Nonsurgical Management of Adductor-related groin pain with Ultrasound-Guided Platelet-Rich Plasma Injection and Physical Therapy in a Competitive Soccer Player: A Case Report.

Introduction: Adductor-related groin pain involves an injury to the common aponeurosis connecting the rectus abdominus and adductor longus to the pubis. It commonly occurs in sports that require cutting and pivoting and can result in significant loss of playing time. Platelet-Rich Plasma (PRP) is often indicated for treatment of musculoskeletal disorders and may represent an alternative treatment for patients with adductor-related groin pain. The purpose of this case report is to describe the non-surgical management of adductor-related groin pain in a competitive soccer player with a with an ultrasound (US)-guided PRP injection and physical therapy management. Case Description: A 17-year-old male competitive soccer player with right-sided adductor-related groin pain was treated with an US-guided PRP and a multi-phased physical therapy regimen based on tissue healing and individual patient/criteria progression. The patient completed 12 physical therapy sessions over six weeks post PRP injection. Outcomes: At the end of treatment, clinically meaningful improvements were observed in pain intensity, passive range of motion, strength (handheld dynamometry, Biodex), functional tests, psychosocial (OSPRO-YF) and patient-reported outcomes (HAGOS, LEFS). The subject returned to sport at six weeks post injection without limitation and at three months follow up, the subject reported that he had returned to 95% of his previous level of play. Discussion: This case report may offer support for PRP as an alternative treatment in the management of adductor-related groin pain. Incorporation of PRP as an adjunct to physical therapy led to improvements on all outcomes that surpassed the clinical significance change criteria. Level of evidence: 5.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

Priorities for Clinical Research in Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From the Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Understanding Public Perceptions of Nipple and Scar Characteristics After Chest Wall Masculinization Surgery.

BACKGROUND: Surgical chest masculinization procedures, especially gender-affirming top surgery (GATS), are becoming increasingly prevalent in the USA. While a variety of surgical techniques have been established as both safe and effective, there is limited research examining ideal aesthetic nipple appearance and incision scar pattern. This study employs patient images to understand the public's perception on top surgery outcomes when adjusting for BMI ranges and Fitzpatrick skin types. METHODS: Images from RealSelf modified via Adobe Photoshop depicted various scar types and nipple-areolar complex (NAC) sizes/positions. A Qualtrics survey was distributed utilizing Amazon Mechanical Turk. Statistical analysis was performed through JMP Pro 17 for ordinal and categorical values, with a p value less than or equal to 0.05 statistically significant. RESULTS: A moderately sized and laterally placed NAC was preferred. A transverse scar that resembles the pectoral border between the level of the inframammary fold and pectoral insertion was deemed most masculine and aesthetic. Majority of results demonstrated that this is unaffected by Fitzpatrick skin types. Increased BMI images impacted public preferences, as a nipple placed farther from the transverse incision (p = 0.04) and a transverse scar position closer to the IMF was preferred in higher BMI patients. CONCLUSIONS: An understanding of the most popular NAC and scar choices, as well as how these factors may differ when considering a Fitzpatrick skin type or BMI categorization was attained. This validates the importance of patient-centered approach when employing surgical techniques in GATS. Future studies intend to obtain reports from actual patients considering GATS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable.

Sustainability in surgical practice: a collaborative call toward environmental sustainability in operating rooms.

BACKGROUND: The healthcare system plays a pivotal role in environmental sustainability, and the operating room (OR) significantly contributes to its overall carbon footprint. In response to this critical challenge, leading medical societies, government bodies, regulatory agencies, and industry stakeholders are taking measures to address healthcare sustainability and its impact on climate change. Healthcare now represents almost 20% of the US national economy and 8.5% of US carbon emissions. Internationally, healthcare represents 5% of global carbon emissions. US Healthcare is an outlier in both per capita cost, and per capita greenhouse gas emission, with almost twice per capita emissions compared to every other country in the world. METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the European Association for Endoscopic Surgery (EAES) established the Sustainability in Surgical Practice joint task force in 2023. This collaborative effort aims to actively promote education, mitigation, and innovation, steering surgical practices toward a more sustainable future. RESULTS: Several key initiatives have included a survey of members' knowledge and awareness, a scoping review of terminology, metrics, and initiatives, and deep engagement of key stakeholders. DISCUSSION: This position paper serves as a Call to Action, proposing a series of actions to catalyze and accelerate the surgical sustainability leadership needed to respond effectively to climate change, and to lead the societal transformation towards health that our times demand.

