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1.
Eat Disord ; 32(4): 369-386, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389388

RESUMO

Eating disorders are serious mental health conditions that are accompanied by negative health outcomes, high mortality rates, impaired functioning, and comorbid mental health conditions. Despite many empirically supported interventions for eating disorders, it remains one of the most challenging mental disorders to treat, as individuals often struggle to maintain treatment gains. One method of improving our understanding of effective eating disorder treatment is to identify important processes of change to target during therapy. The aim of the current study was to test two candidate mediators of disordered eating symptom change during residential treatment: self-compassion and body image inflexibility. In the present study, women and adolescent girls (N = 132) completed a battery of measures, including eating disorder severity, self-compassion, and body image inflexibility, at admission to and discharge from a residential eating disorder facility. Our results indicated that changes in body image inflexibility and self-compassion, specifically self-judgment, were both mediators between ED symptom severity from pre- to post-treatment. These results have potential treatment implications, pointing to the possible importance of targeting body image inflexibility, self-judgment, and self-compassion while treating eating disorders.


Assuntos
Imagem Corporal , Empatia , Transtornos da Alimentação e da Ingestão de Alimentos , Tratamento Domiciliar , Autoimagem , Humanos , Feminino , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Imagem Corporal/psicologia , Adolescente , Adulto , Adulto Jovem , Resultado do Tratamento
2.
Birth Defects Res ; 116(1): e2294, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38155422

RESUMO

BACKGROUND: Birth defects and preterm birth co-occur, with some overlapping risk factors. Many birth defects and preterm births tend to have a male preponderance. We explored potential risk factors impacting sex and preterm (<37 weeks of gestation) birth differences among infants with selected birth defects delivered from 1997 to 2011 using data from the National Birth Defects Prevention Study (NBDPS). METHODS: The NBDPS was a large multisite, population-based case-control study. Using random forests, we identified important predictors of male preterm, female preterm, and male term, each compared with female term births for each birth defect. Using logistic regression, we estimated odds ratios for associations between important predictors and sex-preterm birth status by birth defect. RESULTS: We examined 11,379 infants with nine specific birth defects. The top 10 most important predictors of sex-preterm birth status from the random forests varied greatly across the birth defects and sex-preterm comparisons within a given defect group, with several being novel factors. However, one consistency was that short interpregnancy interval was associated with sex-preterm birth status for many of the studied birth defects. Although obesity has been identified as a risk factor for preterm birth and birth defects in other research, it was not associated with sex-preterm birth status for any of the examined defects. CONCLUSIONS: We confirmed expected associations for sex-preterm birth status differences and found new potential risk factors for further exploration among the studied birth defects.


Assuntos
Nascimento Prematuro , Lactente , Humanos , Recém-Nascido , Masculino , Feminino , Nascimento Prematuro/epidemiologia , Estudos de Casos e Controles , Modelos Logísticos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38102868

RESUMO

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

4.
Mol Ther Nucleic Acids ; 34: 102066, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38034032

RESUMO

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing's potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

5.
Am J Clin Nutr ; 118(3): 720-728, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37661108

RESUMO

BACKGROUND: Neural tube defects (NTDs) still occur among some women who consume 400 µg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. OBJECTIVES: To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. METHODS: Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 µg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. RESULTS: NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. CONCLUSIONS: Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.


