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Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11-MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat-Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11-MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11-MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half-lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide-3-kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11-MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11-MIF mRNA is regulated by CCCTC-binding factor and stabilized through RNA N4-acetylcytidine modification facilitated by N-acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11-MIF-PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.
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Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets.
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Análisis de Secuencia de ARN , Programas Informáticos , Análisis de Secuencia de ARN/métodos , Humanos , ARN/genética , Biología Computacional/métodos , Exones , Algoritmos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Callous-unemotional (CU) traits are characterized by low empathy, guilt, and prosociality, putting children at risk for lifespan antisocial behavior. Elevated CU traits have been linked separately to difficulties with emotion understanding (i.e., identifying emotional states of others) and disrupted parasympathetic nervous system (PNS) functioning. However, no study has investigated how PNS functioning and emotion understanding are jointly related to CU traits. METHOD: We explored associations between CU traits, emotion understanding, and PNS functioning (indexed via respiratory sinus arrhythmia [RSA]) among children aged 7-10 years old (n = 55). We also tested whether deficits in emotion understanding differ across specific emotions (i.e., fear, pain, happiness, anger). Each child's RSA was continuously recorded while they watched a film that included emotionally evocative social interactions. To assess emotion understanding, children identified emotions replayed in 1s animations of scenes from the film. Parents reported on child CU traits, conduct problems, and demographic information. RESULTS: Higher CU traits were related to lower emotion understanding (ß = -0.43, p = 0.03). PNS activity during the film moderated this association (ß = -0.47, p < 0.001), such that CU traits were associated with lower emotion understanding among children with mean (B = -0.01, t = -2.46, p = 0.02) or high (i.e., 1 SD > M; B = -0.02, t = -3.00, p < 0.001) RSA levels during the film, but not among children with low RSA levels (i.e., 1 SD < M; B = 0.00, t = -0.53, p = 0.60). Moreover, we found that the observed moderated associations are driven by deficits in fear, specifically. CONCLUSIONS: The link between poorer emotion understanding, fear understanding in particular, and CU traits was attenuated for children who demonstrated patterns of PNS functioning consistent with attentional engagement while viewing the emotion stimuli.
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PURPOSE: Ultramarathon running has gained popularity over several decades. Although there has been considerable research on training for other running events, from the 100-m to the marathon at 26.2 miles (42.2 km), there is little evidence on best practices for ultramarathons, where distances potentially exceed 100 miles (160.9 km). METHODS: In this case study, we examine the training regimen of an elite ultramarathon runner who broke 8 world records in 2021 and 2022, including the 24-hour run in which he ran 319.6 km in September 2022. Training data from December 28, 2020, to September 17, 2022, were collected from the Strava application database (recorded on Coros watch) and analyzed using Microsoft Excel and Tableau. RESULTS: Our subject completed 5 training blocks, with volume per training block averaging 172.1 to 263 km/wk. Peak running volume per training block occurred on average 3.2 weeks out from races and reached a maximum of 378 km/wk. Recovery was emphasized the week following a race, with less running (19 km/wk) and more cross-training. Interval-type workouts (1- to 10-km repeats) were completed throughout training blocks. The average pace during the 24-hour world-record run was 4 minutes and 30 seconds per kilometer (4:30/km), closely matching the overall average training pace. CONCLUSIONS: These findings suggest that training for ultramarathon races should include high-volume running at varied paces and intensity with cross-training to avoid injuries. We hope that this evidence helps athletes understand how to prepare for these ultraendurance events.
