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The author, a birth doula and Lamaze Certified Childbirth Educator, agreed to attend the birth of a second child to a mother whose military husband was serving overseas. Because labor seemed to be progressing slowly, they waited at a hotel near the birth center. A very quick labor progression led to a rapid birth in the hotel, with the midwife still on her way. The author shares how learning to trust the power of natural childbirth helped her to remain calm and present for the mother for a once-in-a-lifetime moment. [ABSTRACT FROM AUTHOR]

Behavioral economics offers a unique opportunity to understand the social, cognitive, and psychological nuances that may influence health behavior. The purpose of this article is to demonstrate the application of NUDGE, a novel behavioral economics and design thinking framework, to address barriers to antiretroviral therapy adherence among adolescents living with HIV in eSwatini. NUDGE comprises five steps: (1) Narrow the focus to a specific target behavior, (2) Understand the context of the behavior through inquiry, (3) Discover behavioral insights related to the target behavior, (4) Generate intervention design features to address behavioral barriers to the target behavior, and (5) Evaluate the design features through iterative pilot testing. This article demonstrates the application of the Discover and Generate steps using qualitative data. In showing the utility of the NUDGE framework, we provide a practical tool for creating interventions informed by behavioral insights.

In the adolescent mental health crisis, negative narrative communication has unitended consequences. Supportive communication involves reframing communications to find a new narrative that does not evoke biases. This narrative must emphasize agency and highlight the strengths, potential, and common experiences of young people. It is clear that supporting positive development and well-being is an "us" endeavor. There is a place in this communication strategy for pediatric professionals to address young people, caregivers, other health care professionals, and the community. The science of framing helps us shape a more supportive and productive discourse., Competing Interests: Disclosure The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anomalous peak abundances of platinum and Fe-rich microspherules with high-temperature minerals have previously been demonstrated to be a chronostratigraphic marker for the lower Younger Dryas Boundary (YDB) dating to 12.8 ka. This study used Bayesian analyses to test this hypothesis in multiple sequences (units) of sandy, weakly stratified sediments at Wakulla Springs, Florida. Our investigations included platinum geochemistry, granulometry, optically stimulated luminescence (OSL) dating, and culturally dated lithics. In addition, sediments were analyzed using scanning electron microscopy and energy dispersive x-ray spectroscopy to investigate dendritic, iron-rich microspherules previously identified elsewhere in peak abundances at the onset of the Younger Dryas (YD) cool climatic episode. Our work has revealed this abundance peak in platinum and dendritic spherules in five sediment sequences at Wakulla Springs. A YDB age of ~ 12.8 ka for the platinum and spherule chronostratigraphic datum in these Wakulla Springs sequences is consistent with the archaeological data and OSL dating. This study confirms the utility of this YDB datum layer for intersequence correlation and for assessing relative ages of Paleoamerican artifacts, including those of likely Clovis, pre-Clovis, and post-Clovis age and their possible responses to environmental changes known to have occurred during the Younger Dryas cool climatic episode., (© 2023. The Author(s).)

Despite widespread availability of life-saving antiretroviral therapy (ART) in sub-Saharan Africa, AIDS remains one of the leading causes of death among adolescents living with HIV (ALHIV) in sub-Saharan Africa. The purpose of this article was to review the state of the science regarding interventions to improve ART adherence and/or HIV care retention among ALHIV throughout sub-Saharan Africa. The primary aim of this review was to describe the impact of peer support interventions in improving treatment outcomes (i.e., ART adherence and retention in HIV care) among ALHIV in sub-Saharan Africa. The secondary aim of this review was to determine whether these interventions may be efficacious at improving mental health outcomes. We identified 27 articles that met the eligibility criteria for our review, and categorized each article based on the type of peer support provided to ALHIV-individualized peer support, group-based support, and individualized plus group-based support. Results regarding the efficacy of these interventions are mixed and most of the studies included were deemed moderate in methodological quality. Although studies evaluating group-based peer support interventions were the most common, most of these studies were not associated with retention, adherence, or mental health outcomes. More robust, fully powered studies are needed to strengthen our knowledge base regarding peer support for ALHIV.

In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle., Competing Interests: Declaration of interests K.P. is a consultant to Polgenix, Inc. His relationship with Polgenix, Inc., has been reviewed and approved by the University of California, Irvine, in accordance with its conflict-of-interest policies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points. Post-Clovis points tested positive for Equidae and Bovidae but not Proboscidea. Microwear results are consistent with projectile usage, butchery, fresh- and dry hide scraping, the use of ochre-coated dry hides for hafting, and dry hide sheath wear. This study represents the first direct evidence of the exploitation of extinct megafauna by Clovis and other Paleoamerican cultures in the Carolinas and more broadly, across the eastern United States, where there is generally poor to non-existent faunal preservation. Future CIEP analysis of stone tools may provide evidence on the timing and demography of megafaunal collapse leading to eventual extinction., (© 2023. The Author(s).)

We investigated perceived impacts of COVID-19 on the delivery of adolescent HIV treatment and prevention services in sub-Saharan Africa (SSA) by administering a survey to members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) from February to April 2021. We organized COVID-19 impacts, as perceived by AHISA teams, under three themes: service interruptions, service adjustments, and perceived individual-level health impacts. AHISA teams commonly reported interruptions to prevention programs, diagnostic testing, and access to antiretroviral therapy (ART). Common service adjustments included decentralization of ART refills, expanded multi-month ART distribution, and digital technology use. Perceived individual-level impacts included social isolation, loss to follow-up, food insecurity, poverty, and increases in adolescent pregnancies and sexually transmitted infections. The need for collaboration among stakeholders were commonly cited as lessons learned by AHISA teams. Survey findings highlight the need for implementation science research to evaluate the effects of pandemic-related HIV service adaptations in SSA., (© 2022. The Author(s).)

