The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence.

JOURNAL/nrgr/04.03/01300535-202504000-00030/figure1/v/2024-07-06T104127Z/r/image-tiff Our previous studies have reported that activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been shown to restore the neuroinflammatory response, along with myelin and synaptic structural alterations in the prefrontal cortex, and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice. Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles, the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue, which inhibited the activation of the NLRP3 inflammasome, was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking. We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes (e.g., pyrin domain-containing 1, caspase recruitment domain-containing 4, and absent in melanoma 2, as well as the alterations in inflammatory genes (interleukin-1ß, interleukin-18, inducible nitric oxide synthase, nuclear factor-kappa B, monocyte chemoattractant protein-1, and C-X3-C motif chemokine ligand 1) and miRNAs (miR-21a-5p, miR-146a-5p, and miR-141-5p) induced by binge-like ethanol treatment in adolescent mice. Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways. Taken together, these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Hyperangulated versus Macintosh blades for intubation with videolaryngoscopy in ICU: the randomised multicentre INVIBLADE-ICU trial study protocol.

INTRODUCTION: Compared with the operating room, tracheal intubations in the intensive care unit (ICU) are associated with worsened glottic view, decreased first-time success rate and increase in the technical difficulty of intubation and incidence of complications. Videolaryngoscopes (VLs) have been proposed to improve airway management, and while recent studies have confirmed that VLs improve intubation conditions in this patient population, there remains a lack of clarity regarding the selection between a standard Macintosh blade or a hyperangulated one, to determine which yields the best outcomes. The purpose of this study was to compare successful intubation on the first attempt with the Macintosh VL versus the hyperangulated VL during tracheal intubation in ICU patients. We hypothesise that tracheal intubation using the hyperangulated VL will improve the frequency of successful intubation on the first attempt. METHODS AND ANALYSIS: The INtubation VIdeolaryngoscopy BLADE-ICU trial is a prospective, multicentre, open-label, interventional, randomised, controlled superiority study conducted in 29 ICUs in Spain. Patients will be randomly assigned in a 1:1 ratio to undergo intubation using a Macintosh VL (control group) or a hyperangulated VL (experimental group) for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcomes include the time to intubation, attempts for successful intubation, laryngoscopic vision assessed with the modified Cormack-Lehane scale, the need for adjuvant airway devices for intubation, difficulty assessed by the anaesthesiologist and complications during tracheal intubation. Enrolment began on 1 May 2024 and is expected to be completed in 2025. ETHICS AND DISSEMINATION: The study protocol was approved on 29 February 2024, by the Ethics Committee of Galicia (CEImG, code No. 2024-031).The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06322719.

Zoonotic potential of urban wildlife faeces, assessed through metabarcoding.

Monitoring zoonoses in urban environments is of great relevance, where the incidence of certain pathogens may be higher and where population density makes the spread of any contagious disease more likely. In this study we applied a metabarcoding approach to study potentially zoonotic pathogens in faecal samples of 9 urban vertebrate species. We applied this methodology with two objectives. Firstly, to obtain information on potential pathogens present in the urban fauna of a large European city (Madrid, Spain) and to determine which are their main reservoirs. In addition, we tested for differences in the prevalence of these potential pathogens between urban and rural European rabbits, used as ubiquitous species. Additionally, based on the results obtained, we evaluated the effectiveness of metabarcoding as a tool for monitoring potential pathogen. Our results revealed the presence of potentially zoonotic bacterial genera in all studied host species, 10 of these genera with zoonotic species of mandatory monitoring in the European Union. Based on these results, urban birds (especially house sparrows and pigeons) and bats are the species posing the greatest potential risk, with Campylobacter and Listeria genera in birds and of Chlamydia and Vibrio cholerae in bats as most relevant pathogens. This information highlights the risk associated with fresh faeces from urban wildlife. In addition, we detected Campylobacter in >50 % of the urban rabbit samples, while we only detected it in 11 % of the rural rabbit samples. We found that urban rabbits have a higher prevalence of some pathogens relative to rural rabbits, which could indicate increased risk of pathogen transmission to humans. Finally, our results showed that metabarcoding can be an useful tool to quickly obtain a first screening of potentially zoonotic organisms, necessary information to target the monitoring efforts on the most relevant pathogens and host species.

