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https://www.readbyqxmd.com/read/28822390/physiologic-features-of-brain-death
#1
Eno-Obong Essien, Kristina Fioretti, Thomas M Scalea, Deborah M Stein
Brain death is known to be associated with physiologic derangements but their incidence is poorly described. Knowledge of the changes that occur during brain death is important for management of the potential organ donor. Thus, we sought to characterize the pathophysiology that occurs during brain death in patients with traumatic injuries. All brain-dead patients over a 10-year period were identified from the trauma registry at a level 1 urban trauma center. Patient demographics, injury characteristics, and clinical data for defining organ dysfunction were reviewed for the 24 hours surrounding brain-death declaration...
August 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28819446/incremental-value-of-circulating-mir-122-5p-to-predict-outcome-after-out-of-hospital-cardiac-arrest
#2
Yvan Devaux, Antonio Salgado-Somoza, Josef Dankiewicz, Adeline Boileau, Pascal Stammet, Anna Schritz, Lu Zhang, Mélanie Vausort, Patrik Gilje, David Erlinge, Christian Hassager, Matthew P Wise, Michael Kuiper, Hans Friberg, Niklas Nielsen
Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation...
2017: Theranostics
https://www.readbyqxmd.com/read/28814434/combined-cdk4-6-and-mtor-inhibition-is-synergistic-against-glioblastoma-via-multiple-mechanisms
#3
Inan Olmez, Breanna Brenneman, Aizhen Xiao, Vlad Serbulea, Mouadh Benamar, Ying Zhang, Laryssa Manigat, Tarek Abbas, Jeongwu Lee, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Roger Abounader, Norbert Leitinger, Benjamin Purow
PURPOSE: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents. We investigate the efficacy of the combination of CDK4/6 inhibition and mTOR inhibition against GBM. EXPERIMENTAL DESIGN: Preclinical in vitro and in vivo assays using primary GBM cell lines were performed...
August 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28808012/bdnf-trkb-controls-cocaine-induced-dendritic-spines-in-rodent-nucleus-accumbens-dissociated-from-increases-in-addictive-behaviors
#4
Ethan M Anderson, Anne Marie Wissman, Joyce Chemplanikal, Nicole Buzin, Daniel Guzman, Erin B Larson, Rachael L Neve, Eric J Nestler, Christopher W Cowan, David W Self
Chronic cocaine use is associated with prominent morphological changes in nucleus accumbens shell (NACsh) neurons, including increases in dendritic spine density along with enhanced motivation for cocaine, but a functional relationship between these morphological and behavioral phenomena has not been shown. Here we show that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic spine formation by using either localized TrkB knockout or viral-mediated expression of a dominant negative, kinase-dead TrkB mutant...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28804551/a-tumor-suppressive-microrna-mirna-485-5p-inhibits-glioma-cell-proliferation-and-invasion-by-down-regulating-tpd52l2
#5
Jin Yu, Shi-Wen Wu, Wei-Ping Wu
Glioblastoma multiforme is the most deadly primary brain tumor and has no effective treatment. Therefore, it is important to identify novel and effective therapies that impede glioma tumorigenesis. MicroRNAs (miRNAs) are helpful analytical biomarkers and may be useful targets for treating multiple human cancers. Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in glioma is not well understood. In this study, we demonstrated that miRNA-485-5p expression was reduced in gliomat issues and cell lines...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801937/in-situ-split-liver-splitting-under-extra-corporeal-membrane-oxygenation-in-brain-dead-donor
#6
Assalino Michela, Pietro Majno, Christian Toso, Thierry Berney, Raphaël Giraud, Philipp Dutkowski, Axel Andres, Barbara Wildhaber, Laure Elkrief
Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in-situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs and four kidneys...
August 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28800774/angiostrongylus-vasorum-in-wolves-in-italy-prevalence-and-pathological-findings
#7
Claudio De Liberato, Goffredo Grifoni, Raniero Lorenzetti, Roberta Meoli, Cristiano Cocumelli, Antonio Mastromattei, Francesco Scholl, Pasquale Rombolà, Pietro Calderini, Gianpaolo Bruni, Claudia Eleni
BACKGROUND: Angiostrongylus vasorum is a nematode residing in the heart and pulmonary vessels of dogs and wild carnivores. In Europe the red fox is its reservoir, while only three records from wolves have been published. Angiostrongylus vasorum has a worldwide distribution, and many pieces of evidence demonstrate that it is spreading from endemic areas to new ones. In Italy, A. vasorum was reported with increasing frequency in dogs and foxes in the last decades, and now it is considered endemic throughout the country...
