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Closed loop titrate

Nicole Ribeiro Marques, William E Whitehead, Upendar R Kallu, Michael P Kinsky, Joe S Funston, Taoufik Wassar, Muzna N Khan, Mindy Milosch, Daniel Jupiter, Karolos Grigoriadis, George C Kramer
BACKGROUND: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required...
March 31, 2017: Anesthesia and Analgesia
Nicole Ribeiro Marques, Brent J Ford, Muzna N Khan, Michael Kinsky, Donald J Deyo, William J Mileski, Hao Ying, George C Kramer
BACKGROUND: Hemorrhagic shock is the leading cause of trauma-related death in the military setting. Definitive surgical treatment of a combat casualty can be delayed and life-saving fluid resuscitation might be necessary in the field. Therefore, improved resuscitation strategies are critically needed for prolonged field and en route care. We developed an automated closed-loop control system capable of titrating fluid infusion to a target endpoint. We used the system to compare the performance of a decision table algorithm (DT) and a fuzzy logic controller (FL) to rescue and maintain the mean arterial pressure (MAP) at a target level during hemorrhages...
2017: Disaster and Military Medicine
Thomas Peters, Lena Lisbeth Grimm, Sophie Weissbach, Friedemann Flügge, Nora Begemann, Monica Palcic
Donor and acceptor substrate binding to human blood group A and B glycosyltransferases (GTA, GTB) has been studied by a variety of protein NMR experiments. Prior crystallographic studies have shown these enzymes to adopt an open conformation in the absence of substrates. Binding of either the donor substrate UDP-Gal, or of UDP induces a semi-closed conformation. In the presence of both, donor- and acceptor substrates, the enzymes shift towards a closed conformation with ordering of an internal loop and the C-terminal residues, which then completely cover the donor-binding pocket...
March 3, 2017: Chembiochem: a European Journal of Chemical Biology
Joseph Rinehart, Michael Ma, Michael-David Calderon, Maxime Cannesson
Blood pressure management is a central concern in critical care patients. For a variety of reasons, titration of vasopressor infusions may be an ideal use-case for computer assistance. Using our previous experience gained in the bench-to-bedside development of a computer-assisted fluid management system, we have developed a novel controller for this purpose. The aim of this preliminary study was to assess the feasibility of using this controller in simulated patients to maintain a target blood pressure in both stable and variable blood-pressure scenarios...
January 25, 2017: Journal of Clinical Monitoring and Computing
François Lellouche, Erwan L'Her, Pierre-Alexandre Bouchard, Cynthia Brouillard, François Maltais
BACKGROUND: Arterial oxygen desaturation frequently occurs in patients with COPD during daily activities at home. Oxygen flow is usually set at fixed and low rates for ambulatory patients. We evaluated an innovative closed-loop system (FreeO2) that automatically adjusts the oxygen flow to the patient's needs in subjects with COPD during walking followed by recovery time, such as during ambulatory conditions. METHODS: Patients with COPD who exhibited oxygen desaturation on exertion were included in the study...
November 2016: Respiratory Care
Yi-Hsuan Chen, Hua-Yi Hsu, Ming-Tyng Yeh, Chen-Cheng Chen, Chang-Yu Huang, Ying-Hsuan Chung, Zee-Fen Chang, Wei-Chen Kuo, Nei-Li Chan, Jui-Hsia Weng, Bon-Chu Chung, Yu-Ju Chen, Cheng-Bang Jian, Ching-Chieh Shen, Hwan-Ching Tai, Sheh-Yi Sheu, Jim-Min Fang
Targeting thymidylate kinase (TMPK) that catalyzes the phosphotransfer reaction for formation of dTDP from dTMP is a new strategy for anticancer treatment. This study is to understand the inhibitory mechanism of a previously identified human TMPK (hTMPK) inhibitor YMU1 (1a) by molecular docking, isothermal titration calorimetry, and photoaffinity labeling. The molecular dynamics simulation suggests that 1a prefers binding at the catalytic site of hTMPK, whereas the hTMPK inhibitors that bear pyridino[d]isothiazolone or benzo[d]isothiazolone core structure in lieu of the dimethylpyridine-fused isothiazolone moiety in 1a can have access to both the ATP-binding and catalytic sites...