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Resistencia Física , Carrera , Masculino , Humanos , Carrera de Maratón , AtletasRESUMEN
Wheelchair users face an elevated risk of metabolic syndromes due to their sedentary lifestyles. One of the methods to prevent and treat various metabolic syndromes is regular physical activity, which varies among individuals based on their abilities. Monitoring physical activity among them can be performed by using wearable physical activity monitors (WPAMs), which utilize accelerometers and algorithms to track wheelchair push counts. However, the accuracy of push count detection varies among the devices due to technological limitations. The objective of this literature review was to evaluate the accuracy of WPAMs, specifically smartwatches, in measuring physical activity in the wheelchair population. This systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in November 2022 for relevant articles. The initial search yielded 447 articles, seven of which were selected based on the inclusion criteria, which were as follows: participant ability to maneuver a wheelchair, arm- or wrist-worn WPAMs, and articles published after 2017. Among the devices studied, the Apple Watch was determined to be the most accurate calibration system for wheelchair users, with the lowest mean absolute percentage error (MAPE). Each succeeding generation of the Apple Watch (first to fourth) studied was more accurate than the previous. The review demonstrates that research on wheelchair fitness tracking remains scarce and further studies are required to address this issue.
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INTRODUCTION: Children with callous-unemotional (CU) traits are at high lifetime risk of antisocial behaviour. Low affiliation (ie, social bonding difficulties) and fearlessness (ie, low threat sensitivity) are proposed risk factors for CU traits. Parenting practices (eg, harshness and low warmth) also predict risk for CU traits. However, few studies in early childhood have identified attentional or physiological markers of low affiliation and fearlessness. Moreover, no studies have tested whether parenting practices are underpinned by low affiliation or fearlessness shared by parents, which could further shape parent-child interactions and exacerbate risk for CU traits. Addressing these questions will inform knowledge of how CU traits develop and isolate novel parent and child targets for future specialised treatments for CU traits. METHODS AND ANALYSIS: The Promoting Empathy and Affiliation in Relationships (PEAR) study aims to establish risk factors for CU traits in children aged 3-6 years. The PEAR study will recruit 500 parent-child dyads from two metropolitan areas of the USA. Parents and children will complete questionnaires, computer tasks and observational assessments, alongside collection of eye-tracking and physiological data, when children are aged 3-4 (time 1) and 5-6 (time 2) years. The moderating roles of child sex, race and ethnicity, family and neighbourhood disadvantage, and parental psychopathology will also be assessed. Study aims will be addressed using structural equation modelling, which will allow for flexible characterisation of low affiliation, fearlessness and parenting practices as risk factors for CU traits across multiple domains. ETHICS AND DISSEMINATION: Ethical approval was granted by Boston University (#6158E) and the University of Pennsylvania (#850638). Results will be disseminated through conferences and open-access publications. All study and task materials will be made freely available on lab websites and through the Open Science Framework (OSF).
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Trastorno de la Conducta , Empatía , Preescolar , Humanos , Trastorno de Personalidad Antisocial/etiología , Trastorno de Personalidad Antisocial/psicología , Trastorno de la Conducta/complicaciones , Trastorno de la Conducta/psicología , Emociones/fisiología , Estudios Longitudinales , Responsabilidad Parental/psicología , Masculino , FemeninoRESUMEN
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab's identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.
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Proteínas de Microfilamentos , Rabdomiosarcoma , Niño , Humanos , Proteínas de Microfilamentos/genética , Rabdomiosarcoma/genética , Citoesqueleto , Agresión , Transformación Celular Neoplásica , FeniraminaRESUMEN
This study explored how patterns of physiological stress reactivity underpin individual differences in sensitivity to early rearing experiences and childhood risk for psychopathology. To examine individual differences in parasympathetic functioning, past research has largely relied on static measures of stress reactivity (i.e., residual and change scores) in infancy which may not adequately capture the dynamic nature of regulation across contexts. Using data from a prospective longitudinal study of 206 children (56% African Americans) and their families, this study addressed these gaps by employing the latent basis growth curve model to characterize the dynamic, non-linear patterns of change in infants' respiratory sinus arrhythmia (i.e., vagal flexibility) across the Face-to-Face Still-Face Paradigm. Furthermore, it investigated whether and how infants' vagal flexibility moderates the links between sensitive parenting, observed during a free play task when children were 6 months of age, and parent-report of children's externalizing problems at 7 years of age. Results of the structural equation models revealed that infants' vagal flexibility moderates the predictive relations between sensitive parenting in infancy and children's later externalizing problems. Simple slope analyses revealed that low vagal flexibility, characterized by less suppression and flatter recovery patterns, exacerbated risk for externalizing psychopathology in the context of insensitive parenting. Children with low vagal flexibility also benefited most from sensitive parenting, as indicated by the lower number of externalizing problems. Findings are interpreted in the light of the biological sensitivity to context model and provide evidence for vagal flexibility as a biomarker of individual's sensitivity to early rearing contexts.
