Impact of Simulated Human Gastrointestinal Digestion on the Functional Properties of Dietary Fibres Obtained from Broccoli Leaves, Grape Stems, Pomegranate and Tomato Peels.

This study aimed to analyse the impact of a simulated human digestion process on the composition and functional properties of dietary fibres derived from pomegranate-peel, tomato-peel, broccoli-stem and grape-stem by-products. For this purpose, a computer-controlled simulated digestion system consisting of three bioreactors (simulating the stomach, small intestine and colon) was utilised. Non-extractable phenols associated with dietary fibre and their influence on antioxidant capacity and antiproliferative activity were investigated throughout the simulated digestive phases. Additionally, the modifications in oligosaccharide composition, the microbiological population and short-chain fatty acids produced within the digestion media were examined. The type and composition of each dietary fibre significantly influenced its functional properties and behaviour during intestinal transit. Notably, the dietary fibre from the pomegranate peel retained its high phenol content throughout colon digestion, potentially enhancing intestinal health due to its strong antioxidant activity. Similarly, the dietary fibre from broccoli stems and pomegranate peel demonstrated anti-proliferative effects in both the small and the large intestines, prompting significant modifications in colonic microbiology. Moreover, these fibre types promoted the growth of bifidobacteria over lactic acid bacteria. Thus, these results suggest that the dietary fibre from pomegranate peel seems to be a promising functional food ingredient for improving human health.

Study on the additional financial burden of breast cancer disease on cancer patients and their families. Financial toxicity in cancer.

Introduction: Breast cancer is among the most frequently diagnosed cancers worldwide, with 2.3 million new cases reported annually. The condition causes a social and economic impact known as financial toxicity of cancer. The study aims to explore the extra expenses borne by patients and their families on being diagnosed with breast cancer. Methodology: An observational, descriptive, cross-sectional study was conducted. The data was collected between November 2021 and March 2022 at the Medical Oncology Service in Complejo Asistencial Universitario de Salamanca, Spain. The variables under investigation were additional economic costs, physical disability (as measured by the Barthel Index), instrumental activities of daily living (as measured by the Lawton-Brody Scale), and caregiver burden (measured using the ZARIT scale). Results: The final sample size was N = 107. The study yielded the following outcomes: the median age was 55 years old and the majority of participants were female, with a proportion of 99.1%. The incidence rates for stage I and II were 31.8 and 35.5%, respectively. The median Barthel score was 100 points, while the Lawton and Brody score were 8 points and the ECOG score was 2 points. The analysis of primary caregiver burden resulted in a median ZARIT score of 15 points. The expenses related solely to the cancer diagnosis totaled 1511.22 euros per year (316.82 euros for pharmaceuticals; 487.85 euros for orthopedic equipment; 140.19 euros for home help; and 566.36 euros for housing adaptation or transfer to a hospital). The average annual income before diagnosis was 19962.62 euros. However, after being diagnosed with breast cancer, there is a significant income decrease of 15.91%, resulting in a reduced average annual income of 16785.98 euros. Additionally, a significant correlation was found between total expenditure and the level of dependency (p = 0.032) and functional status (p = 0.045). Conclusion: These findings indicate that breast cancer patients experience a considerable economic burden, which worsens as their functional status deteriorates. Therefore, we believe policies should be implemented to help control this economic deterioration resulting from a serious health condition.

Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis.

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1-/- mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.

Sex differences in strength, functional capacity and mobility in patients with multiple sclerosis: An exploratory analysis.

BACKGROUND: Physical exercise programs are commonly designed without consideration for sex differences. Nevertheless, disease progression exhibits sex-specific patterns, resulting in different functionality and strength performances. OBJECTIVES: To analyze sex differences in strength, functional capacity, and mobility, and to evaluate sex-dependent differences in leg strength in multiple sclerosis (MS) patients. METHODS: A cross-sectional study was conducted with 35 participants (female: n = 19; Expanded Disability Status Scale (EDSS)= 3.0 ± 1.2, male: n = 16; EDSS= 3.3 ± 1.2). Body composition, maximal voluntary isometric contraction (MVIC), explosive strength (rate of force development, RFD), central activation ratio (CAR), functional capacity, and mobility were assessed. RESULTS: Differences were observed between males and females (p = 0.001) in height, lean body mass and MVIC. No differences were observed in the other variables. Regarding the leg asymmetry, men showed higher values in the stronger leg for both MVIC (p < 0.001, d=large) and RFD, whereas women showed higher values only in RFD. Men with MS demonstrated a greater capacity to produce maximal strength than women with this disease. CONCLUSIONS: The results found suggest that maximum strength differs between men and women in our sample of patients with multiple sclerosis. Furthermore, the weaker leg, regardless of sex, exhibits poorer results in explosive strength compared to the stronger leg. However, maximum strength only shows differences in men and not in women. Therefore, these findings should serve as a basis for rehabilitation professionals when planning training programs for this population.

