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Background: Identifying children and adolescents with cardiometabolic risk at an early stage is crucial for effective treatment and prevention. From a practical perspective, this could be accomplished by assessing the presence of abdominal obesity, which serves as a surrogate indicator of increased cardiometabolic risk and is easy to measure. However, the assessment of abdominal obesity via waist circumference has not yet become a standard procedure in pediatric healthcare. The present study aimed to analyze the secular trends in increased cardiometabolic risk, as indicated by waist circumference among Spanish children and adolescents., Methods: This study included 4861 children and adolescents aged 8 to 16 years from two nationwide representative cross-sectional surveys, the EnKid study and the PASOS study, conducted in 1998-2000 and 2019-2020, respectively. Anthropometric variables were measured in both surveys by trained personnel. Three different waist-to-height (WHtR) cutoffs were used to define abdominal obesity as criteria for cardiometabolic risk. BMI categories were defined according to the IOTF and WHO growth charts., Results: Abdominal obesity [waist to height ratio (cm/cm) > 0.49] significantly increased from 40.7 to 56.1% and 93.8 to 97.2% in participants with overweight and obesity, respectively, between 1998-2000 and 2019-2020 (p < 0.05). Logistic regression analysis, adjusted for sex and age, revealed that the odds of being at increased cardiometabolic risk in 2019-2020 was 1.99 (95% CI 1.48-2.67) in participants with overweight in comparison with 1998-2000. The effect size was comparable among the three WHtR criteria for abdominal obesity or the BMI categories according to IOTF and WHO boundaries., Conclusions: The prevalence of Spanish children with increased cardiometabolic risk, identified by abdominal obesity, significantly increased among those with overweight during the last two decades. This finding underlines the need of including the measurement of waist circumference as a standard procedure in pediatric practice., (© 2024. The Author(s).)

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.

