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We compare the power of quantum and classical physics in terms of randomness certification from devices which are only partially characterized. We study randomness certification based on state discrimination and take noncontextuality as the notion of classicality. A contextual advantage was recently shown to exist for state discrimination. Here, we develop quantum and noncontextual semi-device independent protocols for random-number generation based on maximum-confidence discrimination, which generalizes unambiguous and minimum-error state discrimination. We show that, for quantum eavesdroppers, quantum devices can certify more randomness than noncontextual ones whenever none of the input states are unambiguously identified. That is, a quantum-over-classical advantage exists.
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The stimuli-responsive conformational transformation of peptides possessing a constrained form triggered by specific biological microenvironment would provide an effective strategy for the development of highly specific peptide therapeutics. Here, we developed a peptide containing a cytotoxic helical KLA sequence with therapeutic specificity through the use of stimuli-responsive conformational transformation. The KLA peptide is modified to form a cyclic structure to allow for constrained helicity that confers low cytotoxicity. The modified KLA peptide is electrostatically complexed to hyaluronic acid to facilitate enhanced endocytosis into the cancer cells. After endocytosis, the peptide is released from the complex into the cellular cytoplasm by hyaluronidases on the surface of the cellular membrane. Specific intracellular stimuli then trigger the release of the strain that suppresses peptide helicity, and the inherent helical conformation of the KLA peptide is restored. Therefore, the stimuli-responsive conformational transformation of a peptide from low to high helicity selectively induces cell death by disruption of the plasma and mitochondrial membrane.
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Antineoplásicos/química , Antineoplásicos/farmacología , Descubrimiento de Drogas , Péptidos y Proteínas de Señalización Intercelular/química , Péptidos y Proteínas de Señalización Intercelular/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Membranas Mitocondriales/efectos de los fármacos , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Conformación Proteica en Hélice alfaRESUMEN
Epithelial-to-mesenchymal transition (EMT) is a critical cellular phenomenon regulating tumor metastases. In the present study, we investigated whether ginkgolic acid can affect EMT in lung cancer cells and the related underlying mechanism(s) of its actions. We found that ginkgolic acid C15:1 (GA C15:1) inhibited cell proliferation, invasion, and migration in both A549 and H1299 lung cancer cells. GA C15:1 also suppressed the expression of EMT related genes (Fibronectin, Vimentin, N-cadherin, MMP-9, MMP-2, Twist and Snail) and suppressed TGF-ß-induced EMT as assessed by reduced expression of mesenchymal markers (Fibronectin, Vimentin, N-cadherin), MMP-9, MMP-2, Twist and Snail. However, GA C15:1 did not affect the expression of various epithelial marker proteins (Occludin and E-cadherin) in both A549 and H1299 cells. TGF-ß-induced morphologic changes from epithelial to mesenchymal cells and induction of invasion and migration were reversed by GA C15:1. Finally, GA C15:1 not only abrogated basal PI3K/Akt/mTOR signaling cascade, but also reduced TGF-ß-induced phosphorylation of PI3K/Akt/mTOR pathway in lung cancer cells. Overall, these findings suggest that GA C15:1 suppresses lung cancer invasion and migration through the inhibition of PI3K/Akt/mTOR signaling pathway and provide a source of potential therapeutic compounds to control the metastatic dissemination of tumor cells. J. Cell. Physiol. 232: 346-354, 2017. © 2016 Wiley Periodicals, Inc.
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Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Salicilatos/farmacología , Factor de Crecimiento Transformador beta/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Salicilatos/química , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Alcaloides Indólicos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Antineoplásicos Fitogénicos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Alcaloides Indólicos/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/prevención & control , Oxindoles , Uncaria/químicaRESUMEN
Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c-Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin-induced down-modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP-1 and PTEN proteins and its mRNAs. Further, deletion of SHP-1 and PTEN genes by siRNA suppressed the induction of SHP-1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down-regulation of STAT3-regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP-1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis.
