Pre-operative care intensity and cost for renal colic: implications for surgical value-based reforms.

OBJECTIVES: To identify pre-operative patient/facility factors associated with post-operative and total episode-related costs using renal colic as a model surgical condition to improve value-based payment models. METHODS: Using state Healthcare Cost and Utilization Project data, we performed a retrospective cohort study examining peri-operative costs for individuals presenting to an emergency department for renal colic and who ultimately underwent definitive surgical management. We estimated multivariable ordered and binary logistic regressions to examine the association between pre-operative and operative cost quartiles on the probability of specific post-operative cost quartiles after accounting for hospital and individual factors. We also performed logistic regressions to identify patients who deviated from predicted perioperative cost pathways. RESULTS: Among 2,736 individuals included in our analysis, episode-related costs ranged from $4,536 (bottom quartile) to $26,662 (top quartile). Individuals in the highest pre-operative cost quartile experienced an 11.7%-point higher probability of remaining in the highest post-operative cost quartile relative to those in the lowest pre-operative cost quartile (95% CI 0.0709, 0.163; p<0.001). Delays in surgery (95% CI 0.0869, 0.163; P<0.001) and Medicaid vs. private insurance (95% CI 0.01, 0.0728; P<0.01) were associated with a 12.5% and 4.1%-point higher probability of being in the top quartile of pre-operative costs, respectively. Treating facility experience with value-based payment models did not influence peri-operative costs. CONCLUSIONS: Using renal colic as a model surgical condition, our novel findings suggest that pre-operative costs are associated with both post-operative and total episode-related costs, and should be accounted for when designing future value-based payment models.

Upper extremity orthopedic softball injuries presenting to the emergency department: epidemiology across the lifespan.

BACKGROUND: Softball is a popular lifetime sport due to its inclusion of both fastpitch and slowpitch varieties, although associated injuries are common. OBJECTIVE: To compare softball injury rates across patient sex, age, race, injury location, mechanism, and activity. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for all upper extremity softball injuries in patients 10-85+ years old presenting to United States emergency departments between 2012 and 2021. RESULTS: Significantly more of the 178,303 total weighted upper extremity injuries occurred in female (68.1%) than male (31.9%) athletes (p < .001). Male patients (mean 34.9 ± 13.6 years) were older than female patients (17.4 ± 8.4; p = .019). The average incidence rate of UE injuries from 2012-2021 was 187.9 per 100,000 persons, with a significant decrease in injury incidence across the timespan (p < .001). The lowest annual injury incidence (74.7 per 100,000 persons) occurred in 2020. In patients 10-18 years old, female patients accounted for 95.1% of all injuries, whereas male patients accounted for 72.1% of all injuries in patients aged ≥23. Compared to male patients, females more frequently experienced hand (p < .001), lower arm (p = .007), shoulder (p < .001), and wrist (p < .001) injuries in patients 10-18 years old, finger (p < .001), upper arm (p = .016), and wrist (p < .001) injuries in patients 19-22, and finger injuries (p < .001) in patients aged 23 +. Across all ages, the greatest proportion of injuries were treated and released (p < .001). Most injuries occurred while fielding (41.8%) and due to player-ball contact (36.8%). CONCLUSION: Softball injury ED presentations declined across a decade, including a precipitous drop and rebound effect due to the COVID-19 pandemic. Across the lifespan, upper extremity injuries progressively shifted from female-predominant in younger athletes to male-predominant in adults.

