Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: NHLBI Workshop Report.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.

Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Evaluation of an artificial intelligence-facilitated sperm detection tool in azoospermic samples for use in ICSI.

RESEARCH QUESTION: Can artificial intelligence (AI) improve the efficiency and efficacy of sperm searches in azoospermic samples? DESIGN: This two-phase proof-of-concept study began with a training phase using eight azoospermic patients (>10,000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify spermatozoa. Second, side-by-side testing was undertaken on two cohorts of non-obstructive azoospermia patient samples: an embryologist versus the AI identifying all the spermatozoa in the still images (cohort 1, n = 4), and a side-by-side test with a simulated clinical deployment of the AI model with an intracytoplasmic sperm injection microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, n = 4). RESULTS: In cohort 1, the AI model showed an improvement in the time taken to identify all the spermatozoa per field of view (0.02 ± 0.30  ×  10-5s versus 36.10 ± 1.18s, P < 0.0001) and improved recall (91.95 ± 0.81% versus 86.52 ± 1.34%, P < 0.001) compared with an embryologist. From a total of 2660 spermatozoa to find in all the samples combined, 1937 were found by an embryologist and 1997 were found by the AI in less than 1000th of the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90 ± 3.19 s versus 168.7 ± 7.84 s, P < 0.0001) and found 1396 spermatozoa, while 1274 were found without AI, although no significant difference was observed. CONCLUSIONS: AI-powered image analysis has the potential for seamless integration into laboratory workflows, to reduce the time to identify and isolate spermatozoa from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.

Expert assessment of illegal collecting impacts on Venus flytraps and priorities for research on illegal trade.

Illegal collecting of wild Venus flytraps (Dionaea muscipula) for the horticultural trade represents a persistent threat to populations of the species across their endemic range in the coastal plain of North and South Carolina (United States). Although wild collecting of Venus flytraps is not a novel threat, there has been very little research on the impacts of collecting on the species' conservation to date or why an illegal trade persists alongside a legal one. We drew on qualitative expert stakeholder elicitation to contextualize the threat of illegal collecting to the long-term conservation of Venus flytraps in relation to other anthropogenic threats. Expert elicitation included botanical and conservation researchers, cognizant state and federal agency staff, land managers, and conservation nonprofit actors. The workshop included mapping of supply chain structures and prioritization of social and environmental harms. Expert consensus determined illegal collecting is an ongoing problem for Venus flytrap conservation, but habitat destruction, degradation, and fire suppression are the most significant threats to flytrap conservation. Supply chain analysis showed that observable social and environmental harms of the trade are focused at the supply stage and that less is known about transit and demand stages. Key research gaps identified include a lack of understanding of plant laundering practices relevant to a range of desirable plant taxa; the role of commercial nurseries in illicit horticultural supply chains; motivations for engaging in Venus flytrap collecting; and the persistent demand for illegally harvested plants when cultivated, legally obtainable plants are readily available. Our findings and methodology are relevant to a range of ornamental plants affected by illegal trade for which robust social data on illegal collecting drivers are lacking.

