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1.
J Bioenerg Biomembr ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833042

RESUMO

Numerous studies have indicated that N6-methyladenosine (m6A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m6A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m6A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m6A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M6A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m6A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m6A-dependent manner.

2.
J Healthc Qual ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742984

RESUMO

BACKGROUND: The accuracy of documentation of body weight and fluid balance in hospitalized patients is frequently questioned. METHODS: We conducted a survey to understand provider perceptions of the accuracy of intake, output, and weight charting in the electronic medical record. We sent a six-item questionnaire to nurses and physicians who provide inpatient service in a community-based teaching hospital of the Northeastern United States. We compared the response difference between nurses and physicians by Fisher exact test. RESULTS: One hundred eight nurses and 39 physicians participated in the survey. Both nurses and physicians responded that the accuracy of documentation is crucial. However, only 25.7% of participating physicians and 38.3% of participating nurses considered that documentation in the electronic medical record is reliable. Both physicians and nurses assumed that the nurses are too busy to collect and document the data, and the variability of non-patient weight and variations in body weight measurement under different conditions account for inaccuracies in the documented body weight. CONCLUSIONS: Assessing the accuracy of documenting intake, output, and body weight in the electronic medical record is warranted. Providers believe that educating patients about fluid balance and volume assessment help to improve the accuracy in charting intake, output, and body weight in the electronic medical record.

3.
Plant Divers ; 46(3): 406-415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798721

RESUMO

Bamboo plants are an essential component of tropical ecosystems, yet their vulnerability to climate extremes, such as drought, is poorly understood due to limited knowledge of their hydraulic properties. Cephalostachyum pergracile, a commonly used tropical bamboo species, exhibited a substantially higher mortality rate than other co-occurring bamboos during a severe drought event in 2019, but the underlying mechanisms remain unclear. This study investigated the leaf and stem hydraulic traits related to drought responses, including leaf-stem embolism resistance (P50leaf; P50stem) estimated using optical and X-ray microtomography methods, leaf pressure-volume and water-releasing curves. Additionally, we investigated the seasonal water potentials, native embolism level (PLC) and xylem water source using stable isotope. We found that C. pergracile exhibited strong resistance to embolism, showing low P50leaf, P50stem, and turgor loss point, despite its rapid leaf water loss. Interestingly, its leaves displayed greater resistance to embolism than its stem, suggesting a lack of effective hydraulic vulnerability segmentation (HVS) to protect the stem from excessive xylem tension. During the dry season, approximately 49% of the water was absorbed from the upper 20-cm-deep soil layer. Consequently, significant diurnal variation in leaf water potentials and an increase in midday PLC from 5.87 ± 2.33% in the wet season to 12.87 ± 4.09% in the dry season were observed. In summary, this study demonstrated that the rapid leaf water loss, high reliance on surface water, and a lack of effective HVS in C. pergracile accelerated water depletion and increased xylem embolism even in the typical dry season, which may explain its high mortality rate during extreme drought events in 2019.

4.
Ann Nucl Med ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602614

RESUMO

OBJECTIVE: To investigate the survival benefit of preoperative bone scan in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with radical resection for stage T1N0M0 NSCLC between March 2013 and December 2018. During postoperative follow-up, we monitored patient survival and the development of bone metastasis. We compared overall survival, bone metastasis-free survival, and recurrence-free survival in patients with or without preoperative bone scan. Propensity score matching and inverse probability of treatment weighting were used to minimize election bias. RESULTS: A total of 868 patients (58.19 ± 9.69 years; 415 men) were included in the study. Of 87.7% (761 of 868) underwent preoperative bone scan. In the multivariable analyses, bone scan did not improve overall survival (hazard ratio [HR] 1.49; 95% confidence intervals [CI] 0.91-2.42; p = 0.113), bone metastasis-free survival (HR 1.18; 95% CI 0.73-1.90; p = 0.551), and recurrence-free survival (HR 0.89; 95% CI 0.58-1.39; p = 0.618). Similar results were obtained after propensity score matching (overall survival [HR 1.28; 95% CI 0.74-2.23; p = 0.379], bone metastasis-free survival [HR 1.00; 95% CI 0.58-1.72; p = 0.997], and recurrence-free survival [HR 0.76; 95% CI 0.46-1.24; p = 0.270]) and inverse probability of treatment weighting. CONCLUSION: There were no significant differences in overall survival, bone metastasis-free survival, and recurrence-free survival between asymptomatic patients with clinical stage IA NSCLC with or without preoperative bone scan.

