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https://www.readbyqxmd.com/read/28938602/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#1
Ming Zhao, Erin W Howard, Amanda B Parris, Zhiying Guo, Qingxia Zhao, Zhikun Ma, Ying Xing, Bolin Liu, Susan M Edgerton, Ann D Thor, Xiaohe Yang
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938590/ocular-toxicities-associated-with-targeted-anticancer-agents-an-analysis-of-clinical-data-with-management-suggestions
#2
Chen Fu, Dan S Gombos, Jared Lee, Goldy C George, Kenneth Hess, Andrew Whyte, David S Hong
Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938468/long-term-natural-course-of-small-non-functional-pancreatic-neuroendocrine-tumors-in-men1-results-from-the-dmsg
#3
Carolina R C Pieterman, Joanne M de Laat, Jos W R Twisk, Rachel S van Leeuwaarde, Wouter W de Herder, Koen M A Dreijerink, Ad R M M Hermus, Olaf M Dekkers, Anouk N A van der Horst-Schrivers, Madeleine L Drent, Peter H Bisschop, Bastiaan Havekes, Inne H M Borel Rinkes, Menno R Vriens, Gerlof D Valk
Background: Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in patients with Multiple Endocrine Neoplasia type 1 (MEN1) and metastatic disease is an important cause of MEN1-related mortality. Especially small non-functional (NF) pNETs pose a challenge to the treating physician and more information is needed regarding their natural course. We assessed long-term natural history of small NF-pNETs and its modifiers in the Dutch MEN1 population. Patients and Methods: Retrospective longitudinal observational cohort study of patients with small (<2cm) NF-pNETs from the Dutch national MEN1 database which includes >90% of the Dutch MEN1 population...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938413/prenatal-diagnosis-of-resistance-to-thyroid-hormone-and-its-clinical-implications
#4
Theodora Pappa, João Anselmo, Sunnee Mamanasiri, Alexandra M Dumitrescu, Roy E Weiss, Samuel Refetoff
Context: Resistance to thyroid hormone beta (RTHβ) is an autosomal dominant disorder characterized by reduced sensitivity of target tissues to thyroid hormones (TH). Individuals with RTHβ have high TH levels usually due to mutations in the TH receptor beta (THRB) gene. The management of RTHβ during pregnancy is challenging as wild-type (WT) fetuses born to RTHβ mothers have low birth weight and suppressed postnatal TSH, due to intrauterine exposure to excess TH. Objective: To determine birth weight and postnatal TSH of WT fetuses carried by mothers with RTHβ whose fT4 levels were maintained below 20% the upper limit of normal (ULN)...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938363/reconstruction-of-the-heel-middle-foot-sole-and-plantar-forefoot-with-the-medial-plantar-artery-perforator-mpap-flap-clinical-experience-with-28-cases
#5
Mario F Scaglioni, Daniel Rittirsch, Pietro Giovanoli
INTRODUCTION: Defects in the weight-bearing region of the foot sole can represent a substantial restriction in quality of life and pose a challenge for reconstructive plastic surgery.The purpose of this article is to report our experience with the use of medial plantar artery perforator (MPAP) flap for reconstruction of defects of the foot sole in 3 different regions: heel, middle foot sole and plantar forefoot. PATIENTS AND METHODS: From January 2003 to May 2016, 28 patients (13 males and 15 females) with an average age of 54 years (range 12 to 84 y...
September 15, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28938340/paediatric-traumatic-brain-injury-prognostic-insights-and-outlooks
#6
Alicia K Au, Robert S B Clark
PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Prognostication of outcome following TBI is challenging in this population and likely requires complex, multimodal models to achieve clinically relevant accuracy. This review highlights injury characteristics, physiological indicators, biomarkers and neuromonitoring modalities predictive of outcome that may be integrated for future development of sensitive and specific prognostic models...
September 21, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28938252/emotional-impact-of-end-of-life-decisions-on-professional-relationships-in-the-icu-an-obstacle-to-collegiality
#7
Alexandra Laurent, Magalie Bonnet, Gilles Capellier, Pierre Aslanian, Paul Hebert
OBJECTIVES: End-of-life decisions are not only common in the ICU but also frequently elicit strong feelings among health professionals. Even though we seek to develop more collegial interprofessional approaches to care and health decision-making, there are many barriers to successfully managing complex decisions. The aim of this study is to better understand how emotions influence the end-of-life decision-making process among professionals working in ICU. DESIGN: Qualitative study with clinical interviews...
