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Weaning is a decisive event in piglets' life. This study aimed to evaluate whether the inclusion of fish oil, rich in eicosapentaenoic and docosahexaenoic acids (EPA and DHA), in sow and piglet diets, increased the concentration of anti-inflammatory molecules in the blood of weaned piglets and whether the effect was dependent on the pigs being born with either low or a high birth BW (bBW). Thirty-six sows in four consecutive batches were randomly distributed between a control diet with animal fat (15 g/kg in gestation and 30 g/kg in lactation) or a n-3 long-chain fatty acid diet (LCFA; totally or half replacing animal fat by fish oil during gestation and lactation, respectively) from service until weaning (ca. 28 days). At birth, the two lightest (LBW) and the two heaviest (HBW) piglets in each litter were identified and, at weaning, grouped in pens by pairs prioritising their bBW. Pens were further distributed into a control (30 g/kg animal fat) or n-3 LCFA diet (totally replacing animal fat by fish oil) for 28 days. At the end of the trial, blood was collected from piglets in the first batch (n = 48). Serum fatty acids (FAs) were quantified by GC, plasma oxylipins by ultra-HPLC-MS, and plasma immune indicators by ELISA. An interaction between piglet diet and bBW for average daily gain (P = 0.020) and average daily feed intake (P = 0.014) during the whole postweaning indicated that dietary n-3 LCFA-promoted LBW piglets to have a similar growth and intake than HBW piglets reaching 1.5 kg average BW more at the end of the postweaning period than LBW control piglets. Fish oil in piglet diets also increased the concentrations of total n-3 FA, EPA and DHA (all P < 0.001), their resultant oxylipins, particularly their hydroxy derivatives from lipoxygenase enzymatic pathway (all P < 0.001) and tended to increase immunoglobulin M (P = 0.067) in blood. Regarding the bBW category, LBW piglets tend to increase tumour necrosis factor α in plasma (P = 0.083) compared to HBW. It is concluded that fish oil in postweaning diets could enhance the daily gain and feed intake of LBW piglets, increasing the concentration of serum n-3 FAs and their derived oxylipins in plasma., (Copyright © 2024. Published by Elsevier B.V.)

Many women have sought alternative therapies to address menopause. Recently, a multi-ingredient supplement (MIS) containing L-histidine, L-carnosine, L-serine, and L-cysteine has been shown to be effective at ameliorating hepatic steatosis (HS) in ovariectomized (OVX) rats, a postmenopausal oestrogen deficiency model. Considering that HS frequently accompanies obesity, which often occurs during menopause, we aimed to investigate the effects of this MIS for 8 weeks in OVX rats. Twenty OVX rats were orally supplemented with either MIS (OVX-MIS) or vehicle (OVX). Ten OVX rats received vehicle orally along with subcutaneous injections of 17β-oestradiol (OVX-E2), whereas 10 rats underwent a sham operation and received oral and injected vehicles (control group). MIS consumption partly counteracted the fat mass accretion observed in OVX animals, leading to decreased total fat mass, adiposity index and retroperitoneal white adipose tissue (RWAT) adipocyte hypertrophy. OVX-MIS rats also displayed increased lean mass and lean/fat ratio, suggesting a healthier body composition, similar to the results reported for OVX-E2 animals. MIS consumption decreased the circulating levels of the proinflammatory marker CRP, the total cholesterol-to-HDL-cholesterol ratio and the leptin-to-adiponectin ratio, a biomarker of diabetes risk and metabolic syndrome. RWAT transcriptomics indicated that MIS favourably regulated genes involved in adipocyte structure and morphology, cell fate determination and differentiation, glucose/insulin homeostasis, inflammation, response to stress and oxidative phosphorylation, which may be mechanisms underlying the beneficial effects described for OVX-MIS rats. Our results pave the way for using this MIS formulation to improve the body composition and immunometabolic health of menopausal women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples., Results: The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals., Conclusions: In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA., (© 2024. The Author(s).)

