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Background: Early identification of patients colonized with MDROs can help healthcare facilities improve infection control and treatment. We evaluated whether a model previously validated to predict carbapenem-resistant Enterobacterales (CRE) carriage on hospital admission (area under the curve [AUC]=0.86, Lin et al. OFID 2019) would generalize to predict a patient’s likelihood of CRE and non-CRE MDRO colonization at the time of medical intensive care unit (MICU) admission. Methods: We analyzed data collected previously in a retrospective observational cohort study of patients admitted to Rush University Medical Center’s MICU from 1/2017-1/2018 and screened within the first two days for rectal MDRO colonization. Organisms of interest included CRE, carbapenem-resistant Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE), and third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization at admission was determined by routine clinical screening. Each patient’s first MICU admission during the study period was linked to Illinois’ hospital discharge database and assigned a CRE colonization risk probability using the existing model. Model covariates were age, and during the prior 365 days, number of short-term acute care hospitalizations (STACH) and mean STACH length of stay, number of long-term acute care hospitalizations (LTACH) and mean LTACH length of stay, prior hospital admission with an ICD-10 diagnosis code indicating bacterial infection, and current admission to LTACH. Predictive value of the model was evaluated by receiver operating characteristic (ROC) curves. Results: We analyzed 1237 MICU admissions. MDRO admission prevalence is shown in the Table. The model performed well to predict carriage of healthcare-associated MDROs, including CRE, CRPA, composite CR-MDROs (CRE & CRPA), and VRE. However, the model performed poorly for MDROs with known community reservoirs, including 3GCR-E and MRSA (Table). In general, MDRO admission prevalence increased in parallel with predicted CRE colonization risk (Figure). The number needed to screen (NNS) to detect one healthcare-associated MDRO carrier was inversely related to the CRE colonization risk score. For example, NNS in the total cohort compared to those with CRE risk score of >0.5% was: CRE 111 vs 32 patients, CRPA 333 vs 42 patients, composite CR-MDRO 83 vs 18 patients, and VRE 12 vs 4 patients. However, higher CRE risk score cutoff was inversely related to screening sensitivity. Conclusion: A prediction model using prior healthcare exposure information successfully discriminated patients likely to harbor healthcare-associated MDROs upon MICU admission. Prediction scores generated by a public-health accessible database could be used to target screening/isolation or enact protective measures for high-risk patients.

Purpose: The purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. Methods: This study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values

Objectives To evaluate if vaginal metronidazole for 5 days before hysterectomy decreases postoperative infections and patient issues.Design This randomized trial compared vaginal metronidazole for 5 days before a scheduled hysterectomy to no intervention. Sample size calculation was based on a 20% difference in issues and infection (30% incidence and 10% in the intervention arm) with 80% power and an alpha error of 0.05 and indicated 62 subjects needed in each arm.Setting Outpatient gynecology clinics at a single academic institution.Participants 154 subjects were screened for eligibility between July 2020 and September 2022. 133 underwent hysterectomy including 68 subjects (51.1%) randomized to the metronidazole and 65 (48.9%) controls. Overall, the population was racially and ethnically diverse. There was no significant difference in characteristics between the two groups.Interventions Vaginal metronidazole for 5 days before hysterectomy.Main outcome measures Postoperative patient issues and documented postoperative infections at 4–8 weeks after surgery.Results There was no difference in the composite rate of patient-reported issues and/or documented postoperative infection (53/133 (39.8%) with no difference between groups (29/68 (42.6%) vs 24/65 (36.9%), p=0.50). There was no difference in patient-reported issues which was 51/133 (38.3%) with no difference between groups (28/68 (41.2%) vs 23/65 (33.8%), p=0.49) or in documented infections with a rate of 25/133 (18.8%) with no significant difference between groups (15/68 (22.0%) vs 10/65 (15.4%), p=0.33). In the intervention arm, the compliance rate was 73.5% for all 5 days of vaginal metronidazole, and a per-protocol analysis was performed which resulted in no significant difference between groups.Conclusions There is insufficient evidence to suggest a significant benefit of preoperative vaginal metronidazole to prevent surgical site infections and postoperative patient issues in patients undergoing hysterectomy.Trial registration number ClinicalTrials.gov, NCT04478617.

