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A study was developed for a limb-different accessible video game controller that utilizes an electromyographic sensor to control gameplay actions. Data was collected from 50 college-aged student participants. This biofeedback-based serious game trains users in a virtual capacity, through the visualization of muscle contraction, via the movement of the video game character. The training platform has been developed to accompany the corresponding electromyographic actuated prosthetic arm device, leveraging the same control scheme to enable the translation of hand gesture states. This study evaluated the controller, user interface, and gameplay to identify training improvement outcomes and user satisfaction. Study participants were divided into two cohorts that differed in their intervention between the pre-test and post-test challenge course. Cohort one had a free play environment that encouraged learning through algorithmically generated track patterns and the use of powerups. In contrast, cohort two repeated the challenge mode, which was made up of a course of rings to jump through and focused on targeted muscle discretization via character jump heights correlated to muscle output. Data were collected to develop and validate training methods and identify overall game satisfaction and usability. The results of this study indicated an increase in the user's ability to be successful based on time on task with the intervention. The study also evaluated the usability and participant experience with the intervention.
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Miembros Artificiales , Juegos de Video , Humanos , Adulto Joven , Brazo , Extremidad Superior , Movimiento/fisiologíaRESUMEN
ISSUE ADDRESSED: Philippine contact centres are rife with factors that contribute to work-related stress; health promotion strategies are needed to mitigate the impacts. With a transactional framework with the environment, this study examined the relationship of stress with resilience and the presence of urban green spaces (UGS) in the environment, while accounting for individual characteristics (ie, age, household income, exercise frequency). METHODS: Participants include employees (Stage 1 N = 186; Stage 2 N = 89) from six contact centres in the capital region of the Philippines. A two-stage online survey included standardised instruments to measure stress (10-item Perceived Stress Scale) and resilience (Connor-Davidson Resilience Scale), customised questions to gather demographic information and probe on participants' insights. Google Earth Pro was used for satellite mapping of UGS, followed by on-site ocular inspection. RESULTS: Participants' average stress level was categorised as high; primary stressors included client demands and workload. The objectively measured percentages of UGS in the study sites' vicinity were categorised as low. Participants found UGS visible after careful observation, and majority were aware of UGS in their workplace vicinity. Resilience, household income and awareness of UGS in the vicinity significantly predicted stress levels. CONCLUSION: Contact centre workers experienced high stress levels and their workplaces had little accessible UGS. Resilience, household income and awareness of UGS are significant contributors to stress levels. SO WHAT?: Health promotion in Philippine contact centres could consider strategies that include building resilience, enhancing income security and promoting the awareness of UGS within the workplace vicinity.
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Parques Recreativos , Lugar de Trabajo , Humanos , Filipinas , Encuestas y CuestionariosRESUMEN
BACKGROUND AND OBJECTIVE: Addressing adverse social determinants of health is an upstream approach to potentially improve child health outcomes and health equity. We aimed to determine if systematically screening and referring for social needs in hospitalized pediatric patients increased families' enrollment in publicly available resources. METHODS: Randomized controlled trial at a large urban children's hospital enrolled English-speaking caregivers of patients 0 to 36 months of age on the general pediatrics service from June 2016 to July 2017. The intervention arm received the WE CARE Houston social needs intervention (screener and resource referrals based on screening results and receptiveness to help); the control arm received standard of care. Baseline social risk data were collected for all participants. Caregivers who screened positive for mental health need, substance abuse, or domestic violence received additional support, including from social workers. The primary outcome was enrollment in resources at 6 months postdischarge. Univariate and multivariable analysis was performed to identify associations. RESULTS: Our study sample consisted of 413 caregivers from diverse sociodemographic/socioeconomic backgrounds. Overall, 85% of study participants had ≥1 social risk (median 2, range 0-9). WE CARE Houston identified caregiver employment, health insurance, primary care physician, depression, childcare, smoking, and food resources as the most prevalent social needs. Among these, caregivers were most receptive to resources for childcare, mental health, health insurance, and primary care. There was no significant difference in enrollment in new resources by study arm. CONCLUSION: Screening for social needs in the hospital is feasible and can result in the identification of social needs, but further work is needed to successfully address these needs.
