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1.
Prev Sci ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225944

RESUMEN

Beginning with the successful sequencing of the human genome two decades ago, the possibility of developing personalized health interventions based on one's biology has captured the imagination of researchers, medical providers, and individuals seeking health care services. However, the application of a personalized medicine approach to emotional and behavioral health has lagged behind the development of personalized approaches for physical health conditions. There is potential value in developing improved methods for integrating biological science with prevention science to identify risk and protective mechanisms that have biological underpinnings, and then applying that knowledge to inform prevention and intervention services for emotional and behavioral health. This report represents the work of a task force appointed by the Board of the Society for Prevention Research to explore challenges and recommendations for the integration of biological and prevention sciences. We present the state of the science and barriers to progress in integrating the two approaches, followed by recommended strategies that would promote the responsible integration of biological and prevention sciences. Recommendations are grounded in Community-Based Participatory Research approaches, with the goal of centering equity in future research aimed at integrating the two disciplines to ultimately improve the well-being of those who have disproportionately experienced or are at risk for experiencing emotional and behavioral problems.

2.
Eur J Neurosci ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251212

RESUMEN

Combined use of fentanyl and methamphetamine (FENT + METH) has increased in recent years and has been documented in a growing number overdose deaths each year. The impact of FENT + METH on behavior and neurobiology is not well understood. In this study, male and female Long Evans rats were tested on a limited access, fixed ratio 1 self-administration schedule for increasing doses (1.25-5 µg/kg/infusion; iv) of fentanyl, with and without a single dose (0.1 mg/kg/infusion; iv) of methamphetamine, for 15 days. FENT + METH abolished dose responsiveness to fentanyl in all rats and accelerated intake in males, resulting in patterns of responding that may be more likely to result in adverse effects. Ex vivo slice voltammetry in the nucleus accumbens core showed decreases in dopamine release and reuptake (Vmax) following FENT + METH exposure, compared with saline, fentanyl, and methamphetamine alone groups at baseline parameters. Further, significant decreases in dopamine release were observed across a range of stimulation intensities following FENT + METH exposure. Overall, male and female rats displayed sex-specific behavioral and neurobiological responses to FENT + METH exposure, with males displaying increased vulnerability.

3.
Midwifery ; 139: 104150, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39260127

RESUMEN

BACKGROUND: Diet during pregnancy is a key factor in the success of pregnancy. However, several studies have found pregnant women have low adherence to dietary recommendations. The midwife is a key health professional to provide nutrition education for pregnant women. Thus, it is important to know in detail her role in this respect. AIM: To explore how Spanish midwives undertake nutrition education in order to assess the need for specific interventions aimed at improving the health of pregnant women. METHODS: A cross-sectional descriptive observational study was undertaken using an online questionnaire (466 responses). FINDINGS: Spanish midwives recognise the importance of nutrition in pregnancy and that advising pregnant women in this regard is part of their role. In fact, all community midwives discuss nutrition to pregnant women, although they recognise that they do not feel particularly comfortable in dealing with certain topics, which could be related to a lack of mastery of the subjects. Midwives (56.5 %) rated the nutrition training their received as poor. CONCLUSION: In order to guarantee the quality in the nutrition education provided by Spanish midwives to promote the health of pregnant women, our results demonstrate the importance of strengthening both the nutrition content of midwives' training programmes and the ongoing support they receive throughout their professional life.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39152272

RESUMEN

In child disruptive behavior treatment, successful parent management training (PMT) outcomes are dependent on parents' use of strategies outside of sessions. This study aimed to identify the influence of parental locus of control (PLOC) on a key treatment acceptability variable: parents' willingness to implement PMT strategies. We sought to investigate this relationship for individual strategies within PMT, given the composite nature of the intervention. In this study, 109 parents of children (ages 2-12) with disruptive behavior watched brief videos detailing three proactive PMT strategies (child-directed interaction, effective commands, positive attention) and three reactive PMT strategies (ignoring, time out, and removal of privileges) and rated their willingness to implement each strategy. Internal PLOC predicted greater overall willingness to use PMT strategies, above and beyond the influence of child age, child gender, and disruptive behavior severity. Notably, the relationship between willingness and PLOC differed across individual strategies. PLOC predicted willingness to implement proactive PMT strategies to a greater degree than willingness to implement reactive strategies. External PLOC may be a greater barrier to use of proactive strategies because of these strategies' misalignment with external PLOC-related beliefs. Results have implications for the personalization of PMT based on parent cognitions, as well as for the separate analysis of individual components of PMT in future research.

