Detection of Viral RNA and DNA and Immune Response Following Administration of Live Attenuated Measles and Varicella Vaccines in Children with Chronic Liver Disease.

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLD) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pre-transplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles and varicella RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles RNA and varicella DNA real-time PCR were measured weekly following vaccination; measles RNA was undetectable in all by 14 days post-vaccination, but varicella DNA, which can be managed with antivirals, was detected in one child in the CLD group at 21 days and one control at 28 days post-vaccination. Humoral or cell-mediated vaccine response was 100% to measles and 94% to varicella in the CLD group post-vaccination, while it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14-days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine preventable infections in vulnerable children with CLD.

Adapting an Efficacious Peer-Delivered Physical Activity Program for Survivors of Breast Cancer for Web Platform Delivery: Protocol for a 2-Phase Study.

BACKGROUND: Interventions promoting physical activity (PA) among survivors of cancer improve their functioning, reduce fatigue, and offer other benefits in cancer recovery and risk reduction for future cancer. There is a need for interventions that can be implemented on a wider scale than that is possible in research settings. We have previously demonstrated that a 3-month peer-delivered PA program (Moving Forward Together [MFT]) significantly increased the moderate to vigorous PA (MVPA) of survivors of breast cancer. OBJECTIVE: Our goal is to scale up the MFT program by adapting an existing peer mentoring web platform, Mentor1to1. InquistHealth's web platform (Mentor1to1) has demonstrated efficacy in peer mentoring for chronic disease management. We will partner with InquisitHealth to adapt their web platform for MFT. The adaptation will allow for automating key resource-intensive components such as matching survivors with a coach via the web-based peer mentoring platform and collecting key indexes to prepare for large-scale implementation. The aim is to streamline intervention delivery, assure fidelity, and improve survivor outcomes. METHODS: In phase 1 of this 2-phase study, we will interview 4 peer mentors or coaches with experience in delivering MFT and use their feedback to create Mentor1to1 web platform adapted for MFT (webMFT). Next, another 4 coaches will participate in rapid, iterative user-centered testing of webMFT. In phase 2, we will conduct a randomized controlled trial by recruiting and training 10 to 12 coaches from cancer organizations to deliver webMFT to 56 survivors of breast cancer, who will be assigned to receive either webMFT or MVPA tracking (control) for 3 months. We will assess effectiveness with survivors' accelerometer-measured MVPA and self-reported psychosocial well-being at baseline and 3 months. We will assess implementation outcomes, including acceptability, feasibility, and program costs from the perspective of survivors, coaches, and collaborating organizations, as guided by the expanded Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. RESULTS: As of September 2023, phase 1 of the study was completed, and 61 survivors were enrolled in phase 2. Using newer technologies for enhanced intervention delivery, program management, and automated data collection has the exciting promise of facilitating effective implementation by organizations with limited resources. Adapting evidence-based MFT to a customized web platform and collecting data at multiple levels (coaches, survivors, and organizations) along with costs will provide a strong foundation for a robust multisite implementation trial to increase MVPA and its benefits among many more survivors of breast cancer. CONCLUSIONS: The quantitative and qualitative data collected from survivors of cancer, coaches, and organizations will be analyzed to inform a future larger-scale trial of peer mentoring for PA delivered by cancer care organizations to survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT05409664; https://clinicaltrials.gov/study/NCT05409664. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52494.

Type 2 diabetes is linked to higher physiologic markers of effort during exercise.