Objective : A well-functioning healthcare team is important to optimizing the health outcomes of patients. As such, the use of Team Based Learning (TBL) in the education of health professionals has emerged as one of the more common active learning strategies. In various anecdotes with preceptors, it had been observed that student pharmacists educated in a TBL classroom exhibited increased skills in the affective domain. This qualitative pilot study begins to examine affective domain skills that are important to pharmacy practice and which of those skills may be developed uniquely through TBL. Methods : Random samples of preceptors and students (first through fourth-year cohorts), were engaged using a predesigned interview protocol to guide the discussion. Ad hoc questions resulting from the interview were also captured. A grounded theory approach was utilized to develop an a priori theme codebook that was utilized to analyze the interviews with preceptors and focus groups with students. Results : Nine preceptors were interviewed, and 23 student pharmacists participated in focus groups. Preceptors identified 1) communication, 2) emotional intelligence, 3) education, 4) time management, and 5) advocacy as the top themes important to being a leader. While students identified 1) communicate with or listen to others, 2) accountability/responsibility, 3) patience, 4) self-reflection / feedback as skills developed by TBL. Participants indicated that they believed that TBL was a contributor to the development of affective domain skills among student pharmacists. Conclusion : Among preceptors and student pharmacists, this initial study found both alignment and divergence with identified skills in the affective domain related to the development of leadership skills. Additional research is needed to further explore and develop an instrument to measure the role of TBL in affective skill development, in the context of being a leader in the pharmacy profession., (© Individual authors.)

The basic motif-leucine zipper (bZIP) transcription factor neural retina leucine zipper (NRL) determines rod photoreceptor cell fate during retinal development, and its loss leads to cone-only retina in mice. NRL works synergistically with homeodomain protein Cone-Rod Homeobox and other regulatory factors to control the transcription of most genes associated with rod morphogenesis and functional maturation, which span over a period of several weeks in the mammalian retina. We predicted that NRL gradually establishes rod cell identity and function by temporal and dynamic regulation of stage-specific transcriptional targets. Therefore, we mapped the genomic occupancy of NRL at four stages of mouse photoreceptor differentiation by CUT&RUN analysis. Dynamics of NRL binding revealed concordance with the corresponding changes in transcriptome of the developing rods. Notably, we identified c-Jun proto-oncogene as one of the targets of NRL, which could bind to specific cis-elements in the c-Jun promoter and modulate its activity in HEK293 cells. Coimmunoprecipitation studies showed the association of NRL with c-Jun, also a bZIP protein, in transfected cells as well as in developing mouse retina. Additionally, shRNA-mediated knockdown of c-Jun in the mouse retina in vivo resulted in altered expression of almost 1000 genes, with reduced expression of phototransduction genes and many direct targets of NRL in rod photoreceptors. We propose that c-Jun-NRL heterodimers prime the NRL-directed transcriptional program in neonatal rod photoreceptors before high NRL expression suppresses c-Jun at later stages. Our study highlights a broader cooperation among cell-type restricted and widely expressed bZIP proteins, such as c-Jun, in specific spatiotemporal contexts during cellular differentiation., (Published by Oxford University Press 2022.)

The inappropriate use of opioids is a national concern. Experts suggest a multifaceted, collaborative practice approach to reduce mortality rates in complex healthcare issues is effective. Before practice, students require education to address the development of interprofessional (IP) skills. The purpose of this mixed-methods cohort study was to identify changes in student self-perceived value of IP socialization skills and to explore student perceptions of IP engagement in the context of the opioid crisis, before and after a combined IP panel and focus group discussion using a healthcare professional's journey from addiction into recovery. Thirty-three pre-licensure healthcare students in Schools of Counseling, Nursing, Occupational Therapy, Pharmacy, and Physical Therapy assessed their IP experience using the Interprofessional Socialization and Valuing Scale (ISVS). The IP event included interactive discussions with a panel of healthcare providers, a pharmacist in recovery from opioid use disorder, and a local prescription drug awareness and prevention advocate. Significant differences occurred between pre and post ISVS scores in the perceived value of IP collaborative work. Results from the qualitative analysis revealed a need for student-driven self-reflection before the discussions evolved to address the perspectives of future practitioner, the patient, and the healthcare system. Creating a real-time, face-to-face interaction with a panel of healthcare practitioners, an opioid survivor in concert with a local prescription drug prevention advocate may be an effective means toward improving teaching IP value and progressing student outcomes toward IP skill attainment.

Background: When planning interventions for adolescents, adult interventions should not be used 'as is' in youth settings. Stakeholder engagement can help understand the overall adolescent mental health ecosystem and adapt existing evidence-based interventions for the youth., Objective: To understand the overall mental health needs of adolescents in Botswana and the necessary adaptations required for an adolescent lay counselor based intervention in the country., Methods: We used the theory of change model and the nominal group technique in five stakeholder meetings. Meetings were held to discuss the mental health needs of youth in Botswana and identify priorities for a lay counsellor based intervention modelled after the Friendship Bench intervention, an existing mental health intervention for adults., Results: The root causes of mental health problems among Botswana's youth identified by stakeholders included limited mental health knowledge among the youth and the community, family problems, poor communication, low self-esteem, the rapid growth of technology, and biological/genetic predisposition. Structurally barriers included: mental illness-related stigma, lack of psychosocial support, incomplete follow up for health services, cultural beliefs about mental illness, and fragmented mental health services. The stakeholders envisage a program that could empower adolescents and youth counselors to address mental health concerns for a healthier community. The group identified and prioritized several key elements of an effective lay counselor intervention., Conclusions: A diverse group of community stakeholders can illustrate critical mental health needs and elements that countries could use to adapt and contextualize a lay counsellor based mental health intervention for new populations such as the youth., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Disclosure of interest: The authors completed the ICMJE Declaration of Interest form (available upon request from the corresponding author) and declare no conflicts of interest.