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Cuidados Posteriores , Tamizaje Masivo , Niño , Humanos , Alta del Paciente , Fumar , Cuidadores/psicologíaRESUMEN
Background: Advertising of traditional alcopops contains elements that appeal to youth, especially females. Supersized alcopops are marketed differently than traditional alcopops and contain up to 5.5 standard alcoholic drinks. Young females are more likely to underestimate the alcohol content of supersized alcopops, putting them at higher risk of overconsumption. Similar to supersized alcopops, beer is packaged in large cans and in the same areas of store shelves.Objective: This study examined among young people whether supersized alcopops versus beer products disproportionately appealed to females.Methods: Eleven adolescents (13-17 years old) and 72 college students (21-26 years old) were recruited during 2019-2020. Participants viewed 19 photos of convenience store display cases containing both supersized alcopop and beer products. While viewing each image, participants were instructed to click on the beverage that looked the "coolest" (i.e. most appealing). Eye-tracking hardware and software measured the amount of time participants visually fixated on each product. Participants completed a survey to record demographic characteristics.Results: Compared to males (n=25), females (n=58) fixated on supersized alcopops for 6.8 seconds longer (95%CI 0.3,13.3). Females also had 3.7 times the odds of selecting a supersized alcopop as the product they found most appealing compared to males (95%CI 1.68,8.01), adjusting for amount of time visually fixating on supersized alcopops, which was also a significant predictor.Conclusions: Young females' strong preference for supersized alcopops is concerning given they disproportionately underestimate their potency, relative to males, and are more likely to obtain dangerously high BAC levels from consuming one or two supersized alcopops.
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Tecnología de Seguimiento Ocular , Humanos , Adolescente , Adulto Joven , AdultoRESUMEN
In May 2020, Baltimore City, Maryland, implemented the Lord Baltimore Triage, Respite, and Isolation Center (LBTC), a multiagency COVID-19 isolation and quarantine site tailored for people experiencing homelessness. In the first year, 2020 individuals were served, 78% completed isolation at LBTC, and 6% were transferred to a hospital. Successful isolation can mitigate outbreaks in shelters and residential recovery programs, and planning for sustainable isolation services integrated within these settings is critical as the COVID-19 pandemic continues. (Am J Public Health. 2022;112(6):876-880. https://doi.org/10.2105/AJPH.2022.306778).
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COVID-19 , Baltimore/epidemiología , COVID-19/epidemiología , Humanos , Pandemias/prevención & control , Cuarentena , SARS-CoV-2RESUMEN
BACKGROUND AND OBJECTIVES: Unique ethical, epidemiological, and economic factors are barriers to performing research in children. The landscape of pediatric clinical trials, including drivers of completion and timely dissemination of results, is not well understood. We aimed to characterize the prevalence of and factors associated with early discontinuation, results reporting, and publication of pediatric clinical trials registered at ClinicalTrials.gov. METHODS: Cross-sectional analysis of clinical trials enrolling participants <18 years old registered at ClinicalTrials.gov from October 2007 to March 2020. Multivariable logistic regressions were performed to assess the association between trial characteristics and primary outcomes. Publication data were obtained through PubMed, ClinicalTrials.gov, Embase, and Scopus. RESULTS: Overall, 11.1% trials were stopped early, with recruitment failure being the predominant reason for discontinuation. Only 23.5% of completed trials reported results, and 38.8% were published within 3 years of completion. Rates of discontinuation and publication significantly improved over the study period. Among funding sources, government-sponsored trials (adjusted odds ratio [aOR], 0.72; 95% CI, 0.47-0.97) and academic trials (aOR, 0.64; 95% CI, 0.50-0.82) had lower odds of discontinuation compared with industry trials and were more likely to be published (government: aOR, 1.94 [95% CI, 1.52-2.48] academic: aOR, 1.61 [95% CI, 1.35-1.92). Academic trial investigators were the least likely to report results (aOR, 0.34; 95% CI, 0.31-0.52). CONCLUSIONS: Early discontinuation and nonreporting/nonpublication of findings remain common in registered pediatric clinical trials and were associated with funding source and other trial features. Targeted efforts are needed to support trial completion and timely results dissemination toward strengthening evidence-based pediatric medicine.