Assuntos
Defeitos do Tubo Neural , Oligoelementos , Feminino , Humanos , Ácido Fólico , Micronutrientes , Betaína , Estudos de Casos e Controles , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/prevenção & controle , Metionina , Racemetionina , Colina , Vitamina B 6 , Carbono
6.
J Nutr ; 153(8): 2369-2379, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37271415

RESUMO

BACKGROUND: Racism is a key determinant of perinatal health disparities. Poor diet may contribute to this effect, but research on racism and dietary patterns is limited. OBJECTIVE: We aimed to describe the relation between experiences of racial discrimination and adherence to the 2015‒2020 Dietary Guidelines for Americans. METHODS: We used data from a prospective pregnancy cohort study conducted at 8 United States medical centers (2010‒2013). At 6‒13 weeks of gestation, 10,038 nulliparous people with singleton pregnancies were enrolled. Participants completed a Block food frequency questionnaire, assessing usual diet in the 3 mo around conception, and the Krieger Experiences of Discrimination Scale, assessing the number of situational domains (e.g., at school and on the street) in which participants ever experienced racial discrimination. Alignment of dietary intake with the 2015-2020 Dietary Guidelines for Americans was assessed using the Healthy Eating Index (HEI)-2015. RESULTS: The study showed that 49%, 44%, 35%, and 17% of the Asian, Black, Hispanic, and White participants reported experiences of racial discrimination in any domain. Most participants experienced discrimination in 1 or 2 situational domains. There were no meaningful differences in HEI-2015 total or component scores in any racial or ethnic group according to count of self-reported domains in which individuals experienced discrimination. For example, mean total scores were 57‒59 among Black, 61‒66 among White, 61‒63 among Hispanic, and 66‒69 among Asian participants across the count of racial discrimination domains. CONCLUSIONS: This null association stresses the importance of going beyond interpersonal racial discrimination to consider the institutions, systems, and practices affecting racialized people to eliminate persistent inequalities in diet and perinatal health.


Assuntos
Racismo , Feminino , Gravidez , Humanos , Estados Unidos , Estudos de Coortes , Estudos Prospectivos , Etnicidade , Dieta
7.
J Cogn Psychother ; 37(2): 142-155, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37258302

RESUMO

Sexual orientation intrusive thoughts are a debilitating form of obsessive-compulsive disorder. The present study aimed to elucidate how psychological inflexibility and dysfunctional beliefs may impact the relationships of sexual orientation intrusive thoughts and obsessive-compulsive (OC) symptoms with well-being. A total of 181 undergraduate students completed measures of sexual orientation intrusive thoughts, OC symptoms, psychological inflexibility, dysfunctional beliefs, and well-being. Results indicated positive correlations between psychological inflexibility, sexual orientation intrusive thoughts, dysfunctional beliefs, and OC symptoms, along with negative correlations between well-being and sexual orientation intrusive thoughts, OC symptoms, dysfunctional beliefs, and psychological inflexibility. Psychological inflexibility acted as a mediator between sexual orientation intrusive thoughts and well-being and between OC symptoms and well-being. Dysfunctional beliefs were not a significant mediator. These results suggest that psychological inflexibility may partially explain the association between OC symptoms and well-being, pointing toward the need for future research on the impact of psychological inflexibility on well-being in the context of OC symptoms.


Assuntos
Transtorno Obsessivo-Compulsivo , Humanos , Masculino , Feminino , Inquéritos e Questionários , Transtorno Obsessivo-Compulsivo/diagnóstico , Cognição , Comportamento Sexual , Estudantes
8.
Ann Epidemiol ; 83: 30-34, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37121376

RESUMO

PURPOSE: A strength of SuperLearner is that it may accommodate key interactions between model variables without a priori specification. In prior research, protective associations between fruit intake and preeclampsia were stronger when estimated using SuperLearner with targeted maximum likelihood estimation (TMLE) compared with multivariable logistic regression without any interaction terms. We explored whether heterogeneity (i.e., differences in the effect estimate due to interactions between fruit intake and covariates) may partly explain differences in estimates from these two models. METHODS: Using a U.S. prospective pregnancy cohort (2010-2013, n = 7781), we estimated preeclampsia risk differences (RDs) for higher versus lower fruit density using multivariable logistic regression and included two-way statistical interactions between fruit density and each of the 25 model covariates. We compared the RDs with those from SuperLearner with TMLE (gold standard) and logistic regression with no interaction. RESULTS: From the logistic regression models with two-way statistical interactions, 48% of the preeclampsia RDs were ≤-0.02 (closer to SuperLearner with TMLE estimate); 40% equaled -0.01 (same as logistic regression with no interaction estimate); the minority of RDs were at or crossed the null. CONCLUSIONS: Our exploratory analysis provided preliminary evidence that heterogeneity may partly explain differences in estimates from logistic regression versus SuperLearner with TMLE.


Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Modelos Logísticos , Estudos Prospectivos , Pré-Eclâmpsia/epidemiologia , Funções Verossimilhança , Análise de Regressão
9.
Obesity (Silver Spring) ; 31(4): 1133-1145, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36942419

RESUMO

OBJECTIVE: This case-cohort study estimated associations between gestational weight gain (GWG) and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births stratified by obesity class (I: 30-34.9 kg/m2 ; II: 35-39.9 kg/m2 ; III: ≥40 kg/m2 ) (Magee-Womens Hospital, Pittsburgh, Pennsylvania, 1998-2011). METHODS: First-trimester GWG was categorized as being below (<0.2 kg), within (0.2-2.0 kg), or above (>2.0 kg) the Institute of Medicine recommendations. For second- and third-trimester GWG, four linear trajectories were derived: approximating maintenance (slope -0.05 ± 0.03 kg/wk), approximating the recommendations (0.27 ± 0.01 kg/wk; reference), higher than the recommendations (0.54 ± 0.01 kg/wk), and highest among those above the recommendations (0.91 ± 0.02 kg/wk). RESULTS: For classes I, II, and III, respectively, there were 1290, 1247, and 1198 pregnancies in the subcohort; 262, 171, and 123 SGA cases; and 353, 286, and 257 LGA cases. First-trimester GWG was not associated with SGA/LGA births. Second- and third-trimester weight maintenance was associated with potentially lower LGA risk (risk ratio [RR]: 0.80; 95% confidence interval [CI]: 0.55-1.1) but not higher SGA risk (RR: 0.98; 95% CI: 0.64-1.5) for class III. In addition, some sensitivity analyses supported no increased SGA risk with second- and third-trimester weight maintenance for classes I and II. CONCLUSIONS: Second- and third-trimester weight maintenance may be associated with more optimal birth weight for gestational age. However, how this could be achieved (e.g., through diet and exercise interventions) is unclear, given the observational design of our study.


Assuntos
Ganho de Peso na Gestação , Aumento de Peso , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos de Coortes , Obesidade/epidemiologia , Peso ao Nascer , Recém-Nascido Pequeno para a Idade Gestacional , Índice de Massa Corporal , Resultado da Gravidez
10.
Lancet ; 401(10378): 762-771, 2023 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739882

