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https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#1
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28424208/architecture-of-the-rat-nephron-arterial-network-analysis-with-micro-computed-tomography
#2
Donald J Marsh, Dmitry D Postnov, Douglas Rowland, Anthony S Wexler, Olga V Sosnovtseva, Niels-Henrik Holstein-Rathlou
Among solid organs the kidney's vascular network stands out because each nephron has 2 distinct capillary structures in series, and because tubuloglomerular feedback (TGF), one of the mechanisms responsible for blood flow autoregulation, is specific to renal tubules. TGF and the myogenic mechanism, acting jointly, autoregulate single nephron blood flow. Each generates a self-sustained periodic oscillation and an oscillating electrical signal that propagates upstream along arterioles. Similar electrical signals from other nephrons interact, allowing nephron synchronization...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28421173/cerebral-autoregulation-brain-injury-and-the-transitioning-premature-infant
#3
REVIEW
Zachary A Vesoulis, Amit M Mathur
Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia-reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28416148/alterations-in-autonomic-cerebrovascular-control-after-spinal-cord-injury
#4
Dong-Il Kim, Can Ozan Tan
Among chronic cardiovascular and metabolic sequelae of spinal cord injury (SCI) is an up-to four-fold increase in the risk of ischemic and hemorrhagic stroke, suggesting that individuals with SCI cannot maintain stable cerebral perfusion. In able-bodied individuals, the cerebral vasculature is able to regulate cerebral perfusion in response to swings in arterial pressure (cerebral autoregulation), blood gases (cerebral vasoreactivity), and neural metabolic demand (neurovascular coupling). This ability depends, at least partly, on intact autonomic function, but high thoracic and cervical spinal cord injuries result in disruption of sympathetic and parasympathetic cerebrovascular control...
April 4, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28411965/dynamic-cerebral-autoregulation-assessment-using-extracranial-internal-carotid-artery-doppler-ultrasonography
#5
Nai-Fang Chi, Hsiao-Lun Ku, Chen-Yen Wang, Yanhui Liu, Lung Chan, Ying-Chin Lin, Chung-Kang Peng, Vera Novak, Han-Hwa Hu, Chaur-Jong Hu
Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) is frequently used to assess dynamic cerebral autoregulation (dCA); however, this is difficult in patients with poor temporal bone windows. In the study described here, we investigated the agreement and sensitivity of dCA indices determined from the extracranial internal carotid artery (ICA) and those determined from the MCA. Measurements for 32 stroke patients and 59 controls were analyzed. Measurement of the mean flow correlation index (Mx) and transfer function analysis based on spontaneous blood pressure fluctuation were simultaneously performed for the extracranial ICA and MCA...
April 12, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28404769/a-decrease-in-blood-pressure-is-associated-with-unfavorable-outcome-in-patients-undergoing-thrombectomy-under-general-anesthesia
#6
Kilian M Treurniet, Olvert A Berkhemer, Rogier V Immink, Hester F Lingsma, Vivian M C Ward-van der Stam, Markus W Hollmann, Jaap Vuyk, Wim H van Zwam, Aad van der Lugt, Robert J van Oostenbrugge, Diederik W J Dippel, Jonathan M Coutinho, Yvo B W E M Roos, Henk A Marquering, Charles B L M Majoie
BACKGROUND: Up to two-thirds of patients are either dependent or dead 3 months after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral autoregulation may render patients with AIS vulnerable to decreases in mean arterial pressure (MAP). OBJECTIVE: To determine whether a fall in MAP during intervention under general anesthesia (GA) affects functional outcome. METHODS: This subgroup analysis included patients from the MR CLEAN trial treated with thrombectomy under GA...
April 12, 2017: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/28404593/physiopathological-implications-of-p2x1-and-p2x7-receptors-in-regulation-of-glomerular-hemodynamics-in-angiotensin-ii-induced-hypertension
#7
Martha Franco, Rocio Bautista-Pérez, Agustina Cano-Martínez, Ursino Pacheco, José Santamaría, Leonardo Del Valle-Mondragón, Oscar Pérez-Méndez, L Gabriel Navar
Deleterious effects of purinergic P2X1 and P2X7 receptors (P2XR) in angiotensin II (AngII)-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2X1R, P2X7R and P2X4R with NF449, A438079 and PSB12054 respectively, were evaluated in AngII-infused rats (435 ng/kg/min)...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28403909/clinical-pathophysiology-of-hypoxic-ischemic-brain-injury-after-cardiac-arrest-a-two-hit-model
#8
REVIEW
Mypinder S Sekhon, Philip N Ainslie, Donald E Griesdale
Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia...
