[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Green synthesis of MIL53(Al)-modified paper-based analytical device for efficient extraction of neonicotinoid insecticides from environmental water samples.

BACKGROUND: There is a need to develop low-cost, reliable and portable devices to enhance the efficiency of microextraction techniques in complex samples. Metal-organic frameworks (MOFs) have proven to be promising sorbents due to their well-documented properties. However, their green preparation and combination with paper-based substrates have not been satisfactorily explored to fabricate sustainable sorptive phases. RESULTS: In this work, the hybridization of a paper substrate (as a sustainable support) with MOFs (as a sorptive phase) was carried out by one-pot approach. Concretely, the selected MOF, MIL-53(Al), was in-situ growth onto the paper surface in aqueous solution without the need for high temperature or pressure, thereby aligning with the Green Analytical Chemistry principles. The optimized composite (MIL-53(Al)@cellulose paper) was characterized and evaluated as extraction sorbent for five neonicotinoids (NEOs) (thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid). Furthermore, its feasibility was demonstrated by isolating these pollutants from environmental water samples, followed their determination by HPLC coupled to diode array detection. The whole method showed satisfactory analytical performance with recoveries between 86 and 114 %, suitable precision (with RSD lower than 14 %), and limits of detection ranged from 1.0 to 1.6 µg L-1. Besides, the greenness of the method was assessed by application of different existing metrics. The developed extraction device was affordable (<0.08 €/device) and mechanical and chemically stable, being possible its reuse more than 11 cycles, thus demonstrating its suitability for rapid screening of pesticides in environmental samples. SIGNIFICANCE: This report presents, for the first time, the green synthesis of MIL-53(Al)cellulose paper composite and its application as a sorptive phase for the extraction of NEOs from environmental water samples. We believe that the proposed strategy for fabricating these sustainable paper-based sorptive phases paves the way for further hybridizations with other MOFs or materials. Additionally, it opens up large possibilities for their application in extraction of pollutants or other hazardous compounds in aquatic environments.

Synthesis, Structural Analysis, and Peroxidase-Mimicking Activity of AuPt Branched Nanoparticles.

Bimetallic nanomaterials have generated significant interest across diverse scientific disciplines, due to their unique and tunable properties arising from the synergistic combination of two distinct metallic elements. This study presents a novel approach for synthesizing branched gold-platinum nanoparticles by utilizing poly(allylamine hydrochloride) (PAH)-stabilized branched gold nanoparticles, with a localized surface plasmon resonance (LSPR) response of around 1000 nm, as a template for platinum deposition. This approach allows precise control over nanoparticle size, the LSPR band, and the branching degree at an ambient temperature, without the need for high temperatures or organic solvents. The resulting AuPt branched nanoparticles not only demonstrate optical activity but also enhanced catalytic properties. To evaluate their catalytic potential, we compared the enzymatic capabilities of gold and gold-platinum nanoparticles by examining their peroxidase-like activity in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Our findings revealed that the incorporation of platinum onto the gold surface substantially enhanced the catalytic efficiency, highlighting the potential of these bimetallic nanoparticles in catalytic applications.

New experimental model to evaluate the effect of negative pressure wound therapy and viscosity exudates in foam dressings using confocal microscopy.

Negative pressure wound therapy is currently one of the most popular treatment approaches that provide a series of benefits to facilitate healing, including increased local blood perfusion with reduced localized oedema and control of wound exudate. The porous foam dressing is a critical element in the application of this therapy and its choice is based on its ability to manage exudate. Industry standards often employ aqueous solutions devoid of proteins to assess dressing performance. However, such standardized tests fail to capture the intricate dynamics of real wounds, oversimplifying the evaluation process. This study aims to evaluate the technical characteristics of two different commercial polyurethane foam dressings during negative pressure wound therapy. We introduce an innovative experimental model designed to evaluate the effects of this therapy on foam dressings in the presence of viscous exudates. Our findings reveal a proportional increase in dressing fibre occupancy as pressure intensifies, leading to a reduction in dressing pore size. The tests underscore the pressure system's diminished efficacy in fluid extraction with increasing fluid viscosity. Our discussion points to the need of establishing standardized guidelines for foam dressing selection based on pore size and the necessity of incorporating real biological exudates into industrial standards.

Global trend and epidemiological profiles of climate-related disasters from 2000 to 2021.

