Mechanism of Hydrogen-Bonded Complex Formation between Ibuprofen and Nanocrystalline Hydroxyapatite.

Nanocrystalline hydroxyapatite (nanoHA) is the main hard component of bone and has the potential to be used to promote osseointegration of implants and to treat bone defects. Here, using active pharmaceutical ingredients (APIs) such as ibuprofen, we report on the prospects of combining nanoHA with biologically active compounds to improve the clinical performance of these treatments. In this study, we designed and investigated the possibility of API attachment to the surface of nanoHA crystals via the formation of a hydrogen-bonded complex. The mechanistic studies of an ibuprofen/nanoHA complex formation have been performed using a holistic approach encompassing spectroscopic (Fourier transform infrared (FTIR) and Raman) and X-ray diffraction techniques, as well as quantum chemistry calculations, while comparing the behavior of the ibuprofen/nanoHA complex with that of a physical mixture of the two components. Whereas ibuprofen exists in dimeric form both in solid and liquid state, our study showed that the formation of the ibuprofen/nanoHA complex most likely occurs via the dissociation of the ibuprofen dimer into monomeric species promoted by ethanol, with subsequent attachment of a monomer to the HA surface. An adsorption mode for this process is proposed; this includes hydrogen bonding of the hydroxyl group of ibuprofen to the hydroxyl group of the apatite, together with the interaction of the ibuprofen carbonyl group to an HA Ca center. Overall, this mechanistic study provides new insights into the molecular interactions between APIs and the surfaces of bioactive inorganic solids and sheds light on the relationship between the noncovalent bonding and drug release properties

A computable pathology report for precision medicine: extending an observables ontology unifying SNOMED CT and LOINC

Background The College of American Pathologists (CAP) introduced the first cancer synoptic reporting protocols in 1998. However, the objective of a fully computable and machine-readable cancer synoptic report remains elusive due to insufficient definitional content in Systematized Nomenclature of Medicine – Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC). To address this terminology gap, investigators at the University of Nebraska Medical Center (UNMC) are developing, authoring, and testing a SNOMED CT observable ontology to represent the data elements identified by the synoptic worksheets of CAP. Methods Investigators along with collaborators from the US National Library of Medicine, CAP, the International Health Terminology Standards Development Organization, and the UK Health and Social Care Information Centre analyzed and assessed required data elements for colorectal cancer and invasive breast cancer synoptic reporting. SNOMED CT concept expressions were developed at UNMC in the Nebraska Lexicon© SNOMED CT namespace. LOINC codes for each SNOMED CT expression were issued by the Regenstrief Institute. SNOMED CT concepts represented observation answer value sets. Results UNMC investigators created a total of 194 SNOMED CT observable entity concept definitions to represent required data elements for CAP colorectal and breast cancer synoptic worksheets, including biomarkers. Concepts were bound to colorectal and invasive breast cancer reports in the UNMC pathology system and successfully used to populate a UNMC biobank. Discussion The absence of a robust observables ontology represents a barrier to data capture and reuse in clinical areas founded upon observational information. Terminology developed in this project establishes the model to characterize pathology data for information exchange, public health, and research analytics

Strong, Light, Multifunctional Fibers of Carbon Nanotubes with Ultrahigh Conductivity

Broader applications of carbon nanotubes to real-world problems have largely gone unfulfilled because of difficult material synthesis and laborious processing. We report high-performance multifunctional carbon nanotube (CNT) fibers that combine the specific strength, stiffness, and thermal conductivity of carbon fibers with the specific electrical conductivity of metals. These fibers consist of bulk-grown CNTs and are produced by high-throughput wet spinning, the same process used to produce high-performance industrial fibers. These scalable CNT fibers are positioned for high-value applications, such as aerospace electronics and field emission, and can evolve into engineered materials with broad long-term impact, from consumer electronics to long-range power transmission

STAT-HI: A Socio-Technical Assessment Tool for Health Informatics Implementations

This paper proposes a socio-technical assessment tool (STAT-HI) for health informatics implementations. We explore why even projects allegedly using sound methodologies repeatedly fail to give adequate attention to socio-technical issues, and we present an initial draft of a structured assessment tool for health informatics implementation that encapsulates socio-technical good practice. Further work is proposed to enrich and validate the proposed instrument. This proposal was presented for discussion at a meeting of the UK Faculty of Health Informatics in December 2009

Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis

<p>Abstract</p> <p>Aim</p> <p>We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis.</p> <p>Methods</p> <p>Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack^®) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test.</p> <p>Results</p> <p>15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress.</p> <p>Conclusion</p> <p>Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants. </p> <p><b>Trial registration number</b>: ClinicalTrials.gov NCT00361452</p

A Tale of Switched Functions: From Cyclooxygenase Inhibition to M-Channel Modulation in New Diphenylamine Derivatives

Cyclooxygenase (COX) enzymes are molecular targets of nonsteroidal anti-inflammatory drugs (NSAIDs), the most used medication worldwide. However, the COX enzymes are not the sole molecular targets of NSAIDs. Recently, we showed that two NSAIDs, diclofenac and meclofenamate, also act as openers of Kv7.2/3 K+ channels underlying the neuronal M-current. Here we designed new derivatives of diphenylamine carboxylate to dissociate the M-channel opener property from COX inhibition. The carboxylate moiety was derivatized into amides or esters and linked to various alkyl and ether chains. Powerful M-channel openers were generated, provided that the diphenylamine moiety and a terminal hydroxyl group are preserved. In transfected CHO cells, they activated recombinant Kv7.2/3 K+ channels, causing a hyperpolarizing shift of current activation as measured by whole-cell patch-clamp recording. In sensory dorsal root ganglion and hippocampal neurons, the openers hyperpolarized the membrane potential and robustly depressed evoked spike discharges. They also decreased hippocampal glutamate and GABA release by reducing the frequency of spontaneous excitatory and inhibitory post-synaptic currents. In vivo, the openers exhibited anti-convulsant activity, as measured in mice by the maximal electroshock seizure model. Conversion of the carboxylate function into amide abolished COX inhibition but preserved M-channel modulation. Remarkably, the very same template let us generating potent M-channel blockers. Our results reveal a new and crucial determinant of NSAID-mediated COX inhibition. They also provide a structural framework for designing novel M-channel modulators, including openers and blockers

The Impact of eHealth on the Quality and Safety of Health Care: A Systematic Overview

Aziz Sheikh and colleagues report the findings of their systematic overview that assessed the impact of eHealth solutions on the quality and safety of health care

Thrive: Success Strategies for the Modern-Day Faculty Member

The THRIVE collection is intended to help faculty thrive in their roles as educators, scholars, researchers, and clinicians. Each section contains a variety of thought-provoking topics that are designed to be easily digested, guide personal reflection, and put into action. Please use the THRIVE collection to help: Individuals study topics on their own, whenever and wherever they want Peer-mentoring or other learning communities study topics in small groups Leaders and planners strategically insert faculty development into existing meetings Faculty identify campus experts for additional learning, grand rounds, etc. If you have questions or want additional information on a topic, simply contact the article author or email [email protected]://digitalcommons.unmc.edu/facdev_books/1000/thumbnail.jp