Pediatric mental health emergency department visits from 2017 to 2022: A multicenter study.

BACKGROUND: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends. METHODS: We retrospectively studied MH ED visits by children 5 to <18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics. RESULTS: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected rates during the midpandemic (RR 1.01, 95% CI 0.96-1.07), and then decreased below expected rates during the late pandemic (RR 0.92, 95% CI 0.86-0.98). During the late pandemic, visit rates were higher than expected for females (RR 1.10, 95% CI 1.02-1.20) and for bipolar disorders (RR 1.83, 95% CI 1.38-2.75), schizophrenia spectrum disorders (RR 1.55, 95% CI 1.10-2.59), and substance-related and addictive disorders (RR 1.50, 95% CI 1.18-2.05). CONCLUSIONS: During the late pandemic, pediatric MH ED visits decreased below expected rates; however, visits by females and for specific conditions remained elevated, indicating a need for increased attention to these groups. Prolonged ED visit lengths may reflect inadequate availability of MH services.

Macrophage extracellular traps require peptidylarginine deiminase 2 and 4 and are a source of citrullinated antigens bound by rheumatoid arthritis autoantibodies.

Introduction: Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis, but the sources of citrullinated antigens as well as which peptidylarginine deiminases (PADs) are required for their production remain incompletely defined. Here, we investigated if macrophage extracellular traps (METs) could be a source of citrullinated proteins bound by APCAs, and if their formation requires PAD2 or PAD4. Methods: Thioglycolate-induced peritoneal macrophages from wild-type, PAD2-/-, and PAD4-/- mice or human peripheral blood-derived M1 macrophages were activated with a variety of stimulants, then fixed and stained with DAPI and either anti-citrullinated histone H4 (citH4) antibody or sera from ACPA+ or ACPA- rheumatoid arthritis subjects. METs were visualized by immunofluorescence, confirmed to be extracellular using DNase, and quantified. Results: We found that ionomycin and monosodium urate crystals reliably induced murine citH4+ METs, which were reduced in the absence of PAD2 and lost in the absence of PAD4. Also, IgG from ACPA+, but not ACPA-, rheumatoid arthritis sera bound to murine METs, and in the absence of PAD2 or PAD4, ACPA-bound METs were lost. Finally, ionomycin induced human METs that are citH4+ and ACPA-bound. Discussion: Thus, METs may contribute to the pool of citrullinated antigens bound by ACPAs in a PAD2- and PAD4-dependent manner, providing new insights into the targets of immune tolerance loss in rheumatoid arthritis.

Novel and unique rheumatoid factors cross-react with viral epitopes in COVID-19.

Rheumatoid factors (RFs), polyreactive antibodies canonically known to bind two conformational epitopes of IgG Fc, are a hallmark of rheumatoid arthritis but also can arise in other inflammatory conditions and infections. Also, infections may contribute to the development of rheumatoid arthritis and other autoimmune diseases. Recently, RFs only in rheumatoid arthritis were found to bind novel linear IgG epitopes as well as thousands of other rheumatoid arthritis autoantigens. Specific epitopes recognized by infection-induced polyreactive RFs remain undefined but could provide insights into loss of immune tolerance. Here, we identified novel linear IgG epitopes bound by RFs in COVID-19 but not rheumatoid arthritis or other conditions. The main COVID-19 RF was polyreactive, binding two IgG and multiple viral peptides with a tripeptide motif, as well as IgG Fc and SARS-CoV-2 spike proteins. In contrast, a rheumatoid arthritis-specific RF recognized IgG Fc, but not tripeptide motif-containing peptides or spike. Thus, RFs have disease-specific IgG reactivity and distinct polyreactivities that reflect the broader immune response. Moreover, the polyreactivity of a virus-induced RF appears to be attributable to a very short peptide motif. These findings refine our understanding of RFs and provide new insights into how viral infections may contribute to autoimmunity.

Research Priorities for Pediatric Emergency Care to Address Disparities by Race, Ethnicity, and Language.