Background: People with type 2 diabetes (T2D) have lower rates of physical activity (PA) than the general population. This is significant because insufficient PA is linked to cardiovascular morbidity and mortality, particularly in individuals with T2D. Previously, we identified a novel barrier to physical activity: greater perceived effort during exercise in women. Specifically, women with T2D experienced exercise at low-intensity as greater effort than women without T2D at the same low-intensity - based on self-report and objective lactate measurements. A gap in the literature is whether T2D confers greater exercise effort in both sexes and across a range of work rates. Objectives: Our overarching objective was to address these gaps regarding the influence of T2D and relative work intensity on exercise effort. We hypothesized that T2D status would confer greater effort during exercise across a range of work rates below the aerobic threshold. Methods: This cross-sectional study enrolled males and post-menopausal females aged 50-75 years. Measures of exercise effort included: 1) heart rate, 2) lactate and 3) self-report of Rating of Perceived Exertion (RPE); each assessment was during the final minute of a 5-minute bout of treadmill exercise. Treadmill exercise was performed at 3 work rates: 1.5 mph, 2.0 mph, and 2.5 mph, respectively. To determine factors influencing effort, separate linear mixed effect models assessed the influence of T2D on each outcome of exercise effort, controlling for work rate intensity relative to peak oxygen consumption (%VO2peak). Models were adjusted for any significant demographic associations between effort and age (years), sex (male/female), baseline physical activity, or average blood glucose levels. Results: We enrolled n=19 people with T2D (47.4% female) and n=18 people (55.6% female) with no T2D. In the models adjusted for %VO2peak, T2D status was significantly associated with higher heart rate (p = 0.02) and lactate (p = 0.01), without a significant association with RPE (p = 0.58). Discussions: Across a range of low-to-moderate intensity work rates in older, sedentary males and females, a diagnosis of T2D conferred higher objective markers of effort but did not affect RPE. Greater objective effort cannot be fully attributed to impaired fitness, as it persisted despite adjustment for %VO2peak. In order to promote regular exercise and reduce cardiovascular risk for people with T2D, 1) further efforts to understand the mechanistic targets that influence physiologic exercise effort should be sought, and 2) comparison of the effort and tolerability of alternative exercise training prescriptions is warranted.

Best practices for genetic and genomic data archiving.

Genetic and genomic data are collected for a vast array of scientific and applied purposes. Despite mandates for public archiving, data are typically used only by the generating authors. The reuse of genetic and genomic datasets remains uncommon because it is difficult, if not impossible, due to non-standard archiving practices and lack of contextual metadata. But as the new field of macrogenetics is demonstrating, if genetic data and their metadata were more accessible and FAIR (findable, accessible, interoperable and reusable) compliant, they could be reused for many additional purposes. We discuss the main challenges with existing genetic and genomic data archives, and suggest best practices for archiving genetic and genomic data. Recognizing that this is a longstanding issue due to little formal data management training within the fields of ecology and evolution, we highlight steps that research institutions and publishers could take to improve data archiving.

Neuropsychiatric Comorbidities and Psychotropic Medication Use in Medicare Beneficiaries With Dementia by Sex and Race.

BACKGROUND: Neuropsychiatric symptoms affect the majority of dementia patients. Past studies report high rates of potentially inappropriate prescribing of psychotropic medications in this population. We investigate differences in neuropsychiatric diagnoses and psychotropic medication prescribing in a local US cohort by sex and race. METHODS: We utilize Medicare claims and prescription fill records in a cohort of 100% Medicare North and South Carolina beneficiaries ages 50 and above for the year 2017 with a dementia diagnosis. We identify dementia and quantify diagnosis of anxiety, depression and psychosis using validated coding algorithms. We search Medicare claims for antianxiety, antidepressant and antipsychotic medications to determine prescriptions filled. RESULTS: Anxiety and depression were diagnosed at higher rates in White patients; psychosis at higher rates in Black patients. (P < .001) Females were diagnosed with anxiety, depression and psychosis at higher rates than males (P < .001) and filled more antianxiety and antidepressant medications than males. (P < .001) Black and Other race patients filled more antipsychotic medications for anxiety, depression and psychosis than White patients. (P < .001) Antidepressants were prescribed at higher rates than antianxiety or antipsychotic medications across all patients and diagnoses. Of patients with no neuropsychiatric diagnosis, 11.4% were prescribed an antianxiety medication, 22.8% prescribed an antidepressant and 7.6% prescribed an antipsychotic. CONCLUSIONS: The high fill rate of antianxiety (benzodiazepine) medications in dementia patients, especially females is a concern. Patients are prescribed psychotropic medications at high rates. This practice may represent potentially inappropriate prescribing. Patient/caregiver education with innovative community outreach and care delivery models may help decrease medication use.

Health Expenditures After Bariatric Surgery: A Retrospective Cohort Study.

