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https://www.readbyqxmd.com/read/29775114/oxygen-dependency-of-mitochondrial-metabolism-indicates-outcome-of-newborn-brain-injury
#1
Gemma Bale, Subhabrata Mitra, Isabel de Roever, Magdalena Sokolska, David Price, Alan Bainbridge, Roxana Gunny, Cristina Uria-Avellanal, Giles S Kendall, Judith Meek, Nicola J Robertson, Ilias Tachtsidis
There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29774780/increased-levels-of-circulating-gfap-and-crmp2-autoantibodies-in-the-acute-stage-of-spinal-cord-injury-predict-the-subsequent-development-of-neuropathic-pain
#2
Georgene W Hergenroeder, John B Redell, Huimahn Alex Choi, Lisa Hollan Schmitt, William Donovan, Gerard E Francisco, Karl M Schmitt, Anthony N Moore, Pramod K Dash
Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774052/therapeutic-drug-monitoring-of-vedolizumab-in-inflammatory-bowel-disease-current-data-and-future-directions
#3
REVIEW
Mark G Ward, Miles P Sparrow, Xavier Roblin
The introduction of vedolizumab, a lymphocyte adhesion inhibitor, has expanded the relatively limited therapeutic armamentarium available for Crohn's disease and ulcerative colitis. Despite its effectiveness, both primary nonresponse and secondary loss of response to vedolizumab do occur, as is observed with the use of anti-tumour necrosis factor (TNF) therapy. Further, in a proportion, onset of efficacy may be relatively slow. A large body of data support an exposure-response relationship with anti-TNF drug levels, which has led to therapeutic drug monitoring becoming incorporated into everyday clinical management...
2018: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29773794/calreticulin-and-integrin-alpha-dissociation-induces-anti-inflammatory-programming-in-animal-models-of-inflammatory-bowel-disease
#4
Masayoshi Ohkuro, Jun-Dal Kim, Yoshikazu Kuboi, Yuki Hayashi, Hayase Mizukami, Hiroko Kobayashi-Kuramochi, Kenzo Muramoto, Manabu Shirato, Fumiko Michikawa-Tanaka, Jun Moriya, Teruya Kozaki, Kazuma Takase, Kenichi Chiba, Kishan Lal Agarwala, Takayuki Kimura, Makoto Kotake, Tetsuya Kawahara, Naoki Yoneda, Shinsuke Hirota, Hiroshi Azuma, Nobuko Ozasa-Komura, Yoshiaki Ohashi, Masafumi Muratani, Keiji Kimura, Ieharu Hishinuma, Akiyoshi Fukamizu
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773139/systemic-humoral-immunity-in-beef-bulls-following-therapeutic-vaccination-against-tritrichomonas-foetus
#5
Christopher Alling, D Owen Rae, Xiaojie Ma, Laura Neumann, L Gene Lollis, Elizabeth Steele, John Yelvington, Hemant K Naikare, Heather Stockdale Walden, John Crews, Raoul Boughton
The utility of therapeutic vaccination of bulls against Tritrichomonas foetus has been advocated in previous studies, but anecdotal reports suggest this practice does not clear infections and may additionally confound diagnostic testing by reducing parasite burdens below detectable limits. The objective of this study was to characterize the systemic humoral immune response to therapeutic vaccination in T. foetus-infected bulls over a period of four months using an indirect ELISA and to compare the dynamics of this response to culture and PCR results to establish the existence of a relationship (or lack thereof) between immunization and infection status...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29772912/relations-between-empathy-and-anxiety-dimensions-in-inpatient-adolescents
#6
Malgorzata Gambin, Carla Sharp
BACKGROUND AND OBJECTIVES: A better understanding of the relationships between empathy and internalizing disorders is needed to plan therapeutic interventions for children and adolescents. Several studies have revealed positive relations of internalizing symptoms to personal distress and affective empathy. However, there is a lack of studies that take into account the multidimensional nature of anxiety in its relation to empathy. DESIGN: Structural equation modeling was used to test the moderated mediation model of the relations between empathy, depression and anxiety dimensions and the moderating role of gender on these associations in inpatient adolescents...