April 13, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28401995/orthostatic-dizziness-in-parkinson-s-disease-is-attributed-to-cerebral-hypoperfusion-a-transcranial-doppler-study
#9
Jinse Park, Hee-Tae Kim, Kang Min Park, Sam Yeol Ha, Sung Eun Kim, Kyong Jin Shin, Si Eun Kim, Wooyoung Jang, Ji Sun Kim, Jinyoung Youn, Engsoek Oh, Suyeon Park
OBJECTIVES: Orthostatic hypotension (OH) is controversially regarded as the cause of orthostatic dizziness in Parkinson's disease (PD). We sought to evaluate whether cerebral autoregulation is an alternative cause for orthostatic dizziness in PD patients, using transcranial Doppler monitoring during head-up tilting. METHODS: Forty-five PD patients with dizziness, 13 PD patients without dizziness, and 10 age-matched healthy controls were enrolled. Participants were divided into the following four groups: patients with dizziness and OH (group 1, n = 22), patients with dizziness but no OH (n = 23, group 2), patients without dizziness (n = 11, group 3), and age-matched healthy controls (n = 10, group 4)...
April 12, 2017: Journal of Clinical Ultrasound: JCU
https://www.readbyqxmd.com/read/28401379/kidney-lung-pathophysiological-crosstalk-its-characteristics-and-importance
#10
REVIEW
Pilar Domenech, Tomas Perez, Agustina Saldarini, Pedro Uad, Carlos G Musso
Crosstalk between the lung and the kidney is based on the similarities that these organs share. This is why different diseases that affect one organ can have repercussions on the other. Patients with acute kidney injury can present complications such as pulmonary edema and require mechanical ventilation in respiratory failure. This interaction occurs due to the increase in systemic immune mediators that cause inflammatory reactions, oxidative stress, and an increase in vascular permeability in the lung. With regard to lung-induced renal damage, the kidney can also be affected by chemical mediators, which are translocated into the bloodstream...
April 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28400529/control-of-gdhr-expression-in-neisseria-gonorrhoeae-via-autoregulation-and-a-master-repressor-mtrr-of-a-drug-efflux-pump-operon
#11
Corinne E Rouquette-Loughlin, Yaramah M Zalucki, Vijaya L Dhulipala, Jacqueline T Balthazar, Raúl G Doyle, Robert A Nicholas, Afrin A Begum, Erica L Raterman, Ann E Jerse, William M Shafer
The MtrCDE efflux pump of Neisseria gonorrhoeae contributes to gonococcal resistance to a number of antibiotics used previously or currently in treatment of gonorrhea, as well as to host-derived antimicrobials that participate in innate defense. Overexpression of the MtrCDE efflux pump increases gonococcal survival and fitness during experimental lower genital tract infection of female mice. Transcription of mtrCDE can be repressed by the DNA-binding protein MtrR, which also acts as a global regulator of genes involved in important metabolic, physiologic, or regulatory processes...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28397372/k-channel-impairment-determines-sex-and-age-differences-in-epinephrine-mediated-outcomes-after-brain-injury
#12
William M Armstead, John Riley, Monica S Vavilala
Traumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children under 4 years having particularly poor outcomes. Activation of ATP- and calcium-sensitive (KATP and KCa ) channels produces cerebrovasodilation and contributes to autoregulation, both of which are impaired after TBI, contributing to poor outcomes. Upregulation of the c-Jun-terminal kinase (JNK) isoform of mitogen-activated protein kinase produces K channel function impairment after CNS injury. Vasoactive agents can be used to normalize cerebral perfusion pressure...
April 11, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28394326/intraflagellar-transport-dynein-is-autoinhibited-by-trapping-of-its-mechanical-and-track-binding-elements
#13
Katerina Toropova, Miroslav Mladenov, Anthony J Roberts
Cilia are multifunctional organelles that are constructed using intraflagellar transport (IFT) of cargo to and from their tip. It is widely held that the retrograde IFT motor, dynein-2, must be controlled in order to reach the ciliary tip and then unleashed to power the return journey. However, the mechanism is unknown. Here, we systematically define the mechanochemistry of human dynein-2 motors as monomers, dimers, and multimotor assemblies with kinesin-II. Combining these data with insights from single-particle EM, we discover that dynein-2 dimers are intrinsically autoinhibited...
April 10, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28392959/restricted-blood-flow-exercise-in-sedentary-overweight-african-american-females-may-increase-muscle-strength-and-decrease-endothelial-function-and-vascular-autoregulation
#14
Vernon Bond, Bryan Heath Curry, Krishna Kumar, Sudhakar Pemminati, Vasavi Rakesh Gorantla, Kishan Kadur, Richard Mark Millis
OBJECTIVES: Exercise with partially restricted blood flow is a low-load, low-intensity resistance training regimen which may have the potential to increase muscle strength in the obese, elderly and frail who are unable to do high-load training. Restricted blood flow exercise has also been shown to affect blood vessel function variably and can, therefore, contribute to blood vessel dysfunction. This pilot study tests the hypothesis that unilateral resistance training of the leg extensors with partially restricted blood flow increases muscle strength and decreases vascular autoregulation...