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Bibliometría , Edición , Adolescente , Niño , Estudios Transversales , Humanos , Modelos Logísticos , Oportunidad RelativaRESUMEN
OBJECTIVE: Dermatologic complaints are common in outpatient pediatrics. However, pediatric dermatology specialty care can be difficult to access. We aimed to test the feasibility of co-locating dermatology services within primary care and increase the proportion of patients treated for basic skin complaints within the medical home while decreasing wait times. METHODS: The Rapid Assessment of Skin Health (RASH) clinic was created within a hospital-based primary care clinic in 11/2013. The clinic was staffed by 2 pediatricians trained in the dermatology department and supported with specialist advice as needed. Referral volume and wait times to dermatology and RASH clinic were tracked for visits between 11/1/12 and 10/31/18. A chart review was also conducted on a subset of RASH clinic visits. Primary care providers (PCPs) were surveyed about their experiences. RESULTS: Fifty-eight percent of patients referred for a dermatologic complaint were scheduled in RASH clinic. Wait times for new patient appointments in RASH clinic were significantly shorter than for new dermatology appointments in the previous 12 months (mean 36 days vs 65 days, P < .001). The monthly number of referrals to dermatology also decreased significantly after the RASH clinic opened (24/month vs 12/month, P < .001). Ten percent of RASH patients were referred on to dermatology. In a survey of PCPs (N = 67), 76% said the RASH clinic was "extremely/very helpful." CONCLUSIONS: Providing dermatologic care to low or moderate complexity patients within the medical home is feasible and leads to better access to care. This innovative model could be spread to other clinics and subspecialties.
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Dermatología , Instituciones de Atención Ambulatoria , Citas y Horarios , Niño , Humanos , Atención Primaria de Salud , Derivación y ConsultaAsunto(s)
Esclerosis Múltiple , Neurología , Academias e Institutos , Adulto , Humanos , Informe de Investigación , Estados UnidosRESUMEN
The feeding of three co-occurring freshwater mussel species (Ptychobranchus fasciolaris, Quadrula quadrula and Potamilus alatus) of differing conservation status on river water from their collection site was examined under static and ecologically relevant flow conditions using three characteristics of the suspended river seston from a turbid river (Sydenham River, Ontario): (1) Chlorophyll a fluorescence; (2) size of fluorescent particles determined under flow cytometry; and (3) individual algal taxa identified under flow cytometry. Differences in the clearance rate (CR; water volume cleared of material per mussel and time) based on changes in chlorophyll a concentration were observed among species (P. alatusâ¯>â¯Q. quadrula). Mussels had higher CR under flowing conditions and higher CR were observed on four of the nine algal taxa under flowing conditions. Feeding electivity analysis indicated that all mussel species selected for larger particles (28-35⯵m size fraction) while rejecting smaller ones (12-19⯵m). Whereas mussels did not appear to partition resources by size, mussel species exhibited resource partitioning of algal taxa (i.e., selectively feeding on different algal species; under flowing conditions: small centric diatoms were preferred by P. fasciolaris and Q. quadrula and avoided by P. alatus; Cryptomonas were preferred by P. fasciolaris and avoided by Q. quadrula and P. alatus; Chloromonas were preferred by P. alatus and avoided by P. fasciolaris). This study provides a novel mechanism, hydrodynamically mediated resource partitioning, in which the partitioning of resources occurs from within a flowing fluid rather than through the spatial or temporal partitioning of resources by organisms exploiting different microhabitats, to explain the existence of high mussel species richness within the same river reach (i.e., 24 species in this study). Unfortunately the species specific relationships noted above are likely vulnerable to climate change and changes in land use practice due to agriculture and urbanization.