OBJECTIVE: The objective of this study is to analyse the epidemiological profile of global climate-related disasters in terms of morbidity and mortality, as well as to examine their temporal trends. METHOD: This cross-sectional study analysed climate-related global disasters from 2000 to 2021, utilising definitions and criteria from the United Nations Strategy for Disaster Reduction and the Centre for Research on the Epidemiology of Disasters. Data were sourced from the EM-DAT database. The study assessed trends over the entire period and compared them with previous years (1978-2000). RESULTS: A total of 7398 climate-related disasters were recorded, with hydrological disasters being the most frequent, followed by meteorological and climatological disasters. Statistically significant differences were noted in the average rates of affected individuals and injuries per million inhabitants. No significant trends were found in mortality rates, but the frequency trends for the entire period (1978-2021) and the subperiod (1978-2000) were increasing and statistically significant. However, the trend from 2000 onwards showed a non-significant decrease, potentially reflecting better disaster preparedness and response strategies under the Hyogo and Sendai Framework. CONCLUSION: The study highlights hydrological disasters as the most frequent and deadliest climate-related events, with climatological disasters affecting and injuring the most people. The lack of standardised criteria for disaster inclusion in databases presents a significant challenge in comparing results and analysing trends. Establishing uniform inclusion criteria is crucial for effective data analysis and disaster management.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

Preserving the efficacy of antibiotics to tackle antibiotic resistance.

Different international agencies recognize that antibiotic resistance is one of the most severe human health problems that humankind is facing. Traditionally, the introduction of new antibiotics solved this problem but various scientific and economic reasons have led to a shortage of novel antibiotics at the pipeline. This situation makes mandatory the implementation of approaches to preserve the efficacy of current antibiotics. The concept is not novel, but the only action taken for such preservation had been the 'prudent' use of antibiotics, trying to reduce the selection pressure by reducing the amount of antibiotics. However, even if antibiotics are used only when needed, this will be insufficient because resistance is the inescapable outcome of antibiotics' use. A deeper understanding of the alterations in the bacterial physiology upon acquisition of resistance and during infection will help to design improved strategies to treat bacterial infections. In this article, we discuss the interconnection between antibiotic resistance (and antibiotic activity) and bacterial metabolism, particularly in vivo, when bacteria are causing infection. We discuss as well how understanding evolutionary trade-offs, as collateral sensitivity, associated with the acquisition of resistance may help to define evolution-based therapeutic strategies to fight antibiotic resistance and to preserve currently used antibiotics.

Importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, Ucayali, Perú / Cultural importance of the flora used by the Asheninka Sheremashe native community, Ucayali, Peru

The cultural significance of the flora used by the native Asheninka Sheremashe community in Ucayali, Peru was determined. To do this, a fieldwork of over 4 months was conducted, involving semi-structured interviews with 106 residents through non-probabilistic convenience sampling. The community utilizes 139 plant species in their daily lives, belonging to 120 genera and 52 families, with the most abundant being Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae, and Rutaceae. Furthermore, 25.9% of the species are of significant importance to theinhabitants according to the Cultural Index (CI), such as Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, among others. It can be concluded that the flora plays a prominent role in the life of the community, with the categories reporting the highest number of species being: food (29.35%), medicine (28.36%), culture (9.95%), construction (9.45%), lumber (6.97%), commerce (3.48%), craftsmanship (2.49%), toxic (2.49%), and other uses (7.46%)

Se determinó la importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, en Ucayali, Perú. Para ello, se realizó un trabajo de campo de más de 4 meses, donde se aplicaron entrevistas semiestructuradas a 106 habitantes mediante un muestreo no probabilístico por conveniencia. La comunidad emplea 139 especies vegetales en su día a día, pertenecientes a 120 géneros y 52 familias; siendo las más abundantes las Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae y Rutaceae. Además, el 25.9% de las especies tiene gran importancia para los pobladores según el Índice Cultural (IC): Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, entre otras. Se concluye que la flora tiene un rol preponderante en la vida de la comunidad, siendo las categorías que presentaron mayor reporte de especies: alimentación (29.35%), medicina (28.36%), cultura (9.95%), construcción (9.45%), aserrío (6.97%), comercio (3.48%), artesanía (2.49%), tóxico (2.49%) y otros usos (7.46%)

Challenges in prompt identification and surgical correction of Marfan Syndrome aortic disease in a middle-income country: a case series study.

