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Abstract Background Incorporating post-discharge data into trauma registries would allow for better research on patient outcomes, including disparities in outcomes. This pilot study tested a follow-up data collection process to be incorporated into existing trauma care systems, prioritizing low-cost automated response modalities. Methods This investigation was part of a larger study that consisted of two protocols with two distinct cohorts of participants who experienced traumatic injury. Participants in both protocols were asked to provide phone, email, text, and mail contact information to complete follow-up surveys assessing patient-reported outcomes six months after injury. To increase follow-up response rates between protocol 1 and protocol 2, the study team modified the contact procedures for the protocol 2 cohort. Frequency distributions were utilized to report the frequency of follow-up response modalities and overall response rates in both protocols. Results A total of 178 individuals responded to the 6-month follow-up survey: 88 in protocol 1 and 90 in protocol 2. After implementing new follow-up contact procedures in protocol 2 that relied more heavily on the use of automated modalities (e.g., email and text messages), the response rate increased by 17.9 percentage points. The primary response modality shifted from phone (72.7%) in protocol 1 to the combination of email (47.8%) and text (14.4%) in protocol 2. Conclusions Results from this investigation suggest that follow-up data can feasibly be collected from trauma patients. Use of automated follow-up methods holds promise to expand longitudinal data in the national trauma registry and broaden the understanding of disparities in patient experiences.

Abstract Background Head injuries are the most common cause of death in some motorized vehicles for which helmet use can significantly decrease the risk. Our objective was to determine rural adolescents’ attitudes regarding helmets and their use while riding ATVs, motorcycles and dirt bikes. Methods A convenience sample of 2022 Iowa FFA (formerly Future Farmers of America) Leadership Conference attendees were surveyed. After compilation, data were imported into the statistical program, R ( https://www.R-project.org/ ). Descriptive statistics, contingency table, logistic regression and non-parametric alternatives to ANOVA analyses were performed. Results 1331 adolescents (13–18 years) participated. One half lived on a farm, 21% lived in the country/not on a farm and 28% were from towns. Nearly two-thirds (65%) owned an ATV with 77% of all having ridden one in the past year. Farm residents had the highest ATV ownership (78%) and having ridden (80%) proportions, both p

Abstract Microeukaryotes are key contributors to marine carbon cycling. Their physiology, ecology, and interactions with the chemical environment are poorly understood in offshore ecosystems, and especially in the deep ocean. Using the Autonomous Underwater Vehicle Clio, microbial communities along a 1050 km transect in the western North Atlantic Ocean were surveyed at 10–200 m vertical depth increments to capture metabolic signatures spanning oligotrophic, continental margin, and productive coastal ecosystems. Microeukaryotes were examined using a paired metatranscriptomic and metaproteomic approach. Here we show a diverse surface assemblage consisting of stramenopiles, dinoflagellates and ciliates represented in both the transcript and protein fractions, with foraminifera, radiolaria, picozoa, and discoba proteins enriched at >200 m, and fungal proteins emerging in waters >3000 m. In the broad microeukaryote community, nitrogen stress biomarkers were found at coastal sites, with phosphorus stress biomarkers offshore. This multi-omics dataset broadens our understanding of how microeukaryotic taxa and their functional processes are structured along environmental gradients of temperature, light, and nutrients.

Abstract Background Individualized treatment for commercial tobacco smoking cessation, such as through the utilization of the nicotine metabolite ratio (NMR), offers potential clinical benefit. NMR is a metabolism-informed biomarker that can be used to guide medication selection. NMR testing is particularly promising for tobacco cessation efforts in populations with high rates of smoking, such as some Alaska Native and American Indian (AN/AI) communities. To date, no prior study has evaluated the implementation of NMR-guided tobacco cessation with AN/AI populations. Methods The present “QUIT” protocol is a two-phase study that will occur at Southcentral Foundation (SCF), an Alaska Native-owned health system, serving 70,000 AN/AI people, based in Anchorage, Alaska. In Phase one, qualitative interviews with customer-owners (patients), providers and administrators (n = 36) and a 10-participant beta-test will be used to refine a strategy to implement NMR testing in the health system. Phase two will involve a single-arm pilot trial (n = 50) and qualitative interviews throughout data collection (n = 48) to evaluate the implementation strategy and explore the real-world acceptability and feasibility of NMR testing to guide tobacco cessation with AN/AI populations. Discussion This study utilizes a community-based participatory approach to refine and implement a nicotine metabolism-informed smoking cessation program in a Tribal healthcare setting. The process and findings from this study will reflect the importance of customer-owner choice and honor the lived experience involved in quitting commercial tobacco. Pilot study data will inform the effect and sample sizes required for a future pragmatic trial of NMR-guided smoking cessation. Trial registration This study will be registered with clinicaltrials.gov after the beta test is complete and the final IRB protocol is approved.

Abstract Background Infectious disease outbreaks are an ongoing public health concern, requiring extensive resources to prevent and manage. Invasive Meningococcal Disease (IMD) is a severe outcome of infection with Neisseria meningitidis bacteria, which can be carried and transmitted asymptomatically. IMD is not completely vaccine-preventable, presenting an ongoing risk of outbreak development. This review provides a retrospective assessment of public health management of IMD outbreaks. Methods A systematic search was performed in PubMed and EMBASE. English-language studies reporting on IMD outbreaks and associated public health response were considered eligible. Reporting on key characteristics including outbreak size, duration, location, and public health response were assessed against Strengthening the Reporting of Observational studies in Epidemiology guidelines. A summary of lessons learned and author recommendations for each article were also discussed. Results 39 eligible studies were identified, describing 35 outbreaks in seven regions. Responses to outbreaks were mostly reactive, involving whole communities over prioritising those at highest risk of transmission. Recent responses identified a need for more proactive and targeted controls. Reporting was inconsistent, with key characteristics such as outbreak size, duration, or response absent or incompletely described. Conclusion There is a need for clear, comprehensive reporting on IMD outbreaks and their public health response to inform policy and practice for subsequent outbreaks of IMD and other infectious diseases.

