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https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#1
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550746/zn-doped-cdo-nanoparticles-structural-morphological-optical-photocatalytic-and-anti-bacterial-properties
#2
Vinod Kumar Gupta, Ali Fakhri, Shiva Tahami, Shilpi Agarwal
Pure and zinc-doped CdO NPs (Zn-CdO NPs) were synthesized through a facile co-precipitation method. The structural, morphology, chemical composition, optical and antibacterial activity of the NPs were studied with respect to pure and Zn-doped CdO concentration (0-7.5mol.%). Scanning electron microscope (SEM) images reveal that pure and Zn-doped CdO NPs were in the nano-scale regime with different crystalline morphology. The energy dispersive X-ray spectroscopy (EDS) spectrum predicts the presence of Cadmium (Cd), Zinc (Zn) and Oxygen (O) in the prepared samples...
May 21, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28550641/a-fascia-lata-free-flap-in-pelvic-exenteration-for-fournier-gangrene-due-to-advanced-rectal-cancer-a-case-report
#3
Hiroshi Sawayama, Nobutomo Miyanari, Hidetaka Sugihara, Shiro Iwagami, Takao Mizumoto, Tatsuo Kubota, Yoshio Haga, Hideo Baba
BACKGROUND: Fournier gangrene due to advanced rectal cancer is a rapidly progressive gangrene of the perineum and buttocks. Emergency surgical debridement of necrotic tissue is crucial, and secondary surgery to resect tumors is necessary for wound healing. However, pelvic exenteration damages the pelvic floor, increasing the likelihood of herniation of internal organs into the infectious wound. The management of pelvic exenteration for rectal cancer with Fournier gangrene has not yet been established...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28550526/fetoscopic-patch-coverage-of-experimental-myelomenigocele-using-a-two-port-access-in-fetal-sheep
#4
Lucie Guilbaud, Nathalie Roux, Stéphanie Friszer, Charles Garabedian, Ferdinand Dhombres, Bettina Bessières, Catherine Fallet-Bianco, Federico Di Rocco, Michel Zerah, Jean-Marie Jouannic
PURPOSE: This study aims to assess the feasibility and the effectiveness of a fetoscopic myelomeningocele (MMC) coverage using a sealed inert patch through a two-port access, in the sheep model. METHODS: Forty-four fetuses underwent surgical creation of a MMC defect at day 75 and were divided into four groups according to the MMC repair technique, performed at day 90. Group 1 remained untreated. Group 2 had an open surgery using suture of the defect. Groups 3 and 4 underwent defect coverage using a Gore®-polytetrafluoroethylene patch secured with surgical adhesive (Bioglue®), with an open approach (group 3) and a fetoscopic one (group 4)...
May 26, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28550521/assessment-of-periodontal-bone-level-revisited-a-controlled-study-on-the-diagnostic-accuracy-of-clinical-evaluation-methods-and-intra-oral-radiography
#5
Véronique Christiaens, Hugo De Bruyn, Eric Thevissen, Sebastiaan Koole, Melissa Dierens, Jan Cosyn
OBJECTIVES: The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2). MATERIALS AND METHODS: The study sample included 49 interdental sites in 17 periodontitis patients...
May 26, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28550434/flagellin-fljb-as-an-adjuvant-to-the-recombinant-adenovirus-rabies-glycoprotein-vaccine-increases-immune-responses-against-rabies-in-mice
#6
Xingxing Xiao, Yun Zhang, Qiaolin Wei, Xiangping Yin
Rabies virus (RABV) causes an acute progressive viral encephalitis. Although currently licensed vaccines have an excellent safety and efficacy record, the development of a safer and more cost-effective vaccine is still being sought. An E1-deleted, replication-defective human adenovirus type 5 (HAd5) vector expressing RABV glycoprotein (HAd5-G) is thought to be a promising candidate vaccine for immune prophylaxis against rabies. Salmonella enterica serovar Typhimurium (S. Typhimurium) flagellin is a well-known immune adjuvant...