BACKGROUND: Marfan Syndrome is an autosomal dominant disease caused by pathogenetic variants in the FBN1 gene. The progressive dilatation of the aorta and the potential risk of acute aortic syndromes influence the prognosis of these patients. We aim to describe population characteristics, long-term survival, and re-intervention patterns in patients who underwent aortic surgery with a previously confirmed clinical diagnosis of Marfan Syndrome in a middle-income country. METHODS: A retrospective single-center case series study was conducted. All Marfan Syndrome patients who underwent aortic procedures from 2004 until 2021 were included. Qualitative variables were frequency-presented, while quantitative ones adopted mean ± standard deviation. A subgroup analysis between elective and emergent procedures was conducted. Kaplan-Meier plots depicted cumulative survival and re-intervention-free. Control appointments and government data tracked out-of-hospital mortality. RESULTS: Fifty patients were identified. The mean age was 38.79 ± 14.41 years, with a male-to-female ratio of 2:1. Common comorbidities included aortic valve regurgitation (66%) and hypertension (50%). Aortic aneurysms were observed in 64% without dissection and 36% with dissection. Surgical procedures comprised elective (52%) and emergent cases (48%). The most common surgery performed was the David procedure (64%), and the Bentall procedure (14%). The in-hospital mortality rate was 4%. Complications included stroke (10%), and acute kidney injury (6%). The average follow-up was 8.88 ± 5.78 years. Survival rates at 5, 10, and 15 years were 89%, 73%, and 68%, respectively. Reintervention rates at 1, 2.5, and 5 years were 10%, 14%, and 17%, respectively. The emergent subgroup was younger (37.58 ± 14.49 years), had the largest number of Stanford A aortic dissections, presented hemodynamic instability (41.67%), and had a higher requirement of reinterventions in the first 5 years of follow-up (p = 0.030). CONCLUSION: In our study, surveillance programs played a pivotal role in sustaining high survival rates and identifying re-intervention requirements. However, challenges persist, as 48% of the patients required emergent surgery. Despite not affecting survival rates, a greater requirement for reinterventions was observed, emphasizing the necessity of timely diagnosis. Enhanced educational initiatives for healthcare providers and increased patient involvement in follow-up programs are imperative to address these concerns.

Microbiome Modulation in Acne Patients and Clinical Correlations.

BACKGROUND: The imbalance of skin microbiota in acne can induce changes leading to induction or to aggravation of chronic inflammatory lesions; complex mechanisms are involved. Cutibacterium acnes (C. acnes) ribotypes RT4 and RT5 express more biofilm and are associated with inflammatory acne lesions. C. acnes RT6 is a non-acne ribotype, beneficial for the skin. OBJECTIVES: In an open clinical trial, acne adults were included and assessed clinically at baseline and at month 2 using the Investigator Global Assessment of Acne (IGA) score. A topical emulsion was applied twice daily for 2 months (M2) in each included patient. In the same series of acne patients, skin swab samples were collected from acne patients at baseline and M2 from lesional and non-lesional skin; skin swabs were collected for the metagenomic long-read analysis of microbiota. MATERIALS AND METHODS: Acne patients with a gravity score IGA of >1<3 were included in this pilot study. An emulsion of O/W formulated with vegetal extract of Umbelliferae associated with a polysaccharide at 1% was applied twice daily for 2 months. At baseline and M2 clinical assessments were made; skin swab samples were also taken for microbiota analysis from lesional and non-lesional skin in each included patient. Extractions of genomic DNA (gDNA) from swab samples from baseline and from M2 were made, followed by full-length (V1-V9) amplification of the 16S rDNA and sequencing of amplicon libraries for strain-level bacterial community profiling. RESULTS: In a series of 32 adult acne patients, the mean initial IGA scale was 3.1; at M2 the IGA scale was 1.5 (p < 0.001). The mean decrease in acne lesions was by 63%. Microbiome metagenomic long-read analysis in these series was mainly dominated by C. acnes followed by Staphylococcus epidermidis (S. epidermidis). The density of C. acnes ribotypes RT6 (non-acne strain) was increased at M2 compared to baseline and the density of ribotypes C. acnes RT1 to RT5 was decreased at M2, compared to baseline (p < 0.0001). S. epidermidis ribotypes (1 to 36) were non significantly increased at M2, compared to baseline (p < 0.1). CONCLUSIONS: In a series of 32 acne patients that applied an emulsion based on vegetal extract of Umbelliferae and a polysaccharide at 1% twice daily, a significant clinical improvement in IGA scale for acne lesions was seen at M2, compared to baseline (p < 0.0001). The clinical improvement was correlated with an improvement in skin microbiome at M2 compared to baseline, indicated by the increase in the relative abundance of non-acne strain of C. acnes ribotype 6 and of the decrease in the relative abundance of acne strains ribotypes C. acnes RT1 to RT5.

