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1.
Community Health Equity Res Policy ; : 2752535X241238095, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486412

ABSTRACT

OBJECTIVE: The goal of this study was to partner with community organizations to understand the research experiences of communities who speak languages other than English (LOE). METHODS: We conducted semi-structured qualitative interviews in Spanish, Nepali, Mandarin, French, or Kizigua with LOE community members and community leaders who completed recruitment and data collection. Audio-recordings of the interviews were transcribed and translated. We conducted qualitative coding using a mixed deductive-inductive analysis approach and thematic analyses using three rounds of affinity clustering. This study occurred in partnership with an established community-academic collaboration. RESULTS: Thirty community members and six community leaders were interviewed. 83% of LOE participants were born outside of the US and most participants (63%) had never participated in a prior research study. Six themes emerged from this work. Many participants did not understand the concept of research, but those that did thought that inclusion of LOE communities is critical for equity. Even when research was understood as a concept, it was often inaccessible to LOE individuals, particularly because of the lack of language services. When LOE participants engaged in research, they did not always understand their participation. Participants thought that improving research trust was essential and recommended partnering with community organizations and disseminating research results to the community. CONCLUSION: This study's results can serve as an important foundation for researchers seeking to include LOE communities in future research to be more inclusive and scientifically rigorous.

2.
Sci Adv ; 9(51): eadj3003, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38134286

ABSTRACT

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate (P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.


Subject(s)
Obesity , Stomach , Humans , Animals , Swine , Obesity/therapy , Obesity/metabolism , Mechanoreceptors/metabolism , Weight Gain , Vagus Nerve/physiology
3.
Article in English | MEDLINE | ID: mdl-37930649

ABSTRACT

OBJECTIVE: Interpersonal discrimination has been associated with adverse birth outcomes among Black populations, but few studies have examined the impact of discrimination among Latinx/Hispanic populations in the United States, especially in conjunction with resources that could be protective. The present study examined (a) if exposure to discrimination is associated with adverse birth outcomes for Latina/Hispanic women and (b) if prenatal social support buffers these links. METHOD: In two independent prospective studies of Latina/Hispanic women in Southern California (N = 84 and N = 102), the relation between maternal experience of discrimination and birth outcomes (length of gestation and birth weight) was examined. Additionally, social support was tested as a moderator of these relations. RESULTS: In both Studies 1 and 2, exposures to discrimination predicted adverse birth outcomes. Specifically, lifetime experiences of major discrimination predicted lower birth weight. Additionally, in Study 2, chronic experiences of everyday discrimination were linked to lower birth weight. In Study 1, major discrimination also predicted shorter gestational length. Importantly, in both studies, the presence of prenatal social support buffered associations between discrimination and poorer birth outcomes. CONCLUSIONS: Findings implicate discrimination as an important risk factor for adverse birth outcomes among women of Latina/Hispanic descent. Further policies, practice, and research on reducing discrimination and enhancing factors that promote resilience such as social support are needed to facilitate healthy births among Latina/Hispanic women, mitigate intergenerational harm of discrimination-related stress, and advance health equity at birth and across the lifespan. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

