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https://www.readbyqxmd.com/read/28803389/gastrointestinal-manifestations-of-stat3-deficient-hyper-ige-syndrome
#1
Manish Arora, Preet Bagi, Anna Strongin, Jennifer Heimall, Xiongce Zhao, Monica G Lawrence, Apurva Trivedi, Carolyn Henderson, Amy Hsu, Martha Quezado, David E Kleiner, Aradhana M Venkatesan, Steven M Holland, Alexandra F Freeman, Theo Heller
OBJECTIVE: STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations. We sought to describe the gastrointestinal (GI) manifestations of this disease. METHODS: Seventy subjects aged five to 60 years with a molecular diagnosis of AD-HIES were evaluated at the National Institutes of Health (NIH)...
August 13, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28756200/erbb4-protects-against-neuronal-apoptosis-via-activation-of-yap-pik3cb-signaling-pathway-in-a-rat-model-of-subarachnoid-hemorrhage
#2
Feng Yan, Xiaoxiao Tan, Weifeng Wan, Brandon J Dixon, Ruiming Fan, Budbazar Enkhjargal, Qian Li, Jianmin Zhang, Gao Chen, John H Zhang
Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28719561/arterial-topographic-anatomy-near-the-femoral-head-neck-perforation-with-surgical-relevance
#3
Paulo Rego, Vasco Mascarenhas, Diego Collado, Ana Coelho, Luis Barbosa, Reinhold Ganz
BACKGROUND: Knowledge of the vascular supply of the femoral head is crucial for hip-preserving surgical procedures. The critical area for reshaping cam deformity is at the retinacular vessel penetration, an area with ill-defined topographic anatomy. We performed a cadaver study of the extension of the lateral retinaculum near the head-neck junction, distribution of the arterial vascular foramina, and initial intracapital course of these vessels. METHODS: In 16 fresh proximal parts of the femur without head-neck deformities, the deep branch of the medial femoral circumflex artery was injected with gadolinium for magnetic resonance imaging (MRI) sequences to identify arterial structures...
July 19, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28716954/synaptically-driven-phosphorylation-of-ribosomal-protein-s6-is-differentially-regulated-at-active-synapses-versus-dendrites-and-cell-bodies-by-mapk-and-pi3k-mtor-signaling-pathways
#4
Patricia Salgado Pirbhoy, Shannon Farris, Oswald Steward
High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR and MAPK/ERK-dependent kinases. Using phospho-specific antibodies for rpS6 at different sites (ser235/236 versus ser240/244), we show that delivery of the PI3-kinase inhibitor, wortmannin, decreased rpS6 phosphorylation throughout the somatodendritic compartment (granule cell layer, inner molecular layer, outer molecular layer), especially in granule cell bodies while sparing phosphorylation at activated synapses (middle molecular layer)...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28704727/nrf2-deficiency-replicates-transcriptomic-changes-in-alzheimer-s-patients-and-worsens-app-and-tau-pathology
#5
Ana I Rojo, Marta Pajares, Patricia Rada, Angel Nuñez, Alejo J Nevado-Holgado, Richard Killik, Fred Van Leuven, Elena Ribe, Simon Lovestone, Masayuki Yamamoto, Antonio Cuadrado
Failure to translate successful neuroprotective preclinical data to a clinical setting in Alzheimer's disease (AD) indicates that amyloidopathy and tauopathy alone provide an incomplete view of disease. We have tested here the relevance of additional homeostatic deviations that result from loss of activity of transcription factor NRF2, a crucial regulator of multiple stress responses whose activity declines with ageing. A transcriptomic analysis demonstrated that NRF2-KO mouse brains reproduce 7 and 10 of the most dysregulated pathways of human ageing and AD brains, respectively...
July 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28701394/single-particle-detection-of-transcription-following-rotavirus-entry
#6
Eric N Salgado, Srigokul Upadhyayula, Stephen C Harrison
Infectious rotavirus particles are triple-layered, icosahedral assemblies. The outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a transcriptionally competent, double-layer particle (DLP), which they deliver into the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell-surface gangliosides, allowing engulfment into a membrane vesicle by a clathrin-independent process. Escape into the cytosol and outer-layer shedding depend on interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a large-scale conformational change...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28698029/critical-role-of-epha4-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rat
#7
Ruiming Fan, Budbazar Enkhjargal, Richard Camara, Feng Yan, Lei Gong, ShengtaoYao, Jiping Tang, Yangmei Chen, John H Zhang
Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH...