Abstract Objective In past work in budding yeast, we identified a nucleosomal region required for proper interactions between the histone chaperone complex yFACT and transcribed genes. Specific histone mutations within this region cause a shift in yFACT occupancy towards the 3’ end of genes, a defect that we have attributed to impaired yFACT dissociation from DNA following transcription. In this work we wished to assess the contributions of DNA sequences at the 3’ end of genes in promoting yFACT dissociation upon transcription termination. Results We generated fourteen different alleles of the constitutively expressed yeast gene PMA1, each lacking a distinct DNA fragment across its 3’ end, and assessed their effects on occupancy of the yFACT component Spt16. Whereas most of these alleles conferred no defects on Spt16 occupancy, one did cause a modest increase in Spt16 binding at the gene’s 3’ end. Interestingly, the same allele also caused minor retention of RNA Polymerase II (Pol II) and altered nucleosome occupancy across the same region of the gene. These results suggest that specific DNA sequences at the 3’ ends of genes can play roles in promoting efficient yFACT and Pol II dissociation from genes and can also contribute to proper chromatin architecture.

Introduction: Primary vitreoretinal lymphoma (PVRL) is a rare malignant tumor that typically involves the retina, vitreous, or optic nerve head. PVRL often occurs concurrently with central nervous system lymphoma. Here, we present the first report of a patient with biopsy-confirmed PVRL presenting solely with asymptomatic peripheral drusenoid lesions. Case Presentation: A woman in her 70s presented with new elevated amelanotic yellow lesions with overlying pigment in both of her eyes not previously seen prior to cataract surgery. Over the next 4 months, there was waxing and waning of lesions which resolved and first appeared in the right eye and then the left. A diagnostic vitrectomy of the left eye revealed B-cell lymphoma. The patient elected for initial treatment with radiation therapy of both orbits. A new lesion was identified in her right eye nearly 18 months after starting maintenance therapy with ibrutinib, following which systemic chemotherapy with methotrexate was initiated. Conclusion: Elevated clinical suspicion for a malignant process is needed for patients with progressive new retinal lesions in older age. Local radiation therapy to the orbits alone may not be sufficient to prevent progression despite initial presentation showing confinement of disease to the intraocular space.

Background: Reducing sedentary behavior is a promising intervention target for improving health for older adults; however, few interventions include African American communities. The purpose of this research was to extend the reach of an effective sedentary behavior intervention to African American elders. Methods: Two pilot studies assessed the feasibility (retention, adherence, and safety) and acceptability (participant and leader perspectives) of a 4-wk "Stand Up and Move More" (SUMM) intervention. Sedentary behavior (self-reported and monitor-derived), function (short physical performance battery), and quality of life (SF-36) were measured at baseline (wk0), postintervention (wk4), and follow up (wk12; study 1) to examine preliminary effectiveness of the intervention. Participants (N=26) attended SUMM or an attention-matched stress management intervention (study 2). The magnitude of treatment effects were determined using Hedge’s g effect size calculations [small (g=0.20 to 0.49), moderate (g=0.50 to 0.79), large (g>0.80)]. Results: Retention and adherence rates ranged from 50%-100% and 80%-100%, respectively. There were no adverse events. Participants expressed high satisfaction, and the leader of the SUMM intervention indicated that the intervention content was beneficial. Hedges’ g revealed negligible to small changes in sedentary behavior (g

Abstract Introduction There is little research on how medical school matriculants’ experiences prior to medical school effects their choice of specialty or performance in medical school. This research attempts to fill that gap in research in regards to surgical and radiological fields. Methods An anonymous survey was sent to fourth year medical students asking them their background in anatomy studies prior to medical school and their anatomy grades in medical school and interest in surgical and radiological fields. Students were also asked whether they identified with under-represented demographic groups in those specialties. Results Prior anatomy experience did not significantly affect performance in anatomy courses or Step 1 and Step 2 scores. However, students who applied to surgical specialties had higher performance in anatomical courses and higher Step 1 scores compared to those who did not apply to surgical specialties. There was interestingly no difference in under-represented and not under-represented student application to these fields. Discussion For shareholders interested in increasing medical student performance, or interest in specific specialties, more information needs to be gathered.

Abstract We make decisions by comparing values, but it is not yet clear how value is represented in the brain. Many models assume, if only implicitly, that the representational geometry of value is linear. However, in part due to a historical focus on noisy single neurons, rather than neuronal populations, this hypothesis has not been rigorously tested. Here, we examine the representational geometry of value in the ventromedial prefrontal cortex (vmPFC), a part of the brain linked to economic decision-making, in two male rhesus macaques. We find that values are encoded along a curved manifold in vmPFC. This curvilinear geometry predicts a specific pattern of irrational decision-making: that decision-makers will make worse choices when an irrelevant, decoy option is worse in value, compared to when it is better. We observe this type of irrational choices in behavior. Together, these results not only suggest that the representational geometry of value is nonlinear, but that this nonlinearity could impose bounds on rational decision-making.

Abstract Background Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. Methods This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. Results We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of sexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. Conclusions This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.

Abstract Background Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. Method This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2–19), and following (Study Days 20–21) residential treatment. Discussion This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. Trial registration: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . Protocol Version 10 May 2023

Abstract The diversity of chemical and structural attributes of proteins makes it inherently difficult to produce a wide range of proteins in a single recombinant protein production system. The nature of the target proteins themselves, along with cost, ease of use, and speed, are typically cited as major factors to consider in production. Despite a wide variety of alternative expression systems, most recombinant proteins for research and therapeutics are produced in a limited number of systems: Escherichia coli, yeast, insect cells, and the mammalian cell lines HEK293 and CHO. Recent interest in Vibrio natriegens as a new bacterial recombinant protein expression host is due in part to its short doubling time of ≤ 10 min but also stems from the promise of compatibility with techniques and genetic systems developed for E. coli. We successfully incorporated V. natriegens as an additional bacterial expression system for recombinant protein production and report improvements to published protocols as well as new protocols that expand the versatility of the system. While not all proteins benefit from production in V. natriegens, we successfully produced several proteins that were difficult or impossible to produce in E. coli. We also show that in some cases, the increased yield is due to higher levels of properly folded protein. Additionally, we were able to adapt our enhanced isotope incorporation methods for use with V. natriegens. Taken together, these observations and improvements allowed production of proteins for structural biology, biochemistry, assay development, and structure-based drug design in V. natriegens that were impossible and/or unaffordable to produce in E. coli.