Pancreatic cancer tumor organoids exhibit subtype-specific differences in metabolic profiles.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease characterized by complex metabolic rewiring that enables growth in changing nutrient availability and oxygen conditions. Transcriptome-based prognostic PDAC tumor subtypes, known as 'basal-like' and 'classical' subtypes are associated with differences in metabolic gene expression including genes involved in glycolysis. Tumor subtype-specific metabolism phenotypes may provide new targets for treatment development in PDAC, but their functional relevance has not been fully elucidated. We aimed to investigate differences in metabolic profiles and transcriptomes in tumor models derived from patients with basal-like and classical tumors. METHODS: Patient-derived organoids (PDOs) were established from tumor biopsies collected from patients with metastatic PDAC, including three PDOs from basal-like and five PDOs from classical tumors. Metabolic analyses included assessment of differences in metabolic activity using Seahorse Glycolysis and Mito Stress tests and 13C-glucose metabolites tracing analysis. In order to investigate the influence of mitochondrial pyruvate transport on metabolic differences, PDOs were treated with the mitochondrial pyruvate carrier 1 (MPC1) inhibitor UK-5099. Prognostic relevance of MPC1 was determined using a tumor tissue microarray (TMA) in resectable, and proteomics profiling in metastatic PDAC datasets. Whole genome and transcriptome sequencing, differential gene expression and gene set enrichment analyses were performed in PDOs. RESULTS: Metastatic PDAC PDOs showed subtype-specific differences in glycolysis and oxidative phosphorylation (OXPHOS). Basal-like tumor-derived PDOs had a lower baseline extracellular acidification rate, but higher glycolytic reserves and oxygen consumption rate (OCR) than classical tumor-derived PDOs. OCR difference was eliminated following treatment with UK-5099. In the 13C-glucose metabolites tracing experiment, a basal-like tumor PDO showed lower fractions of some M + 2 metabolites but higher sensitivity to UK-5099 mediated reduction in M + 2 metabolites than a classical tumor PDO. Protein level analyses revealed lower MPC1 protein levels in basal-like PDAC cases and association of low MPC1 levels with clinicopathologic parameters of tumor aggressiveness in PDAC. PDO differential gene expression analyses identified additional subtype-specific cellular pathways and potential disease outcome biomarkers. CONCLUSIONS: Our findings point to distinct metabolic profiles in PDAC subtypes with basal-like tumor PDOs showing higher OXPHOS and sensitivity to MPC1 inhibition. Subtypes-specific metabolic vulnerabilities may be exploited for selective therapeutic targeting.

Physiological and behavioural implications of the portosystemic shunt in C57Bl/6J mice.

A significant fraction of the popular inbred C57Bl/6J mice show structural and biochemical features of the congenital portosystemic shunt (PSS). How this hepatic abnormality affects physiological and behavioural parameters has not been explored in detail. Here, we confirmed the frequent occurrence of the PSS in C57Bl/6J mice by three different methods. We screened a cohort of 119 C57Bl/6J mice for total bile acids (TBA) in plasma, identified 11 animals (9.2%) with high TBA (>11 µm; 171.1 ± 76.8 µm), and confirmed PSS presence in that subset by magnetic resonance angiography and 1H-magnetic resonance spectroscopy of brain metabolites in the hippocampal area. In addition to the high glutamine and low myo-inositol levels, we detected lower levels of several neurotransmitters and metabolites in the hippocampus, higher brain weight and volume, as well as enhanced brain glucose utilisation in the PSS mice. We also observed differences in peripheral organ weights, haematological cell counts and clinical chemistry parameters in C57Bl/6J mice with and without PSS. Animals with PSS were slightly hyperlocomotive, had better balance on the rotarod, showed altered gait properties, and displayed attenuated fear memory in the fear conditioning test. Furthermore, we revealed a significant alteration of the pharmacokinetic profile of diazepam in C57Bl/6J mice with PSS. Our data support previous reports of hepatic disturbances and demonstrate an altered neurobiological phenotype in C57Bl/6J mice with PSS. Such congenital differences between inbred C57Bl/6J littermates may significantly distort experimental outcomes of pharmacological, behavioural and genetic studies. KEY POINTS: A significant proportion of C57Bl/6J mice, an inbred strain popular in preclinical research, have congenital portosystemic shunts (PSS) that allow venous blood to enter systemic circulation bypassing the liver. In this study, we extended existing knowledge of PSS consequences, particularly with respect to the effects on brain structure and function. We demonstrated that C57Bl/6J mice with PSS differ from their normal counterparts in brain size and contents of several neuroactive substances, as well as in peripheral organ weights, rate of glucose utilisation, blood cell counts and blood clinical chemistry parameters. C57Bl/6J mice with PSS showed altered locomotor behaviour, performed worse in a memory test and had abnormal blood pharmacokinetics of a benzodiazepine drug after a single administration. PSS presence may significantly complicate the interpretation of experiments in C57Bl/6J mice; therefore, we propose that before their use in biomedical studies, these mice should be screened with a simple blood test.