A cloud-based training module for efficient de novo transcriptome assembly using Nextflow and Google cloud.

This study describes the development of a resource module that is part of a learning platform named "NIGMS Sandbox for Cloud-based Learning" (https://github.com/NIGMS/NIGMS-Sandbox). The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on de novo transcriptome assembly using Nextflow in an interactive format that uses appropriate cloud resources for data access and analysis. Cloud computing is a powerful new means by which biomedical researchers can access resources and capacity that were previously either unattainable or prohibitively expensive. To take advantage of these resources, however, the biomedical research community needs new skills and knowledge. We present here a cloud-based training module, developed in conjunction with Google Cloud, Deloitte Consulting, and the NIH STRIDES Program, that uses the biological problem of de novo transcriptome assembly to demonstrate and teach the concepts of computational workflows (using Nextflow) and cost- and resource-efficient use of Cloud services (using Google Cloud Platform). Our work highlights the reduced necessity of on-site computing resources and the accessibility of cloud-based infrastructure for bioinformatics applications.

An Analysis of Clinical Outcomes of Exploratory Pediatric Metformin Ingestions Reported to the Texas Poison Center Network From 2011 to 2021.

Background: Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. Objective: To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network. Methods: We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables. Results: Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%). Conclusion: Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.

Loss of neuronal lysosomal acid lipase drives amyloid pathology in Alzheimer's disease.

Underlying drivers of late-onset Alzheimer's disease (LOAD) pathology remain unknown. However, multiple biologically diverse risk factors share a common pathological progression. To identify convergent molecular abnormalities that drive LOAD pathogenesis we compared two common midlife risk factors for LOAD, heavy alcohol use and obesity. This revealed that disrupted lipophagy is an underlying cause of LOAD pathogenesis. Both exposures reduced lysosomal flux, with a loss of neuronal lysosomal acid lipase (LAL). This resulted in neuronal lysosomal lipid (NLL) accumulation, which opposed Aß localization to lysosomes. Neuronal LAL loss both preceded (with aging) and promoted (targeted knockdown) Aß pathology and cognitive deficits in AD mice. The addition of recombinant LAL ex vivo and neuronal LAL overexpression in vivo prevented amyloid increases and improved cognition. In WT mice, neuronal LAL declined with aging and correlated negatively with entorhinal Aß. In healthy human brain, LAL also declined with age, suggesting this contributes to the age-related vulnerability for AD. In human LOAD LAL was further reduced, correlated negatively with Aß1-42, and occurred with polymerase pausing at the LAL gene. Together, this finds that the loss of neuronal LAL promotes NLL accumulation to impede degradation of Aß in neuronal lysosomes to drive AD amyloid pathology.

The spatial organization of ascending auditory pathway microstructural maturation from infancy through adolescence using a novel fiber tracking approach.

Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.

Discovery of Potent Degraders of the Dengue Virus Envelope Protein.

Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here we report the development of small molecule degraders of the envelope (E) protein of dengue virus. We developed two classes of bivalent E-degraders, linking two previously reported E-binding small molecules, GNF-2 and CVM-2-12-2, to a glutarimide-based recruiter of the CRL4CRBN ligase to effect proteosome-mediated degradation of the E protein. ZXH-2-107 (based on GNF-2) is an E degrader with ABL inhibition while ZXH-8-004 (based on CVM-2-12-2) is a selective and potent E-degrader. These two compounds provide proof-of-concept that difficult-to-drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class antiviral drugs.

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: To inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. METHODS: We conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults' preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers' data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose-response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. RESULTS: We identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces). General public studies. From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97-1.34, 95% prediction interval (PI): 0.83-1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96-1.36, 95% PI: 0.84-1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02-1.24, 95% PI: 0.99-1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth. Occupational studies. In occupational studies, based on dose-response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94-1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DISCUSSION: Most of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes. Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

Feeding en route: Prey availability and traits influence prey selection by an avian predator on migration.

