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Three-dimensional (3D) ex vivo cultures allow the study of cancer progression and drug resistance mechanisms. Here, we present a protocol for measuring on-target drug sensitivity in a scaffold-free 3D culture system through quantification of apoptotic tumor cells. We provide detailed steps for sample processing, immunofluorescence staining, semi-high-throughput confocal imaging, and imaged-based quantification of 3D cultures. This protocol is versatile and can be applied in principle to any patient-derived material.
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Recent years have seen the creation and popularization of various complexin vitromodels (CIVMs), such as organoids and organs-on-chip, as a technology with the potential to reduce animal usage in pharma while also enhancing our ability to create safe and efficacious drugs for patients. Public awareness of CIVMs has increased, in part, due to the recent passage of the FDA Modernization Act 2.0. This visibility is expected to spur deeper investment in and adoption of such models. Thus, end-users and model developers alike require a framework to both understand the readiness of current models to enter the drug development process, and to assess upcoming models for the same. This review presents such a framework for model selection based on comparative -omics data (which we term model-omics), and metrics for qualification of specific test assays that a model may support that we term context-of-use (COU) assays. We surveyed existing healthy tissue models and assays for ten drug development-critical organs of the body, and provide evaluations of readiness and suggestions for improving model-omics and COU assays for each. In whole, this review comes from a pharma perspective, and seeks to provide an evaluation of where CIVMs are poised for maximum impact in the drug development process, and a roadmap for realizing that potential.
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Organoides , Humanos , Animales , Organoides/efectos de los fármacos , Organoides/metabolismo , Evaluación Preclínica de Medicamentos , Industria FarmacéuticaRESUMEN
BACKGROUND: Young refugees' resilience is linked to involvement in socio-ecological systems that contribute to their well-being. OBJECTIVE: This study aimed to understand the experiences and factors contributing to resilience among young Sudanese and South Sudanese refugees (aged 16, M = 16 years; N = 40; 21 males, 19 females) residing at the Sherkole refugee camp in Ethiopia's Benishangul-Gumuz region. METHOD: Six focus groups (N = 40) and four key informant interviews with government officials, caregivers, and school teachers explored themes related to resilience using thematic analysis. Member checking ensured findings aligned with participants' perspectives. A socio-ecological framework guided the exploration of multidimensional factors. RESULTS: Five themes emerged: (1) support systems, (2) work engagement, (3) access to education, (4) role of religion, and (5) community engagement. Work opportunities helped young refugees cope with challenges, but key informants raised concerns about potential risks to education. Social connection and community engagement fostered a harmonious relationship with the host community. Religion and education alleviated stress and worries. The themes interrelated - community engagement improved host community relationships, increasing job opportunities and income (leading to better support systems). Religious activities and education also benefited relationships and provided relaxation. CONCLUSION: This study supports the dynamic and multi-systemic nature of resilience within a socio-ecological framework. Findings can inform future resilience-promoting interventions and policies for young refugees.
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INTRODUCTION: This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation. MATERIAL AND METHODS: This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups. RESULTS: Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82). CONCLUSIONS: Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.
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In this work, the hexane, chloroform, and methanol extracts from Kalanchoe fedtschenkoi were utilized to green-synthesize silver nanoparticles (Kf1-, Kf2-, and Kf3-AgNPs). The Kf1-, Kf2-, and Kf3-AgNPs were characterized by spectroscopy and microscopy techniques. The antibacterial activity of AgNPs was studied against bacteria strains, utilizing the microdilution assay. The DPPH and H2O2 assays were considered to assess the antioxidant activity of AgNPs. The results revealed that Kf1-, Kf2-, and Kf3-AgNPs exhibit an average diameter of 39.9, 111, and 42 nm, respectively. The calculated ζ-potential of Kf1-, Kf2-, and Kf3-AgNPs were -20.5, -10.6, and -7.9 mV, respectively. The UV-vis analysis of the three samples demonstrated characteristic absorption bands within the range of 350-450 nm, which confirmed the formation of AgNPs. The FTIR analysis of AgNPs exhibited a series of bands from 3500 to 750 cm-1, related to the presence of extracts on their surfaces. SEM observations unveiled that Kf1- and Kf2-AgNPs adopted structural arrangements related to nano-popcorns and nanoflowers, whereas Kf3-AgNPs were spherical in shape. It was determined that treatment with Kf1-, Kf2-, and Kf3-AgNPs was demonstrated to inhibit the growth of E. coli, S. aureus, and P. aeruginosa in a dose-dependent manner (50-300 µg/mL). Within the same range, treatment with Kf1-, Kf2-, and Kf3-AgNPs decreased the generation of DPPH (IC50 57.02-2.09 µg/mL) and H2O2 (IC50 3.15-3.45 µg/mL) radicals. This study highlights the importance of using inorganic nanomaterials to improve the biological performance of plant extracts as an efficient nanotechnological approach.
