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1.
J Glob Health ; 14: 04094, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38845456

RESUMEN

Background: Maternal empowerment - the capacity to make decisions within households - is linked to better child feeding and nutritional outcomes, but few studies have considered the mediating role of caregiver knowledge. Further, existing literature centres primarily on the husband-wife dyad while overlooking grandmothers as important childcare decision-makers. Methods: We collected primary data through household surveys in 2019 and 2021 from 1190 households with infants zero to six months living in rural western China. We identified the primary and secondary caregivers for each infant and assessed their feeding knowledge and practices, as well as infant nutritional status. We constructed a maternal empowerment index using a seven-item decision-making questionnaire and examined the relationship between maternal empowerment in childcare and household decisions, caregivers' feeding knowledge, and infant feeding practices and nutritional outcomes. Results: Mothers had significantly higher levels of feeding knowledge than secondary caregivers (most were grandmothers, 72.7%), with average knowledge scores of 5.4 vs. 4.1, respectively, out of 9. Mothers and secondary caregivers with higher levels of feeding knowledge had significantly higher exclusive breastfeeding rates by 13-15 percentage points (P < 0.01) and 11-13 percentage points (P < 0.01), respectively. The knowledge of secondary caregivers was even more strongly associated with not feeding formula (15 percentage points, P < 0.01). Mothers empowered to make childcare decisions were more likely to exclusively breastfeed (12-13 percentage points, P < 0.01), less likely to formula feed (9-10 percentage points, P < 0.05), and more likely to have children with higher Z-scores for length-for-age (0.32-0.33, P < 0.01) and weight-for-age (0.24-0.25, P < 0.05). Effects remained after controlling for maternal feeding knowledge. Conclusions: While mothers' and grandmothers' feeding knowledge was both important for optimal infant feeding, grandmothers' knowledge was particularly critical for practicing exclusive breastfeeding. Given the disparity in feeding knowledge between the two caregivers, our study further shows that mothers empowered in childcare decision-making were more likely to exclusively breastfeed their infants. This implies that some mothers with adequate knowledge may not practice optimal feeding because of lower decision-making power. Overall, our study highlights the role of secondary caregivers (grandmothers) in infant care and suggests that future child nutritional interventions may benefit from involving secondary caregivers (grandmothers). Registration: Parent trial registration: ISRCTN16800789.


Asunto(s)
Lactancia Materna , Empoderamiento , Conocimientos, Actitudes y Práctica en Salud , Fenómenos Fisiológicos Nutricionales del Lactante , Madres , Población Rural , Humanos , China , Lactante , Femenino , Madres/psicología , Madres/estadística & datos numéricos , Adulto , Recién Nacido , Lactancia Materna/psicología , Lactancia Materna/estadística & datos numéricos , Masculino , Estado Nutricional , Encuestas y Cuestionarios , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Abuelos/psicología , Toma de Decisiones
2.
Neurooncol Pract ; 11(3): 319-327, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38737617

RESUMEN

Background: Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to neuropsychological evaluations, helping ensure findings reflect true abilities or concerns. It is unclear how PVTs and SVTs perform in children who received radiotherapy for brain tumors. Accordingly, we investigated the rate of noncredible performance on validity indicators as well as associations with fatigue and lower intellectual functioning. Methods: Embedded PVTs and SVTs were investigated in 98 patients with pediatric craniopharyngioma undergoing proton radiotherapy (PRT). The contribution of fatigue, sleepiness, and lower intellectual functioning to embedded PVT performance was examined. Further, we investigated PVTs and SVTs in relation to cognitive performance at pre-PRT baseline and change over time. Results: SVTs on parent measures were not an area of concern. PVTs identified 0-31% of the cohort as demonstrating possible noncredible performance at baseline, with stable findings 1 year following PRT. Reliable digit span (RDS) noted the highest PVT failure rate; RDS has been criticized for false positives in pediatric populations, especially children with neurological impairment. Objective sleepiness was strongly associated with PVT failure, stressing need to consider arousal level when interpreting cognitive performance in children with craniopharyngioma. Lower intellectual functioning also needs to be considered when interpreting task engagement indices as it was strongly associated with PVT failure. Conclusions: Embedded PVTs should be used with caution in pediatric craniopharyngioma patients who have received PRT. Future research should investigate different cut-off scores and validity indicator combinations to best differentiate noncredible performance due to task engagement versus variable arousal and/or lower intellectual functioning.