5.
Ophthalmol Retina ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38485090

RESUMO

OBJECTIVE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects aged ≥ 18 years who were followed at the Johns Hopkins Genetic Eye Disease Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into 2 groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURES: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n = 180/230) had a history of more than 1 surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by yttrium aluminum garnet capsulotomy, refractive surgery, retinal surgery, and others. Cataract extraction with intraocular lens implantation occurred more frequently in RP than in MCCRD subjects (POR, 2.59; P = 0.002). Retinitis pigmentosa subjects underwent CEIOL at a younger age than patients with MCCRD (HR, 2.11; P < 0.001). CONCLUSIONS: Approximately one-third of patients with IRD had a history of laser or incisional surgery. Cataract extraction with intraocular lens implantation was the most common surgery; its frequency and timing may be associated with the IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

6.
Asian J Surg ; 47(1): 100-106, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37183108

RESUMO

BACKGROUND: This study compared the effectiveness and safety of laparoscopic radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) in the treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) involving specific sites. METHODS: This retrospective cohort study included patients with HBV-related HCC involving specific sites treated with LRFA or PRFA between January 2012 and December 2020. The overall survival (OS), disease-free survival (DFS), and complications were compared between the LRFA and PRFA groups. The Cox proportional-hazards regression model was used to determine the factors affecting prognosis. RESULTS: This study included 109 patients: 69 in the LRFA group and 40 cases in the PRFA group. No significant differences were found in the 3-year OS rate between the two groups (73.7% vs. 70.0%, P = 0.514), but the LRFA group showed a higher 3-year DFS rate than the PRFA group (58.2% vs. 42.5%, P = 0.018). The RFA method was not associated with OS but was independently associated with DFS (LRPA vs. PRFA, HR = 2.078, P = 0.012). The common complications were ascites, pleural effusion, and fever in the two groups. The occurrence of complications in patients treated with LRFA or PRFA was similar (15.9% vs. 12.5%, P = 0.785). CONCLUSION: LRFA was associated with a better DFS in patients with HBV-related HCC involving specific sites. Thus, LRFA might have more advantages in treating liver cancer involving specific sites.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Hepatite B Crônica , Laparoscopia , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Hepatite B Crônica/complicações , Ablação por Cateter/métodos , Recidiva Local de Neoplasia , Ablação por Radiofrequência/métodos , Laparoscopia/métodos , Resultado do Tratamento
7.
Small ; 20(10): e2305076, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37909382

RESUMO

Chronic diabetic wounds remain a worldwide challenge for both the clinic and research. Given the vicious circle of oxidative stress and inflammatory response as well as the impaired angiogenesis of the diabetic wound tissues, the wound healing process is disturbed and poorly responds to the current treatments. In this work, a nickel-based metal-organic framework (MOF, Ni-HHTP) with excellent antioxidant activity and proangiogenic function is developed to accelerate the healing process of chronic diabetic wounds. The Ni-HHTP can mimic the enzymatic catalytic activities of antioxidant enzymes to eliminate multi-types of reactive species through electron transfer reactions, which protects cells from oxidative stress-related damage. Moreover, this Ni-based MOF can promote cell migration and angiogenesis by activating transforming growth factor-ß1 (TGF-ß1) in vitro and reprogram macrophages to the anti-inflammatory phenotype. Importantly, Ni-HHTP effectively promotes the healing process of diabetic wounds by suppressing the inflammatory response and enhancing angiogenesis in vivo. This study reports a versatile and promising MOF-based nanozyme for diabetic wound healing, which may be extended in combination with other wound dressings to enhance the management of diabetic or non-healing wounds.


Assuntos
Diabetes Mellitus Experimental , Estruturas Metalorgânicas , Animais , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/farmacologia , Níquel , Angiogênese , Cicatrização/fisiologia , Antioxidantes , Hidrogéis
8.
BMC Surg ; 23(1): 349, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974183