August 11, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28790173/hu-antigen-r-hur-multimerization-contributes-to-glioma-disease-progression
#8
Natalia Filippova, Xiuhua Yang, Subramaniam Ananthan, Anastasia Sorochinsky, James R Hackney, Zachery Gentry, Sejong Bae, Peter King, L Burt Nabors
Among primary brain cancers, gliomas are the most deadly and most refractory to current treatment modalities. Previous reports overwhelmingly support the role of the RNA-binding protein HuR as a positive regulator of glioma disease progression. HuR expression is consistently elevated in tumor tissues, and a cytoplasmic localization appears essential for HuR-dependent oncogenic transformation. In this manuscript, we report HuR aggregation (multimerization) in glioma and performed an analysis of this tumor-specific HuR protein multimerization in clinical brain tumor samples...
August 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28769762/loss-of-irf2bp2-in-microglia-increases-inflammation-and-functional-deficits-after-focal-ischemic-brain-injury
#9
Shelly A Cruz, Aswin Hari, Zhaohong Qin, Pascal Couture, Hua Huang, Diane C Lagace, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic stroke causes neuronal cell death and triggers a cascade of inflammatory signals that contribute to secondary brain damage. Microglia, the brain-resident macrophages that remove dead neurons, play a critical role in the brain's response to ischemic injury. Our previous studies showed that IRF2 binding protein 2 (IRF2BP2) regulates peripheral macrophage polarization, limits their inflammatory response and reduces susceptibility to atherosclerosis. Here, we show that loss of IRF2BP2 in microglia leads to increased inflammatory cytokine expression in response to lipopolysaccharide challenge and impaired activation of anti-inflammatory markers in response to interleukin-4 (IL4) stimulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28768153/effects-of-mechanical-ventilation-on-gene-expression-profiles-in-renal-allografts-from-brain-dead-rats
#10
Maximilia C Hottenrott, Joerg Krebs, Paolo Pelosi, Thomas Luecke, Patricia R M Rocco, Carsten Sticht, Annette Breedijk, Benito Yard, Charalambos Tsagogiorgas
Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP...
July 30, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28766722/fatal-diabetic-ketoacidosis-a-potential-complication-of-mdma-ecstasy-use
#11
John D Gilbert, Roger W Byard
A 19-year-old woman with insulin-dependent diabetes mellitus was found dead in bed having allegedly recently taken ecstasy and consumed alcohol. At autopsy, there were microhemorrhages in the brain with subnuclear vacuolization and Armanni-Ebstein changes in renal tubules. Biochemical analyses confirmed diabetic ketoacidosis (vitreous glucose-46.5 mmol/L; β-OH butyrate-13.86 mmol/L.). Toxicological analyses of blood showed a low level of 3,4-methylenedioxy-methamphetamine (MDMA) (0.01 mg/L), with acetone but no alcohol or other common drugs...
August 2, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28757019/genomic-comparison-of-virulent-and-non-virulent-serotype-v-st1-streptococcus-agalactiae-in-fish
#12
Rui Wang, Li-Ping Li, Ting Huang, Ai-Ying Lei, Yan Huang, Fu-Guang Luo, Dong-Ying Wang, Wei-Yi Huang, Ming Chen, Jun Huang
Streptococcus agalactiae or Group B Streptococcus (GBS) is the major pathogen causing pneumonia and meningitis in human, mastitis in dairy cows, and streptococcal disease in tilapia. Previous studies have shown that fish GBS strains are correlated with human GBS strains in evolution and might have cross-host infection ability. Although the invasive disease caused by ST1 GBS in non-pregnant adults and cows is increasing worldwide, infection of fish by ST1 GBS has not been reported. The aim of this study was to determine whether ST1 GBS was virulent in fish and to investigate the genomic characteristics of ST1 GBS strains with different pathogenicity in tilapia...
August 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28755756/brain-extracellular-space-the-final-frontier-of%C3%A2-neuroscience
#13
REVIEW
Charles Nicholson, Sabina Hrabětová
Brain extracellular space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of extracellular matrix molecules. The space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the extracellular space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful...