Chronobiological Spatial Clusters of Cortical Regions in the Human Brain.

PURPOSE: We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs). METHODS: High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us. RESULTS: We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2). CONCLUSIONS: This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.

Provision of ankle foot orthoses for children with cerebral palsy in Norway.

Introduction: Practice of ankle-foot orthoses (AFO) provision for ambulatory children with cerebral palsy is underreported and the literature is not consistent on choice of AFO-design. This study describes clinical practice of AFO provision for children with cerebral palsy and evaluates how clinical practice aligns with existing recommendations. Methods: An online, cross-sectional survey was conducted, inviting all Norwegian orthotists working with children with cerebral palsy. Orthotic practice was investigated using a self-reported survey design. Results: From all eligible orthotists, 54% responded, revealing that AFO provision involves patients, physicians, and physiotherapists at different stages. Patient preference directly influenced the ultimate AFO-design. Shank vertical angle was evaluated by 79%. For children with crouch gait and those with short gastrocnemius, a majority preferred a combination of rigid and articulated/flexible AFO-designs. Instrumented gait analysis was conducted by 51% at AFO delivery stage. Conclusions: The findings show that AFO provision in Norway is collaborative, involving clinical team members and consideration of patient preferences. A discrepancy between clinical practice and existing recommendations for children with crouch gait and those with short gastrocnemius is observed.

Braids and beyond: a comprehensive study on pipeline device braid stability from PREMIER data.

BACKGROUND: The pipeline embolization device (PED) has been increasingly used to treat brain aneurysms; however, concerns have been raised about braid stability with newer drawn filled tubing technology devices. OBJECTIVE: To evaluate braid stability of PED early generations using data from the PREMIER trial. METHODS: All consecutive intracranial aneurysms treated with PED (Classic and Flex) within the PREMIER trial were reviewed for braid stability (fish mouthing, foreshortening, braid bump, braid collapsing). Immediate postprocedure cone-beam CT and angiography were compared with 1- and 2- years' follow-up. Analyses included safety, measured with the modified Rankin Scale (mRS) score, including +1 mRS point and a good clinical outcome (mRS score 0-2), vessel stenosis ≥50%, effectiveness measured with Raymond-Roy Scale, and re-treatment rates. RESULTS: 133/141 aneurysms had a complete dataset. 8/133 (6%) aneurysms showed braid deformations. Inter-reader agreement was excellent (κ=0.83). Braid deformations were statistically significantly associated with in-stent vessel stenosis >50% (P=0.029), without impact on effectiveness or safety. Fish mouthing was found in 1/133 (0.75%) at 1 year, causing >50% vessel stenosis. Foreshortening occurred in 6/133 (4.5%), and braid bump in 1/133 (0.75%) associated with severe in-stent stenosis. Four other cases (3.0%) of asymptomatic in-stent stenosis due to neointimal hyperplasia were seen without braid changes. No new braid stability deformations were found at the 2-year follow-up. CONCLUSION: Our study demonstrates excellent braid stability among patients treated with the PED Classic and Flex in the PREMIER trial. Within the uncommon braid changes observed, none affected the PED safety or efficacy. TRIAL REGISTRATION NUMBER: NCT02186561.