July 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28653239/adapted-eras-pathway-vs-standard-care-in-patients-with-perforated-duodenal-ulcer-a-randomized-controlled-trial
#8
Subair Mohsina, Dasarathan Shanmugam, Sathasivam Sureshkumar, Pankaj Kundra, T Mahalakshmy, Vikram Kate
OBJECTIVES: The objective of this study was to evaluate the feasibility and efficacy of ERAS pathways in patients undergoing emergency simple closure of perforated duodenal ulcer (PDU). METHODS: This single-center, prospective, open-labeled, superiority, RCT was carried out from August 2014 to July 2016. Patients of PDU undergoing open simple closure were randomized preoperatively in 1:1 ratio into standard care and adapted ERAS group. Patients with refractory shock, ASA class ≥3, and perforation size ≥1 cm were excluded...
June 26, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28652412/extracellular-zn-2-is-essential-for-amyloid-%C3%AE-1-42-induced-cognitive-decline-in-the-normal-brain-and-its-rescue
#9
Atsushi Takeda, Haruna Tamano, Munekazu Tempaku, Miku Sasaki, Chihiro Uematsu, Shoko Sato, Hiroaki Kanazawa, Zsolt L Datki, Paul A Adlard, Ashley I Bush
Brain Aβ1-42 accumulation is considered an upstream event in pathogenesis of Alzheimer's disease. However, accumulating evidence indicates that other neurochemical changes potentiate the toxicity of this constitutively generated peptide. Here we report that the interaction of Aβ1-42 with extracellular Zn(2+) is essential for in vivo rapid uptake of Aβ1-42 and Zn(2+) into dentate granule cells in the normal rat hippocampus. The uptake of both Aβ1-42 and Zn(2+) was blocked by CaEDTA, an extracellular Zn(2+) chelator, and by Cd(2+), a metal that displaces Zn(2+) for Aβ1-42 binding...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28630160/listeriolysin-o-from-bazooka-to-swiss-army-knife
#10
REVIEW
Suzanne E Osborne, John H Brumell
Listeria monocytogenes (Lm) is a Gram-positive facultative intracellular pathogen. Infections in humans can lead to listeriosis, a systemic disease with a high mortality rate. One important mechanism of Lm dissemination involves cell-to-cell spread after bacteria have entered the cytosol of host cells. Listeriolysin O (LLO; encoded by the hly gene) is a virulence factor present in Lm that plays a central role in the cell-to-cell spread process. LLO is a member of the cholesterol-dependent cytolysin (CDC) family of toxins that were initially thought to promote disease largely by inducing cell death and tissue destruction-essentially acting like a 'bazooka'...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28629607/post-operative-management-of-perforated-appendicitis-can-clinical-pathways-improve-outcomes
#11
Robert R Gerard, Barrett A Kielhorn, Brent Petersen, Andrew J Mullard, Laurence E McCahill
BACKGROUND: We sought to decrease organ space infection (OSI) following appendectomy for perforated acute appendicitis (PAA) by minimizing variation in clinical management. OBJECTIVE: A postoperative treatment pathway was developed and four recommendations were implemented: 1) clear documentation of post-operative diagnosis, 2) patients with unknown perforation status to be treated as perforated pending definitive diagnosis, 3) antibiotic therapy to be continued post operatively for 4-7 days after SIRS resolution, and 4) judicious use of abdominal computed tomography (CT) scanning prior to post-operative day 5...