September 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28938247/challenges-with-percent-predicted-maximum-vo2-in-patients-with-heart-failure
#8
Clinton A Brawner, Jonathan K Ehrman, Ali Shafiq, Matthew A Saval, Stuart D Russell, David E Lanfear, Steven J Keteyian
PURPOSE: To describe the influence of different equations to predict maximum oxygen uptake (MVO2) on the percent predicted MVO2 (ppMVO2) and the resultant categorization of patients with heart failure with reduced ejection fraction (HFrEF) into high or low risk. METHODS: In this retrospective cohort study, ppMVO2 was calculated using six different equations to predict MVO2 among 1,168 patients with HFrEF (33% women). Repeated measures analysis of variance was used to compare within-subject differences in mean ppMVO2 between the prediction equations...
September 21, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28938237/fertility-restoration-with-spermatogonial-stem-cells
#9
Francesca de Michele, Maxime Vermeulen, Christine Wyns
PURPOSE OF REVIEW: This review evaluates the state of the art in terms of challenges and strategies used to restore fertility with spermatogonial stem cells retrieved from prepubertal boys affected by cancer. Although these boys do not yet produce spermatozoa, the only option to preserve their fertility is cryopreservation of spermatogonial stem cells in the form of testicular cell suspensions or whole tissue pieces. Different techniques have been described to achieve completion of spermatogenesis from human, spermatogonial stem cells but none is yet ready for clinical application...
September 21, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28938087/emerging-opportunities-for-target-discovery-in-rare-cancers
#10
REVIEW
Tanaz Sharifnia, Andrew L Hong, Corrie A Painter, Jesse S Boehm
Rare cancers pose unique challenges to research due to their low incidence. Barriers include a scarcity of tissue and experimental models to enable basic research and insufficient patient accrual for clinical studies. Consequently, an understanding of the genetic and cellular features of many rare cancer types and their associated vulnerabilities has been lacking. However, new opportunities are emerging to facilitate discovery of therapeutic targets in rare cancers. Online platforms are allowing patients with rare cancers to organize on an unprecedented scale, tumor genome sequencing is now routinely performed in research and clinical settings, and the efficiency of patient-derived model generation has improved...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28938048/a-predictive-score-for-hypotension-in-patients-with-confirmed-dengue-fever-in-cayenne-hospital-french-guiana
#11
Félix Djossou, Guillaume Vesin, Narcisse Elenga, Magalie Demar, Loïc Epelboin, Gaëlle Walter, Philippe Abboud, Thierry Le-Guen, Dominique Rousset, Brigitte Moreau, Aba Mahamat, Denis Malvy, Mathieu Nacher
Background: Identifying patients at risk of developing severe dengue is challenging. The objective of the present study was to determine the incidence of hypotension and its predictive factors during the Dengue 2 epidemic in 2013. Methods: In 2013, a longitudinal study was performed using data from all confirmed cases of dengue seen in Cayenne General Hospital. The analysis used Cox proportional modeling to obtain adjusted hazards ratios for hypotension. Results: A total of 806 confirmed patients were included 78 (9...
December 1, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28938046/the-value-that-infectious-diseases-physicians-bring-to-the-healthcare-system
#12
Daniel P McQuillen, Ann T MacIntyre
While a career in infectious diseases (ID) has always been challenging and exciting, recognition of the value that ID physicians provide to the healthcare system as a whole, over and above the value they provide to individual patients, has been poor in this system. In response to this disparity, the Infectious Diseases Society of America Clinical Affairs Committee has long endeavored to quantify the value of ID physicians to the system, which is challenging in part because of the many avenues through which they influence healthcare...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28937953/the-biological-basis-of-chronic-traumatic-encephalopathy-following-blast-injury-a-literature-review
#13
Matt Aldag, Regina C Armstrong, Faris Bandak, Patrick S F Bellgowan, Timothy Bentley, Sean Biggerstaff, Katrina Caravelli, Joan Cmarik, Alicia Crowder, Thomas J DeGraba, Travis A Dittmer, Richard G Ellenbogen, Colin Greene, Raj K Gupta, Ramona Hicks, Stuart Hoffman, Robert C Latta, Michael J Leggieri, Donald Marion, Robert Mazzoli, Michael McCrea, John O'Donnell, Mark Packer, James B Petro, Todd E Rasmussen, Wendy Sammons-Jackson, Richard Shoge, Victoria Tepe, Ladd A Tremaine, James Zheng
The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury...