Preliminary profile of the gut microbiota from amerindians in the Brazilian amazon experiencing a process of transition to urbanization.

The Yanomami are one of the oldest indigenous tribes in the Amazon and are direct descendants of the first people to colonize South America 12,000 years ago. They are located on the border between Venezuela and Brazil, with the Venezuelan side remaining uncontacted. While they maintain a hunter-gatherer society, they are currently experiencing contact with urbanized populations in Brazil. The human gut microbiota of traditional communities has become the subject of recent studies due to the Westernization of their diet and the introduction of antibiotics and other chemicals, which have affected microbial diversity in indigenous populations, thereby threatening their existence. In this study, we preliminarily characterized the diversity of the gut microbiota of the Yanomami, a hunter-gatherer society from the Amazon, experiencing contact with urbanized populations. Similarly, we compared their diversity with the population in Manaus, Amazonas. A metabarcoding approach of the 16 S rRNA gene was carried out on fecal samples. Differences were found between the two populations, particularly regarding the abundance of genera (e.g., Prevotella and Bacteroides) and the higher values of the phyla Bacteroidetes over Firmicutes, which were significant only in the Yanomami. Some bacteria were found exclusively in the Yanomami (Treponema and Succinivibrio). However, diversity was statistically equal between them. In conclusion, the composition of the Yanomami gut microbiota still maintains the profile characteristic of a community with a traditional lifestyle. However, our results suggest an underlying Westernization process of the Yanomami microbiota when compared with that of Manaus, which must be carefully monitored by authorities, as the loss of diversity can be a sign of growing danger to the health of the Yanomami.

Comparative Analysis of Shapley Values Enhances Transcriptomics Insights across Some Common Uterine Pathologies.

Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Optimizing Thermoelectric Properties through Compositional Engineering in Ag-Deficient AgSbTe2 Synthesized by Arc Melting.

Thermoelectric materials offer a promising avenue for energy management, directly converting heat into electrical energy. Among them, AgSbTe2 has gained significant attention and continues to be a subject of research at further improving its thermoelectric performance and expanding its practical applications. This study focuses on Ag-deficient Ag0.7Sb1.12Te2 and Ag0.7Sb1.12Te1.95Se0.05 materials, examining the impact of compositional engineering within the AgSbTe2 thermoelectric system. These materials have been rapidly synthesized using an arc-melting technique, resulting in the production of dense nanostructured pellets. Detailed analysis through scanning electron microscopy (SEM) reveals the presence of a layered nanostructure, which significantly influences the thermoelectric properties of these materials. Synchrotron X-ray diffraction reveals significant changes in the lattice parameters and atomic displacement parameters (ADPs) that suggest a weakening of bond order in the structure. The thermoelectric characterization highlights the enhanced power factor of Ag-deficient materials that, combined with the low glass-like thermal conductivity, results in a significant improvement in the figure of merit, achieving zT values of 1.25 in Ag0.7Sb1.12Te2 and 1.01 in Ag0.7Sb1.12Te1.95Se0.05 at 750 K.

Diagnostic accuracy of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil-lymphocyte-to-platelet ratio biomarkers in predicting bacteremia and sepsis in immunosuppressive patients with cancer: literature review.

Background: This literature review explores the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-lymphocyte-to-platelet ratio (NLPR) biomarkers, as potential indicators for predicting bacteremia and sepsis in patients with cancer. Objective: Tracing the evolution of interest in this area since 2001, the aim of this review was to report a comprehensive overview of current knowledge and gaps, particularly in patients undergoing immunosuppression. Summary of Findings: The literature research indicates the potential of NLR, PLR, and other biomarkers in diagnosing and predicting sepsis, with some studies emphasizing their value in mortality prediction. A specific focus on bacteremia shows the effectiveness of NLR and PLR as early indicators and prognostic tools, though mostly in noncancer patient populations. While NLR and PLR are promising in general cancer patient populations, the review addresses the challenges in applying these biomarkers to patients with neutropenic and lymphopenic cancer. The NLPR could be considered a significant biomarker for inflammation and mortality risk in various medical conditions, yet its diagnostic accuracy in patients with immunosuppressed cancer is not extensively validated. Conclusion: This review offers a snapshot of the current research on biomarkers in patients with immunocompromised cancer in the sepsis and bacteremia area. More focused research on their application is necessary. This gap underscores an opportunity for future studies to enhance diagnostic and prognostic capabilities in this high-risk group.

