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https://www.readbyqxmd.com/read/28934823/comprehensive-analysis-of-non-synonymous-natural-variants-of-g-protein-coupled-receptors
#1
Hee Ryung Kim, Nguyen Minh Duc, Ka Young Chung
G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs...
September 19, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28934822/stent-placement-for-benign-esophageal-leaks-perforations-and-fistulae-a-clinical-prediction-rule-for-successful-leakage-control
#2
Emo E van Halsema, Wouter F W Kappelle, Bas L A M Weusten, Robert Lindeboom, Mark I van Berge Henegouwen, Paul Fockens, Frank P Vleggaar, Manon C W Spaander, Jeanin E van Hooft
Background and study aims Sealing esophageal leaks by stent placement allows healing in 44 % - 94 % of patients. We aimed to develop a prediction rule to predict the chance of successful stent therapy. Patients and methods In this multicenter retrospective cohort study, patients with benign upper gastrointestinal leakage treated with stent placement were included. We used logistic regression analysis including four known clinical predictors of stent therapy outcome. The model performance to predict successful stent therapy was evaluated in an independent validation sample...
September 21, 2017: Endoscopy
https://www.readbyqxmd.com/read/28934804/comparison-of-7-surgical-interventions-for-lumbar-disc-herniation-a-network-meta-analysis
#3
Fan Feng, Qianqian Xu, Feifei Yan, Yuanlong Xie, Zhouming Deng, Chao Hu, Xiaobin Zhu, Lin Cai
BACKGROUND: The number of interventions on intervertebral discs rapidly increased and the treatment options for lumbar disc surgery quickly evolved. It is important that the safety and efficacy of all new innovative procedures be compared with currently accepted forms of treatment; however, the previous pairwise meta-analyses could not develop the hierarchy of these treatments. OBJECTIVES: The purpose of the study is to perform a network meta-analysis to evaluate the clinical results of 7 surgical interventions for the treatment of lumbar disc herniation...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934799/factors-influencing-the-application-of-a-biopsychosocial-perspective-in-clinical-judgement-of-chronic-pain-interactive-management-with-medical-students
#4
Christopher P Dwyer, Phoebe E McKenna-Plumley, Hannah Durand, Emer M Gormley, Brian W Slattery, Owen M Harney, Padraig MacNeela, Brian E McGuire
BACKGROUND: Though there is wide support for the application of biopsychosocial perspectives in clinical judgement of chronic pain cases, such perspectives are often overlooked due to either inadequate training or attitudes favoring a biomedical approach. Recent research has indicated that despite such explanations, both established general practitioners (GP) and medical students account for some psychosocial factors when making clinical judgements regarding chronic pain cases, but report not being likely to apply these in real-world, clinical settings due to numerous factors, including available time with patients...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934779/what-are-the-predictors-of-altered-central-pain-modulation-in-chronic-musculoskeletal-pain-populations-a-systematic-review
#5
Jacqui Clark, Jo Nijs, Gillian Yeowell, Peter Charles Goodwin
BACKGROUND: Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. OBJECTIVES: To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934778/the-effect-of-early-use-of-supplemental-therapy-on-preventing-postherpetic-neuralgia-a-systematic-review-and-meta-analysis
#6
Xiu-Fang Xing, Zhen-Feng Zhou, Feng-Jiang Zhang, Min Yan
BACKGROUND: Postherpetic neuralgia (PHN) is the most common and refractory complication of herpes zoster (HZ). Aggressive treatment of acute pain in HZ has the potential to prevent the development of PHN, but the preventive efficacy of supplemental therapy commonly used in clinical practice is controversial. OBJECTIVES: Our aim is to examine the efficacy of supplemental therapy in preventing PHN. STUDY DESIGN: A meta-analysis. SETTING: All of the selected studies are randomized controlled trials (RCTs)...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934777/effectiveness-of-thermal-annular-procedures-in-treating-discogenic-low-back-pain
#7
Standiford Helm Ii, Thomas T Simopoulos, Milan Stojanovic, Salahadin Abdi, Mohamed Ahamed El Terany
BACKGROUND: Discogenic low back is a distinct clinic entity characterized by pain arising from a damaged disc. The diagnosis is clouded by the controversy surrounding discography. The treatment options are limited, with unsatisfactory results from both conservative treatment and surgery. Multiple interventional therapies have been developed to treat discogenic pain, but most have not yet been validated by high quality studies.The best studied treatment for discogenic pain is the use of heat, which has been labeled as thermal intradiscal procedures (TIPs) by the Centers for Medicare and Medicaid Services (CMS)...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934771/stimulating-the-clinical-academics-of-tomorrow-a-survey-of-research-opportunities-for-medical-students-in-new-zealand
#8
Ibrahim S Al-Busaidi, Cameron I Wells
Developing the clinical academic workforce of the future is a priority of international relevance. Despite a number of measures implemented to address this challenge, a small proportion of medical students engage in research. Lack of knowledge of available research opportunities, and difficulty finding projects and suitable mentors are key barriers to undergraduate medical research. To date, there is no consolidated source of information on undergraduate research training opportunities and their outcomes available to medical students in New Zealand...
