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Examined agreement statistics (kappas) to assess the extent to which 2 groups of experts (those nominated by important peer scholars as having expertise in cultural competence and therapists with extensive experience and training in working with African Americans) agreed on the specific composition of constructs related to cultural competence. Using items from existing psychotherapy process measures, peer-nominated experts indicated whether each item was relevant to the construct of cultural competence. Therapists with expertise in treating African Americans indicated whether an item fit the same cultural competence categories generated through expert consensus. Peer nominated experts and therapist experts showed poor agreement (kappas) in their classification of which items were relevant to cultural competence. Despite poor overall agreement, however, the groups concurred that a small subset of items were relevant to culturally competent practice with African Americans. These results indicate the need for improved operationalization of the construct of cultural competence. [ABSTRACT FROM AUTHOR]

Context: In fiscal year 2019, the Department of Health and Human Services (DHHS) received an appropriation from Congress specifically to update guidelines for investigating community cancer concerns. This resulted in the DHHS directing the Centers for Disease Control and Prevention (CDC) to fulfill this responsibility., Program: The CDC and the Agency for Toxic Substances and Disease Registry (ATSDR) provide guidance to state, tribal, local, and territorial (STLT) health departments and play important roles in supporting STLT programs in addressing community cancer concerns., Implementation: The updated guidelines offer enhancements addressing limitations and challenges regarding the process for investigating cancer clusters as expressed by STLT programs responsible for responding to inquiries and by communities impacted by unusual patterns of cancer. Additionally, the updated guidelines offer new tools and approaches associated with scientific advancements. Issues associated with improving communications and community engagement were a priority. Details in the updated guidelines provide suggestions for building and maintaining trust; provide resources via additional tools, templates, and methodology to facilitate sharing of information; provide suggestions for identifying agency and community points of contacts; and provide suggestions for establishing a community advisory committee., Conclusion: Enhancements to the previous guidelines were included to address advancements in statistical approaches and methods for understanding exposure pathways and also to respond to limitations described in the previous guidelines. Furthermore, these enhancements ensure communities have a voice in the process and offer methods to enhance transparency throughout the investigative process. Ultimately, the 2022 Guidelines are designed to ensure that community engagement, community input, and communication remains paramount to the process of assessing unusual patterns of cancer and environmental concerns., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.

There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18-65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = -229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Evolution has created complex mechanisms to sense environmental danger and protect tissues, with the nervous and immune systems playing pivotal roles. These systems work together, coordinating local and systemic reflexes to restore homeostasis in response to tissue injury and infection. By sharing receptors and ligands, they influence the pathogenesis of various diseases. Recently, a less-explored aspect of neuroimmune communication has emerged: the release of neuropeptides from immune cells and cytokines/chemokines from sensory neurons. This article reviews evidence of this unique neuroimmune interplay and its impact on the development of allergy, inflammation, itch, and pain. We highlight the effects of this neuroimmune signaling on vital processes such as host defense, tissue repair, and inflammation resolution, providing avenues for exploration of the underlying mechanisms and therapeutic potential of this signaling., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Correlations between altered body temperature and depression have been reported in small samples; greater confidence in these associations would provide a rationale for further examining potential mechanisms of depression related to body temperature regulation. We sought to test the hypotheses that greater depression symptom severity is associated with (1) higher body temperature, (2) smaller differences between body temperature when awake versus asleep, and (3) lower diurnal body temperature amplitude. Data collected included both self-reported body temperature (using standard thermometers), wearable sensor-assessed distal body temperature (using an off-the-shelf wearable sensor that collected minute-level physiological data), and self-reported depressive symptoms from > 20,000 participants over the course of ~ 7 months as part of the TemPredict Study. Higher self-reported and wearable sensor-assessed body temperatures when awake were associated with greater depression symptom severity. Lower diurnal body temperature amplitude, computed using wearable sensor-assessed distal body temperature data, tended to be associated with greater depression symptom severity, though this association did not achieve statistical significance. These findings, drawn from a large sample, replicate and expand upon prior data pointing to body temperature alterations as potentially relevant factors in depression etiology and may hold implications for development of novel approaches to the treatment of major depressive disorder., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA) + CD90 - CD200 + and SIRPA + CD90 - CD200 - , identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias., (© 2024. The Author(s).)