RESUMO

BACKGROUND: Laparoscopic pancreaticoduodenectomy(LPD) has become the goal of lots of minimally invasive surgical centers in recent years. Postoperative pancreatic fistula(POPF) is still the barrier to attaining the above goal. Thus, improving anastomosis techniques to reduce the rate of POPF has been a hotspot of surgery. Blumgart pancreaticojejunostomy is considered one of the best anastomosis procedures, with low rates of POPF. However, the original Blumgart pancreaticojejunostomy method is not easy for laparoscopic operation. In consequence, we modified a Blumgart pancreaticojejunostomy technique with a simple and practicable procedure and applied to LPD. METHODS: We collected and retrospectively analyzed the perioperative clinical data of patients who underwent modified Blumgart anastomosis from February 2017 to September 2022. The above patients included 53 cases in open pancreaticojejunostomy(OPD) and 58 cases in LPD. After propensity score matching, 44 cases were included for comparison in each group. RESULTS: After propensity score matching, the average time for pancreaticojejunostomy was about 30 min in the LPD group. The Clinically relevant POPF(CR-POPF) rate was 9.1%. The length of postoperative hospitalization was 13.1 days. Compared with the OPD group, The CR-POPF rate in the LPD group are not significant differences. But the postoperative length of hospital stay was significantly shorter in the LPD group. Besides, there were no other severely postoperative complications between two groups. CONCLUSION: The modified Blumgart anastomosis technique applied to LPD in our Center not only has simple and convenient properties but also low rate of CR-POPF. And this method may be a good choice for surgeons to begin to carry out LPD.


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Anastomose Cirúrgica/métodos , Pancreaticojejunostomia/métodos , Fístula Pancreática/etiologia , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia
10.
Materials (Basel) ; 16(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37512222

RESUMO

High-strength steel-fiber-reinforced concrete (HSFRC) has become increasingly popular as a cast-in-place jointing material in precast concrete bridges and buildings due to its excellent tensile strength and crack resistance. However, working conditions such as emergency repairs and low-temperature constructions require higher demands on the workability and mechanical properties of HSFRC. To this end, a novel rapid-hardening HSFRC has been proposed, which is produced using sulphoaluminate cement (SC) instead of ordinary Portland cement. In this study, quasi-static and dynamic tests were carried out to compare the compressive behavior of conventional and rapid-hardening HSFRCs. The key test variables included SC replacement ratios, concrete curing ages, and strain rates. Test results showed: (1) Rapid-hardening HSFRC exhibited high early strengths of up to 33.14 and 44.9 MPa at the curing age of 4 h, respectively, but its compressive strength and elastic modulus were generally inferior to those of conventional HSFRC. (2) The strain rate sensitivity of rapid-hardening HSFRC was more significant compared to its conventional counterpart and increased with increasing curing ages and strain rates. This study highlights the great potential of rapid-hardening HSFRC in rapid bridge construction.

11.
Mol Carcinog ; 62(10): 1460-1473, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37278569

RESUMO

RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport of neurotrophic receptors and inflammatory cytokines. RAB6A-mediated secretory pathway is involved in many physiological and pathological processes. Defects in RAB6A-mediated secretory pathway may lead to the development of many diseases, including cancer. However, its role in cholangiocarcinoma (CCA) has not yet been revealed. We explored the regulatory role of RAB6A in the stem-like subsets of CCA. We showed that RAB6A knockdown (KD) impedes cancer stem cells (CSCs) properties and epithelial-mesenchymal transition in vitro and that suppression of RAB6A inhibits tumor growth in vivo. We screened target cargos of RAB6A in CCA cells and identified a extracellular matrix component as the target cargo. RAB6A binds directly to OPN, and RAB6A KD suppressed OPN secretion and inhibited the interaction between OPN and αV integrin receptor. Moreover, RAB6A KD inhibited the AKT signaling pathway, which is a downstream effector of the integrin receptor signaling. In addition, shRNA targeting OPN blocked endogenous expression of OPN and consequently weakened CSCs properties in RAB6A-formed spheres. Similarly, inhibitor of AKT signaling, MK2206 also impedes oncogenic function of RAB6A in the stem-like subsets of CCA cells. In conclusion, our findings showed that RAB6A sustains CSCs phenotype maintenance by modulating the secretion of OPN and consequentially activating the downstream AKT signaling pathway. Targeting the RAB6A/OPN axis may be an effective strategy for CCA therapy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
12.
J Nutr ; 153(5): 1502-1511, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147034