Retinal diseases exhibit extensive genetic heterogeneity and complex etiology with varying onset and severity. Mutations in over 200 genes can lead to photoreceptor dysfunction and/or cell death in retinal neurodegeneration. To deduce molecular pathways that initiate and/or drive cell death, we adopted a temporal multiomics approach and examined molecular and cellular events in newborn and developing photoreceptors before the onset of degeneration in a widely-used Pde6brd1/rd1 (rd1) mouse, a model of autosomal recessive retinitis pigmentosa caused by PDE6B mutations. Transcriptome profiling of neonatal and developing rods from the rd1 retina revealed early downregulation of genes associated with anabolic pathways and energy metabolism. Quantitative proteomics of rd1 retina showed early changes in calcium signaling and oxidative phosphorylation, with specific partial bypass of complex I electron transfer, which precede the onset of cell death. Concurrently, we detected alterations in central carbon metabolism, including dysregulation of components associated with glycolysis, pentose phosphate and purine biosynthesis. Ex vivo assays of oxygen consumption and transmission electron microscopy validated early and progressive mitochondrial stress and abnormalities in mitochondrial structure and function of rd1 rods. These data uncover mitochondrial overactivation and related metabolic alterations as determinants of early pathology and implicate aberrant calcium signaling as an initiator of higher mitochondrial stress. Our studies thus provide a mechanistic framework with mitochondrial damage and metabolic disruptions as early drivers of photoreceptor cell death in retinal degeneration., (Published by Oxford University Press 2022.)

Stress and burnout afflict medical students and professionals at alarming rates, which has led institutions to invest in counseling services and other traditional wellness programming. However, the stigma of utilizing these services permeates the medical community. This narrative explores the founding of the Nebraska Medical Orchestra-an orchestra created as a nontraditional antidote to reduce stress and burnout among health care students and professionals-and also examines the concept of wellness through interactions between the orchestra's director and health care-related musicians., (Copyright 2022 American Medical Association. All Rights Reserved.)

Background: Inspired by research indicating that exposure to humanities correlates with reduced burnout, the Nebraska Medical Orchestra was founded in 2018 as a collaboration between the University of Nebraska Medical Center and the University of Nebraska at Omaha School of Music., Methods: Semistructured interviews about orchestra participants' experiences were conducted with 9 musicians and recorded and transcribed. Transcripts were analyzed using the constant comparative method., Results: The interviews suggested that participants are drawn to the orchestra to pursue a love of music, to be part of an ensemble, and to connect with others in an environment that provides a lighthearted, nonjudgmental, noncompetitive forum in which to create and enjoy music for its own sake., Conclusions: This study has implications for designing arts-based wellness activities for clinicians and scaling them nationwide., (Copyright 2022 American Medical Association. All Rights Reserved.)

We conducted a pilot trial of an intervention targeting intersectional stigma related to being pregnant and living with HIV while promoting capabilities for achieving 'respected motherhood' ('what matters most') in Botswana. A pragmatic design allocated participants to the intervention (N = 44) group and the treatment-as-usual (N = 15) group. An intent-to-treat, difference-in-difference analysis found the intervention group had significant decreases in HIV stigma (d = - 1.20; 95% CI - 1.99, - 0.39) and depressive symptoms (d = - 1.96; 95% CI - 2.89, - 1.02) from baseline to 4-months postpartum. Some, albeit less pronounced, changes in intersectional stigma were observed, suggesting the importance of structural-level intervention components to reduce intersectional stigma., (© 2022. The Author(s).)

