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1.
Pediatrics ; 154(1)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38860305

ABSTRACT

Patients who speak languages other than English are frequently excluded from research. This exclusion exacerbates inequities, biases results, and may violate federal regulations and research ethics. Language justice is the right to communicate in an individual's preferred language to address power imbalances and promote equity. To promote language justice in research, we propose a method to translate and culturally-adapt multifaceted research materials into multiple languages simultaneously. Our method involves a multistep approach, including professional translation, review by bilingual expert panels to refine and reach consensus, and piloting or cognitive interviews with patients and families. Key differences from other translation approaches (eg, the World Health Organization) include omitting back-translation, given its limited utility in identifying translation challenges, and limiting expert panelist and piloting-participant numbers for feasibility. We detail a step-by-step approach to operationalizing this method and outline key considerations learned after utilizing this method to translate materials into 8 languages other than English for an ongoing multicenter pediatric research study on family safety-reporting. Materials included family brochures, surveys, and intervention materials. This approach took ∼6 months overall at a cost of <$2000 per language (not including study personnel costs). Key themes across the project included (1) tailor scope to timeline, budget, and resources, (2) thoughtfully design English source materials, (3) identify and apply guiding principles throughout the translation and editing process, and (4) carefully review content and formatting to account for nuances across multiple languages. This method balances feasibility and rigor in translating participant-facing materials into multiple languages simultaneously, advancing language justice in research.


Subject(s)
Multilingualism , Humans , Translating , Biomedical Research/ethics , Child
4.
Curr Opin Pediatr ; 35(1): 8-13, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36301135

ABSTRACT

PURPOSE OF REVIEW: This review provides a critical assessment of recent pediatric population health research with a specific focus on child health equity. The review addresses: the role of the healthcare sector in addressing fundamental social drivers of health, challenges within healthcare organizations in addressing health-related social needs and the social determinants of health, and the rationale for incorporating race and racism in pediatric population health research and practice. RECENT FINDINGS: The coronavirus disease 2019 pandemic brought greater attention to the disparities and inequities in American health and healthcare. In response to these stark inequities, many health systems are adopting efforts and initiatives to address social needs, social determinants of health, racism, and health equity. However, empirical evaluation detailing the effectiveness of these interventions and initiatives is limited. SUMMARY: While attention to identifying social needs among pediatric populations is increasing, there is limited evidence regarding the effectiveness of these interventions in producing sustained reductions in health disparities. To advance child health equity, researchers should move beyond individual behavior modification and directly examine fundamental drivers of health inequities. These drivers include government and health policies as well as societal forces such as systemic racism.


Subject(s)
COVID-19 , Health Equity , Humans , Child , Social Determinants of Health , COVID-19/epidemiology , COVID-19/prevention & control , Health Inequities , Delivery of Health Care
5.
Cell Rep ; 41(4): 111521, 2022 10 25.
Article in English | MEDLINE | ID: mdl-36288710

ABSTRACT

Sudden unexpected environmental changes capture attention and, when perceived as potentially dangerous, evoke defensive behavioral states. Perturbations of the lateral septum (LS) can produce extreme hyperdefensiveness even to innocuous stimuli, but how this structure influences stimulus-evoked defensive responses and threat perception remains unclear. Here, we show that Crhr2-expressing neurons in mouse LS exhibit phasic activation upon detection of threatening but not rewarding stimuli. Threat-stimulus-driven activity predicts the probability but not vigor or type of defensive behavior evoked. Although necessary for and sufficient to potentiate stimulus-triggered defensive responses, LSCrhr2 neurons do not promote specific behaviors. Rather, their stimulation elicits negative valence and physiological arousal. Moreover, LSCrhr2 activity tracks brain state fluctuations and drives cortical activation and rapid awakening in the absence of threat. Together, our findings suggest that LS directs bottom-up modulation of cortical function to evoke preparatory defensive internal states and selectively enhance responsivity to threat-related stimuli.


Subject(s)
Fear , Neurons , Animals , Mice , Fear/physiology , Neurons/physiology , Brain , Attention
6.
Elife ; 92020 08 11.
Article in English | MEDLINE | ID: mdl-32779566

ABSTRACT

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms remain poorly understood. RNAseq from BLApn identified changes in multiple candidate learning-related transcripts including the expected immediate early gene Fos and Stk11, a master kinase of the AMP-related kinase pathway with important roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 in BLApn blocked memory prior to training, but not following it and increased neuronal excitability. Conversely, BLApn had reduced excitability following CTA. BLApn knockout of a second learning-related gene, Fos, also increased excitability and impaired learning. Independently increasing BLApn excitability chemogenetically during CTA also impaired memory. STK11 and C-FOS activation were independent of one another. These data suggest key roles for Stk11 and Fos in CTA long-term memory formation, dependent at least partly through convergent action on BLApn intrinsic excitability.