RESUMO

BACKGROUND: Vitamin D deficiency is common in pregnancy. Vitamin D plays an important role in the developing brain, and deficiency may impair childhood behavioral development. OBJECTIVES: This study examined the relationship between gestational 25(OH)D concentrations and childhood behavior in the Environmental influences on Child Health Outcomes (ECHO) Program. METHODS: Mother-child dyads from ECHO cohorts with data available on prenatal (first trimester through delivery) or cord blood 25(OH)D and childhood behavioral outcomes were included. Behavior was assessed using the Strengths and Difficulties Questionnaire or the Child Behavior Checklist, and data were harmonized using a crosswalk conversion. Linear mixed-effects models examined associations of 25(OH)D with total, internalizing, and externalizing problem scores while adjusting for important confounders, including age, sex, and socioeconomic and lifestyle factors. The effect modification by maternal race was also assessed. RESULTS: Early (1.5-5 y) and middle childhood (6-13 y) outcomes were examined in 1688 and 1480 dyads, respectively. Approximately 45% were vitamin D deficient [25(OH)D < 20 ng/mL], with Black women overrepresented in this group. In fully adjusted models, 25(OH)D concentrations in prenatal or cord blood were negatively associated with externalizing behavior T-scores in middle childhood [-0.73 (95% CI: -1.36, -0.10) per 10 ng/mL increase in gestational 25(OH)D]. We found no evidence of effect modification by race. In a sensitivity analysis restricted to those with 25(OH)D assessed in prenatal maternal samples, 25(OH)D was negatively associated with externalizing and total behavioral problems in early childhood. CONCLUSIONS: This study confirmed a high prevalence of vitamin D deficiency in pregnancy, particularly among Black women, and revealed evidence of an association between lower gestational 25(OH)D and childhood behavioral problems. Associations were more apparent in analyses restricted to prenatal rather than cord blood samples. Interventions to correct vitamin D deficiency during pregnancy should be explored as a strategy to improve childhood behavioral outcomes.


Assuntos
Comportamento Problema , Deficiência de Vitamina D , Criança , Gravidez , Humanos , Feminino , Pré-Escolar , Vitamina D , Desenvolvimento Infantil , Avaliação de Resultados em Cuidados de Saúde
13.
EMBO Rep ; 24(6): e55873, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-36994853

RESUMO

The membrane-tethered protease Tiki antagonizes Wnt3a signaling by cleaving and inactivating Wnt3a in Wnt-producing cells. Tiki also functions in Wnt-receiving cells to antagonize Wnt signaling by an unknown mechanism. Here, we demonstrate that Tiki inhibition of Wnt signaling at the cell surface requires Frizzled (FZD) receptors. Tiki associates with the Wnt-FZD complex and cleaves the N-terminus of Wnt3a or Wnt5a, preventing the Wnt-FZD complex from recruiting and activating the coreceptor LRP6 or ROR1/2 without affecting Wnt-FZD complex stability. Intriguingly, we demonstrate that the N-terminus of Wnt3a is required for Wnt3a binding to LRP6 and activating ß-catenin signaling, while the N-terminus of Wnt5a is dispensable for recruiting and phosphorylating ROR1/2. Both Tiki enzymatic activity and its association with the Wnt-FZD complex contribute to its inhibitory function on Wnt5a. Our study uncovers the mechanism by which Tiki antagonizes Wnt signaling at the cell surface and reveals a negative role of FZDs in Wnt signaling by acting as Tiki cofactors. Our findings also reveal an unexpected role of the Wnt3a N-terminus in the engagement of the coreceptor LRP6.


Assuntos
Receptores Frizzled , Via de Sinalização Wnt , Receptores Frizzled/metabolismo , Proteína Wnt3A/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Membrana Celular/metabolismo , beta Catenina/metabolismo
14.
Bioact Mater ; 25: 95-106, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36789001

RESUMO

The excessive reactive oxygen species (ROS) is a hallmark associated with the initiation and progression of inflammatory bowel disease (IBD), which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression. Here, the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS. The Au/CeO2 with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles, likely due to the effective exposure of catalytic sites, higher content of Ce (III) and oxygen vacancy, and accelerated reduction from Ce (IV) to Ce (III). Being coated with negatively-charged hyaluronic acid, the Au/CeO2@HA facilitates accumulation in inflamed colon tissues via oral administration, reduces pro-inflammatory cytokines, and effectively alleviates colon injury in colitis mice. Overall, the Au/CeO2@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.