Importance: Health care disparities are well-documented among children based on race, ethnicity, and language for care. An agenda that outlines research priorities for disparities in pediatric emergency care (PEC) is lacking. Objective: To investigate research priorities for disparities in PEC among medical personnel, researchers, and health care-affiliated community organizations. Design, Setting, and Participants: In this survey study, a modified Delphi approach was used to investigate research priorities for disparities in PEC. An initial list of research priorities was developed by a group of experienced PEC investigators in 2021. Partners iteratively assessed the list through 2 rounds of electronic surveys using Likert-type responses in late 2021 and early 2022. Priorities were defined as achieving consensus if they received a score of highest priority or priority by at least 60% of respondents. Asynchronous engagement of participants via online web-conferencing platforms and email correspondence with electronic survey administration was used. Partners were individuals and groups involved in PEC. Participants represented interest groups, research and medical personnel organizations, health care partners, and laypersons with roles in community and family hospital advisory councils. Participants were largely from the US, with input from international PEC research networks. Outcome: Consensus agenda of research priorities to identify and address health care disparities in PEC. Results: PEC investigators generated an initial list of 27 potential priorities. Surveys were completed by 38 of 47 partners (80.6%) and 30 of 38 partners (81.1%) in rounds 1 and 2, respectively. Among 30 respondents who completed both rounds, there were 7 family or community partners and 23 medical or research partners, including 4 international PEC research networks. A total of 12 research priorities achieved the predetermined consensus threshold: (1) systematic efforts to reduce disparities; (2) race, ethnicity, and language data collection and reporting; (3) recognizing and mitigating clinician implicit bias; (4) mental health disparities; (5) social determinants of health; (6) language and literacy; (7) acute pain-management disparities; (8) quality of care equity metrics; (9) shared decision-making; (10) patient experience; (11) triage and acuity score assignment; and (12) inclusive research participation. Conclusions and Relevance: These results suggest a research priority agenda that may be used as a guide for investigators, research networks, organizations, and funding agencies to engage in and support high-priority disparities research topics in PEC.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased ß-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1ß, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.

Paired ATAC- and RNA-seq offer insight into the impact of HIV on alveolar macrophages: a pilot study.

People with HIV remain at greater risk for both infectious and non-infectious pulmonary diseases even after antiretroviral therapy initiation and CD4 cell count recovery. These clinical risks reflect persistent HIV-mediated defects in innate and adaptive immunity, including in the alveolar macrophage, a key innate immune effector in the lungs. In this proof-of-concept pilot study, we leveraged paired RNA-seq and ATAC-seq analyses of human alveolar macrophages obtained with research bronchoscopy from people with and without HIV to highlight the potential for recent methodologic advances to generate novel hypotheses about biological pathways that may contribute to impaired pulmonary immune function in people with HIV. In addition to 35 genes that were differentially expressed in macrophages from people with HIV, gene set enrichment analysis identified six gene sets that were differentially regulated. ATAC-seq analysis revealed 115 genes that were differentially accessible for people with HIV. Data-driven integration of the findings from these complementary, high-throughput techniques using xMWAS identified distinct clusters involving lipoprotein lipase and inflammatory pathways. By bringing together transcriptional and epigenetic data, this analytic approach points to several mechanisms, including previously unreported pathways, that warrant further exploration as potential mediators of the increased risk of pulmonary disease in people with HIV.

Primary tracheal carcinoid tumor misdiagnosed as asthma: a rare case report.

About 2% of all lung malignancies are pulmonary carcinoid tumors, a family of neuroendocrine tumors. Rarely does a typical tracheal carcinoid of the trachea manifest as an endoluminal polypoidal tumor. Case presentation: The author describe a 61-year-old nonsmoker who complained of growing nonexertional shortness of breath 5 years ago. She also had a wheezy chest and a dry cough. The results of the chest radiography and electrocardiogram revealed no noteworthy abnormalities. The results of the pulmonary function test supported the diagnosis of bronchial asthma. A patient's treatment has not advanced. After performing a bronchoscopy, a biopsy was taken and sent for pathological analysis. The endobronchial lining was found to have a subepithelial tumor infiltrate made up of nests of homogeneous bland cells with central nuclei and mild granular cytoplasm, according to histopathologic analysis. Considering all of these findings, the patient was diagnosed with a primary tracheal carcinoid tumor, which was misdiagnosed and treated as bronchial asthma. Discussion and conclusion: People with stridor or trepopnea symptoms should undergo a computed tomography scan since central airway tumors can mimic the symptoms of bronchial asthma while a chest radiograph may be normal. Tracheal carcinoid that has not progressed to the mediastinum can be successfully removed with flexible bronchoscopy and electrocautery, but the excision site needs to be continuously watched for recurrence.