Invention education is an emerging field that shows promise for fostering equitable student engagement, especially related to disciplines of science, technology, engineering, arts, and mathematics (STEAM), in both classroom and informal learning. A central concept for practitioners, researchers, and evaluators, student engagement connects with academic, socioemotional, career, and civic success. Nonetheless, more work is needed to ensure more equitable approaches to educational design for student engagement, especially with youth of one or more minoritized identity markers (e.g., Black, Brown, or Indigenous youth; female or non-binary youth; youth from lower socioeconomic statuses; etc.). This Curriculum, Instruction, and Pedagogy article describes six iterations of educational designs for invention education with grades 6–8 classes and camps. Three of the iterations revised the same curriculum for grade 7 classes (N ~ 160 students/year), and the other three iterations involved similar yet distinct curricula for grades 6–8 camps (N ~ 25 students/year). Taking a cultural psychology approach to design-based research, we conducted a phenomenological mixed-methods study for convergence. That is, we iteratively refined educational designs within given microcultures, and we sought to better understand participants’ lived experiences. We share evidence of high affective, behavioral, and cognitive engagement, within and between both individual and social levels, alongside development of self-efficacy with respect to ability beliefs and anxiety management. With a few exceptions, our findings suggest equitable participation of youth. These findings we connect with educational design considerations, including individual vs. social supports, explicit attention to youths’ hobbies and peer-inventors, and formative assessment that broadens response scales and gradations of challenge. Our work supports a more nuanced and socially-situated six-dimensional framework for student engagement, expanding upon commonly-used three-and four-dimensional models. We conclude with local and transferrable implications, towards the main goal of fostering equitable student engagement in science and engineering through invention education.

Purpose: A radiation anatomist was trained and integrated into clinical practice at a multi-site academic center. The primary objective of this quality improvement study was to determine whether a radiation anatomist improves the quality of organ-at-risk (OAR) contours, and secondarily to determine the impact on efficiency in the treatment planning process. Methods and Materials: From March to August 2020, all patients undergoing computed tomography–based radiation planning at 2 clinics at Memorial Sloan Kettering Cancer Center were assigned using an “every other” process to either (1) OAR contouring by a radiation anatomist (intervention) or (2) contouring by the treating physician (standard of care). Blinded dosimetrists reported OAR contour quality using a 3-point scoring system based on a common clinical trial protocol deviation scale (1, acceptable; 2, minor deviation; and 3, major deviation). Physicians reported time spent contouring for all cases. Analyses included the Fisher exact test and multivariable ordinal logistic regression. Results: There were 249 cases with data available for the primary endpoint (66% response rate). The mean OAR quality rating was 1.1 ± 0.4 for the intervention group and 1.4 ± 0.7 for the standard of care group (P < .001), with subset analysis showing a significant difference for gastrointestinal cases (n = 49; P

Removal of hydrocarbons from sediments could be achieved using various techniques such as hydraulic flushing aided by surfactants, which works well for sand and gravel but not as effective for finer textured media, such as clay. Electrokinetics (EK) emerged as an effective method to remediate fine-grained soils, especially when combined with the application of surfactants. Here, we analyzed the removal efficiency of EK and a nonionic surfactant (Tween 80) when applied through a fine soil (80% clay) contaminated with n-hexadecane. The study compared the EK results with hydraulic flushing under the same surfactant concentration. After 18 days of treatment, EK removed 80%, which was significantly more efficient than hydraulic flushing which removed 52%. The investigation revealed that EK causes the surfactant to tackle the clayey soil from various directions due to the whole aquifer's electrification. This would be an advantage in field studies as it precludes the need to place numerous electrodes into the soil, as done in hydraulic flushing where multiple wells are placed to direct the surfactant's movement.