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Bivalvos , Monitoreo del Ambiente , Animales , Agua Dulce , Ontario , RíosRESUMEN
We investigated factors associated with quality of life (QOL) in children with eczema. We conducted a cross-sectional analysis of survey data from 224 parents of children with eczema attending a large, hospital-based pediatric clinic. Parents completed a validated eczema severity scale (Patient-Oriented Eczema Measure), a QOL scale (Infants' Dermatitis QOL Index or Children's Dermatology Life Quality Index), and a knowledge and understanding questionnaire. In adjusted multivariate analyses, worse eczema severity was associated with worse overall QOL (ß = 0.5; 95% confidence interval [CI] = [0.5, 0.6]), while a higher knowledge score was associated with better QOL (ß = -3.4; 95% CI = [-6.6, -0.2]). Similarly, even after adjustment for eczema severity, greater understanding of a child's individual treatment plan was associated with better QOL (ß = -0.7; 95% CI = [-1.4, -0.08]), while increased frequency of worrying about a child's eczema was associated with worse QOL (ß = 0.7; 95% CI = [0.03, 1.1]). These results suggest primary care providers may be able to influence QOL through optimal eczema management and family education.
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Eccema/complicaciones , Eccema/psicología , Conocimientos, Actitudes y Práctica en Salud , Padres/psicología , Calidad de Vida , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Atención Primaria de Salud , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The quality of children's health is compromised by poor care coordination between primary care providers (PCPs) and specialists. Our objective was to determine how an electronic consultation and referral system impacts referral patterns and PCP-specialist communication. METHODS: The primary care clinic at Boston Children's Hospital piloted an electronic referral and consultation system with the neurology and gastroenterology departments from April 1, 2014, to October 31, 2016. PCPs completed an electronic consult form, and if needed, specialists replied with advice or facilitated expedited appointments. Specialist response times, referral rates, wait times, and completion rates for specialty visits were tracked. PCPs and specialists also completed a survey to evaluate feasibility and satisfaction. RESULTS: A total of 82 PCPs placed 510 consults during the pilot period. Specialists responded to 88% of requests within 3 business days. Eighteen percent of specialty visits were deferred and 21% were expedited. Wait times for specialty appointments to both departments significantly decreased, from 48 to 34 days (P < .001), and completion rates improved from 58% to 70% (P < .01), but referral volumes remained stable (25 per month to 23 per month; P = .29). Most PCPs said the Shared Care system facilitated better communication with specialists (89%) and enabled them to provide superior patient care (92%). Specialists reported that the system required a minimal amount of time and enabled them to educate PCPs and triage referrals. CONCLUSIONS: Implementation of an electronic referral and consultation system was feasible and provided timely access to specialty care, but did not affect referral volume. This system could serve as a model for other health care organizations and specialties.
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Registros Electrónicos de Salud , Comunicación Interdisciplinaria , Pediatras , Derivación y Consulta/organización & administración , Adolescente , Citas y Horarios , Niño , Preescolar , Continuidad de la Atención al Paciente , Estudios de Factibilidad , Femenino , Gastroenterólogos , Humanos , Masculino , Neurólogos , Proyectos PilotoRESUMEN
OBJECTIVE: To test whether an eczema care plan (ECP) would improve provider documentation and management, decrease eczema severity, and increase patient quality of life (QOL) in the pediatric primary care setting. METHODS: We conducted a randomized controlled trial from June 2015 to September 2016 at a large hospital-based pediatric primary care clinic. Participants included children from 1 month to 16 years of age with a diagnosis of eczema. The intervention group received the ECP and the control group received usual care. Both groups completed a validated eczema severity scale (Patient-Oriented Eczema Measure [POEM]) and a QOL scale (Infant's Dermatitis Quality of Life Index [IDQOL]) or Children's Dermatology Life Quality Index [CDLQI]) before the visit and again ~1 month later. RESULTS: A total of 211 caregivers completed both the pre- and postintervention surveys (100 control group and 111 intervention group [94% completion]). Intervention group providers were more likely to recommend a comprehensive "step-up" plan (88%) vs 28%; P < .001, bleach baths (45%) vs 9%; P < .001, and wet wraps (50%) vs 7%; P < .001. They were also more likely to document providing a written plan to families (80%) vs 2%; P < .001. In the intervention and control groups, eczema severity and QOL improved between the pre- and postintervention periods. However, there was not a significant difference between the groups on either measure: POEM difference -0.8, 95% confidence interval (CI) -3.2 to 1.7; IDQOL difference -0.1, 95% CI -1.8 to 1.6; CDLQI difference 0.8, 95% CI -0.9 to 2.6. CONCLUSIONS: Intervention group providers documented more comprehensive eczema care than control group providers. Although patients improved on all measures in the postintervention period, the ECP did not augment that improvement.