Asymmetric neuronal expansion is thought to drive evolutionary transitions between lissencephalic and gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes together sustain neurogenic continuity and lissencephaly in rodent cortices. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double + NPCs, at the hierarchical apex, are least lineage restricted due to Neurog2-Ascl1 cross-repression and display unique features of multipotency (more open chromatin, complex gene regulatory network, G 2 pausing). Strikingly, selectively eliminating double + NPCs by crossing Neurog2-Ascl1 split-Cre mice with diphtheria toxin-dependent "deleter" strains locally disrupts Notch signaling, perturbs neurogenic symmetry, and triggers cortical folding. In support of our discovery that double + NPCs are Notch-ligand-expressing "niche" cells that control neurogenic periodicity and cortical folding, NEUROG2, ASCL1, and HES1 transcript distribution is modular (adjacent high/low zones) in gyrencephalic macaque cortices, prefiguring future folds., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Objective: Botswana has a high pregnancy rate among adolescent girls and young women (AGYW). Long-acting reversible contraceptive (LARC) use among AGYW in Botswana is low, despite its high effectiveness for preventing pregnancy. Using an implementation science framework, we assessed barriers and facilitators to LARC implementation among AGYW in Botswana., Design: Cross-sectional mixed methods., Setting: Gaborone, Botswana., Participants: Twenty sexually active AGYW ages 18-24 years; 20 health system stakeholders., Interventions: Surveys and semistructured interviews grounded in the Consolidated Framework for Implementation Research., Main Outcome Measures: Themes reflecting barriers and facilitators of LARC implementation., Results: The median age for AGYW was 22 (interquartile range, 21-23) years. Twenty percent were using an implant and none had ever used an intrauterine device. Barriers and facilitators of LARC implementation spanned factors at each Consolidated Framework for Implementation Research domain: (1) LARC characteristics like side effects; (2) the clinics' inner settings, including availability of youth-friendly services; (3) characteristics of health system stakeholders, such as LARC skills, and AGYW experiences, attitudes, and beliefs about LARCs; (4) the outer setting external to clinics and Botswana's health system including reproductive health law and policy for minor adolescents; and (5) the implementation process level such as the availability of free or low-cost LARCs., Conclusion: We identified multilevel, context-specific factors that affect LARC implementation. Our findings can inform the development of interventions to increase LARC implementation in Botswana by addressing intersecting factors across patient, clinic, health system, and sociopolitical levels, such as providing confidential services to minors and improving LARC training and supply chain pipelines., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To understand RS1 gene interaction networks in the X-linked retinoschisis (XLRS) mouse retina ( Rs1 -/y ), we analyzed the transcriptome by RNA sequencing before and after in vivo expression of exogenous retinoschisin ( RS1 ) gene delivered by AAV8. RS1 is a secreted cell adhesion protein that is critical for maintaining structural lamination and synaptic integrity of the neural retina. RS1 loss-of-function mutations cause XLRS disease in young boys and men, with splitting ("schisis") of retinal layers and synaptic dysfunction that cause progressive vision loss with age. Analysis of differential gene expression profiles and pathway enrichment analysis of Rs1 -KO ( Rs1 -/y ) retina identified cell surface receptor signaling and positive regulation of cell adhesion as potential RS1 gene interaction networks. Most importantly, it also showed massive dysregulation of immune response genes at early age, with characteristics of a microglia-driven proinflammatory state. Delivery of AAV8- RS1 primed the Rs1 -KO retina toward structural and functional recovery. The disease transcriptome transitioned toward a recovery phase with upregulation of genes implicated in wound healing, anatomical structure (camera type eye) development, metabolic pathways, and collagen IV networks that provide mechanical stability to basement membrane. AAV8- RS1 expression also attenuated the microglia gene signatures to low levels toward immune quiescence. This study is among the first to identify RS1 gene interaction networks that underlie retinal structural and functional recovery after RS1 gene therapy. Significantly, it also shows that providing wild-type RS1 gene function caused the retina immune status to transition from a degenerative inflammatory phenotype toward immune quiescence, even though the transgene is not directly linked to microglia function. This study indicates that inhibition of microglial proinflammatory responses is an integral part of therapeutic rescue in XLRS gene therapy, and gene therapy might realize its full potential if delivered before microglia activation and photoreceptor cell death. Clinical Trials. gov Identifier NTC 02317887.

Cigarette smoking, a powerful mixture of chemical oxidants, is the strongest environmental risk factor for developing age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western societies. Despite intensive study, the full impact of smoking on the retinal pigment epithelium (RPE), a central cell type involved in AMD pathobiology, remains unknown. The relative contribution of the known dysfunctional pathways to AMD, at what stage they are most pathogenic, or whether other processes are relevant, is poorly understood, and furthermore, whether smoking activates them, is unknown. We performed global RNA-sequencing of the RPE from C57BL/6J mice exposed to chronic cigarette smoke for 6 months to identify potential pathogenic and cytoprotective pathways. The RPE transcriptome induced by chronic cigarette smoking exhibited a mixed response of marked suppression of the innate immune response including type I and II interferons and upregulation of cell differentiation and morphogenic gene clusters, suggesting an attempt by the RPE to maintain its differentiated state despite smoke-induced injury. Given that mice exposed to chronic smoke develop early features of AMD, these novel findings are potentially relevant to the transition from aging to AMD., Competing Interests: Declaration of competing interest JTH received grant funding and royalties, and MC grant funding from Bayer Pharmaceutical, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Retinal pigment epithelium (RPE) differentiated from human induced pluripotent stem cells, called induced retinal pigment epithelium (iRPE), is being explored as a cell-based therapy for the treatment of retinal degenerative diseases, especially age-related macular degeneration. The success of RPE implantation is linked to the use of biomimetic scaffolds that simulate Bruch's membrane and promote RPE maturation and integration as a functional tissue. Due to difficulties associated with animal protein-derived scaffolds, including sterility and pro-inflammatory responses, current practices favor the use of synthetic polymers, such as polycaprolactone (PCL), for generating nanofibrous scaffolds. In this study, we tested the hypothesis that plant protein-derived fibrous scaffolds can provide favorable conditions permissive for the maturation of RPE tissue sheets in vitro . Our natural, soy protein-derived nanofibrous scaffolds exhibited a J-shaped stress-strain curve that more closely resembled the mechanical properties of native tissues than PCL with significantly higher hydrophilicity of the natural scaffolds, favoring in vivo implantation. We then demonstrate that iRPE sheets growing on these soy protein scaffolds are equivalent to iRPE monolayers cultured on synthetic PCL nanofibrous scaffolds. Immunohistochemistry demonstrated RPE-like morphology and functionality with appropriate localization of RPE markers RPE65, PMEL17, Ezrin, and ZO1 and with anticipated histotypic polarization of vascular endothelial growth factor and pigment epithelium-derived growth factor as indicated by enzyme-linked immunosorbent assay. Scanning electron microscopy revealed dense microvilli on the cell surface and homogeneous tight junctional contacts between the cells. Finally, comparative transcriptome analysis in conjunction with principal component analysis demonstrated that iRPE on nanofibrous scaffolds, either natural or synthetic, matured more consistently than on nonfibrous substrates. Taken together, our studies suggest that the maturation of cultured iRPE sheets for subsequent clinical applications might benefit from the use of nanofibrous scaffolds generated from natural proteins. Impact statement Induced retinal pigment epithelium (iRPE) from patient-derived induced pluripotent stem cells (iPSCs) may yield powerful treatments of retinal diseases, including age-related macular degeneration. Recent studies, including early human clinical trials, demonstrate the importance of selecting appropriate biomaterial scaffolds to support tissue-engineered iRPE sheets during implantation. Electrospun scaffolds show particular promise due to their similarity to the structure of the native Bruch's membrane. In this study, we describe the use of electroprocessed nanofibrous soy protein scaffolds to generate polarized sheets of human iPSC-derived iRPE sheets. Our evaluation, including RNA-seq transcriptomics, indicates that these scaffolds are viable alternatives to scaffolds electrospun from synthetic polymers.

