Listening and spoken language outcomes after 5 years of cochlear implant use for children born preterm and at term.

AIM: To compare listening and spoken language outcomes after cochlear implantation for children born preterm and at term, and to examine patterns associated with additional disabilities or gestational age. METHOD: Children were included if they underwent cochlear implantation in 2013 or 2014 and had complete 5-year follow-up data available. An analysis of assessment data recorded annually was conducted, including outcomes as measured by the Category of Auditory Performance (CAP), the Speech Intelligibility Rating, Second Edition (SIR 2) scale, and the British Picture Vocabulary Scales, Third Edition (BPVS-3). Analyses were conducted to measure the impact of preterm birth and of additional causes of disability on these outcomes. RESULTS: Eighty-two children (39 males, 43 females; median corrected age at first cochlear implantation 28.5mo [interquartile range 16.3-48.5]) were included in the study. Children who underwent cochlear implantation experienced significant improvements as measured by the CAP, SIR 2, and BPVS-3. Comparable improvements were seen in the groups born at term and preterm. Children with additional disabilities experienced significant improvement in all measures but performed less well than children without additional disabilities. INTERPRETATION: Infants born preterm benefit from cochlear implantation to a degree comparable to their peers born at term. Additional disabilities may limit improvements in speech intelligibility, listening performance, and receptive vocabulary. Children with additional disabilities, nonetheless, derived significant benefit from cochlear implantation; additional benefits of cochlear implantation for this subgroup may go unmeasured by the outcome tools used in this study.

Glamorized Exploitation: Visual Images of Meiji-Period "Factory Girls" (joko).

The cover image of this issue of Technology and Culture is a collage crafted from two figures in this essay. On the right side of the image is a detail of a black and white photograph from around 1900 of female silk mill workers () juxtaposed on the left with detail of a color woodblock print from 1877 depicting a mock-up of the Tomioka silk mill featured in an industrial exposition staged that year in Tokyo (). The collage was composed by reversing the two figures to create a dynamic "V" designed to draw the viewer's eye from left to right and, by implication, from the glamorized rendition of silk mill work in the woodblock print to a more real-world photograph documenting actual working conditions in a silk mill. This essay provides a socio-historical matrix for, and critical analysis of, representative visual images of sericulture and silk mills.

TIGIT regulates apoptosis of risky memory T cell subsets implicated in belatacept-resistant rejection.

Belatacept confers increased patient and graft survival in renal transplant recipients relative to calcineurin inhibitors, but is associated with an increased rate of acute rejection. Recent immunophenotypic studies comparing pretransplant T cell phenotypes of patients who reject versus those who remain stable on belatacept identified three potential "risky" memory T cell subsets that potentially underlie belatacept-resistant rejection: CD4+ CD28+ TEM , CD8+ CD28null , and CD4+ CD57+ PD1- subsets. Here, we compared key phenotypic and functional aspects of these human memory T cell subsets, with the goal of identifying additional potential targets to modulate them. Results demonstrate that TIGIT, an increasingly well-appreciated immune checkpoint receptor, was expressed on all three risky memory T cell subsets in vitro and in vivo in the presence of belatacept. Coculture of human memory CD4+ and CD8+ T cells with an agonistic anti-TIGIT mAb significantly increased apoptotic cell death of all three risky memory T cell subsets. Mechanistically, TIGIT-mediated apoptosis of risky memory T cells was dependent on FOXP3+ Treg, suggesting that agonism of the TIGIT pathway increases FOXP3+ Treg suppression of human memory T cell populations. Overall, these data suggest that TIGIT agonism could represent a new therapeutic target to inhibit belatacept-resistant rejection during transplantation.

Every 2-month belatacept maintenance therapy in kidney transplant recipients greater than 1-year posttransplant: A randomized, noninferiority trial.

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).

Preliminary Characterization of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity.

