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https://www.readbyqxmd.com/read/29666143/truncated-c-terminus-of-fibrillin-1-induces-marfanoid-progeroid-lipodystrophy-mpl-syndrome-in-rabbit
#1
Mao Chen, Bing Yao, Qiangbing Yang, Jichao Deng, Yuning Song, Tingting Sui, Lina Zhou, HaoBing Yao, Yuanyuan Xu, Hongsheng Ouyang, Daxin Pang, Zhanjun Li, Liangxue Lai
Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system...
April 9, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29665937/-current-understanding-of-myeloproliferative-neoplasm-related-gene-mutations-and-cytokine-review
#2
Zhi-Peng He, Yong Wu
Myeloproliferative neoplasm(MPN) is clonal hematopoietic stem cell disorder characterized by abnormal proliferation and expansion of one or more myeloid lineages. BCR-ABL-negative MPN includes polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The mutations of JAK2, CALR and MPL genes are involved in the pathogenesis of MPN that provided a more complete molecular diagnostic standard for MPN. More and more new mutated genes related to prognosis of MPN were discovered in the past few years, at same time it was found that cytokines were also involved in the genesis and development of MPN...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665657/recent-advances-in-the-diagnosis-and-management-of-primary-myelofibrosis
#3
Katsuto Takenaka, Kazuya Shimoda, Koichi Akashi
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) in which dysregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways is the major pathogenic mechanism. Most patients with PMF carry a driver mutation in the JAK2, MPL (myeloproliferative leukemia), or CALR (calreticulin) genes. Mutations in epigenetic regulators and RNA splicing genes may also occur, and play critical roles in PMF disease progression. Based on revised World Health Organization diagnostic criteria for MPNs, both screening for driver mutations and bone marrow biopsy are required for a specific diagnosis...
April 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29664759/characteristics-of-medical-professional-liability-claims-in-pediatric-orthopedics
#4
Jessica Burns, M Wade Shrader, Carla Boan, Mohan Belthur
OBJECTIVES: Medical malpractice is burdensome to the U.S. healthcare system. The following is an epidemiological analysis of the closed medical professional liability (MPL) claims in pediatric orthopedics using data maintained by the Physician Insurers Association of America. METHODS: The Physician Insurers Association of America registry of MPL claims from 1985 to 2013 for all specialties included 286,021 closed claims in the United States. All closed MPL claims for orthopedic surgery in patients younger than 18 years were retrospectively reviewed (N = 2,671)...
April 16, 2018: Journal of Patient Safety
https://www.readbyqxmd.com/read/29660737/treatment-of-a-paediatric-distal-femoral-malunion-deformity
#5
Greta S Pavarotti, Randy J Boudrieau
OBJECTIVE:  The aim of this article was to describe the surgical re-alignment technique and stabilization of a distal femoral deformity in a 6-week-old, male, Foxhound. METHODS:  A healing metaphyseal fracture, resulting in a valgus deformity with internal rotation, was observed just proximal to the distal femoral physis. The deformity was treated by an opening wedge osteotomy with lateral translation and external rotation of the distal epiphysis using a guide-wire technique; a corticocancellous allograft bridged the defect, which was stabilized with a 2...
April 16, 2018: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
https://www.readbyqxmd.com/read/29657017/assessment-of-the-antigenic-and-neuroprotective-activity-of-the-subunit-anti-toxoplasma-vaccine-in-t-gondii-experimentally-infected-mice
#6
Justyna Gatkowska, Marek Wieczorek, Bożena Dziadek, Katarzyna Dzitko, Jarosław Dziadek, Henryka Długońska
The aim of this study was to evaluate the immunogenic and immunoprotective activities and to determine the neuroprotective capacity of the tetravalent vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 + MAG1) administered with safe adjuvants (MPL and alum) using male and female inbred mice. The tested antigenic combination provided partial protection against brain cyst formation, especially in males (reduction in cyst burden by 72%). The decrease in cyst burden was observed for the whole brain as well as for specified brain regions associated with natural defensive behaviors, emotion processing and integration of motor and sensory stimuli...
