Culture with apically applied healthy or disease sputum alters the airway surface liquid proteome and ion transport across human bronchial epithelial cells.

Airway secretions contain many signalling molecules and peptides/proteins that are not found in airway surface liquid (ASL) generated by normal human bronchial epithelial cells (NHBE) in vitro. These play a key role in innate defence and mediate communication between the epithelium, immune cells and the external environment. We investigated how culture of NHBE with apically applied secretions from healthy or disease (Cystic Fibrosis, CF) lungs affected epithelial function with a view to providing better in vitro models of the in vivo environment. NHBE from 6-8 different donors were cultured at air-liquid interface (ALI), with apically applied sputum from normal healthy donors (NLS) or CF donors (CFS) for 2-4 hours, 48 hours or with sputum reapplied over 48 hours. Proteomic analysis was carried out on the sputa and on NHBE ASL before and after culture with sputa. Transepithelial electrical resistance (TEER), short circuit current (Isc) and changes to ASL height were measured. There were 71 proteins common to both sputa but not ASL. The protease:protease inhibitor balance was increased in CFS compared to NLS and ASL. Culture of NHBE with sputa for 48 hours identified additional factors not present in NLS, CFS or ASL alone. Culture with either NLS or CFS for 48 hours increased CFTR activity, calcium activated chloride channel (CaCC) activity and changed ASL height. These data indicate that culture with healthy or disease sputum changes the proteomic profile of ASL and ion transport properties of NHBE and this may increase physiological relevance when using in vitro airway models

Proposta de um algoritmo de recomendação usando uma rede bayesiana no health simulator

Este artigo apresenta o projeto Health Simulator no contexto de inteligência artificial, no que se refere ao armazenamento do conhecimento especializado na área da saúde e estratégia pedagógica, que permite o auxílio ao aluno no seu processo de aprendizagem. Para tanto é apresentada a teoria de redes bayesianas, sistemas de recomendação, o projeto Health Simulator e a proposta de aplicação das técnicas utilizadas neste ambiente

Geology of the Waste Treatment Plant Seismic Boreholes

In 2006, DOE-ORP initiated the Seismic Boreholes Project (SBP) to emplace boreholes at the Waste Treatment Plant (WTP) site in order to obtain direct Vs measurements and other physical property measurements in Columbia River basalt and interbedded sediments of the Ellensburg Formation. The goal was to reduce the uncertainty in the response spectra and seismic design basis, and potentially recover design margin for the WTP. The characterization effort within the deep boreholes included 1) downhole measurements of the velocity properties of the suprabasalt, basalt, and sedimentary interbed sequences, 2) downhole measurements of the density of the subsurface basalt and sediments, and 3) confirmation of the geometry of the contact between the various basalt and interbedded sediments through examination of retrieved core from the corehole and data collected through geophysical logging of each borehole. This report describes the results of the geologic studies from three mud-rotary boreholes and one cored borehole at the WTP. All four boreholes penetrated the entire Saddle Mountains Basalt and the upper part of the Wanapum Basalt where thick sedimentary interbeds occur between the lava flows. The basalt flows penetrated in Saddle Mountains Basalt included the Umatilla Member, Esquatzel Member, Pomona Member and the Elephant Mountain Member. The underlying Priest Rapids Member of the Wanapum Basalt was also penetrated. The Ellensburg Formation sediments consist of the Mabton Interbed, the Cold Creek Interbed, the Selah Interbed and the Rattlesnake Ridge Interbed; the Byron Interbed occurs between two flows of the Priest Rapids Member. The Mabton Interbed marks the contact between the Wanapum and Saddle Mountains Basalts. The thicknesses of the basalts and interbedded sediments were within expected limits. However, a small reverse fault was found in the Pomona Member flow top. This fault has three periods of movement and less than 15 feet of repeated section. Most of the movement on the fault appears to have occurred before the youngest lava flow, the 10.5 million year old Elephant Mountain Member was emplaced above the Pomona Member

