Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear. METHODS: In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA). RESULTS: In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, PCM1 for the microtubule anchoring module, LIMS1 for the cell-substrate junction module. CONCLUSIONS: In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

The prominent role of Charcot and the French neurological tradition in Latin America.

The establishment of neurology schools in Latin America during the late-nineteenth and early-twentieth centuries profoundly influenced the French neurology school. In the latter half of the nineteenth century, the neurology department at the Salpêtrière Hospital in Paris held a preeminent position as the global hub of neurology. Professor Jean-Martin Charcot, widely acclaimed as the father of modern neurology, was the most revered neurology professor of the nineteenth century. Many physicians from diverse countries across South America (notably Argentina, Uruguay, Peru, Brazil, and Colombia), the Caribbean (Cuba), and Mexico pursued specialized training in neurology under Charcot's tutelage, and even after his passing in 1893, they continued their training with his numerous disciples. As a result, nearly two centuries after the birth of Charcot, his enduring contributions to the field of neurology remain vibrantly influential, particularly in Latin America.

Genomic Characterization of a Clinical NDM-1-Producing Klebsiella michiganensis from Brazil.

Public health faces daily challenges due to increasing reports of pathogenic microorganisms with new antimicrobial resistance. Klebsiella michiganensis, an emerging pathogen, poses difficulty in its identification using conventional techniques. This study presents the first documented case of NDM-1-producing K. michiganensis in Brazil, identified as the new ST418. Initially, the isolate from a tracheal secretion was misidentified as K. oxytoca. However, accurate identification was achieved through ANI analyses. Whole-genome sequencing was conducted to characterize the genetic context of the resistance genes, to identify virulence factors, and to construct a phylogenetic tree. The blaNDM-1 gene was found to be harbored on an IncFIB plasmid approximately 112 kb in length, which was transferable in conjugation assays. The detection of carbapenem resistance genes in this species highlights the importance of public health vigilance, as it may serve as a reservoir and disseminator of significant resistance genes.

A hiatus in the rivalry between Pierre Marie and Jules Dejerine: a collaborative study on sensory disorders by Andre Pierre Marie and Gustave Roussy.

Personal and professional rivalries involving prominent neurologists mark the history of nineteenth-century French neurology. One of the great examples is the feud between Pierre Marie and Jules Dejerine. The dispute between the two, nevertheless, did not prevent Pierre Marie's son, André Marie, and Gustave Roussy - one of Dejerine's favorite pupils, from collaborating on significant research that led to the doctoral dissertation by Andre Marie regarding sensory disturbances associated with painful hemiagnosia found in thalamic lesions.

As rivalidades pessoais e profissionais entre neurologistas proeminentes marcaram a história da neurologia francesa do século XIX. Um dos grandes exemplos é a rivalidade entre Pierre Marie e Jules Dejerine. A disputa entre os dois, no entanto, não impediu que o filho de Pierre Marie, André Marie, e Gustave Roussy, um dos pupilos preferidos de Dejerine, colaborassem numa investigação significativa que resultou na tese de doutorado de André Marie sobre os distúrbios sensoriais associados à hemiagnosia dolorosa encontrada nas lesões talâmicas.

Defining Levels of US Hospitals' Pediatric Capabilities.

Importance: Classifying hospitals across a wide range of pediatric capabilities, including medical, surgical, and specialty services, would improve understanding of access and outcomes. Objective: To develop a classification system for hospitals' pediatric capabilities. Design, Setting, and Participants: This cross-sectional study included data from 2019 on all acute care hospitals with emergency departments in 10 US states that treated at least 1 child per day. Statistical analysis was performed from September 2023 to February 2024. Exposure: Pediatric hospital capability level, defined using latent class analysis. The latent class model parameters were the presence or absence of 26 functional capabilities, which ranged from performing laceration repairs to performing organ transplants. A simplified approach to categorization was derived and externally validated by comparing each hospital's latent class model classification with its simplified classification using data from 3 additional states. Main Outcomes and Measures: Health care utilization and structural characteristics, including inpatient beds, pediatric intensive care unit (PICU) beds, and referral rates (proportion of patients transferred among patients unable to be discharged). Results: Using data from 1061 hospitals (716 metropolitan [67.5%]) with a median of 2934 pediatric ED encounters per year (IQR, 1367-5996), the latent class model revealed 4 pediatric levels, with a median confidence of hospital assignment to level of 100% (IQR, 99%-100%). Of 26 functional capabilities, level 1 hospitals had a median of 24 capabilities (IQR, 21-25), level 2 hospitals had a median of 13 (IQR, 11-15), level 3 hospitals had a median of 8 (IQR, 6-9), and level 4 hospitals had a median of 3 (IQR, 2-3). Pediatric level 1 hospitals had a median of 66 inpatient beds (IQR, 42-86), level 2 hospitals had a median of 16 (IQR, 9-22), level 3 hospitals had a median of 0 (IQR, 0-6), and level 4 hospitals had a median of 0 (IQR, 0-0) (P < .001). Level 1 hospitals had a median of 19 PICU beds (IQR, 10-28), level 2 hospitals had a median of 0 (IQR, 0-5), level 3 hospitals had a median of 0 (IQR, 0-0), and level 4 hospitals had a median of 0 (IQR, 0-0) (P < .001). Level 1 hospitals had a median referral rate of 1% (IQR, 1%-3%), level 2 hospitals had a median of 25% (IQR, 9%-45%), level 3 hospitals had a median of 70% (IQR, 52%-84%), and level 4 hospitals had a median of 100% (IQR, 98%-100%) (P < .001). Conclusions and Relevance: In this cross-sectional study of hospitals from 10 US states, a system to classify hospitals' pediatric capabilities in 4 levels was developed and was associated with structural and health care utilization characteristics. This system can be used to understand and track national pediatric acute care access and outcomes.

Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis.

BACKGROUND: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (ß: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß: 1.98; 95% CI: 0.33, 3.64). CONCLUSIONS: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions.

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy's development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and ß adrenergic receptors, which are the key components of epinephrine's mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.

Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts.

OBJECTIVE: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. STUDY DESIGN: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines. RESULTS: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts. CONCLUSIONS: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

Estimating the size and scope of the academic emergency physician workforce.

BACKGROUND: Academic emergency medicine (EM) is foundational to the EM specialty through the development of new knowledge and clinical training of resident physicians. Despite recent increased attention to the future of the EM workforce, no evaluations have specifically characterized the U.S. academic EM workforce. We sought to estimate the national proportion of emergency physicians (EPs) identified as academic and the proportion of emergency department (ED) visits that take place at academic sites. METHODS: We performed a cross-sectional analysis of EPs and EDs using data from the American Hospital Association, the Centers for Medicare & Medicaid Services, and Doximity's Residency Navigator. EPs were identified as "academic" if they were affiliated with at least one facility determined to be academic, defined as EDs officially designated by the Accreditation Council for Graduate Medical Education (ACGME) as clinical training sites at accredited EM residency programs. Our primary outcomes were to estimate the national proportion of EPs identified as academic and the proportion of ED visits performed at academic sites. RESULTS: Our analytic sample included 26,937 EPs practicing clinically across 4920 EDs and providing care during 130,471,386 ED visits. Among EPs, 11,720 (43.5%) were identified as academic, and among EDs, 635 (12.9%) were identified as academic sites, including 585 adult/general sites, 45 pediatric-specific sites, and 10 sites affiliated with the Department of Veterans Affairs. In 2021, academic EDs provided care for 42,794,106 ED visits or 32.8% of all ED visits nationally. CONCLUSIONS: Approximately four in 10 EPs practice in at least one clinical training site affiliated with an ACGME-accredited EM residency program, and approximately one in three ED visits nationally occur in these academic EDs. We encourage further work using alternative definitions of an academic EPs and EDs, along with longitudinal research to identify trends in the workforce's composition.

"Right now, it's kind of haphazard"-Pediatric emergency care coordinators and quality of emergency care for children: A qualitative study.

Objectives: Pediatric readiness varies widely among emergency departments (EDs). The presence of a pediatric emergency care coordinator (PECC) has been associated with improved pediatric readiness and decreased mortality, but adoption of PECCs has been limited. Our objective was to understand factors associated with PECC implementation in general EDs. Methods: We conducted semistructured qualitative interviews with a purposively sampled set of EDs with and without PECCs. Interviews were completed, transcribed, and coded until thematic saturation was reached. Themes were identified through a consensus process and mapped to the Consolidated Framework for Implementation Research (CFIR). Results: Twenty-four interviews were conducted and mapped to themes related to innovation, individuals and implementation process, outer setting (health system), and inner setting (hospital/ED). Addressing innovation, individuals, and implementation process, the primary theme was variability in how the PECC role was defined and who was responsible for implementing it. Regarding the outer setting, participants reported that limited system resources affected their ability to implement the PECC role. Key inner setting themes included concerns about limited visit volume, a lack of systems for measuring pediatric quality of care, and significant tension around change. Conclusions: Implementation of the PECC role appears to be limited by heterogeneous interpretations of the PECC, de-prioritization of pediatrics, and limited system resources. However, many participants described motivation to improve pediatric care and implement the PECC role in context of increasing pediatric visits; they offered strategies for future implementation efforts.

Development and Evaluation of Modified Criteria for Infant and Toddler Anaphylaxis.

BACKGROUND: Current clinical criteria for identifying anaphylaxis do not account for unique aspects of infant anaphylaxis presentation and have not been validated in patients younger than 2 years of age. This may contribute to under recognition and is thus an unmet need. OBJECTIVE: To demonstrate age-specific signs and symptoms that more accurately identify anaphylaxis in young children and to develop and compare modified criteria for "likely anaphylaxis" against the widely used 2006 National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria. METHODS: Retrospective chart review of 337 clinical encounters presenting with suspected allergic or anaphylactic reactions to a pediatric emergency department. Modified criteria for likely anaphylaxis were developed and evaluated against the NIAID/FAAN criteria. RESULTS: The study population included 33% infants (age < 12 mo), 39% toddlers (age 12 mo to < 36 mo), and 29% children (age ≥ 36 mo). The NIAID/FAAN criteria captured 85% of all patient encounters in the study and the modified criteria captured 98% (P < .001). Compared with NIAID/FAAN criteria, modified criteria had 22.8% improved performance among infants (p < .001) and 10.3% improved performance among toddlers (P = .04). CONCLUSIONS: We developed modified anaphylaxis clinical criteria that incorporated symptoms specific to infants and young children. The modified criteria increased identification of anaphylaxis in infants and potentially toddlers. Future research is needed to validate our findings on a larger cohort.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Other Antimicrobial-Resistant Gram-Negative Pathogens Isolated from Bovine Mastitis: A One Health Perspective.