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Responsabilidad Parental , Problema de Conducta , Humanos , Niño , Lactante , Estudios Longitudinales , Estudios Prospectivos , Nervio VagoRESUMEN
The COVID-19 pandemic has had worldwide impacts, including disrupting community services. One interrupted service was syringe service programs (SSPs), community-established initiatives that provide sterile supplies and aid in overcoming addiction in drug-using participants. In the United States (U.S.), SSPs have been key in combating the recent opioid use crisis and associated infections such as the human immunodeficiency virus (HIV) and hepatitis C. While some published reports on the pandemic's overall impacts on SSPs exist, certain aspects such as operational changes and repercussions on staff and participants may still be lacking. Information about the impact of interrupted SSP services due to the pandemic may provide insight into how to prepare to mitigate similar outcomes during possible future health outbreaks. The aim of this scoping review was thus to explore the effects of the COVID-19 pandemic on the operations, staff, and participants of SSPs in the U.S. The initial search of the databases PubMed, Embase, and Web of Science with selected keywords yielded 117 articles published in English between January 1, 2020, and August 31, 2022. After screening each article for study eligibility, 11 articles were included in the final review. Of the seven articles exploring SSP operational impacts from the pandemic, five acknowledged that mitigation strategies influenced functions, seven highlighted supply changes, and four emphasized the resulting staffing changes. Four studies inspected the pandemic's impacts on SSP participants, which included two articles highlighting participants' struggles with isolation and loneliness, one referencing the fear of exposure to the SARS-CoV-2 virus, and two examining the overall negative psychological effects experienced during this time. SSPs in various settings and regions across the U.S. experienced changes due to the COVID-19 pandemic. Many of these modifications negatively impacted operations, staffing, and participant relationships. Examining the issues that individual SSPs encountered highlights opportunities for structured solutions for the present and in the case of future infectious disease outbreaks. With the severity of the opioid use crisis in the U.S. and the dependence on SSPs for its mitigation, future work in this space should be prioritized.
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BACKGROUND: Hormonal contraceptives are a popular option for pregnancy prevention and other indications and require a prescription. Since 2013, 24 states have given pharmacists legal authority to initiate self-administered hormonal contraceptives, allowing for direct pharmacy access (DPA). New York State (NYS) did not allow for DPA of any hormonal contraceptives during the survey period, but passed a bill in 2023 allowing pharmacists to dispense hormonal contraceptives in accordance with a nonpatient-specific order. OBJECTIVES: This study aimed to characterize the experiences, perceptions, and knowledge of access to and DPA to hormonal contraceptives. METHODS: A survey was developed to gather responses to demographic- and opinion-related questions and administered online using the Pollfish survey platform. Participants were women between the ages of 16 and 44 years who lived in NYS. To ensure geographic representation, at least one response was gathered from each of the 27 NYS congressional districts. Chi-square tests were used to assess differences in hormonal contraceptive use by patient demographics. RESULTS: Most of the 500 respondents reported past (76.2%) or current/planned (76.8%) use of hormonal contraceptives. Older age (P = 0.033) and higher income (P = 0.0016) were associated with significantly greater rates of use. The most common challenges when visiting a provider for birth control included needing to schedule an appointment and wait times at the provider. Almost three-quarters of respondents (72.6%) were not aware that pharmacists could initiate contraceptives in other states, and 74.2% reported feeling comfortable with a pharmacist prescribing and dispensing hormonal contraceptives. CONCLUSION: Contraceptive initiation by pharmacists would be acceptable to most respondents, but there is room for increased acceptance based on patient education and experience. DPA to hormonal contraceptives may eliminate some of the barriers identified in this survey.