SPLUNC1 degradation by the cystic fibrosis mucosal environment drives airway surface liquid dehydration

The multi-organ disease cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR) that lead to diminished transepithelial anion transport. CF lungs are characterised by airway surface liquid (ASL) dehydration, chronic infection/inflammation and neutrophilia. Dysfunctional CFTR may upregulate the epithelial Na+ channel (ENaC), further exacerbating dehydration. We previously demonstrated that short palate lung and nasal epithelial clone 1 (SPLUNC1) negatively regulates ENaC in normal airway epithelia. Here, we used pulmonary tissue samples, sputum and human bronchial epithelial cells (HBECs) to determine whether SPLUNC1 could regulate ENaC in a CF-like environment. We found reduced endogenous SPLUNC1 in CF secretions, and rapid degradation of recombinant SPLUNC1 (rSPLUNC1) by CF secretions. Normal sputum, containing SPLUNC1 and SPLUNC1-derived peptides, inhibited ENaC in both normal and CF HBECs. Conversely, CF sputum activated ENaC, and rSPLUNC1 could not reverse this phenomenon. Additionally, we observed upregulation of ENaC protein levels in human CF bronchi. Unlike SPLUNC1, the novel SPLUNC1-derived peptide SPX-101 resisted protease degradation, bound apically to HBECs, inhibited ENaC and prevented ASL dehydration following extended pre-incubation with CF sputum. Our data indicate that CF mucosal secretions drive ASL hyperabsorption and that protease-resistant peptides, e.g. SPX-101, can reverse this effect to rehydrate CF ASL

Mechanistic Basis for the Failure of Cone Transducin to Translocate: Why Cones Are Never Blinded by Light

The remarkable ability of our vision to function under ever-changing conditions of ambient illumination is mediated by multiple molecular mechanisms regulating the light-sensitivity of rods and cones. One such mechanism involves massive translocation of signaling proteins, including the G protein transducin, into and out of the light-sensitive photoreceptor outer segment compartment. Transducin translocation extends the operating range of rods, but in cones transducin never translocates, which is puzzling because cones typically function in much brighter light than rods. Using genetically manipulated mice in which the rates of transducin activation and inactivation were altered, we demonstrate that, like in rods, transducin translocation in cones can be triggered when transducin activation exceeds a critical level essentially saturating the photoresponse. However, this level is never achieved in wild type cones: their superior ability to tightly control the rates of transducin activation and inactivation, responsible for avoiding saturation by light, also accounts for prevention of transducin translocation at any light intensity

A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope.

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission. OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB). DESIGN: Prospective, multicenter, comparative study. SETTING: Six academic hospitals. PATIENTS: A total of 105 patients with OGIB. INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion. MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination. RESULTS: Data analysis resulted in 43 (48%) abnormal cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P \u3c .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10). LIMITATIONS: Readers were not blinded to the particular capsule they were reading. CONCLUSION: A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. (Clinical trial registration number: NCT00878982.)

Bilateral cystoid macular edema following docetaxel chemotherapy in a patient with retinitis pigmentosa: a case report.

BACKGROUND: Docetaxel is a chemotherapeutic agent of the taxane class of drugs for the treatment of breast cancer. We present a female patient who noted decreased vision after docetaxel treatment. CASE PRESENTATION: A 45-year-old female patient received docetaxel treatment after resection of a breast carcinoma. Funduscopy and optical coherence tomography (OCT) showed cystoid macular edema on both eyes. Dilated funduscopy also showed bone spicule-like pigmented deposits, typical for retinitis pigmentosa. Besides the fundus appearance restricted peripheral vision and scotopic electroretinogram confirmed the diagnosis of retinitis pigmentosa. Chemotherapy was discontinued following a consulation with the oncologist of the patient. After five weeks, visual acuity improved significantly along with decrease of retinal thickness measured by OCT. CONCLUSION: Docetaxel may cause ocular adverse effects such as cystoid macular edema. Ophthalmological examination is warranted for patients with visual complaints during docetaxel chemotherapy

