishnamurthy Bonanthaya, Renu Parmar, Pritham N Shetty, Pradeep Sharma
CONTEXT: Presurgical nasoalveolar moulding (PNAM) is a non-surgical method of reshaping the cleft lip, alveolus, palate and the nose to minimize the severity of the cleft deformity, before primary cheiloplastyand palatoplasty. In this context, PNAM proves to be an invaluable asset in the management of unilateral cleft lip and palate. AIMS: The study was conducted to evaluate the efficacy of PNAM in the management of unilateral cleft lip and palate with the following objectives: (1) To assess and compare the degree of reduction in the size of cleft palate and alveolus (pre-PNAM and post-PNAM)...
January 2016: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
Seth G Disner, Christopher G Beevers, Francisco Gonzalez-Lima
BACKGROUND: Low-level light therapy (LLLT) with transcranial laser is a non-invasive form of neuroenhancement shown to regulate neuronal metabolism and cognition. Attention bias modification (ABM) is a cognitive intervention designed to improve depression by decreasing negative attentional bias, but to date its efficacy has been inconclusive. Adjunctive neuroenhancement to augment clinical effectiveness has shown promise, particularly for individuals who respond positively to the primary intervention...
September 2016: Brain Stimulation
Richard D Wood, Sylvie Doublié
DNA polymerase theta (pol θ) is encoded in the genomes of many eukaryotes, though not in fungi. Pol θ is encoded by the POLQ gene in mammalian cells. The C-terminal third of the protein is a family A DNA polymerase with additional insertion elements relative to prokaryotic homologs. The N-terminal third is a helicase-like domain with DNA-dependent ATPase activity. Pol θ is important in the repair of genomic double-strand breaks (DSBs) from many sources. These include breaks formed by ionizing radiation and topoisomerase inhibitors, breaks arising at stalled DNA replication forks, breaks introduced during diversification steps of the mammalian immune system, and DSB induced by CRISPR-Cas9...
August 2016: DNA Repair
R J M Bashford-Rogers, K A Nicolaou, J Bartram, N J Goulden, L Loizou, L Koumas, J Chi, M Hubank, P Kellam, P A Costeas, G S Vassiliou
The strongest predictor of relapse in B-cell lymphoblastic leukemia (B-ALL) is the level of persistence of tumor cells after initial therapy. The high mutation rate of the B-cell receptor (BCR) locus allows high-resolution tracking of the architecture, evolution and clonal dynamics of B-ALL. Using longitudinal BCR repertoire sequencing, we find that the BCR undergoes an unexpectedly high level of clonal diversification in B-ALL cells through both somatic hypermutation and secondary rearrangements, which can be used for tracking the subclonal composition of the disease and detect minimal residual disease with unprecedented sensitivity...
May 23, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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