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Anticonceptivos , Farmacia , Embarazo , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Masculino , Farmacéuticos , New York , Anticoncepción , Anticonceptivos Hormonales OralesRESUMEN
Read-through chimeric RNAs are gaining attention in cancer and other research fields, yet current tools often fail in predicting them. We have thus developed the first read-through chimeric RNA specific prediction method, RTCpredictor, utilizing a fast ripgrep algorithm to search for all possible exon-exon combinations of parental gene pairs. Compared with other ten popular tools, RTCpredictor achieved top performance on both simulated and real datasets. We randomly selected up to 30 candidate read-through chimeras predicted from each software method and experimentally validated a total of 109 read-throughs and on this set, RTCpredictor outperformed all the other methods. In addition, RTCpredictor ( https://github.com/sandybioteck/RTCpredictor ) has less memory requirements and faster execution time.
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The serious nature of post-vaccination anaphylaxis requires healthcare professionals to be adequately trained to respond to these hypersensitivity emergencies. The aim of this study was to compare outcomes reported with cases of vaccine anaphylaxis stratified by administration setting. We queried reports in the Vaccine Adverse Event Reporting System (VAERS) database from 2017 to 2022 and identified cases involving anaphylaxis with an onset within one day of vaccine administration. The primary outcome was the combined prevalence of death or disability for each setting while the secondary outcome was the prevalence of hospitalization. Adjusted (age, sex, prior history of allergy, vaccine type) odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated using logistic regression analysis. A total of 2041 cases of anaphylaxis comprised the primary study cohort with representation in the sample from all 50 US states and the District of Columbia. The mean age was 43.3 ± 17.5 years, and most cases involved women (79.9%). Cases of anaphylaxis were reported after receiving a coronavirus vaccine (85.2%), influenza vaccine (5.9%), tetanus vaccine (2.2%), zoster vaccine (1.6%), measles vaccine (0.7%), and other vaccine (4.5%). Outcomes associated with reports of vaccine anaphylaxis included 35 cases of death and disability and 219 hospitalizations. Compared with all other settings, the aOR of death and disability when anaphylaxis occurred was 1.92 (95% CI, 0.86-4.54) in a medical provider's office, 0.85 (95% CI, 0.26-2.43) in a pharmacy and 1.01 (95% CI, 0.15-3.94) in a public health clinic. Compared with all other settings, the aOR of hospitalization when anaphylaxis occurred was 1.02 (95% CI, 0.71-1.47) in a medical provider's office, 1.06 (95% CI, 0.72-1.54) in a pharmacy, and 1.12 (95% CI, 0.61-1.93) in a public health clinic. An analysis of a national database across six years revealed no significant differences in the odds of death/disability and odds of hospitalization associated with post-vaccination anaphylaxis in the medical office, pharmacy, and public health clinic compared with all other settings. This study expands our understanding of the safety of immunization services and reinforces that all settings must be prepared to respond to such an emergency.