Evaluación experta del impacto de la colecta ilegal de venus atrapamoscas y las prioridades de investigación sobre el mercado ilegal Resumen La colecta ilegal de venus atrapamoscas (Dionaea muscipula) silvestres para el mercado de horticultura representa una amenaza constante para las poblaciones de la especie a lo largo de su distribución endémica en la planicie costera de Carolina del Norte y del Sur, Estados Unidos. Aunque esta colecta no es una amenaza novedosa, a la fecha se ha investigado muy poco sobre su impacto en la conservación de la especie o por qué el mercado ilegal persiste a la par del legal. Partimos del conocimiento cualitativo de los actores expertos para contextualizar la amenaza de la colecta ilegal para la conservación a largo plazo de la venus atrapamoscas en relación con otras amenazas antropogénicas. Este conocimiento involucró a investigadores de la conservación y la botánica, personal consciente de agencias federales y estatales y actores de la conservación sin fines de lucro. El taller incluyó el mapeo de las estructuras de las cadenas de suministro y la priorización de los daños sociales y ambientales. El consenso de los expertos determinó que la colecta ilegal es un problema continuo para la conservación de la venus atrapamoscas, pero la destrucción y degradación del hábitat, así como la contención de incendios son las amenazas más significativas. El análisis de las cadenas de suministro mostró que los daños ambientales y sociales observables en el mercado se enfocan en la fase de suministro y que se sabe poco sobre las fases de tránsito y demanda. Los vacíos de investigación más importantes incluyen la falta de entendimiento de las prácticas de lavado de plantas relevantes para un rango de taxones deseables de plantas; el papel de los viveros comerciales en las cadenas de suministro de la horticultura ilícita; los motivos para participar en la colecta de venus atrapamoscas; y la demanda continua de plantas cosechadas ilegalmente cuando ya hay disponibilidad de plantas cultivadas que se obtienen legalmente. Nuestros descubrimientos y metodología son relevantes para una gama de plantas ornamentales afectadas por el mercado ilegal para las cuales hay carencia de datos sociales sólidos sobre los factores de colecta ilegal.

Specialized and versatile antisocial behavioral profiles in preschoolers: Associations with persistent behavioral problems.

This study investigated specialized and versatile antisocial patterns in preschoolers and examined the link between these patterns and the risk of developing chronic antisocial behaviors throughout childhood. A total of 556 children (50.6% boys, 88% White) participated in this three-wave longitudinal study at 3-5, 6-8, and 10-12 years old. A latent transition analysis revealed that most preschoolers (89.5%) who adopt several subtypes of antisocial behaviors simultaneously exhibit stable and severe antisocial behaviors throughout childhood. In contrast, most preschoolers (60%) who favor one specific subtype of antisocial behaviors desist from such behaviors between preschool and preadolescence. Importantly, aggression accompanied by other subtypes of antisocial behaviors predicted chronicity better than aggression alone, casting doubt on the notion that aggression is the strongest predictor of chronicity.

Delirium Screening in Critically Ill Children: Secondary Analysis of the Multicenter PICU Up! Pilot Trial Dataset, 2019-2020.

OBJECTIVES: To determine the patient-level factors associated with performing daily delirium screening in PICUs with established delirium screening practices. DESIGN: A secondary analysis of 2019-2020 prospective data from the baseline phase of the PICU Up! pilot stepped-wedge multicenter trial (NCT03860168). SETTING: Six PICUs in the United States. PATIENTS: One thousand sixty-four patients who were admitted to a PICU for 3 or more days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1064 patients, 74% (95% CI, 71-76%) underwent delirium screening at least once during their PICU stay. On 57% of the 8965 eligible patient days, screening was conducted. The overall prevalence of delirium was 46% across all screened days, and 64% of screened patients experienced delirium at some point during their PICU stay. Factors associated with greater adjusted odds ratio (aOR) of increased daily delirium screening included PICU stay longer than 15 days compared with 1-3 days (aOR 3.36 [95% CI, 2.62-4.30]), invasive mechanical ventilation as opposed to room air (aOR 1.67 [95% CI, 1.32-2.12]), dexmedetomidine infusions (aOR 1.23 [95% CI, 1.04-1.44]) and propofol infusions (aOR 1.55 [95% CI, 1.08-2.23]). Conversely, decreased aOR of daily delirium screening was associated with female gender (aOR 0.78 [95% CI, 0.63-0.96]), and the administration of continuous infusions of opioids (aOR 0.75 [95% CI, 0.63-0.90]) or ketamine (aOR 0.48 [95% CI, 0.29-0.79]). Neither patient age, the presence of family or physical restraints, or benzodiazepine infusions were associated with daily delirium screening rates. CONCLUSIONS: In the 2019-2020 PICU UP! cohort, across six PICUs, delirium screening occurred on only 57% of days, despite the presence of established practices. Female gender, patients in the early stages of their PICU stay, and patients not receiving mechanical ventilation were associated with lower odds of daily delirium screening. Our results highlight the need for structured quality improvement processes to both standardize and increase the frequency of delirium screening.