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug-resistant fungi, toxicity, and drug-drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida, Aspergillus, and Cryptococcus, as well as others. NP339 was designed based on endogenous cationic human defense peptides, which are constituents of the cornerstone of immune defense against pathogenic microbes. NP339 specifically targets the fungal cell membrane through a charge-charge-initiated membrane interaction and therefore possesses a differentiated safety and toxicity profile to existing antifungal classes. NP339 is rapidly fungicidal and does not elicit resistance in target fungi upon extensive passaging in vitro. Preliminary analyses in murine models indicate scope for therapeutic application of NP339 against a range of systemic and mucocutaneous fungal infections. Collectively, these data indicate that NP339 can be developed into a highly differentiated, first-in-class antifungal candidate for poorly served invasive and other serious fungal diseases.

Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.

OBJECTIVE: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS). METHODS: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review. RESULTS: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine. CONCLUSIONS: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.

Longer-Term Impact of the Flavored Tobacco Restriction in Two Massachusetts Communities: A Mixed-Methods Study.

INTRODUCTION: In response to high rates of youth tobacco use, many states and localities are considering regulations on flavored tobacco products. The purpose of this study was to assess whether flavored tobacco restrictions (FTRs) in Massachusetts curb youth tobacco use over time and whether a dose-response effect of length of policy implementation on tobacco-related outcomes exists. AIMS AND METHODS: Using a quasiexperimental design, two municipalities with a FTR (adopting municipalities) were matched to a comparison municipality without a FTR. Surveys were administered before (December 2015) and after (January and February 2018) policy implementation to high school students in these municipalities (more than 2000 surveys completed at both timepoints). At follow-up, adopting municipalities had a policy in place for 1 and 2 years, respectively. In 2019, focus groups were conducted with high school students in each municipality. RESULTS: Increases seen in current tobacco use from baseline to follow-up were significantly smaller in adopting municipalities compared to the comparison (-9.4% [-14.2%, -4.6%] and -6.3% [-10.8%, -1.8%], respectively). However, policy impact was greater in one adopting municipality despite shorter length of implementation. Focus groups indicated reasons for differential impact, including proximity to localities without FTRs. CONCLUSIONS: Restrictions implemented in adopting municipalities had positive impacts on youth tobacco awareness and use 1-2 years postimplementation. Policy impact varies depending on remaining points of access to flavored tobacco, as such policy effectiveness may increase as more localities restrict these products. IMPLICATIONS: In response to high rates of youth flavored tobacco use (including flavored vape products), federal, state, and localities have passed FTRs that reduce availability of flavored tobacco in youth-accessible stores. Previous research has found that FTRs may curb youth tobacco use in the short-term; however, the long-term effectiveness remains unknown.This is the first study to show FTRs can curb youth tobacco use and reduce youth awareness of tobacco prices and brands even 2 years after policy passage. Municipality-specific factors, including proximity to localities without FTRs, may attenuate policy impact, highlighting the importance of widespread policy adoption.

Type I IFN signaling blockade by a PASylated antagonist during chronic SIV infection suppresses specific inflammatory pathways but does not alter T cell activation or virus replication.

Chronic activation of the immune system in HIV infection is one of the strongest predictors of morbidity and mortality. As such, approaches that reduce immune activation have received considerable interest. Previously, we demonstrated that administration of a type I interferon receptor antagonist (IFN-1ant) during acute SIV infection of rhesus macaques results in increased virus replication and accelerated disease progression. Here, we administered a long half-life PASylated IFN-1ant to ART-treated and ART-naïve macaques during chronic SIV infection and measured expression of interferon stimulated genes (ISG) by RNA sequencing, plasma viremia, plasma cytokines, T cell activation and exhaustion as well as cell-associated virus in CD4 T cell subsets sorted from peripheral blood and lymph nodes. Our study shows that IFN-1ant administration in both ART-suppressed and ART-untreated chronically SIV-infected animals successfully results in reduction of IFN-I-mediated inflammation as defined by reduced expression of ISGs but had no effect on plasma levels of IL-1ß, IL-1ra, IL-6 and IL-8. Unlike in acute SIV infection, we observed no significant increase in plasma viremia up to 25 weeks after IFN-1ant administration or up to 15 weeks after ART interruption. Likewise, cell-associated virus measured by SIV gag DNA copies was similar between IFN-1ant and placebo groups. In addition, evaluation of T cell activation and exhaustion by surface expression of CD38, HLA-DR, Ki67, LAG-3, PD-1 and TIGIT, as well as transcriptome analysis showed no effect of IFN-I blockade. Thus, our data show that blocking IFN-I signaling during chronic SIV infection suppresses IFN-I-related inflammatory pathways without increasing virus replication, and thus may constitute a safe therapeutic intervention in chronic HIV infection.