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Apoptosis/efectos de los fármacos , Biflavonoides/farmacología , Fosfohidrolasa PTEN/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Proteína Tirosina Quinasa CSK , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Janus Quinasa 1/metabolismo , Fosforilación , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Familia-src Quinasas/metabolismoRESUMEN
Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)-9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA-MB-231 cells under noncytotoxic concentrations but not in MCF-7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA-MB-231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor-kappa B (NF-κB) activation. It further reduced the binding of NF-κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP-9/2 expressions, and inhibition of epithelial-mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
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Benzoquinonas/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Receptores CXCR4/metabolismo , Benzoquinonas/administración & dosificación , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Femenino , Humanos , Células MCF-7 , Invasividad Neoplásica , Transducción de Señal , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
Background: Despite the growing research on environment-physical activity (PA) relationships, field experimental studies are limited. Such studies offer opportunities to focus on real-world environmental exposure and related PA and health outcomes, allowing researchers to better isolate the causal effect of exposures/interventions. Focusing on the street/pedestrian environment as a routine setting for people's daily activities, this research aims to develop and test a field experiment protocol that integrates instantaneous assessments of the environment, PA, and health outcomes. The protocol involves the use of state-of-the-art environmental monitoring and biosensing techniques and focuses on physically active road users (pedestrians and bicyclists) who are more directly exposed to their surrounding environment than others such as drivers. Methods/Design: An interdisciplinary research team first identified the target measurement domains for the health outcomes (e.g., stress, thermal comfort, PA) and the street-level environmental exposures (e.g., land use, greenery, infrastructure conditions, air quality, weather) guided by the previous literature which was primarily observational. Portable or wearable measurement instruments (e.g., GPS, accelerometer, biosensor, mini camera, smartphone app, weather station, air quality sensor) were identified, pilot tested, and selected for the identified measures. We ensured that these measures are readily linkable using the time stamp and include eye-level exposures as they impact the users' experiences more directly yet missing in most prior studies relying on secondary, aerial-level measures. A 50-min experimental route was then determined to include typical everyday environments in park and mixed-use settings and to engage participants in three common modes of transportation (walking, bicycling, and driving). Finally, a detailed staff protocol was developed, pilot-tested, and used in a 36-participant within-subject field experiment in College Station, TX. The experiment was successfully executed, showing its potential to support future field experiments that can provide more accurate real-time, real-environment, and multi-dimensional information. Discussion: Our study demonstrates the feasibility of capturing the multifold health benefits/harms related to walking and bicycling in varying urban environments by combining field experiments with environmental, behavioral, and physiological sensing. Our study protocol and reflections can be helpful for a broad spectrum of research addressing the complex and multi-level pathways between the environment, behavior, and health outcomes.
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Conducción de Automóvil , Humanos , Ciclismo , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Ejercicio FísicoRESUMEN
BACKGROUND: Creating activity-friendly communities (AFCs) is an important strategy to increase physical activity (PA). While cross-sectional links between community environments and PA are well documented, their causal relationships remain insufficiently explored. METHODS: Using the accelerometer and survey data collected from adults who moved to an AFC (cases) and similar non-AFC-residing adults who did not move (comparisons), this pre-post, case-comparison study examines if moving to an AFC increases PA. Data came from 115 participants (cases = 37, comparisons = 78) from Austin, Texas, who completed 2 waves of 1-weeklong data collection. Difference-in-difference analyses and fixed-effect models were used to test the significance of the pre-post differences in moderate-to-vigorous PA (MVPA) between cases and comparisons, for the full sample and the subsample of 37 pairs matched in key covariates using the Propensity Score Matching method. RESULTS: Average treatment effect generated based on Propensity Score Matching and difference-in-difference showed that moving to this AFC led to an average of 10.88 additional minutes of daily MVPA (76.16 weekly minutes, P = .015). Fixed-effect models echoed the result with an increase of 10.39 minutes of daily MVPA after moving to the AFC. We also found that case participants who were less active at baseline and had higher income increased their MVPA more than their counterparts. CONCLUSIONS: This study showed that, among our study sample, moving to an AFC increased residents' PA significantly when compared to their premove level and the comparison group. This causal evidence suggests the potential of AFCs as sustainable interventions for PA promotion.