May 17, 2018: Anxiety, Stress, and Coping
https://www.readbyqxmd.com/read/29772816/alpha-mannosidosis-therapeutic-strategies
#7
REVIEW
Maria Rachele Ceccarini, Michela Codini, Carmela Conte, Federica Patria, Samuela Cataldi, Matteo Bertelli, Elisabetta Albi, Tommaso Beccari
Alpha-mannosidosis (α-mannosidosis) is a rare lysosomal storage disorder with an autosomal recessive inheritance caused by mutations in the gene encoding for the lysosomal α-d-mannosidase. So far, 155 variants from 191 patients have been identified and in part characterized at the biochemical level. Similarly to other lysosomal storage diseases, there is no relationship between genotype and phenotype in alpha-mannosidosis. Enzyme replacement therapy is at the moment the most effective therapy for lysosomal storage disease, including alpha-mannosidosis...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772540/hsp70-and-gama-semino-protein-as-possible-prognostic-marker-of-prostate-cancer
#8
Sanjay Kumar, Sanjeev Gurshaney, Yori Adagunodo, Erica Gage, Shezreen Qadri, Mahak Sharma, Shalie Malik, Upender Manne, Udai P Singh, Rajesh Singh, Manoj K Mishra
In the United States, Prostate Cancer (PCa) is the leading cause of cancer-related mortality in men. PCa resulted in abnormal growth and function of prostate gland such as secretion of high level of gamma-seminoprotein (gama-SM)/Prostate-Specific Antigen (PSA) which could be detected in the blood. Beside gama-SM protein, the levels of heat shock proteins (Hsp70) were also observed significantly high. Therefore, gama-SM and Hsp70 are unique proteins with high potential for PCa therapeutics and diagnostics. High level of Hsp70 suppresses apoptosis, thus allowing PCa cells to exist; however, depletion of Hsp70 induces apoptosis in PCa cells...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772439/long-noncoding-rna-meg3-inhibits-proliferation-of-chronic-myeloid-leukemia-cells-by-sponging-microrna21
#9
Ziye Li, Lin Yang, Xiaojun Liu, Ziyuan Nie, Jianmin Luo
The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29771408/microrna-16-suppressed-the-invasion-and-migration-of-osteosarcoma-by-directly-inhibiting-rab23
#10
Z-H Jiao, J-D Wang, X-J Wang
OBJECTIVE:   Osteosarcoma is the most frequent primary bone malignancy that affects young adults and adolescents around the world. Increasing evidence suggests that dysfunctions of microRNAs (miRNAs) used to play an important role in human cancers. We aimed at evaluating the potential function of miR-16 and verify its influence on the function of RAB23 in osteosarcoma. PATIENTS AND METHODS: miR-16 expressions in osteosarcoma tissues and cell lines were examined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29771004/cytotoxic-activity-and-structure-activity-relationship-of-triazole-containing-bis-aryl-ether-macrocycles
#11
Eduardo Hernández-Vázquez, Alejandra Chávez-Riveros, Adriana Romo-Pérez, María Teresa Ramírez-Apán, Alma D Chávez-Blanco, Rocío Morales-Bárcenas, Alfonso Dueñas-González, Luis D Miranda
Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC50 <13 μm)...
May 17, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29769800/the-therapeutic-potential-of-blocking-galectin-3-expression-in-acute-myocardial-infarction-and-mitigating-inflammation-of-infarct-region-a-clinical-outcome-based-translational-study
#12
Wassim Mosleh, Milind R Chaudhari, Swati Sonkawade, Supriya Mahajan, Charl Khalil, Kevin Frodey, Tanvi Shah, Suraj Dahal, Roshan Karki, Rujuta Katkar, W Matthijs Blankesteijn, Brian Page, Saraswati Pokharel, Minhyung Kim, Umesh C Sharma
Introduction: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/29769145/phylogenetic-relationships-stage-specific-expression-and-localisation-of-a-unique-family-of-inactive-cysteine-proteases-in-sarcoptes-scabiei
#13
Deepani D Fernando, Simone L Reynolds, Martha Zakrzewski, Ehtesham Mofiz, Anthony T Papenfuss, Deborah Holt, Katja Fischer
BACKGROUND: Scabies is worldwide one of the most common, yet neglected, parasitic skin infections, affecting a wide range of mammals including humans. Limited treatment options and evidence of emerging mite resistance against the currently used drugs drive our research to explore new therapeutic candidates. Previously, we discovered a multicopy family of genes encoding cysteine proteases with their catalytic sites inactivated by mutation (SMIPP-Cs). This protein family is unique in parasitic scabies mites and is absent in related non-burrowing mites...
May 16, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29768353/correlation-of-increased-th17-treg-cell-ratio-with-endoplasmic-reticulum-stress-in-chronic-kidney-disease
#14
Xiaojing Zhu, Shuiqin Li, Qiaona Zhang, Dan Zhu, Yang Xu, Pengqian Zhang, Jin Han, Zhaoyang Duan, Jie Gao, Yan Ou
To investigate the relationship between the regulatory immune network and endoplasmic reticulum stress (ERS) in patients with different stages of chronic kidney disease (CKD).A total of 91 patients diagnosed with CKD were divided into different groups according to the stage of disease and treatment with hemodialysis (HD) or peritoneal dialysis (PD). Routine blood and biochemical tests were performed in patients in the different CKD groups and in healthy controls (n = 20). The frequencies of T helper type 17 (Th17) and regulatory T (Treg) cells in the overall T cell population were measured by flow cytometric analysis...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29768316/evaluation-of-compliance-with-a-weight-based-nurse-driven-heparin-nomogram-in-a-tertiary-academic-medical-center
#15
James W Schurr, Craig A Stevens, Anne Bane, Sarah E Culbreth, Amy Leigh Miller, Jean M Connors, Katelyn W Sylvester
BACKGROUND: Recently, our institution adopted a weight-based nurse-driven heparin titration protocol that relies on nurses ordering laboratories, adjusting doses, and initiating boluses. Numerous institutions have implemented similar protocols with reported success. METHODS: A single-center retrospective analysis was conducted at the Brigham and Women's Hospital in Boston, Massachusetts that included all patients who were initiated on the weight-based nurse-driven heparin nomogram during a 30-day period...
