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Jia Zhu, Mingxi Qiao, Qi Wang, Yuqing Ye, Shuang Ba, Jingjing Ma, Haiyang Hu, Xiuli Zhao, Dawei Chen
Despite the extracellular barriers for siRNA delivery have been overcome by utilizing advanced nanoparticle delivery systems, the key intracellular barriers after internalization including efficient disassembly of siRNA and endosomal escape still remains challenging. To address the issues, we developed a unique pH- and redox potential-responsive polyplex delivery system based on the copolymer of mPEG-b-PLA-PHis-ssPEI1.8 k, which is composed of a pH-responsive copolymer of PEG-b-PLA-PHis (Mw 5 k) and a branched PEI (Mw1...
February 3, 2018: Biomaterials
Joshua M Kaplan, Neeraj Sharma, Sean Dikdan
Hypoxia-inducible factor (HIF) plays a crucial role in the response to hypoxia at the cellular, tissue, and organism level. New agents under development to pharmacologically manipulate HIF may provide new and exciting possibilities in the treatment of anemia of chronic kidney disease (CKD) as well as in multiple other disease states involving ischemia-reperfusion injury. This article provides an overview of recent studies describing current standards of care for patients with anemia in CKD and associated clinical issues, and those supporting the clinical potential for targeting HIF stabilization with HIF prolyl-hydroxylase inhibitors (HIF-PHI) in these patients...
January 29, 2018: International Journal of Molecular Sciences
Ari M Wes, Daniel Mazzaferro, Sanjay Naran, Scott P Bartlett, Jesse A Taylor
BACKGROUND: How hospital case-volume affects operative outcomes and cost continues to grow in importance. The purpose of this study is to examine the relationship of case volume with operative outcomes and cost in cleft palate repair. METHODS: Subjects undergoing cleft palate repair between 2004 and 2015 were identified in the Pediatric Health Information System (PHIS). Outcomes were compared between two exposure groups, those undergoing treatment at a high-volume institution (>85th percentile; >60 cases per year), and those undergoing treatment at a low-volume institution...
January 12, 2018: Plastic and Reconstructive Surgery
Margaret J Trost, Nathan Robison, Dean Coffey, Mary Rose Mamey, R Aaron Robison
BACKGROUND: Children with ventriculoperitoneal shunts (VPS) undergoing brain computed tomography (CT) for shunt malfunction evaluation are at risk for later malignancy due to radiation exposure. We aimed to determine if and how hospitals have adopted radiation-avoiding magnetic resonance imaging (MRI) techniques. METHODS: We performed a secondary analysis of the Pediatric Health Information System (PHIS) database. Children with VPS presenting to acute wards at 31 PHIS hospitals between January 1, 2007 and January 2, 2015 and receiving noncontrast neuroimaging on day of service 0/1 were included...
January 19, 2018: Pediatric Neurosurgery
Monica L Koncicki, Philip Zachariah, Adam R Lucas, Jeffrey D Edwards
OBJECTIVES: To characterize a multi-institutional cohort of children with chronic respiratory failure that use long-term, non-invasive respiratory support, perform a time-to-event analysis of transitions to transtracheal ventilation and identify factors associated with earlier transition to transtracheal ventilation. STUDY DESIGN: A retrospective cohort study of patients less than 21 years of age with diagnoses associated with chronic respiratory failure and discharged on non-invasive respiratory support was performed using data from the Pediatric Health Information System (PHIS) between 2007 and 2015...
January 17, 2018: Pediatric Pulmonology
Müberra Fatma Cesur, Saliha Durmuş
Pathogen-host interactions (PHIs) underlie the process of infection. The systems biology view of the whole PHI system is superior to the investigation of the pathogen or host separately in understanding the infection mechanisms. Especially, the identification of host-oriented drug targets for the next-generation anti-infection therapeutics requires the properties of the host factors targeted by pathogens. Here, we provide an outline of computational analysis of PHI networks, focusing on the properties of the pathogen-targeted host proteins...
2018: Methods in Molecular Biology
James Muleme, Clovice Kankya, John C Ssempebwa, Stella Mazeri, Adrian Muwonge
Knowledge, attitude, and practice (KAP) studies guide the implementation of public health interventions (PHIs), and they are important tools for political persuasion. The design and implementation of PHIs assumes a linear KAP relationship, i.e., an awareness campaign results in the desirable societal behavioral change. However, there is no robust framework for testing this relationship before and after PHIs. Here, we use qualitative and quantitative data on pesticide usage to test this linear relationship, identify associated context specific factors as well as assemble a framework that could be used to guide and evaluate PHIs...
2017: Frontiers in Public Health
Guihua Ye, Yajun Jiang, Xiaoying Yang, Hongxiang Hu, Beibei Wang, Lu Sun, Victor C Yang, Duxin Sun, Wei Gao
The inefficient cellular uptake and intracellular drug release at tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticles undergo phase transition in tumor microenvironment. The smart nanoparticles are generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH sensitive hydrophobic poly-L-histidine (PHIS) core, and is loaded with antitumor drug doxorubicin (DOX)...
December 20, 2017: ACS Applied Materials & Interfaces
Jill J Savla, Brian T Fisher, Jennifer A Faerber, Yuan-Shung V Huang, Laura Mercer-Rosa
BACKGROUND: The surgical strategy for neonates with tetralogy of Fallot (TOF) consists of complete or staged repair. Assessing the comparative effectiveness of these approaches is facilitated by a large multicenter cohort. We propose a novel process for cohort assembly using the Pediatric Health Information System (PHIS), an administrative database that contains clinical and billing data for inpatient and emergency department stays from tertiary children's hospitals. METHODS: A 4-step process was used to identify neonates with TOF: (1) screen neonates in PHIS with International Classification of Diseases-9 (ICD-9) diagnosis or procedure codes for TOF; (2) include patients with TOF procedures before 30 days of age; (3) exclude patients with missing 2-year follow-up data; (4) analyze patients' 2-year surgery sequence patterns, exclude patients inconsistent with a treatment strategy for TOF, and designate patients as complete or staged repair...