In recent years, there has been increased focus on strategic learning from impact analysis, including in the field of science, technology, and innovation. In this paper, we propose combining techniques from two fields of study. Firstly, we adopt the approach of addressing impact through productive interactions between science and society, and secondly, we incorporate an anticipatory dimension by integrating game analysis involving key actors. Through a theory-driven evaluation design, we consider expected impacts as promises of the future. Within an anticipatory perspective, the future can be shaped by the interactions among different actors in the present. In this article, we apply this approach step-by-step to a research institute program in Uruguay. We demonstrate how the achieved results offer strategic insights to the program manager for anticipating and attaining the desired impacts. Additionally, we provide summative inputs for accountability using a flexible technique applicable at any stage of the program life cycle. The article concludes with a discussion of the advantages and disadvantages compared to other techniques, along with lessons learned that may benefit other evaluators seeking to replicate this approach. Furthermore, we explore potential extensions and opportunities for further improvement in this research., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Common beans (Phaseolus vulgaris L.) are among the most important legumes for human nutrition. The aim of the present study was to characterize the composition and in vitro bioaccessibility of tocochromanols, carotenoids, and iron from 14 different landraces and 2 commercial common bean varieties. Phytic acid, dietary fiber, and total (poly)phenolic content were determined as factors that can modify the bioaccessibility of the studied compounds. Two carotenoids were identified, namely lutein (4.6-315 ng/g) and zeaxanthin (12.2-363 ng/g), while two tocochromanols were identified, namely γ-tocopherol (2.62-18.01 µg/g), and δ-tocopherol (0.143-1.44 µg/g). The iron content in the studied samples was in the range of 58.7-144.2 µg/g. The contents of carotenoids, tocochromanols, and iron differed significantly among the studied samples but were within the ranges reported for commercial beans. After simulated gastrointestinal digestion, the average bioaccessibility of carotenoids was 30 %, for tocochromanols 50 %, and 17 % for iron. High variability in the bioaccessible content yielded by the bean varieties was observed. Dietary fiber, phytic acid and total (poly)phenol contents were negatively correlated with the bioaccessibility of carotenoids, while iron bioaccessibility was negatively correlated with the total (poly)phenol content. The principal component analysis indicated that the bioaccessibility of lutein was the main variable involved in class separations. The composition of the food matrix plays an important role in the bioaccessibility of carotenoids, tocochromanols and iron from cooked beans., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein-coupled receptor P2Y 1 receptors, increasing intracellular Ca 2+ that activates small conductance calcium-activated potassium (SK Ca ) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α-adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α-adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon., Methods: Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally., Results: The α 1 -adrenoceptor agonist phenylephrine (PE) (10 -8 -10 -5  M) evoked concentration-dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid-circular colon at low PE concentrations, a contraction sensitive to 10 -5  M phentolamine (non-selective α-adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10 -6  M), and atropine (10 -6  M) was recorded. PE-induced relaxations were insensitive to TTX (10 -6  M) and the nonselective β-adrenoceptor blocker propranolol (10 -6  M). In contrast, PE-induced relaxations were blocked by phentolamine (10 -5  M), prazosin (10 -6  M) (α 1 -adrenoceptor blocker), and RS17053 (10 -6  M) (α 1A -blocker), but not by yohimbine (10 -6  M) (α 2 -adrenoceptor blocker). Apamin (10 -6  M), a SK Ca channel blocker, abolished PE-induced relaxations., Conclusions: Contractile responses in the circular muscle of the mid colon could be attributed to α-adrenoceptors located on enteric cholinergic neurons. Stimulation of α 1A -adrenoreceptors activates SK Ca channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y 1 receptors., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Introduction: Local resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME., Patients and Method: An international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/- endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy., Discussion: The prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information. The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients., Trial Registration Number: NCT05927584., (Copyright © 2024 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Peptide surfactants (PEPS) are studied to capture and retain rare earth elements (REEs) at air-water interfaces to enable REE separations. Peptide sequences, designed to selectively bind REEs, depend crucially on the position of ligands within their binding loop domain. These ligands form a coordination sphere that wraps and retains the cation. We study variants of lanthanide binding tags (LBTs) designed to complex strongly with Tb 3+ . The peptide LBT 5- (with net charge -5) is known to bind Tb 3+ and adsorb with more REE cations than peptide molecules, suggesting that undesired non-specific coulombic interactions occur. Rheological characterization of interfaces of LBT 5- and Tb 3+ solutions reveal the formation of an interfacial gel. To probe whether this gelation reflects chelation among intact adsorbed LBT 5- :Tb 3+ complexes or destruction of the binding loop, we study a variant, LBT 3- , designed to form net neutral LBT 3- :Tb 3+ complexes. Solutions of LBT 3- and Tb 3+ form purely viscous layers in the presence of excess Tb 3+ , indicating that each peptide binds a single REE in an intact coordination sphere. We introduce the variant RR-LBT 3- with net charge -3 and anionic ligands outside of the coordination sphere. We find that such exposed ligands promote interfacial gelation. Thus, a nuanced requirement for interfacial selectivity of PEPS is proposed: that anionic ligands outside of the coordination sphere must be avoided to prevent the non-selective recruitment of REE cations. This view is supported by simulation, including interfacial molecular dynamics simulations, and interfacial metadynamics simulations of the free energy landscape of the binding loop conformational space.

Background: Schizophrenia is a chronic mental illness that affects millions of individuals worldwide. The etiological origin of schizophrenia is heterogeneous, but it has been shown to be associated with dysfunction in serotonin activity, serotonin receptors, and serotonin metabolism in the brain. Bibliometric analysis is a tool used to scrutinise and analyse research activities and evidence in a specific research area. No existing bibliometric analyses have considered both serotonin and schizophrenia., Methods: We conducted a bibliometric analysis including 12,027 studies related to the schizophrenia-serotonin link published from the inception of the study to 2023 and available in the Scopus database. We used VOSviewer software to identify global trends, analyse the author and editors keywords, the most cited articles and author, as well as the most productive institutes and journals publishing research on schizophrenia-serotonin link., Results: Most publications related to the link between schizophrenia and serotonin are focused on adult humans and examine topics such as antipsychotic agents, depression, and serotonin uptake inhibitors. The Journal of Clinical Psychiatry has published the most papers on the schizophrenia-serotonin relationship. Among nations, the United States is the leader in publications. King's College London is the institution with the highest number of publications, and H. Y. Meltzer is the most influential author. Growing trends in schizophrenia-serotonin research are personalised medicine, alternative medicine, transcranial magnetic stimulation, artificial intelligence, nervous system inflammation, brain-gut axis, and the gut microbiome., Conclusion: Since 1950, there have been several fluctuations in the number of published studies related to schizophrenia and serotonin. We believe that the development of novel medications and treatments for schizophrenia will be increased in the future, as well as research into genetic risks, psychological factors, and cranial neuroimaging components. Future schizophrenia and serotonin research is likely to focus on personalised medicine, alternative therapies, novel pathogenesis of schizophrenia, and the use of emerging technologies such as artificial intelligence., 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 © 2024 Canul-Medina, López-Pech and Jiménez-Trejo.)