4.
Front Psychol ; 14: 1181055, 2023.
Article in English | MEDLINE | ID: mdl-37818418

ABSTRACT

Introduction: Evidence suggests that executive function (EF) may play a key role in development of PTSD, possibly influenced by factors such as trauma type and timing. Since EF can be improved through intervention, it may be an important target for promoting resilience to trauma exposure. However, more research is needed to understand the relation between trauma exposure, EF, and PTSD. The goal of this study was to improve understanding of EF as a potential antecedent or protective factor for the development of PTSD among military personnel. Method: In a cohort of U.S. Marines and Navy personnel (N = 1,373), the current study tested the association between exposure to traumatic events (pre-deployment and during deployment) and PTSD severity, and whether EF moderated these associations. Three types of pre-deployment trauma exposure were examined: cumulative exposure, which included total number of events participants endorsed as having happened to them, witnessed, or learned about; direct exposure, which included total number of events participants endorsed as having happened to them; and interpersonal exposure, which included total number of interpersonally traumatic events participants' endorsed. EF was measured using the Penn Computerized Neurocognitive Battery. Results: EF was associated with less PTSD symptom severity at pre-deployment, even when adjusting for trauma exposure, alcohol use, traumatic brain injury, and number of years in the military. EF also moderated the relation between cumulative trauma exposure and interpersonal trauma exposure and PTSD, with higher EF linked to a 20 and 33% reduction in expected point increase in PTSD symptoms with cumulative and interpersonal trauma exposure, respectively. Finally, higher pre-deployment EF was associated with reduced PTSD symptom severity at post-deployment, independent of deployment-related trauma exposure and adjusting for pre-deployment PTSD. Conclusion: Our results suggest that EF plays a significant, if small role in the development of PTSD symptoms after trauma exposure among military personnel. These findings provide important considerations for future research and intervention and prevention, specifically, incorporating a focus on improving EF in PTSD treatment.

5.
Article in English | MEDLINE | ID: mdl-37737880

ABSTRACT

The present study aimed to investigate the relationship between parental leave length and maternal depressive symptoms at six- and twelve-months postpartum and whether this relation was influenced by women's attitudes towards leave, whether leave was paid or unpaid, and the reason they returned to work. The sample included 115 working women recruited during pregnancy as part of a larger longitudinal study. Analyses revealed that maternal attitudes toward leave influenced the association between leave length and depressive symptoms. Specifically, longer leaves were associated with increased depressive symptoms for women who missed their previous activities at work. Furthermore, women who missed work and had leave for 16 weeks or more, exhibited higher depressive symptoms at six- and twelve-months. Last, results also indicated that women who returned to work solely for monetary reasons exhibited more depressive symptoms at six-months postpartum than those who returned to work for other reasons. This study is among the first to show that women's attitudes towards parental leave and their individual reasons for returning to work are important factors to consider that may have potential implications for parental leave policies.

6.
bioRxiv ; 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37503258

ABSTRACT

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

7.
Med ; 4(8): 541-553.e5, 2023 08 11.
Article in English | MEDLINE | ID: mdl-37339635

ABSTRACT

BACKGROUND: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. METHODS: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. FINDINGS: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). CONCLUSION: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. FUNDING: This work was supported by K. Lisa Yang Center for Bionics at MIT.


Subject(s)
Transcutaneous Electric Nerve Stimulation , Animals , Swine , Sciatic Nerve , Ultrasonography , Nerve Regeneration/physiology
8.
J Adolesc Health ; 72(6): 885-891, 2023 06.
Article in English | MEDLINE | ID: mdl-36788046

ABSTRACT

PURPOSE: In 2020, racially/ethnically minoritized (REMD) youth faced the "dual pandemics" of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). METHODS: A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). RESULTS: REMD adolescents' depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. DISCUSSION: REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth.


Subject(s)
COVID-19 , Racism , Female , Humans , Adolescent , Male , Depression , Longitudinal Studies , Pandemics
9.
Dev Psychopathol ; 35(2): 899-911, 2023 05.
Article in English | MEDLINE | ID: mdl-35256027

ABSTRACT

Preconception and prenatal stress impact fetal and infant development, and women of color are disproportionately exposed to sociocultural stressors like discrimination and acculturative stress. However, few studies examine links between mothers' exposure to these stressors and offspring mental health, or possible mitigating factors. Using linear regression, we tested associations between prenatally assessed maternal acculturative stress and discrimination on infant negative emotionality among 113 Latinx/Hispanic, Asian American, Black, and Multiethnic mothers and their children. Additionally, we tested interactions between stressors and potential pre- and postnatal resilience-promoting factors: community cohesion, social support, communalism, and parenting self-efficacy. Discrimination and acculturative stress were related to more infant negative emotionality at approximately 12 months old (M = 12.6, SD = .75). In contrast, maternal report of parenting self-efficacy when infants were 6 months old was related to lower levels of infant negative emotionality. Further, higher levels of parenting self-efficacy mitigated the relation between acculturative stress and negative emotionality. Preconception and prenatal exposure to sociocultural stress may be a risk factor for poor offspring mental health. Maternal and child health researchers, policymakers, and practitioners should prioritize further understanding these relations, reducing exposure to sociocultural stressors, and promoting resilience.