Genetic polymorphisms of CYP2C19 in ecuadorian population: An interethnic approach.

Introduction: CYP2C19 is a highly polymorphic gene responsible for metabolizing commonly used drugs. CYP2C19*2,*3 (loss of activity alleles) and *17 (increased activity allele) are the principal alleles included in clinical guidelines, however their prevalence varies among different ethnicities. Ecuadorian population is formed by Mestizos, Afrodescendants and Native Americans and frequency of CYP2C19 alleles could be different among them. The objective of this study was to establish the frequency of these variants in the different populations of Ecuador and to compare them with other populations. Materials and methods: DNA from 105 Afrodescendants, 75 Native Americans of the Kichwa ethnicity, and 33 Mestizos Ecuadorians was analyzed by nested-PCR to identify CYP2C19*17 carriers. CYP2C19*2 allele was analyzed in DNA from 78 Afrodescendants, 29 Native Americans of the Kichwa, and 16 Mestizos by TaqMan Allelic Discrimination Assay. CYP2C19*3 was analyzed in 33 Afrodescendants by nested-PCR. Results: The global frequencies of the alternate alleles were 14.22% (CYP2C19*2) and 2.10% (CYP2C19*17). No differences (p > 0.05) were observed among the subgroups. No CYP2C19*3 carrier was identified. CYP2C19*2 frequencies in Ecuador were similar to the ones reported in Europe, Africa and Middle East countries and to some American populations. Low CYP2C19*17 frequencies, like the ones in our population, were also observed in East and South Asia and in Native American groups. Discussion: Absence of differences in the ethnic groups in Ecuador for CYP2C19*2 and *17 could be due to either a bias in sample selection (ethnic group was assed by self-identification) or to a high interethnic admixture in the Ecuadorian population that would had diluted genetic differences. In addition, CYP2C19*2, *3, and *17 alleles frequencies in our study suggest that Ecuadorians ancestry is mostly of Native American origin.

Acidithiobacillia class members originating at sites within the Pacific Ring of Fire and other tectonically active locations and description of the novel genus 'Igneacidithiobacillus'.

Recent studies have expanded the genomic contours of the Acidithiobacillia, highlighting important lacunae in our comprehension of the phylogenetic space occupied by certain lineages of the class. One such lineage is 'Igneacidithiobacillus', a novel genus-level taxon, represented by 'Igneacidithiobacillus copahuensis' VAN18-1T as its type species, along with two other uncultivated metagenome-assembled genomes (MAGs) originating from geothermally active sites across the Pacific Ring of Fire. In this study, we investigate the genetic and genomic diversity, and the distribution patterns of several uncharacterized Acidithiobacillia class strains and sequence clones, which are ascribed to the same 16S rRNA gene sequence clade. By digging deeper into this data and contributing to novel MAGs emerging from environmental studies in tectonically active locations, the description of this novel genus has been consolidated. Using state-of-the-art genomic taxonomy methods, we added to already recognized taxa, an additional four novel Candidate (Ca.) species, including 'Ca. Igneacidithiobacillus chanchocoensis' (mCHCt20-1TS), 'Igneacidithiobacillus siniensis' (S30A2T), 'Ca. Igneacidithiobacillus taupoensis' (TVZ-G3 TS), and 'Ca. Igneacidithiobacillus waiarikiensis' (TVZ-G4 TS). Analysis of published data on the isolation, enrichment, cultivation, and preliminary microbiological characterization of several of these unassigned or misassigned strains, along with the type species of the genus, plus the recoverable environmental data from metagenomic studies, allowed us to identify habitat preferences of these taxa. Commonalities and lineage-specific adaptations of the seven species of the genus were derived from pangenome analysis and comparative genomic metabolic reconstruction. The findings emerging from this study lay the groundwork for further research on the ecology, evolution, and biotechnological potential of the novel genus 'Igneacidithiobacillus'.

