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https://www.readbyqxmd.com/read/28316308/where-we-fail-location-and-timing-of-failure-to-rescue-in-trauma
#1
Jennifer J Chung, Emily C Earl-Royal, M Kit Delgado, Jose L Pascual, Patrick M Reilly, Douglas J Wiebe, Daniel N Holena
Failure to rescue (FTR) is an outcome metric that reflects a center's ability to prevent mortality after a major complication. Identifying the timing and location of FTR events could help target efforts to reduce FTR rates. We sought to characterize the timing and location of FTR occurrences at our center, hypothesizing that FTR rates would be highest early after injury and in settings of lower intensity of care. We used data, prospectively collected from 2009 to 2013, on patients ≥16 years old with minimum Abbreviated Injury Score ≥2 from a single institution...
March 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28315684/bcl6-mediates-the-effects-of-gastrodin-on-promoting-m2-like-macrophage-polarization-and-protecting-against-oxidative-stress-induced-apoptosis-and-cell-death-in-macrophages
#2
Jing Jia, Xiaojie Shi, Xiaoqian Jing, Jianguo Li, Jie Gao, Mengya Liu, Chi-Iou Lin, Xinzhi Guo, Qian Hua
Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip(®) PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315329/atorvastatin-prevents-angiotensin-ii-induced-myocardial-hypertrophy-in-vitro-via-ccaat-enhancer-binding-protein-%C3%AE
#3
Yintao Chen, Shasha Yu, Naijin Zhang, Yuan Li, Shuang Chen, Ye Chang, Guozhe Sun, Yingxian Sun
Previous evidences suggested that atorvastatin not only reduced blood lipids but also reduced myocardial hypertrophy and remodeling. And it was reported that C/EBPβ (CCAAT/enhancer-binding protein β) played a pivotal role both in the physiologic and pathological cardiac hypertrophy. However, it has not been reported before whether this signaling pathway of C/EBPβ participates in protective effect of atorvastatin for hypertrophy cardiomyocytes. In present study, We found that overexpression of C/EBPβ significantly abrogated the effect of atorvastatin on increasing Bcl-2/Bax and PGC-1α while the early and late apoptosis rate increased and mitochondrial membrane potential (MMP) was reduced...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302654/palmitate-induced-vacuolar-type-h-atpase-inhibition-feeds-forward-into-insulin-resistance-and-contractile-dysfunction
#4
Yilin Liu, Laura K M Steinbusch, Miranda Nabben, Dimitris Kapsokalyvas, Marc van Zandvoort, Patrick Schönleitner, Gudrun Antoons, Peter J Simons, Will A Coumans, Amber Geomini, Dipanjan Chanda, Jan F C Glatz, Dietbert Neumann, Joost J F P Luiken
Dietary fat overconsumption leads to myocardial lipid accumulation through mechanisms that are incompletely resolved. Previously, we identified increased translocation of the fatty acid transporter CD36 from its endosomal storage compartment to the sarcolemma as primary mechanism of excessive myocellular lipid import. Here, we show that increased CD36 translocation is caused by alkalinization of endosomes due to inhibition of proton pumping activity of vacuolar-type H(+)-ATPase (v-ATPase). Endosomal alkalinization was observed in hearts from rats fed a lard-based high fat-diet and in rodent and human cardiomyocytes upon palmitate overexposure, and appeared as early lipid-induced event preceding the onset of insulin resistance...
March 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28302146/relationship-of-acute-axonal-damage-wallerian-degeneration-and-clinical-disability-in-multiple-sclerosis
#5
Shailender Singh, Tobias Dallenga, Anne Winkler, Shanu Roemer, Brigitte Maruschak, Heike Siebert, Wolfgang Brück, Christine Stadelmann
BACKGROUND: Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. METHODS: Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28301478/retrotransposon-activation-contributes-to-neurodegeneration-in-a-drosophila-tdp-43-model-of-als
#6
Lisa Krug, Nabanita Chatterjee, Rebeca Borges-Monroy, Stephen Hearn, Wen-Wei Liao, Kathleen Morrill, Lisa Prazak, Nikolay Rozhkov, Delphine Theodorou, Molly Hammell, Josh Dubnau
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28301072/pre-conditions-for-eliminating-mitochondrial-dysfunction-and-maintaining-liver-function-after-hepatic-ischaemia-reperfusion
#7
REVIEW
Chenxia Hu, Lanjuan Li
The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood...