The amygdalae are a pair of small brain structures, each of which is composed of three main subregions and whose function is implicated in neuropsychiatric conditions. Functional Magnetic Resonance Imaging (fMRI) has been utilized extensively in investigation of amygdala activation and functional connectivity (FC) with most clinical research sites now utilizing 3 Tesla (3T) MR systems. However, accurate imaging and analysis remains challenging not just due to the small size of the amygdala, but also its location deep in the temporal lobe. Selection of imaging parameters can significantly impact data quality with implications for the accuracy of study results and validity of conclusions. Wide variation exists in acquisition protocols with spatial resolution of some protocols suboptimal for accurate assessment of the amygdala as a whole, and for measuring activation and FC of the three main subregions, each of which contains multiple nuclei with specialized roles. The primary objective of this scoping review is to provide a broad overview of 3T fMRI protocols in use to image the activation and FC of the amygdala with particular reference to spatial resolution. The secondary objective is to provide context for a discussion culminating in recommendations for a standardized protocol for imaging activation of the amygdala and its subregions. As the advantages of big data and protocol harmonization in imaging become more apparent so, too, do the disadvantages of data heterogeneity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Marburg virus (MARV) has caused numerous sporadic outbreaks of severe hemorrhagic fever in humans. Human case fatality rates of Marburg virus disease (MVD) outbreaks range from 20% to 90%. Viral genotypes of MARV can differ by over 20%, suggesting variable virulence between lineages may accompany this genetic divergence. Comparison of existing animal models of MVD employing different strains of MARV support differences in virulence across MARV genetic lineages; however, there are few systematic comparisons in models that recapitulate human disease available., Methods: We compared features of disease pathogenesis in uniformly lethal hamster models of MVD made possible through serial adaptation in rodents., Results: No further adaptation from a previously reported guinea pig-adapted (GPA) isolate of MARV-Angola was necessary to achieve uniform lethality in hamsters. Three passages of GPA MARV-Ci67 resulted in uniform lethality, where 4 passages of a GPA Ravn virus was 75% lethal. Hamster-adapted MARV-Ci67 demonstrated delayed time to death, protracted weight loss, lower viral burden, and slower histologic alteration compared to GPA MARV-Angola., Conclusions: These data suggest isolate-dependent virulence differences are maintained even after serial adaptation in rodents and may serve to guide choice of variant and model used for development of vaccines or therapeutics for MVD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Speculation exists as to whether lisdexamfetamine dimesylate (LDX) acts on the functional connectivity (FC) of brain networks that modulate appetite, reward, or inhibitory control in binge-eating disorder (BED). Better insights into its action may help guide the development of more targeted therapeutics and identify who will benefit most from this medication. Here, we use a comprehensive data-driven approach to investigate the brain FC changes that underlie the therapeutic action of LDX in patients with BED., Methods: Forty-six participants with moderate to severe BED received LDX titrated to 50 or 70 mg for an 8-week period. Twenty age-matched healthy control participants were also recruited. Resting-state functional magnetic resonance imaging was used to probe changes in brain FC pre- and post treatment and correlated with change in clinical measures., Results: Ninety-seven percent of trial completers ( n  = 31) experienced remission or a reduction to mild BED during the 8-week LDX trial. Widespread neural FC changes occurred, with changes in default mode to limbic, executive control to subcortical, and default mode to executive control networks associated with improvements in clinical outcomes. These connections were not distinct from control participants at pretreatment but were different from control participants following LDX treatment. Pretreatment connectivity did not predict treatment response., Conclusions: FC between networks associated with self-referential processing, executive function, and reward seem to underlie the therapeutic effect of LDX in BED. This suggests that LDX activates change via multiple systems, with most changes in compensatory networks rather than in those characterizing the BED diagnosis., (© 2023 The Authors.)

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Inflammation and mitochondrial-dependent oxidative stress are interrelated processes implicated in multiple neuroinflammatory disorders, including Alzheimer's disease (AD) and depression. Exposure to elevated temperature (hyperthermia) is proposed as a non-pharmacological, anti-inflammatory treatment for these disorders; however, the underlying mechanisms are not fully understood. Here we asked if the inflammasome, a protein complex essential for orchestrating the inflammatory response and linked to mitochondrial stress, might be modulated by elevated temperatures. To test this, in preliminary studies, immortalized bone-marrow-derived murine macrophages (iBMM) were primed with inflammatory stimuli, exposed to a range of temperatures (37-41.5 °C), and examined for markers of inflammasome and mitochondrial activity. We found that exposure to mild heat stress (39 °C for 15 min) rapidly inhibited iBMM inflammasome activity. Furthermore, heat exposure led to decreased ASC speck formation and increased numbers of polarized mitochondria. These results suggest that mild hyperthermia inhibits inflammasome activity in the iBMM, limiting potentially harmful inflammation and mitigating mitochondrial stress. Our findings suggest an additional potential mechanism by which hyperthermia may exert its beneficial effects on inflammatory diseases.