Antimicrobial resistance (AMR) poses an imminent threat to global public health, driven in part by the widespread use of antimicrobials in both humans and animals. Within the dairy cattle industry, Gram-negative coliforms such as Escherichia coli and Klebsiella pneumoniae stand out as major causative agents of clinical mastitis. These same bacterial species are frequently associated with severe infections in humans, including bloodstream and urinary tract infections, and contribute significantly to the alarming surge in antimicrobial-resistant bacterial infections worldwide. Additionally, mastitis-causing coliforms often carry AMR genes akin to those found in hospital-acquired strains, notably the extended-spectrum beta-lactamase genes. This raises concerns regarding the potential transmission of resistant bacteria and AMR from mastitis cases in dairy cattle to humans. In this narrative review, we explore the distinctive characteristics of antimicrobial-resistant E. coli and Klebsiella spp. strains implicated in clinical mastitis and human infections. We focus on the molecular mechanisms underlying AMR in these bacterial populations and critically evaluate the potential for interspecies transmission. Despite some degree of similarity observed in sequence types and mobile genetic elements between strains found in humans and cows, the existing literature does not provide conclusive evidence to assert that coliforms responsible for mastitis in cows pose a direct threat to human health. Finally, we also scrutinize the existing literature, identifying gaps and limitations, and propose avenues for future research to address these pressing challenges comprehensively.

François Rabelais and his dystonic giants.

Spasmodic torticollis was an early designation used for cervical dystonia. The origin of this name is attributed to French physician and writer François Rabelais in the mid-sixteenth century. This early description of torticollis in the book Pantagruel was an inspiration for the understanding of cervical dystonia. The art expressed in Rabelais' literature ‒ which was immortalized by the drawings of Gustave Doré ‒ influenced poetry, art, and photography, and led to the adoption of the term torticollis in the neurological sciences.

Uma designação inicial usada para distonia cervical era torcicolo espasmódico. A origem desse termo é atribuída ao médico e escritor francês François Rabelais em meados do século XVI. Essa descrição inicial do torcicolo no livro Pantagruel foi uma inspiração para a compreensão da distonia cervical. A arte exibida na literatura de Rabelais ‒ imortalizada pelos desenhos de Gustave Doré ‒ influenciou a poesia, a arte e a fotografia, e levou à adoção do termo torcicolo nas ciências neurológicas.

Patient-related Factors Associated with Potentially Unnecessary Transfers for Pediatric Patients with Asthma: A Retrospective Cohort Study.

Background/Objective: Asthma is a common chronic medical condition among children and the most common diagnosis associated with interfacility transports for pediatric patients. As many as 40% of pediatric transfers may be unnecessary, resulting in potential delays in care and unnecessary costs. Our objective was to identify the patient-related factors associated with potentially unnecessary transfers for pediatric patients with asthma. Methods: We used patient care data from the California Department of Health Care Access and Information patient discharge and emergency department (ED) datasets to capture ED visits where a pediatric patient (age 2-17 years) presented with asthma and was transferred to another ED or acute care hospital. The outcome of interest was a potentially unnecessary transfer, defined as a visit where length of stay after transfer was <24 hours and no advanced services were used, such as respiratory therapy or critical care. Patient-related characteristics were extracted, including age, gender, race/ethnicity, primary language, insurance status, and clinical characteristics. First, we used descriptive statistics to compare necessary vs unnecessary transfers. Second, we used generalized estimating equations accounting for clustering by ED to estimate odds ratios (OR) and identify factors associated with potentially unnecessary transfers. Results: A total of 4,233 pediatric ED patients were transferred with a diagnosis of asthma, including 461 (11%) transfers that met criteria as potentially unnecessary. Median age was 12 years (interquartile range 7-15), and 46% were female. Factors associated with increased odds of potentially unnecessary transfer while controlling for key factors included younger age (eg, 2-5 years, OR 2.0, 95% confidence interval [CI] 1.4-2.9), male gender (OR 1.4, 95% CI 1.1-1.7), and Hispanic ethnicity (OR 1.6, 95% CI 1.2-2.1), while multiple hospitalizations for asthma per year was associated with decreased odds (OR 0.2, 95% CI 0.1-0.4). Conclusion: Several patient-related factors were associated with increased or decreased odds of potentially unnecessary transfers among pediatric patients presenting to the ED with asthma. These factors can be considered in future work to better understand, predict, and reduce unnecessary transfers and their negative consequences.