Invited Review: Improved control of Johne's disease in dairy cattle through advancements in diagnostics, testing and management of young stock.

Johne's disease (JD; paratuberculosis) control programs have been regionally implemented across the globe, but few have successfully eradicated the pathogen (Mycobacterium avium ssp. paratuberculosis (MAP)) causing this disease. The limited success may partly be attributed to excluding young stock (calves and replacement heifers or bulls) from testing strategies aimed at identifying MAP-infected cattle. Young stock can shed MAP in feces and can have detectable MAP-specific antibodies in blood, as confirmed in experimentally and naturally infected cattle. Furthermore, MAP transmission causes new infections in young stock. Calves and heifers are often included in JD management strategies on dairy farms but excluded from conventional diagnostic tests due to a presumed lag between infection and detection of MAP shedding and/or MAP-specific serum antibodies. We summarize evidence of MAP shedding early in the course of infection and discuss promising diagnostics, testing and management strategies to support inclusion of young stock in JD control programs. Improvements in fecal Polymerase Chain Reaction, interferon-gamma release assay (IGRA), and enzyme-linked immunosorbent assay (ELISA) enable earlier detection of MAP and specific early immune responses. Studies on IGRA and ELISA have focused on evaluation of new antigens and optimal age of testing. There are new diagnostics, including phage-based tests to detect viable MAP, and gene expression patterns and metabolomics to detect MAP-infected young stock. In addition, refinements in testing and management of calves and heifers may enable reductions in MAP prevalence. We provide recommendations for dairy farmers, researchers, veterinarians, and other stakeholders that may improve JD control programs with an objective to control and potentially eradicate JD. Additionally, we have identified the most pressing gaps in knowledge that currently hamper inclusion of young stock in JD prevention and control programs. In summary, transmission among young stock may cause new MAP infections, and appropriate use of new diagnostic tests, testing and management strategies for young stock may improve the efficacy of JD control programs.

Assessing the therapeutic role of trehalose and hyaluronic acid: implications for patient care.

OBJECTIVE: This Systematic review aims to assess the efficacy of trehalose and hyaluronic acid in enhancing ocular recovery post-cataract surgery, focusing on their impact on tear film stability, ocular surface integrity, and patient-reported outcomes. METHODS: A comprehensive search was conducted across MEDLINE, PubMed, and Cochrane Library databases to identify randomized controlled trials investigating the efficacy of trehalose, hyaluronic acid, or their combination in post-cataract surgery care. The inclusion criteria focused on peer-reviewed studies in English, detailing outcomes relevant to ocular recovery such as tear film stability, ocular surface integrity, patient-reported discomfort, or visual acuity (VA). The quality of the included studies was assessed using the Cochrane Risk of Bias Tool and synthesized the data qualitatively. RESULTS: Four qualitative investigations met the inclusion criteria. The studies collectively assessed the efficacy of a 3% trehalose and 0.15% hyaluronic acid eye drop solution in reducing postoperative eye symptoms compared to various control solutions. Parameters measured included tear break-up time (TBUT), Fluorescein staining, tear production (Schirmer test), and Ocular Surface Disease Index (OSDI) scores. The results indicated significant improvements in tear film stability and ocular surface health for the treatment groups compared to controls, with a notable decrease in patient-reported discomfort. The study showed an improvement of - 18 (± 14.6) in the treatment group compared to - 7 (± 8.0) in the control group for OSDI. For TBUT, the treatment group improved by 3 (± 1.2) s, whereas the control group improved by 0.3 (± 0.71) s. VA, measured on a scale of 0-100, increased to 17 (± 0.7) in the treatment group compared to 15 (± 1.1) in the control group. CONCLUSIONS: Trehalose and hyaluronic acid may be beneficial in the postoperative period by enhancing tear film stability and ocular surface health. While the results are promising, further research is needed to confirm these findings, understand the mechanisms of action, and explore broader applications.