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BACKGROUND: Several states have passed legislation allowing pharmacists to prescribe hormonal contraceptives in an effort to expand access to family planning options for patients. OBJECTIVE: The primary objective of this research is to evaluate participant knowledge and perception, attitudes, and preparedness regarding pharmacist-prescribed hormonal contraception before and after completion of the American Pharmacists Association's interactive online training program, "Increasing Access to Hormonal Contraceptive Products: A Training Program for Pharmacists." METHODS: Training program participants were assessed on their knowledge after each module, and they were invited to participate in a pre- and postsurvey about practice environments and opinions related to hormonal contraceptive prescribing. Descriptive statistics were calculated for categorical survey responses, and means and standard deviations were calculated for program knowledge assessment scores. Pre- and postsurvey responses were analyzed using the Wilcoxon signed-rank test or McNemar's test according to the type of response options. RESULTS: More than 450 participants completed the Hormonal Contraception Training Program; 61% completed the presurvey and 39% completed the postsurvey. Participants had an average score of 86% across modules for both surveys. Comfort level increased statistically significantly in all areas surveyed after program completion. Survey results identified statistically significant changes between pre- and postsurvey in the belief that pharmacists are trained and educated to counsel on and initiate hormonal contraceptives (P < 0.001 and P < 0.001) and that prescribing hormonal contraceptives should be within a pharmacist's scope of practice (P < 0.001). Most respondents (83%) agreed that pharmacy schools should expand content on contraceptive prescribing, although more than half (56%) reported that their pharmacy school taught them the requisite hormonal contraceptive clinical content. CONCLUSION: Training programs play an important role in preparing pharmacists for prescribing roles by providing knowledge and increasing confidence and generally positively affecting perceptions of and attitudes toward prescribing hormonal contraceptives.
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Anticonceptivos , Farmacéuticos , Anticoncepción Hormonal , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Although research suggests that callous-unemotional (CU) traits are underpinned by deficits in social affiliation and reduced sensitivity to threat, there has been little investigation of the biophysiological regulatory mechanisms underlying these processes in infancy. The current study uses data from the Durham Child Health and Development Study (DCHD; n = 206) to examine whether and how the combination of infants' behavioral reactivity and levels of respiratory sinus arrhythmia (RSA), an indicator of parasympathetic nervous system functioning, during the still-face episode of the still-face paradigm at 6 months differentiates risk for CU traits and oppositional defiant behaviors (ODD) at age 3 years, as well as whether these relations vary by children's attachment security. Results indicate that reduced negative affect during the still-face episode at 6 months predicts higher CU traits (B = -0.28, ß = -0.27, p = 0.003) and ODD (B = -0.35, ß = -0.24, p = 0.007) at 3 years. Results also show that comparatively lower RSA, i.e. engaged parasympathetic system, predicts higher CU traits (B = -0.10, ß = -0.34, p = 0.013), but not ODD. Tests of moderation suggest the combination of blunted negative affect but comparatively lower RSA levels during a social stressor constitutes risk for later CU traits for children who are also insecurely attached (simple slope = -0.70, t = 2.88, p = 0.006 at -1 SD). Findings contribute to our understanding of the complex and interactive risk processes which precede the development of CU traits.
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Trastorno de la Conducta , Arritmia Sinusal Respiratoria , Niño , Preescolar , Trastorno de la Conducta/psicología , Emociones , Cara , Humanos , Lactante , Sistema Nervioso ParasimpáticoRESUMEN
OBJECTIVE: To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. DATA SOURCES: Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. STUDY SELECTION/DATA EXTRACTION: Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. DATA SYNTHESIS: Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. CONCLUSIONS: Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.
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Leiomioma , Menorragia , Preparaciones Farmacéuticas , Neoplasias Uterinas , Femenino , Hormona Liberadora de Gonadotropina , Humanos , Leiomioma/complicaciones , Leiomioma/tratamiento farmacológico , Menorragia/tratamiento farmacológico , Menorragia/etiología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/tratamiento farmacológicoRESUMEN
Glioblastoma (GBM) is the most common adult neural malignancy and the deadliest. The standard of care is optimal, safe, cytoreductive surgery followed by combined radiation therapy and alkylating chemotherapy with temozolomide. Recurrence is common and therapeutic options in the recurrent setting are limited. The dismal prognosis of GBM has led to novel treatments being a serious roadblock in the field, with most new treatments failing to show efficacy. Targeted therapies have shown some success in many cancers, but GBM remains one of the most difficult to treat, especially in recurrence. New chemotherapeutic directions need to be explored, possibly expanding the targeted chemotherapy spectrum in previously unforeseen ways. In this perspective paper, we will explain why AVIL, an actin-binding protein recently found to be overexpressed in GBM and a driving force for GBM, could prove versatile in the fight against cancer. By looking at AVIL and its potential to regulate FOXM1 and LIN28B, we will be able to highlight a way to improve outcomes for GBM patients who normally have very little hope.