To maintain economic profitability and stabilize fuel prices, refineries actively explore alternatives for efficiently processing (extra) heavy crude oils. These oils are challenging to process due to their complex composition, which includes significant quantities of asphaltenes, resins, and sulfur and nitrogen heteroatoms. A critical initial step in upgrading these oils is the hydrogenation of polyaromatic compounds, requiring substantial hydrogen sources. Methane from natural gas streams is known to act as an effective hydrogen donor. This study investigates the use of a heteropolyacid (HPA) catalyst modified with nickel and methane to enhance the quality of heavy crude oil with an initial 8.0°API (at 15.5 °C) and 2200 cSt viscosity (at 37.5 °C). After treatment in a batch reactor at 380 °C and 4.4 MPa for 2 h, the oil properties markedly improved: API gravity increased from 8.0 to 16.0 (at 15.5 °C), and kinematic viscosity reduced from 2200 to 125 cSt (at 37.5 °C). Additionally, there was a significant decrease in asphaltenes (from 38.7 to 16.4% by weight), sulfur (from 5.9 to 4.0% by weight), and nitrogen (from 971 to 695 ppm). This was accompanied by an increase in the volume of light distillates from 1.3 to 4.9%, and middle distillates from 8.8 to 21.0%. These results suggest that nickel-modified HPA catalysts, combined with methane as a hydrogen donor, are a promising option for upgrading heavy crude oils., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.

The objective was to evaluate changes in fitness after an integrated neuromuscular training (INT) intervention in primary school children and to evaluate how lifestyle behaviors and parental education modulate these changes. One hundred and seventy children (7.45 ± 0.34 years; 52% girls) were included. Cardiorespiratory fitness (half-mile run test), a 10 × 5 m shuttle run test, standing broad jump (SBJ), handgrip dynamometer, body mass index (BMI) and fat mass percentage (FM%) were assessed before and after the 3-month intervention (20 min of INT in the physical education class, twice per week). The Mediterranean diet (MD), sleep time and parental education level (PEL) were evaluated by questionnaires, and adherence to physical activity (PA) recommendations was measured with a triaxial accelerometer before the intervention. After the intervention, there were improvements in the 10 × 5 test and the SBJ. Only girls had improvements in the handgrip test, BMI SDS and FM%. After correcting for confounding variables, only BMI was significantly improved whereas strength improved in the participants non-compliant with the PA recommendations or pertaining to families of high PEL. The INT produced improvements in fitness in a brief period and in different subgroups of pupils (inactive and with diverse sociocultural environments).

A new statistical analysis is presented to assess cycle-to-cycle variability in resistive memories. This method employs two-dimensional (2D) distributions of parameters to analyse both set and reset voltages and currents, coupled with a 2D coefficient of variation (CV). This 2D methodology significantly enhances the analysis, providing a more thorough and comprehensive understanding of the data compared to conventional one-dimensional methods. Resistive switching (RS) data from two different technologies based on hafnium oxide are used in the variability study. The 2D CV allows a more compact assessment of technology suitability for applications such as non-volatile memories, neuromorphic computing and random number generation circuits.

Introduction: Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics., Areas Covered: We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms., Expert Opinion: We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation., Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models., Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts., Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Choreño-Parra, Ramon-Luing, Castillejos, Ortega-Martínez, Tapia-García, Matías-Martínez, Cruz-Lagunas, Ramírez-Martínez, Gómez-García, Ramírez-Noyola, Garcia-Padrón, López-Salinas, Jiménez-Juárez, Guadarrama-Ortiz, Salinas-Lara, Bozena-Piekarska, Muñóz-Torrico, Chávez-Galán and Zúñiga.)