March 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28298786/comparison-of-dexmedetomidine-and-magnesium-sulfate-as-adjuvants-with-ropivacaine-for-spinal-anesthesia-in-infraumbilical-surgeries-and-postoperative-analgesia
#8
Reena Makhni, Joginder Pal Attri, Payal Jain, Veena Chatrath
INTRODUCTION: Postoperative pain is a major cause of fear and anxiety in hospitalized patients and so if patients remain pain-free during this period, they can cooperate with the circumstances well, leading to early recovery. Over the last two decades, there has been considerable revival of interest in the use of regional anesthesia techniques for surgery and pain management. As very few studies have been conducted using ropivacaine with dexmedetomidine and magnesium sulfate (MgSO4) as adjuvants, the present study was undertaken with primary aims to compare the hemodynamic stability, onset and duration of sensory and motor block and with secondary aims of the postoperative analgesic effect of dexmedetomidine and MgSO4 along with ropivacaine...
January 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/28298636/the-purinergic-receptor-p2x5-regulates-inflammasome-activity-and-hyper-multinucleation-of-murine-osteoclasts
#9
Hyunsoo Kim, Matthew C Walsh, Noriko Takegahara, Sarah A Middleton, Hong-In Shin, Junhyong Kim, Yongwon Choi
Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298041/randomized-double-blinded-placebo-controlled-trial-comparing-two-multimodal-opioid-minimizing-pain-management-regimens-following-transsphenoidal-surgery
#10
Deborah M Shepherd, Heidi Jahnke, William L White, Andrew S Little
OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo...
March 3, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28289682/stent-grafts-can-convert-unusable-upper-arm-arteriovenous-fistulas-into-a-functioning-hemodialysis-access-a-retrospective-case-series
#11
Charudatta S Bavare, Tiffany K Street, Eric K Peden, Mark G Davies, Joseph J Naoum
INTRODUCTION: Not all newly created arteriovenous fistulas (AVFs) successfully mature and develop into a functioning access for hemodialysis. Percutaneous transluminal angioplasty (PTA) and balloon-assisted maturation (BAM) have been utilized to either treat flow-limiting stenoses or to promote and accelerate maturation. We hypothesized that unusable upper arm AVFs can be rescued by conversion to a functional access using the percutaneous placement of a stent graft (SG). METHODS: Clinical data on 12 patients with an early non-usable upper arm AVF underwent percutaneous revision using SGs...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28289282/the-schizophrenia-and-autism-associated-gene-transcription-factor-4-regulates-the-columnar-distribution-of-layer-2-3-prefrontal-pyramidal-neurons-in-an-activity-dependent-manner
#12
S C Page, G R Hamersky, R A Gallo, M D Rannals, N E Calcaterra, M N Campbell, B Mayfield, A Briley, B N Phan, A E Jaffe, B J Maher
Disruption of the laminar and columnar organization of the brain is implicated in several psychiatric disorders. Here, we show in utero gain-of-function of the psychiatric risk gene transcription factor 4 (TCF4) severely disrupts the columnar organization of medial prefrontal cortex (mPFC) in a transcription- and activity-dependent manner. This morphological phenotype was rescued by co-expression of TCF4 plus calmodulin in a calcium-dependent manner and by dampening neuronal excitability through co-expression of an inwardly rectifying potassium channel (Kir2...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289135/the-chromatin-modifier-satb1-regulates-cell-fate-through-fgf-signalling-in-the-early-mouse-embryo
#13
Mubeen Goolam, Magdalena Zernicka-Goetz
The separation of embryonic from extra-embryonic tissues within the inner-cell-mass (ICM) to generate the epiblast (EPI), that will form the new organism, from the primitive endoderm (PE), that will form the yolk sac, is a crucial developmental decision. Here we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos with higher expression levels in the ICM progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28289097/human-cytomegalovirus-v-cdk-ul97-phosphorylates-and-inactivates-the-retinoblastoma-protein-related-p107-and-p130-proteins
#14
Satoko Iwahori, Angie C Umaña, Halena R VanDeusen, Robert F Kalejta
The human cytomegalovirus (HCMV)-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates the retinoblastoma (Rb) tumor suppressor. Here we identify the other Rb family members p107 and p130 as novel targets of UL97. UL97 phosphorylates p107 and p130 thereby inhibiting their ability to repress the E2F-responsive E2F1 promoter. As with Rb, this phosphorylation, and the rescue of E2F-responsive transcription, is dependent on the L1 LXCXE motif in UL97 and its interacting clefts on p107 and p130. Interestingly, UL97 does not induce the disruption of all p107-E2F or p130-E2F complexes, as it does to Rb-E2F complexes...