The incorporation of nanoparticles can significantly enhance the properties of polymers. However, the industrial production of nanocomposites presents a technological challenge in achieving the proper dispersion of nanoparticles within the polymer matrix. In this work, a novel device is presented that can be seamlessly integrated with standard twin-screw extruders, enabling the application of ultrasonic vibration to molten polymeric material. The primary objective of this study is to experimentally validate the effectiveness of this technology in improving the dispersion of nanoparticles. To accomplish this, a comparative analysis was carried out between nanocomposites obtained through conventional compounding extrusion and those processed with the assistance of ultrasonic vibrations. The nanocomposites under investigation consist of a polypropylene (PP) matrix reinforced with nano clays (Cloisite 20A) at a target loading ratio of 5% by weight. To comprehensively evaluate the impact of the ultrasound-assisted compounding, various key properties were assessed, such as the melt flow index (MFI) to characterize the flow behavior, mechanical properties to evaluate the structural performance, oxygen barrier properties to assess potential gas permeability, and microstructure analysis using Scanning Electron Microscopy (SEM) for detailed morphology characterization. The results suggested an improvement in nanoparticle dispersion when using the ultrasound device, particularly when the intensity was adjusted to 60%.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.

Mangroves in Southeast Asia provide numerous supporting, provisioning, regulating, and cultural services that are crucial to the environment and local livelihoods since they support biodiversity conservation and climate change resilience. However, Southeast Asia mangroves face deforestation threats from the expansion of commercial aquaculture, agriculture, and urban development, along with climate change-related natural processes. Ecotourism has gained prominence as a financial incentive tool to support mangrove conservation and restoration. Through a systematic literature review approach, we examined the relationships between ecotourism and mangrove conservation in Southeast Asia based on scientific papers published from 2010 to 2022. Most of the studies were reported in Indonesia, Malaysia, Philippines, Thailand, and Vietnam, respectively, which were associated with the highest number of vibrant mangrove ecotourism sites and largest mangrove areas compared to the other countries of Southeast Asia. Mangrove-related ecotourism activities in the above countries mainly include boat tours, bird and wildlife watching, mangrove planting, kayaking, eating seafood, and snorkeling. The economic benefits, such as an increase in income associated with mangrove ecotourism, have stimulated infrastructural development in ecotourism destinations. Local communities benefited from increased access to social amenities such as clean water, electricity, transportation networks, schools, and health services that are intended to make destinations more attractive to tourists. Economic benefits from mangrove ecotourism motivated the implementation of several community-based mangrove conservation and restoration initiatives, which attracted international financial incentives and public-private partnerships. Since mangroves are mostly located on the land occupied by indigenous people and local communities, ensuring respect for their land rights and equity in economic benefit sharing may increase their intrinsic motivation and participation in mangrove restoration and conservation initiatives. Remote sensing tools for mangrove monitoring, evaluation, and reporting, and integrated education and awareness campaigns can ensure the long-term conservation of mangroves while sustaining ecotourism's economic infrastructure and social amenities benefits., Competing Interests: Declaration of competing interest The authors declare that they have no potential real or perceived conflict of interest. Authors Ewane Basil Ewane, Jorge F. Montenegro, Redeat Daneil, Austin Blanton, Freddie McTavish, Luisa Fernanda Valasquez-Camacho, Pavithra S. Pitumpe Arachchige, G.A. Pabodha Galgamuwa, Shalini A.L. King, Shruthi Srinivasan, Meshal M. Abdullah, Wan Shafrina Wan Mohd Jaafar, Tarig Ali, and Midhun Mohan are affiliated with Ecoresolve Inc. Ewane Basil Ewane, Jorge F. Montenegro, and Midhun Mohan were also employed by BlueForests Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