Rosehip fruits, characterized by their high concentrations of bioactive compounds and antioxidant activity (AA), have been traditionally used to make jams, infusions, and juices. Thus, the objective of this research was to evaluate the stability of rosehip juice by determining the concentrations of bioactive compounds and total phenols and the AA using chromatographic and spectroscopic methods. The stability of the juice was evaluated with three treatments and different storage conditions, namely, unpasteurized-refrigerated, pasteurized-room temperature, and pasteurized-refrigerated, and measurements were taken for eight months. Individual and total phenolic compounds, evaluated by chromatographic methods, reported differences until the end of this study. The total phenolic compounds by Folin-Ciocalteu method presented an average decrease of 57% in the three treatments in relation to the initial conditions. On the other hand, the ascorbic acid content decreased considerably, disappearing at week six. Furthermore, for the unpasteurized-refrigerated and pasteurized-refrigerated samples, a correlation was found between flavonols, total phenols, ascorbic acid, and antioxidant activity determined by the TEAC method. For the pasteurized-room temperature samples, correlations were found between the levels of several flavonols, hydroxycinnamic acid, total phenols, and ascorbic acid and the antioxidant activity determined by the CUPRAC method. The stability of the compounds was mainly correlated with the storage conditions of the juice and not with pasteurization. The highest stability was observed for the unpasteurized-refrigerated and pasteurized-refrigerated samples. Although the concentrations of the compounds evaluated decreased during this study, significant levels of AA persisted, providing beneficial characteristics for consumer health.

Individuals with intellectual and developmental disabilities (IDD) continue to experience disparities in health and well-being despite improved provisions of person-centered care. Patient-centered outcomes research (PCOR) translates evidence into practice for meaningful outcomes. This piece describes findings from an environmental scan and stakeholder outreach to identify and prioritize opportunities to enhance IDD PCOR data infrastructure. These opportunities include developing a standardized research definition; advancing data standards for service systems; improving capture of IDD at point of care; developing standardized outcome measures; and encouraging Medicaid data use for IDD research. Within this piece, we discuss the implications of addressing data gaps for enhanced research. While the identified activities provide a path towards advancing IDD PCOR data infrastructure, collaborative efforts between government, researchers, and others are paramount., (©AAIDD.)

Study Design: This was a retrospective longitudinal observational study., Purpose: The purpose of this study was to analyze the results of cervical sagittal parameters on preoperative and postoperative lateral radiographs in anterior cervical discectomy and fusion (ACDF). ACDF is believed to change craniocervical parameters and thus cervical curvature using polyetheretherketone (PEEK) or titanium cages with or without self-locking as well as an anterior plate, the latter of which has not been shown to provide better clinical or radiological results., Overview of Literature: Cervical spondylotic myelopathy (CSM) is a common degenerative pathology that can affect one or more levels and treatment has varied over time trying to maintain sagittal parameters within acceptable values where the ACDF is the main treatment., Materials and Methods: The study was performed in patients with CSM who underwent anterior cervical discectomy, and their pre- and postoperative radiographs were analyzed using Surgimap software a few days before and 3 months after surgery., Results: Fifteen files were included in the study. Statistically significant sagittal balance variables were observed in cervical lordosis (CL) with an increase of 4.73° ( P = 0.019) and T1 slope (T1S)-CL with a decrease of -5.93° ( P = 0.007)., Conclusions: CL and T1S-CL showed favorably modified values when performing ACDF using stand-alone PEEK cages without the need for self-blocking or an anterior plate., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Craniovertebral Junction and Spine.)

Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.