6.
Am J Vet Res ; : 1-9, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39163891

RESUMEN

OBJECTIVE: To determine the ability of bacteria commonly isolated from equine limb wounds to survive in saltwater obtained from an equine hydrotherapy unit at different salinity concentrations and temperatures. METHODS: Saltwater samples were obtained over a 2-week period (January 22, 2024 to February 2, 2024) from an equine hydrotherapy unit used for clinical patients, kept at either full salinity per manufacturer recommendations or diluted to half salinity to mimic the dilution that likely occurs in the clinical setting between cases when holding tanks are replenished with tap water only. Samples were then autoclaved to eliminate preexisting bacterial contamination before individual inoculation with Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus zooepidemicus. Each inoculated sample was maintained at 2, 22, or 44 °C to represent typical holding tank conditions. The bacterial concentration was determined at each condition every 24 hours up to and including 96 hours. The lower limit of detection was set at 1 CFU/mL. RESULTS: Salinity did not affect bacterial survival. Bacterial concentrations generally decreased with increasing temperature over time. Escherichia coli, S aureus, and S zooepidemicus concentrations decreased to the lower limit of detection at 44 °C by 24 to 48 hours, while P aeruginosa concentrations significantly decreased over 24 hours but remained well above the lower limit of detection. CONCLUSIONS: Common bacterial isolates of equine limb wounds can survive in typical saltwater hydrotherapy conditions. CLINICAL RELEVANCE: Further investigation is warranted to determine the clinical relevance of these findings including protocols for hydrotherapy unit disinfection, wastage of treatment water, and case inclusion/exclusion criteria.

7.
Eur J Neurosci ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39161062

RESUMEN

For over four decades, fast-scan cyclic voltammetry (FSCV) has been used to selectively measure neurotransmitters such as dopamine (DA) with high spatial and temporal resolution, providing detailed information about the regulation of DA in the extracellular space. FSCV is an optimal method for determining concentrations of stimulus-evoked DA in brain tissue. When modelling diseases involving disturbances in DA transmission, preclinical rodent models are especially useful because of the availability of specialized tools and techniques that serve as a foundation for translational research. There is known heterogeneity in DA dynamics between and within DA-innervated brain structures and between males and females. However, systematic evaluations of sex- and species-differences across multiple areas are lacking. Therefore, using FSCV, we captured a broad range of DA dynamics across five sub-regions of the dorsal and ventral striatum of males and females of both rats and mice that reflect the functional heterogeneity of DA kinetics and dynamics within these structures. While numerous differences were found, in particular, we documented a strong, consistent pattern of increased DA transporter activity in females in all of the regions surveyed. The data herein are intended to be used as a resource for further investigation of DA terminal function.

8.
Behav Sci (Basel) ; 14(8)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39199065

RESUMEN

Children and adolescents with autism spectrum disorder (ASD) are at a greater risk of seeking emergency department (ED) services during behavioral crises, such as acute aggression, suicidal or homicidal ideation, self-injury, or other types of challenging behavior (e.g., pica, dangerous behaviors). Research demonstrates children and adolescents with ASD often return to the ED due to challenging behavior, suggesting that gaps in care exist (e.g., follow-up appointments, referrals). However, the current knowledge basis is largely based on data from other countries. Given the unique landscape of healthcare in the United States, it is prudent to elucidate characteristics of children and adolescents with ASD who are seeking emergency care due to challenging behavior, as well as systems-level factors that both contribute to our understanding of challenging behavior and ASD in ED settings. In this study, we focus on frequency and characteristics of children and adolescents with ASD presenting to the ED with challenging behavior over the course of a 6-year period in the Midwest region of the United States. Clinical implications for ED staff are discussed.

9.
JCI Insight ; 9(14)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-39133651

RESUMEN

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.