RESUMO

BACKGROUND: One in four pregnancies end in a pregnancy loss. Although the effect on couples is well documented, evidence-based treatments and prediction models are absent. Fetal aneuploidy is associated with a higher chance of a next successful pregnancy compared with euploid pregnancy loss in which underlying maternal conditions might be causal. Ploidy diagnostics are therefore advantageous but challenging as they require collection of the pregnancy tissue. Cell-free fetal DNA (cffDNA) from maternal blood has the potential for evaluation of fetal ploidy status, but no large-scale validation of the method has been done. METHODS: In this prospective cohort study, women with a pregnancy loss were recruited as a part of the Copenhagen Pregnancy Loss (COPL) study from three gynaecological clinics at public hospitals in Denmark. Women were eligible for inclusion if older than 18 years with a pregnancy loss before gestational age 22 weeks (ie, 154 days) and with an intrauterine pregnancy confirmed by ultrasound (including anembryonic sac), and women with pregnancies of unknown location or molar pregnancies were excluded. Maternal blood was collected while pregnancy tissue was still in situ or within 24 h after pregnancy tissue had passed and was analysed by genome-wide sequencing of cffDNA. Direct sequencing of the pregnancy tissue was done as reference. FINDINGS: We included 1000 consecutive women, at the time of a pregnancy loss diagnosis, between Nov 12, 2020, and May 1, 2022. Results from the first 333 women with a pregnancy loss (recruited between Nov 12, 2020, and Aug 14, 2021) were used to evaluate the validity of cffDNA-based testing. Results from the other 667 women were included to evaluate cffDNA performance and result distribution in a larger cohort of 1000 women in total. Gestational age of fetus ranged from 35-149 days (mean of 70·5 days [SD 16·5], or 10 weeks plus 1 day). The cffDNA-based test had a sensitivity for aneuploidy detection of 85% (95% CI 79-90) and a specificity of 93% (95% CI 88-96) compared with direct sequencing of the pregnancy tissue. Among 1000 cffDNA-based test results, 446 (45%) were euploid, 405 (41%) aneuploid, 37 (4%) had multiple aneuploidies, and 112 (11%) were inconclusive. 105 (32%) of 333 women either did not manage to collect the pregnancy tissue or collected a sample classified as unknown tissue giving a high risk of being maternal. INTERPRETATION: This validation of cffDNA-based testing in pregnancy loss shows the potential and feasibility of the method to distinguish euploid and aneuploid pregnancy loss for improved clinical management and benefit of future reproductive medicine and women's health research. FUNDING: Ole Kirks Foundation, BioInnovation Institute Foundation, and the Novo Nordisk Foundation.


Assuntos
Aborto Espontâneo , Ácidos Nucleicos Livres , Gravidez , Humanos , Feminino , Lactente , Recém-Nascido , Estudos Prospectivos , Feto , Aneuploidia , DNA , Diagnóstico Pré-Natal/métodos
11.
Scand J Caring Sci ; 37(1): 196-206, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36349680

RESUMO

BACKGROUND: Involving patients and families in nursing care is essential to improve patients' health outcomes. Furthermore, families play an essential role in supporting patients by helping nurses understand the patient's everyday life. However, families also need support. Involvement of patients and families is especially important when patients are transferred between hospital and home as transitions heighten the risk of compromising quality and safety in care. However, no consensus exists on how to involve them. Consequently, this may challenge a systematic approach toward patient and family involvement. AIM: To describe hospital and homecare nurses' experiences with involving patients and their family members in nursing care in the transition between hospital and municipalities. METHOD: Focus group interviews were conducted in the Gastro unit at a large university hospital in Denmark. Participants included 10 hospital nurses from three wards at the Gastro unit and six homecare nurses from one of three municipalities in the hospital catchment area (total n = 16). Data were analysed using qualitative content analysis. The study is reported according to the Consolidated Criteria for Reporting Qualitative Research. FINDINGS: Our analysis revealed one overall theme - "The complexity of involvement" - based on four categories: gap between healthcare sectors increases the need for patient and family involvement, lack of time is a barrier to patient and family involvement, involvement is more than information, and involvement as a balancing act. CONCLUSION: The nurses experienced patients' and families' involvement as essential, but a discrepancy was found between nurses' intentions and their actions. Aspects related to a gap between healthcare sectors and various understandings of involvement challenged the systematic involvement of patients and families in the transition between healthcare sectors. However, the nurses were highly motivated to achieve a close cross-sectoral collaboration and to show commitment towards patients and families.