Caught in the crossfire: biodiversity conservation paradox of sociopolitical conflict.

The current state of global biodiversity is confronted with escalating threats arising from human-induced environmental changes and a growing array of unpredictable challenges. However, effective conservation efforts are often hindered by limited knowledge, especially in developing economies such as the Philippines. The limitations imposed by these shortfalls in biodiversity knowledge hamper the capacity to protect biodiversity in light of the continuing extinction crisis. Our study revealed that areas with higher conflict levels exhibited lower species richness, fewer occurrence records, and reduced forest cover. This finding provides initial evidence for the relationship between sociopolitical conflict and biodiversity in the Philippines. We posit that the security risks caused by sociopolitical conflicts could have a negative impact on conservation efforts, particularly in terms of monitoring and implementing measures to protect natural resources. The links that bind armed conflict and biodiversity conservation are multifaceted and complex issues that warrant greater scientific and political attention. Finally, we identified 10 meaningful approaches to address shortfalls in biodiversity knowledge in conflicted areas, particularly incorporating conflict-sensitive approaches, considering the geopolitical context and conflict dynamics to adapt and align their strategies with local realities for more effective conservation efforts.

"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

EGFR-mutated lung cancer as a secondary neoplasm in a patient with Li-Fraumeni syndrome: case report.

Background: Li-Fraumeni syndrome (LFS) is a rare hereditary disorder caused by mutations in the tumor protein p53 (TP53). It causes a predisposition for the development of multiple malignancies, primarily including breast cancers, sarcomas, and central nervous system tumors. There are a few cases reported in the literature of patients with LFS presenting with an epidermal growth factor receptor (EGFR) mutated lung cancer. Still, it has been suggested that there may be an association between the TP53 pathogenic variant and lung cancer with EGFR mutation in somatic cells. Case Description: A 47-year-old non-smoker woman with LFS with a history of multiple tumors, including bilateral breast cancer, pecoma, and sarcoma. In one of her computed tomography, a lesion in the lingula of the lung was detected. It was biopsied, which diagnosed lung adenocarcinoma, and genetic studies detected an EGFR exon 19 deletion. She was treated with a left inferior lobectomy, followed by pemetrexed and cisplatin. Conclusions: The association between TP53 and lung cancer with EGFR mutation has been suggested in case reports. Studies in lung cancer cell lines have shown a link between TP53 mutation and EGFR overexpression. Nonetheless, as more cases are reported, further research is needed to comprehend the interrelation between these two pathologies and the risk posed by LFS to the emergence of EGFR-mutated lung cancer.

Comparative profiling of whole-cell and exosome samples reveals protein signatures that stratify breast cancer subtypes.

Identifying novel breast cancer biomarkers will improve patient stratification, enhance therapeutic outcomes, and help develop non-invasive diagnostics. We compared the proteomic profiles of whole-cell and exosomal samples of representative breast cancer cell subtypes to evaluate the potential of extracellular vesicles as non-invasive disease biomarkers in liquid biopsies. Overall, differentially-expressed proteins in whole-cell and exosome samples (which included markers for invasion, metastasis, angiogenesis, and drug resistance) effectively discriminated subtypes; furthermore, our results confirmed that the proteomic profile of exosomes reflects breast cancer cell-of-origin, which underscores their potential as disease biomarkers. Our study will contribute to identifying biomarkers that support breast cancer patient stratification and developing novel therapeutic strategies. We include an open, interactive web tool to explore the data as a molecular resource that can explain the role of these protein signatures in breast cancer classification.

MetaFun: unveiling sex-based differences in multiple transcriptomic studies through comprehensive functional meta-analysis.