This paper explores the therapeutic perspectives of polyphenols and chitosan as potential anticancer agents in the mouthwash formulations. Taking into account the high incidence of squamous cell carcinoma (SCC) among oral cancers, this discussion will concentrate on the potential advantages of these compounds in oral care, focusing on their impact on improving oral health and cancer prevention. According to the data, it appears that the mixture of BACs extract and chitosan may increase the efficiency of the apoptosis of cancer cells while reducing the undesired side effects. The cytotoxicity assays demonstrate a significant reduction in squamous carcinoma cell viability after incubation with BACs extract, with a marked decrease observed over 24-72 hours up to 76%. The anti-cancer properties of the BAC extract are related to luteolin, which is a predominant compound. The addition of 0.025% chitosan reduced the metabolic activity of cancer cells by 37.5%, suggesting a synergistic interaction between the compounds. This research highlights the potential of BACs and chitosan in modulating important molecular targets associated with cancer cell., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The COVID-19 pandemic has underscored the importance of understanding the role of animals in the transmission of coronaviruses (CoVs) and their impact on human health. A One Health approach, integrating human, animal, and environmental health, is essential for effective CoVs control. Next-generation sequencing has played a pivotal role in identifying and monitoring the evolution of novel CoVs strains, like SARS-CoV-2. However, viral occurrence and diversity studies in environmental and animal samples are challenging because of the complexity of viral communities and low abundance of viruses in these samples. Target enrichment sequencing (TES) has emerged as a valuable tool for investigating viral families in challenging samples. This approach involves the specific capture and enrichment of viral genomes using sequence-specific probes, thereby enhancing the efficiency of detection and characterization. In this study, we aimed to develop and validate a TES panel to study CoVs in various complex environmental and animal derived samples. The results demonstrated the panel's effectiveness in capturing and sequencing a wide diversity of CoVs providing valuable insights into their abundance and host diversity in urban wastewater, farm animal corpses lixiviates and bat guano samples. In sewage samples, CoVs were detected solely when TES was employed while in guano samples, sequencing of CoVs species was achieved in 2 out of 4 samples showing an almost three-logarithmic increase in the number of reads obtained in comparison with the untargeted approach. For animal lixiviates, only the TES application enabled the acquisition of CoVs reads. The information obtained can significantly contribute to early detection, surveillance, and control measures for CoVs, including viral discovery and potential spillover events. Additionally, this sequencing panel shows potential for studying other significant viral families and monitoring viral diversity in different animal populations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Silvia Bofill Mas reports financial support was provided by "La Marató de TV3". Silvia Bofill-Mas reports financial support was provided by Spain 10.13039/501100004837Ministry of Science and Innovation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Biogas serves as a crucial renewable energy vector to ensure a more sustainable energy future. However, the presence of hydrogen sulfide (H 2 S) limits its application in various sectors, emphasizing the importance of effective H 2 S removal techniques for maximizing its potential. In the present study, the limits of a pilot-scale bioscrubber for biogas desulfurization was study in a real scenario. An increase in the superficial liquid velocity resulted in significant improvements in the H 2 S removal efficiency, increasing from 76 ± 8% (elimination capacity of 6.2 ± 0.5 gS-H 2 S m - 3 h -1 ) to 97.7 ± 0.5% (elimination capacity of 8 ± 1 gS-H 2 S m - 3 h -1 ) as the superficial liquid velocity increased from 50 ± 3 m h -1 to 200 ± 8 m h -1 . A U SL of 161.4 ± 0.5 m h -1 was able to achieve outlet H 2 S concentrations as low as 3 ± 1 ppm v (H 2 S removal efficiency of 97 ± 1%) for 7 days. High superficial liquid velocity favoured the aerobic H 2 S oxidation reducing the nitrate demand. The maximum EC reached throughout the operation was 50.8 ± 0.6 gS-H 2 S m - 3 h -1 (H 2 S removal efficiency of 96 ± 1%) and a sulfur production of 60%. Studies in batch flocculation experiments showed sulfur removal rates up to 97.6 ± 0.9% with a cationic flocculant dose of 75 mg L -1 . Microbial analysis revealed that the predominant genus with sulfo-oxidant capacity during periods of low H 2 S inlet load was Thioalkalispira-sulfurivermis (61-69%), while in periods of higher H 2 S inlet load, family Arcobacteraceae was the most prevalent (11%)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Poor nutrition links to chronic diseases, emphasizing the need for optimized diets. The EU-funded project PREVENTOMICS, introduced personalized nutrition to address this. This study aims to perform a health technology assessment (HTA) comparing personalized nutrition interventions developed through this project, with non-personalized nutrition interventions (control) for people with normal weight, overweight, or obesity. The goal is to support decisions about further development and implementation of personalized nutrition., Methods: The PREVENTOMICS interventions were evaluated using the European Network for HTA Core Model, which includes a methodological framework that encompasses different domains for value assessment. Information was gathered via [1] different statistical analyses and modeling studies, [2] questions asked of project partners and, [3] other (un)published materials., Results: Clinical trials of PREVENTOMICS interventions demonstrated different body mass index changes compared to control; differences ranged from -0.80 to 0.20 kg/m 2 . Long-term outcome predictions showed generally improved health outcomes for the interventions; some appeared cost-effective (e.g., interventions in UK). Ethical concerns around health inequality and the lack of specific legal regulations for personalized nutrition interventions were identified. Choice modeling studies indicated openness to personalized nutrition interventions; decisions were primarily affected by intervention's price., Conclusions: PREVENTOMICS clinical trials have shown promising effectiveness with no major safety concerns, although uncertainties about effectiveness exist due to small samples (n=60-264) and short follow-ups (10-16 weeks). Larger, longer trials are needed for robust evidence before implementation could be considered. Among other considerations, developers should explore financing options and collaborate with policymakers to prevent exclusion of specific groups due to information shortages.

Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial-mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes.

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d'Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles-hyperinflammatory, low perfusion, and hypogammaglobulinemic-which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition.

Tropical rainforests of Latin America (LATAM) are one of the world's largest carbon sinks, with substantial future carbon sequestration potential and contributing a major proportion of the global supply of forest carbon credits. LATAM is poised to contribute predominantly towards high-quality forest carbon offset projects designed to reduce emissions from deforestation and forest degradation, halt biodiversity loss, and provide equitable conservation benefits to people. Thus, carbon markets, including compliance carbon markets and voluntary carbon markets continue to expand in LATAM. However, the extent of the growth and status of forest carbon markets, pricing initiatives, stakeholders, amongst others, are yet to be explored and extensively reviewed for the entire LATAM region. Against this backdrop, we reviewed a total of 299 articles, including peer-reviewed and non-scientific gray literature sources, from January 2010 to March 2023. Herein, based on the extensive literature review, we present the results and provide perspectives classified into five categories: (i) the status and recent trends of forest carbon markets (ii) the interested parties and their role in the forest carbon markets, (iii) the measurement, reporting and verification (MRV) approaches and role of remote sensing, (iv) the challenges, and (v) the benefits, opportunities, future directions and recommendations to enhance forest carbon markets in LATAM. Despite the substantial challenges, better governance structures for forest carbon markets can increase the number, quality and integrity of projects and support the carbon sequestration capacity of the rainforests of LATAM. Due to the complex and extensive nature of forest carbon projects in LATAM, emerging technologies like remote sensing can enable scale and reduce technical barriers to MRV, if properly benchmarked. The future directions and recommendations provided are intended to improve upon the existing infrastructure and governance mechanisms, and encourage further participation from the public and private sectors in forest carbon markets in LATAM., Competing Interests: Declaration of competing interest The authors declare that they have no potential real or perceived conflict of interest. Authors Marcela Rondon, Ewane Basil Ewane, Jorge F. Montenegro, Austin Blanton, Judith Pons, and Midhun Mohan, were employed by the company Ecoresolve Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Human viruses released into the environment can be detected and characterized in wastewater. The study of wastewater virome offers a consolidated perspective on the circulation of viruses within a population. Because the occurrence and severity of viral infections can vary across a person's lifetime, studying the virome in wastewater samples contributed by various demographic segments can provide valuable insights into the prevalence of viral infections within these segments. In our study, targeted enrichment sequencing was employed to characterize the human virome in wastewater at a building-level scale. This was accomplished through passive sampling of wastewater in schools, university settings, and nursing homes in two cities in Catalonia. Additionally, sewage from a large urban wastewater treatment plant was analysed to serve as a reference for examining the collective excreted human virome., Results: The virome obtained from influent wastewater treatment plant samples showcased the combined viral presence from individuals of varying ages, with astroviruses and human bocaviruses being the most prevalent, followed by human adenoviruses, polyomaviruses, and papillomaviruses. Significant variations in the viral profiles were observed among the different types of buildings studied. Mamastrovirus 1 was predominant in school samples, salivirus and human polyomaviruses JC and BK in the university settings while nursing homes showed a more balanced distribution of viral families presenting papillomavirus and picornaviruses and, interestingly, some viruses linked to immunosuppression., Conclusions: This study shows the utility of building-level wastewater-based epidemiology as an effective tool for monitoring the presence of viruses circulating within specific age groups. It provides valuable insights for public health monitoring and epidemiological studies., (© 2024. The Author(s).)