Optimizing the hemodynamics of hand injections in neuroangiography.

PURPOSE: Optimizing the preparation of a 10 ml syringe for manual injection of contrast media can help operators obtain easier and faster injections. This study aims to compare the flow rates of different contrast media injection methods. METHODS: Different contrast media solutions were compared: 100% contrast (10 ml contrast), mixed contrast solution (8:2 contrast/saline), and layered contrast below saline ("Parfait") in different volumes. Contrast media were injected at room temperature (20°C) and after heating (37°C). Four operators injected 10 ml syringes filled with different mediums through 5-French angiographic catheters. The average flow rate was used to compare different contrast injection mediums. The Kruskal-Wallis test with post-hoc pairwise comparisons using Bonferroni correction or Mann-Whitney U-tests were employed depending on the type of comparison. RESULTS: Compared to the 100% contrast solution, every Parfait media and mixed contrast solution demonstrated significantly higher flow rates (p < 0.001). The 5 ml saline Parfait had the highest flow rate among the Parfait solutions. The 5 ml saline Parfait and the mixed solution had comparable flow rates (p = 0.237). Higher flow rates were observed upon heating both 100% contrast (p < 0.001) and mixed contrast solutions (p < 0.001) in comparison to their flow rates at room temperature. CONCLUSION: This study demonstrates the capability of the Parfait and mixed contrast injections to achieve higher flow rates than the 100% contrast solutions. Heating the contrast media to 37°C also proves to be a viable strategy for further enhancing the flow rates for 100% and mixed contrast solutions.

Swashing motility: A novel propulsion-independent mechanism for surface migration in Salmonella and E. coli.

Bacterial motility over surfaces is crucial for colonization, biofilm formation, and pathogenicity. Surface motility in Escherichia coli and Salmonella enterica is traditionally believed to rely on flagellar propulsion. Here, we report a novel mode of motility, termed "swashing," where these bacteria migrate on agar surfaces without functional flagella. Mutants lacking flagellar filaments and motility proteins exhibit rapid surface migration comparable to wild-type strains. Unlike previously described sliding motility, swashing is inhibited by surfactants and requires fermentable sugars. We propose that the fermentation of sugars at the colony edge produces osmolytes, creating local osmotic gradients that draw water from the agar, forming a fluid bulge that propels the colony forward. Our findings challenge the established view that flagellar propulsion is required for surface motility in E. coli and Salmonella, and highlight the role of a fermentation in facilitating bacterial spreading. This discovery expands our understanding of bacterial motility, offering new insights into bacterial adaptive strategies in diverse environments.

A Study of the Psychometric Properties of the Pediatric Symptom Checklist-17 for Children With Developmental Delays and Disorders.

Primary care physicians (PCPs) frequently serve pediatric patients with developmental delays and disorders (DD/D). Although the most widely used primary care behavioral health screener, the Pediatric Symptom Checklist-17 (PSC-17), is validated for use with children without DD/D, it is unclear whether this measure accurately identifies behavioral health symptoms in youth with DD/D. Thus, the purpose of this study was to assess the psychometric properties of the PSC-17 for children with DD/D. Medical record data from 3596 pediatric patients at a primary care clinic were analyzed. Descriptive analyses, measurement invariance testing, and internal consistency evaluations were conducted to assess the psychometric properties of the PSC-17. The results of these analyses support the use of the PSC-17 for behavioral health screening for children with DD/D. Behavioral health screening in this population is critical, because the timely identification of behavioral health concerns can facilitate early intervention, which may enhance long-term functioning.

Ten Years of the Synthetic Biology Summer Course at Cold Spring Harbor Laboratory.