This article examines how 'trauma' has been conceptualised in the unresolved state of mind classification in the Adult Attachment Interview, introduced by Main and Hesse in 1990. The unresolved state of mind construct has been influential for three decades of research in developmental psychology. However, not much is known about how this measure of unresolved trauma was developed, and how it relates to other conceptualisations of trauma. We draw on previously unavailable manuscripts from Main and Hesse's personal archive, including various editions of unpublished coding manuals, and on Main-Bowlby correspondence from the John Bowlby Archive at the Wellcome Trust in London. This article traces the emergence of the unresolved state of mind classification, and examines the assumptions about trauma embedded in the construct. These assumptions are situated both in the immediate context of the work of Main and Hesse and in terms of wider discourses about trauma in the period. Our analysis considers how a particular form of trauma discourse entered into attachment research, and in doing so partly lost contact with wider disciplinary study of trauma., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The emergence of the novel henipavirus, Langya virus, received global attention after the virus sickened over three dozen people in China. There is heightened concern that henipaviruses, as respiratory pathogens, could spark another pandemic, most notably the deadly Nipah virus (NiV). NiV causes near-annual outbreaks in Bangladesh and India and induces a highly fatal respiratory disease and encephalitis in humans. No licensed countermeasures against this pathogen exist. An ideal NiV vaccine would confer both fast-acting and long-lived protection. Recently, we reported the generation of a recombinant vesicular stomatitis virus-based (rVSV-based) vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% of nonhuman primates from NiV-associated lethality within a week. Here, to evaluate the durability of rVSV-ΔG-NiVBG, we vaccinated African green monkeys (AGMs) one year before challenge with an uniformly lethal dose of NiV. The rVSV-ΔG-NiVBG vaccine induced stable and robust humoral responses, whereas cellular responses were modest. All immunized AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication. Transcriptomic analyses indicated that adaptive immune signatures correlated with vaccine-mediated protection. While vaccines for certain respiratory infections (e.g., COVID-19) have yet to provide durable protection, our results suggest that rVSV-ΔG-NiVBG elicits long-lasting immunity.

The objective of the study is to identify challenges and associated factors for privacy and security related to telehealth visits during the COVID-19 pandemic. The systematic search strategy used the databases of PubMed, ScienceDirect, ProQuest, Embase, CINAHL, and COCHRANE, with the search terms of telehealth/telemedicine, privacy, security, and confidentiality. Reviews included peer-reviewed empirical studies conducted from January 2020 to February 2022. Studies conducted outside of the US, non-empirical, and non-telehealth related were excluded. Eighteen studies were included in the final analysis. Three risk factors associated with privacy and security in telehealth practice included: environmental factors (lack of private space for vulnerable populations, difficulty sharing sensitive health information remotely), technology factors (data security issues, limited access to the internet, and technology), and operational factors (reimbursement, payer denials, technology accessibility, training, and education). Findings from this study can assist governments, policymakers, and healthcare organizations in developing best practices in telehealth privacy and security strategies., (Copyright © 2023 by the American Health Information Management Association.)

Background: Despite homogenous clinical presentations between bipolar and unipolar disorders, there are distinct neurobiological differences. Chronicity of illness may be a factor impacting and sustaining certain neural features. The goal of this study was to investigate common and shared neural mechanisms underlying mood disorders, and possible sustained neural changes relating to illness chronicity by investigating a cohort of euthymic patients with bipolar disorder (BD), unipolar depression who had responded to treatment (treatment-sensitive depression, TSD), and a chronically treatment-resistant depressed (TRD) group., Methods: One hundred and seventy-two participants (40 BD, 39 TSD, 40 TRD, and 53 age-gender-matched healthy controls) underwent resting-state fMRI scans. Seed-based and independent component analyses were performed to investigate group differences in resting-state connectivity between the four groups., Results: All three clinical groups had significantly lower connectivity within the frontoparietal network (FPN) relative to controls. TRD and BD were significantly different from TSD (TRD, BD > TSD) but were not significantly different from each other. TRDs were also significantly different from both BD and TSD for salience network connectivity with the posterior cingulate (DMN) and the FPN with frontal pole (DMN). Additionally, the BD group exhibited greater DMN-FPN (sgACC-RDLPFC) connectivity relative to TRD, TSD, and controls, which was correlated with a previous number of depressive episodes, in the BD group only., Conclusions: BD demonstrated shared and differential connectivity features relative to symptomatic TRD and euthymic TSD groups. The increased sgACC-RDLPFC connectivity in BD and its correlation with a number of depressive episodes could be a neural feature associated with illness chronicity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination., Methods: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively., Results: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses., Conclusion: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems 1-5 . Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)-one such nociceptor-produced neuropeptide-directly increases the exhaustion of cytotoxic CD8 + T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8 + T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8 + T cells, Ramp1 -/ - CD8 + T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1-deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1-expressing CD8 + T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8 + T cells., (© 2022. The Author(s).)

We describe rapid detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant using targeted spike single-nucleotide polymorphism polymerase chain reaction and viral genome sequencing. This case occurred in a fully vaccinated and boosted returning traveler with mild symptoms who was identified through community surveillance rather than clinical care., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID 50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost., Competing Interests: Declaration of interests K.S.C. is an inventor on U.S. Patent no. 10,960,070 B2 and International Patent Application no. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” K.S.C. is an inventor on U.S. Patent Application no. 62/972,886 entitled “2019-nCoV Vaccine.” A.R.H., L.W., W.S., Y.Z., E.S.Y., J.R.M., P.D.K., M.R., N.J.S., and D.C.D. are inventors on U.S. Patent Application no. 63/147,419 entitled “Antibodies Targeting the Spike Protein of Coronaviruses.” L.P., A.V.R., B.N., D.V., A. Cook, A.D., K.S., H.A., and M.G.L. are employees of Bioqual. K.S.C., L.W., W.S., and Y.Z. are inventors on multiple U.S. Patent Applications entitled “Anti-Coronavirus Antibodies and Methods of Use.” G.-Y.C., G.S.-J., I.R., Y.-T.L., A.M., K.W., A. Carfi, and D.K.E. are employees of Moderna. M.S.S. serves on the scientific board of advisors for Moderna and Ocugen. The other authors declare no competing interests., (Published by Elsevier Inc.)