Summary: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Most DS patients carry de novo variants in SCN1A, resulting in Nav1.1 haploinsufficiency. Because SCN1A is expressed in heart and in brain, we proposed that cardiac arrhythmia contributes to SUDEP in DS. We generated DS patient and control induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). We observed increased sodium current (INa) and spontaneous contraction rates in DS patient iPSC-CMs versus controls. For the subject with the largest increase in INa, cardiac abnormalities were revealed upon clinical evaluation. Generation of a CRISPR gene-edited heterozygous SCN1A deletion in control iPSCs increased INa density in iPSC-CMs similar to that seen in patient cells. Thus, the high risk of SUDEP in DS may result from a predisposition to cardiac arrhythmias in addition to seizures, reflecting expression of SCN1A in heart and brain. : In this article, Isom, Parent, and colleagues show that the high risk of SUDEP in the developmental and epileptic encephalopathy, Dravet syndrome, may result from a predisposition to cardiac arrhythmias in addition to neuronal hyperexcitability, reflecting haploinsufficiency of SCN1A in heart and brain causing potential compensatory overexpression of other sodium-channel genes in those tissues. Keywords: epilepsy, cardiac arrhythmia, sodium channel, SUDEP, induced pluripotent stem cell (iPSC), developmental and epileptic encephalopathy

OBJECTIVES/GOALS: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in epilepsy patients. This study aims to determine whether cardiac mechanisms contribute to SUDEP in epilepsy patients with variants in DEPDC5, a gene encoding a member of the mTOR GATOR complex, to identify SUDEP biomarkers. METHODS/STUDY POPULATION: SUDEP has been reported in 10% of epilepsy patients with DEPDC5 loss-of-function variants. We used human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to measure changes in cellular excitability that are known to be substrates for cardiac arrhythmias. CRISPR-derived isogenic DEPDC5 iPSC-CMs and DEPDC5 patient-derived iPSC-CMs were used in this study. Whole-cell patch-clamp was used to measure voltage-gated sodium current (INa) and calcium current (I>Ca) in single iPSC-CMs in voltage-clamp mode; and to measure action potentials (APs) in 3-dimentional iPSC-CM-derived micro-tissues in current-clamp mode. RESULTS/ANTICIPATED RESULTS: CRISPR generated heterozygous deletion of 1 base-pair in the first coding exon of DEPDC5 gene, resulting in a premature stop codon, simulated the variants identified in DEPDC5 epilepsy patients. In CRISPR generated heterozygousDEPDC5 iPSC-CMs, whole-cell voltage-clamp recordings revealed that INa was increased and ICa was reduced compared with isogenic control iPSC-CMs. Whole-cell current-clamp recordings revealed that AP duration at 80% and 90% of repolarization, APD80 and APD90, respectively, were prolonged compared to isogenic control iPSC-CMs. Similar measurements will be performed for iPSC-CMs derived from DEPDC5 patients. DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows that epilepsy patients with non-ion channel gene variants in DEPDC5 have altered CM excitability, which may serve as a substrate for cardiac arrhythmias in DEPDC5 patients. Importantly, this work may allow us to identify biomarkers for SUDEP risk in these patients in the future. CONFLICT OF INTEREST DESCRIPTION: L.L.I. is the recipient of a collaborative research grant from Stoke Therapeutics.

MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a. Additionally, in vitro culture of MPPs and sorted MPP transplants showed that these cells have decreased myeloid and increased lymphoid potential in vitro and in vivo. We investigated the mechanism by which mirn23a regulates hematopoietic differentiation and observed that mirn23a promotes myeloid development of hematopoietic progenitors through regulation of hematopoietic transcription factors and signaling pathways. Early transcription factors that direct the commitment of MPPs to CLPs (Ikzf1, Runx1, Satb1, Bach1 and Bach2) are increased in the absence of mirn23a miRNAs as well as factors that commit the CLP to the B cell lineage (FoxO1, Ebf1, and Pax5). Mirn23a appears to buffer transcription factor levels so that they do not stochastically reach a threshold level to direct differentiation. Intriguingly, mirn23a also inversely regulates the PI3 kinase (PI3K)/Akt and BMP/Smad signaling pathways. Pharmacological inhibitor studies, coupled with dominant active/dominant negative biochemical experiments, show that both signaling pathways are critical to mirn23a's regulation of hematopoietic differentiation. Lastly, consistent with mirn23a being a physiological inhibitor of B cell development, we observed that the essential B cell transcription factor EBF1 represses expression of mirn23a. In summary, our data demonstrates that mirn23a regulates a complex array of transcription and signaling pathways to modulate adult hematopoiesis.

Background5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo.MethodsNeuroprotection was assessed in vitro using models of excitotoxicity in primary neurons, mixed astrocyte-neuron and primary oligodendrocyte cultures. The capacity of MTA to cross the BBB was measured in an artificial membrane assay and using an in vitro cell model. Finally, in vivo tests were performed in models of hypoxic brain damage, Parkinson's disease and epilepsy.ResultsMTA displays a wide array of neuroprotective activities against different insults in vitro. While the data from the two complementary approaches adopted indicate that MTA is likely to cross the BBB, the in vivo data showed that MTA may provide therapeutic benefits in specific circumstances. Whereas MTA reduced the neuronal cell death in pilocarpine-induced status epilepticus and the size of the lesion in global but not focal ischemic brain damage, it was ineffective in preserving dopaminergic neurons of the substantia nigra in the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-mice model. However, in this model of Parkinson's disease the combined administration of MTA and an A2A adenosine receptor antagonist did produce significant neuroprotection in this brain region.ConclusionMTA may potentially offer therapeutic neuroprotection.

We examine the impact of transparency on the convenience yield of AAA-rated asset-backed security (ABS) tranches. AAA tranches of ABS are commonly held by investors to manage financial liquidity and therefore enjoy a price premium beyond what is determined solely by the expected monetary payoff (i.e., convenience yield). The Securities and Exchange Commission (SEC) requires ABS issuers to provide monthly disclosures about the performance of the underlying individual loans for ABS issued after November 23, 2016 to improve transparency. We document that AAA tranches of ABS experience a significant increase in price volatility after the loan-level disclosure mandate. As a result, the use of these tranches as collateral for short-term funding and their convenience yield decrease significantly after the increased disclosure. Our collective evidence highlights an important unintended consequence of increased transparency in the ABS market; it diminishes the pledgeability of long-term safe assets. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention. METHODS: This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021. Medical records were reviewed and consolidated. Descriptive analyses were used to summarize patient characteristics, and differences in characteristics sub grouped by triage acuity and discharge status were analyzed. RESULTS: The study included 272 patients with a mean age of 43 years and a male predominance (71.7%). Most presented without referrals (88.2%) and were not conveyed by ambulances (70.6%). Based on acuity category, there were 24 (8.8%) Priority 1 (P1) patients with 7 trauma activations, 174 (64.0%) and 74 (27.2%) P2 and P3 patients respectively. The most common injuries were fractures (34.2%), followed by superficial abrasion/contusion (29.4%) and laceration/wound (19.1%). Thirteen (4.8%) patients experienced head injury and 85 patients (31.3%) were documented to be wearing a helmet. The majority occurred on the roads as traffic accidents (32.7%). Forty-two patients (15.4%) were admitted with a mean length of stay of 4.1 d and 17 (6.3%) undergone surgical procedures. Out of 214 (78.7%) discharged patients, no re-attendances or mortality were observed. In the subgroup analysis, higher acuity patients were generally older, with higher proportions of head injuries leading to admission. CONCLUSION: Our study highlights significant morbidities in bicycle-related injuries. There is also a high proportion of fractures in the young healthy male population. Injury prevention is paramount and we propose emphasizing helmet use and road user safety. [ABSTRACT FROM AUTHOR]