Asunto(s)
Linfocitos T CD8-positivos , Oligodesoxirribonucleótidos , Receptor Toll-Like 9 , Animales , Receptor Toll-Like 9/agonistas , Ratones , Oligodesoxirribonucleótidos/farmacología , Oligodesoxirribonucleótidos/administración & dosificación , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Sarcoma/radioterapia , Sarcoma/terapia , Sarcoma/patología , Inyecciones Intralesiones , Sistemas CRISPR-Cas , Sarcoma Experimental/patología , Sarcoma Experimental/radioterapia , Femenino
10.
Sensors (Basel) ; 24(16)2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39205017

RESUMEN

Assessing physical activity is important in the treatment of chronic conditions, including chronic low back pain (cLBP). ActiGraph™, a widely used physical activity monitor, collects raw acceleration data, and processes these data through proprietary algorithms to produce physical activity measures. The purpose of this study was to replicate ActiGraph™ algorithms in MATLAB and test the validity of this method with both healthy controls and participants with cLBP. MATLAB code was developed to replicate ActiGraph™'s activity counts and step counts algorithms, to sum the activity counts into counts per minute (CPM), and categorize each minute into activity intensity cut points. A free-living validation was performed where 24 individuals, 12 cLBP and 12 healthy, wore an ActiGraph™ GT9X on their non-dominant hip for up to seven days. The raw acceleration data were processed in both ActiLife™ (v6), ActiGraph™'s data analysis software platform, and through MATLAB (2022a). Percent errors between methods for all 24 participants, as well as separated by cLBP and healthy, were all less than 2%. ActiGraph™ algorithms were replicated and validated for both populations, based on minimal error differences between ActiLife™ and MATLAB, allowing researchers to analyze data from any accelerometer in a manner comparable to ActiLife™.


Asunto(s)
Algoritmos , Ejercicio Físico , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/fisiopatología , Dolor de la Región Lumbar/diagnóstico , Ejercicio Físico/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Actigrafía/métodos , Actigrafía/instrumentación , Acelerometría/métodos , Acelerometría/instrumentación , Dolor Crónico/fisiopatología , Dolor Crónico/diagnóstico , Estudios de Casos y Controles
11.
Mol Ther ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39205389

RESUMEN

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

12.
Sex Reprod Healthc ; 41: 101011, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39102769

RESUMEN

OBJECTIVE: Given the call to reduce rates of non-medically indicated cesarean deliveries (CDs) by encouraging trials of labor after cesarean (TOLAC), this study looks at social characteristics of patients choosing a TOLAC versus a scheduled repeat cesarean delivery (SRCD) to determine disparities regarding delivery method choice. METHODS: This was a retrospective cohort study of patients with a history of one CD between April 29, 2015-April 29, 2020. Patients were divided based on type of delivery chosen at admission. Chi-squared tests examined proportional differences between groups and logistic regression models examined odd ratios of choosing TOLAC versus SRCD according to socially dependent categories including race/ethnicity, health insurance, pre-pregnancy body mass index, and Social Vulnerability Index (SVI). RESULTS: 1,983 patients were included. Multivariable logistic regression models revealed that patients with a high SVI (reference: low/medium SVI) (AOR 2.0, CI: 1.5, 2.5), self-identified as Black/ African American (AOR: 2.4, CI: 1.6, 3.6) or Hispanic/Latina (AOR: 2.0, CI: 1.4, 2.8) (reference: White), had public insurance (reference: private insurance) (AOR: 3.7, CI: 2.8, 5.0), and who had an obese BMI (reference: non-obese BMI) were more likely to opt for a TOLAC rather than SRCD. CONCLUSION: These findings demonstrate differences in delivery method preferences. Specifically, more disadvantaged patients are more likely to choose TOLAC, suggesting that social and economic factors may play a role in delivery preferences. These findings have implications for improving individualized counselling and engaging in shared decision-making around mode of delivery.


