Endothelial cell signature in muscle stem cells validated by VEGFA-FLT1-AKT1 axis promoting survival of muscle stem cell.

Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs) (satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNAseq to show that MuSCs express low levels of canonical EC markers in mice. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.

Prebiotic fiber blend supports growth and development and favorable digestive health in puppies.

Introduction: A healthy gastrointestinal (GI) microbiome has been shown to be essential for proper nutrient absorption and metabolism, maintenance of intestinal epithelial integrity and osmolarity, gut immunomodulation, and overall health. One of the most effective ways to promote a healthy GI microbiome is through dietary interventions, such as the addition of prebiotics. Prebiotics are substrates that are selectively utilized by the host GI microbiome through fermentation to confer a health benefit. However, research on prebiotics in companion animals is limited, especially in growing animals. Thus, this study was conducted to assess the effects of a novel prebiotic fiber blend on key parameters related to intestinal health and growth in puppies. Methods: Twenty-two puppies at least 4 months of age but not older than 10 months were fed a commercially available dry food during a prefeed period, and then fed a similarly formulated test food with the addition of the prebiotic fiber blend for a minimum of 90 days. Serum and fecal samples were collected at the end of the prefeed period and throughout the test period. Results: Puppies fed the test food grew as expected for puppies of this age. Complete blood count and serum chemistry analyses were clinically normal for all animals. Fecal score increased linearly, fecal moisture decreased linearly, and pH exhibited a cubic trend throughout the study duration. There was a linear increase in short-chain fatty acids throughout the study, which is associated with favorable digestive and overall health. The inflammatory cytokine interleukin-7 decreased linearly and interleukin-18 trended towards linear decrease. Conclusion: This study showed that puppies continued to grow and develop normally, and experienced serum and stool characteristics indicative of improved GI health when fed a growth food fortified with a novel prebiotic fiber blend. Furthermore, these results contribute to the overall understanding of the effects of prebiotics on the GI health of growing companion animals.

Patient and clinician preferences for diabetes management among older adults with co-morbid HIV: A qualitative exploration.

BACKGROUND: Older adults with HIV are at increased risk of developing certain chronic health conditions including type 2 diabetes mellitus (T2DM). As the number and complexity of conditions increases, so do treatment and health care needs. We explored patient and clinician preferences for HIV+T2DM care and perceived solutions to improving care. METHODS: We conducted an exploratory qualitative study comprised of individual in-depth interviews. Participants included English-speaking patients aged 50 and older living with HIV and T2DM and infectious disease (ID) and primary care (PC) clinicians from a large academic health center in Chicago. Thematic analysis drew from the Framework Method. RESULTS: A total of 19 patient and 10 clinician participants were interviewed. Many patients reported seeking HIV and T2DM care from the same clinician; they valued rapport and a 'one-stop-shop'. Others reported having separate clinicians; they valued perceived expertise and specialty care. Nearly all clinicians reported comfort screening for T2DM and initiating first line oral therapy; ID clinicians reported placing referrals for newer, complex therapies. Patients would like educational support for T2DM management; clinicians would like to learn more about newer therapies and easier referral processes. CONCLUSIONS: Patient-centered care includes managing T2DM from a variety of clinical settings for individuals with HIV, yet strategies are needed to better support clinicians. Future research should examine how best to implement these strategies.

Multivariate Bayesian Optimization of CoO Nanoparticles for CO2 Hydrogenation Catalysis.

The hydrogenation of CO2 holds promise for transforming the production of renewable fuels and chemicals. However, the challenge lies in developing robust and selective catalysts for this process. Transition metal oxide catalysts, particularly cobalt oxide, have shown potential for CO2 hydrogenation, with performance heavily reliant on crystal phase and morphology. Achieving precise control over these catalyst attributes through colloidal nanoparticle synthesis could pave the way for catalyst and process advancement. Yet, navigating the complexities of colloidal nanoparticle syntheses, governed by numerous input variables, poses a significant challenge in systematically controlling resultant catalyst features. We present a multivariate Bayesian optimization, coupled with a data-driven classifier, to map the synthetic design space for colloidal CoO nanoparticles and simultaneously optimize them for multiple catalytically relevant features within a target crystalline phase. The optimized experimental conditions yielded small, phase-pure rock salt CoO nanoparticles of uniform size and shape. These optimized nanoparticles were then supported on SiO2 and assessed for thermocatalytic CO2 hydrogenation against larger, polydisperse CoO nanoparticles on SiO2 and a conventionally prepared catalyst. The optimized CoO/SiO2 catalyst consistently exhibited higher activity and CH4 selectivity (ca. 98%) across various pretreatment reduction temperatures as compared to the other catalysts. This remarkable performance was attributed to particle stability and consistent H* surface coverage, even after undergoing the highest temperature reduction, achieving a more stable catalytic species that resists sintering and carbon occlusion.

