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https://www.readbyqxmd.com/read/29458233/pharmacokinetic-modelling-to-predict-fviii-c-response-to-desmopressin-and-its-reproducibility-in-nonsevere-haemophilia-a-patients
#1
L M Schütte, R M van Hest, S C M Stoof, F W G Leebeek, M H Cnossen, M J H A Kruip, R A A Mathôt
BACKGROUND: Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict. OBJECTIVES: Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. PATIENTS AND METHODS: Retrospective data of 128 nonsevere HA patients (age 7-75 years) receiving an intravenous or intranasal dose of desmopressin were used...
February 19, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29458230/perioperative-complications-of-congenital-diaphragmatic-hernia-repair
#2
Catarina Barroso, Jorge Correia-Pinto
Although improvements have been made, the management of congenital diaphragmatic hernia (CDH) remains a major challenge for perinatologists and neonatal surgeons. Many aspects of the disease remain unknown and, being a rare entity, evidence-based data are hard to find. Surgical morbidity is considerable and affects long-term quality of life. Perioperative complications have been reviewed focusing on thoracoscopic repair. Intraoperative acidosis was more severe during thoracoscopy when compared with open surgery (OS), though it is possible that later neurodevelopment was not affected...
February 19, 2018: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29458229/primary-closure-versus-bedside-silo-and-delayed-closure-for-gastroschisis-a-truncated-prospective-randomized-trial
#3
Ashwini S Poola, Pablo Aguayo, Jason D Fraser, Richard J Hendrickson, Katrina L Weaver, Katherine W Gonzalez, Shawn D St Peter
BACKGROUND: We report a prospective randomized trial comparing primary closure (PC) to bedside silo and delayed closure (DC) for babies with gastroschisis. METHODS: Patients were randomized to PC versus DC. We excluded those with atresia/necrosis, <34 weeks' gestation, or congenital anomalies. The primary outcome was length of stay (LOS). RESULTS: A total of 38 patients were included from August 2011 to August 2016; 18 patients underwent DC and 20 PC...
February 19, 2018: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29458225/-indication-quality-concepts-and-ethical-implications
#4
Andrea Dörries
BACKGROUND: In recent times - also due to new laws - a good "indication quality" has been called for. The aim of this paper is to contribute to the debate about "indication quality" by looking into the meaning of the term "indication" as well as the meaning of an adequate understanding of quality. METHODS: Initially, a conceptual analysis is made of how indication is an integral part of the therapeutic decision-making process between physician and patient, in which, next to evidence-based elements, also normative elements are included (step 1)...
February 19, 2018: Das Gesundheitswesen
https://www.readbyqxmd.com/read/29458220/incidence-of-autoimmune-and-related-disorders-after-resolution-of-endogenous-cushing-syndrome-in-children
#5
Christina Tatsi, Meg Keil, Charalampos Lyssikatos, Elena Belyavskaya, Constantine A Stratakis, Maya B Lodish
Glucocorticoids are widely used for immunosuppression in autoimmune diseases. After the resolution of hypercortisolemia, the immune system recovers allowing for autoimmune diseases to manifest. Here we investigated the presence of autoimmune and related diseases that developed after cure of endogenous Cushing syndrome (CS) in children. We identified 129 children who were diagnosed and successfully treated for endogenous CS at the National Institutes of Health from 1997 until 2017, and who were followed for at least 6 months after treatment...
February 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29458213/selective-targeting-and-degradation-of-doxorubicin-loaded-folate-functionalized-dna-nanocages
#6
Sofia Raniolo, Giulia Vindigni, Alessio Ottaviani, Valeria Unida, Federico Iacovelli, Antonio Manetto, Mariangela Figini, Lorenzo Stella, Alessandro Desideri, Silvia Biocca
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458210/preparation-of-a-solid-self-microemulsifying-drug-delivery-system-by-hot-melt-extrusion
#7
Luis Antonio D Silva, Susana L Almeida, Ellen C P Alonso, Priscila B R Rocha, Felipe T Martins, Luís A P Freitas, Stephania F Taveira, Marcilio S S Cunha-Filho, Ricardo N Marreto
Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458207/co-spray-drying-of-hygroscopic-kanamycin-with-the-hydrophobic-drug-rifampicin-to-improve-the-aerosolization-of-kanamycin-powder-for-treating-respiratory-infections
#8
Mohammad A M Momin, Ian G Tucker, Colin S Doyle, John A Denman, Shubhra Sinha, Shyamal C Das
High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve this, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would produce inhalable particles with surfaces enriched in rifampicin. Such particles would have higher aerosolization than kanamycin alone, and minimise the mass of powder for inhalation avoiding use of non-active excipients...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458206/mucoadhesive-self-emulsifying-delivery-systems-for-ocular-administration-of-econazole
#9
Ibrahim A Elbahwy, Noemi Lupo, Hany M Ibrahim, Hatem R Ismael, Alaa A Kasem, Cagri Caliskan, Barbara Matuszczak, Andreas Bernkop-Schnürch
AIM: Development of mucoadhesive self-emulsifying drug delivery systems (SEDDS) providing a prolonged ocular residence time for poorly soluble active pharmaceutical ingredient. METHODS: L-Cysteine was covalently linked to 6-mercaptonicotinamide. The obtained ligand, Cysteine-6- mercaptonicotinamide (Cys-6-MNA) was attached to Eudragit® L100-55 via a carbodiimide mediated amide bond formation. The resulting entirely S-protected thiolated Eudragit® L100-55 was characterized regarding the degree of modification as well as stability toward oxidation in the presence of strong oxidizing agent (H2 O2 )...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#10
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458202/validity-of-the-intra-operative-measurement-of-stem-anteversion-and-factors-for-the-erroneous-estimation-in-cementless-total-hip-arthroplasty-using-postero-lateral-approach
#11
Y K Lee, J W Kim, T Y Kim, Y C Ha, K H Koo
BACKGROUND: Intra-operative estimation of stem anteversion in total hip arthroplasty (THA) using postero-lateral approach is made by the surgeon's visual assessment, using the tibia as a guide, with the assumption that tibial axis is vertical to the trans-epicondylar axis. However, the accuracy of the intra-operative estimation has rarely been verified with postoperative CT-scans, with controversies regarding these measurements particularly in case of knee osteoarthritis. Therefore we performed a prospective study to: 1) determine the accuracy of the intra-operative measurement and 2) investigate factors affecting the discrepancy between the surgeon's estimation and the real stem anteversion HYPOTHESIS: Intra-operative estimation of stem anteversion correlated with the real stem anteversion on CT scan...