NP213 (Novexatin®): A unique therapy candidate for onychomycosis with a differentiated safety and efficacy profile.

NP213 (Novexatin®) is a novel antifungal peptide specifically designed for the topical treatment of onychomycosis. NP213 was designed using host defense peptides (HDP), essential components of the innate immune response to infection, as a template. NP213 is a water-soluble cyclic fungicidal peptide that effectively penetrates human nail. NP213 demonstrated a promising preclinical and clinical safety profile, with no evidence of systemic exposure following topical application to the skin and nails. NP213 was efficacious in two phase IIa human trials with 43.3% of patients having no fungi detectable by culture of fragments from NP213-treated nails after 180 days in the first study and likewise 56.5% of patients were culture negative for dermatophytes after 360 days in the second phase IIa study. In both trials, NP213 was applied daily for only 28 days in marked contrast to other topical onychomycosis treatments that require application for up to 52 weeks. Patient reported outcomes from the phase IIa studies were positive with participants recording an improved appearance of their nails after only 14 days of application. All fungi identified in these studies were Trichophyton spp. NP213 (Novexatin®) is a promising, highly differentiated peptide-based candidate for the topical treatment of onychomycosis, addressing the infectious cause and cosmetic issues of this very common condition.

Impact of flavoured tobacco restriction policies on flavoured product availability in Massachusetts.

OBJECTIVE: This study aimed to evaluate the effectiveness of flavoured tobacco product restriction policies in reducing availability of flavoured products in Massachusetts communities. METHODS: Data were obtained from surveys of tobacco retailers conducted from July 2015 to March 2017. On a community level, flavoured product availability was defined as the per cent of retailers during a given 3-month quarter that sold flavoured cigars/cigarillos, electronic cigarettes and/or e-liquids. Communities that implemented the policy during the study period were grouped into wave 1 (n=18; 1481 retail surveys) and wave 2 (n=20; 483 retail surveys) by date of policy implementation; communities without a flavoured product restriction served as the control group (n=234; 4932 retail surveys). A difference-in-difference analysis was used to compare the change in flavoured product availability in wave 1 and wave 2 communities 3 months pre-policy and post-policy implementation to the change over the same time periods in the control group. RESULTS: From pre-policy to post-policy implementation period, communities in both waves experienced significant reductions in flavoured product availability (ranging from 27.2% to 50.9%), even after adjusting for community-level characteristics. In both waves 1 and 2, reductions in flavoured product availability were significantly greater compared with comparison communities during the same time frame, adjusting for community-level characteristics. CONCLUSIONS: Compliance with flavoured product restriction policies is high among tobacco retailers throughout Massachusetts, regardless of community demographic and retail characteristics. Reduced availability of flavoured tobacco in the retail environment has the potential to reduce youth exposure, access and use of these products.

Evaluating tobacco retailer experience and compliance with a flavoured tobacco product restriction in Boston, Massachusetts: impact on product availability, advertisement and consumer demand.