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Documentación , Eccema/terapia , Planificación de Atención al Paciente , Adolescente , Corticoesteroides/uso terapéutico , Baños , Niño , Preescolar , Manejo de la Enfermedad , Emolientes/uso terapéutico , Femenino , Humanos , Lactante , Masculino , Pediatría , Atención Primaria de Salud , Mejoramiento de la CalidadRESUMEN
BACKGROUND: Bone marrow stromal cells (BMSCs) have classically been cultured in media supplemented with fetal bovine serum (FBS). As an alternative to FBS, pooled solvent detergent apheresis platelets, HPGF-C18, was evaluated for BMSC culture. METHODS: A comparison of passage 2 BMSC growth revealed that 10% HPGF-C18 produced similar cell numbers as 20% FBS. Marrow aspirates from 5 healthy subjects were cultured for 4 passages in 10% HPGF-C18 or 20% FBS and were analyzed for proliferation, colony formation efficiency (CFE), surface marker expression, suppression of mixed lymphocyte reactions (MLRs), global gene and microRNA expression analysis. BMSC supernatant cytokine and growth factor concentrations were also compared. RESULTS: Primary cultures of marrow aspirates in 10% HPGF-C18 and 20% FBS yielded similar numbers and CFE. After 4 passages, 10% HPGF-C18 and 20% FBS yielded similar numbers of BMSCs, surface marker expression patterns and immunosuppression effects. Gene and microRNA expression analysis revealed that BMSCs cultured under the two conditions had distinct expression profiles. Gene Set Enrichment Analysis (GSEA) revealed HPGF-C18-cultured BMSCs were enriched in metabolic processing and biosynthetic pathways, cell proliferation and cell cycle pathways, and immune response pathways. FBS-cultured BMSCs were enriched in MAPK signaling, TGF-beta signaling, cell adhesion and extracellular matrix pathways. Differently expressed microRNAs were related to the osteogenesis of BMSCs. The supernatant of HPGF-C18 BMSCs had higher levels of PEDF and TGFB1 and lower levels of IL6, VEGF, SDF1 and PLGF. CONCLUSIONS: Traditional measures, expansion, surface marker expression and inhibition of MLRs suggest that BMSC cultured in HPGF-C18 and FBS were similar, but analysis at the molecular level revealed many differences. BMSCs cultured in HPGF-C18 should be assessed in specific functional assays that reflect application-specific potency before substituting FBS with HPGF-C18.
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Células de la Médula Ósea/citología , Técnicas de Cultivo de Célula/métodos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Suero/metabolismo , Animales , Biomarcadores/metabolismo , Células de la Médula Ósea/efectos de los fármacos , Bovinos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Prueba de Cultivo Mixto de Linfocitos , MicroARNs/genética , MicroARNs/metabolismo , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Transcriptoma/genéticaRESUMEN
EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes.
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Numerous responsible gambling (RG) strategies are promoted to assist consumers to "gamble responsibly". However, consumer adoption of RG strategies, how this varies by gambler risk group, and whether usage is associated with non-problematic gambling are largely unknown. This study aimed to (1) determine how use of RG-related strategies differs amongst regular gamblers by gambler risk group; and (2) identify RG-related strategies whose usage predicts non-problem/low risk gambling. Regular Australian gamblers on high-risk products (N = 860), recruited through gambling venues and an online wagering operator, were surveyed about their use of RG strategies promoted on the website of their jurisdiction's main RG agency. Knowledge of RG strategies was reasonably high amongst all gambler risk groups, but lower-risk groups were more likely to use RG strategies. A logistic regression correctly predicted 82.1 % of lower-risk gamblers and 77.2 % of higher-risk gamblers. Predictors of lower-risk gambling included: greater confidence in their understanding of RG; endorsement of lower gambling expenditure and frequency limits; fewer erroneous gambling beliefs; being less likely to gamble to win money, challenge their skills/beat the odds, or forget about worries and stresses; and being more likely to gamble for pleasure/entertainment. Lower-risk gamblers were more likely to set a money limit in advance of gambling and to balance their gambling with other activities. These findings contribute to understanding which strategies are favoured by different risk groups, and which are associated with safer levels of gambling. They can guide consumer information aimed at enhancing RG consumption and future research on RG consumption.
