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https://www.readbyqxmd.com/read/29650281/recent-developments-and-obstacles-in-the-treatment-of-melanoma-with-braf-and-mek-inhibitors
#1
REVIEW
Mohd Wahid, Arshad Jawed, Raju K Mandal, Sajad A Dar, Naseem Akhter, Pallavi Somvanshi, Farah Khan, Mohtashim Lohani, Mohammed Y Areeshi, Shafiul Haque
Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29649514/endogenous-neuronal-replacement-in-the-juvenile-brain-following-cerebral-ischemia
#2
Krista M Rodgers, Jared T Ahrendsen, Olivia P Patsos, Frank A Strnad, Joan C Yonchek, Richard J Traystman, Wendy B Macklin, Paco S Herson
Replacement of dead neurons following ischemia, either via enhanced endogenous neurogenesis or stem cell therapy, has long been sought. Unfortunately, while various therapies that enhance neurogenesis or stem cell therapies have proven beneficial in animal models, they have all uniformly failed to truly replace dead neurons in the ischemic core to facilitate long-term recovery. Remarkably, we observe robust repopulation of medium-spiny neurons within the ischemic core of juvenile mice following experimental stroke...
April 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29625893/interleukin-15-complex-treatment-protects-mice-from-cerebral-malaria-by-inducing-interleukin-10-producing-natural-killer-cells
#3
Kristina S Burrack, Matthew A Huggins, Emily Taras, Philip Dougherty, Christine M Henzler, Rendong Yang, Sarah Alter, Emily K Jeng, Hing C Wong, Martin Felices, Frank Cichocki, Jeffrey S Miller, Geoffrey T Hart, Aaron J Johnson, Stephen C Jameson, Sara E Hamilton
Cerebral malaria is a deadly complication of Plasmodium infection and involves blood brain barrier (BBB) disruption following infiltration of white blood cells. During experimental cerebral malaria (ECM), mice inoculated with Plasmodium berghei ANKA-infected red blood cells develop a fatal CM-like disease caused by CD8+ T cell-mediated pathology. We found that treatment with interleukin-15 complex (IL-15C) prevented ECM, whereas IL-2C treatment had no effect. IL-15C-expanded natural killer (NK) cells were necessary and sufficient for protection against ECM...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29625607/asparagus-cochinchinensis-stimulates-release-of-nerve-growth-factor-and-abrogates-oxidative-stress-in-the-tg2576-model-for-alzheimer-s-disease
#4
Hyun Ah Lee, Ji Eun Kim, Ji Eun Sung, Woo Bin Yun, Dong Seob Kim, Hee Seob Lee, Jin Tae Hong, Dae Youn Hwang
BACKGROUD: Use of multifunctional drugs with neurotrophic supporting and oxidative stress suppressing activity may be considered a therapeutic strategy to protect or repair cellular damage caused during the progression of Alzheimer's disease (AD). In this study, we investigated the therapeutic effects of aqueous extract of A. cochinchinesis root (AEAC), particularly its role as a nerve growth factor (NGF) stimulator and anti-oxidant in Tg2576 mice showing AD phenotypes of human. METHODS: Tg2576 mice were received 100 mg/kg/day AEAC via oral administration, while mice in the Vehicle treated group received dH2 O for 4 weeks...
April 6, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29619907/severe-atherosclerosis-in-donor-liver-vasculature-an-illustrative-case-report-and-review-of-the-literatur
#5
Ayokunle S Olowofela, Oscar K Serrano, Raja Kandaswamy
As the scarcity of transplantable organs continues to increase, juxtaposed with an aging donor population, transplant surgeons are increasingly confronted with marginal organ offers. The presence of atherosclerosis in the donor allograft has been shown to compromise the vascular integrity and predispose to vascular complications in the transplanted liver. Here, we present a case of 54-year-old brain-dead donor who was discovered to have a severely diseased aorta during organ recovery. Pathologic evaluation revealed severe atherosclerosis with calcifications...