BACKGROUND: Flavoured tobacco products are widely available in youth-accessible retailers and are associated with increased youth initiation and use. The city of Boston, Massachusetts restricted the sale of flavoured tobacco products, including cigars, smokeless tobacco and e-cigarettes, to adult-only retailers. This paper describes the impact of the restriction on product availability, advertisement and consumer demand. METHODS: Between January and December 2016, data were collected in 488 retailers in Boston at baseline and 469 retailers at 8-month follow-up, measuring the type, brand and flavour of tobacco products being sold. Process measures detailing the educational enforcement process, and retailer experience were also captured. McNemar tests and t-tests were used to assess the impact of the restriction on product availability. RESULTS: After policy implementation, only 14.4% of youth-accessible retailers sold flavoured products compared with 100% of retailers at baseline (p<0.001). Flavoured tobacco product advertisements decreased from being present at 58.9% of retailers to 28.0% at follow-up (p<0.001). Postimplementation, retailers sold fewer total flavoured products, with remaining products often considered as concept flavours (eg, jazz, blue). At follow-up, 64.0% of retailers reported that customers only asked for flavoured products a few times a week or did not ask at all. Retailers reported that educational visits and the flavoured product guidance list aided with compliance. CONCLUSION: Tobacco retailers across Boston were largely in compliance with the regulation. Availability of flavoured tobacco products in youth-accessible retailers declined city-wide after policy implementation. Strong educational and enforcement infrastructure may greatly enhance retailer compliance.

T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy.

BACKGROUND: Uremic cardiomyopathy, characterized by left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, contributes to increased cardiovascular mortality in patients with CKD. Emerging evidence suggests a pathogenic role for T cells during chronic heart failure. METHODS: To determine whether T cells contribute to uremic cardiomyopathy pathogenesis, we modeled this condition by inducing CKD via 5/6th nephrectomy in mice. We used flow cytometry to assess expression of markers of T cell memory or activation by lymphocytes from CKD mice and controls, as well as lymphocyte capacity for cytokine production. Flow cytometry was also used to quantify immune cells isolated from heart tissue. To test effects of T cell depletion on cardiac function, we gave CKD mice anti-CD3 antibody injections to deplete T cells and compared heart function (assessed by echocardiography) with that of controls. Finally, we correlated T cell phenotypes with structural and functional measures on clinically acquired echocardiograms in children with CKD. RESULTS: Mice with CKD accumulated T cells bearing markers of memory differentiation (CD44hi) and activation (PD-1, KLRG1, OX40), as reported previously in human CKD. In addition, mice with CKD showed T cells infiltrating the heart. T cell depletion significantly improved both diastolic function and myocardial strain in CKD mice without altering hypertension or degree of renal dysfunction. In children with CKD, increasing frequency of T cells bearing activation markers PD-1 and/or CD57 was associated with worsening diastolic function on echocardiogram. CONCLUSIONS: CKD results in an accumulation of proinflammatory T cells that appears to contribute to myocardial dysfunction.

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation.

A majority of kidney transplant recipients receive calcineurin inhibitor-based immunosuppression. However, some do not tolerate calcineurin inhibitors and require other immunosuppressive strategies. Until recently, alternative approaches have been associated with inferior outcomes, but recent methods have effectively utilized belatacept in calcineurin inhibitor-intolerant patients. Though promising, belatacept uptake has been limited by higher acute rejection rates, unavailability due to production shortages, and logistical challenges as a result of intravenous infusion requirements. Interestingly, its predecessor abatacept is clinically available in subcutaneous formulation to treat autoimmune disorders but has not been used in clinical transplantation. Here we report on a series of 9 calcineurin inhibitor-intolerant transplant recipients converted to abatacept early after transplant as rescue immunosuppression during periods of belatacept unavailability. Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients received abatacept for a median duration of 82 months with stable, long-term renal allograft function, a single cellular rejection episode, and no clinically apparent protective immunity concerns. Hence our findings suggest that future clinical studies utilizing abatacept either de novo or as conversion therapy in transplant recipients should be considered.

Improved Methods for Assessing Therapeutic Potential of Antifungal Agents against Dermatophytes and Their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate.

