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https://www.readbyqxmd.com/read/28526268/structural-and-functional-aspects-of-the-nonribosomal-peptide-synthetase-condensation-domain-superfamily-discovery-dissection-and-diversity
#1
REVIEW
Kristjan Bloudoff, T Martin Schmeing
Nonribosomal peptide synthetases (NRPSs) are incredible macromolecular machines that produce a wide range of biologically- and therapeutically-relevant molecules. During synthesis, peptide elongation is performed by the condensation (C) domain, as it catalyzes amide bond formation between the nascent peptide and the amino acid it adds to the chain. Since their discovery more than two decades ago, C domains have been subject to extensive biochemical, bioinformatic, mutagenic, and structural analyses. They are composed of two lobes each with homology to chloramphenicol acetyltransferase, have two binding sites for their two peptidyl carrier protein-bound ligands, and have an active site with conserved motif HHxxxDG located between the two lobes...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28518132/mind-the-gap-can-videolaryngoscopy-bridge-the-competency-gap-in-neonatal-endotracheal-intubation-among-pediatric-trainees-a-randomized-controlled-study
#2
S Parmekar, J L Arnold, C Anselmo, M Pammi, J Hagan, C J Fernandes, K Lingappan
BACKGROUND: To study the impact of videolaryngoscopy (VL) on intubation success among pediatric trainees compared with direct laryngoscopy (DL). METHODS: One hundred pediatric residents were enrolled in a randomized, crossover, simulation study comparing VL to DL. Following a didactic session on neonatal intubation, residents intubated a standard neonatal mannequin. Three Neonatal Resuscitation Program (NRP) scenarios were then conducted, followed by a mannequin intubation with the alternate device...
May 18, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28508994/disease-modifying-effects-of-neural-regeneration-peptide-2945-in-the-gaers-model-of-absence-epilepsy
#3
Gabi Dezsi, Frank Sieg, Mark Thomas, Terence J O'Brien, Marieke van der Hart, Nigel C Jones
Epilepsy is a common neurological condition characterised by spontaneous recurrent seizures. Current anti-epileptic drugs are only effective and tolerated in ~70% of patients, leaving a substantial proportion of patients untreated. As such, there is a pressing need to develop new therapies. We assessed the anti-seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS model of absence epilepsy. Drug effects on seizures were assessed using two study designs. Male adult GAERS were implanted with EEG electrodes to measure seizure frequency...
May 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28507177/evidence-for-a-derangement-of-the-microvascular-system-in-patients-with-a-very-early-diagnosis-of-systemic-sclerosis
#4
Inês Chora, Eloisa Romano, Mirko Manetti, Celestina Mazzotta, Raquel Costa, Vera Machado, Alice Cortez, Cosimo Bruni, Gemma Lepri, Serena Guiducci, Amato De Paulis, Raquel Soares, Marco Matucci-Cerinic
OBJECTIVE: To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. METHODS: Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28487284/implementation-of-a-timed-electronic-assessment-driven-potassium-replacement-protocol
#5
Christopher Zielenski, Adam Crabtree, Tien Le, Alyse Marlatt, Dana Ng, Alan Tran
PURPOSE: The adherence to and effectiveness and safety of a timed, electronic, assessment-driven potassium-replacement protocol (TARP) were compared with an electronic nurse-driven replacement protocol (NRP) are reported. METHODS: A retrospective observational study was conducted in a community hospital evaluating protocol adherence, effectiveness, and safety for 2 potassium-replacement protocols. All adults on medical units with an order for potassium replacement per protocol during the 3-month trial periods were reviewed...
May 9, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28473849/directed-bee-colony-optimization-algorithm-to-solve-the-nurse-rostering-problem
#6
M Rajeswari, J Amudhavel, Sujatha Pothula, P Dhavachelvan
The Nurse Rostering Problem is an NP-hard combinatorial optimization, scheduling problem for assigning a set of nurses to shifts per day by considering both hard and soft constraints. A novel metaheuristic technique is required for solving Nurse Rostering Problem (NRP). This work proposes a metaheuristic technique called Directed Bee Colony Optimization Algorithm using the Modified Nelder-Mead Method for solving the NRP. To solve the NRP, the authors used a multiobjective mathematical programming model and proposed a methodology for the adaptation of a Multiobjective Directed Bee Colony Optimization (MODBCO)...
