Implementing Montessori approaches after training: A mixed methods study to examine staff understanding and movement toward action.

Background: This paper uses Normalization Process Theory (NPT) to examine staff impressions of Montessori-based program training and implementation at Veterans Affairs Community Living Centers (VA CLCs; nursing homes). Methods: We conducted a mixed-methods evaluation of Montessori Approaches to Person-Centered Care (MAP-VA) at eight VA CLCs. Trainings were conducted as either a live virtual course or a pre-recorded asynchronous class. Two NPT constructs, coherence building and cognitive participation, informed qualitative interview questions, surveys, and analyses focused on staff movement from knowledge to action during initial implementation. Data collection included staff-completed standardized post-training exams (N = 906), post-training evaluations (N = 761), and optional validated surveys on perceptions of Montessori training (N = 307). Champions (peer-leaders) from each CLC completed semi-structured qualitative interviews post-training (N = 22). Findings: The majority of staff (83%-90%) passed all courses. Staff evaluated the training highly (80%+ agreement) on learning relevant new knowledge and confidence applying new skills. On average, staff felt MAP-VA would become a normal part of their work (7.68/10 scale), and reported increased familiarity with Montessori approaches after training (p = .002). Qualitative interview data from staff trained in Montessori supported three themes concordant with the NPT dimensions of coherence building and cognitive participation. (1) Coherence regarding Montessori: staff demonstrated an understanding of the program and mentioned the benefits of Montessori compared to their previous usual routines. Cognitive participation or engagement with Montessori: (2) staff had positive feelings about Montessori principles/applications and demonstrated a willingness to try the Montessori approach, and (3) staff made sense of the new intervention through early rehearsal of Montessori principles/practices and recognized opportunities for using Montessori in future interactions. Conclusions: Montessori virtual training resulted in high levels of coherence and cognitive participation among multidisciplinary staff, evidenced by high knowledge, self-efficacy, and readiness to act. The asynchronous and synchronous trainings were accessible, relevant, and supported diverse learners.

The Relationship Between State-Level Earned Income Tax Credits and Violent Crime.

Policies that provide economic support, such as the earned income tax credit (EITC), improve peoples' ability to meet their basic needs and reduce stress, which can reduce violence perpetration. Refundable state-level EITCs have been associated with decreases in multiple forms of violence (e.g., child abuse and neglect); however, it is unknown whether there is an association between the EITC and violent crime as captured by Uniform Crime Reports. Crime and violence remain a pressing concern for many communities across the nation. Using a longitudinal data set, we conducted fixed-effects regression models with year and state specified as fixed effects, to determine whether variations in generosity of state-level EITCs are related to the rate of violent crime. After adjusting for demographic covariates, refundable state-level EITCs remained significantly associated with reductions in criminal homicide compared to states without an EITC. As many states attempt to combat crime and prevent violence in their communities, anti-poverty measures such as the EITC provide a promising strategy for reducing the social and economic costs associated with violence.

Safely Doing Less for Febrile Infants: Reviewing Management in the Setting of the 2021 American Academy of Pediatrics Clinical Practice Guideline.

For more than 4 decades, pediatricians have sought the best practices for effectively managing well-appearing young febrile infants. In 2021, the American Academy of Pediatrics released a clinical practice guideline for the management of well-appearing febrile infants aged 8 to 60 days. The guideline incorporates advancements in testing, such as biomarkers and diagnostic testing in the setting of changing epidemiology, to help risk stratify infants in the newly formed group age 22 to 28 days as well as the group age 29 to 60 days. The new guideline uses inflammatory markers (procalcitonin, C-reactive protein, absolute neutrophil count, and a temperature >38.4°C) to identify infants at low risk for invasive bacterial infection who can potentially avoid the invasive procedures of lumbar puncture, hospitalization, and broad-spectrum antimicrobials. Because of continued ambiguity, incorporating shared decision-making with families in the care of these infants will be important, as will ongoing clinical research to better inform future practice. [Pediatr Ann. 2024;53(6):e202-e207.].