Redox regulation of UPR signalling and mitochondrial ER contact sites.

Mitochondria and the endoplasmic reticulum (ER) have a synergistic relationship and are key regulatory hubs in maintaining cell homeostasis. Communication between these organelles is mediated by mitochondria ER contact sites (MERCS), allowing the exchange of material and information, modulating calcium homeostasis, redox signalling, lipid transfer and the regulation of mitochondrial dynamics. MERCS are dynamic structures that allow cells to respond to changes in the intracellular environment under normal homeostatic conditions, while their assembly/disassembly are affected by pathophysiological conditions such as ageing and disease. Disruption of protein folding in the ER lumen can activate the Unfolded Protein Response (UPR), promoting the remodelling of ER membranes and MERCS formation. The UPR stress receptor kinases PERK and IRE1, are located at or close to MERCS. UPR signalling can be adaptive or maladaptive, depending on whether the disruption in protein folding or ER stress is transient or sustained. Adaptive UPR signalling via MERCS can increase mitochondrial calcium import, metabolism and dynamics, while maladaptive UPR signalling can result in excessive calcium import and activation of apoptotic pathways. Targeting UPR signalling and the assembly of MERCS is an attractive therapeutic approach for a range of age-related conditions such as neurodegeneration and sarcopenia. This review highlights the emerging evidence related to the role of redox mediated UPR activation in orchestrating inter-organelle communication between the ER and mitochondria, and ultimately the determination of cell function and fate.

Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/µm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

Early feeding practices and eating behaviour in preschool children: The CORALS cohort.

This study aimed to investigate if the duration of breastfeeding and the method at initiation of complementary feeding affect eating behaviour in children aged 3-6 years. This is a cross-sectional analysis from the Childhood Obesity Risk Assessment Longitudinal Study project, an ongoing longitudinal cohort study that aims to identify childhood obesity risk factors in Spanish children. A total of 1215 children aged 3-6 years were included. Breastfeeding duration and the method of initiation of complementary feeding [baby-led weaning (BLW), traditional/spoon or mixed method] were evaluated. Eating behaviour at 3-6 years was assessed with the Child Eating Behaviour Questionnaire. Generalized linear models were fitted to assess the association between the aforementioned exposures and eating behaviour. Children breastfed for ≥4 months were less likely to be fussy eaters at 3-6 years compared to those breastfed for <1 month (OR: 0.86 95% CI: 0.76-0.98; p = 0.031). Compared to those children using the traditional/spoon-feeding method, those initiating complementary feeding through BLW or through a mixed approach were more likely to have higher scores on the enjoyment of food (EF) (OR, 95% CI: 1.33, 1.13-1.57; p = 0.001 and 1.17, 1.05-1.30; p = 0.002, respectively) and lower scores on food fussiness (FF) at 3-6 years (0.76, 0.62-0.91; p = 0.004 and 0.87, 0.78-0.98; p = 0.033, respectively). Breastfeeding for ≥4 months and initiation of complementary feeding with the BLW and a mixed approach were associated with greater EF and lower FF, which should endure practice.

Phage display identification of high-affinity ligands for human TSG101-UEV: A structural and thermodynamic study of PTAP recognition.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disrupting TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of novel host-oriented antivirals with a broad spectrum of action. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood. Here we present a detailed thermodynamic, structural, and dynamic characterization viral PTAP Late domain recognition by TSG101-UEV, combining isothermal titration calorimetry, X-ray diffraction structural studies, molecular dynamics simulations, and computational analysis of intramolecular communication pathways. Our analysis highlights key contributions from conserved hydrophobic contacts and water-mediated hydrogen bonds at the PTAP binding interface. We have identified additional electrostatic hotspots adjacent to the core motif that modulate affinity. Using competitive phage display screening we have improved affinity by 1-2 orders of magnitude, producing novel peptides with low micromolar affinities that combine critical elements found in the best natural binders. Molecular dynamics simulations revealed that optimized peptides engage new pockets on the UEV domain surface. This study provides a comprehensive view of the molecular forces directing TSG101-UEV recognition of PTAP motifs, revealing that binding is governed by conserved structural elements yet tuneable through targeted optimization. These insights open new venues to design inhibitors targeting TSG101-dependent pathways with potential application as novel broad-spectrum antivirals.

Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay.

The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' → 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.