June 10, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28600325/hira-deficiency-in-muscle-fibers-causes-hypertrophy-and-susceptibility-to-oxidative-stress
#12
Nicolas Valenzuela, Benjamin Soibam, Lerong Li, Jing Wang, Lauren A Byers, Yu Liu, Robert J Schwartz, M David Stewart
Nucleosome assembly proceeds through DNA replication-coupled or replication-independent mechanisms. For skeletal myocytes, whose nuclei have permanently exited the cell cycle, replication-independent assembly is the only mode available for chromatin remodeling. For this reason, any nucleosome composition alterations accompanying transcriptional responses to physiological signals must occur through a DNA replication-independent pathway. HIRA is the histone chaperone primarily responsible for replication-independent incorporation of histone variant H3...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#13
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
September 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28547527/weakened-intracellular-zn-2-buffering-in-the-aged-dentate-gyrus-and-its-involvement-in-erasure-of-maintained-ltp
#14
Atsushi Takeda, Haruna Tamano, Taku Murakami, Hiroyuki Nakada, Tatsuya Minamino, Yuta Koike
Memory is lost by the increased influx of extracellular Zn(2+) into neurons. It is possible that intracellular Zn(2+) dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn(2+) dynamics was compared between young and aged rats...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28538438/differential-regulation-of-the-autophagy-and-proteasome-pathways-in-skeletal-muscles-in-sepsis
#15
Flavia Stana, Marija Vujovic, Dominique Mayaki, Jean-Philippe Leduc-Gaudet, Philippe Leblanc, Laurent Huck, Sabah N A Hussain
OBJECTIVES: Skeletal muscle fiber atrophy develops in response to severe sepsis, but it is unclear as to how the proteolytic pathways that are involved in its development are differentially regulated. We investigated the link between sepsis-induced fiber atrophy and activation of the proteasome and autophagy pathways and whether the degree of activation is more severe and sustained in limb muscles than it is in the diaphragm. DESIGN: Randomized controlled experiment...
September 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28534197/pcmt1-ameliorates-neuronal-apoptosis-by-inhibiting-the-activation-of-mst1-after-subarachnoid-hemorrhage-in-rats
#16
Ligen Shi, Ammar Al-Baadani, Keren Zhou, Anwen Shao, Shenbin Xu, Sheng Chen, Jianmin Zhang
Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation...
May 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28526701/netrin-1-preserves-blood-brain-barrier-integrity-through-deleted-in-colorectal-cancer-focal-adhesion-kinase-rhoa-signaling-pathway-following-subarachnoid-hemorrhage-in-rats
#17
Zongyi Xie, Budbazar Enkhjargal, Cesar Reis, Lei Huang, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
BACKGROUND: Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. METHODS AND RESULTS: A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH...
May 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28499377/calculating-hospital-length-of-stay-using-the-hospital-episode-statistics-a-comparison-of-methodologies
#18
John Busby, Sarah Purdy, William Hollingworth
BACKGROUND: Accurate calculation of hospital length of stay (LOS) from the English Hospital Episode Statistics (HES) is important for a wide range of audit and research purposes. The two methodologies which are commonly used to achieve this differ in their accuracy and complexity. We compare these methods and make recommendations on when each is most appropriate. METHODS: We calculated LOS using continuous inpatient spells (CIPS), which link care spanning across multiple hospitals, and spells, which do not, for six conditions with short (dyspepsia or other stomach function, ENT infection), medium (dehydration and gastroenteritis, perforated or bleeding ulcer), and long (stroke, fractured proximal femur) average LOS...
May 12, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28488626/surgery-for-superior-hypophyseal-artery-aneurysms-a-new-classification-and-surgical-considerations
#19
Chaitanya Godbole, Sanjay Behari, Kamlesh K Bhaisora, Jayesh Sardhara, Arun Srivastava, Anant Mehrotra, Kuntal Kanti Das, Raj Kumar, Awadhesh K Jaiswal
BACKGROUND: Superior hypophyseal artery (SHA) aneurysms form a unique subgroup of paraclinoid aneurysms having a propensity to grow to a large size in the suprasellar region resulting in compression of the optic nerve, chiasma, and/or tract. AIM: A new classification of SHA aneurysms is proposed that helps in identifying the surgical issues encountered during surgical clipping of these medially directed aneurysms located at different segments of the medial surface of the internal carotid artery (ICA)...
May 2017: Neurology India
https://www.readbyqxmd.com/read/28485406/inducing-a-long-term-potentiation-in-the-dentate-gyrus-is-sufficient-to-produce-rapid-antidepressant-like-effects
#20
A Kanzari, C Bourcier-Lucas, A Freyssin, D N Abrous, N Haddjeri, G Lucas
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects...
May 9, 2017: Molecular Psychiatry
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