Advances in Vascular Diagnostics using Magnetic Particle Imaging (MPI) for Blood Circulation Assessment.

Rapid and accurate assessment of conditions characterized by altered blood flow, cardiac blood pooling, or internal bleeding is crucial for diagnosing and treating various clinical conditions. While widely used imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound offer unique diagnostic advantages, they fall short for specific indications due to limited penetration depth and prolonged acquisition times. Magnetic particle imaging (MPI), an emerging tracer-based technique, holds promise for blood circulation assessments, potentially overcoming existing limitations with reduction in background signals and high temporal and spatial resolution, below the millimeter scale. Successful imaging of blood pooling and impaired flow necessitates tracers with diverse circulation half-lives optimized for MPI signal generation. Recent MPI tracers show potential in imaging cardiovascular complications, vascular perforations, ischemia, and stroke. The impressive temporal resolution and penetration depth also position MPI as an excellent modality for real-time vessel perfusion imaging via functional MPI (fMPI). This review summarizes advancements in optimized MPI tracers for imaging blood circulation and analyzes the current state of pre-clinical applications. This work discusses perspectives on standardization required to transition MPI from a research endeavor to clinical implementation and explore additional clinical indications that may benefit from the unique capabilities of MPI.

Postoperative pain scores and opioid use after standard bupivacaine vs. liposomal bupivacaine regional blocks for abdominal cancer surgery: A propensity score matched study.

BACKGROUND: Fascial plane blocks (FPBs) are widely used for abdominal surgery with the assumption that liposomal bupivacaine (LB) is more effective than standard bupivacaine (SB). METHODS: This was a single-institution retrospective cohort study of patients administered FPBs with LB or SB â€‹+ â€‹admixtures (dexamethasone/dexmedetomidine) for open abdominal cancer surgery. Propensity score matching generated a 2:1 (LB:SB) matched cohort. Opioid use (mg oral morphine equivalents, OME) and severe pain (≥3 pain scores ≥7 in a 24-h period) were compared. RESULTS: Opioid use was >150 â€‹mg OME in 19.9 â€‹% (29/146) LB and 16.4 â€‹% (12/73) SB patients (p â€‹= â€‹0.586). Severe pain was experienced by 44 â€‹% (64/146) LB and 53 â€‹% (39/73) SB patients (p â€‹= â€‹0.198). On multivariable analysis, SB vs LB choice was not associated with high opioid volume >150 â€‹mg or severe pain. CONCLUSIONS: FPBs with standard bupivacaine were not associated with higher 72-h opioid use or more severe pain compared to liposomal bupivacaine.

A case of haemoglobinuria in a cat after near-drowning.

The aim of this study is to describe a case of haemoglobinuria in a cat after near-drowning. A 6-year-old male neutered domestic short hair cat weighing 6.5 kg with a pre-existing seizure disorder presented to an emergency hospital after near-drowning in a swimming pool during a seizure episode. On presentation, the patient was obtunded, dyspnoeic, bradycardic and hypothermic. Imaging revealed evidence of severe bilateral pulmonary infiltrates. Treatment with intravenous diazepam, amoxicillin, fluid therapy, active warming and oxygen therapy was administered. The cat developed haemoglobinuria approximately 6 h after nearly drowning. Despite improvements in mentation, pulse quality and heart rate, respiratory compromise and poor oxygen saturation persisted, prompting euthanasia approximately 10 h after admission. To the author's knowledge, this is the first reported clinical case of haemoglobinuria following near-drowning in veterinary medicine.

Associations with unplanned repeat irrigation and debridement of native septic arthritis.