Mycobacterium tuberculosis-specific cytokine responses according to HIV status among household contacts of people with TB.

Following exposure to Mycobacterium tuberculosis (Mtb), a coordinated host response comprising both pro- and anti-inflammatory cytokines is critical for pathogen control. Although tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (HIV), the impact of HIV infection on Mtb-specific immune responses remains unclear. In this cross-sectional study of TB-exposed household contacts with and without HIV, we collected remaining supernatant from interferon-gamma release assay (IGRA) testing (QuantiFERON-TB Gold Plus [QFT-Plus]) and measured Mtb-specific pro-inflammatory, anti-inflammatory, and regulatory cytokine responses with a multiplex assay of 11 analytes. While people with HIV had lower responses to mitogen stimulation for some cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin [IL]-2, IL-10, IL-17A, IL-22), there was no difference in cytokine levels for people with and without HIV following stimulation with Mtb-specific antigens. Future studies are necessary to explore whether changes in Mtb-specific cytokine responses over time are associated with distinct clinical outcomes following exposure to TB.

Diversity among research coordinators in a pediatric emergency medicine research collaborative network.

We conducted a survey study of clinical research coordinators (CRCs) at the member institutions of the Pediatric Emergency Care Applied Research Network, to determine the demographic and linguistic characteristics of CRCs around the network, and any perceived impact of those characteristics on their duties. A total of 53/74 CRCs completed the survey. Most respondents identified as "female," "white," and "not Hispanic/Latino." Most respondents felt that their race/ethnicity and their ability to speak a language other than English would positively impact recruitment. Four female respondents felt that their gender hindered their recruitment efforts and their sense of belonging within the research team.

Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

MYOSIN LIGHT CHAIN KINASE DELETION WORSENS LUNG PERMEABILITY AND INCREASES MORTALITY IN PNEUMONIA-INDUCED SEPSIS.

ABSTRACT: Increased epithelial permeability in sepsis is mediated via disruptions in tight junctions, which are closely associated with the perijunctional actin-myosin ring. Genetic deletion of myosin light chain kinase (MLCK) reverses sepsis-induced intestinal hyperpermeability and improves survival in a murine model of intra-abdominal sepsis. In an attempt to determine the generalizability of these findings, this study measured the impact of MLCK deletion on survival and potential associated mechanisms following pneumonia-induced sepsis. MLCK -/- and wild-type mice underwent intratracheal injection of Pseudomonas aeruginosa . Unexpectedly, survival was significantly worse in MLCK -/- mice than wild-type mice. This was associated with increased permeability to Evans blue dye in bronchoalveolar lavage fluid but not in tissue homogenate, suggesting increased alveolar epithelial leak. In addition, bacterial burden was increased in bronchoalveolar lavage fluid. Cytokine array using whole-lung homogenate demonstrated increases in multiple proinflammatory and anti-inflammatory cytokines in knockout mice. These local pulmonary changes were associated with systemic inflammation with increased serum levels of IL-6 and IL-10 and a marked increase in bacteremia in MLCK -/- mice. Increased numbers of both bulk and memory CD4 + T cells were identified in the spleens of knockout mice, with increased early and late activation. These results demonstrate that genetic deletion of MLCK unexpectedly increases mortality in pulmonary sepsis, associated with worsened alveolar epithelial leak and both local and systemic inflammation. This suggests that caution is required in targeting MLCK for therapeutic gain in sepsis.

Deep learning based diagnostic quality assessment of choroidal OCT features with expert-evaluated explainability.

Various vision-threatening eye diseases including age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR) are caused due to the dysfunctions manifested in the highly vascular choroid layer of the posterior segment of the eye. In the current clinical practice, screening choroidal structural changes is widely based on optical coherence tomography (OCT) images. Accordingly, to assist clinicians, several automated choroidal biomarker detection methods using OCT images are developed. However, the performance of these algorithms is largely constrained by the quality of the OCT scan. Consequently, determining the quality of choroidal features in OCT scans is significant in building standardized quantification tools and hence constitutes our main objective. This study includes a dataset of 1593 good and 2581 bad quality Spectralis OCT images graded by an expert. Noting the efficacy of deep-learning (DL) in medical image analysis, we propose to train three state-of-the-art DL models: ResNet18, EfficientNet-B0 and EfficientNet-B3 to detect the quality of OCT images. The choice of these models was inspired by their ability to preserve the salient features across all the layers without information loss. To evaluate the attention of DL models on the choroid, we introduced color transparency maps (CTMs) based on GradCAM explanations. Further, we proposed two subjective grading scores: overall choroid coverage (OCC) and choroid coverage in the visible region(CCVR) based on CTMs to objectively correlate visual explanations vis-à-vis DL model attentions. We observed that the average accuracy and F-scores for the three DL models are greater than 96%. Further, the OCC and CCVR scores achieved for the three DL models under consideration substantiate that they mostly focus on the choroid layer in making the decision. In particular, of the three DL models, EfficientNet-B3 is in close agreement with the clinician's inference. The proposed DL-based framework demonstrated high detection accuracy as well as attention on the choroid layer, where EfficientNet-B3 reported superior performance. Our work assumes significance in bench-marking the automated choroid biomarker detection tools and facilitating high-throughput screening. Further, the methods proposed in this work can be adopted for evaluating the attention of DL-based approaches developed for other region-specific quality assessment tasks.

HIV Increases the Risk of Cigarette Smoke-Induced Emphysema Through MMP-9.

BACKGROUND: HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9. METHODS: HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed to the HIV protein Tat, and MMP-9 levels were assessed by Western immunoblotting. MMP-9 protein expression and activity were assessed in AM from the HIV rat model by ELISA and cytoimmunofluoresence, respectively. Serum from human subjects with and without HIV and tobacco dependence was assessed for MMP-9 levels. RESULTS: MMP-9 expression was significantly increased in rat alveolar macrophages after Tat exposure. HIV-1 transgenic rats developed emphysema while wild-type littermates did not. MMP-9 expression was also increased in the serum, BAL, and AM of HIV-1 transgenic rats after exposure to cigarette smoke compared with wild-type rats. In parallel, serum samples from HIV+ smokers had higher levels of MMP-9 than subjects without HIV and those who did not smoke. CONCLUSION: The combination of HIV and cigarette smoke increases MMP-9 expression in experimental rat HIV models and human subjects. HIV and cigarette smoke both induce alveolar oxidative stress and thereby increase MMP-9 activity.

Alcohol impairs recognition and uptake of Mycobacterium tuberculosis by suppressing toll-like receptor 2 expression.

BACKGROUND: Alcohol impairs pulmonary innate immune function and is associated with an increased risk of tuberculosis (TB). Toll-like receptor 2 (TLR2) is a pattern recognition receptor on alveolar macrophages that recognizes Mycobacterium tuberculosis (Mtb). The expression of TLR2 depends, in part, on granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. Given our prior work demonstrating the suppression of GM-CSF signaling following chronic alcohol ingestion, we hypothesized that alcohol impairs TLR2 expression via the suppression of GM-CSF and thereby reduces the ability of the macrophage to recognize and phagocytose Mtb. METHODS: Primary alveolar macrophages were isolated from control-fed and alcohol-fed rats. Prior to cell isolation, some alcohol-fed rats were treated with intranasal GM-CSF and then endotracheally inoculated with an attenuated strain of Mtb. Primary macrophages were then isolated and immunofluorescence was used to determine phagocytic efficiency and TLR2 expression in the presence and absence of GM-CSF treatment and phagocytic efficiency in the presence and absence of TLR2 neutralization. RESULTS: TLR2 expression and phagocytosis of Mtb were significantly lower in the alveolar macrophages of alcohol-fed rats than control-fed rats. In parallel, blocking TLR2 signaling recapitulated this decreased phagocytosis of Mtb. In contrast, intranasal GM-CSF treatment restored TLR2 expression and Mtb phagocytosis in the alveolar macrophages of alcohol-fed rats to levels comparable to those of control-fed rats. CONCLUSIONS: Chronic alcohol ingestion reduces TLR2 protein expression and phagocytosis of Mtb, likely due to impaired GM-CSF signaling. GM-CSF restores membrane-bound TLR2 expression and phagocytic function.

Application of novel Fe3O4/Zn-metal organic framework magnetic nanostructures as an antimicrobial agent and magnetic nanocatalyst in the synthesis of heterocyclic compounds.

Using the microwave-assisted method, novel Fe3O4/Zn-metal organic framework magnetic nanostructures were synthesized. The crystallinity, thermal stability, adsorption/desorption isotherms, morphology/size distribution, and magnetic hysteresis of synthesized Fe3O4/Zn-metal organic framework magnetic nanostructures were characterized by XRD patterns, TGA curve, BET adsorption/desorption technique, SEM image, and VSM curve, respectively. After confirming the Fe3O4/Zn-metal organic framework magnetic nanostructures, its antimicrobial properties against Gram-positive bacterial, Gram-negative bacterial, and fungal strains based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) values were studied. The MIC values in antimicrobial activity for Gram-positive and Gram-negative bacterial strains, between 16-128 µg/ml, and for fungal strain, 128 µg/ml were observed. The results showed that the high specific surface area of Fe3O4/Zn-metal organic framework magnetic nanostructures caused the antimicrobial power of nanoparticles to be high, and the observed antimicrobial effects were higher than some known commercial antimicrobial drugs. Another advantage of the specific surface area of Fe3O4/Zn-metal organic framework magnetic nanostructures was its high catalytic properties in the three-component reaction of isatin, malononitrile, and dimedone. New spiro [indoline-pyranopyrimidines] derivatives were synthesized with high efficiency. The catalytic activity results of Fe3O4/Zn-metal organic framework magnetic nanostructures showed that, in addition to recyclability, derivatives could be synthesized in less time than previously reported methods. The results of investigating the catalytic activity of Fe3O4/Zn-metal organic framework magnetic nanostructures showed that the spiro [indoline-pyranopyrimidines] derivatives were synthesized in the time range of 10-20 min with an efficiency of over 85%. As a final result, it can be concluded that the microwave synthesis method improves the unique properties of magnetic nanostructures, especially its specific surface area, and has increased its efficiency.

Cepheid Xpert Xpress Flu/RSV evaluation performed by minimally trained non-laboratory operators in a CLIA-waived environment.

The COVID-19 pandemic highlighted the significance of readily available and easily performed viral testing for surveillance during future infectious pandemics. The objectives of this study were: to assess the performance of the Xpert Xpress Flu and/or RSV test, a multiplex PCR assay for detecting influenza A and B virus and respiratory syncytial virus nucleic acids in respiratory tract specimens, relative to the Quidel Lyra Influenza A+B assay and the Prodesse ProFlu+ assay, and the system's ease of use by minimally trained operators. Overall, the Xpert Xpress Flu/RSV test demonstrated a high positive and negative percent agreement with the comparator assays, and was easy to use and interpret results, based on the operators' feedback. We concluded that the Xpert Xpress Flu/RSV test is sensitive, specific, and easy to use for the diagnosis of influenza and RSV by minimally trained operators and can be a valuable tool in future infectious clusters or pandemics.

Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination.

BACKGROUND: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. METHODS: We evaluated anti-membrane antibodies in COVID-19 naive, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. RESULTS: We found that anti-membrane antibodies persist for at least 1 year and are a sensitive and specific marker of past COVID-19 infection. CONCLUSIONS: Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naive states to advance public health and research.

Volumetric quantification of choroid and Haller's sublayer using OCT scans: An accurate and unified approach based on stratified smoothing.

BACKGROUND AND OBJECTIVE: The choroid, a dense vascular structure in the posterior segment of the eye, maintains the health of the retina by supplying oxygen and nutrients, and assumes clinical significance in screening ocular diseases including age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR). As a technological assist, algorithmic estimation of choroidal biomarkers has been suggested based on sectional (B-scan) optical coherence tomography (OCT) images. However, most such 2D estimation techniques are compute-intensive, yet enjoy limited accuracy and have only been validated on OCT image datasets of healthy eyes. Not surprisingly, fine-scale analyses, including those involving Haller's sublayer, remain relatively rare and unsophisticated. Against this backdrop, we propose an efficient algorithm to quantify desired biomarkers with improved accuracy based on volume OCT scans. Specifically, we attempted an accurate, computationally light volumetric segmentation method involving stratified smoothing to detect choroid and Haller's sublayer. METHODS: For detecting the various boundaries of the choroid and the Haller's sublayer, we propose a common volumetric method that performs suitable exponential enhancement and maintains smooth spatial continuity across 2D B-scans. Further, we achieve suitable volumetric smoothing by primarily deploying light-duty linear regression, and sparingly using compute-intensive tensor voting, and hence significantly reduce overall complexity. The proposed methodology is tested on five health and five diseased OCT volumes considering various metrics including volumetric Dice coefficient and corresponding quotient measures to facilitate comparison vis-à-vis intra-observer repeatability. RESULTS: On five healthy and five diseased OCT volumes, respectively, the proposed method for choroid segmentation recorded volumetric Dice coefficients of 93.53 % and 93.30 %, which closely approximate the respective reference observer repeatability values of 95.60 % and 95.49 %. In terms of related quotient measures, our method achieved more than 50 % improvement over a recently reported method. In detecting Haller's sublayer as well, our algorithm records statistical performance closely matching that of reference manual method. CONCLUSION: Advancing the state-of-the-art, the proposed volumetric segmentation, tested on both healthy and diseased datasets, demonstrated close match with the manual reference. Our method assumes significance in accurate screening of chorioretinal diseases including AMD, CSCR and pachychoroid. Further, it enables generating accurate training data for developing deep learning models for improved detection of choroid and Haller's sublayer.