September 22, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/28934764/assessment-of-training-capacity-in-new-zealand-general-practices-a-stocktake-in-the-lower-north-island-and-south-island
#9
Samantha A Murton, Susan Rh Pullon
AIM: General practices are providing clinically-based training for rapidly increasing numbers of medical (and other health professional) trainees. This study investigated capacity and intention of general practices to additionally teach junior doctors (now required to undertake community-based attachments by the New Zealand Medical Council) alongside current trainees in their service. METHODS: A web-based/telephone survey of all general practices was developed and administered November 2015-April 2016...
September 22, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/28934750/frontotemporal-dementia-caused-by-the-p301l-mutation-in-the-mapt-gene-clinicopathological-features-of-13-cases-from-the-same-geographical-origin-in-barcelona-spain
#10
Sergi Borrego-Écija, Joana Morgado, Leire Palencia-Madrid, Oriol Grau-Rivera, Ramón Reñé, Isabel Hernández, Consuelo Almenar, Mircea Balasa, Anna Antonell, José Luis Molinuevo, Albert Lladó, Marian Martínez de Pancorbo, Ellen Gelpi, Raquel Sánchez-Valle
BACKGROUND/AIMS: We identified and studied 13 patients carrying the P301L mutation in the MAPT gene from the same area (Baix Llobregat County) in Barcelona, Spain. METHODS: The demographic and clinical features were reviewed retrospectively. Detailed neuropathological characterization was obtained in 9 subjects. To investigate the origin of the P301L mutation in these families, 20 single nucleotide polymorphisms (SNPs) in the MAPT gene were analyzed. RESULTS: The mean age at disease onset was 51 years and the mean disease duration was 7 years...
September 22, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28934637/igf-system-targeted-therapy-therapeutic-opportunities-for-ovarian-cancer
#11
REVIEW
J A L Liefers-Visser, R A M Meijering, A K L Reyners, A G J van der Zee, S de Jong
The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models...
September 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#12
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934554/improvements-in-clinical-practice-for-fertility-preservation-among-young-cancer-patients-results-from-bundled-interventions
#13
Natalie K Bradford, Roderick Walker, Roslyn Henney, Po Inglis, Raymond J Chan
AIMS: The consequences of cancer and treatment on fertility can be a continuing source of distress for adolescents and young adults. The study aims were to assess the effects of bundled interventions on clinical practice concerning fertility in young people aged 14-25 years with cancer. METHODS: Bundled interventions, including development of quality indicators, resources, and targeted education, were introduced during 2015 across five cancer centers. Data before interventions (2012-2014) were compared with data prospectively collected during 2015-2016...