Abstract Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P

Abstract Background We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. Results Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. Conclusions Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.

Abstract Background After settling in the United States (US), immigrants often accumulate obesity and cardiovascular risk factors. As mood is often associated with health behaviors in the US population, mood may be an important mediating factor in immigrant populations. Methods The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention designed to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion. A single-item mood rating of poor or fair was considered “negative”, while ratings of good, very good, or excellent were considered “positive”. Results Hispanic/Latino (n = 268) and Somali (n = 181) adults enrolled in HIC completed baseline measures and were included in this analysis. Participants endorsing negative mood compared to positive mood had lower healthy eating scores (p = 0.02), lower physical activity levels (p = 0.03), lower confidence in eating a healthy diet (p = 0.001), and felt less of a sense of belonging to their community (p = 0.01). Those endorsing negative mood reported receiving less social support to eat healthy (p =

It has long been recognised that a key element in improving student transition, retention and success in higher education is cross-institutional consistency and unity of action among disparate academic, policy and support units. However, transferring this principle into practice often requires overcoming departmental silos, negotiating shared understandings of key concepts, and establishing patterns of cross-institutional collaboration in spaces where this may have been lacking. This study examines the effect of a program of supported communities of practice among teaching academics that sought to improve the culture of learning and teaching in a large science, health and engineering faculty in an Australian university. We found indications that these communities of practice promoted collaboration by functioning as loci of cross-institutional consultation and coordination, providing the basis for an enhanced student experience. We interpret this finding through the lens of Bronfenbrenner’s ecological model of development, and propose an approach based on academic communities of practice as a way of building cross-institutional unity of action and making the student experience everybody’s business.

In March 2024, the US Department of Agriculture’s Animal and Plant Health Inspection Service reported detection of highly pathogenic avian influenza (HPAI) A(H5N1) virus in dairy cattle in the United States for the first time. One factor that determines susceptibility to HPAI H5N1 infection is the presence of specific virus receptors on host cells; however, little is known about the distribution of the sialic acid (SA) receptors in dairy cattle, particularly in mammary glands. We compared the distribution of SA receptors in the respiratory tract and mammary gland of dairy cattle naturally infected with HPAI H5N1. The respiratory and mammary glands of HPAI H5N1–infected dairy cattle are rich in SA, particularly avian influenza virus–specific SA α2,3-gal. Mammary gland tissues co-stained with sialic acids and influenza A virus nucleoprotein showed predominant co-localization with the virus and SA α2,3-gal. HPAI H5N1 exhibited epitheliotropism within the mammary gland, and we observed rare immunolabeling within macrophages.

In September 2021, eight campylobacteriosis cases were identified in a town in Nebraska, USA. We assessed potential exposures for a case–control analysis. We conducted whole-genome sequencing on Campylobacter isolates from patients’ stool specimens. We collected large-volume dead-end ultrafiltration water samples for Campylobacter and microbial source tracking testing at the Centers for Disease Control and Prevention. We identified 64 cases in 2 waves of illnesses. Untreated municipal tap water consumption was strongly associated with illness (wave 1 odds ratio 15.36; wave 2 odds ratio 16.11). Whole-genome sequencing of 12 isolates identified 2 distinct Campylobacter jejuni subtypes (1 subtype/wave). The town began water chlorination, after which water testing detected coliforms. One dead-end ultrafiltration sample yielded nonculturable Campylobacter and avian-specific fecal rRNA genomic material. Our investigation implicated contaminated, untreated, municipal water as the source. Results of microbial source tracking supported mitigation with continued water chlorination. No further campylobacteriosis cases attributable to water were reported.

Abstract People often interact with groups (i.e., ensembles) during social interactions. Given that group-level information is important in navigating social environments, we expect perceptual sensitivity to aspects of groups that are relevant for personal threat as well as social belonging. Most ensemble perception research has focused on visual ensembles, with little research looking at auditory or vocal ensembles. Across four studies, we present evidence that (i) perceivers accurately extract the sex composition of a group from voices alone, (ii) judgments of threat increase concomitantly with the number of men, and (iii) listeners’ sense of belonging depends on the number of same-sex others in the group. This work advances our understanding of social cognition, interpersonal communication, and ensemble coding to include auditory information, and reveals people’s ability to extract relevant social information from brief exposures to vocalizing groups.

Abstract The NuA3 complex is a major regulator of gene transcription and the cell cycle in yeast. Five core subunits are required for complex assembly and function, but it remains unclear how these subunits interact to form the complex. Here, we report that the Taf14 subunit of the NuA3 complex binds to two other subunits of the complex, Yng1 and Sas3, and describe the molecular mechanism by which the extra-terminal domain of Taf14 recognizes the conserved motif present in Yng1 and Sas3. Structural, biochemical, and mutational analyses show that two motifs are sandwiched between the two extra-terminal domains of Taf14. The head-to-toe dimeric complex enhances the DNA binding activity of Taf14, and the formation of the hetero-dimer involving the motifs of Yng1 and Sas3 is driven by sequence complementarity. In vivo assays in yeast demonstrate that the interactions of Taf14 with both Sas3 and Yng1 are required for proper function of the NuA3 complex in gene transcription and DNA repair. Our findings suggest a potential basis for the assembly of three core subunits of the NuA3 complex, Taf14, Yng1 and Sas3.

There is a rare subset of patients with a genetically abnormal hemoglobin structure initially discovered in the Volga region of Europe known as Volga anemia. Key features of this condition include compromised delivery of oxygen to peripheral tissues and altered red blood cells that have a higher likelihood of being broken down or hemolyzed, which can lead to significant hemolytic anemia. Methylene blue is a dye that acts as a reducing agent of oxygen and is commonly used in toxic states that lead to methemoglobin build-up. This paper explores the pathophysiology of this genetic condition and documents three cases across two patients—a father and son—when methylene blue was used during an anemic crisis.