Assuntos
Enfermeiras e Enfermeiros , Humanos , Cidades , Pesquisa Qualitativa , Grupos Focais , Hospitais Universitários
12.
Eat Disord ; 31(4): 388-404, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36469583

RESUMO

Values are freely chosen life directions and/or qualities of being that can motivate behavior change. There is nascent support for the utility of values work as a part of the therapeutic process across treatments, particularly in third wave therapy approaches (e.g., acceptance and commitment therapy). However, therapeutic values work is underresearched in clinical samples of youth. The aim of the present study is to examine the role of the two distinct values processes (engagement and obstruction), body image inflexibility, alongside other common comorbid symptoms of eating disorders (anxiety, depression) in a sample of female adolescents with eating disorders attending a residential eating disorder treatment program. Participants (N = 75) were patients at a residential eating disorder treatment facility and completed a battery of measures at time of admission. Correlational analyses and multiple regression were performed. Results found correlations between eating disorder severity, values engagement, values obstruction, body image flexibility, anxiety, and depression in the expected directions. Regression results found body image inflexibility, progression towards values, and anxiety as significant predictors of eating disorder severity (adjusted R2 = .54). This study points to the importance of emphasizing values engagement in youth with eating disorders, highlighting a potential treatment target for future research.


Assuntos
Terapia de Aceitação e Compromisso , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Adolescente , Feminino , Ansiedade , Índice de Gravidade de Doença , Tratamento Domiciliar
13.
Paediatr Perinat Epidemiol ; 37(4): 350-361, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36441121

RESUMO

BACKGROUND: Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples. OBJECTIVE: We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons. METHODS: Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI). RESULTS: We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference <10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained >1. CONCLUSION: Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.


Assuntos
Doenças Placentárias , Resultado da Gravidez , Recém-Nascido , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Placenta , Estudos Prospectivos , Natimorto/epidemiologia , Doenças Placentárias/epidemiologia , Doenças Placentárias/etiologia , Inflamação
15.
J Extracell Biol ; 2(9): e111, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38938376

RESUMO

The CRISPR gene editing tool holds great potential for curing genetic disorders. However, the safe, efficient, and specific delivery of the CRISPR/Cas9 components into cells and tissues remains a challenge. While many currently available delivery methods achieve high levels of gene editing effects in vivo, they often result in genotoxicity and immunogenicity. Extracellular vesicles (EVs), which are cell-derived lipid nanoparticles, are capable of transferring protein and nucleic acid cargoes between cells, making them a promising endogenous alternative to synthetic delivery methods. This review provides a comprehensive analysis of the currently available strategies for EV-mediated delivery of CRISPR/Cas9. These strategies include cell-based, passive loading obtained by overexpression of CRISPR/Cas9, active loading involving protein or RNA dimerization, and loading into already purified EVs. All these approaches suggest that EV-based CRISPR/Cas9 delivery is useful for achieving both in vitro and in vivo gene editing. Despite that, substantial variations in cellular uptake and gene editing efficiencies indicate that further improvement and standardization are required for the therapeutic use of EVs as a CRISPR/Cas9 delivery vehicle. These improvements include, but is not limited to, the high-yield purification of EVs, increased loading and release efficiencies, as well as improved tissue- or cell-specific targeting specificities.

16.
Birth Defects Res ; 114(14): 785-796, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35652163

RESUMO

BACKGROUND: Medication use during pregnancy is common, with up to 90% of pregnant women taking at least one medication. Women with congenital physical disabilities often report co-occurring conditions during pregnancy that may warrant pharmaceutical treatment, however, research is limited. We aim to describe medication use during pregnancy including: pain, psychotropic, and antibacterial medication, among women with and without congenital physical disabilities. METHODS: We used data from the Slone Birth Defects Study (1976-2015), a case-control study that collected information on pre-pregnancy health conditions and exposures among participating mothers. Women with congenital physical disabilities (n = 132) included women with spina bifida, cerebral palsy, muscular dystrophy, limb deficiencies, and other skeletal/connective tissue conditions and were matched by interview year and study site to women without congenital physical disabilities (n = 528). Proportions and difference in proportions for each medication were compared between groups. Simple proportions were also calculated for duration and multiple medication use variables. RESULTS: Women with congenital physical disabilities more frequently reported use of pain (acetaminophen and opioids), psychotropic (antidepressants), and antibacterial medications during pregnancy. Women with congenital physical disabilities used pain and psychotropic medications for longer, frequent durations, and more frequently reported haven taken multiple medications during pregnancy. CONCLUSION: Women with congenital physical disabilities report higher medication use during pregnancy compared to women without physical disabilities. Patterns may be attributable to co-occurring conditions or increased risk of pregnancy complications in this population. Further research is needed to describe the patterns of medication use for clinical decisions regarding treatment of pregnant women with disabilities.