3.
Cell Rep Med ; 5(3): 101468, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38508144

RESUMEN

Neuroblastoma with MYCN amplification (MNA) is a high-risk disease that has a poor survival rate. Neuroblastoma displays cellular heterogeneity, including more differentiated (adrenergic) and more primitive (mesenchymal) cellular states. Here, we demonstrate that MYCN oncoprotein promotes a cellular state switch in mesenchymal cells to an adrenergic state, accompanied by induction of histone lysine demethylase 4 family members (KDM4A-C) that act in concert to control the expression of MYCN and adrenergic core regulatory circulatory (CRC) transcription factors. Pharmacologic inhibition of KDM4 blocks expression of MYCN and the adrenergic CRC transcriptome with genome-wide induction of transcriptionally repressive H3K9me3, resulting in potent anticancer activity against neuroblastomas with MNA by inducing neuroblastic differentiation and apoptosis. Furthermore, a short-term KDM4 inhibition in combination with conventional, cytotoxic chemotherapy results in complete tumor responses of xenografts with MNA. Thus, KDM4 blockade may serve as a transformative strategy to target the adrenergic CRC dependencies in MNA neuroblastomas.


Asunto(s)
Histona Demetilasas , Neuroblastoma , Humanos , Proteína Proto-Oncogénica N-Myc/genética , Línea Celular Tumoral , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Proteínas Oncogénicas/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética
4.
Ophthalmol Sci ; 4(3): 100458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38317868

RESUMEN

Objective: To determine if baseline diabetic retinopathy (DR) severity mediates the relationship between health insurance status and DR progression. Design: Retrospective cohort study. Subjects: Seven hundred sixteen patients aged ≥ 18 years with a diagnosis of type 1 or 2 diabetes mellitus, and a diagnosis of nonproliferative DR (NPDR) were identified from the electronic health record of a tertiary academic center between June 2012 and February 2022. Methods: NPDR severity at baseline was the proposed mediator in the relationship between insurance status and proliferative DR (PDR) progression. Logistic regression was used to determine the association between insurance status and NPDR severity at baseline, and Cox proportional hazards regression was used to assess the association between insurance status and time to PDR progression. To analyze the mediation effect of NPDR severity at baseline, a counterfactual approach, which decomposes a total effect into a natural direct effect and a natural indirect effect was applied. Main Outcome Measures: Time to progression from first NPDR diagnosis to first PDR diagnosis. Results: Of the 716 patients, 581 (81%) had Medicare or private insurance, 107 (15%) had Medicaid, and 28 (4.0%) were uninsured at their baseline eye visit. Uninsured or Medicaid patients had a higher proportion of moderate or severe NPDR at their baseline eye visit and a higher proportion of progression to PDR. After adjusting for confounders and NPDR severity at baseline, patients who were uninsured had significantly greater risk of progression to PDR compared with that of patients with Medicare/private insurance (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.10-6.25). Patients with Medicaid also had an increased risk of progression to PDR compared with that of patients with Medicare/private insurance, although not statistically significant (HR: 1.53; 95% CI: 0.81-2.89). NPDR severity at baseline mediated 41% of the effect of insurance status (uninsured vs. Medicare/private insurance) on PDR progression. Conclusions: Patients who were uninsured were more likely to have an advanced stage of NPDR at their baseline eye visit and were at significantly greater risk of progression to PDR compared with patients who had Medicare or were privately insured. Mediation analysis revealed that differences in baseline NPDR severity by insurance explained a significant proportion of the relationship between insurance status and DR progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

5.
Angew Chem Int Ed Engl ; 63(9): e202317636, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38242844

RESUMEN

The first total synthesis of incarnatapeptins A and B, two novel marine natural products, was accomplished from readily available (S)-1-benzyloxycarbonylhexahydropyridazine-3-carboxylic acid. This route, whose longest linear sequence was 12 steps, provided the incarnatapeptins A and B in yields of 26.5 % and 19.7 %, respectively, and enabled the structure and stereochemistry of both natural products to be unambiguously confirmed. Highlights of our synthesis include the photoredox-mediated decarboxylative 1,4-addition reaction and a novel and practical N-acylation paradigm promoted by silver carbonate. The unusual facile atropisomerism of some linear peptidic intermediates was also observed by TLC analysis in the course of this work.