SignificanceConcern has increased about the pandemic potential of Nipah virus (NiV). Similar to SARS-CoV-2, NiV is an RNA virus that is transmitted by respiratory droplets. There are currently no NiV vaccines licensed for human use. While several preventive vaccines have shown promise in protecting animals against lethal NiV disease, most studies have assessed protection 1 mo after vaccination. However, in order to contain and control outbreaks, vaccines that can rapidly confer protection in days rather than months are needed. Here, we show that a recombinant vesicular stomatitis virus vector expressing the NiV glycoprotein can completely protect monkeys vaccinated 7 d prior to NiV exposure and 67% of animals vaccinated 3 d before NiV challenge.

Breath-held (BH) cardiac magnetic resonance imaging (CMR) is the gold standard for volumetric quantification. However, large animals for pre-clinical research are unable to voluntarily breath-hold, necessitating general anaesthesia and mechanical ventilation, increasing research costs and affecting cardiovascular physiology. Conducting CMR in lightly sedated, free-breathing (FB) animal subjects is an alternative strategy which can overcome these constraints, however, may result in poorer image quality due to breathing motion artefact. We sought to assess the reproducibility of CMR metrics between FB and BH CMR in a porcine model of ischaemic cardiomyopathy. FB or BH CMR was performed in 38 porcine subjects following percutaneous induction of myocardial infarction. Analysis was performed by two independent, blinded observers according to standard reporting guidelines. Subjective and objective image quality was significantly improved in the BH cohort (image quality score: 3.9/5 vs. 2.4/5; p < 0.0001 and myocardium:blood pool intensity ratio: 2.6-3.3 vs. 1.9-2.3; p < 0.001), along with scan acquisition time (4 min 06 s ± 1 min 55 s vs. 8 min 53 s ± 2 min 39 s; p < 0.000). Intra- and inter-observer reproducibility of volumetric analysis was substantially improved in BH scans (correlation coefficients: 0.94-0.99 vs. 0.76-0.91; coefficients of variation: < 5% in BH and > 5% in FB; Bland-Altman limits of agreement: < 10 in BH and > 10 in FB). Interstudy variation between approaches was used to calculate sample sizes, with BH CMR resulting in greater than 85% reduction in animal numbers required to show clinically significant treatment effects. In summary, BH porcine CMR produces superior image quality, shorter scan acquisition, greater reproducibility, and requires smaller sample sizes for pre-clinical trials as compared to FB acquisition., (© 2022. The Author(s).)

The recent emergence of B.1.1.529, the Omicron variant 1,2 , has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs.  3,4 ), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data., (© 2022. The Author(s).)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. At 2-4 weeks after a primary series of vaccinations, we observe a 30-fold reduction in neutralizing activity against omicron. Six months after the initial two-vaccine doses, sera from naive vaccinated subjects show no neutralizing activity against omicron. In contrast, COVID-19-recovered individuals 6 months after receiving the primary series of vaccinations show a 22-fold reduction, with the majority of the subjects retaining neutralizing antibody responses. In naive individuals following a booster shot (third dose), we observe a 14-fold reduction in neutralizing activity against omicron, and over 90% of subjects show neutralizing activity. These findings show that a third dose is required to provide robust neutralizing antibody responses against the omicron variant., Competing Interests: M.S.S. serves on the advisory board for Moderna and Ocugen., (© 2022.)

Background: During the COVID-19 pandemic, the use of telehealth for patient visits grew rapidly and served an important role as a valuable and necessary resource. Although clinical documentation is critical for telehealth patient visits, there is limited information about how healthcare facilities manage telehealth patient visit documentation, technology used for telehealth visits, and challenges encountered with telehealth patient visit documentation. This study aimed to assess the use of telehealth during the pandemic, the quality of clinical documentation in telehealth practice and to identify challenges and issues encountered with telehealth patient visits in order to develop a strategy for best practices for telehealth documentation and data management., Methods: Data were collected for this cross-sectional study in January-February 2021 via a self-designed survey of administrators/managers from physicians' offices and mental health facilities. Survey questions included four categories: health organization demographic information; telehealth visits; clinical documentation for telehealth visit; and challenges and barriers related to telehealth documentation technology use., Results: Of 76 respondents, more than half (62%) of the healthcare facilities started using telehealth for patient visits within one year of the onset of the COVID-19 pandemic, with 94% of respondents indicating an increased use of telehealth for patient visits since the pandemic. The most common types of telehealth patient care provided during the pandemic included pediatrics, primary care, cardiology, and women's health. The most consistent data documentation of telehealth visits included: date of service, patient identification number, communication methods, patient informed consent, diagnosis and impression, evaluation results, and recommendations. The telehealth visit data was most commonly used for patient care and clinical practice, billing and reimbursement, quality improvement and patient satisfaction, and administrative planning. The top barriers to telehealth use by the healthcare professionals included patient challenges with telehealth services, such as inequities in quality of technology, lack of patient understanding, and lack of patient satisfaction; this was followed by frustration with constant updates of telehealth guidelines and procedures, understanding required telehealth documentation for reimbursement purposes, payer denial for telehealth visits, and legal and risk issues., Conclusions: Findings from this study can assist government entities, policymakers, and healthcare organizations in developing and advocating best practices in telehealth usage and clinical documentation improvement strategies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/mhealth-21-30). The series “mHealth: Innovations on the Periphery” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2022 mHealth. All rights reserved.)

