Profile of etravirine for the treatment of HIV infection

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with the advantages of in vitro potency against many strains of virus resistant to efavirenz and nevirapine, as well as a higher genetic barrier to resistance. Etravirine is indicated for use in treatment-experienced patients, and the approved dose in adults is 200 mg twice daily. Etravirine should be administered after a meal as bioavailability is significantly reduced when taken in the fasting state. Etravirine is a substrate of CYP3A4, CYP2C9, CYP2C19, and uridine diphosphate glucuronyltransferase, and induces CYP3A4, weakly inhibits CYP2C9 and moderately inhibits CYP2C19. Etravirine may be coadministered with nucleoside/tide reverse transcriptase inhibitors, raltegravir and boosted darunavir, lopinavir, and saquinavir without dosage adjustment. Etravirine should not be given with other NNRTIs, unboosted protease inhibitors, and atazanavir/ritonavir, tipranavir/ritonavir, and fosamprenavir/ritonavir due to unfavorable drug interactions. In randomized, controlled trials, twice daily etravirine combined with darunavir/ritonavir plus optimized background therapy demonstrated better efficacy compared to darunavir/ritonavir plus optimized background therapy alone in treatment-experienced populations out to 96 weeks follow-up. The main etravirine-associated toxicity is mild to moderate self-limiting rash, although severe and sometimes fatal hypersensitivity reactions have been reported. Etravirine offers a potent sequencing option after the development of resistance to first-line NNRTIs, and is a welcome addition to this established drug class

Séance d’apprentissage interprofessionnel animée par un pharmacien pour les résidents en médecine familiale spécialisés dans les soins liés au VIH

Implication Statement We developed a pharmacist-led one-month teaching rotation for medical residents to learn HIV pharmacotherapy.  This interprofessional education (IPE) was deemed extremely valuable by postgraduate-year-3 residents who intended to have a future practice in HIV care.  The overarching concept of this rotation was for the medical trainee to “become-the-pharmacist”, learning to recognize, prevent, and manage drug-related issues in HIV patients.  Pharmacist-led IPE should be considered to support medical training in other highly specialized pharmacotherapeutic areas.Énoncé des implications de la recherche Nous avons mis au point une formation sur la pharmacothérapie du VIH, présentée par un pharmacien, pour les résidents en médecine de troisième année. Ces derniers ont trouvé cette expérience d’apprentissage interprofessionnel extrêmement précieuse pour leurs interventions futures dans le traitement du VIH. Le concept au cœur de cette rotation d’une durée d’un mois était de mettre les stagiaires en médecine dans la peau du pharmacien pour leur apprendre à reconnaître, à prévenir et à gérer les problèmes liés à la prise de médicaments chez les patients séropositifs. Nous recommandons la formule d’apprentissage interprofessionnel mené par un pharmacien pour appuyer la formation médicale dans les domaines hautement spécialisés de la pharmacothérapie

Dome-Shaped Ellipsoidal Reflector Antenna for UHF-RFID Readers with Confined Near-Field Detection Region

This letter proposes and demonstrates the concept of ellipsoidal reflector antennas for radio frequency identification reader applications at UHF band. The antenna can be potentially integrated with environmental structures to confine the reader detection region. The energy bounding characteristics result from the dual-focus feature of an ellipsoidal reflector in its near-field region, as the feed located at one of the two foci can create a focused field distribution around the other focus. An axial energy focusing is, thus, formed to confine the energy in a restricted region (near-field beam focusing), also minimizing the interference effects outside of the targeted area. Both numerical simulations and experimental results are presented to demonstrate the feasibility of this antenna concept

Timing of births and oral contraceptive use influences ovarian cancer risk

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139076/1/ijc30910_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139076/2/ijc30910.pd

Assessing, quantifying and valuing the ecosystem services of coastal lagoons

The natural conservation of coastal lagoons is important not only for their ecological importance, but also because of the valuable ecosystem services they provide for human welfare and wellbeing. Coastal lagoons are shallow semi-enclosed systems that support important habitats such as wetlands, mangroves, salt-marshes and seagrass meadows, as well as a rich biodiversity. Coastal lagoons are also complex social-ecological systems with ecosystem services that provide livelihoods, wellbeing and welfare to humans. This study assessed, quantified and valued the ecosystem services of 32 coastal lagoons. The main findings of the study are: (i) the definitions of ecosystem services are still not generally accepted; (ii) the quantification of ecosystem services is made in many different ways, using different units; (iii) the evaluation in monetary terms of some ecosystem service is problematic, often relying on non-monetary evaluation methods; (iv) when ecosystem services are valued in monetary terms, this may represent very different human benefits; and, (v) different aspects of climate change, including increasing temperature, sea-level rise and changes in rainfall patterns threaten the valuable ecosystem services of coastal lagoons.DEVOTES project, from the European Union's Seventh Framework Programme for research, technological development and demonstration [308392]; networks and communities of Eurolag; Future Earth Coasts; SCOR; Fundacao para a Ciencia e a Tecnologia (FCT) Investigador Programme [IF/00331/2013]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; CESAM by FCT/MEC national funds (PIDDAC) [UID/AMB/50017/2013 - POCI-01-0145-FEDER-007638]; FEDER; European Commission, under the 7th Framework Programme through the collaborative research project LAGOONS [283157]; FCT [SFRH/BPD/107823/2015, SFRH/BPD/91494/2012

CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens

The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen article

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Auditory Function in the Tc1 Mouse Model of Down Syndrome Suggests a Limited Region of Human Chromosome 21 Involved in Otitis Media

Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21) in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR) measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs) were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K+ currents characteristic of control hair cells. However, the size of the large conductance (BK) Ca2+ activated K+ current (IK,f), which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe