Higher levels of brain injury biomarker tau are associated with unfavorable outcomes in patients supported with ECMO following cardiac arrest.

Aim: We sought to determine if higher plasma levels of brain injury biomarkers neurofilament light (NfL), phosphorylated tau 181 (pT181), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) were associated with unfavorable outcomes in children supported on extracorporeal membrane oxygenation (ECMO) with and without preceding cardiac arrest. Methods: We conducted a secondary analysis of a two-center prospective observational study of ECMO patients 0-<18 years. Plasma concentrations of NfL, pT181, tau, and UCHL1 were measured on ECMO days 1, 2 and 3. Unfavorable outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category (PCPC) >2 with decline from baseline PCPC among survivors. Results: Among 88 children on ECMO, mean tau levels were significantly higher on each of the first three ECMO days in children who underwent extracorporeal cardiopulmonary resuscitation (ECPR) compared to those with non-ECPR cardiac arrest or with no cardiac arrest preceding ECMO. Higher ECMO day 1 tau levels were significantly associated with increased hazard of unfavorable outcome in unadjusted (HR, 1.35, 95% CI 1.09-1.66) and adjusted (HR, 1.42; 95% CI 1.13-1.79) models. Higher levels of NfL or pT181 were not associated with increased hazard for unfavorable outcome in multivariable models. UCHL1 values were outside of detectable limits and thus deferred from analysis. Conclusions: Levels of tau were significantly associated with increased hazard of death or unfavorable neurologic outcome in unadjusted and adjusted models. Biomarkers of brain injury, particularly tau, may aid in detection of neurologic injury and neuroprognostication in patients on ECMO with and without preceding cardiac arrest.

Evaluating Fixed Single-Point Parameters When Applied to Vestibular Evoked Myogenic Potentials: The Effect of Single Point and Signal Window.

OBJECTIVES: Several studies have applied a common objective detection algorithm (fixed single point [ Fsp ]) for detection of the vestibular evoked myogenic potential (VEMP). However, fundamental parameters of Fsp , such as establishing the location and duration of a signal window, have not been examined. In addition, Fsp criterion values used for response detection have not been established for cervical VEMPs (cVEMPs) or ocular VEMPs (oVEMPs). The purpose of this article was to investigate the effect of various single points and signal windows on Fsp , as well as determining Fsp criteria to determine response presence for cVEMP and oVEMP in a group of young healthy participants. DESIGN: Twenty young healthy adults under the age of 30 and with no history of hearing or balance concerns were enrolled in the study protocol. Air-conducted cVEMPs and oVEMPs were evoked using 500 Hz tone bursts at 123 dB pSPL recorded at a fixed electromyography activation of 50 µV for cVEMPs and 35° gaze angle for oVEMPs. Responses were analyzed off-line using visual and objective detection. Fsp was applied to cVEMPs and oVEMPs using a range of single points and signal windows. RESULTS: Noise variance was lowest for cVEMPs at the latency of P1, and for oVEMPs noise variance was not significantly different across the single-point latencies. On average, extending the length of the signal window lowered the Fsp value in cVEMPs and oVEMPs. An Fsp value of 2.0 was chosen as the criterion cutoff associated with the 95th percentile during no-response conditions using group data for cVEMPs and oVEMPs, respectively. Fsp values for cVEMPs and oVEMPs were not significantly different from each other. DISCUSSION: This study established single-point latency and time-window parameters for VEMP-related applications of the Fsp detection algorithm. Fsp criteria values were established for cVEMP and oVEMP. Using these parameters, responses were detected in all participants.

Social Acceptability of Health Behavior Posts on Social Media: An Experiment.

INTRODUCTION: Social media sites like Twitter (now X) are increasingly used to create health behavior metrics for public health surveillance. Yet little is known about social norms that may bias the content of posts about health behaviors. Social norms for posts about four health behaviors (smoking tobacco, drinking alcohol, physical activity, eating food) on Twitter/X were evaluated. METHODS: This was a randomized experiment delivered via web-based survey to adult, English-speaking Twitter/X users in three Michigan, USA, counties from 2020 to 2022 (n=559). Each participant viewed 24 posts presenting experimental manipulations regarding four health behaviors and answered questions about each post's social acceptability. Principal component analysis was used to combine survey responses into one perceived social acceptability measure. Linear mixed models with the Benjamini-Hochberg correction were implemented to test seven study hypotheses in 2023. RESULTS: Supporting six hypotheses, posts presenting healthier (CI: 0.028, 0.454), less stigmatized behaviors (CI: 0.552, 0.157) were more socially acceptable than posts regarding unhealthier, stigmatized behaviors. Unhealthy (CI: -0.268, -0.109) and stigmatized behavior (CI: -0.261, -0.103) posts were less acceptable for more educated participants. Posts about collocated activities (CI: 0.410, 0.573) and accompanied by expressions of liking (CI: 0.906, 1.11) were more acceptable than activities undertaken alone or disliked. Contrary to one hypothesis, posts reporting unusual activities were less acceptable than usual ones (CI: -0.472, 0.312). CONCLUSIONS: Perceived social acceptability may be associated with the frequency and content of health behavior posts. Users of Twitter/X and other social media platform posts to estimate health behavior prevalence should account for potential estimation biases from perceived social acceptability of posts.

COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.

BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.

Self-Reported Symptoms of Vertigo and Imbalance Are Prevalent Among Adults With Chronic Moderate-Severe Traumatic Brain Injury: A Preliminary Analysis.

PURPOSE: Dizziness and imbalance are common symptoms during the acute phase of traumatic brain injury (TBI). However, there is evidence to suggest that these symptoms persist into the chronic phase of injury. Few prospective studies have examined the frequency and type of dizziness and imbalance in adults with chronic moderate-severe TBI. The aim of this preliminary analysis was to investigate the prevalence of these symptoms in adults with chronic moderate-severe TBI. METHOD: Twenty-four adults with chronic moderate-severe TBI and a group of 19 age-, sex-, and education-matched noninjured comparison participants were recruited. Self-reported dizziness and imbalance were measured using a modified version of a standard case history form. Significant associations between group (TBI group or noninjured comparison [NC] participants) and self-reports of dizziness, imbalance, and related symptoms (endorsed "yes" or "no") were explored. RESULTS: The TBI group most reported lightheadedness (75%), vertigo (38%), and imbalance and/or falling (46%). The most common related symptom reported by the TBI group was headache (63%) and nausea (46%). Significant associations revealed that the TBI group responded "yes" in higher percentages than the NC group across all categories (dizziness, imbalance, and related symptoms). There were no statistically significant relationships among dizziness, imbalance, or headache symptoms within the TBI group. CONCLUSIONS: These preliminary findings suggest that dizziness and imbalance are prevalent in adults with chronic moderate-severe TBI. Persistent vertiginous symptoms may point to an underlying vestibular impairment. However, further research is needed to characterize vestibular function in chronic moderate-severe TBI.

Structure and dynamics of the contractile vacuole complex in Tetrahymena thermophila.

The contractile vacuole complex (CVC) is a dynamic and morphologically complex membrane organelle, comprising a large vesicle (bladder) linked with a tubular reticulum (spongiome). CVCs provide key osmoregulatory roles across diverse eukaryotic lineages, but probing the mechanisms underlying their structure and function is hampered by the limited tools available for in vivo analysis. In the experimentally tractable ciliate Tetrahymena thermophila, we describe four proteins that, as endogenously tagged constructs, localize specifically to distinct CVC zones. The DOPEY homolog Dop1p and the CORVET subunit Vps8Dp localize both to the bladder and spongiome but with different local distributions that are sensitive to osmotic perturbation, whereas the lipid scramblase Scr7p colocalizes with Vps8Dp. The H+-ATPase subunit Vma4 is spongiome specific. The live imaging permitted by these probes revealed dynamics at multiple scales including rapid exchange of CVC-localized and soluble protein pools versus lateral diffusion in the spongiome, spongiome extension and branching, and CVC formation during mitosis. Although the association with DOP1 and VPS8D implicate the CVC in endosomal trafficking, both the bladder and spongiome might be isolated from bulk endocytic input.

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network.

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19-59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%).

The Tetrahymena bcd1 mutant implicates endosome trafficking in ciliate, cortical pattern formation.

Ciliates, such as Tetrahymena thermophila, evolved complex mechanisms to determine both the location and dimensions of cortical organelles such as the oral apparatus (OA: involved in phagocytosis), cytoproct (Cyp: for eliminating wastes), and contractile vacuole pores (CVPs: involved in water expulsion). Mutations have been recovered in Tetrahymena that affect both the localization of such organelles along anterior-posterior and circumferential body axes and their dimensions. Here we describe BCD1, a ciliate pattern gene that encodes a conserved Beige-BEACH domain-containing protein a with possible protein kinase A (PKA)-anchoring activity. Similar proteins have been implicated in endosome trafficking and are linked to human Chediak-Higashi syndrome and autism. Mutations in the BCD1 gene broaden cortical organelle domains as they assemble during predivision development. The Bcd1 protein localizes to membrane pockets at the base of every cilium that are active in endocytosis. PKA activity has been shown to promote endocytosis in other organisms, so we blocked clathrin-mediated endocytosis (using "dynasore") and inhibited PKA (using H89). In both cases, treatment produced partial phenocopies of the bcd1 pattern mutant. This study supports a model in which the dimensions of diverse cortical organelle assembly-platforms may be determined by regulated balance between constitutive exocytic delivery and PKA-regulated endocytic retrieval of organelle materials and determinants.

Dynamic Bayesian Model for Detecting Obstructive Respiratory Events by Using an Experimental Model.

In this study, we propose a model-based tool for the detection of obstructive apnea episodes by using ECG features from a single lead channel. Several sequences of recurrent apnea were provoked in separate 15-min periods in anesthetized rats during an experimental model of obstructive sleep apnea (OSA). Morphology-based ECG markers and the beat-to-beat interval (RR) were assessed in each sequence. These markers were used to train dynamic Bayesian networks (DBN) with different orders and feature combinations to find a good tradeoff between network complexity and apnea-detection performance. By using a filtering approach, the resulting DBNs were used to infer the apnea probability signal for subsequent episodes in the same rat. These signals were then processed using by 15-s epochs to determine whether epochs were classified as apneic or nonapneic. Our results showed that fifth-order models provided suitable RMSE values, since higher order models become significantly more complex and present worse generalization. A global threshold of 0.2 gave the best overall performance for all combinations tested, with Acc = 81.3%, Se = 69.8% and Sp = 81.5%, using only two parameters including the RR and Ds (R-wave downslope) markers. We concluded that multivariate models using DBNs represent a powerful tool for detecting obstructive apnea episodes in short segments, which may also serve to estimate the number of total events in a given time period.

A Comprehensive Review on Bariatric Endoscopy: Where We Are Now and Where We Are Going.

Background: Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings. Primary bariatric endoscopic therapies: Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions. Revisional bariatric therapies: Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.

Whole genome analysis of Gram-negative bacteria using the EPISEQ CS application and other bioinformatic platforms.

OBJECTIVES: To determine genomic characteristics and molecular epidemiology of carbapenem non-susceptible Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa from medical centres of Mexico using whole genome sequencing data analysed with the EPISEQⓇ CS application and other bioinformatic platforms. METHODS: Clinical isolates collected from 28 centres in Mexico included carbapenem-non-susceptible K. pneumoniae (n = 22), E. coli (n = 24), A. baumannii (n = 16), and P. aeruginosa (n = 13). Isolates were subjected to whole genome sequencing using the Illumina (MiSeq) platform. FASTQ files were uploaded to the EPISEQⓇ CS application for analysis. Additionally, the tools Kleborate v2.0.4 and Pathogenwatch were used as comparators for Klebsiella genomes, and the bacterial whole genome sequence typing database was used for E. coli and A. baumannii. RESULTS: For K. pneumoniae, both bioinformatic approaches detected multiple genes encoding aminoglycoside, quinolone, and phenicol resistance, and the presence of blaNDM-1 explained carbapenem non-susceptibility in 18 strains and blaKPC-3 in four strains. Regarding E. coli, both EPISEQⓇ CS and bacterial whole genome sequence typing database analyses detected multiple virulence and resistance genes: 20 of 24 (83.3%) strains carried blaNDM, 3 of 24 (12.4%) carried blaOXA-232, and 1 carried blaOXA-181. Genes that confer resistance to aminoglycosides, tetracyclines, sulfonamides, phenicols, trimethoprim, and macrolides were also detected by both platforms. Regarding A. baumannii, the most frequent carbapenemase-encoding gene detected by both platforms was blaOXA-72, followed by blaOXA-66. Both approaches detected similar genes for aminoglycosides, carbapenems, tetracyclines, phenicols, and sulfonamides. Regarding P. aeruginosa, blaVIM, blaIMP, and blaGES were the more frequently detected. Multiple virulence genes were detected in all strains. CONCLUSION: Compared to the other available platforms, EPISEQⓇ CS enabled a comprehensive resistance and virulence analysis, providing a reliable method for bacterial strain typing and characterization of the virulome and resistome.

Bacterial incidence and drug resistance from pathogens recovered from blood, cerebrospinal and pleural fluids in 2019-2020. Results of the Invifar network.

Background: Antimicrobial resistance is a global concern. Analysis of sterile fluids is essential because microorganisms are defined as significant in most cases. Blood, cerebrospinal, and pleural fluids are frequently received in the microbiology lab because they are associated with considerable rates of morbi-mortality. Knowledge of epidemiology in these samples is needed to choose proper empirical treatments due to the importance of reducing selection pressure. Methods: We used retrospective laboratory data of blood, CSF, and pleural fluid collected from patients in Mexico between 2019 and 2020. Each laboratory identified the strains and tested susceptibility using its routine methods. For Streptococcus pneumoniae, a comparative analysis was performed with data from the broth microdilution method. Results: Forty-five centers participated in the study, with 30,746 clinical isolates from blood, 2,429 from pleural fluid, and 2,275 from CSF. For blood and CSF, Staphylococcus epidermidis was the most frequent. For blood, among gram negatives, the most frequent was Escherichia coli. Among Enterobacterales, 9.8% of K. pneumoniae were carbapenem-resistant. For S. pneumoniae, similar resistance percentages were observed for levofloxacin, cefotaxime, and vancomycin. For CSF, the most frequent gram-negative was E. coli. In Acinetobacter baumannii, carbapenem resistance was 71.4%. The most frequent species detected for pleural fluid was E. coli; in A. baumannii, carbapenem resistance was 96.3%. Conclusion: Gram-negative bacteria, with E. coli most prevalent, are frequently recovered from CSF, blood, and pleural fluid. In S. pneumoniae, the routine, conventional methods showed good agreement in detecting resistance percentages for erythromycin, levofloxacin, and vancomycin.

Diagnostic accuracy of uroflowmetry parameters to predict infravesical obstruction / Exactitud diagnóstica de los parámetros de la flujometría para predecir la obstrucción infravesical

Objective: to evaluate the performance statistics of average flow (Qave), voiding time (Vtime), and time to maximum flow (TQmax), in addition to maximum flow (Qmax), for diagnosis of infravesical obstruction. Methods: we reviewed urodynamic studies performed in men > 40 years. Obstruction was considered a grade 3-6 in the Schäfer nomogram. Sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and the receiver operator characteristic (ROC) curve were calculated for the different components of free uroflowmetry. Results: we analyzed 432 studies. Patients with obstruction had lower values of Qmax and Qave, and higher values of Vtime and TQmax. Considering different thresholds, Qmax had sensitivity, specificity, LR + and LR- values of 12-83%, 50-97%, 1.7-4.46 and 0.32-0.9, respectively; Qave had sensitivity, specificity, LR + and LR- values of 65-95%, 21-66%, 1.22-1.94 and 0.19-0.53, respectively; Vtime had sensitivity, specificity, LR + and LR- values of 49-85%, 26-67%, 1.15-1.54, and 0.57-0.74, respectively; TQmax had a sensitivity, specificity, LR + and LR- of 36-81%, 22-72%, 1.04-1.33 and 0.85-0.87, respectively. The areas under the ROC curves for Qmax, Qave, Vtime and TQmax were 0.75 (95% CI = 0.71-0.79, p < 0.001), 0.71 (95% CI = 0.66-0.75, p < 0.001), 0.62 (95% CI = 0.57-0.67, p < 0.001) and 0.55 (95% CI = 0.5-0.6, p = 0.03), respectively. Conclusions: Qave, Vtime, and TQmax showed a statistically significant discriminatory capacity to predict infravesical obstruction, and therefore they have clinical value as a complement to the information provided by Qmax.

Objetivo: evaluar las estadísticas de desempeño del flujo promedio (Qave), el tiempo de evacuación (Vtime) y el tiempo hasta el flujo máximo (TQmax), además del flujo máximo (Qmax), para el diagnóstico de obstrucción infravesical. Métodos: revisamos urodinamias realizadas en hombres > 40 años. La obstrucción se consideró un grado 3-6 en el nomograma de Schäfer. Se calcularon la sensibilidad, la especificidad, la razón de verosimilitud positiva (LR +), la razón de verosimilitud negativa (LR-) y la curva característica operativa del receptor (ROC) para los diferentes componentes de la flujometría libre. Resultados: analizamos 443 estudios. Los pacientes con obstrucción tenían valores más bajos de Qmax y Qave, y valores más altos de Vtime y TQmax. Considerando diferentes umbrales, el Qmax tuvo valores de sensibilidad, especificidad, LR + y LR- de 12-83%, 50-97%, 1.7-4.46 y 0.32-0.9, respectivamente; Qave tuvo valores de sensibilidad, especificidad, LR + y LR- de 65-95%, 21-66%, 1.22-1.94 y 0.19-0.53, respectivamente; Vtime tuvo valores de sensibilidad, especificidad, LR + y LR- de 49-85%, 26-67%, 1.15-1.54 y 0.57-0.74, respectivamente; TQmax tuvo una sensibilidad, especificidad, LR + y LR- de 36-81%, 22-72%, 1.04-1.33 y 0.85-0.87, respectivamente. Las áreas bajo las curvas ROC para Qmax, Qave, Vtime y TQmax fueron 0,75 (95% CI = 0.71-0.79, p < 0,001), 0.71 (95% CI = 0.66-0.75, p < 0,001), 0.62 (95% CI = 0.57-0.67, p < 0,001) y 0.55 (95% CI = 0.5-0.6, p = 0.03), respectivamente. Conclusiones: Qave, Vtime y TQmax mostraron una capacidad discriminatoria estadísticamente significativa para predecir la obstrucción infravesical, por lo que tienen valor clínico como complemento de la información proporcionada por el Qmax.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Equitable Research PRAXIS: A Framework for Health Informatics Methods.

OBJECTIVES: There is growing attention to health equity in health informatics research. However, the literature lacks a comprehensive framework outlining critical considerations for health informatics research with marginalized groups. METHODS: Literature review and experiences from nine equity-focused health informatics conducted in the United States and Canada. Studies focus on disparities related to age, disability or chronic illness, gender/sex, place of residence (rural/urban), race/ethnicity, sexual orientation, and socioeconomic status. RESULTS: We found four key equity-related methodological considerations. To assist informaticists in addressing equity, we contribute a novel framework to synthesize these four considerations: PRAXIS (Participation and Representation, Appropriate methods and interventions, conteXtualization and structural competence, Investigation of Systematic differences). Participation and representation refers to the necessity for meaningful participation of marginalized groups in research, to elevate the voices of marginalized people, and to represent marginalized people as they are comfortable (e.g., asset-based versus deficit-based). Appropriate methods and interventions mean targeting methods, instruments, and interventions to reach and engage marginalized people. Contextualization and structural competence mean avoiding individualization of systematic disparities and targeting social conditions that (re-)produce inequities. Investigation of systematic differences highlights that experiences of people marginalized according to specific traits differ from those not so marginalized, and thus encourages studying the specificity of these differences and investigating and preventing intervention-generated inequality. We outline guidance for operationalizing these considerations at four research stages. CONCLUSIONS: This framework can assist informaticists in systematically addressing these considerations in their research in four research stages: project initiation; sampling and recruitment; data collection; and data analysis. We encourage others to use these insights from multiple studies to advance health equity in informatics.

Effects of Age and Middle Ear on the Frequency Tuning of the cVEMP and oVEMP.

BACKGROUND: Upward shift in the air conducted (AC) frequency tuning of vestibular evoked myogenic potentials (VEMPs) as an effect of aging is hypothesized to be due to the microstructural stiffening changes in the inner ear. However, with an AC stimulus, it may be possible that the shift in the frequency tuning of VEMPs as an effect of aging may also be due to contributions from the middle ear. PURPOSE: The main aim of this study was to examine the effects of age on the frequency tuning of the cervical VEMP (cVEMP) and ocular VEMP (oVEMP) and determine the role of middle ear transmission characteristics in shaping these effects. RESEARCH DESIGN: Standard group comparison. STUDY SAMPLE: One-hundred seven participants divided in three groups: young adult, middle-age, and older adults with "normal" middle ear and negative history of neurological or vestibular complaints. DATA COLLECTION AND ANALYSES: Middle ear measures included static admittance and middle ear resonant frequency. cVEMP and oVEMPs were elicited with AC tone bursts at 500, 750, and 1,000 Hz. RESULTS: No significant effect of age was observed on any of the middle ear measures. There was a significant effect of age on the amplitude of the cVEMP, but this effect was frequency specific. The age-related reduction in cVEMP corrected amplitude was only observed when the eliciting stimulus was 500 or 750 Hz, with no significant effect observed with a 1,000 Hz stimulus. For the oVEMP, the effects of age were apparent at all stimulus frequencies. We also observed a general upward shift in the frequency tuning of both the cVEMP and oVEMP for middle-age and older adults, with 750 and 1,000 Hz yielding higher response rates and larger amplitudes among middle-aged and older adults. Measurements of middle ear did not significantly contribute to the observed findings. CONCLUSIONS: The upward shift in frequency tuning of VEMPs among middle age and older adults could be due to the changes in the vestibular system and not from the middle ear. These results support the use of different frequency stimuli (i.e., 750 or 1,000 Hz) to elicit a VEMP if a response is absent using a 500 Hz stimulus, especially in patients over the age of 40.

Subcapsular Sinus Macrophages Promote Melanoma Metastasis to the Sentinel Lymph Nodes via an IL1α-STAT3 Axis.

During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLN. We found that macrophages located in the subcapsular sinus (SS) produced protumoral IL1α after recognition of tumoral antigens. Moreover, we confirmed that the elimination of LN macrophages or the administration of an IL1α-specific blocking antibody reduced metastatic spread. To understand the mechanism of action of IL1α in the context of the sLN microenvironment, we applied single-cell RNA sequencing to microdissected metastases obtained from animals treated with the IL1α-specific blocking antibody. Among the different pathways affected, we identified STAT3 as one of the main targets of IL1α signaling in metastatic tumor cells. Moreover, we found that the antitumoral effect of the anti-IL1α was not mediated by lymphocytes because Il1r1 knockout mice did not show significant differences in metastasis growth. Finally, we found a synergistic antimetastatic effect of the combination of IL1α blockade and STAT3 inhibition with stattic, highlighting a new immunotherapy approach to preventing melanoma metastasis.

The effect of EMG magnitude on the masseter vestibular evoked myogenic potential (mVEMP).

Introduction: The masseter vestibular evoked myogenic potential (mVEMP) is a bilaterally generated, electromyographically (EMG)-mediated response innervated by the trigeminal nerve. The purpose of the present investigation was to 1) determine whether subjects could accurately achieve and maintain a range of EMG target levels, 2) to examine the effects of varied EMG levels on the latencies and amplitudes of the mVEMP, and 3) to investigate the degree of side-to-side asymmetry and any effects of EMG activation. Methods: Subjects were nine neurologically and otologically normal young adults. A high-intensity tone burst was presented monaurally while subjects were seated upright and asked to match a range of EMG target levels by clenching their teeth. Recordings were made from the ipsilateral and contralateral masseter muscles referenced to the ear being monaurally stimulated. Results: We found that the tonic EMG target had no effect on mVEMP latency. Additionally, although mVEMP amplitudes "scaled" to the EMG target, there was a tendency for the subjects' EMG level to "undershoot" the EMG target levels greater than 50 µV. While some individuals did generate differences in EMG activation between sides, there were no significant differences on average EMG activation between sides. Further, while average corrected amplitude asymmetry was similar across EMG targets, some individuals demonstrated large, corrected amplitude asymmetry ratios. Conclusions: The results of this investigation suggest that, as with cVEMP recordings, the underlying EMG activation may vary between subjects and could impact mVEMP amplitudes, yet could be mitigated by amplitude correction techniques. Further it is important to be aware that even young normal subjects have difficulty maintaining large, tonic EMG activity during the mVEMP recording.

Sensitive Serology Measurements in the Saliva of Individuals with COVID-19 Symptoms Using a Multiplexed Immunoassay.

BACKGROUND: There are numerous benefits to performing salivary serology measurements for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for coronavirus disease 2019 (COVID-19). Here, we used a sensitive multiplex serology assay to quantitate salivary IgG against 4 SARS-CoV-2 antigens: nucleocapsid, receptor-binding domain, spike, and N-terminal domain. METHODS: We used single samples from 90 individuals with COVID-19 diagnosis collected at 0 to 42 days postsymptom onset (PSO) and from 15 uninfected control subjects. The infected individuals were segmented in 4 groups (0-7 days, 8-14 days, 15-21 days, and >21 days) based on days PSO, and values were compared to controls. RESULTS: Compared to controls, infected individuals showed higher levels of antibodies against all antigens starting from 8 days PSO. When applying cut-offs with at least 93.3% specificity at every time interval segment, nucleocapsid protein serology had the best sensitivity at 0 to 7 days PSO (60% sensitivity [35.75% to 80.18%], ROC area under the curve [AUC] = 0.73, P = 0.034). Receptor-binding domain serology had the best sensitivity at 8 to 14 days PSO (83.33% sensitivity [66.44%-92.66%], ROC AUC = 0.90, P < 0.0001), and all assays except for N-terminal domain had 92% sensitivity (75.03%-98.58%) at >14 days PSO. CONCLUSIONS: This study shows that our multiplexed immunoassay can distinguish infected from uninfected individuals and reliably (93.3% specificity) detect seroconversion (in 60% of infected individuals) as early as the first week PSO, using easy-to-collect saliva samples.

Detecting Obstructive Apnea Episodes using Dynamic Bayesian Networks and ECG-based Time-Series.

In this study, we proposed an automatic detector for obstructive apnea episodes using only ECG-based time-series from a single-ECG channel. Several obstructive apnea episodes were provoked for different separated sequences of 15 minutes in anesthetized Sprague-Dawley rats. In this recurrent obstructive sleep apnea (OSA) model, each episode lasted 15s, while the number of total events per sequence was randomly selected. The beat-to-beat interval ( RR) and the R-wave amplitude ( Ra) time-series were extracted and processed for each sequence, and used to train Dynamic Bayesian Networks with different lags. An optimal trade-off between the lag ( L) and RMSE values was considered to select the best model to be used when detecting apnea episodes. The selected models were then used to estimate the occurrence probability of apnea episodes, p(At), by using a filtering approach. Finally, the time-series of the estimated probabilities were post-processed using non-overlapped 15-s epochs, to determine whether they are classified as apneic or non-apneic segments. Results showed that those lagged models with orders greater than 5, presented suitable RMSE values and become more sensitive as the order increased. A detection threshold of 0.2 seems to provide the best apnea detection performance overall, with Acc=0.81, Se=0.83 and Sp=0.79, using two ECG parameters and L=10. Clinical relevance- Dynamic Bayesian Networks represent a powerful tool to develop personalized models for apnea detection and diagnosis in OSA patients.