Background : Histamine intolerance manifests when there is an imbalance between the production of histamine and the body's capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. Methods : This study delved into the influence of various psychotropic medications on DAO activity through in vitro experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. Results : Notably, the examined drugs-sertraline, pregabalin, paroxetine, alprazolam, and lorazepam-did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in in vitro assays without influencing DAO levels and activity in human enterocytes. Conclusions : These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice.

Background: Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan., Methods: Observational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits., Results: In the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87-88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men., Conclusions: Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans., (© 2023. The Author(s).)

Soil microbial communities are dominated by a relatively small number of taxa that may play outsized roles in ecosystem functioning, yet little is known about their capacities to resist and recover from climate extremes such as drought, or how environmental context mediates those responses. Here, we imposed an in situ experimental drought across 30 diverse UK grassland sites with contrasting management intensities and found that: (1) the majority of dominant bacterial (85%) and fungal (89%) taxa exhibit resistant or opportunistic drought strategies, possibly contributing to their ubiquity and dominance across sites; and (2) intensive grassland management decreases the proportion of drought-sensitive and non-resilient dominant bacteria-likely via alleviation of nutrient limitation and pH-related stress under fertilisation and liming-but has the opposite impact on dominant fungi. Our results suggest a potential mechanism by which intensive management promotes bacteria over fungi under drought with implications for soil functioning., (© 2024. The Author(s).)

In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; 1 H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., Escherichia coli and Akkermansia muciniphila ) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.

Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency., Design: Prospective, observational, single-center study., Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021., Patients: Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included., Interventions: Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients., Measurement: Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L)., Main Results: Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO 2 /F I O 2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients., Conclusion: This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chiscano-Camón, Ruiz-Rodriguez, Plata-Menchaca, Martin, Bajaña, Martin-Rodríguez, Palmada, Ferrer-Costa, Camos, Villena-Ortiz, Ribas, Ruiz-Sanmartin, Pérez-Carrasco and Ferrer.)

Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches., (© 2023. The Author(s).)

The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) generative models driven by the integration of AI and natural language processing technologies, such as OpenAI's chatbot generative pre-trained transformer large language model (LLM), are receiving much public attention and have the potential to transform personalized medicine. Dialysis patients are highly dependent on technology and their treatment generates a challenging large volume of data that has to be analyzed for knowledge extraction. We argue that, by integrating the data acquired from hemodialysis treatments with the powerful conversational capabilities of LLMs, nephrologists could personalize treatments adapted to patients' lifestyles and preferences. We also argue that this new conversational AI integrated with a personalized patient-computer interface will enhance patients' engagement and self-care by providing them with a more personalized experience. However, generative AI models require continuous and accurate updates of data, and expert supervision and must address potential biases and limitations. Dialysis patients can also benefit from other new emerging technologies such as Digital Twins with which patients' care can also be addressed from a personalized medicine perspective. In this paper, we will revise LLMs potential strengths in terms of their contribution to personalized medicine, and, in particular, their potential impact, and limitations in nephrology. Nephrologists' collaboration with AI academia and companies, to develop algorithms and models that are more transparent, understandable, and trustworthy, will be crucial for the next generation of dialysis patients. The combination of technology, patient-specific data, and AI should contribute to create a more personalized and interactive dialysis process, improving patients' quality of life.