Subject(s)
Acculturation , Mental Health , Mothers , Social Discrimination , Stress, Psychological , Female , Humans , Infant , Pregnancy , Child Development , Hispanic or Latino/psychology , Mothers/psychology , Parenting/psychology , Stress, Psychological/psychology , Asian , Black or African American
10.
Front Psychol ; 13: 971350, 2022.
Article in English | MEDLINE | ID: mdl-36438371

ABSTRACT

Unpredictability is increasingly recognized as a primary dimension of early life adversity affecting lifespan mental health trajectories; screening for these experiences is therefore vital. The Questionnaire of Unpredictability in Childhood (QUIC) is a 38-item tool that measures unpredictability in childhood in social, emotional and physical domains. The available evidence indicates that exposure to unpredictable experiences measured with the QUIC predicts internalizing symptoms including depression and anxiety. The purpose of the present study was to validate English and Spanish brief versions (QUIC-5) suitable for administration in time-limited settings (e.g., clinical care settings, large-scale epidemiological studies). Five representative items were identified from the QUIC and their psychometric properties examined. The predictive validity of the QUIC-5 was then compared to the QUIC by examining mental health in four cohorts: (1) English-speaking adult women assessed at 6-months postpartum (N = 116), (2) English-speaking male veterans (N = 95), (3) English-speaking male and female adolescents (N = 155), and (4) Spanish-speaking male and female adults (N = 285). The QUIC-5 demonstrated substantial variance in distributions in each of the cohorts and is correlated on average 0.84 (r's = 0.81-0.87) with the full 38-item version. Furthermore, the QUIC-5 predicted internalizing symptoms (anxiety and depression) in all cohorts with similar effect sizes (r's = 0.16-0.39; all p's < 0.05) to the full versions (r's = 0.19-0.42; all p's < 0.05). In sum, the QUIC-5 exhibits good psychometric properties and is a valid alternative to the full QUIC. These findings support the future use of the QUIC-5 in clinical and research settings as a concise way to measure unpredictability, identify risk of psychopathology, and intervene accordingly.

11.
Sci Robot ; 7(70): eabp9066, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36170378

ABSTRACT

Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap's mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery (P < 0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.


Subject(s)
Nanoparticles , Robotic Surgical Procedures , Administration, Oral , Animals , Gastrointestinal Tract/metabolism , Insulin/metabolism , Mucus/metabolism , Peptides/metabolism , Swine , Vancomycin/metabolism
12.
F S Rep ; 3(2 Suppl): 5-13, 2022 May.
Article in English | MEDLINE | ID: mdl-35937456

ABSTRACT

Currently, racial and ethnic differences in adverse birth outcomes and infant mortality are some of the largest and most persistent health disparities in the United States. This narrative review article synthesizes existing literature to present a conceptual model of how racism-related stress and adversity are critical determinants of such disparities. We describe how historical and ongoing racism has created conditions wherein women of color are disproportionately exposed to chronic, multilayered stress and adversity and how the biological consequences of exposure to these stressors confers risk for adverse birth outcomes. Next, we identify important priorities and considerations for future research, including the heterogeneity of racism-related stressors, biomarkers and mechanisms, chronicity and sensitive periods of exposure, developmental programming of lifespan health, resilience, and community-engaged research methodologies.