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Citoesqueleto/metabolismo , Glioblastoma/metabolismo , Proteínas de Microfilamentos/antagonistas & inhibidores , Proteína Forkhead Box M1 , Glioblastoma/tratamiento farmacológico , Humanos , Proteínas de Microfilamentos/metabolismo , Proteínas de Unión al ARNRESUMEN
Functioning of the parasympathetic nervous system (PNS), most often indexed by respiratory sinus arrhythmia (RSA), influences the volitional, cognitively-mediated forms of self-regulation across development. However, despite its clear relevance to children's self-regulation, and its utility as a transdiagnostic biomarker of emotion dysregulation and psychopathology, the ontogeny of vagal tone under conditions of homeostasis across infancy and early childhood is not well understood. The current research is comprised of two complementary studies. The first aims to address this gap by conducting a systematic review of the literature which has assessed resting RSA in the first three years of life. The second study uses data from two diverse, longitudinal datasets (n = 203 and n = 370) to model change in RSA from infancy to toddlerhood. Results from a systematic review of 62 studies meeting inclusion criteria suggest that measures of resting RSA increase over time and demonstrate moderate stability across infancy, toddlerhood, and preschool ages. Results from a series of models fit to longitudinal data in study two suggest that baseline RSA is characterized by stable increases across infancy and early childhood. Moreover, although there was equivocal evidence for individual variability in trajectories of RSA, the findings suggest that the individual differences in resting RSA may become entrenched in early life based on observed significant variance in growth model intercepts. In all, the current study contributes to our understanding of the developmental trajectories of baseline RSA across infancy and early childhood and should support future research examining links between children's parasympathetic regulation and their adjustment in early life.
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Arritmia Sinusal Respiratoria , Niño , Preescolar , Emociones , Humanos , Estudios Longitudinales , Sistema Nervioso Parasimpático , Nervio VagoRESUMEN
MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine whether MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.
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Proteínas Musculares , Músculo Esquelético , Proteómica , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Animales , Humanos , Ratones , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas Musculares/genética , Proteínas de Motivos Tripartitos/genéticaAsunto(s)
Ácido Cítrico/farmacología , Anticoncepción , Ácido Láctico/farmacología , Tartratos/farmacología , Anticoncepción/economía , Anticoncepción/métodos , Anticonceptivos/farmacología , Efectividad Anticonceptiva , Combinación de Medicamentos , Femenino , Humanos , Resultado del Tratamiento , Cremas, Espumas y Geles Vaginales/farmacologíaRESUMEN
Most research examining the impact of early parental depression on the developing child has focused on the nature of parenting practices observed in depressed adults. Maternal elaborative reminiscing, or the extent to which mothers elaboratively discuss past shared experiences with their children, has a considerable influence on children's emotional and social development and is understudied within the context of maternal depression. The current study is the first to examine whether maternal elaborative reminiscing in middle childhood mediates the association between exposure to maternal depressive symptoms in infancy and later internalizing and externalizing problems. The study included 206 mother-child dyads recruited from the community who participated in a prospective longitudinal study. Maternal depressive symptoms were assessed when offspring were 6-months old. At 5-years old, dyads were observed during a free play task to measure sensitive and harsh-intrusive parenting and during a reminiscing task to measure maternal elaboration. Teacher-reported internalizing and externalizing problems were collected at age 7. A saturated path model revealed that maternal elaborative reminiscing, but not sensitive or harsh-intrusive parenting, fully mediated the association between maternal depression in infancy and externalizing, but not internalizing, problems. Reduced maternal elaboration during parent-child reminiscing constitutes one way in which risk from early maternal depression is associated with later externalizing problems.