BACKGROUND: While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack sufficient tools and methods that allow for an in-depth analysis of sex as a variable in biomedical research. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. DESCRIPTION: MetaFun is a complete suite that allows the analysis of transcriptomics data and the exploration of the results at all levels, performing single-dataset exploratory analysis, differential gene expression, gene set functional enrichment, and finally, combining results in a functional meta-analysis. Which biological processes, molecular functions or cellular components are altered in a common pattern in different transcriptomic studies when comparing male and female patients? This and other biological questions of interest can be answered with the use of MetaFun. This tool is available at https://bioinfo.cipf.es/metafun while additional help can be found at https://gitlab.com/ubb-cipf/metafunweb/-/wikis/Summary . CONCLUSIONS: Overall, Metafun is the first open-access web-based tool to identify consensus biological functions across multiple transcriptomic datasets, helping to elucidate sex differences in numerous diseases. Its use will facilitate the generation of novel biological knowledge that can be used in the research and application of Personalized Medicine considering the sex of patients.

Effectiveness of psychological interventions to decrease cognitive fusion in patients with chronic pain: A systematic review and meta-analysis.

OBJECTIVE: While there is sufficient evidence of Acceptance and Commitment Therapy's effectiveness in allowing patients to deal with chronic pain, the effectiveness in cognitive fusion, one of the six core components of the Psychology Flexibility Model, has yet to be established. The aim of this article is to assess whether psychological interventions decrease cognitive fusion. METHODS: The Web of Science, SCOPUS, Medline, and PsycINFO databases were searched for primary studies up to June 2024. Studies with a cognitive fusion measure in which chronic pain patients received a psychological intervention were included. A methodological quality scale was applied to the selected studies and the average effect sizes (Hedges g) were calculated. RESULTS: This review included 18 articles with 24 studies (19 pre-post/follow-up studies and five randomized control trials). Cognitive fusion decreased significantly after the intervention. The effect sizes were small/medium at post-test, g = -0.39, p < .001, 95% CI [-0.52, -0.26]; and medium at long-term follow-up, g = -0.55, p < .001, 95% CI [-0.74, -0.36]. A similar tendency was found for studies with RCTs at post-test, g = -0.61, p = .006, 95% CI [-1.05, -0.17], short-term follow-up, g = -0.79, p < .001, 95% CI [-1.18, -0.40] and long-term follow-up, g = -0.58, p = .003, 95% CI [-0.95, -0.20]). Moderator variables such as unemployment, gender, pain intensity, level of depression before the intervention, and duration and intervention modality were identified. CONCLUSION: Psychological interventions tended to decrease cognitive fusion in chronic pain patients. Nonetheless, more clinical trials are needed to establish the role of cognitive fusion in psychological flexibility.

18F-FDG positron emission tomography as a marker of disease activity and treatment response in ankylosing spondylitis and psoriatic arthritis.

The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (ßΔgSUVmax > 8.5, p < 0.001). We found no significant association between pre-treatment 18F-FDG uptake and subsequent clinical response. 18F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients.

Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS).

PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer's disease.

BACKGROUND: Age represents a significant risk factor for the development of Alzheimer's disease (AD); however, recent research has documented an influencing role of sex in several features of AD. Understanding the impact of sex on specific molecular mechanisms associated with AD remains a critical challenge to creating tailored therapeutic interventions. METHODS: The exploration of the sex-based differential impact on disease (SDID) in AD used a systematic review to first select transcriptomic studies of AD with data regarding sex in the period covering 2002 to 2021 with a focus on the primary brain regions affected by AD - the cortex (CT) and the hippocampus (HP). A differential expression analysis for each study and two tissue-specific meta-analyses were then performed. Focusing on the CT due to the presence of significant SDID-related alterations, a comprehensive functional characterization was conducted: protein-protein network interaction and over-representation analyses to explore biological processes and pathways and a VIPER analysis to estimate transcription factor activity. RESULTS: We selected 8 CT and 5 HP studies from the Gene Expression Omnibus (GEO) repository for tissue-specific meta-analyses. We detected 389 significantly altered genes in the SDID comparison in the CT. Generally, female AD patients displayed more affected genes than males; we grouped said genes into six subsets according to their expression profile in female and male AD patients. Only subset I (repressed genes in female AD patients) displayed significant results during functional profiling. Female AD patients demonstrated more significant impairments in biological processes related to the regulation and organization of synapsis and pathways linked to neurotransmitters (glutamate and GABA) and protein folding, Aß aggregation, and accumulation compared to male AD patients. These findings could partly explain why we observe more pronounced cognitive decline in female AD patients. Finally, we detected 23 transcription factors with different activation patterns according to sex, with some associated with AD for the first time. All results generated during this study are readily available through an open web resource Metafun-AD (https://bioinfo.cipf.es/metafun-ad/). CONCLUSION: Our meta-analyses indicate the existence of differences in AD-related mechanisms in female and male patients. These sex-based differences will represent the basis for new hypotheses and could significantly impact precision medicine and improve diagnosis and clinical outcomes in AD patients.