Subject(s)
Basolateral Nuclear Complex , Conditioning, Classical/physiology , Memory, Long-Term/physiology , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins c-fos , AMP-Activated Protein Kinases , Animals , Basolateral Nuclear Complex/chemistry , Basolateral Nuclear Complex/cytology , Basolateral Nuclear Complex/metabolism , Female , Gene Knockout Techniques , Male , Mice , Neurons/chemistry , Neurons/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Taste/physiology
7.
Ethn Dis ; 29(4): 549-558, 2019.
Article in English | MEDLINE | ID: mdl-31641322

ABSTRACT

Purpose: Few family-oriented cardiovascular risk reduction interventions exist that leverage the home environment to produce health behavior change among multiple family members. We identified opportunities to adapt disease self-management interventions included in a blood pressure control comparative effectiveness trial for hypertensive African American adults to address family-level factors. Methods: We conducted and analyzed semi-structured interviews with five intervention study staff (all study interventionists and the study coordinator) between December 2016 and January 2017 and with 11 study participants between September and November 2015.1 All study staff involved with intervention delivery and coordination were interviewed. We sampled adult participants from the parent study, and we analyzed interviews that were originally obtained as part of a previous study based on their status as a caregiver of an adolescent family member. Results: Thematic analysis identified family influences on disease management and the importance of relationships between index patients and family members, between index patients and study peers, and between index patients and study staff through study participation to understand social effects on healthy behaviors. We identified four themes: 1) the role of family in health behavior change; 2) the impact of family dynamics on health behaviors; 3) building peer relationships through intervention participation; and 4) study staff role conflict. Conclusions: These findings inform development of family-oriented interventions to improve health behaviors among African American index patients at high risk for cardiovascular disease and their family members.


Subject(s)
Black or African American , Family , Health Behavior , Hypertension/prevention & control , Social Support , Blood Pressure , Family Relations , Female , Humans , Interpersonal Relations , Interviews as Topic , Male , Peer Group , Poverty , Qualitative Research , Risk Reduction Behavior , Self-Management
8.
Front Pediatr ; 6: 386, 2018.
Article in English | MEDLINE | ID: mdl-30687684

ABSTRACT

Background: Despite improvements in cardiovascular disease (CVD) prevention and treatment, low-income African Americans experience disparities in CVD-related morbidity and mortality. Childhood obesity disparities and poor diet and physical activity behaviors contribute to CVD disparities throughout the life course. Given the potential for intergenerational transmission of CVD risk, it is important to determine whether adult disease management interventions could be modified to achieve family-level benefits and improve primary prevention among high-risk youth. Objective: To explore mechanisms by which African-American adults' (referred to as index patients) participation in a hypertension disease management trial influences adolescent family members' (referred to as adolescents) lifestyle behaviors. Design/Methods: The study recruited index patients from the Achieving blood pressure Control Together (ACT) study who reported living with an adolescent ages 12-17 years old. Index patients and adolescents were recruited for in-depth interviews and were asked about any family-level changes to diet and physical activity behaviors during or after participation in the ACT study. If family-level changes were described, index patients and adolescents were asked whether role modeling, changes in the home food environment, meal preparation, and family functioning contributed to these changes. These mechanisms were hypothesize to be important based on existing research suggesting that parental involvement in childhood obesity interventions influences child and adolescent weight status. Thematic content analysis of transcribed interviews identified both a priori and emergent themes. Results: Eleven index patients and their adolescents participated in in-depth interviews. Index patients and adolescents both described changes to the home food environment and meal preparation. Role modeling was salient to index patients, particularly regarding healthy eating behaviors. Changes in family functioning due to study participation were not endorsed by index patients or adolescents. Emergent themes included adolescent care-taking of index patients and varying perceptions by index patients of their influence on adolescents' health behaviors. Conclusions: Our findings suggest that disease management interventions directed at high-risk adult populations may influence adolescent family members' health behaviors. We find support for the hypotheses that role modeling and changes to the home food environment are mechanisms by which family-level health behavior change occurs. Adolescents' roles as caretakers for index patients emerged as another potential mechanism. Future research should explore these mechanisms and ways to leverage disease management to support both adult and adolescent health behavior change.