Soil contamination constitutes a significant threat to the health of soil ecosystems in terms of complexity, toxicity, and recalcitrance. Among all contaminants, aliphatic petroleum hydrocarbons (APH) are of particular concern due to their abundance and persistence in the environment and the need of remediation technologies to ensure their removal in an environmentally, socially, and economically sustainable way. Soil remediation technologies presently available on the market to tackle soil contamination by petroleum hydrocarbons (PH) include landfilling, physical treatments (e.g., thermal desorption), chemical treatments (e.g., oxidation), and conventional bioremediation. The first two solutions are costly and energy-intensive approaches. Conversely, bioremediation of on-site excavated soil arranged in biopiles is a more sustainable procedure. Biopiles are engineered heaps able to stimulate microbial activity and enhance biodegradation, thus ensuring the removal of organic pollutants. This soil remediation technology is currently the most environmentally friendly solution available on the market, as it is less energy-intensive and has no detrimental impact on biological soil functions. However, its major limitation is its low removal efficiency, especially for l ong -c hain h ydrocarbons (LCH), compared to thermal desorption. Nevertheless, the use of fungi for remediation of environmental contaminants retains the benefits of bioremediation treatments, including low economic, social, and environmental costs, while attaining removal efficiencies similar to thermal desorption. Mycoremediation is a widely studied technology at lab scale, but there are few experiences at pilot scale. Several factors may reduce the overall efficiency of on-site mycoremediation biopiles (mycopiles), and the efficiency detected in the bench scale. These factors include the bioavailability of hydrocarbons, the selection of fungal species and bulking agents and their application rate, the interaction between the inoculated fungi and the indigenous microbiota, soil properties and nutrients, and other environmental factors (e.g., humidity, oxygen, and temperature). The identification of these factors at an early stage of biotreatability experiments would allow the application of this on-site technology to be refined and fine-tuned. This review brings together all mycoremediation work applied to aliphatic petroleum hydrocarbons (APH) and identifies the key factors in making mycoremediation effective. It also includes technological advances that reduce the effect of these factors, such as the structure of mycopiles, the application of surfactants, and the control of environmental factors.

There is increasing attention on developing efficient processes including circular economy principles, and obtaining fuels from wastewater treatment feedstocks is among the most promising. As a wastewater treatment byproduct, sewage sludge is a source of lipids that can be converted to biodiesel in a transesterification process. Economic and environmental analysis have been applied to a 60 m 3 /h sewage sludge plant, exploring 32 process alternatives. Using solvent extraction from wet sewage sludge, the high cost associated with the drying step is skipped. The wet alternatives with low amounts of solvent and acid usage depicted higher performance compared to the dry ones. Incorporating additional extraction stages increases both the financial gains and environmental impacts. As a result, a multicriteria analysis is implemented to ascertain the optimum process based on different priorities. The case with 0.5:1 (v/v) of hexane to biomass ratio, 3-stage extractor, 60 min residence time and pH 4 was the optimum alternative in most criteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Histamine intolerance arises when there is a disparity between the production of histamine and the body's ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice.

Sustainability is one of the biggest values of today and for the future of our society; a responsible usage of material in every sector is fundamental to achieving sustainability goals. Aluminum alloys are some of the most promising materials in terms of strength and weight, but their production implies the emission of a high amount of CO 2 . For that reason, the study and development of aluminum alloys with increasing scrap content play a central role in future applications. In the current study, two sheet-aluminum 6181 alloys with different scrap content were analyzed and compared with a 6181 alloy coming from primary production. The alloys were compared in terms of chemical composition, microstructure, tensile properties, and forming behaviors. The results showed that the alloys coming from secondary productions contained a higher amount of manganese, iron, and copper. The metallurgical and mechanical behaviors were very similar to those of the primary produced alloy. Nevertheless, a drop in formability was shown in the aluminum alloys containing a high scrap amount when stressed in a biaxial condition. The study demonstrated the viability of 6181 alloy production using a high scrap amount, highlighting the main difference with the same alloy coming from primary route production.