Asunto(s)
Esfuerzo de Parto , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Conducta de Elección , Parto Vaginal Después de Cesárea/estadística & datos numéricos , Índice de Masa Corporal , Cesárea Repetida/estadística & datos numéricos , Cesárea/estadística & datos numéricos , Seguro de Salud , Etnicidad , Negro o Afroamericano/estadística & datos numéricos , Factores Socioeconómicos , Modelos Logísticos , Hispánicos o Latinos/estadística & datos numéricos , Disparidades en Atención de Salud
13.
J Neurophysiol ; 132(3): 1056-1073, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39110896

RESUMEN

Besides having high potency and efficacy at the µ-opioid (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuron (MSN) activity via opioid receptors or α1-adrenoceptors in dopamine type 1 or type 2 receptor (D1 or D2)-expressing MSNs. In neuronal and mixed-glial cocultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials. Overnight exposure of cocultures to 100 nM fentanyl severely reduced the proportion of MSNs with spontaneous action potentials, which was unaffected by coexposure to the opioid receptor antagonist naloxone (10 µM) but fully negated by coadministering the pan-α1-adrenoceptor inverse agonist prazosin (100 nM) and partially reversed by the selective α1A-adrenoceptor antagonist RS 100329 (300 nM). Acute fentanyl (100 nM) exposure modestly reduced the frequency of action potentials and caused firing rate adaptations in D2, but not D1, MSNs. Prolonged (2-5 h) fentanyl (100 nM) application dramatically attenuated firing rates in both D1 and D2 MSNs. To identify possible cellular sites of α1-adrenoceptor action, α1-adrenoceptors were localized in subpopulations of striatal astroglia and neurons by immunocytochemistry and Adra1a mRNA by in situ hybridization in astrocytes. Thus, sustained fentanyl exposure can inhibit striatal MSN activity via a nonopioid receptor-dependent pathway, which may be modulated via complex actions in α1-adrenoceptor-expressing striatal neurons and/or glia.NEW & NOTEWORTHY Acute fentanyl exposure attenuated the activity of striatal medium spiny neurons (MSNs) in vitro and in dopamine D2, but not D1, receptor-expressing MSNs in ex vivo slices. By contrast, sustained fentanyl exposure suppressed the spontaneous activity of MSNs cocultured with glia through a nonopioid receptor-dependent mechanism modulated, in part, by α1-adrenoceptors. Fentanyl exposure can affect striatal function via a nonopioid receptor mechanism of action that appears mediated by α1-adrenoreceptor-expressing striatal neurons and/or astroglia.


Asunto(s)
Potenciales de Acción , Analgésicos Opioides , Técnicas de Cocultivo , Cuerpo Estriado , Fentanilo , Neuroglía , Neuronas , Animales , Fentanilo/farmacología , Neuroglía/efectos de los fármacos , Neuroglía/fisiología , Neuroglía/metabolismo , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratones , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiología , Analgésicos Opioides/farmacología , Potenciales de Acción/efectos de los fármacos , Receptores Opioides/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/efectos de los fármacos , Masculino , Antagonistas de Narcóticos/farmacología , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/antagonistas & inhibidores , Células Cultivadas
14.
bioRxiv ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39211138

RESUMEN

Synaptogyrin-3, a functionally obscure synaptic vesicle protein, interacts with vesicular monoamine and dopamine transporters, bringing together dopamine release and reuptake sites. Synaptogyrin-3 was reduced by chronic cocaine exposure in both humans and rats, and synaptogyrin-3 levels inversely correlated with motivation to take cocaine in rats. Synaptogyrin-3 overexpression in dopamine neurons reduced cocaine self-administration, decreased anxiety-like behavior, and enhanced cognitive flexibility. Overexpression also enhanced nucleus accumbens dopamine signaling and prevented cocaine-induced deficits, suggesting a putative therapeutic role for synaptogyrin-3 in cocaine use disorder.

15.
Arch Biochem Biophys ; 759: 110088, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38992456

RESUMEN

Ponatinib and tofacitinib, established kinase inhibitors and FDA-approved for chronic myeloid leukemia and rheumatoid arthritis, are recently undergoing investigation in diverse clinical trials for potential repurposing. The aryl hydrocarbon receptor (AhR), a transcription factor influencing a spectrum of physiological and pathophysiological activities, stands as a therapeutic target for numerous diseases. This study employs molecular modelling tools and in vitro assays to identify ponatinib and tofacitinib as AhR ligands, elucidating their binding and molecular interactions in the AhR PAS-B domain. Molecular docking analyses revealed that ponatinib and tofacitinib occupy the central pocket within the primary cavity, similar to AhR agonists 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and (benzo[a]pyrene) B[a]P. Our simulations also showed that these compounds exhibit good stability, stabilizing many hot spots within the PAS-B domain, including the Dα-Eα loop, which serves as a regulatory element for the binding pocket. Binding energy calculations highlighted ponatinib's superior predicted affinity, revealing F295 as a crucial residue in maintaining strong interaction with the two compounds. Our in vitro data suggest that ponatinib functions as an AhR antagonist, blocking the downstream signaling of AhR pathway induced by TCDD and B[a]P. Additionally, both tofacitinib and ponatinib cause impairment in AhR-regulated CYP1A1 enzyme activity induced by potent AhR agonists. This study unveils ponatinib and tofacitinib as potential modulators of AhR, providing valuable insights into their therapeutic roles in AhR-associated diseases and enhancing our understanding of the intricate relationship between kinase inhibitors and AhR.