February 16, 2018: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/29458201/computer-assisted-surgery-in-acetabular-fractures-virtual-reduction-of-acetabular-fracture-using-the-first-patient-specific-biomechanical-model-simulator
#12
M Boudissa, H Oliveri, M Chabanas, J Tonetti
Preoperative planning for the management of acetabular fracture is founded on geometric models allowing virtual repositioning of the bone fragments, but not taking account of soft tissue and the realities of the surgical procedure. The present technical note reports results using the first simulator to be based on a patient-specific biomechanical model, simulating the action of forces on the fragments and also the interactions between soft issue and bone: muscles, capsules, ligaments, and bone contacts. In all 14 cases, biomechanical simulation faithfully reproduced the intraoperative behavior of the various bone fragments and reduction quality...
February 16, 2018: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/29458197/changes-in-motor-function-cognition-and-emotion-related-behavior-after-right-hemispheric-intracerebral-hemorrhage-in-various-brain-regions-of-mouse
#13
Wei Zhu, Yufeng Gao, Jieru Wan, Xi Lan, Xiaoning Han, Shanshan Zhu, Weidong Zang, Xuemei Chen, Wendy Ziai, Daniel F Hanley, Scott J Russo, Ricardo E Jorge, Jian Wang
Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458189/impact-of-time-of-day-on-diffusivity-measures-of-brain-tissue-derived-from-diffusion-tensor-imaging
#14
Cibu Thomas, Neda Sadeghi, Amrita Nayak, Aaron Trefler, Joelle Sarlls, Chris Baker, Carlo Pierpaoli
Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated...
February 16, 2018: NeuroImage
https://www.readbyqxmd.com/read/29458184/defuse-3-reinforcing-evidence-for-extended-endovascular-intervention-time-window-for-ischemic-stroke
#15
Dallas L Sheinberg, David J McCarthy, Eric C Peterson, Robert M Starke
No abstract text is available yet for this article.
February 16, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29458171/toxicology-studies-of-furosine-in-vitro-in-vivo-and-exploration-of-the-related-mechanism
#16
Hui-Ying Li, Lei Xing, Jia-Qi Wang, Nan Zheng
AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored...
February 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458168/apoptosis-of-enterocytes-and-nitration-of-junctional-complex-proteins-promote-alcohol-induced-gut-leakiness-and-liver-injury
#17
Young-Eun Cho, Li-Rong Yu, Mohamed A Abdelmegeed, Seong-Ho Yoo, Byoung-Joon Song
BACKGROUND & AIMS: Binge alcohol causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherent junction (AJ) proteins in binge alcohol-induced gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458166/statistical-approach-for-selection-of-biologically-informative-genes
#18
Samarendra Das, Anil Rai, D C Mishra, S N Rai
Selection of informative genes from high dimensional gene expression data has emerged as an important research area in genomics. Many gene selection techniques have been proposed so far are either based on relevancy or redundancy measure. Further, the performance of these techniques has been adjudged through post selection classification accuracy computed through a classifier using the selected genes. This performance metric may be statistically sound but may not be biologically relevant. A statistical approach, i...
February 16, 2018: Gene
https://www.readbyqxmd.com/read/29458164/structure-dependent-induction-of-apoptosis-by-hepatotoxic-pyrrolizidine-alkaloids-in-the-human-hepatoma-cell-line-heparg-single-versus-repeated-exposure
#19
Julia Waizenegger, Albert Braeuning, Markus Templin, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24 h) or repeated dose treatment (14 d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458156/how-to-isolate-identify-and-determine-antimicrobial-susceptibility-of-anaerobic-bacteria-in-routine-laboratories
#20
REVIEW
Elisabeth Nagy, Lyudmila Boyanova, Ulrik S Justesen
BACKGROUND: There has been an increased interest in the study of anaerobic bacteria, which cause human infection during the past decade. Many new genera and species have been described by to use 16S rRNA gene sequencing of clinical isolates obtained from different infection sites with commercially available special culture media to support the growth of anaerobes. Several systems, such as anaerobic pouches, boxes, jars and chambers provide suitable anaerobic culture conditions to isolate even strict anaerobic bacteria successfully from clinical specimens...
February 16, 2018: Clinical Microbiology and Infection
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