Restructuring of olfactory representations in the fly brain around odor relationships in natural sources.

A core challenge of olfactory neuroscience is to understand how neural representations of odor are generated and progressively transformed across different layers of the olfactory circuit into formats that support perception and behavior. The encoding of odor by odorant receptors in the input layer of the olfactory system reflects, at least in part, the chemical relationships between odor compounds. Neural representations of odor in higher order associative olfactory areas, generated by random feedforward networks, are expected to largely preserve these input odor relationships1-3. We evaluated these ideas by examining how odors are represented at different stages of processing in the olfactory circuit of the vinegar fly D. melanogaster. We found that representations of odor in the mushroom body (MB), a third-order associative olfactory area in the fly brain, are indeed structured and invariant across flies. However, the structure of MB representational space diverged significantly from what is expected in a randomly connected network. In addition, odor relationships encoded in the MB were better correlated with a metric of the similarity of their distribution across natural sources compared to their similarity with respect to chemical features, and the converse was true for odor relationships encoded in primary olfactory receptor neurons (ORNs). Comparison of odor coding at primary, secondary, and tertiary layers of the circuit revealed that odors were significantly regrouped with respect to their representational similarity across successive stages of olfactory processing, with the largest changes occurring in the MB. The non-linear reorganization of odor relationships in the MB indicates that unappreciated structure exists in the fly olfactory circuit, and this structure may facilitate the generalization of odors with respect to their co-occurence in natural sources.

Valve-in-Mitral Annular Calcification Transcatheter Mitral Valve Replacement After Thrombosis of Extracardiac Valved Conduit.

We report a patient with severe mitral annular calcification, mitral stenosis/regurgitation, hypertrophic obstructive cardiomyopathy, and subaortic membrane treated with valved left atrium-left ventricle conduit, septal myectomy, and membrane resection. Subsequent thrombosis of the conduit prompted successful valve-in- mitral annular calcification transcatheter mitral valve replacement and laceration of the anterior mitral leaflet to prevent outflow obstruction. (Level of Difficulty: Advanced.).

Parallel encoding of CO2 in attractive and aversive glomeruli by selective lateral signaling between olfactory afferents.

We describe a novel form of selective crosstalk between specific classes of primary olfactory receptor neurons (ORNs) in the Drosophila antennal lobe. Neurotransmitter release from ORNs is driven by two distinct sources of excitation: direct activity derived from the odorant receptor and stimulus-selective lateral signals originating from stereotypic subsets of other ORNs. Consequently, the level of presynaptic neurotransmitter release from an ORN can be significantly dissociated from its firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO2-a behaviorally important environmental cue that directly excites a single ORN class-in multiple olfactory glomeruli, each with distinct response dynamics. CO2-sensitive glomeruli coupled to behavioral attraction respond preferentially to fast changes in CO2 concentration, whereas those coupled to behavioral aversion more closely follow absolute levels of CO2. Behavioral responses to CO2 also depend on the temporal structure of the stimulus: flies walk upwind to fluctuating, but not sustained, pulses of CO2. Stimulus-selective lateral signaling generalizes to additional odors and glomeruli, revealing a subnetwork of lateral interactions between ORNs that reshapes the spatial and temporal structure of odor representations in a stimulus-specific manner.

Omega-3 Fatty Acid Supplementation in the Primary and Secondary Prevention of Cardiovascular Events: NEW INSIGHTS.

Omega-3 fatty acid (O-3FA) supplementation has garnered interest since cardioprotective properties of dietary fish consumption were observed. In the general population, O-3FA supplementation has not improved cardiovascular outcomes. However, icosapent ethyl, a high-dose, purified form of eicosapentaenoic acid, has demonstrated additive cardioprotection to statins in high-risk patients with elevated triglycerides.

Hydroxychloroquine/Azithromycin Therapy and QT Prolongation in Hospitalized Patients With COVID-19.

OBJECTIVES: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM). BACKGROUND: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population. METHODS: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. RESULTS: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed. CONCLUSIONS: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.