Telehealth services for patient visits have substantially surged during the COVID-19 pandemic. Thus, there is increased importance and demand for high-quality telehealth clinical documentation. However, little is known about how clinical data documentation is collected and the quality of data items included. This study aimed to identify the current state of and gaps in documentation and develop a best practice strategy for telehealth record documentation. Data were collected from January to February 2021 via a self-designed questionnaire for administrators and managers from physicians' offices and mental health facilities, resulting in 76 valid responses. Survey items included health organization demographic information, use of telehealth policies and procedures, and clinical documentation for telehealth patient visits. Findings from this study can be used to assist government, policymakers, and healthcare organizations in developing best practices in telehealth usage and clinical documentation improvement strategies., (Copyright © 2022 by the American Health Information Management Association.)

Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.

Bipolar disorder (BD) is commonly misdiagnosed as major depressive disorder (MDD). This is understandable, as depression often precedes mania and is otherwise indistinguishable in both. It is therefore imperative to identify neural mechanisms that can differentiate the two disorders. Interrogating resting brain neural activity may reveal core distinguishing abnormalities. We adopted an a priori approach, examining three key networks documented in previous mood disorder literature subserving executive function, salience and rumination that may differentiate euthymic BD and MDD patients. Thirty-eight patients with BD, 39 patients with MDD matched for depression severity, and 39 age-gender matched healthy controls, completed resting-state fMRI scans. Seed-based and data-driven Independent Component analyses (ICA) were implemented to examine group differences in resting-state connectivity (pFDR < 0.05). Seed analysis masks were target regions identified from the fronto-parietal (FPN), salience (SN) and default-mode (DMN) networks. Seed-based analyses identified significantly greater connectivity between the subgenual cingulate cortex (DMN) and right dorsolateral prefrontal cortex (FPN) in BD relative to MDD and controls. The ICA analyses also found greater connectivity between the DMN and inferior frontal gyrus, an FPN region in BD relative to MDD. There were also significant group differences across the three networks in both clinical groups relative to controls. Altered DMN-FPN functional connectivity is thought to underlie deficits in the processing, management and regulation of affective stimuli. Our results suggest that connectivity between these networks could potentially distinguish the two disorders and could be a possible trait mechanism in BD persisting even in the absence of symptoms., (© 2021. The Author(s).)

Recent preclinical studies have reported that pretreatment with the novel and highly-selective dopamine D 3 receptor (D 3 R) antagonists R-VK4-40 or VK4-116 attenuates the abuse-related behavioral effects of oxycodone while enhancing its analgesic properties. However, whether these observed effects are generalizable to the broad class of D 3 R antagonists and/or extend to opioids other than oxycodone has not been extensively explored. The present study sought to assess the impact of pretreatment with another selective D 3 R antagonist, PG01037, on several behavioral effects of morphine in mice. C57Bl/6 J mice were pretreated with PG01037 (0-10 mg/kg) and tested for 1) hyperlocomotion induced by acute morphine (5.6-56 mg/kg), 2) locomotor sensitization following repeated morphine (56 mg/kg), 3) antinociception following acute morphine (18 mg/kg), and 4) catalepsy following administration of PG01037 alone or in combination with morphine (56 mg/kg). PG01037 dose-dependently attenuated morphine-induced hyperlocomotion and morphine-induced antinociception at doses that did not alter basal locomotion or nociception alone, but did not prevent the induction of locomotor sensitization following repeated morphine administration. Moreover, PG01037 did not induce catalepsy either alone or in combination with morphine. These results suggest that attenuation of acute opioid-induced hyperactivity may be a behavioral effect shared among D 3 R-selective antagonists, thus supporting continued investigations into their use as potential treatments for opioid use disorder. However, PG01037 is unlike newer, highly-selective D 3 R antagonists in its capacity to reduce opioid-induced antinociception, indicating that modulation of opioid analgesia may vary across different D 3 R antagonists., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This field case study reports findings on disinfection/ammonia removal from aquaculture wastewater and disinfection of irrigation water carried out at an aquaculture farm and two irrigation locations in Hawaii. We used a flow cell incorporating PtRu/graphite anode and graphite cathode for the disinfection/ammonia removal from aquaculture wastewater, and a flow cell assembled with graphite plates as both anode and cathode for the disinfection of irrigation water. The removal of ammonia followed the indirect oxidation mechanism mediated by free chlorine electro-generated at the PtRu/graphite anode. Ammonia removal rate increased with the increase in NaCl concentration, applied current density, or flow rate. The disinfection of aquaculture wastewater can be readily achieved due to the presence of highly germicidal free chlorine species. The disinfection of irrigation water was realized without the addition of chemicals. The disinfection mechanism was attributed to the formation of free chlorine from the anodic oxidation of chloride ions naturally occurring in the water sources. The disinfection efficiency decreased with increasing organic matter concentration. In addition to the flow cell approach, we also successfully demonstrated the disinfection of irrigation water by adding electrolyzed NaCl solution or purging with a mixture of air and chlorine gas, both of which were generated on-site. PRACTITIONER POINTS: Field case study on disinfection/ammonia removal from aquaculture wastewater and disinfection of irrigation water was carried out in Hawaii. Electrochemical flow cell assembled with PtRu/graphite anode and graphite cathode effectively removes ammonia from aquaculture wastewater. Ammonia removal proceeds via the indirect oxidation mechanism mediated by free chlorine electro-generated at the PtRu/graphite anode. Electrochemical flow cell assembled with commercial graphite electrodes enables fast disinfection of coliform bacteria and E. coli. The primary disinfection mechanism is through chlorine species electro-generated from chloride oxidation at the graphite anode., (© 2021 Water Environment Federation.)