April 30, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29650801/the-role-of-jak2-inhibitors-in-mpn-seven-years-after-approval
#7
Francesco Passamonti, Margherita Maffioli
Myeloproliferative neoplasms (MPNs) include essential thrombocythemia, polycythemia vera (PV) and primary myelofibrosis (PMF). Phenotype-driver mutations of JAK2, CALR and MPL genes are present in MPNs and can be variably combined with additional mutations. Driver mutations entail a constitutive activation of the JAK2/STAT pathway, the key signaling cascade in MPNs. Among JAK2 inhibitors (JAKis), ruxolitinib (RUX) has been approved for the treatment of intermediate and high risk myelofibrosis (MF) and of PV inadequately controlled by or intolerant of hydroxyurea...
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29644531/splanchnic-vein-thrombosis-in-the-myeloproliferative-neoplasms
#8
REVIEW
Imo J Akpan, Brady Lee Stein
PURPOSE OF REVIEW: To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis. RECENT FINDINGS: The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women...
April 11, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29615956/initial-clinical-evaluation-of-the-modular-prosthetic-limb
#9
Briana N Perry, Courtney W Moran, Robert S Armiger, Paul F Pasquina, Jamie W Vandersea, Jack W Tsao
The Modular Prosthetic Limb (MPL) was examined for its feasibility and usability as an advanced, dexterous upper extremity prosthesis with surface electromyography (sEMG) control in with two individuals with below-elbow amputations. Compared to currently marketed prostheses, the MPL has a greater number of sequential and simultaneous degrees of motion, as well as wrist modularity, haptic feedback, and individual digit control. The MPL was successfully fit to a 33-year-old with a trans-radial amputation (TR01) and a 30-year-old with a wrist disarticulation amputation (TR02)...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29611379/gata1-expression-in-bcr-abl1-negative-myeloproliferative-neoplasms
#10
Naery Yang, Sholhui Park, Min Sun Cho, Miae Lee, Ki Sook Hong, Yeung Chul Mun, Chu Myong Seong, Hee Jin Huh, Jungwon Huh
BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records...
July 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29607698/the-role-of-mpl-and-imiquimod-adjuvants-in-enhancement-of-immune-response-and-protection-in-balb-c-mice-immunized-with-soluble-leishmania-antigen-sla-encapsulated-in-nanoliposome
#11
Tara Emami, Seyed Mahdi Rezayat, Ali Khamesipour, Rasool Madani, Gholamreza Habibi, Mansure Hojatizade, Mahmoud Reza Jaafari
Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative...
April 1, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29599344/racial-disparities-in-the-molecular-landscape-of-cancer
#12
Elisabeth I Heath, Filipa Lynce, Joanne Xiu, Angela Ellerbrock, Sandeep K Reddy, Elias Obeid, Stephen V Liu, Aliccia Bollig-Fischer, Duska Separovic, Ari Vanderwalde
BACKGROUND/AIM: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. MATERIALS AND METHODS: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29587261/high-frequency-of-copy-neutral-loss-of-heterozygosity-in-patients-with-myelofibrosis
#13
Milton Rego de Paula Junior, Alexandre Nonino, Juliana Minuncio Nascimento, Raphael S Bonadio, Aline Pic-Taylor, Silviene F de Oliveira, Rinaldo Wellerson Pereira, Cintia do Couto Mascarenhas, Juliana Forte Mazzeu
Myelofibrosis is the rarest and most severe type of Philadelphia-negative classical myeloproliferative neoplasms. Although mutually exclusive driver mutations in JAK2, MPL, or CALR that activate JAK-STAT pathway have been related to the pathogenesis of the disease, chromosome abnormalities have also been associated with the phenotype and prognosis of the disease. Here, we report the use of a chromosomal microarray platform consisting of both oligo and SNP probes to improve the detection of chromosome abnormalities in patients with myelofibrosis...
March 22, 2018: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29575945/current-approaches-to-challenging-scenarios-in-myeloproliferative-neoplasms
#14
Eran Zimran, Ronald Hoffman, Marina Kremyanskaya
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia and primary myelofibrosis are clonal hematological malignancies that originate at the level of the hematopoietic stem cell, and are characterized by excessive proliferation of cells belonging to one or more of the myeloid lineages. Central to the pathogenesis of the MPNs is constitutive activation of the JAK/STAT signaling pathway due to a family of driver mutations affecting JAK2, CALR or MPL...