November 10, 2016: Journal of Medicinal Chemistry
Cristiano S Mota, Ana Maria D Gonçalves, Daniele de Sanctis
DR2231 from Deinococcus radiodurans was previously functionally and structurally characterized as an all-α NTP pyrophosphohydrolase with specific dUTPase activity. dUTPases have a central role in the regulation of dUTP intracellular levels and dTTP nucleotide metabolism. DR2231 presents a conserved dimetal catalytic site, similar to all-α dimeric dUTPases, but contrary to these enzymes, it is unable to process dUDP. In this article, we present functional and structural evidence of single-point mutations that affect directly or indirectly the enzyme catalysis and provide a complete description of the all-α NTP pyrophosphohydrolase mechanism...
December 2016: FEBS Journal
Leopoldo C Cancio, Jose Salinas, George C Kramer
Fluid resuscitation of burn patients is commonly initiated using modified Brooke or Parkland formula. The fluid infusion rate is titrated up or down hourly to maintain adequate urine output and other endpoints. Over-resuscitation leads to morbid complications. Adherence to paper-based protocols, flow sheets, and clinical practice guidelines is associated with decreased fluid resuscitation volumes and complications. Computerized tools assist providers. Although completely autonomous closed-loop control of resuscitation has been demonstrated in animal models of burn shock, the major advantages of open-loop and decision-support systems are identifying trends, enhancing situational awareness, and encouraging burn team communication...
October 2016: Critical Care Clinics
A Restoux, S Grassin-Delyle, N Liu, C Paugam-Burtz, J Mantz, M Le Guen
BACKGROUND: Automated titration of propofol and remifentanil guided by the bispectral index (BIS) has been used for numerous surgical procedures. Orthotopic liver transplantation (OLT) uniquely combines major changes in circulating volume, an anhepatic phase, and ischaemia-reperfusion syndrome. We assessed the behaviour of this automated controller during OLT. METHODS: Adult patients undergoing OLT were included in this pilot study. Consumption of propofol and remifentanil was calculated for each surgery period (dissection, anhepatic, and liver reperfusion phases)...
September 2016: British Journal of Anaesthesia
Adeline Zbrzeski, Yannick Bornat, Brian Hillen, Ricardo Siu, James Abbas, Ranu Jung, Sylvie Renaud
Cervical spinal cord injury can disrupt connections between the brain respiratory network and the respiratory muscles which can lead to partial or complete loss of ventilatory control and require ventilatory assistance. Unlike current open-loop technology, a closed-loop diaphragmatic pacing system could overcome the drawbacks of manual titration as well as respond to changing ventilation requirements. We present an original bio-inspired assistive technology for real-time ventilation assistance, implemented in a digital configurable Field Programmable Gate Array (FPGA)...
2016: Frontiers in Neuroscience
Jennifer L Sherr, Neha S Patel, Camille I Michaud, Miladys M Palau-Collazo, Michelle A Van Name, William V Tamborlane, Eda Cengiz, Lori R Carria, Eileen M Tichy, Stuart A Weinzimer
OBJECTIVE: Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS: Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7...
July 2016: Diabetes Care
Alyce S Adams, Elizabeth A Bayliss, Julie A Schmittdiel, Andrea Altschuler, Wendy Dyer, Romain Neugebauer, Marc Jaffe, Joseph D Young, Eileen Kim, Richard W Grant
BACKGROUND: Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy...
June 2016: Clinical Trials: Journal of the Society for Clinical Trials
Aurélien Bataille, Jacques-Florian Letourneulx, Alain Charmeau, Pascale Lemedioni, Philippe Léger, Thierry Chazot, Morgan Le Guen, Pierre Diemunsch, Marc Fischler, Ngai Liu
BACKGROUND: In obese patients, the incidence of postoperative nausea and vomiting (PONV) following sleeve gastrectomy under titration of total intravenous anaesthesia (TIVA) and the relevance of risk factors to indicate prophylaxis is unknown. OBJECTIVES: The hypothesis was that after automated TIVA, prophylaxis reduces PONV following laparoscopic sleeve gastrectomy. Our objective was to determine the incidence of PONV and evaluate the efficacy of dexamethasone and ondansetron as prophylaxis when automated intravenous anaesthesia is employed...
December 2016: European Journal of Anaesthesiology
Yan Jiang, Heli Jiang, Shaoyang Zhou, Bing Meng, Zhi-Jie Liu, Songying Ouyang
The guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2) is identified as a member of the Dbl family of GEFs. It regulates RhoA-dependent cell signaling pathways and plays important roles in biological processes. GEF-H1 contains an N-terminal zinc finger domain, a Dbl-homologous (DH) domain followed by a Pleckstrin homology (PH) domain, and a C-terminal domain. The specific roles of its PH domain are poorly understood. Here we report the crystal structure of human GEF-H1 PH domain to 2.45 Å resolution...