Urban forests provide direct and indirect benefits to human well-being that are increasingly captured in residential property values. Remote Sensing (RS) can be used to measure a wide range of forest and vegetation parameters that allows for a more detailed and better understanding of their specific influences on housing prices. Herein, through a systematic literature review approach, we reviewed 89 papers (from 2010 to 2022) from 21 different countries that used RS data to quantify vegetation indices, forest and tree parameters of urban forests and estimated their influence on residential property values. The main aim of this study was to understand and provide insights into how urban forests influence residential property values based on RS studies. Although more studies were conducted in developed (n = 55, 61.7%) than developing countries (n = 34, 38.3%), the results indicated for the most part that increasing tree canopy cover on property and neighborhood level, forest size, type, greenness, and proximity to urban forests increased housing prices. RS studies benefited from spatially explicit repetitive data that offer superior efficiency to quantify vegetation, forest, and tree parameters of urban forests over large areas and longer periods compared to studies that used field inventory data. Through this work, we identify and underscore that urban forest benefits outweigh management costs and have a mostly positive influence on housing prices. Thus, we encourage further discussions about prioritizing reforestation and conservation of urban forests during the urban planning of cities and suburbs, which could support UN Sustainable Development Goals (SDGs) and urban policy reforms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Antiretroviral therapy (ART) induces persistent suppression of HIV-1 replication and gradual recovery of T-cell counts, and consequently, morbidity and mortality from HIV-related illnesses have been significantly reduced. However, in approximately 30% of people living with HIV (PLHIV) on ART, CD4 + T-cell counts fail to normalize despite ART and complete suppression of HIV viral load, resulting in severe immune dysfunction, which may represent an increased risk of clinical progression to AIDS and non-AIDS events as well as increased mortality. These patients are referred to as "immune inadequate responders", "immunodiscordant responders" or "immune nonresponders (INR)". The molecular mechanisms underlying poor CD4 + T-cell recovery are still unclear. In this sense, the use of omics sciences has shed light on possible factors involved in the activity and metabolic dysregulation of immune cells during the failure of CD4 + T-cell recovery in INR. Moreover, identification of key molecules by omics approaches allows for the proposal of potential biomarkers or therapeutic targets to improve CD4 + T-cell recovery and the quality of life of these patients. Hence, this review aimed to summarize the information obtained through different omics concerning the molecular factors and pathways associated with the INR phenotype to better understand the complexity of this immunological status in HIV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Espineira, Flores-Piñas, Chafino, Viladés, Negredo, Fernández-Arroyo, Mallolas, Villar, Moreno, Vidal, Rull and Peraire.)

Objective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning., Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6 -/- ) mice., Results: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6 -/- mice., Conclusions: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans . Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans . For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.

Histamine intolerance occurs when there is an imbalance between histamine production and the capacity for histamine degradation. Diamine oxidase (DAO) is the main enzyme for the catabolism of ingested histamine degradation in the gastrointestinal tract and its deficiency has been linked to allergy-like symptoms. Psychostimulant drugs are commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD), but their interaction with DAO is not well characterized. In this work, we evaluated the effects of psychostimulant drugs (methylphenidate and lisdexamfetamine) on in vitro DAO activity and in the human cell line of enterocytes (Caco-2), evaluating DAO expression (mRNA and protein) and DAO activity. Methylphenidate and lisdexamfetamine did not repress the in vitro DAO activity. In addition, in Caco-2 cells, lisdexamfetamine promoted a strong upregulation of DAO mRNA levels, whereas methylphenidate tended to induce DAO activity. To sum up, methylphenidate and lisdexamfetamine treatments do not reduce DAO activity. These findings could be useful for physicians prescribing these two drugs to ADHD patients affected by DAO deficiency.

Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS. Alterations in memory processing were evaluated in the Y-Maze and Morris Water Maze (MWM) paradigms. Changes in microglia activation and in gut microbiota content were also investigated. Our results demonstrate that LPS modified long-term memory in the MWM and increased microglia activation in the hippocampus and prefrontal cortex. Preventive treatment with ASXSP ameliorated LPS-cognitive alterations and microglia activation in both brain regions. Moreover, ASXSP was able to partially revert LPS-induced gut dysbiosis. Our results demonstrate the neuroprotective benefits of ASX when microencapsulated with spirulina acting through different mechanisms, including antioxidant, anti-inflammatory and, probably, prebiotic actions.

Background: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota., Results: Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage., Conclusions: Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract., (© 2023. The Author(s).)