July 26, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28751497/cdk5-mcl-1-axis-promotes-mitochondrial-dysfunction-and-neurodegeneration-in-alzheimer-s-disease-model
#14
Kumar Nikhil, Kavita Shah
Cdk5 deregulation is highly neurotoxic in AD. We identified Mcl-1 as a direct Cdk5 substrate using an innovative chemical screen in mouse brain lysates. Our data demonstrate that Mcl-1 levels determine the threshold for cellular damage in response to neurotoxic insults. Mcl-1 is a disease-specific target of Cdk5, which associates with Cdk5 under basal conditions, however, is not regulated by it. Neurotoxic insults hyperactivate Cdk5 causing Mcl-1 phosphorylation at T92. This phosphorylation event triggers Mcl-1 ubiquitylation, which directly correlates with mitochondrial dysfunction...
July 27, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28749083/evidence-of-bone-marrow-downregulation-in-brain-dead-rats
#15
Laura Menegat, Rafael Simas, Julia M Caliman, Fernando L Zanoni, Jacqueline F Jacysyn, Luiz Fernando F da Silva, Primavera Borelli, Luiz Felipe P Moreira, Paulina Sannomiya
Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]...
July 27, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28740770/versatility-of-the-latissimus-dorsi-free-flap-during-the-treatment-of-complex-postcraniotomy-surgical-site-infections
#16
Nobutaka Yoshioka
BACKGROUND: Some intractable cases of postcraniotomy infection, which can involve compromised skin, an open frontal air sinus, and residual epidural dead space, have been reported. In such cases, reconstructing the scalp and skull is challenging. METHODS: Between 2009 and 2016, the author treated 12 patients with recalcitrant postcraniotomy surgical site infections with latissimus dorsi (LD) free flaps. The patients' ages ranged from 37 to 79 years (mean, 63.5 years), and their underlying diseases included subarachnoid hemorrhaging (n = 5), brain tumors (n = 4), and cerebral arteriovenous malformations (n = 3)...
June 2017: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28739114/ethical-and-medical-management-of-a-pregnant-woman-with-brain-stem-death-resulting-in-delivery-of-a-healthy-child-and-organ-donation
#17
A Gopčević, B Rode, M Vučić, A Horvat, M Širanović, Ž Gavranović, V Košec, A Košec
Maternal brain death during pregnancy remains an exceedingly complex situation that requires not only a well-considered medical management plan, but also careful decision-making in a legally and ethically delicate situation. Management of brain dead pregnant patients needs to adhere to special strategies that support the mother in a way that she can deliver a viable and healthy child. Brain death in pregnant women is very rare, with only a few published cases. We present a case of a pregnant woman with previously diagnosed multiple brain cavernomas that led to intracranial hemorrhage and brain stem death during the 21st week of pregnancy...
June 24, 2017: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/28735991/lack-of-impact-of-hyperchloremia-in-brain-dead-organ-donors-on-the-onset-of-kidney-allograft-function-in-the-recipients
#18
E Uchytilova, M Protus, D Merta, R Kula, E Pokorna, E Kieslichova
BACKGROUND: Hyperchloremia produces renal vasoconstriction and fall in glomerular filtration rate. In 90% of brain-dead organ donors, diabetes insipidus develops, characterized by inappropriate diuresis, hyperosmolality, and hyperchloremia. The aim of this study was to determine the relationship between the serum concentration of chlorides of the donor and the onset of the function of the kidney allograft in the recipient. METHODS: We retrospectively studied 213 donors and kidney allograft recipients...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28734446/successful-lung-transplantation-using-a-deceased-donor-mechanically-ventilated-for-ten-months
#19
Shin Tanaka, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Motomu Kobayashi, Takahiro Oto
A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donor's lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO2 ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly...
August 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28731906/c1-inhibitor-treatment-decreases-renal-injury-in-an-established-brain-dead-rat-model
#20
Felix Poppelaars, Neeltina M Jager, Juha Kotimaa, Henri G D Leuvenink, Mohamed R Daha, Cees van Kooten, Marc A Seelen, Jeffrey Damman
BACKGROUND: Kidneys derived from brain-dead (BD) donors have lower graft survival rates compared to kidneys from living donors. Complement activation plays an important role in brain death. The aim of our study was therefore to investigate the effect of C1-inhibitor (C1-INH) on BD-induced renal injury. METHODS: Brain death was induced in rats by inflating a subdurally placed balloon catheter. Thirty minutes after BD, rats were treated with saline, low-dose or high-dose C1-INH...
July 21, 2017: Transplantation
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