September 21, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28934536/glomus-tumor-of-the-sciatic-nerve-an-extraspinal-cause-of-sciatica
#14
Basilia Onyinyechukwu Nwankwo, Robert M Henshaw, Dhruv Kumar
Glomus tumors are small, benign tumors that arise from glomus bodies, structures found normally within the dermis that assist in temperature regulation via their vasoconstrictive response to sympathetic stimuli. Glomus tumors are found typically in the hand and are classically a cause of focal pain and temperature sensitivity. They often present as a small blue lesion seen under the nail bed of a finger or a toe and cause point tenderness. Glomus tumors of peripheral nerves are exceedingly rare and can lead to disability akin to compressive neuropathy when present...
September 21, 2017: Orthopedics
https://www.readbyqxmd.com/read/28934500/a-synthetic-dna-binding-inhibitor-of-sox2-guides-human-induced-pluripotent-stem-cells-to-differentiate-into-mesoderm
#15
Junichi Taniguchi, Ganesh N Pandian, Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Kyeong Kyu Kim, Hiroshi Sugiyama
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#16
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934424/the-impact-of-hepatitis-b-vaccine-failure-on-long-term-natural-course-of-chronic-hepatitis-b-virus-infection-in-hepatitis-b-e-antigen-seropositive-children
#17
Chi-San Tai, Jia-Feng Wu, Huey-Ling Chen, Yen-Hsuan Ni, Hong-Yuan Hsu, Mei-Hwei Chang
Background: Vaccine failure with chronic hepatitis B virus (HBV) infection still develops in children after universal hepatitis B immunization. This study aimed to investigate the natural course of chronic HBV infection in children with vaccine failure and compare it with that of nonvaccinated children. Methods: Three hundred fifty-six hepatitis B e antigen (HBeAg)-seropositive, hepatitis B surface antigen (HBsAg) carrier children, who were followed for at least 1 year without antiviral therapy, were enrolled...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934395/abnormal-polyamine-metabolism-is-unique-to-the-neuropathic-forms-of-mps-potential-for-biomarker-development-and-insight-into-pathogenesis
#18
Christian Hinderer, Nathan Katz, Jean-Pierre Louboutin, Peter Bell, Jakub Tolar, Paul J Orchard, Troy C Lund, Mohamad Nayal, Liwei Weng, Clementina Mesaros, Carolina F M de Souza, Amauri Dalla Corte, Roberto Giugliani, James M Wilson
The mucopolysaccharidoses (MPS) are rare genetic disorders marked by severe somatic and neurological symptoms. Development of treatments for the neurological manifestations of MPS has been hindered by the lack of objective measures of central nervous system disease burden. Identification of biomarkers for central nervous system disease in MPS patients would facilitate the evaluation of new agents in clinical trials. High throughput metabolite screening of cerebrospinal fluid (CSF) samples from a canine model of MPS I revealed a marked elevation of the polyamine, spermine, in affected animals, and gene therapy studies demonstrated that reduction of CSF spermine reflects correction of brain lesions in these animals...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934376/managing-menopausal-symptoms-and-associated-clinical-issues-in-breast-cancer-survivors
#19
Richard J Santen, Cynthia A Stuenkel, Susan R Davis, JoAnn V Pinkerton, Anne Gompel, Mary Ann Lumsden
Objective: Review evidence to guide the management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Evidence: Randomized controlled clinical trials, observational studies, evidence- based guidelines, and expert opinion from professional societies. Background: Several symptoms and clinical problems associated with estrogen depletion -sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia and osteoporosis- confront the estimated 9...
August 2, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28934331/direct-identification-of-microorganisms-from-thioglycolate-broth-by-maldi-tof-ms
#20
Jorge Arca-Suárez, Fátima Galán-Sánchez, Pilar Marin-Casanova, Manuel A Rodríguez-Iglesias
We developed an easy MALDI-TOF MS-based assay to identify microorganisms directly from thioglycolate broth. A total of 101 positive thioglycolate broths inoculated with 15 different kinds of samples were evaluated. In 91 samples (90.1%), direct MALDI-TOF MS identifications were the same as those obtained after conventional laboratory procedures including subcultures. In 10 samples misidentified by direct processing, yeasts or mixed cultures grew in the thioglycolate subcultures, or high cellular debris hampered a correct analysis...
2017: PloS One
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