During animal migration, ephemeral communities of taxa at all trophic levels co-occur over space and time. The interactions between predators and prey along migration corridors are ecologically and evolutionarily significant. However, these interactions remain understudied in terrestrial systems and warrant further investigations using novel approaches. We investigated the predator-prey interactions between a migrating avivorous predator and ephemeral avian prey community in the fall migration season. We tested for associations between avian traits and prey selection and hypothesized that prey traits (i.e. relative size, flocking behaviour, habitat, migration tendency and availability) would influence prey selection by a sexually dimorphic raptor on migration. To document prey consumption, we sampled trace prey DNA from beaks and talons of migrating sharp-shinned hawks Accipiter striatus (n = 588). We determined prey availability in the ephemeral avian community by extracting weekly abundance indices from eBird Status and Trends data. We used discrete choice models to assess prey selection and visualized the frequency of prey in diet and availability on the landscape over the fall migration season. Using eDNA metabarcoding, we detected prey species on 94.1% of the hawks sampled (n = 525/588) comprising 1396 prey species detections from 65 prey species. Prey frequency in diet and eBird relative abundance of prey species were correlated over the migration season for top-selected prey species, suggesting prey availability is an important component of raptor-songbird interactions during fall. Prey size, flocking behaviour and non-breeding habitat association were prey traits that significantly influenced predator choice. We found differences between female and male hawk prey selection, suggesting that sexual size dimorphism has led to distinct foraging strategies on migration. This research integrated field data collected by a volunteer-powered raptor migration monitoring station and public-generated data from eBird to reveal elusive predator-prey dynamics occurring in an ephemeral raptor-songbird community during fall migration. Understanding dynamic raptor-songbird interactions along migration routes remains a relatively unexplored frontier in animal ecology and is necessary for the conservation and management efforts of migratory and resident communities.

Durante la migración animal, las comunidades efímeras de taxones de todos los niveles tróficos coexisten en el espacio y el tiempo. Las interacciones entre depredadores y presas a lo largo de los corredores migratorios son significativas desde el punto de vista ecológica y evolutivo. Sin embargo, estas interacciones siguen siendo poco estudiadas en los sistemas terrestres y justifican más investigaciones utilizando enfoques novedosos. Investigamos las interacciones depredador­presa entre un depredador avívoro migratorio y una comunidad de presas aviares efímeras en la temporada migratoria otoñal. Probamos las asociaciones entre los rasgos de las aves y la selección de presas y planteamos la hipótesis de que los rasgos de las presas (tamaño relativo, comportamiento de bandada, hábitat, tendencia migratoria y disponibilidad) influirían en la selección de presas por parte de una rapaz sexualmente dimórfica durante la migración. Para documentar el consumo de presas, recogimos rastros de ADN de presas de picos y garras de Gavilán Americano Accipiter striatus (n = 588) migratorios. Determinamos la disponibilidad de presas en la comunidad de aves efímeras extrayendo índices de abundancia semanales de los datos de eBird Estado y Tendencias. Utilizamos modelos de elección discreta para evaluar la selección de presas y visualizamos la frecuencia de las presas en la dieta y la disponibilidad en el paisaje durante la temporada migratoria otoñal. Utilizando el metacódigo de barras del ADN ambiental, detectamos especies de presas en el 94,1% de los halcones muestreados (n = 525/588), comprendiendo 1396 detecciones de 65 especies de presas. La frecuencia de presas en la dieta y la abundancia relativa de especies de presas en eBird se correlacionaron a lo largo de la temporada de migración para las principales especies de presas seleccionadas, lo que sugiere que la disponibilidad de presas es un componente importante de las interacciones entre aves rapaces y aves canoras durante el otoño. El tamaño de las presas, el comportamiento de las bandadas y la asociación con el hábitat no reproductivo fueron rasgos de presa que influyeron significativamente en la elección de los depredadores. Encontramos diferencias entre la selección de presas de gavilán hembra y macho, lo que sugiere que el dimorfismo sexual de tamaño ha conducido a distintas estrategias de alimentación durante la migración. Esta investigación integró datos de campo recopilados por una estación de monitoreo de migración de rapaces impulsada por voluntarios y datos generados públicamente por eBird para revelar la esquiva dinámica depredador­presa que ocurre en una comunidad efímera de rapaces y aves canoras durante la migración otoñal. Comprender las interacciones dinámicas entre rapaces y aves canoras a lo largo de las rutas migratorias sigue siendo una frontera relativamente inexplorada en la ecología animal y es necesaria para los esfuerzos de conservación y gestión de las comunidades migratorias y residentes.

Electrocatalysis in Solid Oxide Fuel Cells and Electrolyzers.

