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H-H Brackmann, G C White, E Berntorp, T Andersen, C Escuriola-Ettingshausen
Development of inhibitory antibodies to infused factor VIII (FVIII) concentrates continues to be the most serious complication of haemophilia A management. Induction of immune tolerance by administering high doses of FVIII concentrate (antigen) and prothrombin complex concentrates to control bleeding was originated in the 1970s in Bonn, Germany, by Dr Hans-Hermann Brackmann, and became known as the Bonn protocol. ITI transformed the life of the index patient, who was 19 years of age when he began treatment, and dramatically improved the medical landscape for all patients with haemophilia and inhibitors...
April 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Sandi Dheensa, Gabrielle Samuel, Anneke M Lucassen, Bobbie Farsides
Clinical practice and research are governed by distinct rules and regulations and have different approaches to, for example, consent and providing results. However, genomics is an example of where research and clinical practice have become codependent. The 100 000 genomes project (100kGP) is a hybrid venture where a person can obtain a clinical investigation only if he or she agrees to also participate in ongoing research-including research by industry and commercial companies. In this paper, which draws on 20 interviews with professional stakeholders involved in 100kGP, we investigate the ethical issues raised by this project's hybrid nature...
March 1, 2018: Journal of Medical Ethics
Sean C P Coogan, David Raubenheimer, Gordon B Stenhouse, Nicholas C Coops, Scott E Nielsen
We combine a recently developed framework for describing dietary generalism with compositional data analysis to examine patterns of omnivory in a large widely distributed mammal. Using the brown bear ( Ursus arctos ) as a model species, we collected and analyzed data from the literature to estimate the proportions of macronutrients (protein, carbohydrate, and lipid) in the diets of bear populations. Across their range, bears consumed a diversity of foods that resulted in annual population diets that varied in macronutrient proportions, suggesting a wide fundamental macronutrient niche...
February 2018: Ecology and Evolution
Anna de Cordé, Paweł Krząścik, Renata Wolińska, Patrycja Kleczkowska, Małgorzata Filip, Magdalena Bujalska-Zadrożny
Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioid abstinence syndrome, which occurs as a result of opioid withdrawal. Opioid dependence in mice was induced by subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg for 10 consecutive days...
February 16, 2018: Behavioural Pharmacology
Atharva A Poundarik, Adele Boskey, Caren Gundberg, Deepak Vashishth
Tough natural nanocomposites like bone, nacre and sea sponges contain within their hierarchy, a mineral (phosphate, silicate or carbonate) phase that interacts with an organic phase. In bone, the role of mineral ultrastructure (organization, morphology, composition) is crucial to the mechanical and biological properties of the tissue. Better understanding of mineral interaction with the organic matrix, in particular non-collagenous proteins, osteocalcin (OC) and osteopontin (OPN), can lead to better design of biomimetic materials...
January 19, 2018: Scientific Reports
Bachelot Benedicte, María Uriarte, Robert Muscarella, Jimena Forero-Montaña, Jill Thompson, Krista McGuire, Jess Zimmerman, Nathan G Swenson, James S Clark
Arbuscular mycorrhizal (AM) fungi in the soil may influence tropical tree dynamics and forest succession. The mechanisms are poorly understood, because the functional characteristics and abundances of tree species and AM fungi are likely to be codependent. We used generalized joint attribute modeling to evaluate if AM fungi are associated with three forest community metrics for a sub-tropical montane forest in Puerto Rico. The metrics chosen to reflect changes during forest succession are: the abundance of seedlings of different successional status, the amount of foliar damage on seedlings of different successional status, and community-weighted mean functional trait values (adult specific leaf area (SLA), adult wood density, and seed mass)...
December 27, 2017: Ecology
Jonathon J O'Brien, Jeremy D O'Connell, Joao A Paulo, Sanjukta Thakurta, Christopher M Rose, Michael P Weekes, Edward L Huttlin, Steven P Gygi
Mass spectrometry (MS) has become an accessible tool for whole proteome quantitation with the ability to characterize protein expression across thousands of proteins within a single experiment. A subset of MS quantification methods (e.g., SILAC and label-free) monitor the relative intensity of intact peptides, where thousands of measurements can be made from a single mass spectrum. An alternative approach, isobaric labeling, enables precise quantification of multiple samples simultaneously through unique and sample specific mass reporter ions...