Abstract Background After the military coup in Myanmar in February 2021, the health system began to disintegrate when staff who called for the restoration of the democratic government resigned and fled to states controlled by ethnic minorities. The military retaliated by blocking the shipment of humanitarian aid, including vaccines, and attacked the ethnic states. After two years without vaccines for their children, parents urged a nurse-led civil society organization in an ethnic state to find a way to resume vaccination. The nurses developed a vaccination program, which we evaluated. Methods A retrospective cohort study and participatory evaluation were conducted. We interviewed the healthcare workers about vaccine acquisition, transportation, and administration and assessed compliance with WHO-recommended practices. We analyzed the participating children’s characteristics. We calculated the proportion of children vaccinated before and after the program. We calculated the probability children would become up-to-date after the program using inverse survival. Results Since United Nations agencies could not assist, private donations were raised to purchase, smuggle into Myanmar, and administer five vaccines. Cold chain standards were maintained. Compliance with other WHO-recommended vaccination practices was 74%. Of the 184 participating children, 145 (79%, median age five months [IQR 6.5]) were previously unvaccinated, and 71 (41%) were internally displaced. During five monthly sessions, the probability that age-eligible zero-dose children would receive the recommended number of doses of MMR was 92% (95% confidence interval [CI] 83–100%), Penta 87% (95% CI 80%–94%); BCG 76% (95% CI 69%–83%); and OPV 68% (95% CI 59%–78%). Migration of internally displaced children and stockouts of vaccines were the primary factors responsible for decreased coverage. Conclusions This is the first study to describe the situation, barriers, and outcomes of a childhood vaccination program in one of the many conflict-affected states since the coup in Myanmar. Even though the proportion of previously unvaccinated children was large, the program was successful. While the target population was necessarily small, the program’s success led to a donor-funded expansion to 2,000 children. Without renewed efforts, the proportion of unvaccinated children in other parts of Myanmar will approach 100%.

Abstract In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.

Abstract Consumer engagement and partnership are increasingly recognised as a significant component of healthcare planning, provision, quality improvement and research. This article provides an overview of consumer engagement embedded in two different projects: a quality improvement project and a research project. The considerations and steps taken to effectively engage and partner with consumers throughout both projects will be discussed such as the prompt for consumer engagement, how the consumer/s were recruited and their specific contributions. The commonly reported advantages and challenges as well as reflections on what we might do differently with the benefit of hindsight are presented, including time required by both consumers and health professionals; funding and remuneration; and reporting findings to the wider community. In demonstrating consumer engagement and our learnings, we aim to encourage further consumer engagement activities amongst medical radiation professionals.

Abstract Background Young adult (YA) cancer survivors are a growing, yet underserved population who often face significant and long-lasting cancer-related physical (e.g., pain, fatigue) and emotional (e.g., psychological distress) symptoms. Post-treatment symptoms can persist, disrupting YA’s abilities to complete goals consistent with their developmental stage (e.g., completing their education, achieving autonomy and independence, building their careers, establishing peer and romantic relationships, building their families). While symptom management has been identified as a significant issue in YA’s transitions to survivorship, the symptom management needs of this population largely go unmet. Methods We developed an eight-session, group-based behavioral intervention that is delivered using videoconferencing to address the unique symptom management needs of YA cancer survivors. The intervention was developed in conjunction with YA survivors, leading to the novel combination of traditional behavioral symptom coping strategies, home-based physical activity, strategies from contemporary cognitive-behavioral approaches (e.g., those derived from acceptance and commitment therapy, strategies to foster self-compassion), concepts from meaning centered psychotherapy, and behavioral strategies to improve communication and health care engagement. Participants receive printed intervention materials and access to a study-specific mobile application, both of which are used throughout the program. Herein, we report on a pilot study that is in progress. Recruitment has been completed. YA cancer survivors were recruited in cohorts of n = 10 or n = 11 (n = 61) and randomized to the intervention or waitlist control arms. All participants completed a baseline assessment and four additional assessments over 1 year, with each involving a battery of self-report measures. Discussion The primary objective is to evaluate intervention feasibility and acceptability. As a secondary objective, we will examine patterns of change in intervention targets (i.e., pain, fatigue, emotional distress, symptom interference). Changes from baseline among intervention targets will be estimated for each patient and compared between arms using unadjusted statistical testing. Unadjusted and adjusted multilevel modeling will be used to estimate the effect of the intervention on changes in intervention targets. Interaction models will be used to compare the trajectory of change over time between arms. We expect that this pilot trial will inform our future approach to identify, recruit, and retain participants and provide preliminary data to support a larger, fully powered randomized controlled trial evaluating the intervention. Trial registration NCT04035447 at clinicaltrials.gov; registered July 29, 2019.

Abstract Background A standardized approach to prepare trainees for the job search has not been described. The objective of this study was to describe and evaluate an educational series on the job search for Neonatal-Perinatal Medicine (NPM) fellows and identify participants’ job search knowledge gaps. Methods During the 2020–2021 academic year, we created a virtual, seven-part job search series for NPM fellows that required no funding. The series has been repeated annually. We use REDCap surveys to register participants, collect baseline/demographic information, and evaluate the series’ impact at the beginning and end of the job search timeline. Results In the 2021–2022 academic year, 290 individuals registered for the series, and 89% completed the baseline/demographic survey. The majority were NPM fellows (89%). Early career neonatologists, NPM hospitalists, and pediatric residents also utilized the series (11%). Less than 25% reported being “knowledgeable” or “very knowledgeable” of core job search components, including the timeline of the job search, contract negotiation, and the general roles and responsibilities of junior faculty. Of those who completed the final job search survey and underwent a job search (60%, 97 of 162), the majority (86%) felt that career planning during training was stressful and believed that job search preparation should be structured into the NPM fellowship curriculum (81%). Many felt that the Job Search Series was helpful in elucidating components of the job search. Conclusions We identified several knowledge gaps in NPM fellows’ understanding of how to find, prepare for, and negotiate their first post-training job. We strongly believe these knowledge gaps are not unique to NPM fellows and that all graduate medical education trainees would benefit from a similar, easy-to-implement, no-cost series.