Interest in energy-to-X and X-to-energy (where X represents green hydrogen, carbon-based fuels, or ammonia) technologies has expanded the field of electrochemical conversion and storage. Solid oxide electrochemical cells (SOCs) are among the most promising technologies for these processes. Their unmatched conversion efficiencies result from favorable thermodynamics and kinetics at elevated operating temperatures (400-900 °C). These solid-state electrochemical systems exhibit flexibility in reversible operation between fuel cell and electrolysis modes and can efficiently utilize a variety of fuels. However, electrocatalytic materials at SOC electrodes remain nonoptimal for facilitating reversible operation and fuel flexibility. In this Review, we explore the diverse range of electrocatalytic materials utilized in oxygen-ion-conducting SOCs (O-SOCs) and proton-conducting SOCs (H-SOCs). We examine their electrochemical activity as a function of composition and structure across different electrochemical reactions to highlight characteristics that lead to optimal catalytic performance. Catalyst deactivation mechanisms under different operating conditions are discussed to assess the bottlenecks in performance. We conclude by providing guidelines for evaluating the electrochemical performance of electrode catalysts in SOCs and for designing effective catalysts to achieve flexibility in fuel usage and mode of operation.

A real-time prognostic model for venous thromboembolic events among hospitalized adults.

Background: Hospital-acquired venous thromboembolism (HA-VTE) is a leading cause of morbidity and mortality among hospitalized adults. Guidelines recommend use of a risk-prediction model to estimate HA-VTE risk for individual patients. Extant models do not perform well for broad patient populations and are not conducive to automation in clinical practice. Objectives: To develop an automated, real-time prognostic model for venous thromboembolism during hospitalization among all adult inpatients using readily available data from the electronic health record. Methods: The derivation cohort included inpatient hospitalizations ("encounters") for patients ≥16 years old at Vanderbilt University Medical Center between 2018 and 2020 (n = 132,330). HA-VTE events were identified using International Classification of Diseases, 10th Revision, codes. The prognostic model was developed using least absolute shrinkage and selection operator regression. Temporal external validation was performed in a validation cohort of encounters between 2021 and 2022 (n = 62,546). Prediction performance was assessed by discrimination accuracy (C statistic) and calibration (integrated calibration index). Results: There were 1187 HA-VTEs in the derivation cohort (9.0 per 1000 encounters) and 864 in the validation cohort (13.8 per 1000 encounters). The prognostic model included 25 variables, with placement of a central line among the most important predictors. Prediction performance of the model was excellent (C statistic, 0.891; 95% CI, 0.882-0.900; integrated calibration index, 0.001). The model performed similarly well across subgroups of patients defined by age, sex, race, and type of admission. Conclusion: This fully automated prognostic model uses readily available data from the electronic health record, exhibits superior prediction performance compared with existing models, and generates granular risk stratification in the form of a predicted probability of HA-VTE for each patient.

Investigating the Effect of Trace Levels of Manganese Ions During Solvothermal Synthesis of Massey University Framework-16 on CO2 Uptake Capacity.

The effects of impurities on reaction precursors for metal-organic framework (MOF) synthesis have not been studied in extensive detail. The impact of these impurities can be an important factor while considering scale-up of these materials. In this work, we study the apparently positive impact of the presence of manganese ions for the synthesis of a Co-based MOF, Massey University Framework-16 (MUF-16). The presence of a trace amount of manganese in the reaction mixture led to consistently high CO2 uptake across multiple batches. Characterization including X-ray diffraction, scanning electron microscopy, Fourier transform infrared-attenuated total reflectance, ultraviolet-visible spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, and extended X-ray absorption fine structure spectroscopy led us to hypothesize that the differences in CO2 adsorption among materials with differing synthesis routes arise from variations in the local environment around the cobalt metal center. Aided by density functional theory calculations, we speculate that manganese ions get inserted into the structure during crystallization and act as catalysts for ligand substitution, improving the possibility for octahedral coordination of cobalt with the ligand, thus leading to Co-based pristine structures with higher CO2 uptakes.

Development and validation of the housing instability scale.

Despite increasing attention to the importance of examining factors that impact housing instability and homelessness, the field lacks a validated scale of housing instability. The current study examined the reliability and validity of a seven-item scale that measures housing instability. Data were taken from a larger study which implemented the Domestic Violence Housing First model across five domestic violence agencies in the Pacific Northwest. A total of 406 participants were interviewed every six months over a period of two years. A Spanish version of the scale was administered to Spanish-speaking participants. Results provide an overview of the psychometric functioning of the scale and support its utility in assessing housing instability and homelessness. Specifically, the scale demonstrated concurrent and predictive validity, and showed evidence of scalar equivalence over time and across both language and locality. The current scale is therefore a succinct and psychometrically sound measure of housing instability which can be used moving forward to track housing instability in English and Spanish speakers, as well as in urban and rural settings.