The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions. METHODS: We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. RESULTS: We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. CONCLUSIONS: Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.

Schizophrenia is a serious illness characterised by changes in perception, mood and behaviour that profoundly affect patients and society. The frequency, symptoms and progression of schizophrenia are different in women and men, but the biological reason for this is not understood. The identification of disease mechanisms specific in men and women, is relevant because it would allow a better understanding of this pathology, as well as improving the personalisation of diagnoses and treatments for patients. To achieve this goal, in this work we reviewed all available RNA sequencing studies of post-mortem brain samples from women and men affected by schizophrenia. Then, we compared gene expression in each study by sex, and integrated all study results in different brain regions: prefrontal cortex, hippocampus and all-studies. We discovered significant changes between men and women: 265 genes differentially expressed in the prefrontal cortex, 1414 genes in the hippocampus and 66 genes in meta-analyses of all-studies. The study of these genes revealed increased immune response functions in the prefrontal cortex of men and in the hippocampus of women with schizophrenia, as well as increased neurotransmission and synapses in the prefrontal cortex of women with schizophrenia. Our results report multiple gene expression changes in specific brain regions of patients with schizophrenia, providing new insights into the role of sex in schizophrenia.

Profile of plasma microRNAs as a potential biomarker of Wilson's disease.

BACKGROUND: Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. METHODS: We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b-/- mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. RESULTS: In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b-/- mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. CONCLUSIONS: The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.

A 6-month educational program improves sleep behaviour in community-dwelling frail older adults: A randomised controlled trial.

BACKGROUND: The prevalence of sleep-related issues among older adults is a significant concern, with half of the older population reporting these problems. Consequently, strategies to improve sleep are needed for this population. This study aims to assess the effects of a health educational program on sleep behaviour among pre-frail or frail older adults residing in the community and to explore possible associations with frailty. METHODS: This randomised controlled trial (NCT05610605) included a total of 197 community-dwelling older adults with frailty/pre-frailty, divided into control (n = 88) and educational (n = 109) groups, were assessed at baseline, after the 6-month educational program (6 months), and 6 months after the intervention (12 months). The intervention comprised four group sessions and six follow-up phone calls, focusing on frailty, physical activity, dietary habits, and cognitive training. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and wrist-worn accelerometry. RESULTS: At 6 months, a significant time-by-group interaction was found for self-reported [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] and accelerometer-measured [ß = 0.505, 95%CI (0.085, 0.926), p = 0.019] sleep efficiency, showing improved sleep efficiency in the intervention group vs. controls. A significant time-by-group interaction at 6 months was noted for sleep awakenings [ß = -0.402, 95%CI (-0.825, -0.020), p = 0.047]. The educational program led to a significant decrease in awakenings, while the control group experienced an increase. The change in the number of awakenings (Rs = 0.183, p = 0.020) at 6 months was significantly associated with changes in frailty. Moreover, a significant time-by-group interaction was reported at the 12-month assessment [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] for self-reported sleep quality, indicating better results in the intervention group compared to controls. CONCLUSION: The educational program improved sleep quality and sleep efficiency while reducing the number of awakenings per night among community-dwelling frail older adults, offering a practical approach to addressing sleep-related challenges in this demographic.

Effects of preduodenal ileal surgical transposition on enteroendocrine intestinal cells in wistar rats: Histomorphological and serum changes.