13.
J Affect Disord ; 299: 246-255, 2022 02 15.
Article in English | MEDLINE | ID: mdl-34798146

ABSTRACT

BACKGROUND: The COVID-19 era is a time of unprecedented stress, and there is widespread concern regarding its short- and long-term mental health impact. Adolescence is a sensitive period for the emergence of latent psychopathology vulnerabilities, often activated by environmental stressors. The present study examined COVID-19's impact on adolescent depression and possible influences of different domains of social connectedness (loneliness, social media use, social video game time, degree of social activity participation). METHODS: A community sample of 175 adolescents (51% boys, mean age = 16.01 years) completed questionnaires once before and twice during the COVID-19 pandemic. Piecewise growth modeling examined the acute (7 weeks) and persistent (8 months) effects of COVID-19 on depressive symptoms, and differences across sex and social connectedness. RESULTS: Significant increases in depressive symptoms followed pandemic onset for boys and girls. However, this increase was earlier and more pronounced among girls than boys, whose depression only increased significantly during the persistent period and to a lesser degree. Trajectories of depression were influenced by loneliness and social connections. LIMITATIONS: Most participants had economic stability and minimal exposure to the virus. Exacerbation of depressive symptoms may be more severe in higher risk populations. CONCLUSIONS: Adolescent depression levels have increased during COVID-19, and are higher for girls and those who are lonely. Enhanced screening and management for adolescent depression and social connectedness could play a critical role in mitigating the negative mental health fallout of COVID-19 and future pandemics within this population.


Subject(s)
COVID-19 , Adolescent , Depression/epidemiology , Economic Stability , Female , Humans , Male , Pandemics , SARS-CoV-2 , Sex Characteristics
14.
Philos Trans A Math Phys Eng Sci ; 380(2214): 20210125, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-34802278

ABSTRACT

The outbreak of the novel coronavirus, COVID-19, has become one of the most severe pandemics in human history. In this paper, we propose to leverage social media users as social sensors to simultaneously predict the pandemic trends and suggest potential risk factors for public health experts to understand spread situations and recommend proper interventions. More precisely, we develop novel deep learning models to recognize important entities and their relations over time, thereby establishing dynamic heterogeneous graphs to describe the observations of social media users. A dynamic graph neural network model can then forecast the trends (e.g. newly diagnosed cases and death rates) and identify high-risk events from social media. Based on the proposed computational method, we also develop a web-based system for domain experts without any computer science background to easily interact with. We conduct extensive experiments on large-scale datasets of COVID-19 related tweets provided by Twitter, which show that our method can precisely predict the new cases and death rates. We also demonstrate the robustness of our web-based pandemic surveillance system and its ability to retrieve essential knowledge and derive accurate predictions across a variety of circumstances. Our system is also available at http://scaiweb.cs.ucla.edu/covidsurveiller/. This article is part of the theme issue 'Data science approachs to infectious disease surveillance'.


Subject(s)
COVID-19 , Social Media , Data Mining , Humans , Pandemics , SARS-CoV-2
15.
Am J Orthopsychiatry ; 91(3): 386-397, 2021.
Article in English | MEDLINE | ID: mdl-33793254

ABSTRACT

It is now well understood that exposure to Adverse Childhood Experiences (ACEs) is negatively linked to health and well-being across the lifespan. In an effort to disrupt ACEs exposure and its effects, there is a nationwide movement to screen for ACEs in primary care, despite a lack of well-established guidelines for assessing and responding to risk within routine care. Additionally, developing culturally responsive models of ACEs assessment is imperative, particularly because racial and ethnic minority populations face disproportionate risk of exposure to ACEs and disparities in quality of health care. Using mixed methods, we explored the feasibility, acceptability, and utility of conducting ACEs routine inquiry with an ethnically and economically diverse pediatric population through a unique collaborative practice model (CPM) consisting of an integrated, multidisciplinary team within primary care. In the CPM study, 163 children from a safety-net health system were enrolled; of those, an ACEs questionnaire was collected from 158 (97%) study participants as part of their mental health evaluation. The sample was highly ACEs exposed, with 40% of children and 56% of teens having scores of four or more. There were significant associations between level of ACEs exposure and degree of mental health impairment in both children and teens. Providers viewed the ACEs assessment process as feasible, acceptable, and to have utility for the care of the study's diverse pediatric population. Findings highlight benefits, challenges, cultural considerations and recommendations for promoting health equity through a primary-care integrated ACEs assessment model. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Adverse Childhood Experiences , Health Equity , Adolescent , Child , Ethnicity , Humans , Minority Groups
16.
Am Psychol ; 76(2): 364-378, 2021.
Article in English | MEDLINE | ID: mdl-33734801