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Ambiente , Ejercicio Físico , Adulto , Humanos , Estudios Transversales , Encuestas y Cuestionarios , RentaRESUMEN
Biosignals from wearable sensors have shown great potential for capturing environmental distress that pedestrians experience from negative stimuli (e.g., abandoned houses, poorly maintained sidewalks, graffiti, and so forth). This physiological monitoring approach in an ambulatory setting can mitigate the subjectivity and reliability concerns of traditional self-reported surveys and field audits. However, to date, most prior work has been conducted in a controlled setting and there has been little investigation into utilizing biosignals captured in real-life settings. This research examines the usability of biosignals (electrodermal activity, gait patterns, and heart rate) acquired from real-life settings to capture the environmental distress experienced by pedestrians. We collected and analyzed geocoded biosignals and self-reported stimuli information in real-life settings. Data was analyzed using spatial methods with statistical and machine learning models. Results show that the machine learning algorithm predicted location-based collective distress of pedestrians with 80% accuracy, showing statistical associations between biosignals and the self-reported stimuli. This method is expected to advance our ability to sense and react to not only built environmental issues but also urban dynamics and emergent events, which together will open valuable new opportunities to integrate human biological and physiological data streams into future built environments and/or walkability assessment applications.
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Entorno Construido , Marcha , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , AutoinformeRESUMEN
OBJECTIVES: We explored the importance of environmental and mobility strategies during early COVID-19 by age and ethnicity and investigated predictors of park visitations considering the COVID-19 impacts. BACKGROUND: Parks are safe and accessible venues to stay active and reduce social isolation, which is especially important considering COVID-19 and the associated lockdowns. METHODS: We analyzed online survey data from 683 residents (collected July 2020) of El Paso, TX, and objective measures of neighborhood park characteristics. Chi-square tests and mixed-effects logistic regression analyses were performed to examine the environmental/mobility strategies, personal and environmental factors, and park visitations, considering the COVID-19 impacts. RESULTS: The percentage of those who visited (1+ times/week) parks or trails/paths in the neighborhood dropped from 41.7% to 19.5% since the start of COVID-19 (OR = 0.015, p < .001). Before COVID-19, middle-aged and older adults were less likely to visit parks than younger adults, while this difference became insignificant during early COVID-19. Hispanic adults were more likely to visit parks than non-Hispanics both before and during early COVID-19. Positive environmental predictors of park visitations included park availability in the neighborhood, proximity to the closest park, seeing people being physically active in the neighborhood, and neighborhood aesthetics. CONCLUSIONS: Proximately located parks, trails, and paths well integrated into residential communities, and high aesthetic quality of the neighborhood are the potential features of pandemic-resilient communities and should be considered an important national priority to maintain and promote the health and well-being of the population, especially during pandemics like COVID-19.
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COVID-19 , Control de Enfermedades Transmisibles , Planificación Ambiental , Parques Recreativos , Recreación , Anciano , Humanos , Persona de Mediana Edad , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/prevención & control , Planificación Ambiental/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Aislamiento Social , Cuarentena/estadística & datos numéricos , Parques Recreativos/estadística & datos numéricosRESUMEN
Correction for 'Probing antiferromagnetism in exfoliated Fe3GeTe2 using magneto-transport measurements' by Stasiu T. Chyczewski et al., Nanoscale, 2023, https://doi.org/10.1039/D3NR01022H.
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Among the material class of van der Waals magnets, Fe3GeTe2 (FGT) has emerged as one of the most studied owing to features such as its relatively high Curie temperature, metallic nature, and large spin polarization. Though most studies only investigate its explicitly ferromagnetic properties, FGT is also predicted to have an antiferromagnetic phase in the out-of-plane direction emerging at temperatures below 150 K, leading to a blend of ferromagnetic and antiferromagnetic ordering. Here, we explore the emergence of this phase and its effects in FGT/h-BN heterostructures using magneto-transport measurements. The devices' anomalous Hall and magnetoresistance responses exhibit a complex trend with temperature that is consistent with multiple magnetic phases. In addition to the usual out-of-plane sensing, we also rotate the applied field to the in-plane direction and observe behavior resembling the planar topological Hall effect. Intriguingly, this response follows a similar temperature trend to the out-of-plane response. We also use the out-of-plane anomalous Hall response to show that, at sufficiently low temperatures, both positive and negative field-cooling results in an increased saturation Hall resistance. Such a field-cooling divergence is consistent with antiferromagnetic ordering resulting in a spin-glass like state in the sample. In addition to providing insight into one of the most exciting candidate materials for 2D magnetic devices, our work demonstrates the power of magneto-transport measurements to probe complex behavior in vdW magnets where common magnetometry techniques used on bulk samples may not be viable.