In our study, we focused on the role of the distal ileum as a main endocrine actor in relation to the pancreas. We investigated the effects of intestinally released hormones on the pancreas in terms of type 2 diabetes mellitus (T2DM) improvement, as a main effect of bariatric surgeries. To specifically study the importance of the ileum, we used an experimental surgical model performed in healthy Wistar rats. After preduodenal transposition of the ileum, we analyzed the histology and enterohormonal cells of the intestine. We measured the plasma level of several hormones and effectors in this enteropancreatic axis. We used a surgical control (Sham) group and a surgical group, where ileum preduodenal transposition (PDIT) was performed. We measured basal glycemia and serum levels of several incretins, including GLP-1, PYY, and GIP, and we performed a glucose overdose test. After two test periods, the basal glycemia and glucose overdose results were not different between groups, however, the PDIT group had significantly increased expression of GLP-1, with increased cellular release in the ileum and duodenum compared with the Sham group. Both plasma GIP levels and GIP tissue expression were decreased in the PDIT group compared with the sham group. There were no differences in PPY hormone levels. The ileum crypts and villi of the PDIT group showed improvement in histological parameters. We concluded that model animals had an altered transposed ileum related to the enterohormonal adaptation of the ileum. Our results indicated that the ileum is important in the hormonal control of the enteropancreatic axis.

Relationship of body composition with middle cerebral artery hemodynamic using compositional data analysis: Toledo Study for Healthy Ageing in middle age.

Excess adipose tissue may promote chronic systemic inflammation and oxidative stress, causing endothelial damage. Early evidence indicates that obesity may be associated with poorer cerebral perfusion. The purpose of this study was to examine the relationship between body composition and cerebral hemodynamics. A total of 248 middle-aged adults (50-58 years old; 55% women) underwent a ramp test on a cycle-ergometer until volitional exhaustion. Gas exchange was assessed on a breath-by-breath basis. Mean middle cerebral artery velocity (MCAv) was measured using transcranial Doppler, and pulsatility index (PI) calculated. Body composition was assessed by dual X-ray absorptiometry. Statistical analyses were performed using a compositional data approach including a three-compartment model for body composition (trunk fat mass, extremities fat mass, and fat-free mass). The unadjusted models for the whole sample showed that trunk fat mass relative to other compartments was negatively associated with MCAvrest, MCAvmax, and gain, and positively associated with PImax; extremities fat mass relative to other compartments was positively associated with MCAvrest and MCAvmax, and negatively associated with PImax; and fat-free mass relative to other compartments was positively associated with PImax. These associations were sex-dependent, remaining in the women's subgroup. However, after adjusting for confounders, these associations became non-significant, except for PImax in the whole sample and women's subgroup. These findings suggest a possible association between cerebral hemodynamics and body composition in middle-aged adults, highlighting sex-specific differences. Moreover, our results indicate that higher trunk fat mass relative to other compartments may negatively impact cerebral hemodynamics, reducing MCAv and increasing PImax.

Impact of frailty, early vascular decline and subclinical cognitive impairment in midlife adults: study protocol of the Toledo Study for Healthy Ageing in middle age.

Life expectancy has increased worldwide alongside a rise in disability prevalence during old age. The impact and interrelationship among the precursors of disability in midlife remain to be better understood. Furthermore, investigating whether lifestyle factors may potentially influence health outcomes and the prognosis of vascular disease could be especially relevant among the middle-aged population, which is a priority subpopulation when prevention is the goal. This is an observational, cross-sectional and population-based study. Participants, between 50 and 55 years old, are randomly selected from the municipality of Toledo (Spain). There are six non-consecutive days for the assessments, providing enough rest between evaluations. Participants perform the interview of the Toledo Study for Healthy Aging. Blood pressure monitoring and a resting electrocardiogram are also recorded. Then, resting peripheral and cerebral vascular measurements along with muscle size and architecture are assessed. Blood and urine samples, and body composition data are collected after an overnight fasting. On a different visit, physical performance and muscle function tests are performed. Additionally, brain magnetic resonance imaging is conducted. And finally, an accelerometer is given to the participants for a week. Frailty is evaluated by Frailty Trait Scale and Fried Frailty Phenotype. This project will shed light on the associations between frailty, early cognitive impairment, and vascular aging during midlife, and on the role that lifestyles play in their development. Lastly, this project will provide meaningful implications for public health strategies aimed at promoting healthy aging in later life.