Adolescents living in low-resource settings lack access to adequate psychological care. The barriers to mental health care in low- and middle-income countries (LMIC) include high disease burden, low allocation of resources, lack of national mental health policy and child and adolescent mental health (CAMH) professionals and services, poverty, illiteracy and poor availability of adolescent friendly health services. WHO has recommended a stepped task shifting approach to mental health care in LMIC. Training of non-mental health specialists like peers, teachers, community health workers, paediatricians and primary care physicians by CAMH and framing country-specific evidence-based national mental health policies are vital in overcoming barriers to psychological care in LMIC. Digital technology and telemedicine can be used in providing economical and accessible mental health care services to adolescents.

Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome. Integration of methylome to age-related transcriptome changes, chromatin signatures, and first-order protein-protein interactions uncover an enrichment of DMRs in altered pathways that are associated with rod function, aging, and energy metabolism. In concordance, we detect reduced basal mitochondrial respiration and increased fatty acid dependency with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies a link between DNA methylation and energy metabolism in aging., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

Purpose: Genes involved in the development and differentiation of the mammalian retina are also associated with inherited retinal dystrophies (IRDs) and age-related macular degeneration. Transcriptional regulation of retinal cell differentiation has been addressed by genetic and transcriptomic studies. Much less is known about the posttranslational regulation of key regulatory proteins, although mutations in some genes involved in ubiquitination and proteostasis-E3 ligases and deubiquitinating enzymes (DUBs)-cause IRDs. This study intends to provide new data on DUB gene expression during different developmental stages of mouse and human fetal retinas., Methods: We performed a comprehensive transcriptomic analysis of all the annotated human and mouse DUBs (87) in the developing mouse retina at several embryonic and postnatal time points compared with the transcriptome of the fetal human retina. An integrated comparison of data from transcriptomics, reported chromatin immunoprecipitation sequencing (ChIP-seq) of CRX and NRL transcription factors, and the phenotypic retinal alterations in different animal models is presented., Results: Several DUB genes are differentially expressed during the development of the mouse and human retinas in relation to proliferation or differentiation stages. Some DUB genes appear to be distinctly expressed during the differentiation stages of rod and cone photoreceptor cells, and their expression is altered in mouse knockout models of relevant photoreceptor transcription factors. We complemented this RNA-sequencing (RNA-seq) analysis with other reported expression and phenotypic data to underscore the involvement of DUBs in cell fate decision and photoreceptor differentiation., Conclusions: The present results highlight a short list of potential DUB candidates for retinal disorders, which require further study., (Copyright © 2019 Molecular Vision.)

Stem cell-derived retinal organoids recapitulate many landmarks of in vivo differentiation but lack functional maturation of distinct cell types, especially photoreceptors. Using comprehensive temporal transcriptome analyses, we show that transcriptome shift from postnatal day 6 (P6) to P10, associated with morphogenesis and synapse formation during mouse retina development, was not evident in organoids, and co-expression clusters with similar patterns included different sets of genes. Furthermore, network analysis identified divergent regulatory dynamics between developing retina in vivo and in organoids, with temporal dysregulation of specific signaling pathways and delayed or reduced expression of genes involved in photoreceptor function(s) and survival. Accordingly, addition of docosahexaenoic acid and fibroblast growth factor 1 to organoid cultures specifically promoted the maturation of photoreceptors, including cones. Our study thus identifies regulatory signals deficient in developing retinal organoids and provides experimental validation by producing a more mature retina in vitro, thereby facilitating investigations in disease modeling and therapies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Retinal organoids generated from human pluripotent stem cells exhibit considerable variability during differentiation. Our goals are to assess developmental maturity of the neural retina in vitro and design improved protocols based on objective criteria., Methods: We performed transcriptome analyses of developing retinal organoids from human embryonic and induced pluripotent stem cell lines and utilized multiple bioinformatic tools for comparative analysis. Immunohistochemistry, immunoblotting and electron microscopy were employed for validation., Results: We show that the developmental variability in organoids was reflected in gene expression profiles and could be evaluated by molecular staging with the human fetal and adult retinal transcriptome data. We also demonstrate that the addition of 9-cis retinal, instead of the widely used all-trans retinoic acid, accelerated rod photoreceptor differentiation in organoid cultures, with higher rhodopsin expression and more mature mitochondrial morphology evident by day 120., Conclusion: Our studies provide an objective transcriptome-based modality for determining the differentiation state of retinal organoids and for comparisons across different stem cell lines and platforms, which should facilitate disease modeling and evaluation of therapies in vitro., (Copyright © 2019 Molecular Vision.)