June 2018: Critical Pathways in Cardiology
https://www.readbyqxmd.com/read/29768060/seek-and-destroy-improving-pk-pd-profiles-of-anticancer-agents-with-nanoparticles
#16
Anne Rodallec, Raphaelle Fanciullino, Bruno Lacarelle, Joseph Ciccolini
The Pharmacokinetics/pharmacodynamics (PK/PD) relationships with cytotoxics are usually based on a steepening concentration-effect relationship; the greater the drug amount, the greater the effect. The Maximum Tolerated Dose paradigm, finding the balance between efficacy while keeping toxicities at their manageable level, has been the rule of thumb over the last 50-years. Developing nanodrugs is an appealing strategy to help broaden this therapeutic window. The fact that efficacy and toxicity with cytotoxics are intricately linked is primarily due to the complete lack of specificity towards the tumor tissue during their distribution phase...
May 16, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29767995/structure-activity-relationships-and-therapeutic-potentials-of-5-ht7-receptor-ligands-an-update
#17
Maria N Modica, Enza Lacivita, Sebastiano Intagliata, Loredana Salerno, Giuseppe Romeo, Valeria Pittala, Marcello Leopoldo
Serotonin 5-HT7 receptor (5-HT7R) has been the subject of intense research efforts because of its presence in brain areas such as hippocampus, hypothalamus, and cortex. Preclinical data link the 5-HT7R to a variety of central nervous system processes such as regulation of circadian rhythms, mood, cognitions, pain processing, and mechanisms of addiction. 5-HT7R blockade has antidepressant effects and may ameliorate cognitive deficits associated with schizophrenia. 5-HT7R has been recently shown to modulate neuronal morphology, excitability, and plasticity, thus contributing to shape brain networks during development and to remodel neuronal wiring in the mature brain...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767952/laser-cleavable-probes-based-cell-surface-engineering-for-in-situ-sialoglycoconjugates-profiling-by-ldi-mass-spectrometry
#18
Jie Sun, Huihui Liu, Lingpeng Zhan, Caiqiao Xiong, Xi Huang, Jinjuan Xue, Zongxiu Nie
Cell-surface sialoglycoconjugates (sialoglycoproteins & sialoglycolipids) play important roles in cell-cell interactions and related tumor metastasis process. Although there have been some analytical methods to evaluate the sialoglycoconjugates, an effective method providing both qualitative and quantitative information is still deficient. Here we establish an extraction-free, sensitive and high-throughput platform to realize in-situ detection of the cell-surface sialoglycoconjugates on various cell lines, e...
May 16, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29766480/-the-therapeutic-alliance-in-community-mental-health-services
#19
A Groenendijk, J Van Hecke
The treatment of severe mental illnesses is increasingly taking place in a domiciliary setting due to the deinstitutionalisation.<br/> AIM: Theoretical reflection on the influence of home treatment on the therapeutic alliance.<br/> METHOD: Qualitative review of possible effects of home treatment based on own experiences, the scientific literature, and recent handbooks on community mental health.<br/> RESULTS: The therapeutic relationship appears to be an important general factor in the outcomes of community mental health approaches...
2018: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/29766031/a-rationally-engineered-capsid-variant-of-aav9-for-systemic-cns-directed-and-peripheral-tissue-detargeted-gene-delivery-in-neonates
#20
Dan Wang, Shaoyong Li, Dominic J Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E Goetzmann, Terence R Flotte, Mavis Agbandje-McKenna, Guangping Gao
Adeno-associated virus (AAV) has provided the gene therapy field with the most powerful in vivo gene delivery vector to realize safe, efficacious, and sustainable therapeutic gene expression. Because many clinically relevant properties of AAV-based vectors are governed by the capsid, much research effort has been devoted to the development of AAV capsids for desired features. Here, we combine AAV capsid discovery from nature and rational engineering to report an AAV9 capsid variant, designated as AAV9.HR, which retains AAV9's capability to traverse the blood-brain barrier and transduce neurons...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
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