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.

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.

[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.

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%)

Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteremic urinary tract infections: a post-hoc analysis of a multicenter prospective cohort in Spain.

INTRODUCTION: The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI). METHODS: This is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. RESULTS: 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay. CONCLUSIONS: MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.

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.

Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female mice.

BACKGROUND: In order to prevent the emergence and spread of future variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable of stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) and thus induce protective immunity in the upper respiratory tract. The vaccine is based on Newcastle disease virus (NDV) expressing a stabilised SARS-CoV-2 spike protein. NDV-HXP-S can be produced as influenza virus vaccine at low cost in embryonated chicken eggs. METHODS: The NDV-HXP-S vaccine was genetically engineered to match the Omicron variants of concern (VOC) BA.1 and BA.5 and tested as an IN two or three dose vaccination regimen in female mice. Furthermore, female mice intramuscularly (IM) vaccinated with mRNA-lipid nanoparticles (LNPs) were IN boosted with NDV-HXP-S. Systemic humoral immunity, memory T cell responses in the lungs and spleens as well as immunoglobulin A (IgA) responses in distinct mucosal tissues were characterised. FINDINGS: NDV-HXP-S Omicron variant vaccines elicited high mucosal IgA and serum IgG titers against respective SARS-CoV-2 VOC in female mice following IN administration and protected against challenge from matched variants. Additionally, antigen-specific memory B cells and local T cell responses in the lungs were induced. Host immunity against the NDV vector did not interfere with boosting. Intramuscular vaccination with mRNA-LNPs was enhanced by IN NDV-HXP-S boosting resulting in improvement of serum neutralization titers and induction of mucosal immunity. INTERPRETATION: We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission. FUNDING: This work was partially funded by the NIAIDCenters of Excellence for Influenza Research and Response (CEIRR) and by the NIAID Collaborative Vaccine Innovation Centers and by institutional funding from the Icahn School of Medicine at Mount Sinai. See under Acknowledgements for details.

Unveiling the Structural Properties, Optical Behavior, and Thermoelectric Performance of 2D CsSn2Br5 Halide Obtained by Mechanochemistry.

Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSn2Br5 specimens have been synthesized via ball milling. Differential scanning calorimetry curves show melting at 553 K (endothermic) and recrystallization at 516 K (exothermic). Structural analysis using synchrotron X-ray diffraction data, collected from 100 to 373 K, allows for the determination of Debye model parameters. This analysis provides insights into the relative Cs-Br and Sn-Br chemical bonds within the tetragonal structure (space group: I4/mcm), which remains stable throughout the temperature range studied. Combined with neutron data, X-N techniques permit the identification of the Sn2+ lone electron pair (5s2) in the two-dimensional framework, occupying empty space opposite to the four Sn-Br bonds of the pyramidal [SnBr4] coordination polyhedra. Additionally, diffuse reflectance UV-vis spectroscopy unveils an indirect optical gap of approximately ∼3.3 eV, aligning with the calculated value from the B3LYP-DFT method (∼3.2 eV). The material exhibits a positive Seebeck coefficient as high as 6.5 × 104 µV K-1 at 350 K, which evolves down to negative values of -3.0 × 103 µV K-1 at 550 K, surpassing values reported for other halide perovskites. Notably, the thermal conductivity remains exceptionally low, between 0.32 and 0.25 W m-1 K-1.

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.

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification.

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

Correction: Chaparro et al. Whey as an Alternative Nutrient Medium for Growth of Sporosarcina pasteurii and Its Effect on CaCO3 Polymorphism and Fly Ash Bioconsolidation. Materials 2021, 14, 2470.

The Editorial Office was made aware of an error in Figure S1 within the original publication [...].

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.

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.

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.

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.

Improved efficiency of ion trapping time-of-flight mass spectrometry for the analysis of pesticide residues and mycotoxins at trace levels in baby food.

The analysis of pesticide residues and mycotoxins in baby food demands exceptionally low limits of quantitation, necessitating the use of highly sensitive instruments capable of conducting trace analyses. High-resolution instruments typically fail to detect such low levels. However, the latest advancements in liquid time-of-flight technology, when coupled with ion trapping, enable ion enrichment, thereby improving detection levels. This allows for the analysis of these substances at low concentration levels, benefiting from enhanced mass accuracy. Additionally, the use of mass accuracy data helped eliminate matrix interferences, thereby enabling high-confidence identification. We developed a multi-residue method to analyse 219 pesticide residues and 9 mycotoxin residues in baby food matrices. Utilizing a QuEChERS-based extraction method, the samples were then analysed using an LC-Zeno® trap QTOF with mass window screening acquisition. For pesticides, the limit of quantitation was 0.001-0.003 mg/kg for 81 % of the evaluated compounds, 0.005 mg/kg for 13 %, 0.010 mg/kg for 4 % and 0.020-0.030 for 2 %; good linearities were obtained at these levels. Apparent recoveries were evaluated at 0.003, 0.005, and 0.010 mg/kg. At the lowest recovery level, 93 % of compounds showed recoveries between 70 and 120 %. The rest of the compounds were in the range of 63-129 %, with relative standard deviation values below 20 %. For mycotoxins, the limits of quantitation ranged from 0.0001 to 0.100 mg/kg, with matrix-matched concentrations assessed within this range. Recoveries were evaluated at low concentration range (0.001-0.003 mg/kg) and high range (0.020-0.050) with apparent recoveries values between 92 and 140 %. Finally, a total of 31 commercial baby food samples were analysed using this method. The results indicated that 16 samples contained pesticide residues, while two samples were found to have mycotoxins.

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.

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.