April 4, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29615068/modeling-and-rescue-of-defective-blood-brain-barrier-function-of-induced-brain-microvascular-endothelial-cells-from-childhood-cerebral-adrenoleukodystrophy-patients
#6
Catherine A A Lee, Hannah S Seo, Anibal G Armien, Frank S Bates, Jakub Tolar, Samira M Azarin
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown...
April 4, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29614834/the-use-of-a-mechanical-non-penetrating-captive-bolt-device-for-the-euthanasia-of-neonate-lambs
#7
Andrew Grist, Jeff A Lines, Toby G Knowles, Charles W Mason, Stephen B Wotton
A non-penetrating captive bolt device, powered by a 1-grain 0.22″ cartridge delivering a calculated kinetic energy of 47 Joules was tested as a euthanasia method on 200 neonate lambs (Ovis aries) of 4.464 kg (SD (Standard deviation) ± 1.056) mean dead weight, to assess effectiveness and shot position. Every lamb (n = 200) was effectively stunned when the weapon was applied powered by a brown, 1-grain cartridge but 10/200 (5%) of the lambs displayed rhythmic or agonal breathing and were subsequently euthanased using euthatal (Merial, UK, GTIN: 03661103015550)...
April 2, 2018: Animals: An Open Access Journal From MDPI
https://www.readbyqxmd.com/read/29613813/post-mortem-survival-of-gallibacterium-anatis-in-a-laying-hen-experimental-infection-model
#8
Chong Wang, Susanne Elisabeth Pors, Anders Miki Bojesen
To assess the survival of G. anatis in dead laying hens, 21-week old laying hens were injected intraperitoneally with 0.5 ml brain hearth infusion broth containing 108 CFU of G. anatis 12656-12 liver (n=16), E. coli ST141(n=16), or a mix of G. anatis 12656-12 liver (n=16) and E. coli ST141 (n=16), respectively. Birds were euthanized 24 hours post injection and eight dead birds were kept at 4°C and room temperature, respectively. Swab samples were taken at different time points post euthanization and streaked on blood agar plates...
April 3, 2018: Avian Diseases
https://www.readbyqxmd.com/read/29611441/juvenile-cerebral-ischemia-reveals-age-dependent-bdnf-trkb-signaling-changes-novel-mechanism-of-recovery-and-therapeutic-intervention
#9
Robert M Dietz, James E Orfila, Krista M Rodgers, Olivia P Patsos, Guiying Deng, Nicholas Chalmers, Nidia Quillinan, Richard J Traystman, Paco S Herson
Global ischemia in childhood often leads to poor neurologic outcomes, including learning and memory deficits. Using our novel model of childhood cardiac arrest/cardiopulmonary resuscitation (CA/CPR), we investigate the mechanism of ischemia-induced cognitive deficits and recovery. Memory is impaired seven days after juvenile CA/CPR and completely recovers by 30 days. Consistent with this remarkable recovery not observed in adults, hippocampal long-term potentiation (LTP) is impaired 7-14 days after CA/CPR, recovering by 30 days...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29610404/ischemia-induced-dna-hypermethylation-during-kidney-transplant-predicts-chronic-allograft-injury
#10
Line Heylen, Bernard Thienpont, Maarten Naesens, Pieter Busschaert, Jeroen Depreeuw, Dominiek Smeets, Ina Jochmans, Diethard Monbaliu, Jacques Pirenne, Evelyne Lerut, Bart Ghesquiere, Dirk Kuypers, Diether Lambrechts, Ben Sprangers
Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n =13), after implantation and reperfusion (postischemia; n =13), and at 3 or 12 months after transplant ( n =5 each); a cross-sectional cohort with preimplantation biopsy specimens ( n =82); and a cross-sectional cohort with postreperfusion biopsy specimens ( n =46)...