Rationale: In rodents, exposure to novel environments or psychostimulants promotes locomotion. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addiction. RGS14 is a plasticity-restricting protein with unique functional domains that enable it to suppress ERK-dependent signaling as well as regulate G protein activity. Although recent studies show that RGS14 is expressed in multiple limbic regions implicated in psychostimulant- and novelty-induced hyperlocomotion, its function has been examined mostly in the context of hippocampal physiology and memory., Objective: We investigated whether RGS14 modulates novelty- and cocaine-induced locomotion (NIL and CIL, respectively) and neuronal activity., Methods: We assessed Rgs14 knockout (RGS14 KO) mice and wild-type (WT) littermate controls using NIL and CIL behavioral tests, followed by quantification of c-fos and phosphorylated ERK (pERK) induction in limbic regions that normally express RGS14., Results: RGS14 KO mice were less active than WT controls in the NIL test, driven by avoidance of the center of the novel environment. By contrast, RGS14 KO mice demonstrated augmented peripheral locomotion in the CIL test conducted in either a familiar or novel environment. RGS14 KO mice exhibited increased thigmotaxis, as well as greater c-fos and pERK induction in the central amygdala and dorsal hippocampus, when cocaine and novelty were paired., Conclusions: RGS14 KO mice exhibited anti-correlated locomotor responses to novelty and cocaine, but displayed increased thigmotaxis in response to either stimuli which was augmented by their combination. Our findings also suggest RGS14 may reduce neuronal activity in limbic subregions by inhibiting ERK-dependent signaling., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The neuropeptide galanin is reported to attenuate opioid withdrawal symptoms, potentially by reducing neuronal hyperactivity in the noradrenergic locus coeruleus (LC) via galanin receptor 1 (GalR1). We evaluated this mechanism by using RNAscope in situ hybridization to characterize GalR1 mRNA distribution in the dorsal pons and to compare galanin and GalR1 mRNA expression in tyrosine hydroxylase-positive (TH+) LC cells at baseline and following chronic morphine or precipitated withdrawal. We then used genetically altered mouse lines and pharmacology to test whether noradrenergic galanin (NE-Gal) modulates withdrawal symptoms. RNAscope revealed that, while GalR1 signal was evident in the dorsal pons, 80.7% of the signal was attributable to TH- neurons outside the LC. Galanin and TH mRNA were abundant in LC cells at baseline and were further increased by withdrawal, whereas low basal GalR1 mRNA expression was unaltered by chronic morphine or withdrawal. Naloxone-precipitated withdrawal symptoms in mice lacking NE-Gal (Gal cKO-Dbh ) were largely similar to WT littermates, indicating that loss of NE-Gal does not exacerbate withdrawal. Complementary experiments using NE-Gal overexpressor mice (NE-Gal OX) and systemic administration of the galanin receptor agonist galnon revealed that increasing galanin signaling also failed to alter behavioral withdrawal, while suppressing noradrenergic transmission with the alpha-2 adrenergic receptor agonist clonidine attenuated multiple symptoms. These results indicate that galanin does not acutely attenuate precipitated opioid withdrawal via an LC-specific mechanism, which has important implications for the general role of galanin in regulation of somatic and affective opioid responses and LC activity., (© 2021 Society for the Study of Addiction.)