PURPOSE: To identify associations with unplanned repeat irrigation and debridement (I&D) after arthrotomy for native septic arthritis. METHODS: A retrospective review identified patients with native septic arthritis treated with open arthrotomies. The primary outcome was unplanned repeat I&D within 90 days. Associations evaluated for included comorbidities, ability to bear weight, fever, immunosuppressed status, purulence, C-reactive protein, erythrocyte sedimentation rate, white blood cell count (synovial fluid and serum levels), and synovial fluid polymorphonuclear cell percentage (PMN%). RESULTS: There were 59 arthrotomies in 53 patients involving the knee (n = 32), shoulder (n = 10), elbow (n = 8), ankle (n = 6), and hip (n = 3). The median patient age was 52, and a 71.2% were male. An unplanned repeat I&D was required in 40.7% (n = 24). The median time to the second I&D was 4 days (interquartile range 3 to 9). On univariate analysis, unplanned repeat I&Ds were associated with fever (p = 0.03), purulence (p = 0.01), bacteria growth on cultures (p = 0.02), and the use of deep drains (p = 0.05). On multivariate analysis, the only variables that remained associated with unplanned repeat I&Ds were fever (odds ratio (OR) 5.5, 95% confidence interval (CI) 1.3, 23.6, p = 0.02) and purulence (OR 5.3, CI 1.1, 24.4, p = 0.03). CONCLUSIONS: An unplanned repeat I&D was required in 40.7% of patients and was associated with fever and purulence. These findings highlight the difficulty of controlling these infections and support the need for future research into better methods of management. LEVEL OF EVIDENCE: Diagnostic, Level III.

Discharge medication delivery location and postpartum blood pressure control in patients with hypertensive disorders of pregnancy.

OBJECTIVE: This study examined whether use of bedside medication delivery (Meds to Beds, M2B) or on-campus pharmacy at discharge was associated with improved postpartum blood pressure (BP) control compared to outside pharmacy use in patients with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a secondary analysis of 357 patients with HDP enrolled in STAMPP-HTN (Systematic Treatment and Management of Postpartum Hypertension Program) who were discharged from delivery admission with antihypertensives between October 2018 and June 2020. Patients were grouped by discharge medication location: M2B/on-campus pharmacy (on-site) versus outside pharmacy (off-site). MAIN OUTCOME MEASURES: The primary outcome was BP values at the immediate postpartum visit. Secondary outcomes included six-week visit BP values, attendance at both visits, and readmission within six weeks. RESULTS: Median BP values were no different based on pharmacy location at immediate postpartum visit for both systolic ((135 [IQR 127, 139] on-site vs 137 [127, 145] off-site, p = 0.22) and diastolic (81 [74, 91] vs 83 [76, 92], p = 0.45) values. Similar findings were noted at six weeks. Patients who used an off-site pharmacy had higher attendance rates at the immediate postpartum visit but this difference was attenuated after adjusting for group differences (OR 0.67 [95 % CI 0.37-1.20], p = 0.18). Readmission rates were also not different between groups (12.2 % on-site vs 15.8 % off-site pharmacy, p = 0.43). CONCLUSION: In the context of a preexisting multicomponent HDP quality improvement program, on-campus pharmacy and bedside medication delivery use was not associated with additional improvement in postpartum BP control, follow-up rates, or readmission rates.

Patient Experience and Decision-Making Process for Laser Photocoagulation for Monochorionic Twin Pregnancy: A Qualitative Exploration.

INTRODUCTION: The aim of the study was to explore patients' perspectives on diagnosis and treatment options for complicated monochorionic multiple gestations, and experiences with fetoscopic laser photocoagulation. METHODS: This is a prospective cohort study of patients undergoing laser photocoagulation. Participants were interviewed during pregnancy and the postpartum period. Qualitative analysis was performed. RESULT: Twenty-seven patients who were candidates for laser photocoagulation were included. All elected to have laser photocoagulation. Patients chose surgery with goals of improving survival, decreasing the risk of preterm delivery, and improving the long-term health of their fetuses. They demonstrated accurate knowledge of the risks and benefits of treatment. Most (74%) felt that laser photocoagulation represented their only viable clinical option. Few seriously considered pregnancy termination or selective reduction (7% and 11% respectively). Postpartum, patients expressed no regrets about their decisions for surgery, but many felt unprepared for the challenges of preterm delivery. CONCLUSION: Participants weighed treatment options similarly to fetal specialists. They acknowledged but did not seriously consider treatments other than fetoscopic laser photocoagulation and were highly motivated to do whatever they could to improve outcomes for their fetuses.