Assuntos
Pessoas com Deficiência , Complicações na Gravidez , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Dor , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia
17.
Sci Total Environ ; 837: 155783, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35537508

RESUMO

The northernmost regions of our planet experience twice the rate of climate warming compared to the global average. Despite the currently low air temperatures, tundra shrubs are known to exhibit high leaf temperatures and are increasing in height due to warming, but it is unclear how the increase in height will affect the leaf temperature. To study how temperature, soil moisture, and changes in light availability influence the physiology and emissions of climate-relevant volatile organic compounds (VOCs), we conducted a study on two common deciduous tundra shrubs, Salix glauca (separating males and females for potential effects of plant sex) and Betula glandulosa, at two elevations in South Greenland. Low-elevation Salix shrubs were 45% taller, but had 37% lower rates of net CO2 assimilation and 63% lower rates of isoprene emission compared to high-elevation shrubs. Betula shrubs showed 40% higher stomatal conductance and 24% higher glandular trichome density, in the low-elevation valley, compared to those from the high-elevation mountain slope. Betula green leaf volatile emissions were 235% higher at high elevation compared to low elevation. Male Salix showed a distinct VOC blend and emitted 55% more oxygenated VOCs, compared to females, possibly due to plant defense mechanisms. In our light response curves, isoprene emissions increased linearly with light intensity, potentially indicating adaptation to strong light. Leaf temperature decreased with increasing Salix height, at 4 °C m-1, which can have implications for plant physiology. However, no similar relationship was observed for B. glandulosa. Our results highlight that tundra shrub traits and VOC emissions are sensitive to temperature and light, but that local variations in soil moisture strongly interact with temperature and light responses. Our results suggest that effects of climate warming, alone, poorly predict the actual plant responses in tundra vegetation.


Assuntos
Salix , Compostos Orgânicos Voláteis , Regiões Árticas , Betula/fisiologia , Mudança Climática , Solo , Tundra
18.
J Nutr ; 152(8): 1886-1894, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35641231

RESUMO

BACKGROUND: Adherence to the Dietary Guidelines for Americans is often assessed using the Healthy Eating Index (HEI). The HEI total score reflects overall diet quality, with all aspects equally important. Using the traditional weighting scheme for the HEI, all components are generally weighted equally in the total score. However, there is limited empirical basis for applying the traditional weighting for pregnancy specifically. OBJECTIVES: We aimed to assess associations between the 12 HEI-2010 component scores and select pregnancy outcomes. METHODS: The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was a prospective pregnancy cohort (US multicenter, 2010-2013). Participants enrolled in the study between 6 and 13 weeks of gestation. An FFQ assessed usual dietary intake 3 months prior to pregnancy (n = 7880). Scores for the HEI-2010 components were assigned using prespecified standards based on densities (standard units per 1000 kcal) of relevant food groups for most components, a ratio (PUFAs and MUFAs to SFAs) for fatty acids, and the contribution to total energy for empty calories. Using binomial regression, we estimated risk differences between each component score and cases of small-for-gestational age (SGA) birth, preterm birth, preeclampsia, and gestational diabetes, controlling for total energy and scores for the other HEI-2010 components. RESULTS: Higher scores for greens and beans and total vegetables were associated with fewer cases of SGA birth, preterm birth, and preeclampsia. For instance, every 1-unit increase in the greens and beans score was associated with 1.2 fewer SGA infants (95% CI, 0.7-1.7), 0.7 fewer preterm births (95% CI, 0.3-1.1), and 0.7 fewer preeclampsia cases (95% CI, 0.2-1.1) per 100 deliveries. For gestational diabetes, the associations were null. CONCLUSIONS: Vegetable-rich diets were associated with fewer cases of SGA birth, preterm birth, and preeclampsia, controlling for overall diet quality. Examination of the equal weighting of the HEI components (and underlying guidance) is needed for pregnancy.