Background: Mohs micrographic surgery (MMS) is used for the treatment of high-risk cutaneous squamous cell carcinoma (cSCC). MMS examines the surgical margins in real time and does not commonly examine the central component of the tumor. Objective: To determine if debulk specimens provide additional details relevant to tumor staging not gained from routine MMS. Methods: A retrospective chart review of debulk specimens taken during MMS for cSCC was performed. Dermatopathology reports were analyzed and tumors were staged using Brigham and Women’s Hospital and American Joint Committee on Cancer’s 8th edition staging systems. Results: Permanent section evaluation of debulk specimens did not result in clinically meaningful information for staging that could not be gained from MMS layers or initial biopsy analysis. Limitations: A single institution, and a small sample size of 39 tumors. Conclusions: Evaluation of debulk specimens during MMS may not always be an effective use of time or health care resources.

Abstract Cranial irradiation used to control brain malignancies invariably leads to progressive and debilitating declines in cognition. Clinical efforts implementing hippocampal avoidance and NMDAR antagonism, have sought to minimize dose to radiosensitive neurogenic regions while normalizing excitatory/inhibitory (E/I) tone. Results of these trials have yielded only marginal benefits to cognition, prompting current studies to evaluate the potential of systemic extracellular vesicle (EV) therapy to restore neurocognitive functionality in the irradiated brain. Here we tested the hypothesis that EVs derived from inhibitory but not excitatory neuronal cultures would prove beneficial to cognition and associated pathology. Rats subjected to a clinically relevant, fractionated cranial irradiation paradigm were given multiple injections of either GABAergic- or glutamatergic-derived EV and subjected to behavioral testing. Rats treated with GABAergic but not glutamatergic EVs showed significant improvements on hippocampal- and cortical-dependent behavioral tasks. While each treatment enhanced levels of the neurotrophic factors BDNF and GDNF, only GABAergic EVs preserved granule cell neuron dendritic spine density. Additional studies conducted with GABAergic EVs, confirmed significant benefits on amygdala-dependent behavior and modest changes in synaptic plasticity as measured by long-term potentiation. These data point to a potentially more efficacious approach for resolving radiation-induced neurological deficits, possibly through a mechanism able to restore homeostatic E/I balance.

Abstract Background Eswatini faces persistent challenges in providing care for diabetes and hypertension, exacerbated by a shortage of healthcare workers. The implementation of WHO-PEN interventions aimed to address these issues, yet their effects on healthcare worker time requirements and associated costs remain unclear. Methods This study employed a time-and-motion analysis and a bottom-up cost assessment to quantify the human and financial resources required for scaling up WHO-PEN interventions nationally in Eswatini for all estimated diabetic and hypertensive patients. Results Findings reveal that healthcare workers in intervention-arm clinics reported longer workday durations compared to those in control-arm clinics, yet spent less time per patient while seeing more patients. The implementation of WHO-PEN interventions increased the workload on healthcare workers but also led to a notable increase in patient care utilization. Furthermore, a morning peak in patient visits was identified, suggesting potential opportunities for optimizing patient flow. Notably, scaling up care provision nationally with WHO-PEN interventions proved to be more cost saving than expanding standard-of-care treatment. Conclusion WHO-PEN interventions hold promise in improving access to diabetes and hypertension care in Eswatini while offering an efficient solution. However, addressing challenges in healthcare workforce creation and retention is crucial for sustained effectiveness. Policy makers must consider all aspects of the WHO-PEN intervention for informed decision-making. Trial registration US Clinical Trials Registry. NCT04183413. Trial registration date: December 3, 2019. https://ichgcp.net/clinical-trials-registry/NCT04183413

Abstract Alzheimer’s disease (AD) is broadly characterized by neurodegeneration, pathology accumulation, and cognitive decline. There is considerable variation in the progression of clinical symptoms and pathology in humans, highlighting the importance of genetic diversity in the study of AD. To address this, we analyze cell composition and amyloid-beta deposition of 6- and 14-month-old AD-BXD mouse brains. We utilize the analytical QUINT workflow- a suite of software designed to support atlas-based quantification, which we expand to deliver a highly effective method for registering and quantifying cell and pathology changes in diverse disease models. In applying the expanded QUINT workflow, we quantify near-global age-related increases in microglia, astrocytes, and amyloid-beta, and we identify strain-specific regional variation in neuron load. To understand how individual differences in cell composition affect the interpretation of bulk gene expression in AD, we combine hippocampal immunohistochemistry analyses with bulk RNA-sequencing data. This approach allows us to categorize genes whose expression changes in response to AD in a cell and/or pathology load-dependent manner. Ultimately, our study demonstrates the use of the QUINT workflow to standardize the quantification of immunohistochemistry data in diverse mice, - providing valuable insights into regional variation in cellular load and amyloid deposition in the AD-BXD model.

Abstract The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely “everted” telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

Adolescents and young adults (AYAs; 15–39 years) diagnosed with cancer have unique medical and psychosocial needs. These needs could be better addressed through research that is focused on the topics that matter most to them. However, there is currently no patient-oriented research agenda for AYA cancer in Canada. This manuscript describes the early development and project protocol for a priority-setting partnership (PSP) for establishing the top 10 research priorities for AYA cancer in Canada. This project follows the PSP methodology outlined by the James Lind Alliance (JLA) to engage patients, caregivers, and clinicians in research prioritization. The steps of a JLA PSP include establishing a steering group and project partners, gathering uncertainties, data processing and verifying uncertainties, interim priority setting, and a final priority setting workshop. The AYA cancer PSP will result in a top 10 list of research priorities identified by Canadian AYA patients, caregivers, and clinicians that will be published and shared broadly with the research community. The first steering group meeting was held in April 2023, and the project is ongoing. The establishment of a patient-oriented research agenda for AYA cancer will catalyze a long-term and impactful research focus and ultimately improve outcomes for AYA patients with cancer in Canada.