The Cold Spring Harbor Laboratory (CSHL) Summer Course on Synthetic Biology, established in 2013, has emerged as a premier platform for immersive education and research in this dynamic field. Rooted in CSHL's rich legacy of biological discovery, the course offers a comprehensive exploration of synthetic biology's fundamentals and applications. Led by a consortium of faculty from diverse institutions, the course structure seamlessly integrates practical laboratory sessions, exploratory research rotations, and enriching seminars by leaders in the field. Over the years, the curriculum has evolved to cover essential topics such as cell-free transcription-translation, DNA construction, computational modeling of gene circuits, engineered gene regulation, and CRISPR technologies. In this review, we describe the history, development, and structure of the course, and discuss how elements of the course might inform the development of other short courses in synthetic biology. We also demonstrate the course's impact beyond the lab with a summary of alumni contributions to research, education, and entrepreneurship. Through these efforts, the CSHL Summer Course on Synthetic Biology remains at the forefront of shaping the next generation of synthetic biologists.

Electroless Deposition for Robust and Uniform Copper Nanoparticles on Electrospun Polyacrylonitrile (PAN) Microfiltration Membranes.

Filtration membranes coated in metals such as copper have dramatically improved biofouling resistance and pathogen destruction. However, existing coating methods on polymer membranes impair membrane performance, lack uniformity, and may detach from their substrate, thus contaminating the permeate. To solve these challenges, we developed the first electroless deposition protocol to immobilize copper nanoparticles on electrospun polyacrylonitrile (PAN) fibers for the design of antimicrobial membranes. The deposition was facilitated by prior silver seeding. Distinct mats with average fiber diameters of 232 ± 36 nm, 727 ± 148 nm and 1017 ± 80 nm were evaluated for filtration performance. Well-dispersed copper nanoparticles were conformal to the fibers, preserving the open-cell architecture of the membranes. The copper particle sizes ranged from 20 to 140 nm. Infrared spectroscopy revealed the PAN fiber mats' relative chemical stability/resistance to the copper metallization process. In addition, the classical cyclization of the cyano functional group in PAN was observed. For model polystyrene beads with average sizes of 3 µm, Cu NP-PAN fiber mats had high water flux and separation efficiency with negligible loss of Cu NP from the fibers during flow testing. Fiber size increased flux and somewhat decreased separation efficiency, though the efficiency values were still high.

Central and peripheral physiological responses to decision making in hoarding disorder.

Individuals with hoarding disorder (HD) have difficulty parting with personal possessions, which leads to the accumulation of excessive clutter. According to a proposed biphasic neurobiological model, HD is characterized by blunted central and peripheral nervous system activity at rest and during neutral (non-discarding) decisions, and exaggerated activity during decision-making about discarding personal possessions. Here, we compared the error-related negativity (ERN) and psychophysiological responses (skin conductance, heart rate and heart rate variability, and end tidal CO2) during neutral and discarding-related decisions in 26 individuals with HD, 37 control participants with anxiety disorders, and 28 healthy control participants without psychiatric diagnoses. We also compared alpha asymmetry between the HD and control groups during a baseline resting phase. Participants completed a series of Go/No Go decision-making tasks, one involving choosing certain shapes (neutral task) and the other involving choosing images of newspapers to imaginally "discard" (discarding task). While all participants showed expected increased frontal negativity to commission of an error, contrary to hypotheses, there were no group differences in the ERN or any psychophysiological measures. Alpha asymmetry at rest also did not differ between groups. The findings suggest that the ERN and psychophysiological responses may not differ in individuals with HD during simulated discarding decisions relative to control participants, although the null results may be explained by methodological challenges in using Go/No Go tasks as discarding tasks. Future replication and extension of these results will be needed using ecologically valid discarding tasks.

Accounting for extinction dynamics unifies the geological and biological histories of Indo-Australian Archipelago.