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers. Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans. Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts. Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics. Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.

Trans-tarsal Stair-Step Technique for Lateral Extension of the Transconjunctival Incision: A Technical Note and Case Series.

Background: The transconjunctival approach paired with lateral canthotomy is a commonly used technique for widened exposure of the orbital floor and infraorbital rim. A major drawback of this approach is the severance of lateral canthal ligament fibers, which predisposes to potential postoperative eyelid malpositioning. To avoid these suboptimal aesthetic outcomes, a modification of this approach has been proposed in which the lower eyelid is mobilized with a paracanthal, trans-tarsal stair-step incision. In this pilot study, we describe our experience with the trans-tarsal stairstep incision for lateral extension of the transconjunctival incision and report its outcomes in a Western population. Methods: All patients who underwent facial fracture operative fixation at a single institution by a single senior surgeon were included. Clinical variables were extracted. Patients were stratified by incision type. Results: Compared with patients who underwent subtarsal incision (n = 20) and transconjunctival incision with lateral canthotomy (n = 4), patients who received the trans-tarsal stair-step incision (n = 10) had no incision-related complications or requirements for revision. The most common complications found in the comparison groups were ectropion and hypertrophic or irregular scarring, and 4 patients required revision. Conclusions: Our initial experience with the transconjunctival approach with the trans-tarsal stair-step incision shows promising outcomes. Further study may promote greater utilization of this technique in Western countries.

Divergent Trends in Postoperative Length of Stay and Postdischarge Complications over Time.

BACKGROUND: There is a push toward shorter length of stay (LOS) after surgery by hospitals, payers, and policymakers. However, the extent to which these changes have shifted the occurrence of complications to the postdischarge setting is unknown. The objectives of this study were to (1) evaluate changes in LOS and postdischarge complications over time and (2) assess factors associated with postdischarge complications. STUDY DESIGN: Patients who underwent surgery across five specialties (colorectal, esophageal, hepatopancreatobiliary [HPB], gynecology, and urology) were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) procedure-targeted database (2014-2019). Trends in the proportion of postdischarge complications within 30 days of surgery and predictors of postdischarge complications were assessed using multivariable logistic regression. RESULTS: Among 538,172 patients evaluated, median LOS decreased from 3 (2014) to 2 days (2019) (p < 0.001). Overall, 12.2% of patients experienced a 30-day complication, with 50.4% occurring postdischarge. with the highest in hysterectomy (80.9%), prostatectomy (74.6%), and cystectomy (54.6%). The overall postoperative complication decreased, but the proportion of postdischarge complications increased from 44.6% (2014) to 56.4% (2019) (p < 0.001), including surgical site infection (superficial/deep/organ space/wound dehiscence), other infection (pneumonia/urinary tract infection/sepsis), cardiovascular (myocardial infarction/cardiac arrest/stroke), and venous thromboembolism. Factors associated with an increased odds of postdischarge complications included Hispanic or other race, higher American Society of Anesthesiologists class, dependent functional status, increased body mass index, higher wound class, inpatient complication, longer operation, and procedure type (HPB/colorectal/hysterectomy/esophagectomy, vs. prostatectomy) (all p < 0.001). CONCLUSION: This comprehensive retrospective analysis across five representative surgical specialties highlighted that although LOS has decreased over time, the proportion of postdischarge complications has increased over time. Focusing on the development of a comprehensive, proactive, postdischarge monitoring system to better identify and manage postdischarge complications is necessary.

Broad-spectrum activity against mosquito-borne flaviviruses achieved by a targeted protein degradation mechanism.

Viral genetic diversity presents significant challenges in developing antivirals with broad-spectrum activity and high barriers to resistance. Here we report development of proteolysis targeting chimeras (PROTACs) targeting the dengue virus envelope (E) protein through coupling of known E fusion inhibitors to ligands of the CRL4CRBN E3 ubiquitin ligase. The resulting small molecules block viral entry through inhibition of E-mediated membrane fusion and interfere with viral particle production by depleting intracellular E in infected Huh 7.5 cells. This activity is retained in the presence of point mutations previously shown to confer partial resistance to the parental inhibitors due to decreased inhibitor-binding. The E PROTACs also exhibit broadened spectrum of activity compared to the parental E inhibitors against a panel of mosquito-borne flaviviruses. These findings encourage further exploration of targeted protein degradation as a differentiated and potentially advantageous modality for development of broad-spectrum direct-acting antivirals.