Activity-Based Protein Profiling to Probe Relationships between Cytochrome P450 Enzymes and Early-Age Metabolism of Two Polycyclic Aromatic Hydrocarbons (PAHs): Phenanthrene and Retene.

A growing body of literature has linked early-life exposures to polycyclic aromatic hydrocarbons (PAH) with adverse neurodevelopmental effects. Once in the body, metabolism serves as a powerful mediator of PAH toxicity by bioactivating and detoxifying PAH metabolites. Since enzyme expression and activity vary considerably throughout human development, we evaluated infant metabolism of PAHs as a potential contributing factor to PAH susceptibility. We measured and compared rates of phenanthrene and retene (two primary PAH constituents of woodsmoke) metabolism in human hepatic microsomes from individuals ≤21 months of age to a pooled sample (n = 200) consisting primarily of adults. We used activity-based protein profiling (ABPP) to characterize cytochrome P450 enzymes (CYPs) in the same hepatic microsome samples. Once incubated in microsomes, phenanthrene demonstrated rapid depletion. Best-fit models for phenanthrene metabolism demonstrated either 1 or 2 phases, depending on the sample, indicating that multiple enzymes could metabolize phenanthrene. We observed no statistically significant differences in phenanthrene metabolism as a function of age, although samples from the youngest individuals had the slowest phenanthrene metabolism rates. We observed slower rates of retene metabolism compared with phenanthrene also in multiple phases. Rates of retene metabolism increased in an age-dependent manner until adult (pooled) metabolism rates were achieved at ∼12 months. ABPP identified 28 unique CYPs among all samples, and we observed lower amounts of active CYPs in individuals ≤21 months of age compared to the pooled sample. Phenanthrene metabolism correlated to CYPs 1A1, 1A2, 2C8, 4A22, 3A4, and 3A43 and retene metabolism correlated to CYPs 1A1, 1A2, and 2C8 measured by ABPP and vendor-supplied substrate marker activities. These results will aid efforts to determine human health risk and susceptibility to PAHs exposure during early life.

Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis.

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium extruder ("CalEx") expression recapitulates multiple features of P2Y6 knockout, including reduced lysosome biogenesis and phagocytic interactions. Ultimately, P2Y6 knockout mice retain more CA3 neurons and better cognitive task performance during epileptogenesis. Our results demonstrate that P2Y6 signaling impacts multiple aspects of myeloid cell immune function during epileptogenesis.

The Effect of Crystal Arthropathy on the Diagnostic Criteria of Native Septic Arthritis.

INTRODUCTION: Distinguishing between septic arthritis and crystal arthropathy flares can be challenging. The purpose of this study was to determine how the presence of synovial crystals affects the diagnostic criteria of septic arthritis. METHODS: A retrospective review identified patients undergoing joint aspirations to rule out native septic arthritis. Differences between septic arthritis presenting with and without synovial crystals were analyzed. A receiver-operating characteristic curve was plotted for laboratory markers to determine the area under the curve, or diagnostic accuracy, for septic arthritis and to evaluate thresholds that maximized sensitivity and specificity. RESULTS: There were 302 joint aspirations in 267 patients. Septic arthritis was diagnosed in 17.9% (54/302). Patients with synovial crystals were less likely to have septic arthritis (4.2% [5/119] vs. 26.8% [49/183], P < 0.0001). Septic arthritis in patients with no synovial crystals was associated with fever and a higher synovial white blood cell (WBC) count, synovial polymorphonuclear cell percentage (PMN%), serum WBC, and C-reactive protein (CRP) ( P < 0.05). Septic arthritis in patients with synovial crystals was only associated with inability to bear weight and a higher synovial WBC and CRP ( P < 0.05). Synovial PMN% was considered nondiagnostic of septic arthritis (area under the curve 0.56) in patients with crystals while synovial WBC and CRP had acceptable (0.76) and excellent (0.83) diagnostic utility, respectively. The WBC and CRP value thresholds that maximized sensitivity and specificity for septic arthritis were greater in patients with crystals (21,600 vs. 17,954 cells/µL and 125 vs. 69 mg/L, respectively). DISCUSSION: The presence of synovial crystals reduced the likelihood of septic arthritis and altered the laboratory diagnostic criteria. PMN% was nondiagnostic in the setting of synovial crystals.