ABSTRACT

Widespread implementation of adverse childhood experiences (ACEs) screening is occurring in the United States in response to policies and practice recommendations. However, limited research has established how these screening efforts impact the health care system and ultimately health outcomes. This article examines the current knowledge base on screening in medical settings. A scoping review of articles reporting on ACEs screening and prevalence in the United States was conducted. Of the 1,643 unique studies across two decades, 12 articles meeting criteria included nine on routine screening in medical settings and three on population-based surveys. A Monte Carlo simulation model was designed to synthesize evidence, identify key areas of uncertainty, and explore service system implications. Results indicated significant heterogeneity in the proportion of respondents who reported ACEs, with 6% to 64% of patients reporting 1+ ACEs and .01% to 40.7% reporting 4+ ACEs. Gaps in the literature were identified regarding cut-scores for referrals and referral completion rates. Three scenarios, modeled based on these data and past research on behavioral health screenings in pediatric primary care, demonstrated how ACEs screening may differentially impact behavioral health care systems. Priorities for future research were highlighted to refine estimates of the likely impact of ACEs screening on health care delivery. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Adverse Childhood Experiences , Mental Health Services , Adverse Childhood Experiences/statistics & numerical data , Child , Humans , Mental Health Services/statistics & numerical data , Prevalence , United States
17.
J Interpers Violence ; 36(19-20): 9484-9506, 2021 10.
Article in English | MEDLINE | ID: mdl-31402767

ABSTRACT

Youth community violence has been linked with depressive and anxious symptoms, and aggressive behavior; however, little research has examined different combinations of emotional and behavioral adjustment among community-violence-exposed youth, or individual characteristics that may account for different patterns of emotional and behavioral adjustment in community-violence-exposed youth. This research used person-centered methods to examine how gender, temperament characteristics, and prior exposure to community violence were linked with classes of community violence exposure and internalizing and externalizing adjustment among a sample of urban African American youth. Participants were 464 African American adolescents (46.7% female; mean age = 14.83, SD = .43) who reported their community violence exposure in Grade 9 and for whom reports of depressive and anxious symptoms, and aggressive behavior were available. Latent class analysis identified four classes of adolescents distinguished by their exposure to community violence exposure and internalizing and externalizing behavior. The two classes with high community violence exposure were characterized by internalizing symptoms or aggressive behavior; the two classes with low community violence exposure had low internalizing symptoms with moderate aggression or had all moderate symptoms. These community violence adjustment classes were distinguished by gender, history of community violence exposure, behavioral inhibition, and fight-flight-freeze systems. Findings highlight heterogeneity in internalizing and externalizing responses of community-violence-exposed youth and suggest factors that explain community violence exposure, repeat exposure, and responses to community violence exposure.


Subject(s)
Exposure to Violence , Adolescent , Black or African American , Aggression , Female , Humans , Individuality , Male , Violence
18.
Psychol Trauma ; 12(5): 439-442, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32551756

ABSTRACT

The present commentary offers a timely exploration of the racial trauma experienced by Asian, Black, and Latinx communities as it relates to COVID-19. Instances of individual, cultural, and structural racism and implications for mental health are discussed. Evidence-based strategies are identified for mental health professionals in order to support healing and mitigate the risk of further racial traumas. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Subject(s)
Culturally Competent Care , Healthcare Disparities , Mental Health Services , Psychological Trauma/ethnology , Psychological Trauma/therapy , Racism/ethnology , Adult , COVID-19 , Child , Coronavirus Infections , Humans , Pandemics , Pneumonia, Viral , Socialization , United States/ethnology
19.
Aging Cell ; 19(7): e13176, 2020 07.
Article in English | MEDLINE | ID: mdl-32567221

