Quinolone Allergy

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available

Uncovering Shakespeare\u27s Sisters in Special Collections and College Archives, Musselman Library

Foreword by Professor Suzanne J. Flynn I have taught the first-year seminar, Shakespeare’s Sisters, several times, and over the years I have brought the seminar’s students to the Folger Shakespeare Library in Washington, D.C. There, the wonderful librarians have treated the students to a special exhibit of early women’s manuscripts and first editions, beginning with letters written by Elizabeth I and proceeding through important works by seventeen and eighteenth-century women authors such as Aemelia Lanyer, Anne Finch, Aphra Behn, and Mary Wollstonecraft. This year I worked with Carolyn Sautter, the Director of Special Collections and College Archives, to give my 2018 seminar students the opportunity to produce a sequel to the Folger exhibit of early modern women writers. Special Collections houses an impressive array of first editions from the nineteenth and twentieth centuries, many of them acquired from Thomas Y. Cooper, the former editor of the Hanover Evening Sun newspaper, who donated over 1600 items to Musselman Library in 1965. Working with Kerri Odess-Harnish, we chose first editions of eight significant works of literature written by American and British women from the mid-nineteenth through the mid-twentieth centuries. The students worked in pairs, researching a single book and producing a report that outlines important biographical facts about the author, the book’s publication and reception history, and finally the significance of the book in the years since its publication. We hope that our project will draw attention to the wealth of literary treasures housed in Special Collections at Musselman Library, but especially to these works by eight of “Shakespeare’s Sisters.

L'équipe d’aide et de sensibilisation aux opioïdes : un exemple novateur d'éducation médicale et de partenariat communautaire

Implication Statement  The Opioid Awareness and Support Team (OAST) at the Memorial University Faculty of Medicine is a novel student-led initiative designed to supplement medical student learning related to opioid use disorder and the opioids crisis. OAST has focused on grounding educational initiatives related to opioid use disorder in the local community context, working with community partners, and bringing in individuals with lived experience. We present initial findings from an Opioid Education Day that suggest student-led supplemental education for medical students can improve student knowledge surrounding opioid use.Énoncé des implications de la recherche L’équipe d’aide et de sensibilisation aux opioïdes (OAST) est une initiative des étudiants de la faculté de médecine de l’Université Memorial qui apporte un complément à la formation que reçoivent les étudiants sur le trouble lié à l’usage d’opioïdes. L'OAST s'est efforcée d’inscrire les initiatives éducatives liées à la crise des opïodes dans un contexte local en collaboration avec des partenaires communautaires et de faire participer des personnes ayant une expérience de terrain. Nous présentons les résultats préliminaires d'une journée de sensibilisation aux opioïdes qui suggèrent que cette activité éducative menée par les étudiants en médecine peut améliorer les connaissances des apprenants sur la consommation d’opioïdes

AAK1 Identified as an Inhibitor of Neuregulin-1/ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics

SummaryTarget identification remains challenging for the field of chemical biology. We describe an integrative chemical genomic and proteomic approach combining the use of differentially active analogs of small molecule probes with stable isotope labeling by amino acids in cell culture-mediated affinity enrichment, followed by subsequent testing of candidate targets using RNA interference-mediated gene silencing. We applied this approach to characterizing the natural product K252a and its ability to potentiate neuregulin-1 (Nrg1)/ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)-dependent neurotrophic factor signaling and neuritogenesis. We show that AAK1 (adaptor-associated kinase 1) is a relevant target of K252a, and that the loss of AAK1 alters ErbB4 trafficking and expression levels, providing evidence for a previously unrecognized role for AAK1 in Nrg1-mediated neurotrophic factor signaling. Similar strategies should lead to the discovery of novel targets for therapeutic development

Evidence for multiple rhythmic skills

Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

<p>Abstract</p> <p>Background</p> <p>Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity).</p> <p>Results</p> <p>To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties.</p> <p>Conclusions</p> <p>Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.</p