December 12, 2017: Medical Care
Justin Godown, Cary Thurm, Debra A Dodd, Jonathan H Soslow, Brian Feingold, Andrew H Smith, Bret A Mettler, Bryn Thompson, Matt Hall
BACKGROUND: Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx...
December 2017: American Heart Journal
Mehul V Makwana, Richmond Muimo, Richard Fw Jackson
Protein phosphorylation is an important post-translational modification that is an integral part of cellular function. The O-phosphorylated amino-acid residues, such as phosphoserine (pSer), phosphothreonine (pThr) and phosphotyrosine (pTyr), have dominated the literature while the acid labile N-linked phosphorylated amino acids, such as phosphohistidine (pHis), have largely been historically overlooked because of the acidic conditions routinely used in amino-acid detection and analysis. This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Yu Yang, Ligeng Xu, Wenjun Zhu, Liangzhu Feng, Jingjing Liu, Qian Chen, Ziliang Dong, Jiayue Zhao, Zhuang Liu, Meiwan Chen
Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms featured with biodegradability and versatile functionalities. However, multi-step post-synthesis surface modification is usually required to functionalize as-made NCPs before their biomedical applications. Moreover, efforts are still required to design therapeutic NCPs responsive to the unique tumor microenvironment to achieve more specific and effective therapy. Herein, we uncover a simple yet general strategy to synthesize a series of polyethylene glycol (PEG) modified NCPs via a one-step method by adding poly-histidine-PEG co-polymer into the mixture of metal ions and organic ligands during NCPs formation...
February 2018: Biomaterials
Sarah Keene, Karna Murthy, Eugenia Pallotto, Beverly Brozanski, Jason Gien, Isabella Zaniletti, Cheryl Hulbert, Ruth Seabrook, Natalie Rintoul, Louis Chicoine, Nicolas Porta, Theresa R Grover
BACKGROUND: In addition to substantial medical and surgical intervention, neonates with congenital diaphragmatic hernia (CDH) often have concurrent concerns for acquired infection. However, few studies focus on infection and corresponding antimicrobial utilization in this population. METHODS: The Children's Hospital Neonatal Database was queried for CDH infants hospitalized from Jan 2010- Feb 2016. Patient charts were linked to the Pediatric Health Information Systems (PHIS) database...
November 16, 2017: Pediatric Infectious Disease Journal
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
January 15, 2018: Acta Biomaterialia
Hemalatha G Rangarajan, Joseph R Stanek, Rolla Abu-Arja, Rajinder P S Bajwa, Jeffery J Auletta, Dean A Lee, Sarah H O'Brien, Riten Kumar
Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data...
February 2018: Biology of Blood and Marrow Transplantation
Kibileri Williams, Lauren Baumann, Fizan Abdullah, Shawn D St Peter, Tolulope A Oyetunji
PURPOSE: The role of prophylactic antibiotics for elective laparoscopic cholecystectomy has been questioned over the last decade. Although gradually being discontinued in the adult population, the practice among pediatric surgeons remains unknown. Our aim was to investigate the use of perioperative antibiotics in children undergoing elective laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis and biliary dyskinesia. METHODS: We retrospectively reviewed the Pediatric Health Information System (PHIS) database for 2015 and selected all patients 18years old or younger who underwent LC for cholelithiasis (without cholecystitis) or biliary dyskinesia...
October 9, 2017: Journal of Pediatric Surgery
Kibileri Williams, Lauren Baumann, Adil Shah, Fizan Abdullah, Emilie K Johnson, Tolulope A Oyetunji
PURPOSE: Undescended testis (UDT) is the most common congenital anomaly of the male genitalia. The American Urological Association guidelines recommend orchiopexy by age 18months to ameliorate the risk of subfertility. The study aim was to assess adherence to these guidelines on a national level. METHODS: We retrospectively reviewed both the State Ambulatory Surgery Database (SASD) in 2012 and the Pediatric Health Information System (PHIS) for 2015. All patients aged 18years or less with a diagnosis of UDT who underwent orchiopexy were included...
October 12, 2017: Journal of Pediatric Surgery
Lindsey Korbel, Robert S Easterling, Nidhi Punja, John David Spencer
BACKGROUND: People with diabetes mellitus (DM) have increased infection risk. The healthcare utilization of pediatric and adolescent diabetic patients with infection is not well defined. This study evaluates the number of pediatric and adolescent patients with DM that seek medical treatment for infection management and assesses its socioeconomic impact. METHODS: A retrospective analysis was performed using the Pediatric Health Information System (PHIS) database on children and adolescents with DM who presented to the Emergency Department (ED) or were hospitalized for infection management from 2008 to 2014...
November 2, 2017: Pediatric Diabetes
Kevin Adam, Tony Hunter
Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell's proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Thomas A Moore, Alexander Li, Edmond W K Young
Recent advances in cell-based assays have involved the integration of single-cell analyses and microfluidics technology to facilitate both high-content and high-throughput applications. These technical advances have yielded large datasets with single-cell resolution, and have given rise to the study of cell population dynamics, but statistical analyses of these populations and their properties have received much less attention, particularly for cells cultured in microfluidic systems. The objective of this study was to perform statistical analyses using Pittsburgh Heterogeneity Indices (PHIs) to understand the heterogeneity and evolution of cell population demographics on datasets generated from a microfluidic single-cell-resolution cell-based assay...
October 1, 2017: SLAS Discovery
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