RELACIÓN ENTRE INGESTA ALIMENTICIA Y ESTRÉS ACADÉMICO, REACCIONES FISICAS, PSICOLÓGICAS Y COMPORTAMENTALES EN ESTUDIANTES DE LA UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA, MÉXICO / RELATIONSHIP BETWEEN FOOD INTAKE AND ACADEMIC STRESS, PHYSICAL, PSYCHOLOGICAL AND BEHAVIORAL REACTIONS IN STUDENTS OF THE AUTONOMOUS UNIVERSITY OF CHIHUAHUA, MÉXICO

l estrés académico puede presentarse en estudiantes sometidos a diversas exigencias y requisitos universitarios, provocando diferentes reacciones de estrés, físicas, psicológicas y comportamentales, reduciendo su calidad de vida y provocando consecuencias como: depresión, tristeza, fatiga y dolores de cabeza, afectando su estado nutricional. Se investigó la relación entre ingesta de alimentos y estrés académico en estudiantes del cuarto semestre de la Licenciatura en Medicina de la Universidad Autónoma de Chihuahua. La población de estudio, dado el carácter piloto de la investigación, se realizó mediante muestreo simple, aleatorio, sin reemplazo, con un diseño mixto, descriptivo, comparativo y transversal, utilizándose el cálculo del tamaño muestral con un intervalo de confianza de 95%, resultando N=117; 51 hombres y 66 mujeres entre 19 y 43 años de la generación 2019, a quienes se les aplicó el inventario SISCO de estrés académico. Se encontró mayor frecuencia en situaciones que provocan preocupación y nerviosismo, sobrecarga de tareas y trabajo, inquietud, problemas de concentración, fatiga crónica y apatía. Las estrategias más utilizadas fueron: desarrollo de planes y ejecución de tareas y capacidad asertiva. El 92.2% (n=108) de la población encuestada manifestó preocupación y nerviosismo, resultando 52,1% (n=61) en mujeres y 40.1% (n=47) en hombres. El 38.5% (n=45) de las mujeres entre 21 y 43 años, muestran una mayor relación entre aumentar o reducir el consumo de alimentos en correspondencia con sentimientos de depresión y tristeza. El estrés académico, suele estar relacionado con diferentes manifestaciones psicológicas, físicas y conductuales, que pueden influir directamente en la población estudiantil, afectando gravemente sus hábitos alimenticios y nutricionales

Academic stress can occur in students subjected to various university demands and requirements, causing different, causing different physical, psychological and behavioral reactions. Reducing quality of life and causing consequences such as: depression, sadness, fatigue and headaches, affecting their nutritional status. The relationship between food intake and academic stress was investigated in students in the fourth semester of the Bachelor of Medicine at the Autonomous University of Chihuahua. The study population, given the pilot nature of the research, was carried out through simple, random sampling, without replacement, with a mixed, descriptive, comparative and transversal design, using the sample size calculation with a 95% confidence interval resulting in N=117; 51 men and 66 women between the ages of 19 and 43, from the 2019 generation, to whom the SISCO inventory of academic stress was applied. A greater frequency was found in situations that cause worry and nervousness, overload of tasks and work, restlessness, concentration problems, chronic fatigue and listlessness. The most used strategies were plan development and execution of tasks and assertive ability. 92.2% (n=108) of the surveyed population expressed concern and nervousness, in 52.1% (n=61) women and 40.1% (n=47) men. The 38.5% (n=45) of women between 21 and 43 years old show a greater relationship between increasing or reducing food consumption in correspondence with feelings of depression and sadness. Academic stress is usually related to different psychological, physical and behavioral manifestations, which can directly influence the student population, seriously affecting their eating and nutritional habits