Comparison of ddRADseq and EUChip60K SNP genotyping systems for population genetics and genomic selection in Eucalyptus dunnii (Maiden).

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

Characterization of carboxylated cellulose nanofibrils and oligosaccharides from Kraft pulp fibers and their potential elicitor effect on the gene expression of Capsicum annuum.

Biomass-derived oligo- and polysaccharides may act as elicitors, i.e., bioactive molecules that trigger plant immune responses. This is particularly important to increase the resistance of plants to abiotic and biotic stresses. In this study, cellulose nanofibrils (CNF) gels were obtained by TEMPO-mediated oxidation of unbleached and bleached kraft pulps. The molecular structures were characterized with ESI and MALDI MS. Analysis of the fine sequences was achieved by MS and MS/MS of the water-soluble oligosaccharides obtained by acid hydrolysis of the CNF gels. The analysis revealed the presence of two families: one corresponding to homoglucuronic acid sequences and the other composed by alternating glucose and glucuronic acid units. The CNF gels, alone or with the addition of the water-soluble oligosaccharides, were tested on Chili pepper (Capsicum annuum). Based on the characterization of the gene expression with Next Generation Sequencing (NGS) of the C. annuum's total messenger RNA, the differences in growth of the C. annuum seeds correlated well with the downregulation of the pathways regulating photosynthesis. A downregulation of the response to abiotic factors was detected, suggesting that these gels would improve the resistance of the C. annuum plants to abiotic stress due to, e.g., water deprivation and cold temperatures.

Using metabolic networks to predict cross-feeding and competition interactions between microorganisms.

Understanding the interactions between microorganisms and their impact on bacterial behavior at the community level is a key research topic in microbiology. Different methods, relying on experimental or mathematical approaches based on the diverse properties of bacteria, are currently employed to study these interactions. Recently, the use of metabolic networks to understand the interactions between bacterial pairs has increased, highlighting the relevance of this approach in characterizing bacteria. In this study, we leverage the representation of bacteria through their metabolic networks to build a predictive model aimed at reducing the number of experimental assays required for designing bacterial consortia with specific behaviors. Our novel method for predicting cross-feeding or competition interactions between pairs of microorganisms utilizes metabolic network features. Machine learning classifiers are employed to determine the type of interaction from automatically reconstructed metabolic networks. Several algorithms were assessed and selected based on comprehensive testing and careful separation of manually compiled data sets obtained from literature sources. We used different classification algorithms, including K Nearest Neighbors, XGBoost, Support Vector Machine, and Random Forest, tested different parameter values, and implemented several data curation approaches to reduce the biological bias associated with our data set, ultimately achieving an accuracy of over 0.9. Our method holds substantial potential to advance the understanding of community behavior and contribute to the development of more effective approaches for consortia design.IMPORTANCEUnderstanding bacterial interactions at the community level is critical for microbiology, and leveraging metabolic networks presents an efficient and effective approach. The introduction of this novel method for predicting interactions through machine learning classifiers has the potential to advance the field by reducing the number of experimental assays required and contributing to the development of more effective bacterial consortia.

Study protocol for a randomized controlled trial: Effect of an everyday cognition training program on cognitive function, emotional state, frailty and functioning in older adults without cognitive impairment.