March 29, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29570603/real-time-estimation-of-population-exposure-to-pm-2-5-using-mobile-and-station-based-big-data
#15
Bin Chen, Yimeng Song, Tingting Jiang, Ziyue Chen, Bo Huang, Bing Xu
Extremely high fine particulate matter (PM2.5 ) concentration has been a topic of special concern in recent years because of its important and sensitive relation with health risks. However, many previous PM2.5 exposure assessments have practical limitations, due to the assumption that population distribution or air pollution levels are spatially stationary and temporally constant and people move within regions of generally the same air quality throughout a day or other time periods. To deal with this challenge, we propose a novel method to achieve the real-time estimation of population exposure to PM2...
March 23, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29564177/investigation-of-targetable-predictive-and-prognostic-markers-in-gallbladder-carcinoma
#16
Azfar Neyaz, Nuzhat Husain, Sameer Gupta, Swati Kumari, Aditi Arora, Namrata Puneet Awasthi, Kiran Preet Malhotra, Sanjeev Misra
Background: Gallbladder carcinoma, uncommon in most of the world, is frequent in South East Asia. It presents in advanced stages with limited therapeutic options. We investigated targetable predictive and prognostic Markers in 268 cases including 233 primary site lesions and 35 metastatic gallbladder carcinoma. Methods: EGFR, VEGF, HER2/Neu and p53 were assessed using immunohistochemistry. HER2/Neu was validated in a subset by fluorescent in situ hybridization (FISH) using tissue microarray (TMA)...
February 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29562801/long-term-effect-of-monophosphoryl-lipid-a-adjuvanted-specific-immunotherapy-in-patients-with-grass-pollen-allergy
#17
Stefan Zielen, Jennis Gabrielpillai, Eva Herrmann, Johannes Schulze, Ralf Schubert, Martin Rosewich
BACKGROUND: Ultra-short course pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL) is attractive to conventional allergen-specific immunotherapy (AIT). Long term efficacy of MPL-AIT has not been evaluated. METHODS: 68 patients (age 16.75 ± 5.3 years) with allergic rhinitis to grass pollen were investigated. Group 1: 21 controls; Group 2: 19 after complete AIT, and Group 3: 28 with AIT and treatment cessation: 4 years range 3-6 years ago. RESULTS: The clinical symptoms (running nose, sneezing, conjunctivitis and the weekly overall score) were significantly reduced in patients group 2 and 3 compared with controls without AIT p < 0...
March 22, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29562441/-spectrum-of-somatic-mutations-and-their-prognostic-significance-in-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#18
J Feng, X Y Gong, Y J Jia, K Q Liu, Y Li, X B Dong, Q Y Fang, K Ru, Q H Li, H J Wang, X L Zhao, Y N Jia, Y Song, Z Tian, M Wang, K J Tang, J X Wang, Y C Mi
Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29560522/elevated-expression-of-the-ezh2-gene-in-calr-mutated-patients-with-primary-myelofibrosis
#19
Ni Fan, Yigui Tang, Zhiyuan Wu, Ming Guan, Bobin Chen, Xiaoping Xu, Weizhe Ma, Xiao Xu, Xinju Zhang
Primary myelofibrosis (PMF) is one of the BCR/ABL-negative myeloproliferative neoplasms (MPNs), characterized by the diffuse fibrous hyperproliferation, bone marrow osteosclerosis, extramedullary hematopoiesis, and marked splenomegaly. The patients with PMF have an insidious onset, a long duration of clinical course, and the deteriorated quality of life. It has been reported that the CALR gene 9 exon mutations were detected in 25-30% PMF patients, particularly as high as 80% in the JAK2/MPL-negative ones. As the second most common mutation in BCR/ABL-negative MPNs, CALR mutation has been included in the latest World Health Organization (WHO) classification criteria as one of the main diagnostic criteria for both essential thrombocythemia (ET) and PMF...
March 20, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29554138/plga-particulate-subunit-tuberculosis-vaccines-promote-humoral-and-th17-responses-but-do-not-enhance-control-of-mycobacterium-tuberculosis-infection
#20
Anneliese S Ashhurst, Thaigarajan Parumasivam, John Gar Yan Chan, Leon C W Lin, Manuela Flórido, Nicholas P West, Hak-Kim Chan, Warwick J Britton
Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL)...
2018: PloS One
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