A widespread platinum (Pt) anomaly was recently documented in Greenland ice and 11 North American sedimentary sequences at the onset of the Younger Dryas (YD) event (~12,800 cal yr BP), consistent with the YD Impact Hypothesis. We report high-resolution analyses of a 1-meter section of a lake core from White Pond, South Carolina, USA. After developing a Bayesian age-depth model that brackets the late Pleistocene through early Holocene, we analyzed and quantified the following: (1) Pt and palladium (Pd) abundance, (2) geochemistry of 58 elements, (3) coprophilous spores, (4) sedimentary organic matter (OC and sedaDNA), (5) stable isotopes of C (δ 13 C) and N (δ 15 N), (6) soot, (7) aciniform carbon, (8) cryptotephra, (9) mercury (Hg), and (10) magnetic susceptibility. We identified large Pt and Pt/Pd anomalies within a 2-cm section dated to the YD onset (12,785 ± 58 cal yr BP). These anomalies precede a decline in coprophilous spores and correlate with an abrupt peak in soot and C/OC ratios, indicative of large-scale regional biomass burning. We also observed a relatively large excursion in δ 15 N values, indicating rapid climatic and environmental/hydrological changes at the YD onset. Our results are consistent with the YD Impact Hypothesis and impact-related environmental and ecological changes.

Reloading of atrophied muscles after hindlimb suspension (HLS) can induce muscle injury and prolong recovery after disuse in old rats, especially in fast contracting muscles. Less is known about the responses in mice and whether fast and slow muscles from geriatric mice will respond in a similar fashion to HLS unloading and recovery (HLS + R). Furthermore, while slow muscles undergo atrophy with disuse, they typically are more resistant to sarcopenia than fast contracting muscles. Geriatric (28 mo. of age) male C57BL/6 mice were randomly placed into 3 groups. These included HLS for 14 days n = 9, and HLS followed by 14 days of reloading recovery (HLS + R; n = 9), or normal ambulatory cage controls (n = 9). Control mice were not exposed to unloading. Electrically evoked maximal muscle function was assessed in vivo in anesthetized mice at baseline, after 14 days of HLS or HLS + R. As expected, HLS significantly reduced body weight, wet weight of gastrocnemius and soleus muscles and in vivo maximal force. There were no differences in vivo fatigability of the plantar flexor muscles and overall fiber size. There were only minor fiber type distribution and frequency distribution of fiber sizes that differ between HLS + R and control gastrocnemius and soleus muscles. Soleus muscle wet weight had recovered to control levels after reloading, but type I/IIA fibers in the soleus muscles were significantly smaller after HLS + R than control muscles. In contrast, gastrocnemius muscle wet weight did not recover to control levels after reloading. Plantar flexion muscle force (primarily influenced by the gastrocnemius muscles) did not recover in HLS + R conditions as compared to HLS conditions and both were lower than control force production signaling for apoptosis, autophagy and anabolic markers were not different between control and HLS + R gastrocnemius and soleus muscles in geriatric mice. These results suggest that molecular signaling does not explain attenuated ability to regain muscle wet weight, fiber size or muscle force production after HLS in geriatric mice. It is possible that fluid shifts, reduced blood flow, or shortened muscle fibers which failed to regain control lengths contributed to the attenuation of muscle wet weight after HLS and reloading and this affected force production. Further work is needed to determine if altered/loss of neural activity contributed to the inability of geriatric mice to regain gastrocnemius muscle weight and function after HLS and reloading., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis type I (MPS I) is caused by deficiency of α-l-iduronidase (IDUA), a lysosomal enzyme involved in the breakdown and recycling of glycosaminoglycans (GAGs). Although enzyme replacement therapy is available, the efficacy of the treatment for neuropathic manifestations is limited. To facilitate drug discovery and model disease pathophysiology, we generated neural stem cells (NSCs) from MPS I patient-derived induced pluripotent stem cells (iPSCs). The NSCs exhibited characteristic disease phenotypes with deficiency of IDUA, accumulation of GAGs and enlargement of lysosomes, in agreement with the severity of clinical subgroups of MPS I. Transcriptome profiling of NSCs revealed 429 genes that demonstrated a more extensive change in expression in the most severe Hurler syndrome subgroup compared to the intermediate Hurler-Scheie or the least severe Scheie syndrome subgroups. Clustering and pathway analysis revealed high concordance of the severity of neurological defects with marked dysregulation of GAG biosynthesis, GAG degradation, lysosomal function and autophagy. Gene ontology (GO) analysis identified a dramatic upregulation of the autophagy pathway, especially in the Hurler syndrome subgroup. We conclude that GAG accumulation in the patient-derived cells disrupts lysosomal homeostasis, affecting multiple related cellular pathways in response to IDUA deficiency. These dysregulated processes likely lead to enhanced autophagy and progressively severe disease states. Our study provides potentially useful targets for clinical biomarker development, disease diagnosis and prognosis, and drug discovery.