April 2, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29593726/pretransplant-iga-anti-beta-2-glycoprotein-i-antibodies-as-a-predictor-of-early-graft-thrombosis-after-renal-transplantation-in-the-clinical-practice-a-multicenter-and-prospective-study
#11
Jose M Morales, Manuel Serrano, Jose Angel Martinez-Flores, Fracisco Javier Gainza, Roberto Marcen, Manuel Arias, Fernando Escuin, Dolores Pérez, Amado Andres, Miguel Angel Martínez, Naroa Maruri, Eva Alvarez, José Luis Castañer, Marcos López-Hoyos, Antonio Serrano
Background: Graft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study. Methods: Multicenter prospective observational cohort study. Setting and participants: Seven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed-up for 10 years...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29592635/how-inaccurate-metrics-hide-the-true-potential-for-organ-donation-in-the-united-states
#12
Laura A Siminoff, Heather M Gardiner, Maureen Wilson-Genderson, Teresa J Shafer
BACKGROUND: There is a discrepancy between the reported increase in donor conversion rates and the number of organs available for transplant. METHODS: Secondary analysis of data obtained from the Scientific Registry of Transplant Recipients from January 2003 through December 2015 was performed. The primary outcomes were the (1) number of brain-dead donors from whom solid organs were recovered and (2) number of the organs transplanted. Descriptive statistics and growth plots were used to examine the trajectory of organ donation, recovery, and transplantation outcomes over the 11-year period...
March 2018: Progress in Transplantation
https://www.readbyqxmd.com/read/29582466/unique-cell-tropism-of-hhv-6b-in-an-infantile-autopsy-case-of-primary-hhv-6b-encephalitis
#13
Hiroaki Miyahara, Kouki Miyakawa, Haruto Nishida, Shinji Yano, Tomoko Sonoda, So-Ichi Suenobu, Tatsuro Izumi, Tsutomu Daa, Kenji Ihara
Human herpes virus 6 (HHV-6) is known to cause primary encephalitis in the frontal lobes/cerebral hemisphere or reactivated encephalitis in the hippocampus, but the pathogenesis remains unclear. HHV-6B has also been detected in hippocampal samples in patients with mesial temporal lobe epilepsy. A 1 year and 3 months old female, who had been clinically diagnosed with exanthema subitum and febrile convulsion, was found dead on the third day after onset. Macroscopic findings showed massive brain edema. Microscopic examination revealed gemistocytic astrocytes and ballooned oligodendrocytes in the frontal white matter, along with neuronal cell death with microglial infiltration in the frontal cortex...
March 26, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29581529/enhanced-protection-of-the-renal-vascular-endothelium-improves-early-outcome-in-kidney-transplantation-preclinical-investigations-in-pig-and-mouse
#14
Sofia Nordling, Johan Brännström, Fredrik Carlsson, Bo Lu, Evelyn Salvaris, Alkwin Wanders, Jos Buijs, Sergio Estrada, Vladimir Tolmachev, Peter J Cowan, Tomas Lorant, Peetra U Magnusson
Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage...
March 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580772/acute-brain-dysfunction-development-and-validation-of-a-daily-prediction-model
#15
Annachiara Marra, Pratik P Pandharipande, Matthew S Shotwell, Rameela Chandrasekhar, Timothy D Girard, Ayumi K Shintani, Linda M Peelen, Karl Moons, Robert S Dittus, E Wesley Ely, Eduard E Vasilevskis
BACKGROUND: To develop and validate a dynamic risk model to predict daily changes in acute brain dysfunction (i.e., delirium and coma), discharge and mortality in intensive care unit (ICU) patients. METHODS: Using data from a multicenter prospective ICU cohort, we developed a daily Acute Brain Dysfunction-prediction model (ABD-pm) using multinomial logistic regression that estimated 15 transition probabilities (from 1 of 3 brain function states [normal, delirious, or comatose] to 1 of 5 possible outcomes [normal, delirious, comatose, ICU discharge, and dead]) using baseline and daily risk factors...
