Physicochemical and Inflammatory Analysis of Unconjugated and Conjugated Bone-Binding Carbon Dots.

Carbon nanodots (CDs) have drawn significant attention for their potential uses in diagnostic and therapeutic applications due to their small size, tissue biocompatibility, stable photoluminescence, and modifiable surface groups. However, the effect of cargo molecules on CD photoluminescence and their ability to interact with tissues are not fully understood. Our previous work has shown that CDs produced from the acidic oxidation of carbon nanopowder can bind to mineralized bone with high affinity and specificity in a zebrafish animal model system. Using this model, we investigated the impact of loading Cy5 and biotin cargo on CDs' photoluminescence and bone-binding properties. We report that CD cargo loading alters CD photoluminescence in a pH- and cargo-dependent manner without interfering with the CDs' bone binding properties. In a reciprocal analysis, we show that cargo loading of CDs does not affect the cargo's fluorescence. Significantly, CDs do not trigger nitric oxide production in a mouse macrophage assay, suggesting that they are noninflammatory. Together, these results further support the development of carbon nanopowder-derived CDs for the precise delivery of therapeutic agents to bone tissue.

Disparities in food insecurity between sexual minority and heterosexual adults - a higher burden on bisexual individuals.

Background: Sexual minorities-individuals who identify as gay/lesbian, bisexual, or other non-heterosexual individuals-experience higher rates of food insecurity (FI) compared to heterosexual individuals. During the COVID-19 pandemic, discrimination and structural racism, which are known risk factors for food insecurity, were perpetuated against sexual and racial/ethnic minorities. However, to our knowledge, a nationally representative analysis of the impact of the pandemic on food insecurity by sexual minority status and based on race/ethnicity is missing. We aimed to determine the degree of association between FI and sexual minority adults overall, before (2019) and during (2020-2021) the pandemic, and stratified by race/ethnicity. Methods: We used nationally representative data from the 2019-2021 National Health Interview Survey (NHIS). We specified multivariable logistic regression models to determine the association between FI and identifying as a sexual minority adult (≥18 years old), including gay/lesbian, bisexual, and other non-heterosexual individuals. Results: Overall, we only observed FI disparities between bisexuals and heterosexuals (aOR 1.61 [95% CI 1.31-1.99]). Stratified by year, this association was significant only during the pandemic. Stratified by race/ethnicity, non-Hispanic white and non-Hispanic black individuals identifying as bisexual also experienced a significantly higher FI rate than their heterosexual counterparts. Conclusion: Our results may be a manifestation of the disproportionate impact of discrimination on bisexual individuals' FI experiences. With the growing number of legislative bills targeting the rights of sexual minorities, we expect to see a higher burden of FI among bisexuals, particularly, bisexual people of color. Future intersectional research regarding FI among bisexual and racial/ethnic minority individuals would further elucidate how membership in multiple minority groups may contribute to a higher risk of FI.

Enhanced Understanding of Structure-Function Relationships for Oxomanganese(IV) Complexes.

A series of manganese(II) and oxomanganese(IV) complexes supported by neutral, pentadentate ligands with varied equatorial ligand-field strength (N3pyQ, N2py2I, and N4pyMe2) were synthesized and then characterized using structural and spectroscopic methods. On the basis of electronic absorption spectroscopy, the [MnIV(O)(N4pyMe2)]2+ complex has the weakest equatorial ligand field among a set of similar MnIV-oxo species. In contrast, [MnIV(O)(N2py2I)]2+ shows the strongest equatorial ligand-field strength for this same series. We examined the influence of these changes in electronic structure on the reactivity of the oxomanganese(IV) complexes using hydrocarbons and thioanisole as substrates. The [MnIV(O)(N3pyQ)]2+ complex, which contains one quinoline and three pyridine donors in the equatorial plane, ranks among the fastest MnIV-oxo complexes in C-H bond and thioanisole oxidation. While a weak equatorial ligand field has been associated with high reactivity, the [MnIV(O)(N4pyMe2)]2+ complex is only a modest oxidant. Buried volume plots suggest that steric factors dampen the reactivity of this complex. Trends in reactivity were examined using density functional theory (DFT)-computed bond dissociation free energies (BDFEs) of the MnIIIO-H and MnIV ═ O bonds. We observe an excellent correlation between MnIV═O BDFEs and rates of thioanisole oxidation, but more scatter is observed between hydrocarbon oxidation rates and the MnIIIO-H BDFEs.

Transportation needs and mobility patterns of persons experiencing homelessness following shelter decentralization.