Thinking about Believing: Can Metacognitive Reflection Encourage Belief Updating?

People often cling to their beliefs even in the face of counterevidence. The current study explored metacognitive reflection as a potential driver for belief updating. In a randomized controlled experiment (n = 155), participants rated their degree of agreement with a statement regarding genetic modification in humans. Following this, participants were presented with a passage containing an argument counter to their indicated belief. Participants in the metacognition condition were asked to deeply reflect on the ways in which the passage was similar to or different from their current beliefs. Participants in the control condition were asked to engage in more shallow reflection on the composition of the passage. After reflecting on the counterevidence, participants were asked to again rate their agreement with the statement regarding human gene modification. Both groups updated their initial beliefs to be more consistent with the presented counterevidence. Although greater belief updating was observed in those who metacognitively reflected on the passage, this effect did not reach significance (p = .055). These findings suggest that reflecting on counterevidence has the potential to encourage belief updating, regardless of whether that reflection is metacognitive in nature, and provide promise for future work investigating the role of metacognition in belief updating.

Limited English Proficiency Is an Overlooked Research Demographic.

Excluding this population perpetuates health inequities.

Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021.

Objectives. To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP). Methods. We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP. Results. We included 12 182 outpatient substance use treatment facilities. Of these, 637 (5.2%) offered PrEP. Offering HIV treatment (adjusted odds ratio [AOR] = 45.3; 95% confidence interval [CI] = 36.0, 56.9) and offering programs for LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) people (AOR = 1.3; 95% CI = 1.0, 1.6) were associated with higher likelihoods of offering PrEP. Conclusions. PrEP is highly effective and recommended for patients at risk for HIV from injection drug use. Nearly 95% of US outpatient substance use treatment facilities did not offer PrEP-a missed opportunity for harm reduction through primary HIV prevention. Public Health Implications. Diversification of the array of available HIV PrEP options and the ongoing HIV and opioid use epidemics require outpatient substance use treatment facilities to expand PrEP availability. (Am J Public Health. Published online ahead of print May 30, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307699).

Assessing Patterns of Telehealth Use Among People with Sickle Cell Disease Enrolled in Medicaid During the Start of the COVID-19 Pandemic.

Background: Telehealth can be defined as using remote technologies to provide health care. It may increase access to care among people with sickle cell disease (SCD). This study examined (1) telehealth use, (2) characteristics of telehealth use, and (3) differences between telehealth users and nonusers among people with SCD during the COVID-19 pandemic. Methods: This was a retrospective analysis of Medicaid claims among four states [California (CA), Georgia (GA), Michigan (MI), Tennessee (TN)] participating in the Sickle Cell Data Collection program. Study participants were individuals ≥1 year old with SCD enrolled in Medicaid September 2019-December 2020. Telehealth encounters during the pandemic were characterized by provider specialty. Health care utilization was compared between those who did (users) and did not (nonusers) use telehealth, stratified by before and during the pandemic. Results: A total of 8,681 individuals with SCD (1,638 CA; 3,612 GA; 1,880 MI; and 1,551 TN) were included. The proportion of individuals with SCD that accessed telehealth during the pandemic varied across states from 29% in TN to 80% in CA. During the pandemic, there was a total of 21,632 telehealth encounters across 3,647 users. In two states (MI and GA), over a third of telehealth encounters were with behavioral health providers. Telehealth users had a higher average number of health care encounters during the pandemic: emergency department (pooled mean = 2.6 for users vs. 1.5 for nonusers), inpatient (1.2 for users vs. 0.6 for nonusers), and outpatient encounters (6.0 for users vs. 3.3 for nonusers). Conclusions: Telehealth was frequently used at the beginning of the COVID-19 pandemic by people with SCD. Future research should focus on the context, facilitators, and barriers of its implementation in this population.

Case report: Severe hepatopathy following rivaroxaban administration in a dog.

