Evaluation of Tibial Slope on Radiographs in Pediatric Patients With Tibial Spine Fractures: An Age- and Sex-Matched Study.

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

Mouse sarcopenia model reveals sex- and age-specific differences in phenotypic and molecular characteristics.

Our study was to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition to investigate the underlying molecular mechanisms. Aged male (23-32 months old) and female (27-28 months old) C57BL/6J mice were classified as non-, probable-, or sarcopenic based on assessments of grip strength, muscle mass, and treadmill running time, using 2 SDs below the mean of their young counterparts as cutoff points. A 9%-22% prevalence of sarcopenia was identified in 23-26 month-old male mice, with more severe age-related declines in muscle function than mass. Females aged 27-28 months showed fewer sarcopenic but more probable cases compared with the males. As sarcopenia progressed, a decrease in muscle contractility and a trend toward lower type IIB fiber size were observed in males. Mitochondrial biogenesis, oxidative capacity, and AMPK-autophagy signaling decreased as sarcopenia progressed in males, with pathways linked to mitochondrial metabolism positively correlated with muscle mass. No age- or sarcopenia-related changes were observed in mitochondrial biogenesis, OXPHOS complexes, AMPK signaling, mitophagy, or atrogenes in females. Our results highlight the different trajectories of age-related declines in muscle mass and function, providing insights into sex-dependent molecular changes associated with sarcopenia progression, which may inform the future development of novel therapeutic interventions.

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells.

Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, -3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and -3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis.

High-grade serous ovarian cancer (or HGSOC for short) is the fifth leading cause of cancer-related deaths in women. It is generally diagnosed at an advanced stage of disease when the cancer has already spread to other parts of the body. Surgical removal of tumors and subsequent treatment with chemotherapy often reduces the signs and symptoms of the disease for a time but some cancer cells tend to survive so that patients eventually relapse. The HGSOC cells typically spread from the ovaries by moving through the liquid surrounding organs in the abdomen. The cells clump together and enter an inactive state known as dormancy that allows them to survive chemotherapy and low-nutrient conditions. Understanding how to develop new drug therapies that target dormant cancer cells is thought to be an important step in prolonging the life of HGSOC patients. Cancer cells are hardwired to multiply and grow, so Perampalam et al. reasoned that becoming dormant poses challenges for HGSOC cells, which may create unique vulnerabilities not shared by proliferating cancer cells. To find out more, the researchers used HGSOC cells that had been isolated from patients and grown in the laboratory. The team used a gene editing technique to screen HGSOC cells for genes required by the cells to survive when they are dormant. The experiments found that genes involved in a cell signaling pathway, known as Netrin signaling, were critical for the cells to survive. Previous studies have shown that Netrin signaling helps the nervous system form in embryos and inhibits a program of controlled cell death in some cancers. Perampalam et al. discovered that Netrins were present in the environment immediately surrounding dormant HGSOC cells. Human HGSOC patients with higher levels of Netrin gene expression had poorer prognoses than patients with lower levels of Netrin gene expression. Further experiments demonstrated that Netrins help dormant HGSOC cells to spread around the body. These findings suggest that Netrin signalling may provide useful targets for future drug therapies against dormant cells in some ovarian cancers. This could include repurposing drugs already in development or creating new inhibitors of this pathway.

Anterior Cruciate Ligament Injuries in Female Athletes.

This JAMA Insights discusses anterior cruciate ligament (ACL) injuries in female athletes, including modifiable and nonmodifiable sex-based risk factors and the implementation of ACL injury prevention programs.

Modeling cellular responses to serum and vitamin D in microgravity using a human kidney microphysiological system.

The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long- term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground). Given the profound bone loss observed in microgravity and PTECs produce the active form of vitamin D, we treated 3D cultured PTECs with 25(OH)D3 (vitamin D) and monitored vitamin D metabolite formation, conducted global transcriptomics via RNAseq, and evaluated transcript expression of CYP27B1, CYP24A1, or CYP3A5 in PTECs undergoing flight (microgravity) and respective ground controls. We demonstrated that microgravity neither altered PTEC metabolism of vitamin D nor did it induce a unique response of PTECs to human serum, suggesting that these fundamental biochemical pathways in the kidney proximal tubule are not significantly altered by short-term exposure to microgravity. Given the prospect of extended spaceflight, more study is needed to determine if these responses are consistent with extended (>6 months) exposure to microgravity.

Shared Decision-Making About Returning to Sport After Recovery From Pediatric Concussion: Clinician Perspectives.