The National Institute of Health has made it a priority to identify, develop, and refine strategies to disseminate and implement effective interventions (National Institute of Health, 2015). This study examined qualitative reports of the strategies therapists used to manage common implementation problems they encountered during midtreatment in Multisystemic Therapy ® (MST) and Functional Family Therapy (FFT), two widely disseminated evidence- and family-based treatments for substance abusing and delinquent adolescents. Experienced therapists from dissemination sites across the U.S. described cases in which they encountered midtreatment problems they perceived as serious threats to treatment success. They indicated why each case terminated and rated the outcome of the case. Qualitative analyses examined 16 treatment failures and then 16 treatment successes to identify contextual obstacles that accompanied the problems therapists identified, along with strategies they reported using with families that ultimately succeeded or failed. Therapists reported that midtreatment problems were often embedded in additional related difficulties and that they employed multiple relationship techniques and process-focused strategies to try to resolve these problems. For the most part, therapists described obstacles and strategies for successful and unsuccessful families in similar ways. Patterns of themes and subthemes suggested, however, that therapists in successful cases may be more likely to report "on-script" strategies and therapists in unsuccessful cases may describe more "off-script" strategies as well as more generic relationship building and advice-giving strategies., (© 2020 Family Process Institute.)

Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). To understand functional consequences, we locally ablated neuronal β1-integrins, cell adhesion receptors that adhere cells to the extracellular matrix and thus support dendritic spine stability. Degradation of β1-integrin tone: (1) caused dendritic spine loss, (2) exaggerated cocaine-seeking responses in a cue-induced reinstatement test, and (3) impaired the ability of mice to integrate new learning into familiar routines, a key function of the orbitofrontal cortex. Stimulating Abl-related gene kinase, overexpressing Proline-rich tyrosine kinase, and inhibiting Rho-associated coiled-coil containing kinase corrected response strategies, uncovering a β1-integrin-mediated signaling axis that controls orbitofrontal cortical function. Finally, use of a combinatorial gene silencing/chemogenetic strategy revealed that β1-integrins support the ability of mice to integrate new information into established behaviors by sustaining orbitofrontal cortical connections with the basolateral amygdala. SIGNIFICANCE STATEMENT Cocaine degenerates dendritic spines in the orbitofrontal cortex, a region of the brain involved in interlacing new information into established behaviors. One challenge has been verifying links between cellular structural stability and behavior, if any. In this second of two related investigations, we study integrin family receptors, which adhere cells to the extracellular matrix and thereby stabilize dendritic spines (see also DePoy et al., 2019). We reveal that β1-integrins in the orbitofrontal cortex control food- and cocaine-seeking behaviors. For instance, β1-integrin loss amplifies cocaine-seeking behavior and impairs the ability of mice to integrate new learning into familiar routines. We identify likely intracellular signaling partners by which β1-integrins support orbitofrontal cortical function and connectivity with the basolateral amygdala., (Copyright © 2021 the authors.)

Both the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior. We used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh -/- ) or galanin (Gal cKO-Dbh ) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress. Foot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, both Dbh -/- and Gal cKO-Dbh mice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later. These results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates the development of more persistent responses following a stressor.

Background: Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice., Objective: We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure., Methods: We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor-specific FcεR1γ knockdown (TRPV1 Cre ::FcεR1γ fl/fl ) mice to assess whether this targeted invalidation would affect the severity of allergic inflammation in response to allergen challenges., Results: Lung-innervating jugular nodose complex ganglion neurons express the high-affinity IgE receptor FcεR1, the levels of which increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE-allergen immune complexes, through the release of substance P from their peripheral terminals, directly amplifies T H 2 cell influx and polarization in the airways. Allergic airway inflammation is decreased in TRPV1 Cre ::FcεR1γ fl/fl mice and in FcεR1α -/- mice into which bone marrow has been transplanted. Finally, increased in vivo circulating levels of IgE following allergen sensitization enhances the responsiveness of FcεR1 to immune complexes in both mouse jugular nodose complex ganglion neurons and human induced pluripotent stem cell-derived nociceptors., Conclusions: Allergen sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1-expressing vagal sensory neurons, and T H 2 cells, which helps to both initiate and amplify allergic airway inflammation. These data highlight a novel target for reducing allergy, namely, FcεR1γ expressed by nociceptors., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Ebola virus (EBOV) hemorrhagic fever outbreaks have been challenging to deter due to the lack of health care infrastructure in disease-endemic countries and a corresponding inability to diagnose and contain the disease at an early stage. EBOV vaccines and therapies have improved disease outcomes, but the advent of an affordable, easily accessed, mass-produced rapid diagnostic test (RDT) that matches the performance of more resource-intensive polymerase chain reaction (PCR) assays would be invaluable in containing future outbreaks. Here, we developed and demonstrated the performance of a new ultrasensitive point-of-care immunoassay, the EBOV D4 assay, which targets the secreted glycoprotein of EBOV. The EBOV D4 assay is 1000-fold more sensitive than the U.S. Food and Drug Administration-approved RDTs and detected EBOV infection earlier than PCR in a standard nonhuman primate model. The EBOV D4 assay is suitable for low-resource settings and may facilitate earlier detection, containment, and treatment during outbreaks of the disease., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In this work, we report experimental studies on the disinfection of irrigation water using a flow cell assembled with low-cost graphite plates as both anode and cathode. Natural irrigation waters collected from two irrigation locations (Reservoir 225 and Bott Well Pond) in Hawaii were used, and synthetic irrigation waters were prepared based on the chemical analysis of natural irrigation waters. The concentration of chloride was 10.2 mg/L in the synthetic Reservoir 225 water and 6.9 mg/L in the synthetic Bott Well pond water. Escherichia coli K12 ER2738 was selected as a model bacterium to evaluate the disinfection capability of the flow cell. Experiments performed in the synthetic irrigation waters showed that E. coli was inactivated by free chlorine species electro-generated from oxidation of chloride ions at the graphite anode. Complete removal of E. coli was achieved within 10 min in the synthetic irrigation waters. The disinfection of the natural irrigation waters took about four times longer than the disinfection of the synthetic irrigation waters. This result is most likely due to the presence of organic matter (and possibly other oxidizable species) in the natural irrigation waters. PRACTITIONER POINTS: Electrochemical flow cell disinfects to 99.9% with commercial graphite electrodes. E. coli is removed in 10 min from synthetic irrigation water by a flow cell. E. coli removal takes 4× longer in natural irrigation water. A minimum current density of ≥1 mA/cm 2 is required for disinfection. The primary disinfection mechanism is through chlorine generated from chloride ions., (© 2020 Water Environment Federation.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.