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Juego de Azar/prevención & control , Juego de Azar/psicología , Asunción de Riesgos , Autoimagen , Autoeficacia , Adulto , Australia , Femenino , Humanos , Control Interno-Externo , Masculino , Procesos Mentales , Entrevista Motivacional , Resultado del TratamientoRESUMEN
The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation. Radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in executive function and reduced rates of fear extinction and elevated anxiety. Irradiation caused significant reductions in dendritic complexity, spine density and altered spine morphology along medial prefrontal cortical neurons known to mediate neurotransmission interrogated by our behavioral tasks. Cosmic radiation also disrupted synaptic integrity and increased neuroinflammation that persisted more than 6 months after exposure. Behavioral deficits for individual animals correlated significantly with reduced spine density and increased synaptic puncta, providing quantitative measures of risk for developing cognitive impairment. Our data provide additional evidence that deep space travel poses a real and unique threat to the integrity of neural circuits in the brain.
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Disfunción Cognitiva/etiología , Radiación Cósmica/efectos adversos , Neuronas/efectos de la radiación , Animales , Conducta Animal/efectos de la radiación , Recuento de Células , Dendritas/patología , Dendritas/efectos de la radiación , Homólogo 4 de la Proteína Discs Large/metabolismo , Relación Dosis-Respuesta en la Radiación , Inflamación/etiología , Masculino , Ratones Transgénicos , Neuronas/patología , Corteza Prefrontal/citología , Corteza Prefrontal/efectos de la radiación , Ratas WistarRESUMEN
Malignant gliomas are heterogeneous populations of dynamically interacting cells. Genomic and transcriptional changes define this cellular hierarchy and allow certain tumor cells to co-opt metabolic machinery and adopt gene expression profiles that promote cellular reprogramming. Resultant expansion of privileged subpopulations can then rapidly adapt to microenvironmental stress that ultimately influence tumor response to therapeutic intervention. In this study, primary gliomas were subjected to acute or chronic irradiation and analyzed for changes in survival parameters, oxidative stress, gene expression, and cell invasion before and after treatment with secreted microvesicles isolated from irradiated and nonirradiated glioma cells. We found that primary gliomas exposed to ionizing radiation undergo metabolic changes that increase oxidative stress, alter gene expression, and affect the contents of and response to cellular secreted microvesicles. Radiation-induced changes were exacerbated under chronic as compared to acute irradiation paradigms and promoted cellular reprogramming through enhanced expression of key transcription factors and regulators involved in differentiation and pluripotency (SOX2, POU3F2, SALL2, OLIG2, NANOG, POU5F1v1, MSI1). Irradiation also affected changes in paracrine signaling mediated by cellular secreted microvesicles that significantly altered target cell phenotype. Primary gliomas treated with microvesicles exhibited increased radioresistance and treatment with microvesicles from chronically irradiated gliomas promoted invasion via induction of increased matrix metalloproteinase II activity. Together, our data describe a complex radiation response of primary glioma cells involving metabolic and transcriptional changes that alter radiation sensitivity and induce invasive behavior. These important changes can contribute to tumor growth and recurrence, and confound interventions designed to forestall disease progression. Environ. Mol. Mutagen. 57:405-415, 2016. © 2015 Wiley Periodicals, Inc.
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Neoplasias Encefálicas/patología , Proliferación Celular/efectos de la radiación , Vesículas Extracelulares/metabolismo , Rayos gamma , Glioblastoma/patología , Neoplasias Encefálicas/metabolismo , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Glioblastoma/metabolismo , Humanos , Invasividad Neoplásica , Estrés Oxidativo/efectos de la radiaciónRESUMEN
As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.