Abstract TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL 1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.

Introduction: Infants are at risk for thrombotic conditions due to multiple risk factors such as congenital heart defects and sepsis. According to the American College of Chest Physicians (ACCP) 2012 guidelines, enoxaparin may be given for thrombotic conditions at a dose of 1.5 mg/kg/dose every 12 h for patients less than 2 months of age and 1 mg/kg/dose every 12 h for those older than 2 months. Several studies have reported that infants typically require a higher initial dose of enoxaparin to reach therapeutic antifactor Xa levels than what is currently recommended. Methods: This is a single-center retrospective case-control study of hospitalized infants less than 12 months of age who received treatment with enoxaparin while admitted to the neonatal intensive care unit (NICU) at a freestanding children’s hospital. The primary objective was the difference between the initial enoxaparin dose (mg/kg) compared to the enoxaparin dose in which the patient first achieved a therapeutic antifactor Xa level of 0.5–1.0 units/mL. Results: A total of 56 infants were included in this study. The median enoxaparin dose at initiation was 1.5 mg/kg/dose, and the median enoxaparin dose at the first therapeutic antifactor Xa level was 1.9 mg/kg/dose (z = −12.7, p < 0.0001). There was no correlation between gestational age and weight with the enoxaparin dose required to reach a therapeutic antifactor Xa level. Conclusion: Infants admitted to the NICU, specifically those less than 4 months of age, require higher initial enoxaparin dosing to reach therapeutic antifactor Xa levels than what is currently recommended.

Objective: Donor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data. Methods: We analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance. Results: DCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth. Conclusions: DCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives.

Abstract DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease.

Background: Limited availability and poor quality of data in medical records and trauma registries impede progress to achieve injury-related health equity across the lifespan. Methods: We used a Nominal Group Technique (NGT) in-person workgroup and a national web-based Delphi process to identify common data elements (CDE) that should be collected. Results: The 12 participants in the NGT workgroup and 23 participants in the national Delphi process identified 10 equity-related CDE and guiding lessons for research on collection of these data. Conclusions: These high-priority CDE define a detailed, equity-oriented approach to guide research to achieve injury-related health equity across the lifespan.

Bulk density (Db) and subsequent physical properties are determined by the substrate and packing method. Packing method is the way one fills and compresses a substrate within a given volume. Bulk density produced in the laboratory may not align with “expected” published ranges due to variations in packing. Additionally, it is unknown if ranges identified as “typical” using a small volume sample ring reflect Db occurring in larger production size containers packed using commercial potting practices. Therefore, our objectives were to 1) emulate nursery practices and document the Db associated with a potted 2.8-L (#1) container, 2) develop and test the new “shim and compression” method to determine if it consistently packs sample rings to a Db commensurate with that of a 2.8-L nursery container, and 3) demonstrate how static physical properties are affected by the new “shim and compression” sample ring packing method compared with the traditional bench top tap method. When emulating nursery potting practices with 100% pine bark, coir, and peat, and blends of each, Db ranged from 0.08 g⋅cm−3 (coconut coir) to 0.17 g⋅cm−3 (pine bark). We used an espresso tamp and shims to pack the aforementioned substrates in sample rings. The Db achieved using a range in number of presses and discs was largely dependent on the substrate, but the desired Db was consistently achieved for each substrate. There was no effect of disc number on Db (P = 1.000) for any substrate. There was no effect of tamp number (P ≥ 0.0602) for all substrates except peat-amended, for which five tamps yielded a greater Db than one tamp (P = 0.0324). In an experiment in which a different technician who was accustomed to the conventional benchtop tap packing method performed both methods, method influenced Db (P < 0.0001), and the conventional method more closely attained the target Db. To our knowledge, this is the only report of Db observed in commercial container production facilities (i.e., “native”).

IntroductionIn the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease.MethodsWithin an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease–germline comparator exome analysis, RNA sequencing, and tumor classification by DNA methylation analysis was performed.ResultsThrough the implementation of paired analysis, this study identified 4 of 314 (1.3%) individuals who harbored a germline PTPN11 variant associated with NS, of which 3 individuals were diagnosed with a glioma or glioneuronal tumor. Furthermore, we extend this study through collaboration with a peer institution to identify two additional individuals with NS and a glioma or glioneuronal tumor. Notably, in three of five (60%) individuals, paired genomic profiling led to a previously unrecognized diagnosis of Noonan syndrome despite an average age of cancer diagnosis of 16.8 years. The study of the disease-involved tissue identified signaling pathway dysregulation through somatic alteration of genes involved in cellular proliferation, survival, and differentiation.DiscussionComparative pathologic findings are presented to enable an in-depth examination of disease characteristics. This comprehensive analysis highlights the association of gliomas and glioneuronal tumors with RASopathies and the potential therapeutic challenges and importantly demonstrates the utility of genomic profiling for the identification of germline cancer predisposition.