Predictors of syrinx presentation and outcomes in pediatric Chiari malformation type I: a single institution experience of 218 consecutive syrinx patients.

PURPOSE: Chiari I malformation (CM-I) in pediatric patients can impose substantial neurologic and functional impairment. Additionally, the presence of syrinx is often a harbinger of clinical compromise, but little attention has been devoted to identifying features associated with syrinx development and the clinical impact of syrinx resolution. Therefore, this study aims to identify clinical and radiographic variables associated with preoperative syrinx presence and postoperative syrinx reduction in pediatric patients with CM-I and determine the relationship between postoperative syrinx reduction and clinical symptom improvement. METHODS: The authors performed a retrospective analysis of 435 consecutive pediatric patients who underwent surgical treatment of CM-I from 2001 to 2021 at a single tertiary pediatric medical center. All patients underwent pre- and postoperative MRI, and clinical and radiographic variables were recorded and subject to inferential analysis. RESULTS: Syrinx at presentation was independently associated with symptoms of spinal cord dysfunction at presentation (OR 2.17 (95% CI 1.05-4.48); p = 0.036), scoliosis (OR 5.33 (2.34-10.86); p = 0.001), and greater pB-C2 (posterior basion to C2 distance) measurement length (OR 1.14 (95% CI 1.01-1.30); p = 0.040). Syrinx at presentation was inversely associated with tussive headaches at presentation (OR 0.27 (95% CI 0.16-0.47); p = 0.001) and cranial nerve deficits at presentation (OR 0.49 (95% CI 0.26-0.92); p = 0.025). Postoperatively, patients with radiographic evidence of syrinx improvement had greater rates of symptom improvement (93.1% vs 82.1%; p = 0.049), better CCOS scores (15.4 vs 14.2; p = 0.001), and decreased rates of readmission (6.0% vs 25.0%, p = 0.002) and reoperation (0.5% vs 35.7%; p = 0.001). The difference in syrinx resolution was similar but not statistically significant (10.3% vs 16.7%; p = 0.251). AO joint anomaly (OR 0.20, 95% CI 0.04-0.95; p = 0.026) and foramen magnum diameter (OR 1.12, 95% CI 1.00-1.25; p = 0.049) were the only independent predictors of syrinx improvement, and surgical technique was the only predictor for syrinx resolution (OR 2.44, 95% CI 1.08-5.50; p = 0.031). Patients that underwent tonsil reduction surgery whose syrinx improved had a wider foramen magnum diameter than those whose did not improve (34.3 vs 31.7; p = 0.028). CONCLUSIONS: Radiographic syrinx improvement is associated with greater rates of symptom improvement and less readmissions and reoperations for CM-I. AO joint anomalies and narrower foramen magnums were independent risk factors for the lack of syrinx improvement. These novel insights will help guide preoperative patient counseling, pre- and intraoperative surgical decision-making, and postoperative clinical prognostication in the treatment of pediatric CM-I.

Survivorship After Neurocritical Care: A Scoping Review of Outcomes Beyond Physical Status.

Following intensive care unit hospitalization, survivors of acute neurological injury often experience debilitating short-term and long-term impairments. Although the physical/motor impairments experienced by survivors of acute neurological injury have been described extensively, fewer studies have examined cognitive, mental health, health-related quality of life (HRQoL), and employment outcomes. This scoping review describes the publication landscape beyond physical and/or motor sequelae in neurocritical care survivors. Databases were searched for terms related to critical illness, intensive care, and outcomes from January 1970 to March 2022. English-language studies of critically ill adults with a primary neurological diagnosis were included if they reported on at least one outcome of interest: cognition, mental health, HRQoL or employment. Data extraction was performed in duplicate for prespecified variables related to study outcomes. Of 16,036 abstracts screened, 74 citations were identified for inclusion. The studies encompassed seven worldwide regions and eight neurocritical diagnosis categories. Publications reporting outcomes of interest increased from 3 before the year 2000 to 71 after. Follow-up time points included ≤ 1 (n = 15 [20%] citations), 3 (n = 28 [38%]), 6 (n = 28 [38%]), and 12 (n = 21 [28%]) months and 1 to 5 (n = 19 [26%]) and > 5 years (n = 8 [11%]), with 28 (38%) citations evaluating outcomes at multiple time points. Sixty-six assessment tools were used to evaluate the four outcomes of interest: 22 evaluating HRQoL (56 [76%] citations), 21 evaluating cognition (20 [27%] citations), 21 evaluating mental health (18 [24%] citations), and 2 evaluating employment (9 [12%] citations). This scoping review aimed to better understand the literature landscape regarding nonphysical outcomes in survivors of neurocritical care. Although a rising number of publications highlight growing awareness, future efforts are needed to improve study consistency and comparability and characterize outcomes in a disease-specific manner, including outlining of a minimum core outcomes set and associated assessment tools.

