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Three contrasting sedimentary environments on the continental shelf off the Guadiana River (northern Gulf of Cadiz) were integrated in a chronological framework and analysed in terms of sedimentology and benthic foraminiferal assemblages to understand the Holocene paleoenvironmental evolution. The analysed environments differ in terms of their depositional regimes and benthic foraminiferal assemblages. However, a dominant fluvial origin of the sand fraction was observed in all three environments. Holocene sedimentary processes were mainly controlled by natural (sea level changes and climate variations) and human-induced processes (e.g. deforestation, agriculture) along four evolutionary stages. The three older stages were mainly influenced by natural processes, such as sea level variations and fluvial inputs, whereas the most recent stage reflects a combination of climatic- and human-induced processes. A deepening of sedimentary environments related to a period of rapid sea level rise, strongly influenced by river discharges occurred from c. 11,500 to c. 10,000 cal. yr BP. A reduction in sediment export to the shelf, as a result of the continuous and rapid sea level rise and enhanced estuary infilling reflects the second stage, from c. 10,000 to c. 5000 cal. yr BP. The beginning of the third stage, from c. 5000 to c. 1500–1000 cal. yr BP, is marked by a sea-level slowdown and the relatively stable climate and environmental conditions. The fourth stage, from c. 1500–1000 cal. yr BP to Recent times, reflects the intensification of human-induced processes and climatic variability in the Guadiana River basin. This stage also reflects modern depositional conditions, with the formation of a proximal prodeltaic wedge and a distal muddy body. [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone (FSH), or follitropin, exists in multiple molecular forms due largely to its protein-carbohydrate composition and the complexity of the glycans attached to the protein core. The heterogeneity of gonadotropins exists in two forms, macroheterogeneity, which results from the absence of one or two oligosaccharide chains in the ß-subunit, and microheterogeneity which results from variation in the structures and complexity of the glycans attached to the hormone. In the clinical arena, FSH compounds are widely used by fertility specialists to promote ovarian follicle growth and maturation to a preovulatory follicle containing a fertilization-competent oocyte. Several genetically engineered recombinant human FSH preparations have been added to the arsenal of follitropin preparations in several countries for the treatment of infertility, particularly in women attending assisted reproduction clinics. Although the primary structure of these recombinant proteins is identical to that of naturally occurring FSH, the cell context and variations in the production and purification processes may impact the glycosidic profile of the recombinant FSH macro- and micro-heterogeneity, which may potentially influence the pharmacokinetics and pharmacodynamics of the compound. This review concentrates on the structure-function correlates of follitropin, with emphasis on the physiological and biological importance of the carbohydrates attached to its protein core, including its pharmacokinetics and biological activity. Emphasis is placed on pituitary FSH, and the available data on the various recombinant FSH preparations employed in therapeutics are also discussed, considering that this gonadotropin represents the cornerstone for the treatment of infertility in modern assisted reproduction., Competing Interests: Conflict of Interest All authors declare no conflicts of interest related to this manuscript., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas., (© 2024. The Author(s).)

Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Summary: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations., Availability and Implementation: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available at https://github.com/UW-GAC/admix-kit_workflow., (© The Author(s) 2024. Published by Oxford University Press.)

Nanocomposites based on poly(lactic acid) (PLA) and magnetite nanoparticles (MNP-Fe 3 O 4 ) show promise for applications in biomedical treatments. One key challenge is to improve the stabilization and dispersion of MNP-Fe 3 O 4 . To address this, we synthesized MNP-Fe 3 O 4 /PLA nanocomposites using ultrasound mediation and a single iron(II) precursor, eliminating the need for surfactants or organic solvents, and conducted the process under ambient conditions. The resulting materials, containing 18 and 33 wt.% Fe 3 O 4 , exhibited unique thermal behavior characterized by two mass losses: one at a lower degradation temperature (T d ) and another at a higher T d compared to pure PLA. This suggests that the interaction between PLA and MNP-Fe 3 O 4 occurs through hydrogen bonds, enhancing the thermal stability of a portion of the polymer. Fourier Transform Infrared (FT-IR) analysis supported this finding, revealing shifts in bands related to the terminal -OH groups of the polymer and the Fe-O bonds, thereby confirming the interaction between the groups. Raman spectroscopy demonstrated that the PLA serves as a protective layer against the oxidation of MNP-Fe 3 O 4 in the 18% MNP-Fe 3 O 4 /PLA nanocomposite when exposed to a high-power laser (90 mW). Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) analyses confirmed that the synthetic procedure yields materials with dispersed nanoparticles within the PLA matrix without the need for additional reactants.

Mango and its by-products have traditional medicinal uses. They contain diverse bioactive compounds offering numerous health benefits, including cardioprotective and metabolic properties. This study aimed to explore the impact of mango fruit and its by-products on human health, emphasizing its metabolic syndrome components. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR were searched following PRISMA guidelines, and the COCHRANE handbook was utilized to assess bias risks. In vivo and in vitro studies have shown several benefits of mango and its by-products. For this systematic review, 13 studies met the inclusion criteria. The collective findings indicated that the utilization of mango in various forms-ranging from fresh mango slices and mango puree to mango by-products, mango leaf extract, fruit powder, and mangiferin-yielded many favorable effects. These encompassed enhancements in glycemic control and improvements in plasma lipid profiles. Additionally, mango reduces food intake, elevates mood scores, augments physical performance during exercise, improves endothelial function, and decreases the incidence of respiratory tract infections. Utilizing mango by-products supports the demand for healthier products. This approach also aids in environmental conservation. Furthermore, the development of mango-derived nanomedicines aligns with sustainable goals and offers innovative solutions for healthcare challenges whilst being environmentally conscious.