9.
Aviat Space Environ Med ; 78(4 Suppl): A67-78, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17511301

ABSTRACT

BACKGROUND: The bioeffects of space radiation on organisms outside of the environment of Earth's magnetosphere are a concern for long-duration exploration spaceflights. Potential mutagenic effects from space radiation exposure result from direct DNA damage or indirectly from the production of reactive oxygen species (ROS). HYPOTHESES: 1) Transepithelial electrical resistance (TER) measurements in cell culture monolayers may be used as a model system for detecting cell damage produced by exposure to simulated space radiation and for testing potential chemoprotective agents; 2) biomarkers of exposure that quantitate indirect radiation effects may allow prediction of cellular DNA damage; and 3) a multiple agent, chemoprevention cocktail may reduce the bioeffects of simulated space radiation. METHODS: Normal human and canine lung, breast, and renal epithelial cells were assayed in vitro and exposed to escalating doses of gamma or heavy-ion carbon (290 MeV/u), ceon (400 MeV/u), or iron (600 MeV/u) irradiation. Post-exposure measurements of TER, lipid peroxidation (LP) via measurement of 4-hydroxy-nonenal (4-HNE), and malonaldehyde (MDA) and assessment of chromosome damage via fluorescence in situ hybridization with tandem labeling of chromosome 1 were performed. RESULTS: Cells exposed to intermediate or high doses of radiation (5, 10, and 25 Gy) showed characteristic diminution in TER, thought to be secondary to dysfunction of tight junctions, and associated with membrane LP and other mechanisms. The cells also showed increases in 4-HNE + MDA measurements and increased frequency of chromosomal aberrations. Preliminary studies of cells incubated with media containing a combination of chemoprotective agents at the time of radiation exposure showed a 15-50% reduction in the radiation-induced changes in membrane resistance, levels of LP, and chromosomal aberrations relative to their unprotected cellular counterparts. CONCLUSION: TER measurement, in conjunction with measures of LP, may provide a useful model for determination of physiological changes caused by radiation exposure and the efficacy of chemoprotective agents. A multi-agent mixture of chemoprotective agents may be more effective than previously evaluated single agents alone.


Subject(s)
Astronauts , Epithelial Cells/radiation effects , Extraterrestrial Environment , Radiation, Ionizing , Space Flight , Weightlessness , Animals , Biomarkers , Cell Death/radiation effects , Chemoprevention , Chromosome Aberrations/radiation effects , Dogs , Humans , In Vitro Techniques , Lipid Peroxidation/physiology , Lipid Peroxidation/radiation effects , Oxidative Stress/physiology , Oxidative Stress/radiation effects , Radiation-Protective Agents , Reactive Oxygen Species/radiation effects , Space Simulation
10.
J Radiat Res ; 47 Suppl A: A165-9, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16571933

ABSTRACT

In this paper, the results of a biodosimetry investigation are reported for two villages in the area of the Semipalatinsk nuclear testing site: Chekoman and Dolon. Chekoman village is considered to be relatively less affected by radiation in comparison with Dolon village. The distance between the two villages is about 100 km and the life styles of the residents are similar. Chromosome aberrations in lymphocytes collected from the residents of the two villages were analyzed using the fluorescence in situ hybridization technique. Our results showed that the average frequency of stable translocations for the Dolon group was significantly greater that of the Chekoman group. The elevated level of stable translocations with the Dolon residents corresponds to a dose of about 180 mSv.


Subject(s)
Biological Assay/methods , Chromosome Aberrations/statistics & numerical data , In Situ Hybridization, Fluorescence/statistics & numerical data , Lymphocytes/ultrastructure , Nuclear Warfare/statistics & numerical data , Radiation Injuries/epidemiology , Radiometry/methods , Adult , Body Burden , Humans , Incidence , Kazakhstan/epidemiology , Lymphocytes/radiation effects , Radiation Injuries/genetics , Relative Biological Effectiveness , Risk Assessment/methods , Risk Factors
11.
Radiat Res ; 160(4): 425-35, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12968931

ABSTRACT

Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.


Subject(s)
Chromosome Aberrations , Chromosomes, Human/radiation effects , Chromosomes, Human/ultrastructure , Linear Energy Transfer , Lymphocytes/cytology , Lymphocytes/radiation effects , Dose-Response Relationship, Radiation , Humans , In Situ Hybridization, Fluorescence , Interphase/radiation effects , Metaphase/radiation effects , Radiation Dosage , Relative Biological Effectiveness
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