March 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28287622/a-codon-shuffling-method-to-prevent-reversion-during-production-of-replication-defective-herpesvirus-stocks-implications-for-herpesvirus-vaccines
#15
Gang Li, Charles Ward, Rukhsana Yeasmin, Steven Skiena, Laurie T Krug, J Craig Forrest
Herpesviruses establish life-long chronic infections that place infected hosts at risk for severe disease. Herpesvirus genomes readily undergo homologous recombination (HR) during productive replication, often leading to wild-type (WT) reversion during complementation of replication-defective and attenuated viruses via HR with the helper gene provided in trans. To overcome this barrier, we developed a synthetic-biology approach based on a technique known as codon shuffling. Computer-assisted algorithms redistribute codons in a helper gene, thereby eliminating regions of homology, while enabling manipulation of factors such as codon-pair bias and CpG content to effectively titrate helper-gene protein levels...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28285006/gata5-sumoylation-is-indispensable-for-zebrafish-cardiac-development
#16
Bin Wen, Hao Yuan, Xiaohui Liu, Haihong Wang, Saijuan Chen, Zhu Chen, Hugues de The, Jun Zhou, Jun Zhu
BACKGROUND: SUMOylation is a critical regulatory protein modification in eukaryotic cells and plays a pivotal role in cardiac development and disease. Several cardiac transcription factors are modified by SUMO, but little is known about the impact of SUMOylation on their function during cardiac development. METHODS: We used a zebrafish model to address the impact of SUMOylation on GATA5, an essential transcription factor in zebrafish cardiac development. GATA5 SUMOylation was probed by western blot, the subcellular localization and transcriptional activity of GATA5 mutants were examined by immunostaining and luciferase reporter assay...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28284973/pharmacological-chaperones-for-the-misfolded-melanocortin-4-receptor-associated-with-human-obesity
#17
Hui Huang, Wei Wang, Ya-Xiong Tao
The melanocortin-4 receptor (MC4R) plays a vital role in regulating energy homeostasis. Mutations in the MC4R cause early-onset severe obesity. The majority of loss of function MC4R mutants are retained intracellularly, many of which are not terminally misfolded and can be stabilized and targeted to the plasma membrane by different chaperones. Some of the mutants might be functional once coaxed to the cell surface. Molecular chaperones and chemical chaperones correct the misfolding of some mutant MC4Rs. However, their therapeutic application is very limited due to their non-specific mechanism of action and, for chemical chaperone, high dosage needed to be effective...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28284397/optimizing-the-diagnosis-and-management-of-dravet-syndrome-recommendations-from-a-north-american-consensus-panel
#18
Elaine C Wirrell, Linda Laux, Elizabeth Donner, Nathalie Jette, Kelly Knupp, Mary Anne Meskis, Ian Miller, Joseph Sullivan, Michelle Welborn, Anne T Berg
OBJECTIVES: To establish standards for early, cost-effective, and accurate diagnosis; optimal therapies for seizures; and recommendations for evaluation and management of comorbidities for children and adults with Dravet syndrome, using a modified Delphi process. METHODS: An expert panel was convened comprising epileptologists with nationally recognized expertise in Dravet syndrome and parents of children with Dravet syndrome, whose experience and understanding was enhanced by their active roles in Dravet syndrome associations...
March 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28284154/contribution-of-g-protein-coupled-estrogen-receptor-1-gper-to-17%C3%AE-estradiol-induced-developmental-toxicity-in-zebrafish
#19
Graciel Diamante, Norma Menjivar-Cervantes, Man Sin Leung, David C Volz, Daniel Schlenk
Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf...
March 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28283651/tfe3-regulates-whole-body-energy-metabolism-in-cooperation-with-tfeb
#20
Nunzia Pastore, Anna Vainshtein, Tiemo J Klisch, Andrea Armani, Tuong Huynh, Niculin J Herz, Elena V Polishchuk, Marco Sandri, Andrea Ballabio
TFE3 and TFEB are members of the MiT family of HLH-leucine zipper transcription factors. Recent studies demonstrated that they bind overlapping sets of promoters and are post-transcriptionally regulated through a similar mechanism. However, while Tcfeb knockout (KO) mice die during early embryonic development, no apparent phenotype was reported in Tfe3 KO mice. Thus raising the need to characterize the physiological role of TFE3 and elucidate its relationship with TFEB TFE3 deficiency resulted in altered mitochondrial morphology and function both in vitro and in vivo due to compromised mitochondrial dynamics...
March 10, 2017: EMBO Molecular Medicine
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