May 26, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#7
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#8
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550188/recommendations-for-splenectomy-in-hereditary-hemolytic-anemias
#9
Achille Iolascon, Immacolata Andolfo, Wilma Barcellini, Francesco Corcione, Loïc Garçon, Lucia De Franceschi, Claudio Pignata, Giovanna Graziadei, Dagmar Pospisilova, David C Rees, Mariane de Montalembert, Stefano Rivella, Antonella Gambale, Roberta Russo, Leticia Ribeiro, Jules Vives-Corrons, Patricia Aguilar-Martinez, Antonis Kattamis, Beatrice Gulbis, Maria Domenica Cappellini, Irene Roberts, Hannah Tamary
Hereditary hemolytic anemias are a group of disorders including red cell membrane defects, red blood cells enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and haemoglobinopathies. As damaged red blood cells passing through the spleen red pulp are efficiently removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550161/lymphoid-differentiation-of-hematopoietic-stem-cells-requires-efficient-cxcr4-desensitization
#10
Christelle Freitas, Monika Wittner, Julie Nguyen, Vincent Rondeau, Vincent Biajoux, Marie-Laure Aknin, Françoise Gaudin, Sarah Beaussant-Cohen, Yves Bertrand, Christine Bellanné-Chantelot, Jean Donadieu, Françoise Bachelerie, Marion Espéli, Ali Dalloul, Fawzia Louache, Karl Balabanian
The CXCL12/CXCR4 signaling exerts a dominant role in promoting hematopoietic stem and progenitor cell (HSPC) retention and quiescence in bone marrow. Gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor have been reported in the WHIM Syndrome (WS), a rare immunodeficiency characterized by lymphopenia. The mechanisms underpinning this remain obscure. Using a mouse model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibility that the lymphopenia in WS arises from defects at the HSPC level...
May 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28550061/the-lectin-chaperone-calnexin-is-involved-in-endoplasmic-reticulum-stress-response-by-regulating-ca-2-homeostasis-in-aspergillus-nidulans
#11
Shenghua Zhang, Hailin Zheng, Qiuyi Chen, Yuan Chen, Sha Wang, Ling Lu, Shizhu Zhang
The Ca(2+)-mediated signaling pathway is crucial for environmental adaptation in fungi. Here we show that calnexin, a molecular chaperone located in the endoplasmic reticulum (ER), plays an important role in regulating cytosolic free calcium concentration ([Ca(2+)]c) in Aspergillus nidulans Inactivation of calnexin (ClxA) in A. nidulans caused severe defects in hyphal growth and conidiation under ER stress caused by the ER-stress inducing agent dithiothreitol (DTT) or high temperature. Importantly, defects in the ΔclxA mutant were restored by the addition of extracellular calcium...
May 26, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28550027/exceptional-response-to-nivolumab-and-stereotactic-body-radiation-therapy-sbrt-in-neuroendocrine-cervical-carcinoma-with-high-tumor-mutational-burden-management-considerations-from-the-center-for-personalized-cancer-therapy-at-uc-san-diego-moores-cancer-center
#12
Andrew Sharabi, Sangwoo Shawn Kim, Shumei Kato, Philip D Sanders, Sandip Pravin Patel, Parag Sanghvi, Elizabeth Weihe, Razelle Kurzrock
Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors. Here we report a patient with metastatic, chemotherapy-refractory neuroendocrine carcinoma who presented with partial bowel obstruction due to a large tumor burden...
May 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28549923/maintaining-vitamin-d-sufficiency-is-associated-with-improved-structural-and-symptomatic-outcomes-in-knee-osteoarthritis
#13
Shuang Zheng, Xingzhong Jin, Flavia Cicuttini, Xia Wang, Zhaohua Zhu, Anita Wluka, Weiyu Han, Tania Winzenberg, Benny Antony, Dawn Aitken, Leigh Blizzard, Graeme Jones, Changhai Ding
BACKGROUND: To describe whether maintaining sufficient serum vitamin D levels in people with knee osteoarthritis and baseline vitamin D insufficiency has an association with change in knee structures and symptoms over two years. METHODS: Participants (n=413, age 63.2) with symptomatic knee osteoarthritis and vitamin D insufficiency were enrolled in a clinical trial. 340 participants (82.3%) completed the study with 25-hydroxyvitamin D [25(OH)D] measurements at month 0, 3 and 24...
May 23, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28549686/pilonidal-sinus-disease-surgery-in-children-the-first-study-to-compare-crystallized-phenol-application-to-primary-excision-and-closure
#14
Ufuk Ates, Ergun Ergun, Gulnur Gollu, Sumeyye Sozduyar, Meltem Kologlu, Murat Cakmak, Huseyin Dindar, Aydin Yagmurlu
INTRODUCTION: Pilonidal sinus (PS) is an infectious and inflammatory disease of sacrococcygeal region. Current methods include; surgical excision with/without suturing the defect, rhomboid excision and flap and chemical substance application. In this study, crystallized phenol application was compared to excision and primary closure. PATIENTS AND METHODS: This retrospective study included pediatric patients with PS who were treated with excision and primer closure technique and phenol application...
