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https://www.readbyqxmd.com/read/29793100/the-still-uncertain-identity-of-the-channel-forming-unit-s-of-the-mitochondrial-permeability-transition-pore
#1
REVIEW
Christopher P Baines, Manuel Gutiérrez-Aguilar
Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against- putative channel-forming components of the MPT pore...
May 16, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29789000/spontaneous-splenic-rupture-complicating-primary-varicella-zoster-infection-a-case-report
#2
Aarthy Uthayakumar, David Harrington
BACKGROUND: Primary varicella zoster virus (VZV) infection is a common illness, predominantly affecting children. Its course is typically benign, although severe complications have been described. Splenic rupture is an extremely rare and potentially fatal complication of primary VZV infection, with only a handful of cases reported in the literature. CASE PRESENTATION: A 32-year-old Romanian man with no significant past medical history, presented with a 2 day history of sudden onset, worsening generalised abdominal pain and a 1 day history of vomiting...
May 22, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29725305/development-of-a-high-throughput-flow-cytometry-assay-to-monitor-defective-trafficking-and-rescue-of-long-qt2-mutant-herg-channels
#3
Scott A Kanner, Ananya Jain, Henry M Colecraft
Long QT Syndrome (LQTS) is an acquired or inherited disorder characterized by prolonged QT interval, exertion-triggered arrhythmias, and sudden cardiac death. One of the most prevalent hereditary LQTS subtypes, LQT2, results from loss-of-function mutations in the hERG channel, which conducts I Kr , the rapid component of the delayed rectifier K+ current, critical for cardiac repolarization. The majority of LQT2 mutations result in Class 2 deficits characterized by impaired maturation and trafficking of hERG channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29708508/second-hit-mosaic-mutation-in-mtorc1-repressor-depdc5-causes-focal-cortical-dysplasia-associated-epilepsy
#4
Théo Ribierre, Charlotte Deleuze, Alexandre Bacq, Sara Baldassari, Elise Marsan, Mathilde Chipaux, Giuseppe Muraca, Delphine Roussel, Vincent Navarro, Eric Leguern, Richard Miles, Stéphanie Baulac
DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29684383/prognostic-role-of-haematological-indices-in-sudden-sensorineural-hearing-loss-review-and-meta-analysis
#5
REVIEW
Zaizai Cao, Ziyue Li, Haijie Xiang, Saiyu Huang, Jinjian Gao, Xiang Zhan, Xiuxiu Zhen, Bangliang Li, JianBin Wu, Bobei Chen
BACKGROUND: Complete blood count (CBC) is an important blood test in clinical practice, and it has been recently used to predict the prognosis of patients with sudden sensorineural hearing loss (SSNHL). Some haematological indices of the CBC test have been reported to be associated with the clinical outcome of SSNHL. However, the prognostic value of these haematological indices in SSNHL is currently under debate. Here, we performed a meta-analysis to investigate the association between haematological indices of the CBC test and clinical outcomes in patients with SSNHL...
April 20, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29671682/iconic-memories-die-a-sudden-death
#6
Michael S Pratte
Iconic memory is characterized by its large storage capacity and brief storage duration, whereas visual working memory is characterized by its small storage capacity. The limited information stored in working memory is often modeled as an all-or-none process in which studied information is either successfully stored or lost completely. This view raises a simple question: If almost all viewed information is stored in iconic memory, yet one second later most of it is completely absent from working memory, what happened to it? Here, I characterized how the precision and capacity of iconic memory changed over time and observed a clear dissociation: Iconic memory suffered from a complete loss of visual items, while the precision of items retained in memory was only marginally affected by the passage of time...