Onychomycosis is a common, difficult-to-treat nail infection that is mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects. The development of treatments for onychomycosis is challenging because standard in vitro tests are not predictive of antifungal efficacy within the nail. We have developed a new antifungal agent, NP213, for the treatment of onychomycosis. NP213 is based on endogenous host defense peptides produced within the nail. We compared the in vitro activity of NP213 and existing antifungal agents using conventional antimicrobial susceptibility test (AST) systems and more physiologically relevant models based on the human nail. We observed that the standard in vitro AST methodologies failed to predict the efficacy of antifungal agents within the nail. To address that, we present a more physiologically relevant modified AST method. This method, alongside other standard in vitro assessments of activity (including mechanism-of-action and time-of-kill studies), better reflected the activity of NP213 and other antifungal agents within the nail than standard in vitro AST methods. NP213 is a rapidly acting, fungicidal peptide that is superior to existing antifungal agents in vitro It penetrated the nail more effectively than other antifungals, as confirmed by using an optimized in vitro nail infection model. The data presented here support the current clinical development status of NP213 as a novel agent for treating onychomycosis. We propose that the modified tests developed and applied for NP213 characterization are the most relevant to use for screening any potential therapeutic candidates for onychomycosis.

Left ventricular assist devices and their complications: A review for emergency clinicians.

INTRODUCTION: End stage heart failure is associated with high mortality. However, recent developments such as the ventricular assist device (VAD) have improved patient outcomes, with left ventricular assist devices (LVAD) most commonly implanted. OBJECTIVE: This narrative review evaluates LVAD epidemiology, indications, normal function and components, and the assessment and management of complications in the emergency department (ED). DISCUSSION: The LVAD is a life-saving device in patients with severe heart failure. While first generation devices provided pulsatile flow, current LVAD devices produce continuous flow. Normal components include the pump, inflow and outflow cannulas, driveline, and external controller. Complications related to the LVAD can be divided into those that are LVAD-specific and LVAD-associated, and many of these complications can result in severe patient morbidity and mortality. LVAD-specific complications include device malfunction/failure, pump thrombosis, and suction event, while LVAD-associated complications include bleeding, cerebrovascular event, infection, right ventricular failure, dysrhythmia, and aortic regurgitation. Assessment of LVAD function, patient perfusion, and mean arterial pressure is needed upon presentation. Electrocardiogram and bedside ultrasound are key evaluations in the ED. LVAD evaluation and management require a team-based approach, and consultation with the LVAD specialist is recommended. CONCLUSION: Emergency clinician knowledge of LVAD function, components, and complications is integral in optimizing care of these patients.

Medicine's Shame Problem.

BACKGROUND: Physician mental health is an increasingly discussed topic. Despite the progress made regarding the discussion of physician mental health, these issues remain concerning. In particular, the discussion as to why these issues are so problematic remains limited. Contributors can include bullying, the "hidden curriculum" of medicine, how the medical culture handles errors, and importantly, shame. OBJECTIVE: This narrative review evaluates the literature on bullying and abuse in medicine, how abuse can exacerbate shame, how the handling of medical errors can exacerbate shame, how shame can negatively affect mental health, and how the medical community and leaders can mitigate these issues. DISCUSSION: Physician mental health remains an important issue. Job-related stressors, bullying, medicine's hidden curriculum, medical error, traumatic patient encounters, and perfectionism can contribute to physician depression and burnout. Shame may underlie these factors. Shame is a universal emotion that leads to poor self-esteem, depression, eating disorders, abuse, and addiction. However, shame can be addressed and overcome, especially via acknowledgment, vulnerability, and empathy. The medical community can provide some of these techniques by encouraging environments of kindness and respect, giving constructive rather than destructive feedback, providing empathy and support after a medical error, and encouraging mutual learning environments where questions are asked with respect in order to enhance learning. This is opposed to hierarchies and "pimping," where questions are asked with intimidation and disrespect. CONCLUSIONS: Shame is likely a contributor to physician mental health issues. For shame resilience to occur, it must not be kept secret and mutual support should be provided. By addressing the possible causes behind physician mental health concerns, including shame, more solutions can be proposed.

Emergency Medicine Evaluation and Management of Small Bowel Obstruction: Evidence-Based Recommendations.