Kombucha Tea-associated microbes remodel host metabolic pathways to suppress lipid accumulation.

The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintain C. elegans on a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture. KT microbes robustly colonize the gut of KTM-fed animals and confer normal development and fecundity. Intriguingly, animals consuming KTMs display a marked reduction in total lipid stores and lipid droplet size. We find that the reduced fat accumulation phenotype is not due to impaired nutrient absorption, but rather it is sustained by a programed metabolic response in the intestine of the host. KTM consumption triggers widespread transcriptional changes within core lipid metabolism pathways, including upregulation of a suite of lysosomal lipase genes that are induced during lipophagy. The elevated lysosomal lipase activity, coupled with a decrease in lipid droplet biogenesis, is partially required for the reduction in host lipid content. We propose that KTM consumption stimulates a fasting-like response in the C. elegans intestine by rewiring transcriptional programs to promote lipid utilization. Our results provide mechanistic insight into how the probiotics in Kombucha Tea reshape host metabolism and how this popular beverage may impact human metabolism.

Impact of crystalline domains on long-term stability and mechanical performance of anisotropic silk fibroin sponges.

Sponge-like materials made from regenerated silk fibroin biopolymers are a tunable and advantageous platform for in vitro engineered tissue culture and in vivo tissue regeneration. Anisotropic, three-dimensional (3D) silk fibroin sponge-like scaffolds can mimic the architecture of contractile muscle. Herein, we use silk fibroin solution isolated from the cocoons of Bombyx mori silkworms to form aligned sponges via directional ice templating in a custom mold with a slurry of dry ice and ethanol. Hydrated tensile mechanical properties of these aligned sponges were evaluated as a function of silk polymer concentration (3% or 5%), freezing time (50% or 100% ethanol), and post-lyophilization method for inducing crystallinity (autoclaving, water annealing). Hydrated static tensile tests were used to determine Young's modulus and ultimate tensile strength across sponge formulations at two strain rates to evaluate rate dependence in the calculated parameters. Results aligned with previous reports in the literature for isotropic silk fibroin sponge-like scaffolds, where the method by which beta-sheets were formed and level of beta-sheet content (crystallinity) had the greatest impact on static parameters, while polymer concentration and freezing rate did not significantly impact static mechanical properties. We estimated the crystalline organization using molecular dynamics simulations to show that larger crystalline regions may be responsible for strength at low strain amplitudes and brittleness at high strain amplitudes in the autoclaved sponges. Within the parameters evaluated, extensional Young's modulus is tunable in the range of 600-2800 kPa. Dynamic tensile testing revealed the linear viscoelastic region to be between 0% and 10% strain amplitude and 0.2-2 Hz frequencies. Long-term stability was evaluated by hysteresis and fatigue tests. Fatigue tests showed minimal change in the storage and loss modulus of 5% silk fibroin sponges for more than 6000 min of continuous mechanical stimulation in the linear regime at 10% strain amplitude and 1 Hz frequency. Furthermore, we confirmed that these mechanical properties hold when decellularized extracellular matrix is added to the sponges and when the mechanical property assessments were performed in cell culture media. We also used nano-computed tomography (nano-CT) and simulations to explore pore interconnectivity and tortuosity. Overall, these results highlight the potential of anisotropic, sponge-like silk fibroin scaffolds for long-term (>6 weeks) contractile muscle culture with an in vitro bioreactor system that provides routine mechanical stimulation.

Reconstruction of Urethral Sphincter With Polyacrylamide Hydrogel.