OBJECTIVE: Bariatric surgery leads to substantial improvements in weight and weight-related conditions, but prior literature on post-surgical health expenditures is equivocal. In a retrospective cohort study, we compared expenditures between surgical and matched non-surgical patients. SUMMARY BACKGROUND DATA AND METHODS: In a retrospective study, total, outpatient, inpatient and medication expenditures 3 years before and 5.5 years after surgery were compared between 22,698 bariatric surgery (n=7,127 RYGB, 15,571 sleeve gastrectomy) patients from 2012-2019 and 66,769 matched non-surgical patients, using generalized estimating equations. We also compared expenditures between patients receiving the two leading surgical procedures in weighted analyses. RESULTS: Surgical and non-surgical cohorts were well matched, 80-81% female, with mean body mass index (BMI) of 44, and mean age of 47 (RYGB) and 44 (SG) years. Estimated total expenditures were similar between surgical and non-surgical groups 3 years before surgery ($27 difference, 95% confidence interval (CI): -42, 102)), increased 6 months prior to surgery for surgical patients, and decreased below pre-period levels for both groups after 3-5.5 years to become similar (difference at 5.5 y=-$61, 95% CI: -166, 52). Long-term outpatient expenditures were similar between groups. Surgical patients' lower long-term medication expenditures ($314 lower at 5.5 y, 95% CI: -419, -208) were offset by a higher risk of hospitalization. Total expenditures were similar between RYGB and SG patients 3.5 to 5.5 years after surgery. CONCLUSIONS: Bariatric surgery translated into lower medication expenditures than matched controls, but not lower overall long-term expenditures. Expenditure trends appear similar for the two leading bariatric operations.

Unpacking patient perspectives on social needs screening: A mixed methods study in western Colorado primary care practices.

OBJECTIVE: Explore factors influencing patient comfort with and perceived helpfulness of screening for health-related social needs. METHODS: In a parallel secondary mixed-methods analysis of data from three primary care clinics, we used logistic regression to examine effects of practice- and patient-level factors on comfort with and perceived helpfulness of social needs screening. We applied narrative analysis to 20 patient interviews to further understand how patients' lived experiences influenced their perceptions of screening. RESULTS: Among 511 patients, receiving an explanation about screening was associated with increased odds of comfort (OR 2.1, 95% CI [1.1-4.30]) and perceived helpfulness (OR 4.7 [2.8-7.8]). Those experiencing more needs were less likely to report comfort (3 + needs vs. 0: OR 0.2 [0.1-0.5]). Narratives elucidated how a history of stigmatizing experiences increased discomfort disclosing needs and captured how relationship quality with healthcare teams influenced perceptions of screening for patients with extensive needs. CONCLUSION: Practice-level (screening explanation and therapeutic rapport) and patient-level factors (history and extent of needs) are key influences on comfort with and perceived helpfulness of screening. PRACTICE IMPLICATIONS: Good communication about screening benefits all patients. Patients with extensive social needs may require additional sensitivity to their past experiences.

Implementation of Health IT for Cancer Screening in US Primary Care: Scoping Review.

BACKGROUND: A substantial percentage of the US population is not up to date on guideline-recommended cancer screenings. Identifying interventions that effectively improve screening rates would enhance the delivery of such screening. Interventions involving health IT (HIT) show promise, but much remains unknown about how HIT is optimized to support cancer screening in primary care. OBJECTIVE: This scoping review aims to identify (1) HIT-based interventions that effectively support guideline concordance in breast, cervical, and colorectal cancer screening provision and follow-up in the primary care setting and (2) barriers or facilitators to the implementation of effective HIT in this setting. METHODS: Following scoping review guidelines, we searched MEDLINE, CINAHL Plus, Web of Science, and IEEE Xplore databases for US-based studies from 2015 to 2021 that featured HIT targeting breast, colorectal, and cervical cancer screening in primary care. Studies were dual screened using a review criteria checklist. Data extraction was guided by the following implementation science frameworks: the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework; the Expert Recommendations for Implementing Change taxonomy; and implementation strategy reporting domains. It was also guided by the Integrated Technology Implementation Model that incorporates theories of both implementation science and technology adoption. Reporting was guided by PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). RESULTS: A total of 101 studies met the inclusion criteria. Most studies (85/101, 84.2%) involved electronic health record-based HIT interventions. The most common HIT function was clinical decision support, primarily used for panel management or at the point of care. Most studies related to HIT targeting colorectal cancer screening (83/101, 82.2%), followed by studies related to breast cancer screening (28/101, 27.7%), and cervical cancer screening (19/101, 18.8%). Improvements in cancer screening were associated with HIT-based interventions in most studies (36/54, 67% of colorectal cancer-relevant studies; 9/14, 64% of breast cancer-relevant studies; and 7/10, 70% of cervical cancer-relevant studies). Most studies (79/101, 78.2%) reported on the reach of certain interventions, while 17.8% (18/101) of the included studies reported on the adoption or maintenance. Reported barriers and facilitators to HIT adoption primarily related to inner context factors of primary care settings (eg, staffing and organizational policies that support or hinder HIT adoption). Implementation strategies for HIT adoption were reported in 23.8% (24/101) of the included studies. CONCLUSIONS: There are substantial evidence gaps regarding the effectiveness of HIT-based interventions, especially those targeting guideline-concordant breast and colorectal cancer screening in primary care. Even less is known about how to enhance the adoption of technologies that have been proven effective in supporting breast, colorectal, or cervical cancer screening. Research is needed to ensure that the potential benefits of effective HIT-based interventions equitably reach diverse primary care populations.