Asunto(s)
Imidazoles , Piperidinas , Piridazinas , Pirimidinas , Receptores de Hidrocarburo de Aril , Humanos , Sitios de Unión , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Imidazoles/farmacología , Imidazoles/química , Ligandos , Simulación del Acoplamiento Molecular , Piperidinas/farmacología , Piperidinas/química , Unión Proteica , Piridazinas/farmacología , Piridazinas/química , Pirimidinas/farmacología , Pirimidinas/química , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/química , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , /farmacología
16.
JCI Insight ; 9(16)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012710

RESUMEN

Fibrosis in the lung is thought to be driven by epithelial cell dysfunction and aberrant cell-cell interactions. Unveiling the molecular mechanisms of cellular plasticity and cell-cell interactions is imperative to elucidating lung regenerative capacity and aberrant repair in pulmonary fibrosis. By mining publicly available RNA-Seq data sets, we identified loss of CCAAT enhancer-binding protein alpha (CEBPA) as a candidate contributor to idiopathic pulmonary fibrosis (IPF). We used conditional KO mice, scRNA-Seq, lung organoids, small-molecule inhibition, and potentially novel gene manipulation methods to investigate the role of CEBPA in lung fibrosis and repair. Long-term (6 months or more) of Cebpa loss in AT2 cells caused spontaneous fibrosis and increased susceptibility to bleomycin-induced fibrosis. Cebpa knockout (KO) in these mice significantly decreased AT2 cell numbers in the lung and reduced expression of surfactant homeostasis genes, while increasing inflammatory cell recruitment as well as upregulating S100a8/a9 in AT2 cells. In vivo treatment with an S100A8/A9 inhibitor alleviated experimental lung fibrosis. Restoring CEBPA expression in lung organoids ex vivo and during experimental lung fibrosis in vivo rescued CEBPA deficiency-mediated phenotypes. Our study establishes a direct mechanistic link between CEBPA repression, impaired AT2 cell identity, disrupted tissue homeostasis, and lung fibrosis.


Asunto(s)
Bleomicina , Proteínas Potenciadoras de Unión a CCAAT , Homeostasis , Ratones Noqueados , Animales , Ratones , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Bleomicina/toxicidad , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/inducido químicamente , Humanos , Modelos Animales de Enfermedad , Pulmón/patología , Pulmón/metabolismo , Organoides/metabolismo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Masculino
17.
Implement Sci Commun ; 5(1): 78, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026346

RESUMEN

BACKGROUND: There has been increased attention to the need for, and the positive impact of, engaged or participatory science in recent years. Implementation scientists have an opportunity to leverage and contribute to engagement science (ES) through the systematic integration of engagement into implementation science (IS). The purpose of this study was to gather information from researchers and others to develop a prioritized list of research needs and opportunities at the intersection of IS and ES. METHODS: We conducted three Zoom-based focus groups with 20 researchers to generate a list of unmet needs, barriers, and to describe normative themes about use of ES and IS. Then a panel of nine experts in IS and/or engagement ranked the needs and barriers using a survey and met via a Zoom meeting to discuss and generate research opportunities and questions, with reference to the focus group outputs. RESULTS: Respondents and experts concurred on the importance of engagement in IS. Focus group participants reported 28 needs and barriers under the themes of 1) need for best practice guidance related to engagement processes and outcomes and 2) structural barriers to integrating ES in IS. The expert panel prioritized six structural barriers and four barriers related to generating best practice guidance, with corresponding recommendations on research opportunities. Example research opportunities related to engagement processes included: define "successful" engagement in IS contexts; adapt engagement tools and best practices from other disciplines into IS. Example research opportunities related to outcomes included: assess the impact of engagement on IS outcomes; examine engagement practices that lead to optimal engaged research. Example research opportunities related to structural barriers included: leverage research evidence to create structural changes needed to expand support for engaged IS; examine factors that influence institutional buy-in of engagement in IS. CONCLUSIONS: Research needs exist that relate to engagement processes, outcomes, and structural barriers, even for scientists who value engaged research. Expert panelists recommended sequential and reinforcing research opportunities that implementation and engagement scientists can tackle together to advance both fields and health equity. Future work should assess insights from broader invested parties, particularly patients and community members.