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Antibacterianos , Antioxidantes , Tecnología Química Verde , Kalanchoe , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Plata , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Kalanchoe/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Picratos/antagonistas & inhibidores , Picratos/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Peróxido de HidrógenoRESUMEN
BACKGROUND: In Mexico, anemia prevalence among women of reproductive age (WRA) decreased from 16.4% in 2006 to 11.6% in 2012, only to increase to 18.3% in 2016. The factors associated with this fluctuation are uncertain. OBJECTIVE: We conducted a systematic in-depth assessment of the quantitative and qualitative determinants of anemia among WRA in Mexico between 2006 and 2018. METHODS: Using multivariate stepwise linear regression, we analyzed Mexico's Encuesta Nacional de Salud y Nutrición (ENSANUT) surveys from 2006, 2012, and 2018 to identify determinants of WRA anemia. We also conducted a review of anemia-relevant programs and policies, including financing documents, and conducted in-depth interviews and focus group discussions with key stakeholders in Mexico. RESULTS: Among non-pregnant women (NPW) 15-49 years, mean hemoglobin (Hb) increased from 13.8 g/dL in 2006 to 14.0 g/dL in 2012, decreasing to 13.2 g/dL in 2018 (p<0.001). Inequities by geographical region and household wealth persisted throughout this period, with household wealth, urban residence and gravidity emerging as significant predictors of Hb among NPW. Qualitative analyses generally supported these findings. The most discussed program was Progresa-Oportunidades-Prospera (POP), where most resources for health were invested and most participants acknowledged that its cancellation in 2019 would lead to worsening in health and nutrition among the poor. Financing analyses showed a drop of funding for nutrition-related programs between 2014 and 2018. Cultural norms around gender roles were still prevalent, along with increasing rates of teenage pregnancy. CONCLUSIONS: Anemia prevention efforts need to refocus on poverty alleviation, continuity of adequate coverage and financing of nutrition programs, especially with safety nets, and increase in uptake of family planning, especially among adolescent girls.
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Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
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Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, ß-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.
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Carcinoma Hepatocelular , ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , Antígeno Nuclear de Célula en Proliferación , Piridonas , Animales , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Piridonas/farmacología , Ratas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Células Hep G2 , Antígeno Nuclear de Célula en Proliferación/metabolismo , Masculino , Ratas Endogámicas F344 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Dietilnitrosamina , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/genéticaRESUMEN
Anti-Trypanosoma cruzi activity of compounds from fruits of Schinus terebinthifolius Raddi (pink pepper) were evaluated, using sustainable techniques such as steam distillation (SD) and supercritical fluid extraction (SFE). SD was optimised using a design of experiment and SFE was carried out using supercritical CO2 solvent (300 bar and 60 °C). Results of the anti-T. cruzi activity showed that the essential oil presented high activity (IC50 = 4.5 ± 0.3 µg/mL), whereas the supercritical extract had a moderate effect (IC50 = 19.7 ± 2.9 µg/mL). The differences in the anti-T. cruzi activity can be attributed to the extraction of non-volatile compounds in the SFE, such as moronic and (Z)-masticadienoic acids. In contrast, SD extracted only volatile compounds such as monoterpenes and sesquiterpenes. Therefore, these results suggest that the volatile compounds from pink pepper are involved with the anti-T. cruzi activity.
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The tomato (Licopersicon esculentum Mill.) is considered to be one of the products with the highest demand due to its nutritional value; however, it is susceptible to infection by fungi during its pre- and postharvest stages. In this research, three commercial products (1% Citrocover, 1% Citro 80, and 0.002% Microdyn) and two coatings based on 1.0% chitosan/0.1% lime or 0.1% orange essential oils were evaluated in vitro and on Saladette tomatoes that were previously inoculated with four postharvest fungi. The application of the commercial citrus-based product Citrocover was highly effective in reducing the in vitro development of Aspergillus flavus, Fusarium oxysporum, and Colletotrichum gloeosporioides, but not Rhizopus stolonifer. The sanitizer Microdyn promoted infections with most fungi. Citrus-based products were effective in reducing infections with A. flavus in the tomatoes during storage. Overall, mycotoxin production was very low for all treatments. The use of commercial citrus-based products and coatings did not alter the weight loss, firmness, or total soluble solid contents of the treated tomatoes. The changes observed were, rather, associated with the normal ripening process of Saladette tomatoes. The commercial citrus-based products satisfactorily controlled the in vitro growth of the fungi Aspergillus flavus, Fusarium oxysporum, and Colletotrichum gloeosporioides.