April 1, 2018: Psychological Science
https://www.readbyqxmd.com/read/29476014/positive-allosteric-modulation-as-a-potential-therapeutic-strategy-in-anti-nmda-receptor-encephalitis
#7
Natasha Warikoo, Samuel J Brunwasser, Ann Benz, Hong-Jin Shu, Steven M Paul, Michael Lewis, James Doherty, Michael Quirk, Laura Piccio, Charles F Zorumski, Gregory S Day, Steven Mennerick
N -methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors important for synaptic plasticity, memory, and neuropsychiatric health. NMDAR hypofunction contributes to multiple disorders, including anti-NMDAR encephalitis (NMDARE), an autoimmune disease of the CNS associated with GluN1 antibody-mediated NMDAR internalization. Here we characterize the functional/pharmacological consequences of exposure to CSF from female human NMDARE patients on NMDAR function, and we characterize the effects of intervention with recently described positive allosteric modulators (PAMs) of NMDARs...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29469635/in-the-experimental-model-of-acute-mesenteric-ischemia-the-correlation-of-blood-diagnostic-parameters-with-the-duration-of-ischemia-and-their-effects-on-choice-of-treatment
#8
Mikail Cakir, Dogan Yildirim, Fatma Sarac, Turgut Donmez, Semih Mirapoglu, Adnan Hut, Fazilet Erozgen, Omer Faruk Ozer, Melih Ozgun Gecer, Leyla Zeynep Tigrel, Oguzhan Tas
Purpose/Aim: Acute mesenteric ischemia is a syndrome characterized by sudden onset abdominal pain followed by intestinal necrosis. Morbidity and mortality increase with delayed diagnosis. Even with the latest radiological diagnostic methods, early diagnosis and initiation of treatment can be delayed. Using an experimental model, here we aim to determine the relationship between the laboratory parameters used to detect acute mesenteric ischemia and the duration of irreversible ischemia. MATERIALS AND METHODS: A total of 30 male Wistar albino rats were divided into five groups, all of which underwent general anesthesia: (i) Superior mesenteric artery (SMA) dissection with laparotomy was performed, and blood samples and intestinal segment samples were taken after 2 hr (Sham group); (ii) volvulus of one-third of the small intestines was performed manually by laparotomy, and blood samples and intestinal segment samples were taken after 2 hr (Volvulus group); (iii) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 2 hr (SMA+ligated 2-hr group); (iv) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 4 hr (SMA+ligated 4-hr group); and (v) SMA was ligated with laparotomy, and blood samples and intestinal segment samples were taken after 6 hr (SMA+ligated 6-hr group)...
February 22, 2018: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/29434480/a-rare-presentation-of-neuromyelitis-optica-spectrum-disorders
#9
Navneet K Singh, Alexander J Sweidan, Sarah Strube, Ignacio Carrillo-Nunez
Neuromyelitis optica spectrum disorders (NMOSDs) are a set of demyelinating disorders that primarily target the optic nerves and the spinal cord. Previously thought to be a subset of multiple sclerosis (MS), now is recognized as a distinct entity. We present a 59-year-old female patient who was admitted for acute upper and lower extremity weakness. The patient had woken up from sleep with sudden onset of weakness. Patient was initially diagnosed with a right hemispheric stroke; however, magnetic resonance imaging of the cervical spine later performed showed abnormal enhancement from C2-C4, representing transverse myelitis...
2018: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/29392082/apelin-ameliorates-high-glucose-induced-downregulation-of-connexin-43-via-ampk-dependent-pathway-in-neonatal-rat-cardiomyocytes
#10
Xiaoting Li, Lu Yu, Jing Gao, Xukun Bi, Juhong Zhang, Shiming Xu, Meihui Wang, Mengmeng Chen, Fuyu Qiu, Guosheng Fu
Diabetes Mellitus is a common disorder, with increasing risk of cardiac arrhythmias. Studies have shown that altered connexin expression and gap junction remodeling under hyperglycemia contribute to the high prevalence of cardiac arrhythmias and even sudden death. Connexin 43 (Cx43), a major protein that assembles to form cardiac gap junctions, has been found to be downregulated under high glucose conditions, along with inhibition of gap junctional intercellular communication (GJIC). While, apelin, a beneficial adipokine, increases Cx43 protein expression in mouse and human embryonic stem cells during cardiac differentiation...
February 2018: Aging and Disease
https://www.readbyqxmd.com/read/29350937/light-stops-at-exceptional-points
#11
Tamar Goldzak, Alexei A Mailybaev, Nimrod Moiseyev
Almost twenty years ago, light was slowed down to less than 10^{-7} of its vacuum speed in a cloud of ultracold atoms of sodium. Upon a sudden turn-off of the coupling laser, a slow light pulse can be imprinted on cold atoms such that it can be read out and converted into a photon again. In this process, the light is stopped by absorbing it and storing its shape within the atomic ensemble. Alternatively, the light can be stopped at the band edge in photonic-crystal waveguides, where the group speed vanishes...
January 5, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29341666/mechanism-behind-erosive-bursts-in-porous-media
#12
R Jäger, M Mendoza, H J Herrmann
Erosion and deposition during flow through porous media can lead to large erosive bursts that manifest as jumps in permeability and pressure loss. Here we reveal that the cause of these bursts is the reopening of clogged pores when the pressure difference between two opposite sites of the pore surpasses a certain threshold. We perform numerical simulations of flow through porous media and compare our predictions to experimental results, recovering with excellent agreement shape and power-law distribution of pressure loss jumps, and the behavior of the permeability jumps as a function of particle concentration...