Introduction: We detail the process of developing a workload calculation model (WCM) for a highly integrated curriculum delivered by team-based learning, rationale for workload multipliers, and preliminary results of our effort to implement the WCM., Methods: Our WCM includes teaching, service, and scholarship, with a time buffer. The WCM utilizes multipliers for most work activities (teaching and service). For other activities, a fixed number of hours per year was used. The WCM was set up using Microsoft Excel. The development of the WCM was an iterative process in collaboration with the school's Faculty Affairs Committee, each department, and then individually with all faculty members., Results: The WCM had three sections. A section each for teaching and service workload calculations and a dashboard section to summarize workload calculations per department that added in time for scholarship and a buffer calculation (to allow flexibility for faculty). Teaching included classroom, experiential, and academic advising, all of which had unique multipliers. Service included committee work at all levels and student organization advising. A fourth section for time spent at individual faculty practice sites. Calculations were kept consistent between departments for most activities., Conclusion: We developed a novel WCM to accommodate all of the major areas of workload for faculty at a private institution. The unique approach to building it included representing teaching in a highly integrated curriculum delivered via team-based learning and creating a buffer category to allow for workload individualization. The WCM is actively used in our school to proactively manage workload., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAP serine127 , which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.

Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25) reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies., (Published by Elsevier Inc.)

Loeys-Dietz syndrome (LDS) is a recently described genetic connective tissue disorder with a wide spectrum of multisystem involvement. LDS is characterized by rapidly progressive aortic and peripheral arterial aneurysmal disease. LDS and the other inherited aortopathies such as Marfan syndrome have overlapping phenotypic features. However, LDS is characterized by a more aggressive vascular course; patient morbidity and mortality occur at an early age, with complications developing at relatively smaller aortic dimensions. In addition, there is more diffuse arterial involvement in LDS, with a large proportion of patients developing aneurysms of the iliac, mesenteric, and intracranial arteries. Early diagnosis and careful follow-up are essential for ensuring timely intervention in patients with arterial disease. Cross-sectional angiography has an important role in the baseline assessment, follow-up, and evaluation of acute complications of LDS, the thresholds and considerations of which differ from those of other inherited aortopathies. In this article, LDS is compared with other genetic vascular connective tissue disorders. In addition, the genetic, histopathologic, and cardiovascular manifestations of this disease process are reviewed, with a focus on computed tomographic and magnetic resonance imaging findings. Online DICOM image stacks and supplemental material are available for this article. © RSNA, 2018.

Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: A systematic review and meta-analysis, evaluating ischemic conditioning during percutaneous coronary intervention (PCI)., Methods & Results: A database search of randomized trials of ischemic conditioning in PCI created three subgroups for meta-analysis: mortality in elective PCI with remote ischemic preconditioning (RIPreC; subgroup 1a, n = 3) - no outcome difference between RIPreC and control (odds ratio: 0.34; 95% CI: 0.08-1.56), myocardial salvage index in ST-elevation myocardial infarction (STEMI) with RIPreC (subgroup 1b, n = 2) - favored RIPreC (mean difference: 0.13; 95% CI: 0.07-0.19), and infarct size in STEMI with local ischemic postconditioning (LIPostC) (subgroup 4b, n = 12) - favored LIPostC (mean difference: -4.13 g.m -2 ; 95% CI: -7.36 to -0.90 g.m -2 )., Conclusion: RIPreC and LIPostC improve myocardial salvage index and myocardial infarct size respectively in PCI for STEMI. No mortality benefit detected with RIPreC in elective PCI.

Purpose: Transcriptome analysis by next generation sequencing allows qualitative and quantitative profiling of expression patterns associated with development and disease. However, most transcribed sequences do not encode proteins, and little is known about the functional relevance of noncoding (nc) transcriptome in neuronal subtypes. The goal of this study was to perform a comprehensive analysis of long noncoding (lncRNAs) and antisense (asRNAs) RNAs expressed in mouse retinal photoreceptors., Methods: Transcriptomic profiles were generated at six developmental time points from flow-sorted Nrlp-GFP (rods) and Nrlp-GFP;Nrl-/- (S-cone like) mouse photoreceptors. Bioinformatic analysis was performed to identify novel noncoding transcripts and assess their regulation by rod differentiation factor neural retina leucine zipper (NRL). In situ hybridization (ISH) was used for validation and cellular localization., Results: NcRNA profiles demonstrated dynamic yet specific expression signature and coexpression clusters during rod development. In addition to currently annotated 586 lncRNAs and 454 asRNAs, we identified 1037 lncRNAs and 243 asRNAs by de novo assembly. Of these, 119 lncRNAs showed altered expression in the absence of NRL and included NRL binding sites in their promoter/enhancer regions. ISH studies validated the expression of 24 lncRNAs (including 12 previously unannotated) and 4 asRNAs in photoreceptors. Coexpression analysis demonstrated 63 functional modules and 209 significant antisense-gene correlations, allowing us to predict possible role of these lncRNAs in rods., Conclusions: Our studies reveal coregulation of coding and noncoding transcripts in rod photoreceptors by NRL and establish the framework for deciphering the function of ncRNAs during retinal development.