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INTRODUCTION: Reliance on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes may misclassify perforated appendicitis with resultant research, fiscal, and public health implications. We aimed to improve the accuracy of administrative data for perforated appendicitis classification relying on ICD-10-CM codes from 2015 to 2018. METHODS: We conducted a retrospective study of randomly sampled patients aged ≤18 years diagnosed with acute appendicitis from eight children's hospitals. Patients were identified using the Pediatric Health Information System, and true perforation status was determined by medical record review. We developed two algorithms by leveraging Pediatric Health Information System data elements and data mining (DM) approaches. The two developed algorithm performance was compared against algorithms that exclusively relied on ICD-10-CM codes using area under the curve and other measures. RESULTS: Of 1051 clinically validated encounters that were included, 383 (36.4%) patients were identified to have perforated appendicitis. The two algorithms developed using DM approaches primarily leveraged ICD-10-CM codes and length of stay. DM-developed algorithms had a significantly higher accuracy than algorithms relying exclusively on ICD-10-CM (P value < 0.01): sensitivity and specificity for DM-developed algorithms were 0.86-0.88 and 0.95-0.97, respectively, which were overall higher than algorithms that relied on only ICD-10-CM. CONCLUSIONS: This study provides an algorithm that can improve the accuracy of perforated appendicitis classification using commonly available elements in administrative data. We recommend that this algorithm is used in future appendicitis classification to ensure valid reporting, hospital-level benchmarking, and fiscal or public health assessments.
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Algoritmos , Apendicitis , Clasificación Internacional de Enfermedades , Humanos , Apendicitis/clasificación , Apendicitis/diagnóstico , Niño , Estudios Retrospectivos , Clasificación Internacional de Enfermedades/normas , Masculino , Femenino , Adolescente , Preescolar , Minería de Datos , Exactitud de los DatosRESUMEN
Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.
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Immunogenicity of SARS-CoV-2 mRNA vaccines is highly heterogeneous in patients with inborn errors of immunity (IEIs). This case report analyzes the immune response to mRNA COVID-19 two-dose primary vaccination followed by three boosters in an IEI patient with marked CD4+ T-cell cytopenia and diminished thymic output, in comparison with that raised against latent, chronic cytomegalovirus (CMV) infection. Serum IgG antibodies anti-spike (S) protein of SARS-CoV-2 and anti-CMV were both determined by chemiluminescent microparticle immunoassays (CMIAs). SARS-CoV-2 and CMV memory CD4+ T-cell responses were simultaneously evaluated in vitro using an activation-induced marker (AIM) assay via multicolor flow cytometry. Throughout the 2-year follow-up that included the administration of five doses of SARS-CoV-2 mRNA vaccines, cellular anti-SARS-CoV-2-specific responses remained consistently negative, with extremely weak humoral responses, while the patient showed in vitro persistent CD4+ T-cell reactivity to CMV peptides and high-IgG CMV-specific titers. The assessment of immune responses to vaccines and prevalent viruses is essential in IEI patients in order to take adequate preventive measures.
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INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.
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Ensayos Clínicos como Asunto , Neoplasias , Sistema de Registros , Humanos , Niño , Neoplasias/terapia , España , Oncología Médica , Estudios Observacionales como Asunto , Cooperación Internacional , Selección de PacienteRESUMEN
RNA thermometers are highly structured noncoding RNAs located in the 5'-untranslated regions (UTRs) of genes that regulate expression by undergoing conformational changes in response to temperature. The discovery of RNA thermometers through bioinformatics is difficult because there is little sequence conservation among their structural elements. Thus, the abundance of these thermosensitive regulatory structures remains unclear. Herein, to advance the discovery and validation of RNA thermometers, we developed Robo-Therm, a pipeline that combines an adaptive and user-friendly in silico motif search with a well-established reporter system. Through our application of Robo-Therm, we discovered two novel RNA thermometers in bacterial and bacteriophage genomes found in the human gut. One of these thermometers is present in the 5'-UTR of a gene that codes for σ 70 RNA polymerase subunit in the bacteria Mediterraneibacter gnavus and Bacteroides pectinophilus, and in the bacteriophage Caudoviricetes, which infects B. pectinophilus The other thermometer is in the 5'-UTR of a tetracycline resistance gene (tetR) in the intestinal bacteria Escherichia coli and Shigella flexneri Our Robo-Therm pipeline can be applied to discover multiple RNA thermometers across various genomes.