2017: Computational Intelligence and Neuroscience
https://www.readbyqxmd.com/read/28471440/accuracy-of-the-nasal-tragus-length-measurement-for-correct-endotracheal-tube-placement-in-a-cohort-of-neonatal-resuscitation-simulators
#7
M M Gray, H Delaney, R Umoren, T P Strandjord, T Sawyer
OBJECTIVE: Nasal-tragus length (NTL) estimates of endotracheal tube (ETT) depth are replacing weight-based estimates for endotracheal tube depth in neonates requiring endotracheal intubation. Existing neonatal simulators were designed before interest in using the NTL, and may lack fidelity in this measurement. The objective of this study is to evaluate the accuracy of the adjusted NTL formula and the Neonatal Resuscitation Program (NRP) gestational age/weight-based ETT depth chart in predicting proper endotracheal tube insertion depth in a cohort of neonatal simulators...
May 4, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28466607/conformational-latitude-activity-relationship-of-kppr-tetrapeptide-analogues-toward-their-ability-to-inhibit-binding-of-vascular-endothelial-growth-factor-165-to-neuropilin-1
#8
Bartlomiej Fedorczyk, Piotr F J Lipiński, Dagmara Tymecka, Anna K Puszko, Beata Wilenska, Gerard Y Perret, Aleksandra Misicka
Neuropilin-1 has been found to be overexpressed in several kinds of malignant tumors, and it is postulated that its interaction with the vascular endothelial growth factor 165 leads to progression of tumor vascularization and growth. Several analogues (KxxR) with various conformational latitudes have been synthesized and found as inhibitors of NRP-1. Detailed insight provided by molecular dynamics simulation allowed forming a clear relationship between flexibility of xx part of the molecule and its inhibitory activity...
May 3, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28457385/blood-lactate-concentrations-before-and-after-withdrawal-of-life-sustaining-treatments-in-controlled-donation-after-circulatory-death-a-case-report-from-italy
#9
F Baroncelli, M C Alberione, V Cacciotti, D Artusio, M Vergano, S Livigni
A 20-minute hands-off period with isoelectric electrocardiography (ECG) monitoring is currently required for the declaration of cardiac death in Italy, thus prolonging the warm ischemia time (WIT) during donation after circulatory death (DCD). Normothermic regional perfusion (NRP) can be a valid tool to optimize organ perfusion as a bridge to donation. A 62-year-old woman with catastrophic brain injury due to massive intracranial hemorrage, not fulfilling brain death criteria, underwent controlled DCD after withdrawal of life-sustaining therapies (WLST)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28455448/molecular-impact-of-covalent-modifications-on-nonribosomal-peptide-synthetase-carrier-protein-communication
#10
Andrew C Goodrich, David J Meyers, Dominique P Frueh
Nonribosomal peptide (NRP) synthesis involves the interplay between covalent protein modifications, conformational fluctuations, catalysis, and transient protein-protein interactions. Delineating the mechanisms involved in orchestrating these various processes will deepen our understanding of domain-domain communication in nonribosomal peptide synthetases (NRPSs) and lay the groundwork for the rational reengineering of NRPSs by swapping domains handling different substrates to generate novel natural products...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#11
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#12
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28411062/incidence-and-characteristics-of-positive-pressure-ventilation-delivered-to-newborns-in-a-us-tertiary-academic-hospital
#13
Dana E Niles, Courtney Cines, Elena Insley, Elizabeth E Foglia, Okan U Elci, Christiane Skåre, Theresa Olasveengen, Anne Ades, Michael Posencheg, Vinay M Nadkarni, Jo Kramer-Johansen
INTRODUCTION: The Neonatal Resuscitation Program (NRP) guidelines recommend positive pressure ventilation (PPV) in the first 60s of life to support perinatal transition in non-breathing newborns. Our aim was to describe the incidence and characteristics of newborn PPV using real-time observation in the delivery unit. METHODS: Prospective, observational, quality improvement study conducted at a tertiary academic hospital. Deliveries during randomized weekday/evening 8-h shifts were attended by a trained observer...
April 12, 2017: Resuscitation
https://www.readbyqxmd.com/read/28392736/preanalytical-external-quality-assessment-of-the-croatian-society-of-medical-biochemistry-and-laboratory-medicine-and-croqalm-finding-undetected-weak-spots
#14
Nora Nikolac, Jasna Lenicek Krleza, Ana-Maria Simundic
INTRODUCTION: The aim of this paper is to present results of first two years of preanalytical external quality assessment (EQA) in Croatia. MATERIALS AND METHODS: This paper summarizes results from 6 rounds of preanalytical EQA during 2014-2016 in 161-175 Croatian laboratories (number ranged between cycles). EQA was designed as an online survey of the compliance with National recommendations for phlebotomy (NRP). Forty-seven questions in 5 categories are analyzed (materials and equipment, patient identification, patient preparation, sampling and storage)...