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.

Glutamine synthetase (GS), encoded by GLUL, catalyzes the conversion of glutamate to glutamine. GS is pivotal for the generation of the neurotransmitters glutamate and gamma-aminobutyric acid and is the primary mechanism of ammonia detoxification in the brain. GS levels are regulated post-translationally by an N-terminal degron that enables the ubiquitin-mediated degradation of GS in a glutamine-induced manner. GS deficiency in humans is known to lead to neurological defects and death in infancy, yet how dysregulation of the degron-mediated control of GS levels might affect neurodevelopment is unknown. We ascertained nine individuals with severe developmental delay, seizures, and white matter abnormalities but normal plasma and cerebrospinal fluid biochemistry with de novo variants in GLUL. Seven out of nine were start-loss variants and two out of nine disrupted 5' UTR splicing resulting in splice exclusion of the initiation codon. Using transfection-based expression systems and mass spectrometry, these variants were shown to lead to translation initiation of GS from methionine 18, downstream of the N-terminal degron motif, resulting in a protein that is stable and enzymatically competent but insensitive to negative feedback by glutamine. Analysis of human single-cell transcriptomes demonstrated that GLUL is widely expressed in neuro- and glial-progenitor cells and mature astrocytes but not in post-mitotic neurons. One individual with a start-loss GLUL variant demonstrated periventricular nodular heterotopia, a neuronal migration disorder, yet overexpression of stabilized GS in mice using in utero electroporation demonstrated no migratory deficits. These findings underline the importance of tight regulation of glutamine metabolism during neurodevelopment in humans.

Correlates of Impairment and Growth in Families of Young Autistic Children.

The purpose of this project was to investigate potential correlates of family life impairment in families of young autistic children. This project incorporated measures of specific child and parent challenges in addition to a commonly used unidimensional measure of autism characteristics. In this way, we could assess whether such challenges explain variance in family life impairment, and whether their inclusion diminish associations between autism characteristics and family life impairment. Cross-sectional data were collected from 564 parents of autistic children aged 2 to 5 years who participated in a larger online study. Participants completed measures on child characteristics (autism characteristics, emotion dysregulation, speaking ability, flexibility, and sleep problems), parent depression, and family life impairment, using the Family Life Impairment Scale (FLIS). Multiple linear regression models were generated to examine whether any of the independent variables were associated with the four domains of the FLIS. Models controlled for child age and sex, parent education, and single-parent homes. All independent variables were associated with impairment in one or more FLIS domains. None of the primary independent variables were significantly associated with positive growth. More overt characteristics and behaviors (e.g., autism characteristics, reactivity, speaking ability, and flexibility) were associated with impairment in domains that reflected a family's ability to navigate the community. However, sleep challenges and parent and child emotional difficulties were most strongly associated with parent impairment. Findings suggests that families may have different needs across contexts and provide new avenues through which they might be better supported.

What's Eating You? Carpet Beetles (Dermestidae).

Carpet beetle larvae of the family Dermestidae have been documented to cause both acute and delayed hypersensitivity reactions in susceptible individuals. These larvae have specialized horizontal rows of spear-shaped hairs called hastisetae, which detach easily into the surrounding environment and are small enough to travel by air. Exposure to hastisetae has been tied to adverse effects ranging from dermatitis to rhinoconjunctivitis and acute asthma, with treatment being mostly empiric and symptom based. Due to the pervasiveness of carpet beetles in homes, improved awareness of dermestid-induced manifestations is valuable for clinicians.

Yosemite toad (Anaxyrus canorus) transcriptome reveals interplay between speciation genes and adaptive introgression.