The Impact of Alcohol Use Disorder on Tuberculosis: A Review of the Epidemiology and Potential Immunologic Mechanisms.

Globally, an estimated 107 million people have an alcohol use disorder (AUD) leading to 2.8 million premature deaths each year. Tuberculosis (TB) is one of the leading causes of death globally and over 8% of global TB cases are estimated to be attributable to AUD. Social determinants of health such as poverty and undernutrition are often shared among those with AUD and TB and could explain the epidemiologic association between them. However, recent studies suggest that these shared risk factors do not fully account for the increased risk of TB in people with AUD. In fact, AUD has been shown to be an independent risk factor for TB, with a linear increase in the risk for TB with increasing alcohol consumption. While few studies have focused on potential biological mechanisms underlying the link between AUD and TB, substantial overlap exists between the effects of alcohol on lung immunity and the mechanisms exploited by Mycobacterium tuberculosis (Mtb) to establish infection. Alcohol misuse impairs the immune functions of the alveolar macrophage, the resident innate immune effector in the lung and the first line of defense against Mtb in the lower respiratory tract. Chronic alcohol ingestion also increases oxidative stress in the alveolar space, which could in turn facilitate Mtb growth. In this manuscript, we review the epidemiologic data that links AUD to TB. We discuss the existing literature on the potential mechanisms by which alcohol increases the risk of TB and review the known effects of alcohol ingestion on lung immunity to elucidate other mechanisms that Mtb may exploit. A more in-depth understanding of the link between AUD and TB will facilitate the development of dual-disease interventions and host-directed therapies to improve lung health and long-term outcomes of TB.

Effects of Graphene Oxide and Crumb Rubber on the Fresh Properties of Self-Compacting Engineered Cementitious Composite Using Response Surface Methodology.

Graphene oxide-modified rubberized engineered cementitious composite (GO-RECC) is attracting the attention of researchers because of the reported benefits of the GO and crumb rubber (CR) on the strength and deformation properties of the composite. While it is well established that GO negatively affects the workability of cementitious composites, its influence on the attainment of the desired self-compacting (SC) properties of ECC has not yet been thoroughly investigated, especially when combined with crumb rubber (CR). In addition, to simplify the number of trial mixes involved in designing SC-GO-RECC, there is a need to develop and optimize the process using Design of Experiment (DOE) methods. Hence, this research aims to investigate and model using response surface methodology (RSM), the combined effects of the GO and CR on the SC properties of ECC through the determination of T500, slump flow, V-funnel, and L-box ratio of the SC-GORECC as the responses, following the European Federation of National Associations Representing for Concrete (EFNARC) 2005 specifications. The input factors considered were the GO by wt.% of cement (0.02, 0.04, 0.06, and 0.08) and CR as a replacement of fine aggregate by volume (5, 10, and 15%). The results showed that increasing the percentages of GO and CR affected the fresh properties of the SC-GORECC adversely. However, all mixes have T500 of 2.4 to 5.2 s, slump flow of 645 to 800 mm, V-funnel time of 7.1 to 12.3 s, and L-box ratio (H2/H1) of 0.8 to 0.98, which are all within acceptable limits specified by EFNARC 2005. The developed response prediction models were well fitted with R2 values ranging from 91 to 99%. Through the optimization process, optimal values of GO and CR were found to be 0.067% and 6.8%, respectively, at a desirability value of 1.0.