February 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/28343180/oxygen-saturation-trends-in-normal-healthy-term-newborns-normal-vaginal-delivery-vs-elective-cesarean-section
#15
Rashi Bhargava, Madhu Mathur, Jyoti Patodia
OBJECTIVES: To study the normal oxygen saturation trends and fetomaternal correlates in healthy term newborns within 30 min of life born by normal vaginal delivery (NVD) and elective cesarean section (CS). MATERIALS AND METHODS: A cross-sectional study was conducted on 200 healthy term newborns born by NVD and elective CS at a tertiary care centre. Routine care as per the Neonatal Resuscitation Program (NRP) 2015 (Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, et al...
March 27, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28306594/extending-normothermic-regional-perfusion-to-the-thorax-in-donors-after-circulatory-death
#16
Steven S L Tsui, Gabriel C Oniscu
PURPOSE OF REVIEW: Despite a significant increase in the utilization of donors after circulatory death (DCD), the number of organs recovered and their function are largely inferior to those from donors after brain death. This review summarizes recent advances in in-situ normothermic regional perfusion of DCD organs prior to procurement. RECENT FINDINGS: The combination of warm and cold ischemia in DCD donation are detrimental to organ function. As a consequence, the acceptance criteria are far more restrictive and many organs are discarded...
June 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28306532/evaluation-of-the-sub-chronic-toxicity-profile-of-the-corm-of-xanthosoma-sagittifolium-on-hematology-and-biochemistry-of-alloxan-induced-diabetic-wistar-rats
#17
Olayinka A Oridupa, Oluyemisi F Folasire, Adedotun J Owolabi
Background Hematological and biochemical changes associated with diabetes mellitus and probable reversal were assessed in alloxan-induced diabetic Wistar rats fed with varied percentages of Xanthosoma sagittifolium corm feed (Xs). The changes were compared to normoglycemic rats and diabetic rats treated with glibenclamide. Methods The study had eight groups in all with group 8 (control) consisting of five normoglycemic rats fed with normal rat pellets (Nrp). Diabetes was experimentally induced by intraperitoneal injection of alloxan to normoglycemic rats...
March 11, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28293709/metabolic-perturbation-to-enhance-polyketide-and-nonribosomal-peptide-antibiotic-production-using-triclosan-and-ribosome-targeting-drugs
#18
Yukinori Tanaka, Masumi Izawa, Yoshikazu Hiraga, Yuya Misaki, Tomoko Watanabe, Kozo Ochi
Although transcriptional activation of pathwayspecific positive regulatory genes and/or biosynthetic genes is primarily important for enhancing secondary metabolite production, reinforcement of substrate supply, as represented by primary metabolites, is also effective. For example, partial inhibition of fatty acid synthesis with ARC2 (an analog of triclosan) was found to enhance polyketide antibiotic production. Here, we demonstrate that this approach is effective even for industrial high-producing strains, for example enhancing salinomycin production by 40%, reaching 30...
March 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28288627/a-protocol-for-the-methodological-steps-used-to-evaluate-the-alignment-of-rehabilitation-services-in-the-western-cape-south-africa-with-the-national-rehabilitation-policy
#19
Gubela Mji, Anthea Rhoda, Sue Statham, Conran Joseph
BACKGROUND: Rehabilitation medicine plays an integral part in attainment of optimal functioning after injury or disease. The National Rehabilitation Policy of South Africa (NRP) (2000) highlights the need for access to professional health care services, redistribution and optimal utilisation of resources and research in the field of disability and rehabilitation. The government further ratified the Convention on the Rights of Persons with Disabilities (CRPD) (2007), which validate the urgency in advancing the agenda of persons with disabilities...
March 14, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28287006/opinions-regarding-neonatal-resuscitation-training-for-the-obstetric-physician-a-survey-of-neonatal-and-obstetric-training-program-directors
#20
C J Bruno, L Johnston, C Lee, P S Bernstein, D Goffman
PURPOSE: Our goal was to garner opinions regarding neonatal resuscitation training for obstetric physicians. We sought to evaluate obstacles to neonatal resuscitation training for obstetric physicians and possible solutions for implementation challenges. MATERIALS AND METHODS: We distributed a national survey via email to all neonatal-perinatal medicine fellowship directors and obstetrics & gynecology residency program directors in the United States. This survey was designed by a consensus method...
April 3, 2017: Journal of Maternal-fetal & Neonatal Medicine
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