Genomes are heterogeneous during the early stages of speciation, with small 'islands' of DNA appearing to reflect strong adaptive differences, surrounded by vast seas of relative homogeneity. As species diverge, secondary contact zones between them can act as an interface and selectively filter through advantageous alleles of hybrid origin. Such introgression is another important adaptive process, one that allows beneficial mosaics of recombinant DNA ('rivers') to flow from one species into another. Although genomic islands of divergence appear to be associated with reproductive isolation, and genomic rivers form by adaptive introgression, it is unknown whether islands and rivers tend to be the same or different loci. We examined three replicate secondary contact zones for the Yosemite toad (Anaxyrus canorus) using two genomic data sets and a morphometric data set to answer the questions: (1) How predictably different are islands and rivers, both in terms of genomic location and gene function? (2) Are the adaptive genetic trait loci underlying tadpole growth and development reliably islands, rivers or neither? We found that island and river loci have significant overlap within a contact zone, suggesting that some loci are first islands, and later are predictably converted into rivers. However, gene ontology enrichment analysis showed strong overlap in gene function unique to all island loci, suggesting predictability in overall gene pathways for islands. Genome-wide association study outliers for tadpole development included LPIN3, a lipid metabolism gene potentially involved in climate change adaptation, that is island-like for all three contact zones, but also appears to be introgressing (as a river) across one zone. Taken together, our results suggest that adaptive divergence and introgression may be more complementary forces than currently appreciated.

Pediatric Occupational Therapists' Perspectives on Sleep: A Qualitative Descriptive Study.

IMPORTANCE: Insufficient sleep is common among children seeking occupational therapy services but is rarely a focus of therapy despite sleep's critical impact on health. OBJECTIVE: To examine pediatric occupational therapists' experiences, views, and confidence in addressing sleep concerns in their practice as well as barriers to and supports for doing so. DESIGN: A qualitative descriptive study with thematic analysis of data from 1-hr virtual interviews. Rapport building, multiple-coder analysis, and member checking were used to ensure reliability and validity. SETTING: Interviews were conducted remotely at each participant's preferred time and location. PARTICIPANTS: Pediatric occupational therapists (N = 20) practicing across multiple settings in the United States were recruited through emails directed to their place of work and social media posts. A goal of 20 participants was set a priori with the goal of thematic saturation. OUTCOMES AND MEASURES: A semistructured interview guide. RESULTS: Participants were predominately cisgender (95%), female (85%), and White, non-Hispanic (90%). Overall, they voiced the importance of sleep but reported almost never writing sleep-related goals. Reported barriers that affected the participants' ability to fully address sleep in practice included therapists' lack of confidence and knowledge and low caregiver buy-in. CONCLUSIONS AND RELEVANCE: The findings identify themes on the basis of which actionable steps toward promoting occupational therapists as sleep champions can be developed. Future implications include increasing sleep education opportunities, enhancing awareness of sleep health's impact on goal areas, and facilitating discussions about occupational therapy's role within the medical system and family system in supporting sleep. Plain-Language Summary: This qualitative study identifies what helps and hinders occupational therapists in addressing the sleep health concerns of their clients. We give occupational therapy clinicians and educators key supports to seek out or barriers to address.

Growth capacity of a Wharton's Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets.

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy. Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry. Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded. Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

Protocol to decellularize porcine right ventricular outflow tracts using a 3D printed flow chamber.

Surgical treatment of pediatric congenital heart disease with tissue grafts is a lifesaving intervention. Decellularization to reduce immunogenicity of tissue grafts is an increasingly popular alternative to glutaraldehyde fixation. Here, we present a protocol to decellularize porcine right ventricular outflow tracts using a 3D printed flow chamber. We describe steps for 3D printing the flow rig, preparing porcine tissue, and using the flow rig to utilize shear forces for decellularization. We then detail procedures for characterizing the acellular scaffold. For complete details on the use and execution of this protocol, please refer to Vafaee et al.1.

Incorporating Acute Conditions into Risk-Adjustment for Provider Profiling: The Case of the US News and World Report Best Hospitals Rankings Methodology.

Several years ago, the US News and World Report changed their risk-adjustment methodology, now relying almost exclusively on chronic conditions for risk adjustment. The impacts of adding selected acute conditions like pneumonia, sepsis, and electrolyte disorders ("augmented") to their current risk models ("base") for 4 specialties-cardiology, neurology, oncology, and pulmonology-on estimates of hospital performance are reported here. In the augmented models, many acute conditions were associated with substantial risks of mortality. Compared to the base models, the discrimination and calibration of the augmented models for all specialties were improved. While estimated hospital performance was highly correlated between the 2 models, the inclusion of acute conditions in risk-adjustment models meaningfully improved the predictive ability of those models and had noticeable effects on hospital performance estimates. Measures or conditions that address disease severity should always be included when risk-adjusting hospitalization outcomes, especially if the goal is provider profiling.