In retinal photoreceptors, vectorial transport of cargo is critical for transduction of visual signals, and defects in intracellular trafficking can lead to photoreceptor degeneration and vision impairment. Molecular signatures associated with routing of transport vesicles in photoreceptors are poorly understood. We previously reported the identification of a novel rod photoreceptor specific isoform of Receptor Expression Enhancing Protein (REEP) 6, which belongs to a family of proteins involved in intracellular transport of receptors to the plasma membrane. Here we show that loss of REEP6 in mice (Reep6-/-) results in progressive retinal degeneration. Rod photoreceptor dysfunction is observed in Reep6-/- mice as early as one month of age and associated with aberrant accumulation of vacuole-like structures at the apical inner segment and reduction in selected rod phototransduction proteins. We demonstrate that REEP6 is detected in a subset of Clathrin-coated vesicles and interacts with the t-SNARE, Syntaxin3. In concordance with the rod degeneration phenotype in Reep6-/- mice, whole exome sequencing identified homozygous REEP6-E75K mutation in two retinitis pigmentosa families of different ethnicities. Our studies suggest a critical function of REEP6 in trafficking of cargo via a subset of Clathrin-coated vesicles to selected membrane sites in retinal rod photoreceptors., (© The Author 2017. Published by Oxford University Press.)

Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.). In order to evaluate its geographic extent, fire-assay and inductively coupled plasma mass spectrometry (FA and ICP-MS) elemental analyses were performed on 11 widely separated archaeological bulk sedimentary sequences. We document discovery of a distinct Pt anomaly spread widely across North America and dating to the Younger Dryas (YD) onset. The apparent synchroneity of this widespread YDB Pt anomaly is consistent with Greenland Ice Sheet Project 2 (GISP2) data that indicated atmospheric input of platinum-rich dust. We expect the Pt anomaly to serve as a widely-distributed time marker horizon (datum) for identification and correlation of the onset of the YD climatic episode at 12,800 Cal B.P. This Pt datum will facilitate the dating and correlating of archaeological, paleontological, and paleoenvironmental data between sequences, especially those with limited age control.

Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we compared NIH3T3 cells expressing wildtype (WT) rod opsin with a retinal disease-causing single P23H mutation. Surprisingly, heterologous expression of WT opsin in NIH3T3 cells caused more than a 2-fold change in 783 out of 16,888 protein coding transcripts. The perturbed genes encoded extracellular matrix proteins, growth factors, cytoskeleton proteins, glycoproteins and metalloproteases involved in cell adhesion, morphology and migration. A different set of 347 transcripts was either up- or down-regulated when the P23H mutant opsin was expressed suggesting an altered molecular perturbation compared to WT opsin. Transcriptome perturbations elicited by drug candidates aimed at mitigating the effects of the mutant protein revealed that different drugs targeted distinct molecular pathways that resulted in a similar phenotype selected by a cell-based high-throughput screen. Thus, transcriptome profiling can provide essential information about the therapeutic potential of a candidate drug to restore normal gene expression in pathological conditions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: When school districts choose not to participate in adolescent health behavior surveys, tracking adolescent health indicators can be challenging. We conducted a countywide youth behavior survey outside of the school system. Our purpose is to describe alternative methods used for gathering these data reliably and ethically., Methods: We implemented two parallel surveys with youth ages 14-19 residing in a mid-sized county with urban, suburban, and rural neighborhoods. An anonymous phone-based survey used computer-assisted telephone interviewing with a live interviewer in conjunction with an interactive voice response system to survey youth via random digit dialing of landlines and cell phones. A concurrent in-person anonymous survey was conducted with marginalized youth (from juvenile detention centers, shelters, and residential facilities), using audio computer-assisted self-interviewing technology. The survey measures included the Centers for Disease Control Youth Risk Behavior Surveillance System and additional questions about social supports, neighborhood, and adverse childhood experiences., Results: Data were collected between February and December 2014. The phone-based sample recruited 1813 participants; the marginalized sample included 262 youth. Several strategies ensured anonymity and reduced coercion. The final phone-based sample was similar to demographics of the county population. The marginalized youth sample captured out-of-home youth who may have been missed with phone-based sampling alone., Conclusions: We review alternative strategies for obtaining population-based adolescent health data without the cooperation of schools. These techniques can provide a basis to collect data that may help direct resources and policies relevant to needs of local youth., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene expression patterns. De novo assembly and alternative splicing analyses revealed previously unannotated rod-enriched transcripts and the role of NRL in transcript maturation. Furthermore, we defined the relationship of NRL with other transcriptional regulators and downstream cognate effectors. Our studies provide the framework for comprehensive system-level analysis of the GRN underlying the development of a single sensory neuron, the rod photoreceptor., (Published by Elsevier Inc.)

Background: Hopefulness has been associated with increased treatment retention and reduced substance abuse among adults, and may be a promising modifiable factor to leverage in substance abuse treatment settings. Few studies have assessed the relationship between hopefulness and substance use in adolescents, particularly those with high-risk backgrounds., Objective: We explored whether high hope is associated with less likelihood for engaging in a variety of substance use behaviors in a sample of marginalized adolescents., Methods: Using logistic regression, we assessed results from a cross-sectional anonymous youth behavior survey (n = 256 youth, ages 14 to 19). We recruited from local youth serving agencies (e.g., homeless shelters, group homes, short-term detention)., Results: The sample was almost 60% male and two thirds African American. Unadjusted models showed youth with higher hope had a 50-58% (p = <.05) decreased odds of endorsing heavy episodic drinking, daily tobacco use, recent or lifetime marijuana use, and sex after using substances. Adjusted models showed a 52% decreased odds of lifetime marijuana use with higher hope, and a trend towards less sex after substance use (AOR 0.481; p = 0.065). No other substance use behaviors remained significantly associated with higher hope scores in adjusted models., Conclusions/importance: Hopefulness may contribute to decreased likelihood of substance use in adolescents. Focusing on hope may be one modifiable target in a comprehensive primary or secondary substance use prevention program.