Co-regulation, relationship quality, and infant distress vocalizations observed during mother-infant interactions: Influences of maternal depression and different contexts.

Mother-infant interactions are co-regulated and provide the foundation for mother-infant relationship quality. The implications of maternal depression and contextual demands (i.e., reinstating the interaction following maternal unavailability and vocalized infant distress) on observationally coded co-regulation in mother-infant dyads (n = 40) at 4-months was investigated. Associations among co-regulation patterns and mother-infant relationship quality was also examined. Dyads participated in Still-Face (SF) and Separation (SP) procedures, with periods of maternal emotional and physical unavailability. Co-regulation was captured using the Revised Relational Coding System. Relationship quality was examined using the Emotional Availability Scales. Dyads in the depressed group had significantly more unilateral exchanges than the non-depressed group following the SF and SP perturbations. The depressed group also had significantly more distress vocalizations during the SP perturbation than the non-depressed group. Co-regulation in the depressed group was less disrupted by the SF perturbation. Positive relationship quality dimensions (maternal sensitivity, structuring, and infant responsiveness) were associated with more symmetrical and less unilateral co-regulation regardless of the interaction period. There were also context-specific results pertaining to patterns of co-regulation and associated maternal hostility and infant responsiveness. Results highlight co-regulatory differences in depressed mothers and their infants and how these differences are exacerbated by contextual demands.

Prioritizing river basins for nutrient studies.

Increases in fluxes of nitrogen (N) and phosphorus (P) in the environment have led to negative impacts affecting drinking water, eutrophication, harmful algal blooms, climate change, and biodiversity loss. Because of the importance, scale, and complexity of these issues, it may be useful to consider methods for prioritizing nutrient research in representative drainage basins within a regional or national context. Two systematic, quantitative approaches were developed to (1) identify basins that geospatial data suggest are most impacted by nutrients and (2) identify basins that have the most variability in factors affecting nutrient sources and transport in order to prioritize basins for studies that seek to understand the key drivers of nutrient impacts. The "impact" approach relied on geospatial variables representing surface-water and groundwater nutrient concentrations, sources of N and P, and potential impacts on receptors (i.e., ecosystems and human health). The "variability" approach relied on geospatial variables representing surface-water nutrient concentrations, factors affecting sources and transport of nutrients, model accuracy, and potential receptor impacts. One hundred and sixty-three drainage basins throughout the contiguous United States were ranked nationally and within 18 hydrologic regions. Nationally, the top-ranked basins from the impact approach were concentrated in the Midwest, while those from the variability approach were dispersed across the nation. Regionally, the top-ranked basin selected by the two approaches differed in 15 of the 18 regions, with top-ranked basins selected by the variability approach having lower minimum concentrations and larger ranges in concentrations than top-ranked basins selected by the impact approach. The highest ranked basins identified using the variability approach may have advantages for exploring how landscape factors affect surface-water quality and how surface-water quality may affect ecosystems. In contrast, the impact approach prioritized basins in terms of human development and nutrient concentrations in both surface water and groundwater, thereby targeting areas where actions to reduce nutrient concentrations could have the largest effect on improving water availability and reducing ecosystem impacts.