6.
Molecules ; 28(21)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37959861

RESUMEN

Total synthesis of the proposed noursamycin A has been accomplished, which disproves the original structural assignments. The synthetic strategy described herein has also been employed in the first total synthesis of nicrophorusamide A, a cyclopeptide that is structurally related to noursamycin A.

7.
Int Breastfeed J ; 18(1): 34, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37443078

RESUMEN

BACKGROUND: In rural China, exclusive breastfeeding (EBF) prevalence is low and hospitals often fail to attain baby-friendly feeding objectives, such as ≥ 75% of newborns exclusively breastfed from birth to discharge. Empirical evidence for the impact of increased hospital compliance with recommended feeding guidelines on continued EBF in rural China is lacking. We sought to measure and model the association of newborns' in-hospital feeding experiences with EBF practice in infancy to inform policies for EBF promotion. METHODS: Data were cross-sectional from 785 caregivers of infants < 6 months of age, collected from November to December 2019 in four underdeveloped counties/districts in Sichuan Province. In-hospital feeding practices were determined, and prevalence of current infant feeding practices was calculated from 24-h recall and categorized according to WHO/UNICEF Infant and Young Child Feeding categories as EBF, breastfed with non-milk liquids, mixed feeding, breastfed with solids, and not breastfed. Relative risk ratios were estimated using adjusted multinomial logistic regression to examine risk factors for non-EBF practices compared to EBF, including in-hospital feeding experiences. The regression model was used to investigate change in EBF prevalence under alternative in-hospital experiences. RESULTS: Only 38.1% of under-six-month-old infants were being exclusively breastfed when data were collected; 61.8% and 77.6% had been fed water and infant formula, respectively, in the hospital. Infants who were fed water or formula before discharge were estimated as 2-3 times as likely to be non-EBF than EBF up to age six months. According to our model, EBF prevalence would have increased to 53.7% (95% confidence interval (CI) 46.1, 61.2) had ≥ 75% of infants been exclusively breastfed and water-based feeds eliminated in-hospital. CONCLUSIONS: Given the importance of infants' first feeding experiences in the establishment and continuation of EBF, it is imperative that rural Chinese hospitals actively seek to limit infant formula feeds to medically indicated situations and eliminate water-based feeds.


Asunto(s)
Lactancia Materna , Periodo Posparto , Femenino , Humanos , Lactante , Recién Nacido , Hospitales , Factores de Riesgo , Agua
8.
Ophthalmol Sci ; 3(2): 100276, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36950087

RESUMEN

Purpose: To develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance. Design: Retrospective cohort study. Participants: Electronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR). Methods: Four survival models were developed: Cox proportional hazards, Cox with backward selection, Cox with LASSO regression and Random Survival Forest. For each model, three variable sets were compared to determine the impact of including updated clinical information: Static0 (data up to the index date), Static6m (data updated 6 months after the index date), and Dynamic (data in Static0 plus data change during the 6-month period). The UCSF data were split into 80% training and 20% testing (internal validation). The ZSFG data were used for external validation. Model performance was evaluated by the Harrell's concordance index (C-Index). Main Outcome Measures: Time to PDR. Results: The UCSF cohort included 1130 patients and 92 (8.1%) patients progressed to PDR. The ZSFG cohort included 687 patients and 30 (4.4%) patients progressed to PDR. All models performed similarly (C-indices ∼ 0.70) in internal validation. The random survival forest with Static6m set performed best in external validation (C-index 0.76). Insurance and age were selected or ranked as highly important by all models. Other key predictors were NPDR severity, diabetic neuropathy, number of strokes, mean Hemoglobin A1c, and number of hospital admissions. Conclusions: Our models for progression of NPDR to PDR achieved acceptable predictive performance and validated well in an external setting. Updating the baseline variables with new clinical information did not consistently improve the predictive performance. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

9.
BMJ Open ; 13(1): e065403, 2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36669837

RESUMEN

INTRODUCTION: Millions of young rural children in China still suffer from poor health and malnutrition, partly due to a lack of knowledge about optimal perinatal and child care among rural mothers and caregivers. Meanwhile, there is an urgent need to improve maternal mental health in rural communities. Comprehensive home visiting programmes delivered by community health workers (CHWs) can bridge the caregiver knowledge gap and improve child health and maternal well-being in low-resource settings, but the effectiveness of this approach is unknown in rural China. Additionally, grandmothers play important roles in child care and family decision-making in rural China, suggesting the importance of engaging multiple caregivers in interventions. The Healthy Future programme seeks to improve child health and maternal well-being by developing a staged-based curriculum that CHWs deliver to mothers and caregivers of young children through home visits with the assistance of a tablet-based mHealth system. This protocol describes the design and evaluation plan for this programme. METHODS AND ANALYSIS: We designed a cluster-randomised controlled trial among 119 rural townships in four nationally designated poverty counties in Southwestern China. We will compare the outcomes between three arms: one standard arm with only primary caregivers participating in the intervention, one encouragement arm engaging primary and secondary caregivers and one control arm with no intervention. Families with pregnant women or infants under 6 months of age are invited to enrol in the 12-month study. Primary outcomes include children's haemoglobin levels, exclusive breastfeeding rates and dietary diversity in complementary feeding. Secondary outcomes include a combination of health, behavioural and intermediate outcomes. ETHICS AND DISSEMINATION: Ethical approval has been provided by Stanford University, Sichuan University and the University of Nevada, Reno. Trial findings will be disseminated through national and international peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ISRCTN16800789.


Asunto(s)
Salud Infantil , Telemedicina , Lactante , Niño , Femenino , Humanos , Embarazo , Preescolar , Agentes Comunitarios de Salud , Población Rural , Lactancia Materna , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Int J Public Health ; 67: 1604794, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36147884

RESUMEN

Objectives: To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Methods: Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests. Results: Fifty-six cases were diagnosed from the cohort. The first model was developed based on seven significant predictors, including age, close contact with confirmed/suspected cases, same location of exposure, temperature, leukocyte counts, radiological findings of pneumonia and bilateral involvement (the mean area under the receiver operating characteristic curve [AUC]:0.88, 95% CI: 0.84-0.93). The second model had the same predictors except leukocyte and radiological findings (AUC: 0.84, 95% CI: 0.78-0.89, Z = 2.56, p = 0.01). Both were internally validated using H-L tests and showed good calibration (both p > 0.10). Conclusion: Two clinical risk scores to detect COVID-19 in local outbreaks were developed with excellent predictive performances, using commonly measured clinical variables. Further external validations in new outbreaks are warranted.


Asunto(s)
COVID-19 , COVID-19/epidemiología , China/epidemiología , Estudios de Cohortes , Brotes de Enfermedades , Humanos , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2
11.
Int Breastfeed J ; 17(1): 60, 2022 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-35987837