September 22, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29329111/severe-peri-ictal-respiratory-dysfunction-is-common-in-dravet-syndrome
#13
YuJaung Kim, Eduardo Bravo, Caitlin K Thirnbeck, Lori A Smith-Mellecker, Se Hee Kim, Brian K Gehlbach, Linda C Laux, Xiuqiong Zhou, Douglas R Nordli, George B Richerson
Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of sudden unexplained death in epilepsy (SUDEP), widely believed to be due to cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal respiratory dysfunction. One patient had severe and prolonged postictal hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29274432/a-mouse-model-of-depdc5-related-epilepsy-neuronal-loss-of-depdc5-causes-dysplastic-and-ectopic-neurons-increased-mtor-signaling-and-seizure-susceptibility
#14
Christopher J Yuskaitis, Brandon M Jones, Rachel L Wolfson, Chloe E Super, Sameer C Dhamne, Alexander Rotenberg, David M Sabatini, Mustafa Sahin, Annapurna Poduri
DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor...
March 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29245265/agrypnia-excitata-and-obstructive-apnea-in-a-patient-with-fatal-familial-insomnia-from-china-a-case-report
#15
Congcong Sun, Wen Xia, Ying Liu, Guoyong Jia, Cuilan Wang, Chuanzhu Yan, Yi Li
RATIONALE: Fatal familial insomnia (FFI) linked to a D178N/129M haplotype mutation in the PRNP gene is the most common genetic prion disease in the Han Chinese population. Here, we describe a Han Chinese patient with FFI who exhibited agrypnia excitata and obstructive apnea. PATIENT CONCERNS: A 46-year-old man displayed involuntary movements during sleep time, snoring, autonomic nervous system dysfunction, cognitive deficit, brainstem symptoms, myoclonus and ataxia in order within 8 months...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29167417/loss-of-activity-mutation-in-the-cardiac-chloride-bicarbonate-exchanger-ae3-causes-short-qt-syndrome
#16
Kasper Thorsen, Vibeke S Dam, Kasper Kjaer-Sorensen, Lisbeth N Pedersen, V Arvydas Skeberdis, Jonas Jurevičius, Rimantas Treinys, Ida M B S Petersen, Morten S Nielsen, Claus Oxvig, J Preben Morth, Vladimir V Matchkov, Christian Aalkjær, Henning Bundgaard, Henrik K Jensen
Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi , short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29121108/spatio-temporal-dynamics-of-multimodal-eeg-fnirs-signals-in-the-loss-and-recovery-of-consciousness-under-sedation-using-midazolam-and-propofol
#17
Seul-Ki Yeom, Dong-Ok Won, Seong In Chi, Kwang-Suk Seo, Hyun Jeong Kim, Klaus-Robert Müller, Seong-Whan Lee
On sedation motivated by the clinical needs for safety and reliability, recent studies have attempted to identify brain-specific signatures for tracking patient transition into and out of consciousness, but the differences in neurophysiological effects between 1) the sedative types and 2) the presence/absence of surgical stimulations still remain unclear. Here we used multimodal electroencephalography-functional near-infrared spectroscopy (EEG-fNIRS) measurements to observe electrical and hemodynamic responses during sedation simultaneously...
2017: PloS One
https://www.readbyqxmd.com/read/29112981/adjustment-of-the-dynamic-weight-distribution-as-a-sensitive-parameter-for-diagnosis-of-postural-alteration-in-a-rodent-model-of-vestibular-deficit
#18
Brahim Tighilet, David Péricat, Alais Frelat, Yves Cazals, Guillaume Rastoldo, Florent Boyer, Olivier Dumas, Christian Chabbert
Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision...
2017: PloS One
https://www.readbyqxmd.com/read/29061334/neutrophil-peptidyl-arginine-deiminase-4-has-a-pivotal-role-in-ischemia-reperfusion-induced-acute-kidney-injury
#19
Wesley M Raup-Konsavage, Yanming Wang, Wei Wei Wang, Denis Feliers, Hong Ruan, W Brian Reeves
Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we investigated the role of peptidyl arginine deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in epigenetic regulation and inflammation, in renal ischemia/reperfusion injury. PAD4 expression was highly induced in infiltrating leukocytes 24 hours following renal ischemia and reperfusion. This induction was accompanied by citrullination of histone H3 and formation of neutrophil extracellular traps in kidneys of wild-type mice...
February 2018: Kidney International
https://www.readbyqxmd.com/read/29047318/spontaneous-spinal-epidural-hemorrhage-following-disseminated-intravascular-coagulation-resulting-in-paraplegia-a-case-report
#20
Nazia Dildar, Saeed Bin Ayaz, Muhammad Omer Aamir, Nadeem Ahmad
CONTEXT: Spontaneous spinal epidural hemorrhage (SSEH) mostly presents as low back pain with or without a radiculopathy, and rarely with paraplegia or tetraplegia depending on the site and severity of spinal cord compression. We present here a case who had anemia and developed paraplegia following disseminated intravascular coagulation (DIC) due to a transfusion reaction. FINDINGS: A 65-year-old lady presented with sudden onset chest pain radiating to nape of the neck followed by loss of sensations and power in legs few hours after a blood transfusion...
October 19, 2017: Journal of Spinal Cord Medicine
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