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OBJECTIVES: Nursing homes (NHs) are important health care and residential environments for the growing number of frail older adults. The COVID-19 pandemic highlighted the vulnerability of NHs as they became COVID-19 hotspots. This study examines the associations of NH design with COVID-19 cases, deaths, and transmissibility and provides relevant design recommendations. DESIGN: A cross-sectional, nationwide study was conducted after combining multiple national data sets about NHs. SETTING AND PARTICIPANTS: A total of 7785 NHs were included in the study, which represent 50.8% of all Medicare and/or Medicaid NH providers in the United States. METHODS: Zero-inflated negative binomial models were used to predict the total number of COVID-19 resident cases and deaths, separately. The basic reproduction number (R0) was calculated for each NH to reflect the transmissibility of COVID-19 among residents within the facility, and a linear regression model was estimated to predict log(R0 - 1). Predictors of these models included community factors and NHs' resident characteristics, management and rating factors, and physical environmental features. RESULTS: Increased percentage of private rooms, larger living area per bed, and presence of a ventilator-dependent unit are significantly associated with reductions in COVID-19 cases, deaths, and transmissibility among residents. After setting the number of actual residents as the exposure variable and controlling for staff cases and other variables, increased number of certified beds in the NH is associated with reduced resident cases and deaths. It also correlates with reduced transmissibility among residents when other risk factors, including staff cases, are controlled. CONCLUSIONS AND IMPLICATIONS: Architectural design attributes have significant impacts on COVID-19 transmissions in NHs. Considering the vulnerability of NH residents in congregated living environments, NHs will continue to be high-risk settings for infection outbreaks. To improve safety and resilience of NHs against future health disasters, facility guidelines and regulations should consider the need to increase private rooms and living areas.
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COVID-19 , Anciano , Estudios Transversales , Humanos , Medicare , Casas de Salud , Pandemias , SARS-CoV-2 , Estados UnidosRESUMEN
Background: Stakeholders from multiple sectors are increasingly aware of the critical need for identifying sustainable interventions that promote healthy lifestyle behaviors. Activity-friendly communities (AFCs) have been known to provide opportunities for engaging in physical activity (PA) across the life course, which is a key to healthy living and healthy aging. Purpose: Our purpose is to describe the study protocol developed for a research project that examines: (a) the short- and long-term changes in total levels and spatial and temporal patterns of PA after individuals move from non-AFCs to an AFC; and (b) what built and natural environmental factors lead to changes in PA resulting from such a move, either directly or indirectly (e.g., by affecting psychosocial factors related to PA). Methods: This protocol is for a longitudinal, case-comparison study utilizing a unique natural experiment opportunity in Austin, Texas, USA. Case participants were those adults who moved from non-AFCs to an AFC. Matching comparison participants were residents from similar non-AFCs who did not move during the study period. Recruitment venues included local businesses, social and print media, community events, and individual referrals. Objectively measured moderate-to-vigorous PA and associated spatial and temporal patterns served as the key outcomes of interest. Independent (e.g., physical environments), confounding (e.g., demographic factors), and mediating variables (e.g., psychosocial factors) were captured using a combination of objective (e.g., GIS, GPS, Tanita scale) and subjective measures (e.g., survey, travel diary). Statistical analyses will be conducted using multiple methods, including difference-in-differences models, repeated-measures linear mixed models, hierarchical marked space-time Poisson point pattern analysis, and hierarchical linear mixed models. Conclusion: Natural experiment studies help investigate causal relationships between health and place. However, multiple challenges associated with participant recruitment, extensive and extended data collection activities, and unpredictable intervention schedules have discouraged many researchers from implementing such studies in community-based populations. This detailed study protocol will inform the execution of future studies to explore how AFCs impact population health across the life course.