RESUMEN

BACKGROUND: The importance of breastfeeding in low- and middle- income countries is well recognized, yet the importance of postnatal mental health on breastfeeding practices and beliefs in these settings has been understudied. This study investigates the associations between maternal mental health problems, breastfeeding beliefs and breastfeeding practices in rural China. METHODS: Cross-sectional data were collected in November and December 2019 from 742 mothers of infants under 6 months old in rural Sichuan Province, China. Maternal mental health (depression, anxiety, and stress symptoms) was assessed using the Depression, Anxiety, and Stress Scale (short form). Breastfeeding beliefs were assessed using the Iowa Infant Feeding Attitude Scale and Breastfeeding Self-Efficacy Scale (short form). Breastfeeding practices were assessed through a 24-h dietary recall questionnaire. Ordinary least squares regression, multiple logistic regression and heterogeneous effects analyses were used to identify associations between symptoms of mental health problems and breastfeeding outcomes. RESULTS: The average age of sample infants was 2.7 months. Among mothers, 13% showed symptoms of depression, 16% anxiety, and 9% stress. The prevalence of exclusive breastfeeding in the previous 24 h was 38.0%. Depression symptoms were significantly associated with breastfeeding attitude (𝛽= - 1.11, 95% CI: - 2.07, - 0.14) and breastfeeding self-efficacy (𝛽= - 3.19, 95% CI: - 4.93, - 1.45). Anxiety and stress symptoms were significantly associated with breastfeeding self-efficacy (𝛽= - 1.81, 95% CI: - 3.43, - 0.18 and 𝛽 = - 2.88, 95% CI: - 4.98, - 0.78, respectively). There were no significant associations between symptoms of mental health problems and exclusive breastfeeding. The heterogeneous effects analyses revealed that less educated mothers with symptoms of stress had lower odds of exclusive breastfeeding than educated mothers without symptoms of stress (OR: 0.53, 95% CI: 0.25,1.10). Mothers of younger infants had higher odds of exclusive breastfeeding than the mother of older infants, regardless of depression, anxiety, or stress symptoms. CONCLUSION: Symptoms of maternal mental health problems are significantly associated with breastfeeding attitude and self-efficacy; however, these symptoms are not associated with breastfeeding practices. Maternal educational level and infant age may play a role in mothers' breastfeeding practices. To improve breastfeeding practices, interventions should employ a multi-dimensional approach that focuses on improving maternal mental well-being and considers demographic characteristics.


Asunto(s)
Lactancia Materna , Salud Mental , Lactancia Materna/psicología , China/epidemiología , Estudios Transversales , Femenino , Humanos , Lactante , Población Rural
12.
Sci Transl Med ; 14(653): eabq2096, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35857643

RESUMEN

Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1+ RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1-governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression in preclinical PAX3-FOXO1+ RMS subcutaneous xenograft models. In summary, we identified a targetable mechanism required for maintenance of the PAX3-FOXO1-related transcription factor network, which may translate to a therapeutic approach for fusion-positive RMS.


Asunto(s)
Rabdomiosarcoma Alveolar , Rabdomiosarcoma , Carcinogénesis/genética , Línea Celular Tumoral , Niño , Proteína Forkhead Box O1/metabolismo , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Factor de Transcripción PAX3/genética , Factor de Transcripción PAX3/metabolismo , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Factores de Transcripción Paired Box/uso terapéutico , Rabdomiosarcoma/genética , Rabdomiosarcoma Alveolar/genética , Rabdomiosarcoma Alveolar/metabolismo , Rabdomiosarcoma Alveolar/patología
13.
PLoS One ; 17(4): e0266273, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35390044

RESUMEN

BACKGROUND: Breastfeeding self-efficacy is known to positively influence breastfeeding behaviors. While previous research has studied the determinants of breastfeeding self-efficacy in general, these determinants are unstudied among postpartum women in rural China. This study aims to describe the breastfeeding self-efficacy of postpartum women in rural China and identify determinants of breastfeeding self-efficacy using the Dennis breastfeeding self-efficacy framework. METHODS: Using a multi-stage random cluster sampling design, cross-sectional survey data were collected from 787 women within the 0-6 months postpartum period in 80 rural townships. Surveys collected data on breastfeeding self-efficacy, characteristics related to the Dennis breastfeeding self-efficacy framework, and demographic characteristics. Multiple linear regression analysis was used to identify determinants of breastfeeding self-efficacy. RESULTS: Participants reported a moderate level of breastfeeding self-efficacy, with an item mean score of 3.50. Self-efficacy was lowest for exclusive breastfeeding. Breastfeeding attitudes (ß = 0.088, P< 0.001), breastfeeding family support (ß = 0.168, P< 0.001), and social support from significant others (ß = 0.219, P< 0.001) were positively associated with breastfeeding self-efficacy. Breastfeeding problems, including trouble with latching (ß = -0.170, P< 0.001), not producing enough milk (ß = -0.148, P< 0.001), and milk taking too long to secrete (ß = -0.173, P< 0.001) were negatively associated with breastfeeding self-efficacy. CONCLUSION: The findings indicate that positive attitudes, breastfeeding family support and social support contribute to greater breastfeeding self-efficacy in rural China, whereas difficulties with breastfeeding are associated with reduced self-efficacy. Researchers and practitioners should investigate effective strategies to improve social support and family support for breastfeeding, promote positive attitudes towards breastfeeding, and provide women with actionable solutions to breastfeeding problems.