Crohn disease (CD) is often complicated by bowel strictures that can lead to obstructive symptoms, resistant inflammation, and penetrating complications. Endoscopic balloon dilatation of CD strictures has emerged as a safe and effective technique for relieving these strictures, which may obviate the need for surgical intervention in the short and medium term. This technique appears to be underutilized in pediatric CD. This position paper of the Endoscopy Special Interest Group of European Society for Pediatric Gastroenterology, Hepatology and Nutrition describes the potential applications, appropriate evaluation, practical technique, and management of complications of this important procedure. The aim being to better integrate this therapeutic strategy in pediatric CD management., Competing Interests: S.O. received consulting fees from Medtronic and Sanofi. J.A.D. has participated as a speaker for Danone Nutricia, Takeda, Ferrer, Capricare, and Biocodex, and on advisory boards for Danone, Bristol Myers Squibb, and Adacyte. C.T. received last 3-years payments/honoraria for lectures/consultations from Sanofi, Takeda, Nestle, Nutricia, Abbvie, Novalac, Olympus, and Genpharm. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy., Methods: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse., Results: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031)., Conclusions: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision., Impact: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objetive: To estimate the prevalence of psychological, physical, and sexual violence perpetrated against women by their intimate partner (IP) in Quilombola communities located in Espírito Santo State, Brazil., Methods: The data is from a population-based cross-sectional study of Quilombola women conducted from 2017 to 2018. In-person interviews collected information on women's sociodemographic characteristics, behaviors, and their experience of violence perpetrated by their IP. The analysis used chi-square test and hierarchical logistic regression., Results: 219 women (94.8% of the invited ones) agreed to participate in the study. 59.0% (95%CI: 5.25-65.5) reported psychological violence; 41% (95%CI: 34.5-47.5) physical violence; and 8.2% (95%CI: 4.6-11.8) sexual violence. Psychological violence was associated with having three or more sexual partners in life, when compared to those who had up to two partners (p = 0,009), and previous violence involving other people outside of family increased the chance of suffering psychological violence by an IP more than nine times (p ≤ 0.001). Regarding physical violence, the association with use of barrier contraception (p = 0.031) and having a partner with other sexual partners (p = 0.024) were protective factors for IP violence. Having 3 or more sexual partners in the last 12 months (p = 0.006), partner using illicit drugs (p = 0,006), and alcoholism in the family (p = 0,001), increased the chance of suffer physical violence by the partner. Sexual violence perpetrated by the IP was associated with miscarriage (p = 0.016), partner using drugs (p = 0.020), and gynecological symptoms (p = 0.045)., Conclusions: These results showed the high frequency of intimate partner violence in Quilombola women and highlight the importance of reducing social and race inequities for interrupting the culture of violence against women.

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature., Methods: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement., Results: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas., Conclusions: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science., (Copyright © 2022. Published by Elsevier Inc.)

The worldwide incidence of allergic diseases has been continuously increasing, and up to one in every five people are currently affected by these medical conditions. Although seldom fatal, allergies have a profound impact on children's growth, development, and quality of life, besides being associated with heavy healthcare costs and resource utilisation. In this context, a group of experts in nutrition, paediatric gastroenterology, allergology, and neonatology joined forces to discuss the role of infant formulas in the primary prevention of allergies in infants for whom breastfeeding is not an option and who are at risk of developing allergies. The topics discussed included the assessment of risk, the impact of the microbiota on the modulation of immune tolerance, and the added value of certain formula characteristics, namely, protein integrity (hydrolysed protein vs. intact protein) and the addition of prebiotics, probiotics, or synbiotics. This article describes the latest evidence on each of the above-mentioned points, as well as a number of recommendations made by the experts to guide counselling of parents in the choice of a formula for infants at risk of allergy. Overall, the experts highlighted family history and dysbiosis-promoting factors (namely, caesarean delivery and antibiotic use) as two of the most important risk factors for allergy development. Moreover, in line with international guidelines, the panel advocated that intact protein formula should be offered to all bottle-fed healthy infants, irrespective of their allergic risk (with the exception of short-term bottle feeding of otherwise breastfed babies in their first week of life, for whom a hydrolysed formula may be advisable). Finally, the experts agreed that the use of prebiotic-, probiotic-, or synbiotic-enriched formulas should be considered in infants at risk of developing allergies.

Objectives: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel., Methods: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected., Results: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%)., Conclusions: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response., Competing Interests: Noam Zevit: consultation fees – Dr Falk Pharma, Adare Pharmaceuticals; speaker fees – Rafa inc and Sanofi. Salvatore Oliva: consultation fees – Medtronic, Ocean Farma; speaker fees – Medtronic. Marcus Karl-Heinz Auth – consultation fees: Dr Falk Pharma; educational grants: Nutricia, Mead Johnson. Alexandra Papadopoulou: research grants from Abbvie, United Pharmaceuticals, Dr Falk Pharma GmbH, Takeda, AstraZeneca; speaker or consultation fees from Adare Pharmaceuticals, Dr Falk Pharma GmbH, Specialty Therapeutics, Uni-Pharma Pharmaceuticals Laboratories S.A., Cross Pharmaceuticals, Petsiavas, Nestle, Touch Independent Medical Education, and Sanofi-Aventis. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)