January 5, 2018: Journal of Proteome Research
Abigail Tazzyman, Jane Ferguson, Kieran Walshe, Alan Boyd, John Tredinnick-Rowe, Charlotte Hillier, Samantha Regan De Bere, Julian Archer
PURPOSE: Previous research found professionalism and regulation to be competing discourses when plans for medical revalidation in the United Kingdom were being developed in 2011. The purpose of this study was to explore how these competing discourses developed and how the perceived purposes of revalidation evolved as the policy was implemented. METHOD: Seventy-one interviews with 60 UK policy makers and senior health care leaders were conducted during the development and implementation of revalidation: 31 in 2011, 26 in 2013, and 14 in 2015...
November 7, 2017: Academic Medicine: Journal of the Association of American Medical Colleges
Andrew J Aguirre, William C Hahn
KRAS is the most commonly mutated oncogene in human cancer. Most KRAS-mutant cancers depend on sustained expression and signaling of KRAS, thus making it a high-priority therapeutic target. Unfortunately, development of direct small molecule inhibitors of KRAS function has been challenging. An alternative therapeutic strategy for KRAS-mutant malignancies involves targeting codependent vulnerabilities or synthetic lethal partners that are preferentially essential in the setting of oncogenic KRAS. KRAS activates numerous effector pathways that mediate proliferation and survival signals...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
Amgad N Makaryus, Haisam Ismail, John N Makaryus, Dali Fan
AIM: To apply real time three-dimensional transesophageal echocardiography (RT3D TEE) for quantitative and qualitative assessment of the mitral valve annulus (MVA) and tricuspid valve annulus (TVA) in the same patient. METHODS: Our retrospective cohort study examined the MVA and TVA in 49 patients by RT3D TEE. MVA and TVA shape were examined by TEE. The MVA and TVA volume data set images were acquired in the mid esophageal 4-chamber view. The MVA and TVA were acquired separately, with optimization of each for the highest frame rate and image quality...
September 26, 2017: World Journal of Cardiology
Po-Hao Chen, Hanna Zafar, Maya Galperin-Aizenberg, Tessa Cook
A significant volume of medical data remains unstructured. Natural language processing (NLP) and machine learning (ML) techniques have shown to successfully extract insights from radiology reports. However, the codependent effects of NLP and ML in this context have not been well-studied. Between April 1, 2015 and November 1, 2016, 9418 cross-sectional abdomen/pelvis CT and MR examinations containing our internal structured reporting element for cancer were separated into four categories: Progression, Stable Disease, Improvement, or No Cancer...
October 27, 2017: Journal of Digital Imaging: the Official Journal of the Society for Computer Applications in Radiology
Tom E F Abbott, Rupert M Pearse, R Andrew Archbold, Tahania Ahmad, Edyta Niebrzegowska, Andrew Wragg, Reitze N Rodseth, Philip J Devereaux, Gareth L Ackland
BACKGROUND: The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS). METHODS: Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients...
October 26, 2017: Anesthesia and Analgesia
Joanna Gołębiewska, Andrzej Olechowski, Marta Wysocka-Mincewicz, Dominik Odrobina, Marta Baszyńska-Wilk, Artur Groszek, Mieczysław Szalecki, Wojciech Hautz
PURPOSE: To assess the optical coherence tomography angiography (OCTA) retinal vessel density and foveal avascular zone (FAZ) in children with type 1 diabetes (T1D) and compare potential pathologic early changes in this population to healthy age-matched controls. METHODS: This study included 130 pubescent children: 94 with T1D (188 eyes) and 36 of their age-matched control group (60 eyes). OCTA was performed using AngioVue (Avanti, Optivue). FAZ area (mm2) in superficial plexus, whole superficial capillary vessel density (wsVD), fovea superficial vessel density (fsVD), parafovea superficial vessel density (psVD), whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea deep vessel density (pdVD), foveal thickness (FT) (μm) and parafoveal thickness (PFT) (μm) were taken into analysis...