The provision and siting of homeless emergency shelters have community-wide implications for addressing the needs of people experiencing homelessness (PEH). In Utah, Salt Lake County's transition from a large, centralized emergency shelter sited in a free transit zone to a decentralized scattered-site model outside of a no-cost transit zone provided the context to evaluate how transportation access and mobility patterns of PEH were affected as they were displaced from a centralized service network in a downtown core. We conducted 19 in-depth, semi-structured interviews with PEH aged 18 + who were staying in one of three distributed resource centers who had also previously stayed at the former centralized shelter. Thematic analysis of the interviews resulted in three categories, each with distinct sub-categories: 1) Pre-decentralization transportation and mobility, 2) Post-decentralization transportation and mobility, and 3) Recommendations to improve transportation access for PEH, including lowering or eliminating financial barriers to transportation and expanding transit and shuttle van frequency and route radius. Study findings demonstrate that there is a significant need for community planners to collaborate on the siting of homeless shelters to provide more affordable, flexible, and equitable access to transportation networks.

Community perspectives on how decentralising an emergency shelter influences transportation needs and use for persons experiencing homelessness.

Despite steady increases in homelessness in the U.S., only recently has research on transportation needs and use for persons experiencing homelessness (PEH) been the focus of research endeavours. Moreover, limited research has identified how the geographic relocation of homeless community services and resources impacts the transportation needs of PEH and how this process affects access to health and social services. To fill this gap in the literature, using a community-engaged research approach, we conducted a qualitative research study in which 24 professionals working in planning, transportation, local government, and the homelessness services sector were engaged in in-depth, semi-structured interviews. We examined participant perspectives on how PEH transportation needs and use changed after three new emergency shelters replaced a centralised one, and how access to health and social services was impacted. Data were organised into three overarching categories: (1) Changes in transportation need and use following decentralisation; (2) Impact of transportation changes on PEH access to services; and (3) Recommendations for improving transportation access. Findings suggest the need to offer PEH transportation on demand, provide education on transportation and system navigation, and increase transportation-related funding for homeless service providers and PEH to ensure transportation costs are not a barrier to healthcare and social services.

Spotted lanternfly predicted to establish in California by 2033 without preventative management.

Models that are both spatially and temporally dynamic are needed to forecast where and when non-native pests and pathogens are likely to spread, to provide advance information for natural resource managers. The potential US range of the invasive spotted lanternfly (SLF, Lycorma delicatula) has been modeled, but until now, when it could reach the West Coast's multi-billion-dollar fruit industry has been unknown. We used process-based modeling to forecast the spread of SLF assuming no treatments to control populations occur. We found that SLF has a low probability of first reaching the grape-producing counties of California by 2027 and a high probability by 2033. Our study demonstrates the importance of spatio-temporal modeling for predicting the spread of invasive species to serve as an early alert for growers and other decision makers to prepare for impending risks of SLF invasion. It also provides a baseline for comparing future control options.

Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective.

The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart failure-associated morbidity and lethality requires the special attention of researchers worldwide to develop efficient therapeutics for cardiac repair. Recently, various strategies and approaches have been developed and tested to extrinsically induce regeneration and restoration of the myocardium after cardiac injury have yielded encouraging results. Nevertheless, these interventions still lack adequate success to be used for clinical interventions. This review highlights and discusses both cell-based and cell-free therapeutic approaches as well as current advancements, major limitations, and future perspectives towards developing an efficient therapeutic method for cardiac repair.

Iteratively forecasting biological invasions with PoPS and a little help from our friends.

Ecological forecasting has vast potential to support environmental decision making with repeated, testable predictions across management-relevant timescales and locations. Yet resource managers rarely use co-designed forecasting systems or embed them in decision making. Although prediction of planned management outcomes is particularly important for biological invasions to optimize when and where resources should be allocated, spatial-temporal models of spread typically have not been openly shared, iteratively updated, or interactive to facilitate exploration of management actions. We describe a species-agnostic, open-source framework - called the Pest or Pathogen Spread (PoPS) Forecasting Platform - for co-designing near-term iterative forecasts of biological invasions. Two case studies are presented to demonstrate that iterative calibration yields higher forecast skill than using only the earliest-available data to predict future spread. The PoPS framework is a primary example of an ecological forecasting system that has been both scientifically improved and optimized for real-world decision making through sustained participation and use by management stakeholders.

Mindful Coping Power: Comparative Effects on Children's Reactive Aggression and Self-Regulation.

Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children's reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children's self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children's perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children's reactive aggression as expected, it did have enhancing effects on children's internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children's internal experiences lead to improvements in their observable behavior over time.