OBJECTIVE: Describe how sports medicine clinicians support decision making about sport participation after concussion recovery with adolescent patients and their parents. Specific areas of inquiry related to how clinicians framed the decision, what factors they considered in how they approached the decision process, and how they navigated discordance within families. DESIGN: Qualitative study. SETTING: Tertiary care sports medicine clinics at 4 children's hospitals in the United States. PARTICIPANTS: Individual interviews were conducted with 17 clinicians practicing in sports medicine settings. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Semi-structured interviews explored clinician approaches to supporting decision making, with the question guide informed by components of the Ottawa Decision Support Framework. RESULTS: Clinicians routinely incorporated aspects of shared decision making (SDM) into their conversations with families. This included ensuring all parties were informed about risk and aligned behind a shared value of adolescent well-being. Mediation strategies were used to manage discordance between adolescents and their parents, and between parents. These strategies aimed to facilitate a decision that was adolescent centered. When clinicians believed that there was a medical benefit to modifying the adolescent's sport participation practices, or when they did not believe the athlete was psychologically ready to return to the sport in which they were injured, they initiated conversations about alternative activities. In such situations, they used persuasive communication practices to encourage families to strongly consider this option. CONCLUSION: The strengths and strategies used by sports medicine clinicians in this study provide a foundation for guidance or intervention development aimed at supporting SDM after concussion with adolescents and their families.

Transcriptomic comparison of in vitro models of the human placenta.

Studying the human placenta through in vitro cell culture methods is necessary due to limited access and amenability of human placental tissue to certain experimental methods as well as distinct anatomical and physiological differences between animal and human placentas. Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. Therefore, the aim of this research was to create a comprehensive transcriptomic comparison of common in vitro models of the human placenta compared to bulk placental tissue from the CANDLE and GAPPS cohorts (N=1083). We performed differential gene expression analysis on publicly available RNA sequencing data from 6 common in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, and Villous Explants) and compared to CANDLE and GAPPS bulk placental tissue or cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast cell types derived from bulk placental tissue. All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<0.01) compared to the CANDLE and GAPPS placentas (Average DEGs=10,873), and the individual trophoblast cell types (Average DEGs=5,346), indicating that there are vast differences in gene expression compared to bulk and cell-type specific human placental tissue. Hierarchical clustering identified 53 gene clusters with distinct expression profiles across placental models, with 22 clusters enriched for specific KEGG pathways, 7 clusters enriched for high-expression placental genes, and 7 clusters enriched for absorption, distribution, metabolism, and excretion genes. In vitro placental models were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as being of female origin, while JEG-3, JAR, and BeWo cells are of male origin. Overall, none of the models were a close approximation of the transcriptome of bulk human placental tissue, highlighting the challenges with model selection. To enable researchers to select appropriate models, we have compiled data on differential gene expression, clustering, and fetal sex into an accessible web application: "Comparative Transcriptomic Placental Model Atlas (CTPMA)" which can be utilized by researchers to make informed decisions about their selection of in vitro placental models.

A genome scale transcriptional regulatory model of the human placenta.

Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out-of-sample R2 greater than 0.25 for 73% of target genes. We performed siRNA knockdowns of four TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for three of the four TFs. Our final model contained 113,158 interactions across 391 TFs and 7712 target genes and is publicly available. We identified 29 TFs which were significantly enriched as regulators for genes previously associated with preterm birth, and eight of these TFs were decreased in preterm placentas.

Human Enteroid Monolayers: A Novel, Functionally-Stable Model for Investigating Oral Drug Disposition.

To further the development of an in vitro model which faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from three donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell® inserts, and confirmed transformation into a largely enterocyte population via RNA-seq analysis and immunocytochemical (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins. Enteroid monolayer barrier integrity was demonstrated by elevated transepithelial electrical resistance (TEER) that stabilized after 10 days in culture and persisted for 42 days. These results were corroborated by low paracellular transport probe permeability at 7 and 21 days in culture. The activity of a prominent drug metabolizing enzyme, CYP3A, was confirmed at 7, 21, and 42 days culture under basal, 1α,25(OH)2 vitamin D3-induced, and 6',7'-dihydroxybergamottin-inhibited conditions. The duration of these experiments is particularly noteworthy, as this is the first study assessing drug metabolizing enzymes and transporters (DMET) expression/function for enteroids cultured for greater than 12 days. The sum of these results suggests enteroid monolayers are a promising ex vivo model to investigate and quantitatively predict an orally administered drug's intestinal absorption and/or metabolism. Significance Statement This study presents a novel ex vivo model of the human intestine, human intestinal organoid (enteroid) monolayers, that maintain barrier function and metabolic functionality for up to 42-days in culture. The incorporation of both barrier integrity and metabolic function over an extended period within the same model is an advancement over historically used in vitro systems, which either lack one or both of these attributes or have limited viability.

Associations Between Prenatal Vitamin D and Placental Gene Expression.