March 2017: Journal of Pharmacopuncture
https://www.readbyqxmd.com/read/28392777/efficacy-of-cerebral-autoregulation-in-early-ischemic-stroke-predicts-smaller-infarcts-and-better-outcome
#15
Pedro Castro, Jorge Manuel Serrador, Isabel Rocha, Farzaneh Sorond, Elsa Azevedo
BACKGROUND AND PURPOSE: Effective cerebral autoregulation (CA) may protect the vulnerable ischemic penumbra from blood pressure fluctuations and minimize neurological injury. We aimed to measure dynamic CA within 6 h of ischemic stroke (IS) symptoms onset and to evaluate the relationship between CA, stroke volume, and neurological outcome. METHODS: We enrolled 30 patients with acute middle cerebral artery IS. Within 6 h of IS, we measured for 10 min arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and end-tidal-CO2...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28385097/cerebral-perfusion-pressure-insults-and-associations-with-outcome-in-adult-traumatic-brain-injury
#16
Fabian Giza, Geert Meyfroidt, Ian Piper, Giuseppe Citerio, Iain Chambers, Per Enblad, Pelle Nilsson, Bart Feyen, Philippe Jorens, Andrew Maas, Martin Ulrich Schuhmann, Rob Donald, Laura Moss, Greet Van den Berghe, Bart Depreitere
The definition of cerebral perfusion pressure (CPP) secondary insults in severe traumatic brain injury remains unclear. The purpose of the present study is to visualize the association of intensity and duration of episodes below or above cerebral perfusion pressure thresholds and outcome. The analysis was based on prospectively collected minute-by-minute intracranial pressure (ICP) and blood pressure data and outcome from 259 adult patients. The relationship of episodes of CPP below or above a certain threshold for certain duration with the 6-month Glasgow Outcome Score was visualized, separately for episodes of active or deficient autoregulation (AR)...
April 7, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28384837/the-impact-of-integrated-evaluation-of-hemodynamics-on-management-of-preterm-infants-with-late-onset-compromised-systemic-circulation
#17
Reem Amer, Reem Kalash, Mary M Seshia, Yasser N Elsayed
Objectives To study the impact of integrated evaluation of hemodynamics (IEH), using targeted neonatal echocardiography (TNE), cerebral regional tissue oxygenation (crRTO), and fractional oxygen extraction (FOE), using near-infrared spectroscopy (NIRS) on the management of infants with late-onset compromised systemic circulation (LCSC), and evaluation of the hemodynamic characteristics. Study Design Retrospective cohort study comparing infants with LCSC who underwent IEH (April 2014 to May 2016) with an earlier EPOCH who did not undergo IEH (January 2012 to March 2014)...
April 6, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28383324/cerebral-autoregulation-oriented-therapy-at-the-bedside-a-comprehensive-review
#18
Lucia Rivera-Lara, Andres Zorrilla-Vaca, Romergryko G Geocadin, Ryan J Healy, Wendy Ziai, Marek A Mirski
This comprehensive review summarizes the evidence regarding use of cerebral autoregulation-directed therapy at the bedside and provides an evaluation of its impact on optimizing cerebral perfusion and associated functional outcomes. Multiple studies in adults and several in children have shown the feasibility of individualizing mean arterial blood pressure and cerebral perfusion pressure goals by using cerebral autoregulation monitoring to calculate optimal levels. Nine of these studies examined the association between cerebral perfusion pressure or mean arterial blood pressure being above or below their optimal levels and functional outcomes...
April 6, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28367944/-original-article-tdp-43-in-the-skin-of-amyotrophic-lateral-sclerosis-patients
#19
Keisuke Abe, Takuya Ohkubo, Takanori Yokota
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. A common characteristic of ALS pathology is cytoplasmic inclusions primarily composed of transactive response DNA-binding protein of 43 kDa (TDP-43). Production of TDP-43 in the central nervous system is strictly regulated, but it is not known whether this is also true in the skin of ALS patients. We found a gradual but significant reduction in epidermal TDP-43 mRNA expression with illness progression in ALS patients with upper-limb onset...
2017: Journal of Medical and Dental Sciences
https://www.readbyqxmd.com/read/28367599/inexpensive-rapid-fabrication-of-polymer-film-microfluidic-autoregulatory-valve-for-disposable-microfluidics
#20
Xinjie Zhang, Zhixian Zhu, Zhonghua Ni, Nan Xiang, Hong Yi
This work presents the fabrication of a microfluidic autoregulatory valve which is composed of several layers of thin polymer films (i.e., polyvinyl chloride (PVC), polyethylene terephthalate (PET) double-sided tape, and polydimethylsiloxane (PDMS)). Briefly, pulsed UV laser is employed to cut the microstructures of through grooves or holes in the thermoplastic polymer films, and then the polymer-film valves are precisely assembled through laminating the PDMS membranes to the thermoplastic polymer films through the roll-lamination method...
June 2017: Biomedical Microdevices
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