Substance Use Outcomes from Two Formats of a Cognitive-Behavioral Intervention for Aggressive Children: Moderating Roles of Inhibitory Control and Intervention Engagement.

Although cognitive-behavioral interventions have reduced the risk of substance use, little is known about moderating factors in children with disruptive behaviors. This study examined whether aggressive preadolescents' inhibitory control and intervention engagement moderates the effect of group versus individual delivery on their substance use. Following screening for aggression in 4th grade, 360 children were randomly assigned to receive the Coping Power intervention in either group or individual formats. The sample was primarily African American (78%) and male (65%). Assessments were made of children's self-reported substance use from preintervention through a six-year follow-up after intervention, parent-reported inhibitory control at preintervention, and observed behavioral engagement in the group intervention. Multilevel growth modeling found lower increases in substance use slopes for children with low inhibitory control receiving individual intervention, and for children with higher inhibitory control receiving group intervention. Children with low inhibitory control but who displayed more positive behavioral engagement in the group sessions had slower increases in their substance use than did similar children without positive engagement. Aggressive children's level of inhibitory control can lead to tailoring of group versus individual delivery of intervention. Children's positive behavioral engagement in group sessions is a protective factor for children with low inhibitory control.

Evaluating online and tangible interfaces for engaging stakeholders in forecasting and control of biological invasions.

Ecological forecasts will be best suited to inform intervention strategies if they are accessible to a diversity of decision-makers. Researchers are developing intuitive forecasting interfaces to guide stakeholders through the development of intervention strategies and visualization of results. Yet, few studies to date have evaluated how user interface design facilitates the coordinated, cross-boundary management required for controlling biological invasions. We used a participatory approach to develop complementary tangible and online interfaces for collaboratively forecasting biological invasions and devising control strategies. A diverse group of stakeholders evaluated both systems in the real-world context of controlling sudden oak death, an emerging forest disease killing millions of trees in California and Oregon. Our findings suggest that while both interfaces encouraged adaptive experimentation, tangible interfaces are particularly well suited to support collaborative decision-making. Reflecting on the strengths of both systems, we suggest workbench-style interfaces that support simultaneous interactions and dynamic geospatial visualizations.

Evaluation of Left Ventricular Outflow Gradients During Staged Exercise Stress Echocardiography Helps Differentiate Pediatric Patients With Hypertrophic Cardiomyopathy From Athletes and Normal Subjects.

BACKGROUND: Elevated left ventricular outflow tract (LVOT) gradients during exercise can occur in patients with hypertrophic cardiomyopathy (HCM) as well as in athletes and normal controls. The authors' staged exercise protocol calls for imaging at rest and during each stage of exercise to evaluate the mechanism of LVOT obstruction at each stage. They investigated whether this staged approach helps differentiate HCM from athletes and normal controls. METHODS: They reviewed pediatric exercise stress echocardiograms completed between January 2009 and October 2017 at their center and identified those with gene-positive HCM, athlete's heart, and normal controls. Children with inducible obstruction (those with no LVOT gradient at rest who developed a LVOT peak gradient > 25 mm Hg during exercise) were included. LVOT peak gradient, velocity time integral, acceleration time, and deceleration time were measured at rest, submaximal stages, and peak exercise. RESULTS: Compared with athletes, HCM patients had significantly higher LVOT peak gradients at rest (P = .019), stage 1 of exercise (P = .002), and peak exercise (P = .051), as well as a significantly higher change in LVOT peak gradient from rest to stage 1 (P = .016) and from rest to peak (P = .038). The acceleration time/deceleration time ratio of the LVOT Doppler was significantly lower in HCM patients compared with normal controls at peak exercise. CONCLUSIONS: The HCM patients who develop elevated LVOT gradients at peak exercise typically manifest early obstruction in the submaximal stages of exercise, which helps to differentiate them from athletes and normal controls.

Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis.

BACKGROUND: Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown. OBJECTIVES: The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS. METHODS: In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST. RESULTS: Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group. CONCLUSIONS: The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.

Nutrition Support Therapies on the Medication Administration Record: Impacts on Staff Perception of Nutrition Care.