Assuntos
Diabetes Gestacional , Pré-Eclâmpsia , Nascimento Prematuro , Diabetes Gestacional/epidemiologia , Dieta , Dieta Saudável , Feminino , Humanos , Recém-Nascido , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Estados Unidos , Verduras
19.
Eur J Neurosci ; 55(7): 1798-1809, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35304784

RESUMO

The content and neural representation of autobiographical memories change over time; however, these changes are poorly understood. We hypothesize that the content of memories becomes semanticized, while the neural representation moves from mesial to cortical structures. We conducted an fMRI (functional magnetic resonance imaging) study on the effects of time on autobiographical memory retrieval. Twenty healthy participants were cued by a selection of photographs that represented distinct episodic memories from 1, 2, 6, and 14 years prior to scanning. Our behavioural data of self-report measures of memory qualia suggests a loss of episodic content over time. GLM (general linear model) results demonstrate that across all time points, visual association cortices and mesial temporal lobes were activated. However, we did not observe any GLM differences between memory time points. We used SVM (support vector machine) in order to predict memory time point based on neural activation patterns. We were able to accurately predict classification accuracy for the 1-year (66.7%), 2-year (66.7%), and 14-year (33.4%) memory time points, with an overall classification accuracy of 55.6%. We suggest that our findings can be interpreted in light of cortical semantization; as memories age, they become more semanticized and shift in representation towards cortical structures.


Assuntos
Memória Episódica , Mapeamento Encefálico , Sinais (Psicologia) , Humanos , Imageamento por Ressonância Magnética/métodos , Rememoração Mental/fisiologia , Lobo Temporal
20.
Disabil Health J ; 15(2): 101259, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34980574

RESUMO

BACKGROUND: Women with disabilities are at an increased risk for adverse birth outcomes; however, research among women with congenital neuromuscular disabilities (cNMD) is limited. OBJECTIVE: To describe characteristics and compare birth outcomes among women with and without cNMD. METHODS: Data were from the Slone Birth Defects Study (case-control, conducted from 1976 to 2015), which collected information on demographic, reproductive, and lifestyle characteristics. cNMD included spina bifida, cerebral palsy, muscular dystrophy, contractures, or arthrogryposis and were identified by participant report. Those with cNMD were matched to participants without cNMD by interview year and study site. We use modified Poisson regression to estimate relative risks (RR) for low birthweight, macrosomia, preterm birth, and small/large-for-gestational age (SGA/LGA). Given the case-control design and overrepresentation of infants with congenital anomalies, data were weighted to reflect a 3% national prevalence of infants with congenital anomalies. RESULTS: Women with cNMD (n = 125) were more likely to be white, nulliparous, have a cesarean section, have an unplanned pregnancy, report a pre-pregnancy BMI ≥25 kg/m2, smoke during pregnancy, and report genitourinary infections. Women with cNMD had infants with shorter gestational length (mean difference: -7.44 days, 95% CI: -13.94, -0.95) compared to women without cNMD. cNMD was associated with higher risk of preterm birth (RR = 3.98, 95% CI: 1.33, 11.95) and SGA (RR = 2.14, 95% CI: 0.74, 6.15). CONCLUSION: Women with cNMD were more likely to deliver preterm and have an SGA infant. These findings highlight disparities faced by women with cNMD and stress the need to provide optimal perinatal and reproductive care.


Assuntos
Pessoas com Deficiência , Nascimento Prematuro , Cesárea , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Nascimento Prematuro/epidemiologia
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