Rivaroxaban, a specific factor Xa inhibitor and commonly utilized anticoagulant, has been known to cause hepatotoxicity and liver failure in humans. Although rivaroxaban is frequently used in veterinary medicine, hepatotoxicity has not been previously reported in dogs. The current case report describes a dog that developed severe hepatopathy following rivaroxaban administration for a large right pulmonary artery thrombus. An estimated 6-year-old spayed female mixed-breed dog developed anorexia and lethargy 9 days after rivaroxaban administration began. Subsequent labwork revealed severe hepatocellular hepatopathy, and rivaroxaban was discontinued. Additional diagnostics did not reveal an underlying etiology, although hepatic cytology could be consistent with a toxic injury. The hepatopathy and clinical signs improved after rivaroxaban was discontinued. The time to onset, type of hepatopathy, and time to resolution were all similar to those reported for human cases. This case provides precedence to advocate for improved and closer monitoring of dogs receiving factor Xa inhibitors. In cases of suspected hepatotoxicity with no other identifiable cause, a risk-benefit analysis should be performed, and discontinuation of rivaroxaban administration or alternative anticoagulant medications should be considered.

Assessment of the CLOT (children's likelihood of thrombosis) real-time risk prediction model of hospital-associated venous thromboembolism in children with congenital heart disease.

BACKGROUND: Children with congenital heart disease (CHD) are at high risk for hospital-associated venous thromboembolism (HA-VTE). The children's likelihood of thrombosis (CLOT) trial validated a real-time predictive model for HA-VTE using data extracted from the EHR for pediatric inpatients. We tested the hypothesis that addition of CHD specific data would improve model prediction in the CHD population. METHODS: Model performance in CHD patients from 2010 to 2022, was assessed using 3 iterations of the CLOT model: 1) the original CLOT model, 2) the original model refit using only data from the CHD cohort, and 3) the model updated with the addition of cardiopulmonary bypass time, STAT Mortality Category, height, and weight as covariates. The discrimination of the three models was quantified and compared using AUROC. RESULTS: Our CHD cohort included 1457 patient encounters (median 2.0 IQR [0.5-5.2] years-old). HA-VTE was present in 5% of our CHD cohort versus 1% in the general pediatric population. Several features from the original model were associated with thrombosis in the CHD cohort including younger age, thrombosis history, infectious disease consultation, and EHR coding of a central venous line. Lower height and weight were associated with thrombosis. HA-VTE rate was 12% (18/149) amongst those with STAT Category 4-5 operation versus 4% (49/1256) with STAT Category 1-3 operation (P < .001). Longer cardiopulmonary bypass time (124 [92-205] vs. 94 [65-136] minutes, P < .001) was associated with thrombosis. The AUROC for the original (0.80 95% CI [0.75-0.85]), refit (0.85 [0.81-0.89]), and updated (0.86 [0.81-0.90]) models demonstrated excellent discriminatory ability within the CHD cohort. CONCLUSION: The automated approach with EHR data extraction makes the applicability of such models appealing for ease of clinical use. The addition of cardiac specific features improved model discrimination; however, this benefit was marginal compared to refitting the original model to the CHD cohort. This suggests strong predictive generalized models, such as CLOT, can be optimized for cohort subsets without additional data extraction, thus reducing cost of model development and deployment.

Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Inclusion in an Interdisciplinary Leadership Training Program: Perspectives From Self-Advocates.

Leadership Education in Neurodevelopmental and Related Disabilities (LEND) programs are interdisciplinary, graduate-level training programs that seek to promote improved outcomes for individuals with disabilities and their families. Many of these programs include individuals with disabilities as members of the self-advocacy discipline. In this study, 10 self-advocate trainees were interviewed to provide insight into the value of including self-advocates in training and the kinds of accommodations and supports that facilitated their success and inclusion. Interviewees endorsed the importance of including self-advocates in LEND programs. Although several accommodations were discussed as helpful, interpersonal supports from faculty and peers were equally important in ensuring their success and inclusion in LEND. The findings from this study provide support for the expansion of self-advocacy as a formal discipline in LEND programs.

Acute pulmonary injury in hematology patients supported with pathogen-reduced and conventional platelet components.

ABSTRACT: Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of -1.5% (95% confidence interval [CI], -2.7 to -0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, -2.4%; 95% CI, -4.2 to -0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.

Synchronous retreat of Thwaites and Pine Island glaciers in response to external forcings in the presatellite era.