May 16, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28549654/congenital-heart-defects-and-measures-of-prenatal-brain-growth-a-systematic-review
#15
REVIEW
Thommy Hansen, Tine Brink Henriksen, Cathrine Carlsen Bach, Niels Bjerregård Matthiesen
BACKGROUND: We summarize the evidence for an association between congenital heart defects and prenatal brain growth through a systematic literature review. Congenital heart defects are among the most common malformations, affecting approximately six per 1000 live births. The association between congenital heart defects and long-term neurodevelopmental disorders is well established. Increasing evidence suggests an association between impaired prenatal brain growth and neurodevelopmental disorders in children with congenital heart defects...
April 1, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28549630/-the-successful-saga-of-percutaneous-pulmonary-valvulation-in-congenital-heart-diseases
#16
Sophie Malekzadeh-Milani, Younes Boudjemline
With new surgical techniques, more and more complex congenital heart defects are treated requiring sometimes right ventricle to pulmonary artery conduit implantation. In order to extend RV to PA conduit lifespan, 15 years ago a valved stent was developed. The implantation technique was progressively standardized to decrease risks of procedural complications. Medium and long-term hemodynamic results of the stent were so good that indications were broadened to native or complex right ventricular outflow tracts...
May 23, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28549624/multiparametric-assessment-of-voice-quality-and-quality-of-life-in-patients-undergoing-microlaryngeal-surgery-correlation-between-subjective-and-objective-methods
#17
Anna Rzepakowska, Ewelina Sielska-Badurek, Ewa Osuch-Wójcikiewicz, Kazimierz Niemczyk
The aim of the study was to estimate voice defect and the quality of life deterioration in patients with different laryngeal pathologies qualified for microsurgery treatment. The results of videolaryngostroboscopy (VLS), perception, aerodynamics, acoustics, Dysphonia Severity Index, Voice Handicap Index (VHI), and the World Health Organization Quality of Life Scale Brief Version before microsurgery were analyzed. There were 151 patients enrolled in the study. There were 86 patients in group 1 (benign lesions), 34 in group 2 (premalignant conditions), and 31 in group 3 (malignant neoplasms)...
May 23, 2017: Journal of Voice: Official Journal of the Voice Foundation
https://www.readbyqxmd.com/read/28549617/hematopathological-alterations-of-major-tumor-suppressor-cascade-vital-cell-cycle-inhibitors-and-hematopoietic-niche-components-in-experimental-myelodysplasia
#18
Ritam Chatterjee, Shubhangi Gupta, Sujata Law
Myelodysplastic syndrome (MDS) is a poorly understood dreadful hematopoietic disorder that involves maturational defect and abnormalities in blood cell production leading to dysplastic changes and peripheral blood pancytopenia. The present work aims in establishing the mechanistic relationship of the expressional alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic microenvironmental components with the disease pathophysiologies. The study involves the development of N-N' Ethylnitrosourea (ENU) induced mouse model of MDS, characterization of the disease with blood film and bone marrow smear studies, scanning electron microscopic observation, mitochondrial membrane potential determination, flowcytometric analysis of osteoblastic and vascular niche components along with the expressional study of cleaved caspase-3, PCNA, Chk-2, p53, Ndn, Gfi-1, Tie-2, Sdf-1, Gsk-3β, p18 and Myt-1 in the bone marrow compartment...
May 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#19
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28549518/ganglion-cell-inner-plexiform-layer-change-detected-by-optical-coherence-tomography-indicates-progression-in-advanced-glaucoma
#20
Joong Won Shin, Kyung Rim Sung, Gary C Lee, Mary K Durbin, Daniel Cheng
PURPOSE: To examine the performance of Guided Progression Analysis (GPA; Carl Zeiss Meditec, Dublin, CA) in spectral-domain optical coherence tomography (OCT) in detecting progressive thinning of ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) in glaucoma. DESIGN: Longitudinal, observational study. PARTICIPANTS: A total of 196 eyes of 123 primary open-angle glaucoma patients (mean follow-up, 5.0 years). METHODS: Macular GCIPL and peripapillary RNFL thicknesses were measured by Cirrus HD-OCT (Zeiss, Dublin, CA), and progressive GCIPL and RNFL thinning were assessed by GPA...
May 23, 2017: Ophthalmology
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