BACKGROUND: It has been reported that many hospitals in the United States have fragmented and ineffective ordering, administration, documentation, and evaluation/monitoring of nutrition therapies. This paper reports on a project to investigate if perceived hospital staff awareness and documentation of nutrition support therapies (NSTs) improves by including them as part of the medication administration record (MAR). METHODS: Surveys were conducted with nursing staff, physicians, and dietitians before and after adding NSTs to the MAR to evaluate the perceived impact on the outcome of interest. The outcomes of interest include nurses' perception of ease of finding information, awareness of an order, and ability to assess administration and documentation and dietitian, nurse, and physician staff perceptions of impact of intervention on aspects of the nutrition care process. RESULTS: After adding NST to the MAR, nursing staff perceived improvement in knowing that their patient had an oral nutritional supplement (ONS) order (P = .01), when and how much product was last administered (P = .01), and documentation of the type of product consumed (P = .01) and volume of product consumed (P = .01). The majority of dietitian and nurses surveyed reported perceived improvement in placing and finding ONS orders, in administration of ONS, in ability to evaluate patient nutrition status, and in ONS intake and a positive impact on clinical practice. CONCLUSION: Inclusion of NST in the MAR presents an innovative solution to enhance staff awareness of ordered therapies and perception of improved documentation of nutrition interventions for hospitalized patients.

Isolation, Transfection, and Long-Term Culture of Adult Mouse and Rat Cardiomyocytes.

Ex vivo culture of the adult mammalian cardiomyocytes (CMs) presents the most relevant experimental system for the in vitro study of cardiac biology. Adult mammalian CMs are terminally differentiated cells with minimal proliferative capacity. The post-mitotic state of adult CMs not only restricts cardiomyocyte cell cycle progression but also limits the efficient culture of CMs. Moreover, the long-term culture of adult CMs is necessary for many studies, such as CM proliferation and analysis of gene expression. The mouse and the rat are the two most preferred laboratory animals to be used for cardiomyocyte isolation. While the long-term culture of rat CMs is possible, adult mouse CMs are susceptible to death and cannot be cultured more than five days under normal conditions. Therefore, there is a critical need to optimize the cell isolation and long-term culture protocol for adult murine CMs. With this modified protocol, it is possible to successfully isolate and culture both adult mouse and rat CMs for more than 20 days. Moreover, the siRNA transfection efficiency of isolated CM is significantly increased compared to previous reports. For adult mouse CM isolation, the Langendorff perfusion method is utilized with an optimal enzyme solution and sufficient time for complete extracellular matrix dissociation. In order to obtain pure ventricular CMs, both atria were dissected and discarded before proceeding with the disassociation and plating. Cells were dispersed on a laminin coated plate, which allowed for efficient and rapid attachment. CMs were allowed to settle for 4-6 h before siRNA transfection. Culture media was refreshed every 24 h for 20 days, and subsequently, CMs were fixed and stained for cardiac-specific markers such as Troponin and markers of cell cycle such as KI67.

Effects of a universal prevention program on externalizing behaviors: Exploring the generalizability of findings across school and home settings.

Universal prevention approaches have significantly reduced children's conduct problems and aggressive behavior in the school setting, but it has not been clear whether the effects generalize into children's behavior in home and community settings in later elementary school years. The present study examined this issue using a classroom-randomized design, with 1030 students in 70 fourth and fifth grade Italian classes. The intervention model is the Coping Power Universal and the classroom teachers delivered it. Coping Power Universal produced a significant reduction in both parents' and teachers' rated conduct problems, relative to control classes, indicating that universal prevention can produce significant reductions in children's conduct problems that generalize into the home and community settings. The intervention also increased children's prosocial behaviors in school and home settings. The Coping Power Universal is a short intervention model that is believed to be a useful strategy for children's behavioral problems in the broad population.

Echocardiographic Screening of Cardiovascular Status in Pediatric Sickle Cell Disease.

Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.

Human antigen R as a therapeutic target in pathological cardiac hypertrophy.

RNA binding proteins represent an emerging class of proteins with a role in cardiac dysfunction. We show that activation of the RNA binding protein human antigen R (HuR) is increased in the failing human heart. To determine the functional role of HuR in pathological cardiac hypertrophy, we created an inducible cardiomyocyte-specific HuR-deletion mouse and showed that HuR deletion reduces left ventricular hypertrophy, dilation, and fibrosis while preserving cardiac function in a transverse aortic constriction (TAC) model of pressure overload-induced hypertrophy. Assessment of HuR-dependent changes in global gene expression suggests that the mechanistic basis for this protection occurs through a reduction in fibrotic signaling, specifically through a reduction in TGF-ß (Tgfb) expression. Finally, pharmacological inhibition of HuR at a clinically relevant time point following the initial development of pathological hypertrophy after TAC also yielded a significant reduction in pathological progression, as marked by a reduction in hypertrophy, dilation, and fibrosis and preserved function. In summary, this study demonstrates a functional role for HuR in the progression of pressure overload-induced cardiac hypertrophy and establishes HuR inhibition as a viable therapeutic approach for pathological cardiac hypertrophy and heart failure.