IMPORTANCE: Urethral bulking is an alternative to synthetic midurethral sling for the treatment of stress urinary incontinence (SUI) in women. Urethral bulking agents, which are injected in the submucosal tissues of the proximal urethra/bladder neck, have demonstrated less adverse effects with similar satisfaction rates but lower subjective and objective cure rates when compared with midurethral sling. Cystoscopic Reconstruction of External Sphincter Technique (CREST) is a novel technique, which reinforces the natural closure mechanism of the external urinary sphincter (EUS). OBJECTIVE: The aim of the study was to provide safety and efficacy data for injecting polyacrylamide hydrogel (PAHG) in the components of the female EUS. STUDY DESIGN: This was a retrospective chart review of patients using CREST with PAHG as initial treatment for SUI by a single surgeon from January 2022 to October 2022. Exclusion criteria are as follows: younger than 18 years, prior SUI surgery, concomitant pelvic organ prolapse or reconstructive procedure, neurological conditions, or history of radiation. Subjective and objective cure rates were measured by patient-reported symptoms and cough stress test. Urinary retention, postoperative urinary infection, and de novo urinary urgency were assessed. RESULTS: One hundred and thirteen consecutive patients met inclusion criteria with median follow-up of 3 months. Eighty-five percent of participants reported subjective improvement, 69% reported subjective cure, and 69% demonstrated objective cure. Nine patients reported transient postoperative retention, 8 reported postoperative urinary tract infections, and 5 reported de novo urgency. There were no serious adverse events. CONCLUSIONS: CREST is a novel technique for injection of PAHG, into the EUS to treat SUI. Our data suggest that this technique could improve urethral injection outcomes with minimal complications.

Trends and geographic differences in social work telehealth utilization.

We plotted trends in social work telehealth use among Veterans in a U.S. national social work staffing program and examined the relationship between geographic factors (rurality and neighborhood disadvantage) and telehealth use (audio and video) using linear probability models. Social work telehealth use increased among Veterans during the COVID-19 pandemic. There were no geographic differences in telephone telehealth use. Video telehealth use was less common among Veterans in isolated rural areas and among Veterans in highly disadvantaged areas. Outreach efforts can address barriers that Veterans who live in rural and disadvantaged areas may experience in using video telehealth.

Effect of exogenous melatonin on the cellular response of Holstein heifer calves during vaccination.

Despite rigorous vaccination protocols, calf morbidity is the primary contributor to economic loss in the calf sector of the dairy industry. Melatonin has modulated immune response in other mature animal species. We hypothesized that exogenous melatonin may improve the cellular response to vaccination in dairy calves. Our objective was to evaluate the effect of exogenous melatonin on polymorphonuclear leukocyte (PMN) function in Holstein heifer calves during immunization. Sixty neonatal Holstein heifers were enrolled by birth cohort (block) and randomized to one of four treatments: control (CON), vaccination of 0.5 mg ovalbumin on days 0 and 21 (VAC), implantation of 24 mg melatonin on day 0 (MEL), or both melatonin and vaccine treatments (MVAC). Jugular blood was collected on days 0, 21, 42, and 63 to measure circulating melatonin, anti-ovalbumin immunoglobulin-G, and PMN function. Calves implanted with melatonin had greater circulating melatonin than non-implanted on day 21 (P < 0.01). Anti-ovalbumin IgG was greater for vaccinated than non-vaccinated calves (P < 0.01). Anti-ovalbumin IgG was greater for MVAC than VAC calves on day 63. Percent of cells and mean florescence intensity of cells performing oxidative burst decreased from day 0 to day 63 (P < 0.01) but were not affected by treatment (P ≥ 0.26). There was a tendency (P = 0.10) for an interaction of melatonin, vaccination, and day for the mean florescence intensity of cells performing phagocytosis where MVAC was greater than all other treatments on d 42. Exogenous melatonin may alter PMN function of calves during vaccination. Further research is needed to define the effect of melatonin on development of antigen-specific IgG during programmed vaccination protocols.

Identifying Risk Factors for Cardiovascular Events Among Active-Duty Service Members and Veterans Prescribed Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).