BackgroundMicroRNAs (miRNAs) in Schwann cells (SCs) mediate peripheral nerve function. Ablating Dicer, a key gene in miRNA biogenesis, in SCs causes peripheral neuropathy. Exosomes from healthy SCs (SC-Exo) ameliorate diabetic peripheral neuropathy in part via miRNAs. Thus, using transgenic mice with conditional and inducible ablation of Dicer in proteolipid protein (PLP) expressing SCs (PLP-cKO), we examined whether SC-Exo could reduce peripheral neuropathy in PLP-cKO mice.MethodsPLP-cKO mice at the age of 16 weeks (8 week post-Tamoxifen) were randomly treated with SC-Exo or saline weekly for 8 weeks. Age-and sex-matched wild-type (WT) littermates were used as controls. Peripheral neurological functions, sciatic nerve integrity, and myelination were analyzed. Quantitative RT-PCR and Western blot analyses were performed to examine miRNA and protein expression in sciatic nerve tissues, respectively.ResultsCompared to the WT mice, PLP-cKO mice exhibited a significant decrease in motor and sensory conduction velocities, thermal sensitivity, and motor coordination. PLP-cKO mice exhibited substantial demyelination and axonal damage of the sciatic nerve. Treatment of PLP-cKO mice with SC-Exo significantly ameliorated the peripheral neuropathy and sciatic nerve damage. PLP-cKO mice showed a substantial reduction in a set of Dicer-related miRNAs known to regulate myelination, axonal integrity, and inflammation such as miR-138, −146a and − 338 in the sciatic nerve. In addition, PLP-cKO mice exhibited significant reduction of myelin forming proteins, early growth response 2 (EGR2) and sex determining region Y-box10 (Sox10), but significantly increased myelination inhibitors, Notch1, c-Jun, and Sox2 and the axonal growth inhibitor phosphatase and tens in homolog (PTEN). However, SC-Exo treatment reversed the PLP-cKO altered miRNAs and proteins.ConclusionThis study demonstrates that exogenous SC-Exo ameliorate peripheral neuropathy induced by Dicer ablation in PLP expressing SCs. The therapeutic benefit may be mediated by the SC-Exo altered miRNAs and their targeted genes.

Background. Heart transplantation is always an emergency because the transplant needs to occur within 6 h after procurement to prevent primary graft dysfunction. Static cold storage (SCS) is the gold-standard preservation method. This study describes the outcomes of hearts preserved after prolonged SCS (12 and 24 h); those are then resuscitated with a novel normothermic ex situ heart perfusion (NEHP) system. Methods. Anesthetized piglets (n = 10) were used as heart donors. Hearts were procured and stored at 5 °C CoStorSol following standard SCS protocols. Two groups were studied: SCS-12 h and SCS-24 h. After SCS, 8 h of NEHP (37 °C blood-based perfusate) was performed at 0.7–1.0 mL/min/g of cardiac tissue. NEHP parameters were monitored continuously. Results were corroborated with 3 additional hearts transplanted orthotopically in healthy recipients (n = 3) after SCS (24 h) + NEHP (5 h). Recipients were observed for 90 min after weaning off cardiopulmonary bypass support. Results. All hearts (after 12 and 24 h of SCS) regained normal function and metabolism within 10 min and retained it throughout 8 h of NEHP. No differences were observed in NEHP parameters and histopathology between groups. Three hearts were successfully transplanted after a total ~30 h of preservation (24 h of SCS + 5 h of NEHP + 1 h of second cold ischemia time). The 3 recipients were weaned off cardiopulmonary bypass with mild vasopressor support. Conclusions. NEHP has the potential to routinely resuscitate porcine hearts that have undergone SCS for up to 24 h, restoring them to viable function. By objectively assessing heart function before transplant, NEHP may enhance the success rate of transplants. If these resuscitated hearts can be successfully transplanted, it would support the effectiveness of NEHP in ensuring heart viability.

A hexanucleotide (G4C2) repeat expansion (HRE) within intron one of C9ORF72 is the leading genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). C9ORF72 haploinsufficiency, formation of RNA foci, and production of dipeptide repeat (DPR) proteins have been proposed as mechanisms of disease. Here, we report the first example of disease-modifying siRNAs for C9ORF72 driven ALS/FTD. Using a combination of reporter assay and primary cortical neurons derived from a C9-ALS/FTD mouse model, we screened a panel of more than 150 fully chemically stabilized siRNAs targeting different C9ORF72 transcriptional variants. We demonstrate the lack of correlation between siRNA efficacy in reporter assay versus native environment; repeat-containing C9ORF72 mRNA variants are found to preferentially localize to the nucleus, and thus C9ORF72 mRNA accessibility and intracellular localization have a dominant impact on functional RNAi. Using a C9-ALS/FTD mouse model, we demonstrate that divalent siRNAs targeting C9ORF72 mRNA variants specifically or non-selectively reduce the expression of C9ORF72 mRNA and significantly reduce DPR proteins. Interestingly, siRNA silencing all C9ORF72 mRNA transcripts was more effective in removing intranuclear mRNA aggregates than targeting only HRE-containing C9ORF72 mRNA transcripts. Combined, these data support RNAi-based degradation of C9ORF72 as a potential therapeutic paradigm.

Objectives: This study sought to detect and characterize influenza A (IAV) and influenza D (IDV) viruses circulating among commercial birds and shop owners in Pakistan's live bird markets. Methods: Oropharyngeal swabs (n = 600; n = 300 pools) collected from poultry and nasopharyngeal swabs (n = 240) collected from poultry workers were studied for molecular evidence of IAV and IDV using real-time and conventional real-time reverse transcription polymerase chain reaction protocols. Results: Nineteen (6.3%) poultry pools were positive for IAV and 73.9% of these were positive for H9N2 subtypes. Two (0.83%) poultry workers had evidence of IAV, and both were also H9N2 subtypes. The poultry and human IAV-positive specimens all clustered phylogenetically by Sanger and next-generation sequencing with previously detected H9N2 poultry isolates. No field specimens were positive for IDV. Conclusion: H9N2 IAV is likely enzootic in Punjab Province Pakistan's live bird markets and may be colonizing the noses of workers and market visitors. Regular monitoring for avian influenza-associated human illness in Punjab seems to be a needed public measure.

Chronic health conditions such as cancer, diabetes, and heart disease are highly prevalent in the older adult population. Engaging in health behaviors can help prevent the onset of or better manage these conditions. To better understand how to increase older adult engagement in health behaviors, this rapid evidence review evaluated the relationship between health literacy and health behaviors in adults over the age of 65. The databases utilized for this review were PubMed (Medline), EBSCO (APA PsycInfo, Academic Search, and CINAHL Plus.) All six studies included demonstrated significant and positive associations between adequate health literacy and certain health behaviors including pap-smears, mammograms, physical activity, dietary variety, participation in medical checkups, patient participation in health care, hand hygiene practices, and diabetes self-management behaviors. Adequate health literacy was, however, associated with alcohol consumption in two studies. Knowing this, health professionals can utilize health literacy screening and interventions to promote health behaviors in older adults.