The COVID-19 pandemic has increased the emphasis on population health, therefore potentially amplifying demand for healthcare workforce professionals in this area. There is an urgent need to explore and define the roles of health information management (HIM) professionals in the population health workforce. This study sought to identify the skill sets and qualifications needed, and HIM education alignment with skills necessary for HIM professionals entering the population health workforce. An intentionally broad internet search of job postings was conducted to determine skills in population health. Population health-related job descriptions and qualification requirements were abstracted and analyzed using ATLAS.ti. Three common job categories were identified: management, analytics, and coding. Skill set requirements included soft skills, problem solving, project management, research, and data analysis. The study results identified HIM educational alignment and found that HIM professionals are generally a good fit to meet the increased need in the population health workforce., (Copyright © 2021 by the American Health Information Management Association.)

Understanding how brain circuitry mediates cognitive control of behavior is crucial for understanding both mental health and disease. Cognitive control describes the group of behaviors that guide goal-directed action such as sustaining attention, processing information and inhibiting impulsive responses. We rely on these behaviors for daily social, occupational and emotional functioning. Two brain networks, the cognitive control network (CCN) and default mode network (DMN), are thought to cooperate in an inverse relationship to support these functions. However, we do not yet know how connectivity within and between these networks directly relates to healthy cognitive control behaviors, and whether these interactions change over time. Here, we employed a longitudinal design to investigate if change in intrinsic connectivity in these networks will correlate with change in a range of cognitive control functions. Over two years, 109 healthy individuals, aged eight to thirty-eight, were tested twice using fMRI to assess intrinsic functional connectivity of the CCN and DMN and a validated cognitive battery. We found that increased within-network connectivity through central and left DMN was associated with increased memory performance. Additionally, decreased connectivity between posterior parietal CCN and DMN nodes and decreased connectivity between left and right dorsolateral prefrontal nodes was associated with increased cognitive performance. These findings were age and gender controlled, suggesting that age-independent plastic change in intrinsic connectivity through these networks directly relate to changing behavior. This has implications for targeting intrinsic connectivity as a possible mechanism to improve cognitive function., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Due to the difficulty in conducting clinical trials for vaccines and treatments against Nipah virus (NiV), licensure will likely require animal models, most importantly non-human primates (NHPs). The NHP models of infection have primarily relied on intratracheal instillation or small particle aerosolization of NiV. However, neither of these routes adequately models natural mucosal exposure to NiV. To develop a more natural NHP model, we challenged African green monkeys with the Bangladesh strain of NiV by the intranasal route using the laryngeal mask airway (LMA) mucosal atomization device (MAD). LMA MAD exposure resulted in uniformly lethal disease that accurately reflected the human condition., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Nipah virus (NiV) is a pathogenic paramyxovirus and zoononis with very high human fatality rates. Previous protein over-expression studies have shown that various mutations to the common N-terminal STAT1-binding motif of the NiV P, V, and W proteins affected the STAT1-binding ability of these proteins thus interfering with he JAK/STAT pathway and reducing their ability to inhibit type-I IFN signaling, but due to differing techniques it was unclear which amino acids were most important in this interaction or what impact this had on pathogenesis in vivo. We compared all previously described mutations in parallel and found the amino acid mutation Y116E demonstrated the greatest reduction in binding to STAT1 and the greatest reduction in interferon antagonism. A similar reduction in binding and activity was seen for a deletion of twenty amino acids constituting the described STAT1-binding domain. To investigate the contribution of this STAT1-binding motif in NiV-mediated disease, we produced rNiVs with complete deletion of the STAT1-binding motif or the Y116E mutation for ferret challenge studies (rNiV M -STAT1 blind ). Despite the reduced IFN inhibitory function, ferrets challenged with these rNiV M -STAT1 blind mutants had a lethal, albeit altered, NiV-mediated disease course. These data, together with our previously published data, suggest that the major role of NiV P, V, and W in NiV-mediated disease in the ferret model are likely to be in the inhibition of viral recognition/innate immune signaling induction with a minor role for inhibition of IFN signaling.