BACKGROUND: Ageing entails changes in complex cognitive functions that lead to a decrease in autonomy and quality of life. Everyday cognition is the ability to solve cognitively complex problems in the everyday world, enabling instrumental activities of life. Benefits have been found in studies using everyday cognition-based assessment and intervention, as the results predict improvements in everyday performance, not just in specific cognitive functions. A study protocol is presented based on assessment and training in everyday cognition versus traditional cognitive stimulation for the improvement of functionality, emotional state, frailty and cognitive function. METHODS: A parallel randomised controlled clinical trial with two arms will be conducted. It will be carried out by the University of Salamanca (Spain) in eleven centres and associations for the elderly of the City Council of Salamanca. People aged 60 years or older without cognitive impairment will be recruited. Participants will be randomly distributed into two groups: the experimental group will undergo a training programme in everyday cognition and the control group a programme of traditional cognitive stimulation, completing 25 sessions over 7 months. All participants will be assessed at the beginning and at the end of the intervention, where socio-demographic data and the following scales will be collected: The Medical Outcomes Study (MOS), Questionnaire ARMS-e, Everyday Cognition Test (PECC), Scale Yesavage, Test Montreal Cognitive Assessment (MoCA), The Functional Independence Measure (FIM), Fragility Index and Lawton y Brody Scale. DISCUSSION: The present study aims to improve conventional clinical practice on cognitive function training by proposing a specific assessment and intervention of everyday cognition based on the importance of actual cognitive functioning during the resolution of complex tasks of daily life, giving priority to the improvement of autonomy. TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT05688163. Registered on: January 18, 2023.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 (C4) gene. We found that overexpression of mouse C4 (mC4) in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex. Using a computational network, we demonstrated that these microcircuit deficits led to hyperactivity and disrupted neural communication. Finally, pan-neuronal overexpression of mC4 failed to evoke the same deficits in behavior as PV-specific mC4 overexpression, suggesting that C4 perturbations in fast-spiking neurons are more harmful to brain function than pan-neuronal alterations. Together, these results provide a causative link between C4 and the vulnerability of PV cells in brain disease.

Correction: Vicencio et al. Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis. Int. J. Mol. Sci. 2023, 24, 14835.

In the original publication [...].

Hardware Implementations of a Deep Learning Approach to Optimal Configuration of Reconfigurable Intelligence Surfaces.

Reconfigurable intelligent surfaces (RIS) offer the potential to customize the radio propagation environment for wireless networks, and will be a key element for 6G communications. However, due to the unique constraints in these systems, the optimization problems associated to RIS configuration are challenging to solve. This paper illustrates a new approach to the RIS configuration problem, based on the use of artificial intelligence (AI) and deep learning (DL) algorithms. Concretely, a custom convolutional neural network (CNN) intended for edge computing is presented, and implementations on different representative edge devices are compared, including the use of commercial AI-oriented devices and a field-programmable gate array (FPGA) platform. This FPGA option provides the best performance, with ×20 performance increase over the closest FP32, GPU-accelerated option, and almost ×3 performance advantage when compared with the INT8-quantized, TPU-accelerated implementation. More noticeably, this is achieved even when high-level synthesis (HLS) tools are used and no custom accelerators are developed. At the same time, the inherent reconfigurability of FPGAs opens a new field for their use as enabler hardware in RIS applications.

Effectiveness of Different Neurocognitive Intervention Approaches on Functionality in Healthy Older Adults: A Systematic Review.

Subtle loss of functionality in healthy older adults is considered one of the most important predictors of cognitive decline. Neurocognitive interventions are increasingly being used, from a preventive maintenance approach to functional capacity. This study evaluates the effectiveness of different neurocognitive approaches on the functionality of healthy older adults. In this systematic review (CRD42023473944), an extensive search was conducted for articles published in the last 10 years (2013-2023) in the following databases: Medline, Scopus, and Web of Science. A total of 809 trials were identified, of which 18 were considered to be eligible for inclusion in the review. The data revealed heterogeneity in sample size, measures of functional assessment, neurocognitive interventions used, number of sessions, session duration, and time. Traditional cognitive stimulation is shown to have no significant functional benefit, while other less commonly used neurocognitive interventions, such as those based on everyday cognition, are associated with more significant benefits. Moreover, it is demonstrated that although the Instrumental Activities of Daily Living scale (IADL) is the most used test in similar studies, it is not sensitive enough to detect changes in functionality in healthy elderly individuals, with other tests such as the Timed Instrumental Activities of Daily Living (TIADL) being more advantageous. Therefore, a new guideline is proposed for its use in clinical practice and research, using homogeneous study protocols and neurocognitive interventions that allow for the transfer and generalization of results in daily life.

Daily Consumption of Golden Berry (Physalis peruviana) Has Been Shown to Halt the Progression of Insulin Resistance and Obesity in Obese Rats with Metabolic Syndrome.

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.

Analysis of selective screening for congenital cytomegalovirus in a secondary hospital: Problems and solutions.