Pilot study of an interactive voice response system to improve medication refill compliance

<p>Abstract</p> <p>Background</p> <p>Sub-optimal adherence to prescribed medications is well documented. Barriers to medication adherence include medication side effects, cost, and forgetting to take or refill medications. Interactive Voice Response (IVR) systems show promise as a tool for reminding individuals to take or refill medications. This pilot study evaluated the feasibility and acceptability of using an IVR system for prescription refill and daily medication reminders. We tested two novel features: personalized, medication-specific reminder messages and communication via voice recognition.</p> <p>Methods</p> <p>Patients enrolled in a study of electronic prescribing and medication management in Quebec, Canada who were taking chronic disease-related drugs were eligible to participate. Consenting patients had their demographic, telephone, and medication information transferred to an IVR system, which telephoned patients to remind them to take mediations and/or refill their prescriptions. Facilitators and barriers of the IVR system use and acceptability of the IVR system were assessed through a structured survey and open-ended questions administered by telephone interview.</p> <p>Results</p> <p>Of the 528 eligible patients who were contacted, 237 refused and 291 consented; 99 participants had started the pilot study when it was terminated because of physician and participant complaints. Thirty-eight participants completed the follow-up interview. The majority found the IVR system's voice acceptable, and did not have problems setting up the time and location of reminder calls. However, many participants experienced technical problems when called for reminders, such as incorrect time of calls and voice recognition difficulties. In addition, most participants had already refilled their prescriptions when they received the reminder calls, reporting that they did not have difficulties remembering to refill prescriptions on their own. Also, participants were not receptive to speaking to an automated voice system.</p> <p>Conclusion</p> <p>IVR systems designed to improve medication compliance must address key technical and performance issues and target those individuals with reported memory difficulties or complex medication regimens in order to improve the utility of the system. Future research should also identify characteristics of medication users who are more likely to be receptive to IVR technology.</p

Affective processes as network hubs

The practical problems of designing and coding a web-based flight simulator for teachers has led to a ‘three-tier plus environment’ model (COVE model) for a software agent’s cognition (C), psychologicsal (O), physical (V) processes and responses to tasks and interpersonal relationships within a learning environment (E). The purpose of this article is to introduce how some of the COVE model layers represent preconscious processing hubs in an AI human-agent’s representation of learning in a serious game, and how an application of the Five Factor Model of psychology in the O layer determines the scope of dimensions for a practical computational model of affective processes. The article illustrates the model with the classroom-learning context of the simSchool application (www.simschool.org); presents details of the COVE model of an agent’s reactions to academic tasks; discusses the theoretical foundations; and outlines the research-based real world impacts from external validation studies as well as new testable hypotheses of simSchool

On Distant Speech Recognition for Home Automation

The official version of this draft is available at Springer via http://dx.doi.org/10.1007/978-3-319-16226-3_7International audienceIn the framework of Ambient Assisted Living, home automation may be a solution for helping elderly people living alone at home. This study is part of the Sweet-Home project which aims at developing a new home automation system based on voice command to improve support and well-being of people in loss of autonomy. The goal of the study is vocal order recognition with a focus on two aspects: distance speech recognition and sentence spotting. Several ASR techniques were evaluated on a realistic corpus acquired in a 4-room flat equipped with microphones set in the ceiling. This distant speech French corpus was recorded with 21 speakers who acted scenarios of activities of daily living. Techniques acting at the decoding stage, such as our novel approach called Driven Decoding Algorithm (DDA), gave better speech recognition results than the baseline and other approaches. This solution which uses the two best SNR channels and a priori knowledge (voice commands and distress sentences) has demonstrated an increase in recognition rate without introducing false alarms