ABSTRACT

Oxoaldehyde stress has recently emerged as a major source of tissue damage in aging and age-related diseases. The prevailing mechanism involves methylglyoxal production during glycolysis and modification of arginine residues through the formation of methylglyoxal hydroimidazolones (MG-H1). We now tested the hypothesis that oxidation of vitamin C (ascorbic acid or ASA) contributes to this damage when the homeostatic redox balance is disrupted especially in ASA-rich tissues such as the eye lens and brain. MG-H1 measured by liquid chromatography mass spectrometry is several fold increased in the lens and brain from transgenic mice expressing human vitamin C transporter 2 (hSVCT2). Similarly, MG-H1 levels are increased two- to fourfold in hippocampus extracts from individuals with Alzheimer's disease (AD), and significantly higher levels are present in sarkosyl-insoluble tissue fractions from AD brain proteins than in the soluble fractions. Moreover, immunostaining with antibodies against methylglyoxal hydroimidazolones reveals similar increase in substantia nigra neurons from individuals with Parkinson's disease. Results from an in vitro incubation experiment suggest that accumulated catalytic metal ions in the hippocampus during aging could readily accelerate ASA oxidation and such acceleration was significantly enhanced in AD. Modeling studies and intraventricular injection of 13 C-labeled ASA revealed that ASA backbone carbons 4-6 are incorporated into MG-H1 both in vitro and in vivo, likely via a glyceraldehyde precursor. We propose that drugs that prevent oxoaldehyde stress or excessive ASA oxidation may protect against age-related cataract and neurodegenerative diseases.


Subject(s)
Aldehydes/metabolism , Ascorbic Acid/therapeutic use , Cataract/etiology , Neurodegenerative Diseases/complications , Adult , Aged , Aged, 80 and over , Aging , Animals , Ascorbic Acid/pharmacology , Humans , Mice , Mice, Transgenic , Middle Aged
20.
Invest Ophthalmol Vis Sci ; 61(5): 2, 2020 05 11.
Article in English | MEDLINE | ID: mdl-32392310

ABSTRACT

Purpose: Intraocular pressure (IOP), the primary risk factor for primary open-angle glaucoma, is determined by resistance to aqueous outflow through the trabecular meshwork (TM). IOP homeostasis relies on TM responses to mechanical stretch. To model the effects of elevated IOP on the TM, this study sought to identify coding and non-coding RNAs differentially expressed in response to mechanical stretch. Methods: Monolayers of TM cells from non-glaucomatous donors (n = 5) were cultured in the presence or absence of 15% mechanical stretch, 1 cycle/second, for 24 hours using a computer-controlled Flexcell unit. We profiled mRNAs and lncRNAs with stranded total RNA sequencing and microRNA (miRNA) expression with NanoString-based miRNA assays. We used two-tailed paired t-tests for mRNAs and long non-coding RNAs (lncRNAs) and the Bioconductor limma package for miRNAs. Gene ontology and pathway analyses were performed with WebGestalt. miRNA-mRNA interactions were identified using Ingenuity Pathway Analysis Integrative miRNA Target Finder software. Validation of differential expression was conducted using droplet digital PCR. Results: We identified 219 mRNAs, 42 miRNAs, and 387 lncRNAs with differential expression in TM cells upon cyclic mechanical stretch. Pathway analysis indicated significant enrichment of genes involved in steroid biosynthesis, glycerolipid metabolism, and extracellular matrix-receptor interaction. We also identified several miRNA master regulators (miR-125a-5p, miR-30a-5p, and miR-1275) that regulate several mechanoresponsive genes. Conclusions: To our knowledge, this is the first demonstration of the differential expression of coding and non-coding RNAs in a single set of cells subjected to cyclic mechanical stretch. Our results validate previously identified, as well as novel, genes and pathways.


Subject(s)
MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , Stress, Mechanical , Trabecular Meshwork/metabolism , Cells, Cultured , Down-Regulation , Humans , Up-Regulation
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