2017: PloS One
Shaimaa M Salem, Stevi Weidenbach, Jürgen Rohr
Glycosyltransferases are key enzymes involved in the biosynthesis of valuable natural products providing an excellent drug-tailoring tool. Herein, we report the identification of two cooperative glycosyltransferases from the sqn gene cluster directing the biosynthesis of saquayamycins in Streptomyces sp. KY40-1: SqnG1 and SqnG2. Gene inactivation of sqnG1 leads to 50-fold decrease in saquayamycin production, while inactivation of sqnG2 leads to complete production loss, suggesting that SqnG2 acts as dual O- and C-glycosyltransferase...
October 20, 2017: ACS Chemical Biology
Peter W Wilson, Ceara S Suther, Maureen M Bain, Wiebke Icken, Anita Jones, Fiona Quinlan-Pluck, Victor Olori, Joël Gautron, Ian C Dunn
The cuticle is a unique invisible oviduct secretion that protects avian eggs from bacterial penetration through gas exchange pores. Despite its importance, experimental evidence is lacking for where, when, and what is responsible for its deposition. By using knowledge about the ovulatory cycle and oviposition, we have manipulated cuticle deposition to obtain evidence on these key points. Cuticle deposition was measured using staining and spectrophotometry. Experimental evidence supports the location of cuticle deposition to be the shell gland pouch (uterus), not the vagina, and the time of deposition to be within the final hour before oviposition...
July 1, 2017: Biology of Reproduction
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
August 2017: Current Opinion in Immunology
Fatemeh Karimi Ahmad-Abadi, Masoomeh Maarefvand, Hakimeh Aghaei, Samaneh Hosseinzadeh, Mahboubeh Abbasi, Jagdish Khubchandani
PURPOSE: Social workers in substance abuse treatment settings are responsible for involving families in treatment program to improve family functioning. The effectiveness of available interventions in treating codependency of family members of drug users in Iran is not well explored. We evaluated the effectiveness of the Satir communication family therapy (CFT) in healing codependency of drug dependents' family members in Tehran, Iran. METHODS: The intervention group participants (n = 27) received a seven-session social work intervention with CFT approach and the control group (n = 26) received treatment as usual...
July 2017: Journal of Evidence-informed Social Work
Nancy F Tojais, Aiqin Cao, Ying-Ju Lai, Lingli Wang, Pin-I Chen, Miguel A Alejandre Alcazar, Vinicio A de Jesus Perez, Rachel K Hopper, Christopher J Rhodes, Matthew A Bill, Lynn Y Sakai, Marlene Rabinovitch
OBJECTIVE: We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether in addition to increased production of elastase by PA smooth muscle cells previously reported, PA elastic fibers are susceptible to degradation because of their abnormal assembly. APPROACH AND RESULTS: Fibrillin-1 and elastin are the major components of elastic fibers, and fibrillin-1 binds bone morphogenetic proteins (BMPs) and the large latent complex of transforming growth factor-β1 (TGFβ1)...
August 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Jennifer L Steiner, Charles H Lang
Putative mechanisms leading to the development of alcoholic cardiomyopathy (ACM) include the interrelated cellular processes of mitochondria metabolism, oxidative stress and apoptosis. As mitochondria fuel the constant energy demands of this continually contracting tissue, it is not surprising that alcohol-induced molecular changes in this organelle contribute to cardiac dysfunction and ACM. As the causal relationship of these processes with ACM has already been established, the primary objective of this review is to provide an update of the experimental findings to more completely understand the aforementioned mechanisms...
August 2017: International Journal of Biochemistry & Cell Biology
Guillaume Hennequin, Everton J Agnes, Tim P Vogels
Inhibitory neurons, although relatively few in number, exert powerful control over brain circuits. They stabilize network activity in the face of strong feedback excitation and actively engage in computations. Recent studies reveal the importance of a precise balance of excitation and inhibition in neural circuits, which often requires exquisite fine-tuning of inhibitory connections. We review inhibitory synaptic plasticity and its roles in shaping both feedforward and feedback control. We discuss the necessity of complex, codependent plasticity mechanisms to build nontrivial, functioning networks, and we end by summarizing experimental evidence of such interactions...
July 25, 2017: Annual Review of Neuroscience
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