Background:. The gold standard of microsurgical breast reconstruction is the deep inferior epigastric perforator (DIEP) free flap. As techniques have evolved, DIEP flaps have significantly reduced the morbidity previously caused by transverse rectus abdominis muscle (TRAM) and muscle-sparing TRAM flaps. However, abdominal wall complications continue to persist after DIEP flap surgery, with bulge rates reported as high as 33%. Methods:. The first 25 patients undergoing DIEP flap surgery with the use of Duramesh (MSI, Chicago, Ill.) by the senior author were identified. A retrospective chart review of patient and surgical details was performed. Charts were reviewed for outcomes, including surgical site infections, surgical site events, incisional hernia formation, and/or bulge. Standard descriptive summary statistics were used for patient characteristics, surgical details, and primary and secondary outcomes. Results:. Twenty-five patients were reviewed. Average follow-up duration was 216 ± 39 days. One patient (4%) developed a surgical site infection, and four patients (16%) developed a surgical site event. One patient developed a bulge, but no patients developed an incisional hernia. Conclusions:. Duramesh mesh suture provides a promising opportunity for DIEP surgeons to minimize both abdominal wall morbidity and mesh-related complications. Mesh suture can be used in a similar fashion as other sutures to perform primary closure of the anterior rectus sheath while also providing force-distribution benefits typically unique to planar mesh. This pilot study suggests that Duramesh is a safe, simple alternative to existing techniques in DIEP flap surgery and can be considered by microsurgeons to reduce fascial dehiscence, bulge, and/or hernia formation.

Sickle cell disease (SCD) is a collection of genetic lesions that manifest in the diminished effectiveness of hemoglobin. We collected and reviewed the recent and extant literature on SARS-CoV-2 (COVID-19) and SCD. We posit an answer to the question associated with any adaptive responses to COVID-19 in individuals with SCD. We collected papers from MEDLINE and all available published papers on COVID-19 and SCD. Unlike a formal meta-analysis, given the early phase of this review in the pandemic, we did not seek unpublished papers. We found an emerging literature where case studies dominated, and traditional large N epidemiological studies were absent. Patients with SCD share many comorbid illnesses with an increased risk of mortality associated with contracting COVID-19. There is sufficient empirical justification to accelerate research on the impact of a viral pathogen like COVID-19 on individuals with SCD. *************************************************************** List of all authors: Michaela Boggan,1,2,3 Christopher L. Edwards,1,2,3 Jordan Meek,1,2,3 Mary Wood,4 W. Jeff Bryson,5 John J. Sollers,1,2,3 Debra O. Parker,1,2,3 Camela S. Barker,2,5 Jessica Miller,2,6 Brianna Downey,2,5 Asha Lockett,2,5 Jazmin Rosales,1,2,3 Courtney Munroe, Jr.,2 Noa Wax,2,5 Sharena Scott,1,2,3 Bridget Pittman,1,2,3 Merell Turner,1,2,3 Hillary T. Dietahin,1,2,3 Eric Smith,1,2,3 Alexandria McDougald,1,2,3 Samantha Beavers,1,2,3 Lakaiya Meadows,1,2,3 Maya Walker,1,2,3 Andrea Richardson,1,2,3 John J. Sollers, IV,2,8 Grace D. Donahue,2,8 Goldie Byrd,7 Malik Muhammad,1,2 Alvin Kidd,9 Walter Charles,1,2 Jonathan Livingston,1,2,3 Shiv Sudhakar10 1North Carolina Central University; 2NCCU Psychoneuroendocrine and Rare Diseases Laboratory; 3NCCU Debra O. Parker Research Incubator; 4Duke University Medical Center; 5Fielding Graduate University; 6Bridges Point Sickle Cell Foundation; 7Wake Forest Medical Center; 8Thomas Moore University; 9Livingston College; 10California Northstate University, United States

BackgroundIndividuals living in rural communities experience substantial geographic and infrastructure barriers to attaining health equity in accessing tobacco use cessation treatment. Social media and other digital platforms offer promising avenues to improve access and overcome engagement challenges in tobacco cessation efforts. Research has also shown a positive correlation between faith-based involvement and a lower likelihood of smoking, which can be used to engage rural communities in these interventions. ObjectiveThis study aimed to develop and beta test a social intervention prototype using a Facebook (Meta Platforms, Inc) group specifically designed for rural smokers seeking evidence-based smoking cessation resources. MethodsWe designed a culturally aligned and faith-aligned Facebook group intervention, FaithCore, tailored to engage rural people who smoke in smoking cessation resources. Both intervention content and engagement strategies were guided by community-based participatory research principles. Given the intervention’s focus on end users, that is, rural people who smoked, we conducted a beta test to assess any technical or usability issues of this intervention before any future trials for large-scale implementation. ResultsNo critical beta test technical and usability issues were noted. Besides, the FaithCore intervention was helpful, easy to understand, and achieved its intended goals. Notably, 90% (9/10) of the participants reported that they tried quitting smoking, while 90% (9/10) reported using or seeking cessation resources discussed within the group. ConclusionsThis study shows that social media platform with culturally aligned and faith-aligned content and engagement strategies delivered by trained moderators are promising for smoking cessation interventions in rural communities. Our future step is to conduct a large pilot trial to evaluate the intervention’s effectiveness on smoking cessation outcomes.

Though school and academic librarians both are information science professionals tasked with teaching and supporting information literacy on their campuses, biases inherent in educational institutions create a hierarchy between the two groups. This divide creates inequity in partnerships. Using Tamarack Institute’s Collaboration Spectrum Tool (2017) we seek more precise language to describe these partnerships in order to create conversations as equal colleagues rather than through the divide of secondary and higher education. As the outreach and education librarian tasked with building relationships with students and educators in our local K12 schools, we hope to reimagine our relationship with school librarians in order to strengthen libraries at all levels and support students in becoming proficient in information competency skills.