BACKGROUND: Small bowel obstruction (SBO) is a commonly diagnosed disease in the emergency department (ED). Recent literature has evaluated the ED investigation and management of SBO. OBJECTIVE: This review evaluates the ED investigation and management of adult SBO based on the current literature. DISCUSSION: SBO is most commonly due to occlusion of the small intestine, resulting in fluid and gas accumulation. This may progress to mucosal ischemia, necrosis, and perforation. A variety of etiologies are present, but in adults, adhesions are the most common cause. Several classification systems are present. However, the most important distinction is complete vs. partial and complicated vs. simple obstruction, as complete complicated SBO more commonly requires surgical intervention. History and physical examination can vary, but the most reliable findings include prior abdominal surgery, history of constipation, abdominal distension, and abnormal bowel sounds. Signs of strangulation include fever, hypotension, diffuse abdominal pain, peritonitis, and several others. Diagnosis typically requires imaging, and though plain radiographs are often ordered, they cannot exclude the diagnosis. Computed tomography and ultrasound are reliable diagnostic methods. Management includes intravenous fluid resuscitation, analgesia, and determining need for operative vs. nonoperative therapy. Nasogastric tube is useful for patients with significant distension and vomiting by removing contents proximal to the site of obstruction. Surgery is needed for strangulation and those that fail nonoperative therapy. Surgical service evaluation and admission are recommended. CONCLUSION: SBO is a common reason for admission from the ED. Knowledge of recent literature can optimize diagnosis and management.

Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection.

Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. It is known to have a biological role in oxidative stress, inflammation, and cell migration. There have been several reports demonstrating anti-infective properties targeting viruses, bacteria, and even the malarial parasite. We and others have previously described broad-spectrum antimicrobial and antibiofilm activities of cysteamine. Here, we go further to demonstrate redox-dependent mechanisms of action for the compound and how its antimicrobial effects are, at least in part, due to undermining bacterial defenses against oxidative and nitrosative challenges. We demonstrate the therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotics against a selection of priority antibiotic-resistant pathogens, including colistin (often considered an antibiotic of last resort), and we discuss how this endogenous antimicrobial component of innate immunity has a role in infectious disease that is beginning to be explored and is not yet fully understood.

Task dependence of odor discrimination: choosing between speed and accuracy.

Odor discrimination is a complex task that may be improved by increasing sampling time to facilitate evidence accumulation. However, experiments testing this phenomenon in olfaction have produced conflicting results. To resolve this disparity, Frederick et al. (Frederick DE, Brown A, Tacopina S, Mehta N, Vujovic M, Brim E, Amina T, Fixsen B, Kay LM. J Neurosci 37: 4416-4426, 2017) conducted experiments that suggest that sampling time and performance are task dependent. Their findings have implications for understanding olfactory processing and experimental design, specifically the effect of subtle differences in experimental design on study results.

Emergency medicine considerations in atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is an abnormal heart rhythm which may lead to stroke, heart failure, and death. Emergency physicians play a role in diagnosing AF, managing symptoms, and lessening complications from this dysrhythmia. OBJECTIVE: This review evaluates recent literature and addresses ED considerations in the management of AF. DISCUSSION: Emergency physicians should first assess patient clinical stability and evaluate and treat reversible causes. Immediate cardioversion is indicated in the hemodynamically unstable patient. The American Heart Association/American College of Cardiology, the European Society of Cardiology, and the Canadian Cardiovascular Society provide recommendations for management of AF. If hemodynamically stable, rate or rhythm control are options for management of AF. Physicians may opt for rate control with medications, with beta blockers and calcium channel blockers the predominant medications utilized in the ED. Patients with intact left ventricular function should be rate controlled to <110 beats per minute. Rhythm control is an option for patients who possess longer life expectancy and those with AF onset <48 h before presentation, anticoagulated for 3-4 weeks, or with transesophageal echocardiography demonstrating no intracardiac thrombus. Direct oral anticoagulants are a safe and reliable option for anticoagulation. Clinical judgment regarding disposition is recommended, but literature supports discharging stable patients who do not have certain comorbidities. CONCLUSION: Proper diagnosis and treatment of AF is essential to reduce complications. Treatment and overall management of AF include rate or rhythm control, cardioversion, anticoagulation, and admission versus discharge. This review discusses ED considerations regarding AF management.