Background: The pathological mechanisms of SARS-CoV-2 in humans remain unclear and the unpredictability of COVID-19 progression may be attributed to the absence of biomarkers that contribute to the prognosis of this disease. Therefore, the discovery of biomarkers is needed for reliable risk stratification and to identify patients who are more likely to progress to a critical stage., Methods: Aiming to identify new biomarkers we analysed N-glycan traits in plasma from 196 patients with COVID-19. Samples were classified into three groups according to their severity (mild, severe and critical) and obtained at diagnosis (baseline) and at 4 weeks of follow-up (postdiagnosis), to evaluate their behaviour through disease progression. N-glycans were released with PNGase F and labelled with Rapifluor-MS, followed by their analysis by LC-MS/MS. The Simglycan structural identification tool and Glycostore database were employed to predict the structure of glycans., Results: We determined that plasma from SARS-CoV-2-infected patients display different N-glycosylation profiles depending on the disease severity. Specifically, levels of fucosylation and galactosylation decreased with increasing severity and Fuc1Hex5HexNAc5 was identified as the most suitable biomarker to stratify patients at diagnosis and distinguish mild from critical outcomes., Conclusion: In this study we explored the global plasma glycosignature, reflecting the inflammatory state of the organs during the infectious disease. Our findings show the promising potential of glycans as biomarkers of COVID-19 severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paton, Herrero, Peraire, del Pino, Chafino, Martinez-Picado, Gómez-Bertomeu, Rull, Canela and Suárez.)

Mutation research is crucial for detecting and treating SARS-CoV-2 and developing vaccines. Using over 5,300,000 sequences from SARS-CoV-2 genomes and custom Python programs, we analyzed the mutational landscape of SARS-CoV-2. Although almost every nucleotide in the SARS-CoV-2 genome has mutated at some time, the substantial differences in the frequency and regularity of mutations warrant further examination. C>U mutations are the most common. They are found in the largest number of variants, pangolin lineages, and countries, which indicates that they are a driving force behind the evolution of SARS-CoV-2. Not all SARS-CoV-2 genes have mutated in the same way. Fewer non-synonymous single nucleotide variations are found in genes that encode proteins with a critical role in virus replication than in genes with ancillary roles. Some genes, such as spike ( S ) and nucleocapsid ( N ), show more non-synonymous mutations than others. Although the prevalence of mutations in the target regions of COVID-19 diagnostic RT-qPCR tests is generally low, in some cases, such as for some primers that bind to the N gene, it is significant. Therefore, ongoing monitoring of SARS-CoV-2 mutations is crucial. The SARS-CoV-2 Mutation Portal provides access to a database of SARS-CoV-2 mutations.

Computer-assisted diagnosis (CAD) algorithms have shown its usefulness for the identification of pulmonary nodules in chest x-rays, but its capability to diagnose lung cancer (LC) is unknown. A CAD algorithm for the identification of pulmonary nodules was created and used on a retrospective cohort of patients with x-rays performed in 2008 and not examined by a radiologist when obtained. X-rays were sorted according to the probability of pulmonary nodule, read by a radiologist and the evolution for the following three years was assessed. The CAD algorithm sorted 20,303 x-rays and defined four subgroups with 250 images each (percentiles ≥ 98, 66, 33 and 0). Fifty-eight pulmonary nodules were identified in the ≥ 98 percentile (23,2%), while only 64 were found in lower percentiles (8,5%) (p < 0.001). A pulmonary nodule was confirmed by the radiologist in 39 out of 173 patients in the high-probability group who had follow-up information (22.5%), and in 5 of them a LC was diagnosed with a delay of 11 months (12.8%). In one quarter of the chest x-rays considered as high-probability for pulmonary nodule by a CAD algorithm, the finding is confirmed and corresponds to an undiagnosed LC in one tenth of the cases., (© 2023. The Author(s).)

The human gut microbiome plays an important role in health, and its initial development is conditioned by many factors, such as feeding. It has also been claimed that this colonization is guided by bacterial populations, the dynamic virome, and transkingdom interactions between host and microbial cells, partially mediated by epigenetic signaling. In this article, we characterized the bacteriome, virome, and smallRNome and their interaction in the meconium and stool samples from infants. Bacterial and viral DNA and RNA were extracted from the meconium and stool samples of 2- to 4-month-old milk-fed infants. The bacteriome, DNA and RNA virome, and smallRNome were assessed using 16S rRNA V4 sequencing, viral enrichment sequencing, and small RNA sequencing protocols, respectively. Data pathway analysis and integration were performed using the R package mixOmics. Our findings showed that the bacteriome differed among the three groups, while the virome and smallRNome presented significant differences, mainly between the meconium and stool of milk-fed infants. The gut environment is rapidly acquired after birth, and it is highly adaptable due to the interaction of environmental factors. Additionally, transkingdom interactions between viruses and bacteria can influence host and smallRNome profiles. However, virome characterization has several protocol limitations that must be considered.