March 18, 2016: Biochemical and Biophysical Research Communications
Christian Cuba Samaniego, Giulia Giordano, Jongmin Kim, Franco Blanchini, Elisa Franco
Molecular titration is emerging as an important biochemical interaction mechanism within synthetic devices built with nucleic acids and the CRISPR/Cas system. We show that molecular titration in the context of feedback circuits is a suitable mechanism to enhance the emergence of oscillations and bistable behaviors. We consider biomolecular modules that can be inhibited or activated by input monomeric regulators; the regulators compete with constitutive titrating species to determine the activity of their target...
April 15, 2016: ACS Synthetic Biology
Morgan LE Guen, Ngai Liu, Thierry Chazot, Marc Fischler
Automated anesthesia which may offer to the physician time to control hemodynamic and to supervise neurological outcome and which may offer to the patient safety and quality was until recently consider as a holy grail. But this field of research is now increasing in every component of general anesthesia (hypnosis, nociception, neuromuscular blockade) and literature describes some successful algorithms - single or multi closed-loop controller. The aim of these devices is to control a predefined target and to continuously titrate anesthetics whatever the patients' co morbidities and surgical events to reach this target...
May 2016: Minerva Anestesiologica
Chao He, Xianyu Huang, Yanhong Liu, Fudong Li, Yang Yang, Hongru Tao, Chuanchun Han, Chen Zhao, Yazhong Xiao, Yunyu Shi
Mouse L-threonine dehydrogenase (mTDH), which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and mediates threonine catabolism, plays pivotal roles in both powerful biosynthesis and signaling in mouse stem cells and has a regulatory residue Arg180. Here we determined three crystal structures of mTDH: wild-type (WT) in the apo form; in complex with NAD(+) and a substrate analog, glycerol, or with only NAD(+); as well as the R180K variant with NAD(+). This is the first description of a structure for mammalian SDR-type TDH...
December 2015: Journal of Structural Biology
Fanomezana M Ranaivoson, Qun Liu, Francesca Martini, Francesco Bergami, Sventja von Daake, Sheng Li, David Lee, Borries Demeler, Wayne A Hendrickson, Davide Comoletti
Latrophilins (LPHNs) are adhesion-like G-protein-coupled receptors implicated in attention-deficit/hyperactivity disorder. Recently, LPHN3 was found to regulate excitatory synapse number through trans interactions with fibronectin leucine-rich repeat transmembrane 3 (FLRT3). By isothermal titration calorimetry, we determined that only the olfactomedin (OLF) domain of LPHN3 is necessary for FLRT3 association. By multi-crystal native single-wavelength anomalous diffraction phasing, we determined the crystal structure of the OLF domain...
September 1, 2015: Structure
Goverdhan D Puri, Preethy J Mathew, Indranil Biswas, Amitabh Dutta, Jayashree Sood, Satinder Gombar, Sanjeev Palta, Morup Tsering, P L Gautam, Aveek Jayant, Inderjeet Arora, Vishal Bajaj, T S Punia, Gurjit Singh
BACKGROUND: Closed-loop systems for anesthesia delivery have been shown to outperform traditional manual control in different clinical settings. The present trial was aimed at evaluating the feasibility and efficacy of Bispectral Index (BIS)-guided closed-loop anesthesia delivery system (CLADS) in comparison with manual control across multiple centers in India. METHODS: Adult patients scheduled for major surgical procedures of an expected duration of 1 to 3 hours were randomized across 6 sites into 2 groups: a CLADS group and a manual group...
January 2016: Anesthesia and Analgesia
Eszter Németh, Milan Kožíšek, Gabriella K Schilli, Béla Gyurcsik
The structure of the active site in a metalloenzyme can be a key determinant of its metal ion binding affinity and catalytic activity. In this study, the conformational features of the Zn(2+)-binding HNH motif were investigated by CD-spectroscopy in combination with isothermal microcalorimetric titrations. Various point mutations, including T454A, K458A and W464A, were introduced into the N-terminal loop of the nuclease domain of colicin E7 (NColE7). We show that the folding of the proteins was severely disturbed by the mutation of the tryptophan residue...
October 2015: Journal of Inorganic Biochemistry
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