15.
JAMA Netw Open ; 6(2): e2256157, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36790805

RESUMO

Importance: The COVID-19 pandemic led to widespread lockdowns and school closures that may have affected screen time among children. Although restrictions were strongest early in the pandemic, it is unclear how screen time changed as the pandemic progressed. Objective: To evaluate change in children's screen time from before the pandemic to during the pandemic, from July 2019 through August 2021. Design, Setting, and Participants: This is a longitudinal cohort study with repeated measures of screen time collected before the pandemic and during 2 pandemic periods. Children aged 4 to 12 years and their parent were enrolled in 3 pediatric cohorts across 3 states in the US participating in the Environmental Influences of Child Health Outcomes (ECHO) Program. Data analysis was performed from November 2021 to July 2022. Exposures: COVID-19 pandemic period: prepandemic (July 2019 to March 2020), pandemic period 1 (December 2020 to April 2021), and pandemic period 2 (May 2021 to August 2021). Main Outcomes and Measures: The primary outcomes were total, educational (not including remote school), and recreational screen time assessed via the ECHO Child Media Use questionnaire. Linear mixed-effects models were used for screen time adjusted for child's age, number of siblings, sex, race, ethnicity, and maternal education. Results: The cohort included 228 children (prepandemic mean [SD] age, 7.0 [2.7] years; 100 female [43.9%]) with screen time measured during the prepandemic period and at least once during the pandemic period. Prepandemic mean (SD) total screen time was 4.4 (3.9) hours per day and increased 1.75 hours per day (95% CI, 1.18-2.31 hours per day) in the first pandemic period and 1.11 hours per day (95% CI, 0.49-1.72 hours per day) in the second pandemic period, in adjusted models. Prepandemic mean (SD) recreational screen time was 4.0 (3.5) hours per day and increased 0.89 hours per day (95% CI, 0.39-1.39 hours per day) in the first pandemic period and 0.70 hours per day (95% CI, 0.16-1.25 hours per day) in the second pandemic period. Prepandemic mean (SD) educational screen time was 0.5 (1.2) hours per day (median [IQR], 0.0 [0.0-0.4] hours per day) and increased 0.93 hours per day (95% CI, 0.67-1.19 hours per day) in the first pandemic period and 0.46 hours per day (95% CI, 0.18-0.74 hours per day) in the second pandemic period. Conclusions and Relevance: These findings suggest that screen time among children increased during the COVID-19 pandemic and remained elevated even after many public health precautions were lifted. The long-term association of increased screen time during the COVID-19 pandemic with children's health needs to be determined.


Assuntos
COVID-19 , Humanos , Criança , Feminino , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Estudos Longitudinais , Pandemias , Tempo de Tela
16.
Ophthalmic Epidemiol ; 30(3): 307-316, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35838059

RESUMO

PURPOSE: Both linear regression with generalized estimating equations (GEE) and linear mixed-effects models (LMEM) can be used to estimate the marginal association of an exposure with clustered continuous outcomes. This study compares their performance for bivariate continuous outcomes which are common in eye studies. METHODS: Parametric and non-parametric simulations were used to compare the GEE models including independent, exchangeable, and unstructured working correlation structures and LMEM including random intercept only and random intercept and slope models in R and SAS. Data generation referenced the data distributions from a real-world study for estimating ocular structure-visual function relationships in patients with retinitis pigmentosa. RESULTS: From both parametric and non-parametric simulations, comparing the random intercept LMEM and GEE exchangeable model, bias was similar; coverage probability of the 95% confidence interval (CI) from the random intercept LMEM was often closer to 95%, especially when the sample size was small; the power for testing the association of the exposure was higher from the GEE exchangeable model, but its type-I error rate might be inflated especially when the sample size was small. The type-I error rate from the random intercept LMEM was closer to 0.05, but it might be under 0.05 and coverage probability might be over 95%. The GEE independent model performed worst and the LMEM with both random intercept and slope might not converge. CONCLUSION: To estimate marginal exposure-outcome association with bivariate continuous outcomes, the random intercept LMEM may be preferred. It has the best coverage probability of 95% CI and is the only model with correct type-I error rates in this study. However, it may have low power and overly wide CI in studies with small sample size or low inter-eye correlation.


Assuntos
Modelos Estatísticos , Humanos , Modelos Lineares , Simulação por Computador , Tamanho da Amostra , Viés
17.
Res Child Adolesc Psychopathol ; 51(4): 513-527, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36417100

RESUMO

Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.


Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Criança , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Estudos de Coortes , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Antidepressivos/efeitos adversos
18.
Environ Res ; 216(Pt 2): 114423, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228691

RESUMO

Polycarboxylate (PCE) is a high performance superplasticizer for modern concrete. With the high quality sand becoming precious, more and more low quality sands are used in concrete. However, low quality sands generally contain a relatively high content of montmorillonite (MMT), which could seriously reduce the efficiency of PCE. In order to develop PCE suitable for concrete with low quality sands, the absorption behavior on MMT of PCE with different side chains and acid/ether ratio was investigated. In order to explore the effect of MMT on PCE, two macromonomers were selected, isoprene glycol ether 400(TPEG400) and isoprene glycol ether 2400 (TPEG2400), to synthesize six long and short side chain comb-type PCEs with acid-ether ratios of 1.5:1, 2.5:1 and 3.5:1, respectively. The MMT tolerance mechanism of comb-type PCE in MMT-containing cement slurry was examined by FT-IR, DLS, TOC and other analysis. The PCE with long side chain is much easier to be inserted into the layered structure of MMT, resulting in intercalation absorption. The absorption amount of two kinds of side chain PCE on the MMT particles decreased as the acid ether ratio increases. PCE with long side chains showed shear-thickening properties in MMT-containing cement slurry, on the contrary, short side chains showed shear-thinning properties.

19.
Pediatr Res ; 93(3): 586-594, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36195633

RESUMO

BACKGROUND: Sleep in childhood is affected by behavioral, environmental, and parental factors. We propose that these factors were altered during the COVID-19 pandemic. This study investigates sleep habit changes during the pandemic in 528 children 4-12 years old in the US, leveraging data from the Environmental Influences on Child Health Outcomes (ECHO) Program. METHODS: Data collection occurred in July 2019-March 2020 (pre-pandemic) and two pandemic periods: December 2020-April 2021 and May-August 2021. Qualitative interviews were performed in 38 participants. RESULTS: We found no changes in sleep duration, but a shift to later sleep midpoint during the pandemic periods. There was an increase in latency at the first pandemic collection period but no increase in the frequency of bedtime resistance, and a reduced frequency of naps during the pandemic. Qualitative interviews revealed that parents prioritized routines to maintain sleep duration but were more flexible regarding timing. Children from racial/ethnic minoritized communities slept less at night, had later sleep midpoint, and napped more frequently across all collection periods, warranting in-depth investigation to examine and address root causes. CONCLUSIONS: The COVID-19 pandemic significantly impacted children sleep, but parental knowledge of the importance of sleep might have played a significant protective role. IMPACT: During the COVID-19 pandemic, US children changed their sleep habits, going to bed and waking up later, but their sleep duration did not change. Sleep latency was longer. Parental knowledge of sleep importance might have played a protective role. Regardless of data collection periods, children from racial/ethnic minoritized communities slept less and went to bed later. This is one of the first study on this topic in the US, including prospective pre-pandemic qualitative and quantitative data on sleep habits. Our findings highlight the pandemic long-term impact on childhood sleep. Results warrants further investigations on implications for overall childhood health.


Assuntos
COVID-19 , Pandemias , Humanos , Criança , Pré-Escolar , Estudos Prospectivos , Sono , Coleta de Dados
20.
Cell Rep ; 41(8): 111693, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417851

RESUMO

Long intergenic noncoding RNAs (lincRNAs) are crucial regulators in numerous biological processes. However, the functions and mechanisms of m6A-modified lincRNAs in neuronal development remain unclear. Here, we report an m6A-modified lincRNA, Dppa2 upstream binding RNA (Dubr), abundantly expressed at the early developmental stage of dorsal root ganglion (DRG) and cerebral cortex. Silencing Dubr impairs axon elongation of DRG neurons and axon projection and migration of cortical neurons, whereas lacking m6A modification of Dubr fully loses its functions. Mechanically, Dubr interacts with m6A-binding proteins, the YTHDF1/3 complex, through its m6A motifs to protect YTHDF1/3 from degradation via the proteasome pathway. Furthermore, Tau and Calmodulin are regulated by YTHDF1/3 and m6A-modified Dubr. Overexpression of YTHDF1/3 not only rescues the reduced Tau and Calmodulin but also restores axon elongation of DRG neurons by Dubr knockdown. This study uncovers a critical role of m6A-modified lincRNA in neuronal development by regulating the degradation of RNA-binding protein.


Assuntos
RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Biossíntese de Proteínas , Calmodulina/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neurônios/metabolismo
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