September 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28937952/modeling-the-long-term-consequences-of-repeated-blast-induced-mild-traumatic-brain-injuries
#14
Denes V Agoston
Repeated mild traumatic brain injury (rmTBI) caused by playing collision sports or by exposure to blasts during military operations can lead to late onset, chronic diseases such as chronic traumatic encephalopathy (CTE), a progressive neurodegenerative condition that manifests in increasingly severe neuropsychiatric abnormalities years after the last injury. Currently, because of the heterogeneity of the clinical presentation, confirmation of a CTE diagnosis requires post-mortem examination of the brain. The hallmarks of CTE are abnormal accumulation of phosphorylated tau protein, TDP-43 immunoreactive neuronal cytoplasmic inclusions, and astroglial abnormalities, but the pathomechanism leading to these terminal findings remains unknown...
September 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28937903/guiding-the-child-s-teeth-with-class-iii-dental-malocclusion-into-correct-occlusion-a-clinician-s-parenting
#15
A Kapur, H S Chawla, A Utreja, A Goyal
Pediatric dentists are often the first ones to be consulted for the presence of an anterior cross bite in the primary dentition. The condition requires an early interception to avoid progressive dentoalveolar and skeletal changes. The management, however, poses unique challenges in terms of young age of the child, correct choice of appliance and unpredictability of the response to treatment due to inability to ascertain the inherent growth potential. It is very important therefore for the specialist, to be able to recognize the early signs of a developing class III malocclusion tendency and also know the basic details of successful management of such cases...
September 22, 2017: Journal of Clinical Pediatric Dentistry
https://www.readbyqxmd.com/read/28937888/development-of-a-web-based-nationwide-korean-pediatric-dental-sedation-registry
#16
Sung Chul Choi, Yeonmi Yang, Seunghoon Yoo, Jiyeon Kim, Taesung Jeong, Teo Jeon Shin
OBJECTIVE: Finding a balance between sedation efficacy and safety remains an ongoing challenge. In children, the risk of sedation-related complications is relatively high. It is of utmost importance to determine the factors related to improved overall sedation outcomes. However, most previous reports have been based on small samples at single institutions. The Korean Academy of Pediatric Dentistry (KAPD) developed a Korean Pediatric Dental Sedation Registry using a web-based platform...
September 22, 2017: Journal of Clinical Pediatric Dentistry
https://www.readbyqxmd.com/read/28937879/advax4-delta-inulin-combination-adjuvant-together-with-ecmx-a-fusion-construct-of-three-protective-mtb-antigens-induces-a-potent-th1-immune-response-and-protects-mice-against-mycobacterium-tuberculosis-infection
#17
Bruno de Paula Oliveira Santos, Monalisa Martins Trentini, Renato Beilner Machado, Mara Rúbia Nunes Celes, André Kipnis, Nikolai Petrovsky, Ana Paula Junqueira-Kipnis
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMXformulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. When BALB/c mice were immunized three times intramuscularly with these vaccine formulationsInjection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b(+)) in the draining lymph nodes consistent with a chemotactic adjuvant effect...
September 22, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28937836/optimizing-a-3d-model-system-for-molecular-manipulation-of-tenogenesis
#18
Chun Chien, Brian Pryce, Sara F Tufa, Douglas R Keene, Alice H Huang
PURPOSE: Tendon injuries are clinically challenging due to poor healing. A better understanding of the molecular events that regulate tendon differentiation would improve current strategies for repair. The mouse model system has been instrumental to tendon studies and several key molecules were initially established in mouse. However, the study of gene function has been limited by the absence of a standard in vitro tendon system for efficiently testing multiple mutations, physical manipulations, and mis-expression...
September 22, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28937785/gaining-access-to-providing-medical-care-to-male-sport-teams-the-female-athletic-trainer-perspective
#19
Alicia Pike, Stephanie M Mazerolle, Jessica L Barrett
CONTEXT:   Female athletic trainers (ATs) can face barriers to employment within the profession. Although there is evidence for an increasing percentage of women in athletic training, the portion providing medical care to male sport teams within the professional sport and collegiate settings continues to be small. OBJECTIVE:   To investigate the experiences of female ATs when seeking employment with male sport teams within the Division I setting. DESIGN:   Qualitative study...
September 22, 2017: Journal of Athletic Training
https://www.readbyqxmd.com/read/28937639/sleep-disorders-in-childhood-neurological-diseases
#20
REVIEW
Abdullah Tolaymat, Zhao Liu
Sleep problems are frequently addressed as a primary or secondary concern during the visit to the pediatric neurology clinic. Sleep disorders can mimic other neurologic diseases (e.g., epilepsy and movement disorders), and this adds challenges to the diagnostic process. Sleep disorders can significantly affect the quality of life and functionality of children in general and those with comorbid neurological diseases in particular. Understanding the pathophysiology of sleep disorders, recognizing the implications of sleep disorder in children with neurologic diseases and behavioral difficulties, and early intervention continue to evolve resulting in better neurocognitive outcomes...
September 22, 2017: Children
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