Asunto(s)
Lactancia Materna , Autoeficacia , China , Estudios Transversales , Femenino , Humanos , Madres , Periodo Posparto , Encuestas y Cuestionarios
14.
Int J Radiat Oncol Biol Phys ; 113(1): 152-160, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34990778

RESUMEN

PURPOSE: Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach. METHODS AND MATERIALS: Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biological effectiveness PRT in a clinical trial, NCT01419067. We evaluated VAS type, location, severity, and resolution. VAS events were segmented and related to their location, operative corridor, PRT dose, and vascular territory to facilitate mixed effect logistic regression modeling of spatial predictors of STN events. RESULTS: Forty-five (47.9%) patients had 111 instances of confirmed VAS (pre-PRT n = 37, 33.3%). The median time to post-PRT VAS was 3.41 years (95% confidence interval, 1.86-6.11). STN events were observed post-PRT in 23.4% (n = 22) of patients. Post-PRT VAS was detected by cerebral angiogram in 9.6% (n = 9), severe in 4.3% (n = 4), and compensated on perfusion in 2.1% (n = 2). Revascularization was required for 5 (5.3%) patients. Postsurgical, pre-PRT VAS, and PRT dose to unperturbed vessels were predictive of STN. The effect of PRT on STN was negligible within the surgical corridor. CONCLUSIONS: VAS often precedes PRT and was the strongest predictor of post-PRT STN. The adverse effect of PRT on STN was only apparent in unperturbed vasculature beyond the operative corridor.


Asunto(s)
Craneofaringioma , Neoplasias Hipofisarias , Terapia de Protones , Niño , Craneofaringioma/radioterapia , Craneofaringioma/cirugía , Humanos , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/cirugía , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Protones , Factores de Riesgo
15.
J Clin Oncol ; 40(1): 83-95, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34714708

RESUMEN

PURPOSE: To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03. PATIENTS AND METHODS: Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline. RESULTS: One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose-volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively. CONCLUSION: Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure-informed RT planning may mitigate neurocognitive impairment.


Asunto(s)
Encéfalo/efectos de la radiación , Neoplasias Cerebelosas/radioterapia , Cognición/efectos de la radiación , Irradiación Craneana , Fraccionamiento de la Dosis de Radiación , Meduloblastoma/radioterapia , Dosis de Radiación , Adolescente , Conducta del Adolescente/efectos de la radiación , Desarrollo del Adolescente/efectos de la radiación , Factores de Edad , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/fisiopatología , Niño , Conducta Infantil/efectos de la radiación , Desarrollo Infantil/efectos de la radiación , Preescolar , Ensayos Clínicos Fase III como Asunto , Irradiación Craneana/efectos adversos , Femenino , Humanos , Masculino , Meduloblastoma/diagnóstico por imagen , Meduloblastoma/fisiopatología , Memoria/efectos de la radiación , Pruebas Neuropsicológicas , Planificación de la Radioterapia Asistida por Computador , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
16.
Front Glob Womens Health ; 2: 735264, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34870276

RESUMEN

Background: Maternal mental health problems play an important role in infant well-being. Although western countries have extensively studied the associations between maternal mental disorders, hygiene practices and infant health, little is known in developing settings. This study investigates the correlations between postnatal mental health problems, hand washing practices and infant illness in rural western China. Methods: A total of 720 mothers of infants aged 0-6 months from four poor counties in rural western China were included in the survey. Mental health symptoms were assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Questions about infant illness and hand washing practices followed evaluative surveys from prior studies. Adjusted ordinary least squares regressions were used to examine correlations between postnatal mental health (depression, anxiety, and stress) symptoms, hand washing practices, and infant illness outcomes. Results: Maternal depression, anxiety and stress symptoms were significantly associated with reduced hand washing overall and less frequent hand washing after cleaning the infant's bottom. Mental health symptoms were also associated with a higher probability of infants showing two or more illness symptoms and visiting a doctor for illness symptoms. Individual hand washing practices were not significantly associated with infant illness; however, a composite measure of hand washing practices was significantly associated with reduced probability of infant illness. Conclusion: Postnatal mental health problems are prevalent in rural China and significantly associated with infant illness. Policy makers and practitioners should investigate possible interventions to improve maternal and infant well-being.