March 23, 2018: Chest
https://www.readbyqxmd.com/read/29579874/cold-ischemia-time-as-a-factor-in-post-transplantation-complications-for-orthotopic-hepatic-transplantation
#16
Z Ruiz de Azúa-López, J R Naranjo-Izurieta, J Lameirao, L Martín-Villén, M Porras-López, N Palomo-Lopez, A Vilchez-Arenas, J J Egea-Guerrero
OBJECTIVE: This study aims to compare a shorter cold ischemia time with the present one in relation to the complications developed in liver transplantations. DESIGN: This is a retrospective, observational study of orthotopic liver transplantations performed with grafts from brain-dead donors during 12 months at a University Hospital (Seville). We compare incidence rates of complications (reperfusion syndrome, arterial and biliary complications, and prostaglandin requirements) between two groups according to cold ischemia times (group A < 6 hours; group B > 6 hours)...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29579853/survival-and-evolution-of-renal-function-in-kidney-transplant-recipients-from-type-ii-asystolic-donations-a-single-center-experience
#17
N G Toapanta Gaibor, F M González-Roncero, M Cintra Cabrera, M Suñer Poblet, G Bernal Blanco, A Suarez Benjumea, M A Pérez-Valdivia, J J Egea-Guerrero, J L Rocha Castilla, M A Gentil Govantes
BACKGROUND: In recent years, stagnation in the number of kidneys from after brain-dead donors (DBD) has stimulated the use of non-heart beating donors (NHBDs). Herein we present our 5-year experience with type II Maastricht NHBDs in renal transplantation. METHODS: All patients (n = 50) in this study received type II Maastricht NHBD kidneys (March 2012 to February 2017), with a median follow-up of 33 months. RESULTS: Mean donor age was 39 ± 12 years, mean creatinine 1...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29579766/how-should-lungs-be-allocated-for-transplant
#18
Thomas M Egan
As lung transplantation became established therapy for end-stage lung disease, there were not nearly enough suitable lungs from brain-dead organ donors to meet the need, leading to a focus on how lungs are allocated for transplant. Originally lungs were allocated by the United Network for Organ Sharing (UNOS) like hearts-by waiting time, first to listed recipients in the organ procurement organization of the donor, then to potential recipients in concentric 500 nautical mile circles. This resulted in long waiting times and increasing waitlist deaths...
April 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29571742/family-interview-to-enable-donation-of-organs-for-transplantation-evidence-based-practice
#19
E L de Moraes, M J Dos Santos, L B de Barros E Silva, L A S de Lima Pilan, E A A de Lima, A C de Santana, M S Martins
BACKGROUND: In this study we propose a theoretical and practical basis for the best practices for interviewing relatives of brain-dead eligible organ donors. METHODS: This investigation was a reflective study of the methodologic factors of the family interview that affect their decision regarding the donation of a deceased patient's organs for transplantation. The articles that formed the empirical basis of the trial were obtained from PubMed, which is a free-access tool of the MEDLINE database of the United States National Library of Medicine...
March 21, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29569064/embodiment-and-entangled-subjectivity-a-study-of-robin-cook-s-coma-priscille-sibley-s-the-promise-of-stardust-and-alexander-beliaev-s-professor-dowell-s-head
#20
Manali Karmakar, Avishek Parui
The essay examines Robin Cook's (1977) Coma and Priscille Sibley's (2013) The Promise of Stardust that dramatize the reified and disposable status of the brain-dead patients who are classified as nonpersons. The essay argues that the man-machine entanglement as depicted in the novels constructs a deterritorialized and entangled form of subjectivity that intervenes in the dominant biomedical understanding of personhood and agency that we notionally associate with a conscious mind. The essay concludes its arguments by discussing Alexander Beliaev's (1925) Professor Dowell's Head which depicts human subjectivity as an essentially embodied and distributive phenomenon and interrogates the Cartesian mind body dualism embedded in the dominant biomedical narratives...
March 22, 2018: Journal of Medical Humanities
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