Biogeographical reconstructions of the Indo-Australian Archipelago (IAA) have suggested a recent spread across the Sunda and Sahul shelves of lineages with diverse origins, which appears to be congruent with a geological history of recent tectonic uplift in the region. However, this scenario is challenged by new geological evidence suggesting that the Sunda shelf was never submerged prior to the Pliocene, casting doubt on the interpretation of recent uplift and the correspondence of evidence from biogeography and geology. A mismatch between geological and biogeographical data may occur if analyses ignore the dynamics of extinct lineages, because this may add uncertainty to the timing and origin of clades in biogeographical reconstructions. We revisit the historical biogeography of multiple IAA taxa and explicitly allow for the possibility of lineage extinction. In contrast to models assuming zero extinction, we find that all of these clades, including plants, invertebrates and vertebrates, have a common and widespread geographic origin, and each has spread and colonized the region much earlier than previously thought. The results for the eight clades re-examined in this article suggest that they diversified and spread during the early Eocene, which helps to unify the geological and biological histories of IAA.

Exploring perinatal ketamine for postpartum depression following cesarean section: A systematic review.

The aim of this study was to explore the use of perinatal ketamine to see if it can be used for the reduction of postpartum depression (PPD) following cesarean section (C-section). PubMed, Cochrane, and Web of Science were the primary databases used for this review. Search terms used on January 5, 2024 incorporated "ketamine," "C-section," "postpartum depression," and related synonyms. The criteria for inclusion centered on studies published between January 1, 2008 and January 5, 2024. The final selection of articles was screened based on extraction criteria leaving eight randomized control trials in the final review. The selected data from the studies incorporated sample characteristics, study and population characteristics, and quantitative analyses covering Edinburgh Postpartum Depression Scale (EPDS) scores and depression rates. The Risk of Bias assessment was utilized to gain a deeper understanding of the quality of methodology used by the research studies. The review showed that ketamine can reduce the symptoms of PPD in mothers who have recently undergone C-sections. Some studies showed decreased EPDS scores following the administration of ketamine while two studies also reported no significant differences in PPD following ketamine administration in C-section patients. For example, Ma et al. found that the EPDS score at postpartum day 4 was significantly lower in the ketamine group compared with the control group (p = 0.007) while Yang et al. found that there were no significant differences between the ketamine and control group at 3 days postpartum (p = 0.553). The research from this review suggests that ketamine administration can prevent or decrease the symptoms of PPD, but more research is needed to establish the causal relationship between ketamine dosage and PPD in C-section patients.

Association of genetic variants in CYP3A5, DRD2 and NK1R with opioid overdose.

In 2023, 3651 Ohioans died because of an opioid overdose. Of those opioid overdoses, 3579 (98%) of which were attributed to fentanyl. We evaluated the association between 180 candidate single nucleotide polymorphisms (SNPs) and self-reported, nonfatal opioid overdose history from a prospective sample of 1301 adult patients (≥18 years of age) seen in three urban emergency departments in Ohio. Candidate SNPs included 120 related to the dopamine reward pathway and 60 related to pharmacokinetics. Of the 821 patients who reported having been exposed to opioids in their lifetime, 95 (11.6%) also reported having experienced an opioid-related overdose. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and opioid overdose, correcting for multiple comparisons. Three SNPs, located in three different genes were associated with opioid overdose: increased odds with CYP3A5 (rs776746) and DRD2 (rs4436578), and decreased odds with NKIR (rs6715729). Homozygotic CYP3A5 (rs776746) had the highest adjusted odds ratio (OR) of 6.96 (95% CI [2.45, 29.23]) and homozygotic NK1R (rs6715729) had the lowest OR of 0.28 (95% CI [0.14, 0.54). Given that CYP3A5 (rs776746) has been associated with increased plasma concentrations of fentanyl, rs776746 could potentially be utilized as a prognostic risk indicator for the potential of an opioid overdose. NK1R regulates the expression of the neurokinin-1 receptor, a regulator of respiration and NK1R (rs6715729) represents a novel genetic marker for a decreased risk of opioid overdose risk.