Background: Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. Objective: We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort. Methods: Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks' gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA). Results: The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy (N=774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (N=753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including ARNT2, BHLHE40, FOSL2, JUND, and NFKB1. Conclusions: Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

Taqman PACMAN: a simple molecular approach for positive rapid antigen test confirmation during periods of low prevalence.

Antigen-based rapid diagnostic tests (Ag-RDTs) were widely deployed to enhance SARS-CoV-2 testing capacity during the COVID-19 pandemic. Consistent with national guidance for low prevalence settings, positive Ag-RDTs were confirmed using nucleic acid amplification tests (NAATs) to avoid false positive results. However, increasing demands for positive Ag-RDT confirmation competed with other testing priorities in clinical laboratories. This work hypothesized that real-time RT-PCR without nucleic acid extraction (NAE) would be sufficiently sensitive to support positive Ag-RDT confirmation. Ag-RDT and NAAT results from community-based asymptomatic testing sites prior to the omicron variant wave were compared to calculate the weekly false positive rate (FPR) and false detection rate (FDR). Real-time RT-PCR was compared with and without NAE using 752 specimens previously tested positive for SARS-CoV-2 using commercial NAATs and 344 specimens from Ag-RDT-positive individuals. The impact of SARS-CoV-2 prevalence on laboratory resources required to sustain Ag-RDT confirmation was modeled for the RT-PCR with and without NAE. Overall, FPR was low [0.07% (222/330,763)] in asymptomatic testing sites, but FDR was high [30.7% (222/724)]. When RT-PCR was compared with and without NAE, 100% concordance was obtained with NAAT-positive specimens, including those from Ag-RDT-positive individuals. NAE-free RT-PCR significantly reduced time to results, human resources, and overall costs. A 30.7% FDR reaffirms the need for NAAT-based confirmation of positive Ag-RDT results during low SARS-CoV-2 prevalence. NAE-free RT-PCR was shown to be a simple and cost-sparing NAAT-based solution for positive Ag-RDT confirmation, and its implementation supported data-driven broader Ag-RDT deployment into communities, workplaces, and households. IMPORTANCE: Rapid antigen testing for SARS-CoV-2 was widely deployed during the COVID-19 pandemic. In settings of low prevalence, national guidance recommends that positive antigen test results be confirmed with molecular testing. Given the high testing burden on clinical laboratories during the COVID-19 pandemic, the high volume of positive antigen tests submitted for confirmatory testing posed challenges for laboratory workflow. This study demonstrated that a simple PCR method without prior nucleic acid purification is an accurate and cost-effective solution for positive rapid antigen test confirmation. Implementing this method allowed molecular confirmatory testing for positive antigen tests to be sustained as antigen testing was expanded into large populations such as workplaces, schools, and households.

Managing an epidemic within a pandemic: orthopedic opioid prescribing trends during COVID-19.

INTRODUCTION: In response to the opioid epidemic, a multitude of policy and clinical-guideline based interventions were launched to combat physician overprescribing. However, the sudden rise of the Covid-19 pandemic disrupted all aspects of healthcare delivery. The purpose of this study was to evaluate how opioid prescribing patterns changed during the Covid-19 pandemic within a large multispecialty orthopedic practice. MATERIALS AND METHODS: A retrospective review of 1,048,559 patient encounters from January 1, 2015 to December 31, 2022 at a single orthopedic practice was performed. Primary outcomes were the percent of encounters with opioids prescribed and total morphine milligram equivalents (MMEs) per opioid prescription. Differences in outcomes were assessed by calendar year. Encounters were then divided into two groups: pre-Covid (1/1/2019-2/29/2020) and Covid (3/1/2020-12/31/2022). Univariate analyses were used to evaluate differences in diagnoses and outcomes between periods. Multivariate analysis was performed to assess changes in outcomes during Covid after controlling for differences in diagnoses. Statistical significance was assessed at p < 0.05. RESULTS: The percentage of encounters with opioids prescribed decreased from a high of 4.0% in 2015 to a low of 1.6% in 2021 and 2022 (p < 0.001). MMEs per prescription decreased from 283.6 ± 213.2 in 2015 to a low of 138.6 ± 100.4 in 2019 (p < 0.001). After adjusting for diagnoses, no significant differences in either opioid prescribing rates (post-COVID OR = 0.997, p = 0.893) or MMEs (post-COVID ß = 2.726, p = 0.206) were observed between the pre- and post-COVID periods. CONCLUSION: During the Covid-19 pandemic opioid prescribing levels remained below historical averages. While continued efforts are needed to minimize opioid overprescribing, it appears that the significant progress made toward this goal was not lost during the pandemic era.

Comparison of Postoperative Outcomes of Patients Undergoing Total Hip and Total Knee Arthroplasty Following a Diagnosis of Dementia: A TriNetX Database Study.