Universal hearing screening offers unique possibilities for detection of congenital deafness as a consequence of congenital cytomegalovirus (CMVc) infection, so its selective study in the case of a failed test could be a non-negligible screening opportunity while other guidelines covering the possibility of universal screening are adopted. The aim of this study is to analyse the possibility of selective screening for CMVc after an altered hearing test in a regional hospital. During the period studied, the results obtained were unsatisfactory, especially in children born outside the hospital of residence, showing an excessive delay in hearing screening in many cases and in the few cases where CMVc screening could be performed, only 30% had the test ordered in a timely manner. The reasons for this are varied and the solution is to include selective screening for CMVc in the hearing screening programme. This implies shortening the timing of the hearing screening protocol to allow CMVc testing in saliva or urine (preferably) before 21 days of age and providing screening programmes with the necessary staff and time to perform it properly.

Microbial interactions and the homeostasis of the gut microbiome: the role of Bifidobacterium.

The human gut is home to trillions of microorganisms that influence several aspects of our health. This dense microbial community targets almost all dietary polysaccharides and releases multiple metabolites, some of which have physiological effects on the host. A healthy equilibrium between members of the gut microbiota, its microbial diversity, and their metabolites is required for intestinal health, promoting regulatory or anti-inflammatory immune responses. In contrast, the loss of this equilibrium due to antibiotics, low fiber intake, or other conditions results in alterations in gut microbiota composition, a term known as gut dysbiosis. This dysbiosis can be characterized by a reduction in health-associated microorganisms, such as butyrate-producing bacteria, enrichment of a small number of opportunistic pathogens, or a reduction in microbial diversity. Bifidobacterium species are key species in the gut microbiome, serving as primary degraders and contributing to a balanced gut environment in various ways. Colonization resistance is a fundamental property of gut microbiota for the prevention and control of infections. This community competes strongly with foreign microorganisms, such as gastrointestinal pathogens, antibiotic-resistant bacteria, or even probiotics. Resistance to colonization is based on microbial interactions such as metabolic cross-feeding, competition for nutrients, or antimicrobial-based inhibition. These interactions are mediated by metabolites and metabolic pathways, representing the inner workings of the gut microbiota, and play a protective role through colonization resistance. This review presents a rationale for how microbial interactions provide resistance to colonization and gut dysbiosis, highlighting the protective role of Bifidobacterium species.

Prospective evaluation of acute cerebral injury by DW-MRI following transcarotid artery revascularization using a double-layer micromesh stent.

BACKGROUND: Transcervical carotid artery revascularization (TCAR) has demonstrated a low overall stroke rate in carotid artery stenting (CAS). Furthermore, the use of a double-layer micromesh stent is expected to reduce embolization and plaque prolapse. The combination of TCAR and the double layer stent may lead to improved results compared to previously reported outcomes. The objective of this study is to present the findings of a prospective study including patients treated with the Roadsaver stent and TCAR. METHODS: Between January 2017 and May 2022, 85 patients were enrolled. Every patient underwent TCAR with the Roadsaver stent. As per our protocol, a neurological examination and an ultrasound were performed within 24 hours before and after the procedure, and again 30 days after. A diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted 24 hours before the procedure and 48-72 hours after the procedure. The primary endpoint was the detection of new ischemic lesions on postoperative DW-MRI. The secondary endpoint was a composite of all strokes, death, and myocardial infarction within 30 days. RESULTS: Sixty-four patients (75.29%) were symptomatic, out of which 25 were treated within 14 days of the onset of the symptoms. Pre and postprocedural DW-MRI were performed in 83 patients. Postprocedural lesions were found in nine patients (10.84%). There were no strokes or death within 30 days, but two patients experienced a myocardial infarction. CONCLUSIONS: Our study suggests that the use of TCAR and the Roadsaver stent could be a safe alternative to carotid endarterectomy because it entails a low incidence of cerebral embolization, even in recently symptomatic and elderly patients.

Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. The mitochondrial complex I inhibitor metformin reverses O-EV-induced cell proliferation. Several miRNAs-miR-155-5p, miR-10a-3p, and miR-30a-3p-which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing metabolic reprogramming of breast cancer cells.

Novel mediator in anaphylaxis: decreased levels of miR-375-3p in serum and within extracellular vesicles of patients.

Introduction: Anaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers. Methods: Acute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP. Results: A total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p<.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels. Discussion: These findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.