18.
Child Abuse Negl ; 154: 106887, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981310

RESUMEN

BACKGROUND: In child welfare, caseloads are frequently far higher than optimal. Not all cases are created equal; however, little is known about which combination and interaction of factors make caseloads more challenging and impact child and family outcomes. OBJECTIVE: This study aims to identify which case, provider, and organizational factors most strongly differentiate between families with favorable and less-than-positive treatment outcomes. PARTICIPANTS AND SETTING: Participants were 25 family advocacy program providers and 17 supervisors at 11 Department of the Air Force installations. METHODS: Following informed consent, participants completed demographic and caseload questionnaires, and we collected information about organizational factors. Providers were sent a weekly case update and burnout questionnaire for seven months. We used linear mixed-effects model tree (LMM tree) algorithms to determine the provider, client, and organizational characteristics that best distinguish between favorable vs. unfavorable outcomes. RESULTS: The LMM tree predicting provider-rated treatment success yielded three significant partitioning variables: (a) commander involvement, (b) case complexity, and (c) % of clients in a high-risk field. The LMM predicting client-rated treatment progress yielded seven significant partitioning variables: (a) command involvement; (b) ease of reaching tenant unit command; (c) # of high-risk cases; (d) % of clients receiving Alcohol and Drug Abuse Prevention and Treatment services; (e) ease of reaching command; (f) % of clients with legal involvement; (g) provider age. CONCLUSIONS: This study is a first step toward developing a dynamic caseload management tool. An intelligent, algorithm-informed approach to case assignment could help child welfare agencies operate in their typically resource-scarce contexts in a manner that improves outcomes.


Asunto(s)
Maltrato a los Niños , Humanos , Niño , Femenino , Masculino , Adulto , Encuestas y Cuestionarios , Resultado del Tratamiento , Protección a la Infancia , Carga de Trabajo/psicología , Persona de Mediana Edad
19.
JAMA Intern Med ; 184(9): 1083-1093, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39037795

RESUMEN

Importance: Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Objective: To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Design, Setting, and Participants: This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Exposures: Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Main Outcomes and Measures: Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. Results: The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. Conclusions and Relevance: The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.


Asunto(s)
Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Resultado del Embarazo/epidemiología , Complicaciones del Embarazo/epidemiología , California/epidemiología , Uso de la Marihuana/epidemiología , Uso de la Marihuana/efectos adversos , Adulto Joven , Cannabis/efectos adversos
20.
JAMA Ophthalmol ; 142(9): 808-817, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39052244

RESUMEN

Importance: Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management. Objective: To describe a severe case of SANS associated with 2 potentially predisposing factors. Design, Setting, and Participants: Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS). Exposure: Weightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut's flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 µg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort. Main Outcomes and Measures: Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT. Results: Cycloplegic refraction was -1.00 diopter in both eyes preflight and +0.50 - 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 µm preflight, 613 µm on FD84; left eye, 404 µm preflight, 636 µm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 µm in the right eye on FD154 and 15.0 µm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O. Conclusions and Relevance: To the authors' knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.


Asunto(s)
Astronautas , Vuelo Espacial , Tomografía de Coherencia Óptica , Agudeza Visual , Ingravidez , Humanos , Femenino , Agudeza Visual/fisiología , Ingravidez/efectos adversos , Persona de Mediana Edad , Síndrome , Refracción Ocular/fisiología , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/fisiopatología , Enfermedades del Nervio Óptico/etiología , Vitamina B 12/uso terapéutico , Trastornos de la Visión
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