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Ejercicio Físico , Salud Poblacional , Adulto , Estudios de Casos y Controles , Humanos , Encuestas y Cuestionarios , TexasRESUMEN
Background: Intergenerational interactions and walking are two of the most beneficial forms of activities for older adults. As older adults spend most of their time at or near home, the characteristics of the proximate residential environments are particularly important for supporting those activities. This study aims to (1) explore places used for various social interactions older adults engage in, (2) examine specific neighborhood environmental features associated with intergenerational interactions, and (3) compare similarities and differences in environmental correlates of intergenerational interactions vs. walking. Methods: This cross-sectional study analyzed self-reported survey data from 455 community-dwelling adults aged 65+ from Austin, Texas, as well as Geographic Information System (GIS) measures capturing the neighborhood environment around each participant's home. Descriptive statistics were used for Aim 1. Multivariable binary logistic models were used for Aims 2 and 3, to identify environmental variables predicting the odds of participating in intergenerational interactions (with children 1+ times/week, and with children, teenagers, or adults 1+ times/week) in one's neighborhood, as well as walking 1+ times/week for transportation or recreation purposes. Results: Participants had a mean age of 73 years, and were primarily female (72.1%) and non-Hispanic white (72.8%). Older adults interacted frequently with adults (79.2%, 1+ times/week) and other older adults (66.9%) in their neighborhood, while less frequently with children (28.0%) and teenagers (21.9%). Recreational walking (73.3%, 1+ times/week) was more popular for older adults than transportation walking (43.8%). Multivariable analyses showed that neighborhood perceptions, transportation infrastructure, land uses, land covers, population densities, development activities, and composite scores were significant predictors of intergenerational activities. Both similarities and differences were found in terms of the neighborhood environmental factors associated with intergenerational interactions vs. walking although differences were more evident in the domains of land covers, development activities, and composite scores. Conclusions: Given the significant health benefits, promoting intergenerational interactions and walking among older adults should be a national/global responsibility. Further work is needed to improve our understanding of the specific social and physical environmental facilitators as well as barriers to creating intergenerational communities that can support healthy living of all generations.
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Planificación Ambiental , Caminata , Adolescente , Anciano , Niño , Estudios Transversales , Femenino , Humanos , Características de la Residencia , TexasRESUMEN
BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is persistently activated in squamous cell carcinoma of the head and neck (SCCHN) and can cause uncontrolled cellular proliferation and division. HYPOTHESIS: Thus, its targeted abrogation could be an effective strategy to reduce the risk of SCCHN. Resveratrol is known for its anti-cancer efficacy in a variety of cancer models. STUDY DESIGN: The effect resveratrol on STAT3 activation, associated protein kinases, phosphatases, cellular proliferation and apoptosis was investigated. METHODS: We evaluated the effect of resveratrol on STAT3 signaling cascade and its regulated functional responses in SCCHN cells. RESULTS: We found that HN3 and FaDu cells expressed strongly phosphorylated STAT3 on both tyrosine 705 and serine 727 residues as compared to other SCCHN cells. The phosphorylation was completely suppressed by resveratrol in FaDu cells, but not substantially in HN3 cells. STAT3 suppression was mediated through the inhibition of activation of upstream JAK2, but not of JAK1 and Src kinases. Treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate reversed the resveratrol-induced down-regulation of STAT3, thereby indicating a critical role for a PTP. We also found that resveratrol induced the expression of the SOCS-1 protein and mRNA. Further, deletion of SOCS-1 gene by siRNA suppressed the induction of SOCS-1, and reversed the inhibition of STAT3 activation. Resveratrol down-regulated various STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced the cell accumulation in the sub-G1 phase and caused apoptosis. Beside, this phytoalexin also exhibited the enhancement of apoptosis when combined with ionizing radiation treatment. CONCLUSION: Our results suggest that resveratrol blocks STAT3 signaling pathway through induction of SOCS-1, thus attenuating STAT3 phosphorylation and proliferation in SCCHN cells.