Transthoracic echocardiographic findings in patients admitted with SARS-CoV-2 infection.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients commonly have elevated troponin and D-dimer levels, but limited imaging exists to support most likely etiologies in efforts to avoid staff exposure. The purpose of this study was to report transthoracic echocardiographic (TTE) findings in SARS-CoV-2 patients with correlating troponin and D-dimer levels. METHODS: We identified 66 SARS-CoV-2 patients (mean age 60 ± 15.7 years) admitted within a large, eight-hospital healthcare system over a 6-week period with a TTE performed. TTE readers were blinded to laboratory data with intra-observer and inter-observer analysis assessed. RESULTS: Sixty-six of 1780 SARS-CoV-2 patients were included and represented a high-risk population as 38 (57.6%) were ICU-admitted, 47 (71.2%) had elevated D-dimer, 41 (62.1%) had elevated troponin, and 25 (37.9%) died. Right ventricular (RV) dilation was present in 49 (74.2%) patients. The incidence and average D-dimer elevation was similar between moderate/severe vs. mild/no RV dilation (69.6% vs 67.6%, P = 1.0; 3736 ± 2986 vs 4141 ± 3351 ng/mL, P = .679). Increased left ventricular (LV) wall thickness was present in 46 (69.7%) with similar incidence of elevated troponin and average troponin levels compared to normal wall thickness (66.7% vs 52.4%, P = .231; 0.88 ± 1.9 vs 1.36 ± 2.4 ng/mL, P = .772). LV dilation was rare (n = 6, 9.1%), as was newly reduced LV ejection fraction (n = 2, 3.0%). CONCLUSION: TTE in SARS-CoV-2 patients is scarce, technically difficult, and reserved for high-risk patients. RV dilation is common in SARS-CoV-2 but does not correlate with elevated D-dimer levels. Increased LV wall thickness is common, while newly reduced LV ejection fraction is rare, and neither correlates with troponin levels.

Impact of Emergency Medical Services Activation of the Cardiac Catheterization Laboratory and a 24-Hour/Day In-Hospital Interventional Cardiology Team on Treatment Times (Door to Balloon and Medical Contact to Balloon) for ST-Elevation Myocardial Infarction.

The incremental benefit of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for ST-elevation myocardial infarction (STEMI) in the setting of an established in-house interventional team (IHIT) is uncertain. We evaluated the impact of EMS activation on door-to-balloon (D2B) time and first medical contact-to-balloon (FMC2B) time for STEMI when coupled with a 24-hour/day IHIT. All patients presenting with STEMI to Loyola University Medical Center had demographic, procedural, and outcome data consecutively entered in a STEMI Data Registry. From 223 consecutive patients presenting between April 2009 and December 2015, a retrospective analysis was performed on 190 patients. Patients were divided into 2 groups depending on CCL activation mode (EMS activation or emergency department activation) and STEMI treatment process times were compared. The primary end point was D2B process times. The secondary end point was FMC2B process times in a subgroup analysis of EMS-transported patients. D2B times were shorter (37 ± 14 minutes vs 57 ± 27 minutes, p < 0.001) with EMS activation. Subgroup analysis of EMS-transported patients demonstrated shorter FMC2B times with EMS activation (52 ± 17 minutes vs 67 ± 32 minutes, p = 0.002). EMS activation was the only predictor of D2B ≤60 minutes in multivariable analysis of EMS-transported patients (odds ratio 9.4; 95% confidence interval 2.1 to 43.0; p = 0.04). In conclusion, EMS activation of the CCL in STEMI was associated with significant improvements in already excellent D2B and FMC2B times even in the setting of a 24-hour/day IHIT.

A National Longitudinal Survey of Medical Students' Intentions to Practice Among the Underserved.

PURPOSE: To explore students' intentions to practice in medically underserved areas. METHOD: In January 2011, 960 third-year medical students from 24 MD-granting U.S. medical schools were invited to participate in a survey on their intention to practice in a medically underserved area. A follow-up survey was sent to participants in September 2011. Covariates included student demographics, medical school characteristics, environmental exposures, work experiences, sense of calling, and religious characteristics. RESULTS: Adjusted response rates were 564/919 (61.4%, first survey) and 474/564 (84.0%, follow-up survey). Among fourth-year medical students, an estimated 34.3% had an intention to practice among the underserved. In multivariate logistic regression modeling, predictors for intentions to practice among the underserved included growing up in an underserved setting (odds ratio [OR] range: 2.96-4.81), very strong sense of calling (OR range: 1.86-3.89), and high medical school social mission score (in fourth year: OR = 2.34 [95% confidence interval (CI), 1.31-4.21]). International experience was associated with favorable change of mind in the fourth year (OR = 2.86 [95% CI, 1.13-7.24]). High intrinsic religiosity was associated with intentions to practice primary care in underserved settings (in fourth year: OR = 2.29 [95% CI = 1.13-4.64]). CONCLUSIONS: Growing up in medically underserved settings, work experience in religiously affiliated organizations, very strong sense of calling, and high medical school social mission score were associated with intentions to practice in underserved areas. Lack of formative educational experiences may dissuade students from considering underserved practice.

Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.