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Regiones no Traducidas 5' , Humanos , Biología Computacional/métodos , Bacteriófagos/genética , Bacteroides/genética , Bacteroides/virología , ARN Bacteriano/genética , Conformación de Ácido Nucleico , ARN Viral/genéticaRESUMEN
Urban health faces significant challenges due to the rapid growth of cities and the concentration of population in urban settings that have a strong impact on people's health. The approach to characterize and address these challenges requires increased societal involvement and interdisciplinary solutions to ensure their effectiveness and democratic nature. With this purpose, it is necessary to explore methodologies for citizen participation that foster a critical understanding of the environment and promote their active role in generating scientific knowledge and change. This article describes the creation of a collaborative space for experimentation and learning that, through the intersection of citizen science and social innovation, aims to engage citizens in the research and diagnosis of their local environment, as well as in the design and implementation of local solutions, while raising awareness about the main challenges to urban health. Through a collaborative and participatory framework, the community identified relevant challenges to urban health they wanted to investigate, co-designed and developed the methodology for data collection and analysis, and ultimately, they devised, designed, and implemented innovative solutions based on the scientific evidence obtained. The framework and results of this project hold potential interest for the scientific community, facilities, institutions, and society by offering an innovative and participatory approach to addressing the present and future urban health challenges.
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Ciencia Ciudadana , Humanos , Salud Urbana , Participación de la Comunidad , España , CiudadesRESUMEN
Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.
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Hernia Inguinal , Herniorrafia , Recien Nacido Prematuro , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Asiático/estadística & datos numéricos , Teorema de Bayes , Edad Gestacional , Hernia Inguinal/epidemiología , Hernia Inguinal/etnología , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Herniorrafia/estadística & datos numéricos , Alta del Paciente , Factores de Edad , Hispánicos o Latinos/estadística & datos numéricos , Blanco/estadística & datos numéricos , Estados Unidos/epidemiología , Negro o Afroamericano/estadística & datos numéricosRESUMEN
The San Quintin Kangaroo Rat, a rodent species microendemic to the San Quintin-El Rosario region in Baja California that was considered potentially extinct in the wild, was recently rediscovered. This stimulated subsequent searches by us throughout its known distribution range and on sites that seemed suitable beyond its limits. We captured the species at 19 out of 42 localities surveyed, of which 6 are beyond its historically known distribution range, expanding the latter by ~60 km. Most sites occupied by the species occur on abandoned farmland in early ecological successional stages. Our data support that in the highly transformed agricultural landscape into which the region was converted in the 20th century, the species was able to survive undetected and colonize/recolonize sites once habitat became adequate after agricultural abandonment. This exhibits that the species is highly resilient and persisted as a metapopulation. Further research and conservation actions must be framed within context of the region's agricultural development.
QuintínEl Rosario, Baja California, considerada potencialmente extinta, se redescubrió recientemente. Ello estimuló búsquedas en todo su rango de distribución conocido y en sitios potenciales que parecían adecuados más allá de sus límites geográficos. Capturamos a la especie en 19 de 42 localidades, de las cuales 6 estaban fuera de su rango de distribución históricamente conocido, expandiendo este rango en ~60 km. La mayoría de los sitios ocupados por la especie se encuentran en tierras de cultivo abandonadas en etapas tempranas de sucesión ecológica. Nuestros datos respaldan la hipótesis de que el paisaje agrícola altamente antropizado, en el que se convirtió la región en el siglo XX, la especie sobrevivió en refugios y colonizó/recolonizó sitios una vez que el hábitat se volvió adecuado después de su abandono agrícola. Esto mostró que la especie es altamente resiliente y persistió como una metapoblación. Las futuras acciones de investigación y conservación deben enmarcarse en el contexto del desarrollo agrícola de la región.
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PURPOSE OF REVIEW: This scoping review aims to assess the impact of air pollution, traffic noise, heat, and green and blue space exposures on the physical and cognitive development of school-age children and adolescents. While existing evidence indicates adverse effects of transport-related exposures on their health, a comprehensive scoping review is necessary to consolidate findings on various urban environmental exposures' effects on children's development. RECENT FINDINGS: There is consistent evidence on how air pollution negatively affects children's cognitive and respiratory health and learning performance, increasing their susceptibility to diseases in their adult life. Scientific evidence on heat and traffic noise, while less researched, indicates that they negatively affect children's health. On the contrary, green space exposure seems to benefit or mitigate these adverse effects, suggesting a potential strategy to promote children's cognitive and physical development in urban settings. This review underscores the substantial impact of urban exposures on the physical and mental development of children and adolescents. It highlights adverse health effects that can extend into adulthood, affecting academic opportunities and well-being beyond health. While acknowledging the necessity for more research on the mechanisms of air pollution effects and associations with heat and noise exposure, the review advocates prioritizing policy changes and urban planning interventions. This includes minimizing air pollution and traffic noise while enhancing urban vegetation, particularly in school environments, to ensure the healthy development of children and promote lifelong health.