Background: As life expectancy improves for patients with dementia, the demand for mobility-improving surgeries such as total joint arthroplasty (TJA) will increase. There is little research on patients with dementia undergoing TJA, although dementia has been shown to be a risk factor for complications. The purpose of this study is to compare postoperative outcomes of patients with dementia undergoing TJA at 90 days, 2 years, and 5 years. Methods: The TriNetX database was retrospectively queried for all patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients were divided into cohorts by preoperative diagnosis of dementia and propensity score matched. The following outcomes were evaluated between groups at 90 days, 2 years, and 5 years postoperatively: revision, resection arthroplasty, closed reduction (THA only), femur fracture plating, and prosthetic joint infection. Readmission and manipulation under anesthesia (TKA only) were evaluated at 90 days postoperatively. Univariate and multivariate analyses were performed. Results: After matching, there were no differences in demographics or comorbidities between groups. TKA (odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.42-2.15, P < .001) and THA (OR = 2.17, 95% CI 1.92-2.45, P < .001) patients with dementia were more likely to be readmitted than patients without dementia. At 2 years (OR = 2.07, 95% CI 1.14-3.77, P = .015) and 5 years (OR = 2.14, 95% CI 1.32-3.48, P = .002) postoperatively, THA patients with dementia were more likely to have proximal femur fracture plating than patients without dementia. Conclusions: Patients undergoing THA with dementia had worse outcomes than patients undergoing THA without dementia and TKA with dementia. The overall rate of complications was low, and a diagnosis of dementia should not be an absolute contraindication to proceeding with TJA.

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies.

Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future. Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy. Key Message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.

Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.

The association between losartan potassium prescription and postoperative outcomes following total knee arthroplasty: A TriNetX analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-ß and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA. HYPOTHESIS: Based on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA. PATIENTS AND METHODS: In this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities. RESULTS: Losartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79-0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79-0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively. DISCUSSION: In conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA. LEVEL OF EVIDENCE: III; an observational cohort study.

Rotating curved spacetime signatures from a giant quantum vortex.

Gravity simulators1 are laboratory systems in which small excitations such as sound2 or surface waves3,4 behave as fields propagating on a curved spacetime geometry. The analogy between gravity and fluids requires vanishing viscosity2-4, a feature naturally realized in superfluids such as liquid helium or cold atomic clouds5-8. Such systems have been successful in verifying key predictions of quantum field theory in curved spacetime7-11. In particular, quantum simulations of rotating curved spacetimes indicative of astrophysical black holes require the realization of an extensive vortex flow12 in superfluid systems. Here we demonstrate that, despite the inherent instability of multiply quantized vortices13,14, a stationary giant quantum vortex can be stabilized in superfluid 4He. Its compact core carries thousands of circulation quanta, prevailing over current limitations in other physical systems such as magnons5, atomic clouds6,7 and polaritons15,16. We introduce a minimally invasive way to characterize the vortex flow17,18 by exploiting the interaction of micrometre-scale waves on the superfluid interface with the background velocity field. Intricate wave-vortex interactions, including the detection of bound states and distinctive analogue black hole ringdown signatures, have been observed. These results open new avenues to explore quantum-to-classical vortex transitions and use superfluid helium as a finite-temperature quantum field theory simulator for rotating curved spacetimes19.

The utility of coping through emotional approach: A meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to examine associations between attempts to cope with stressors through the two facets of emotional approach coping (EAC; i.e., processing and expressing stressor-related emotions) and indicators of physical and mental health. METHOD: EBSCO databases including MEDLINE, PsycINFO, and Cochrane Collections were searched from inception to November 2022. In all, 86 studies were included in a meta-analytic evaluation using a random-effects model and meta-regression analysis. RESULTS: EAC was associated with better overall health (r = .05; p = .04; 95% confidence interval = [.003, .10]). Emotional expression (EE) and emotional processing (EP) also were positively associated with better overall health, although these relationships were not statistically significant. In meta-regressions examining specific health domains, EAC was linked to better health in biological/physiological, physical, and resilience-related psychological adjustment domains, as well as to worse outcomes in the risk-related psychological adjustment and mental/emotional distress domains. Results for EE and EP mirrored this pattern; however, only EP was associated with more engagement in health-promoting behaviors. CONCLUSIONS: Coping with stressors through emotional approach appears to be associated with better mental and physical health, with some observed differences for EE and EP. The literature on EAC and health is marked by heterogeneity across study methodologies and measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex-specific associations between placental corticotropin releasing hormone and problem behaviors in childhood.

Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (ß=3.06, 95%CI: 0.40, 5.72), Internalizing (ß=0.89, 95%CI: 0.03, 1.76), and Externalizing (ß=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: ß=-1.99, 95%CI: -3.89, -0.09; Internalizing: ß=-0.82, 95%CI: -1.42, -0.23; Externalizing: ß=-0.56, 95%CI: -1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females.