Today, relatively warm Circumpolar Deep Water is melting Thwaites Glacier at the base of its ice shelf and at the grounding zone, contributing to significant ice retreat. Accelerating ice loss has been observed since the 1970s; however, it is unclear when this phase of significant melting initiated. We analyzed the marine sedimentary record to reconstruct Thwaites Glacier's history from the early Holocene to present. Marine geophysical surveys were carried out along the floating ice-shelf margin to identify core locations from various geomorphic settings. We use sedimentological data and physical properties to define sedimentary facies at seven core sites. Glaciomarine sediment deposits reveal that the grounded ice in the Amundsen Sea Embayment had already retreated to within ~45 km of the modern grounding zone prior to ca. 9,400 y ago. Sediments deposited within the past 100+ y record abrupt changes in environmental conditions. On seafloor highs, these shifts document ice-shelf thinning initiating at least as early as the 1940s. Sediments recovered from deep basins reflect a transition from ice proximal to slightly more distal conditions, suggesting ongoing grounding-zone retreat since the 1950s. The timing of ice-shelf unpinning from the seafloor for Thwaites Glacier coincides with similar records from neighboring Pine Island Glacier. Our work provides robust new evidence that glacier retreat in the Amundsen Sea was initiated in the mid-twentieth century, likely associated with climate variability.

"People are now working together for a common good": The effect on social capital of participatory design for community-level sanitation infrastructure in urban informal settlements.

Communities with higher levels of social capital perform better than communities with lower social capital in community-level water and sanitation interventions and have better health outcomes. Although research recommends bolstering social capital to improve intervention outcomes, few studies provide empirical evidence on the effect of intervention activities on social capital. This study aimed to evaluate the effect of participatory design and community engagement activities on social capital among urban informal settlements in Suva, Fiji and Makassar, Indonesia enrolled in the Revitalizing Informal Settlements and their Environments trial using the Short Adapted Social Capital Assessment Tool. We performed confirmatory factor analyses (CFA) to test tool performance and built structural equation models to assess intervention effect on CFA-informed, sub-scale scores for cognitive and structural social capital. Qualitative in-depth interviews in Fiji and Indonesia and focus group discussions in Fiji provided nuanced understanding of intervention effects on social capital from residents' perspectives. Results confirmed the hypothesized two-factor solution but revealed differences by country and by gender in Indonesia. The intervention appeared positively related to cognitive social capital among men and women in Indonesia and negatively related to cognitive and structural social capital among men and women in Fiji. While effect sizes were small and cluster-adjustment for a small number of settlements yielded non-significant effects, trends were consistent across models and bivariate analyses and were corroborated by qualitative findings. Several contextual factors may explain these results, including timing and duration of intervention activities and influence of COVID-19. Qualitative data suggested that the relationship between participatory design and social capital may be bidirectional, helping to explain why certain settlements appeared to be better equipped to benefit from intervention activities. Practitioners and program designers should carefully consider the social pre-conditions of communities in which they intend to work to optimize program outcomes and avoid unintended consequences.

Acculturation and clinical symptoms of schizophrenia among Latine adults in the United States.

BACKGROUND: Research on acculturation and schizophrenia spectrum disorders has yielded inconsistent findings. This study aimed to clarify the influence of acculturation on symptomatology in Latine individuals with schizophrenia in the United States. METHODS: The analysis involved cross-sectional data from Latine (n = 120) and non-Latine White (n = 60) adults with schizophrenia in San Diego, California. Participants completed the Short Acculturation Scale for Hispanics (SASH), Positive and Negative Symptom Scale, and Hamilton Depression Rating Scale in their preferred language. Univariate linear regressions were implemented to identify proxy measures as predictors of acculturation scores. Analyses of variance were conducted to analyze the relationship of SASH scores and proxy measures of acculturation to symptom severity. RESULTS: Latine participants presented more symptom severity than non-Latine Whites. When categorized by acculturation status (Spanish-preferring, bicultural, and English-preferring), Spanish-preferring participants presented similar psychiatric symptoms to the non-Latine group and less severe symptoms than both other Latine groups. Analyses identified study language as the strongest proxy measure for the SASH. Latine participants assessed in English had significantly worse positive and depressive symptoms than those assessed in Spanish. Nativity status moderated the relationship between study language and symptomatology. CONCLUSIONS: Findings support an association between acculturation and symptom severity among Latine individuals with schizophrenia. The use of proxy measures of acculturation may be useful in settings where time is constrained. Future research should continue to explore acculturation and symptomatology in Latine communities.