Background: Oral NSAIDs are widely used analgesic medications for the treatment of musculoskeletal and inflammatory conditions. NSAIDs are associated with adverse effects that arise from COX enzyme inhibition including cardiovascular events. The combined role of patient and prescription factors associated with NSAID use on cardiovascular risk is not well characterized. Objective: The purpose of this study is to identify the risk factors with cardiovascular events among NSAID users. Methods: This study is a retrospective, nested case-control study, within the DAVINCI database, among active-duty service members and veterans with at least one NSAID pharmacy claim between fiscal year (FY) 2015-FY2020. Inclusion criteria individuals ≥18 years of age received a prescription NSAID for ≥7-day supply and a duration ≥1 month overall. Cases experienced nonfatal myocardial infarction, nonfatal stroke, or new onset heart failure. Ten controls were selected per case. Risk factors were identified through logistic regression modeling. Results: The risk factors with strongest association to the primary outcome included age starting at 45 up to 75 and older, the first 90 days of NSAID exposure, cerebrovascular disease, cardiomyopathy, and history of myocardial infarction. Cox-selectivity and dose did not appear to be clinically significant in their association with cardiovascular events. Conclusion: The results of this study indicate that age, initial NSAID exposure, and comorbidities are more predictive than NSAID-specific factors such as COX-selectivity and dose. The results provide the framework for development of a risk score to improve prediction of NSAID-associated cardiovascular events.

Harvesting Silk Fibers from Plodia interpunctella: Role of Environmental Rearing Conditions in Fiber Production and Properties.

Silk fibers are produced by a wide variety of insects. The silkworm Bombyx mori (Bombyx) was domesticated because the physical properties of its silk fibers were amenable to the production of fine textiles. Subsequently, engineers have regenerated silk fibroin to form biomaterials. The monocular focus on Bombyx silk has underutilized the expanse of diverse silk proteins produced by more than 100,000 other arthropods. This vast array of silk fibers could be utilized for biomedical engineering challenges if sufficient rearing and purification processes are developed. Herein, we show that the moth, Plodia interpunctella (Plodia), represents an alternative silk source that is easily reared in highly regulated culture environments allowing for greater consistency in the silk produced. We controlled the temperature, resource availability (larvae/gram diet), and population density (larvae/mL) with the goal of increasing silk fiber production and improving homogeneity in Plodia silk proteins. We determined that higher temperatures accelerated insect growth and reduced life cycle length. Furthermore, we established initial protocols for the production of Plodia silk with optimal silk production occurring at 24 °C, with a resource availability of 10 larvae/gram and a population density of 0.72 larvae/mL. Population density was shown to be the most prominent driving force of Plodia silk mat formation among the three parameters assessed. Future work will need to link gene expression, protein production and purification, and resulting mechanical properties as a function of environmental cues to further transition Plodia silk into regenerated silk fibroin biomaterials.

Developmental regulation of cellular metabolism is required for intestinal elongation and rotation.

Malrotation of the intestine is a prevalent birth anomaly, the etiology of which remains poorly understood. Here, we show that late-stage exposure of Xenopus embryos to atrazine, a widely used herbicide that targets electron transport chain (ETC) reactions, elicits intestinal malrotation at high frequency. Interestingly, atrazine specifically inhibits the cellular morphogenetic events required for gut tube elongation, including cell rearrangement, differentiation and proliferation; insufficient gut lengthening consequently reorients the direction of intestine rotation. Transcriptome analyses of atrazine-exposed intestines reveal misexpression of genes associated with glycolysis and oxidative stress, and metabolomics shows that atrazine depletes key glycolytic and tricarboxylic acid cycle metabolites. Moreover, cellular bioenergetics assays indicate that atrazine blocks a crucial developmental transition from glycolytic ATP production toward oxidative phosphorylation. Atrazine-induced defects are phenocopied by rotenone, a known ETC Complex I inhibitor, accompanied by elevated reactive oxygen species, and rescued by antioxidant supplementation, suggesting that malrotation may be at least partly attributable to redox imbalance. These studies reveal roles for metabolism in gut morphogenesis and implicate defective gut tube elongation and/or metabolic perturbations in the etiology of intestinal malrotation.