17.
Front Psychiatry ; 12: 636875, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34950062

RESUMEN

Background: Perinatal mental health is important for the well-being of the mother and child, so the relatively high prevalence of perinatal mental health problems in developing settings poses a pressing concern. However, most studies in these settings focus on the demographic factors associated with mental health problems, with very few examing social factors. Hence, this study examines the prevalence of the depressive, anxiety and stress symptoms among pregnant women and new mothers in rural China, and the associations between these mental health problems and social factors, including decision-making power, family conflicts, and social support. Methods: Cross-sectional data were collected from 1,027 women in their second trimester of pregnancy to 6 months postpartum in four low-income rural counties in Sichuan Province, China. Women were surveyed on symptoms of mental health problems using the Depression, Anxiety, and Stress Scale (DASS-21) and social risk factors. Multivariate logistic regression analyses were conducted to examine social risk factors associated with maternal mental health problems, with results reported as odds ratios (OR) and 95% confidence intervals (CI). Results: Among all respondents, 13% showed symptoms of depression, 18% showed symptoms of anxiety, 9% showed symptoms of stress, and 23% showed symptoms of any mental health problem. Decision-making power was negatively associated with showing symptoms of depression (OR = 0.71, CI: 0.60-0.83, p < 0.001) and stress (OR = 0.76, CI: 0.63-0.90, p = 0.002). Family conflict was positively associated with depression (OR = 1.53, CI: 1.30-1.81, p < 0.001), anxiety (OR = 1.34, CI: 1.15-1.56, p < 0.001), and stress (OR = 1.68, CI: 1.41-2.00, p < 0.001). In addition, social support was negatively associated with depression (OR = 0.56, CI: 0.46-0.69, p < 0.001), anxiety (OR = 0.76, CI: 0.63-0.91, p = 0.002), and stress (OR = 0.66, CI: 0.53-0.84, p < 0.001). Subgroup analyses revealed that more social risk factors were associated with symptoms of anxiety and stress among new mothers compared to pregnant women. Conclusion: Perinatal mental health problems are relatively prevalent among rural women in China and are strongly associated with social risk factors. Policies and programs should therefore promote individual coping methods, as well as target family and community members to improve the social conditions contributing to mental health problems among rural women.

18.
Angew Chem Int Ed Engl ; 60(43): 23403-23411, 2021 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-34448341

RESUMEN

Highly reducing polyketide synthases (HR-PKSs) produce structurally diverse polyketides (PKs). The PK diversity is constructed by a variety of factors, including the ß-keto processing, chain length, methylation pattern, and relative and absolute configurations of the substituents. We examined the stereochemical course of the PK processing for the synthesis of polyhydroxy PKs such as phialotides, phomenoic acid, and ACR-toxin. Heterologous expression of a HR-PKS gene, a trans-acting enoylreductase gene, and a truncated non-ribosomal peptide synthetase gene resulted in the formation of a linear PK with multiple stereogenic centers. The absolute configurations of the stereogenic centers were determined by chemical degradation followed by comparison of the degradation products with synthetic standards. A stereochemical rule was proposed to explain the absolute configurations of other reduced PKs and highlights an error in the absolute configurations of a reported structure. The present work demonstrates that focused functional analysis of functionally related HR-PKSs leads to a better understanding of the stereochemical course.


Asunto(s)
Proteínas Fúngicas/química , Sintasas Poliquetidas/química , Policétidos/síntesis química , Ascomicetos/enzimología , Proteínas Fúngicas/genética , Mutación , Oxidación-Reducción , Sintasas Poliquetidas/genética , Estereoisomerismo
20.
Molecules ; 26(14)2021 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-34299497

RESUMEN

The first total synthesis of the thiazole-containing cyclic depsipeptide pagoamide A, is detailed. The longest linear sequence of the liquid-phase synthesis comprises 9 long linear steps from simple known starting materials, which led to the unambiguous structural confirmation of pagoamide A.


Asunto(s)
Depsipéptidos/síntesis química , Péptidos Cíclicos/síntesis química , Estructura Molecular , Tiazoles/química
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