Faecal incontinence (FI) is a major health problem, both for individuals and for health systems. It is obvious that, for all these reasons, there is widespread concern for healing it or, at least, reducing as far as possible its numerous undesirable effects, in addition to the high costs it entails. There are different criteria for the diagnostic tests to be carried out and the same applies to the most appropriate treatment, among the numerous options that have proliferated in recent years, not always based on rigorous scientific evidence. For this reason, the Spanish Association of Coloproctology (AECP) proposed to draw up a consensus to serve as a guide for all health professionals interested in the problem, aware, however, that the therapeutic decision must be taken on an individual basis: patient characteristics/experience of the care team. For its development it was adopted the Nominal Group Technique methodology. The Levels of Evidence and Grades of Recommendation were established according to the criteria of the Oxford Centre for Evidence-Based Medicine. In addition, expert recommendations were added briefly to each of the items analysed., (Copyright © 2023 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Hypertension is the most prevalent modifiable risk factor for stroke and is associated with worse functional outcomes. Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid (SAHA) modulates gene expression and has emerged as a promising therapeutic approach to reduce ischaemic brain injury. Here, we have tested the therapeutic potential of SAHA administered during reperfusion in adult male spontaneously hypertensive (SHR) rats subjected to transient middle cerebral artery occlusion (tMCAO; 90 min occlusion/24 h reperfusion). Animals received a single dose of SAHA (50 mg/kg) or vehicle i.p. at 1, 4, or 6 h after reperfusion onset. The time-course of brain histone H3 acetylation was studied. After tMCAO, drug brain penetrance and beneficial effects on behavioural outcomes, infarct volume, oedema, angiogenesis, blood-brain barrier integrity, cerebral artery oxidative stress and remodelling, and brain and vascular inflammation were evaluated. SAHA increased brain histone H3 acetylation from 1 to 6 h after injection, reaching the ischaemic brain administered during reperfusion. Treatment given at 4 h after reperfusion onset improved neurological score, reduced infarct volume and oedema, attenuated microglial activation, prevented exacerbated MCA angiogenic sprouting and blood-brain barrier breakdown, normalised MCA oxidative stress and remodelling, and modulated brain and cerebrovascular cytokine expression. Overall, we demonstrate that SAHA administered during early reperfusion exerts robust brain and vascular protection after tMCAO in hypertensive rats. These findings are aligned with previous research in ischaemic normotensive mice and help pave the way to optimise the design of clinical trials assessing the effectiveness and safety of SAHA in ischaemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Despite the importance of structural control on metal stable isotope fractionation in inorganic and abiotic systems, the link between metal structural changes and related isotopic fractionation during reactions with organic surfaces and live cells remains poorly established. We conducted reversible adsorption of Fe(II) and Fe(III) on the surface of exopolysaccharide (EPS)-rich and EPS-poor Pseudomonas aureofaciens , and we allowed Fe intracellular uptake by growing cells. We analyzed the Fe isotopic composition of the remaining fluid and cell biomass, and compared the isotopic fractionation during adsorption and assimilation reaction with relative changes in Fe structural status between aqueous solution and bacterial cells, based on available and newly collected X-ray absorption spectroscopy (XAS) observations. Iron(III) adsorption onto P. aureofaciens at 2.8 ≤ pH ≤ 6.0 produced an enrichment of the cell surface in heavier isotopes with Δ 57 Fe cell-solution ranging from +0.7 to +2.1‰, without a link to pH in EPS-rich cultures. In contrast, the magnitude of isotopic fractionation increased with pH in EPS-poor cultures. Iron(II) adsorption produced an even larger enrichment of the cell surface in heavier isotopes, by up to 3.2‰, tentatively linked to Fe(III) hydroxide precipitation. Intracellular assimilation of Fe(II) favored heavier isotopes and led to Δ 57 Fe cell-solution of +0.8‰. In addition, Fe(III) cellular uptake produced an enrichment of the bacterial biomass in lighter isotopes with Δ 57 Fe cell-solution of -1‰. The XAS analyses demonstrated the dominance of Fe(III)-phosphate complexes both at the cell surface and in the cell interior. We suggest that heavier isotope enrichment of the cell surface relative to the aqueous solution is due to strong Fe(III)-phosphoryl surface complexes and Fe complexation to ligands responsible for metal transfer from the surface to the inner cell. In case of Fe(II) adsorption or assimilation, its partial oxidation within the cell compartments may lead to cell enrichment in heavier isotopes. In contrast, loss of symmetry of assimilated Fe(III) relative to the aqueous Fe 3+ ion and longer bonds of intracellular ions relative to aqueous Fe(III)-citrate or hydroxo-complexes could produce an enrichment of cells in lighter isotopes. The versatile nature of Fe(II) and Fe(III) fractionation without a distinct effect of pH and surface exopolysaccharide coverage suggests that, in natural soil and sedimentary environments, Fe isotope fractionation during interaction with heterotrophic bacteria will be primarily governed by Fe complexation with DOM and Fe redox status in the soil pore water.

Resistive switching devices based on the Au/Ti/TiO 2 /Au stack were developed. In addition to standard electrical characterization by means of I - V curves, scanning thermal microscopy was employed to localize the hot spots on the top device surface (linked to conductive nanofilaments, CNFs) and perform in-operando tracking of temperature in such spots. In this way, electrical and thermal responses can be simultaneously recorded and related to each other. In a complementary way, a model for device simulation (based on COMSOL Multiphysics) was implemented in order to link the measured temperature to simulated device temperature maps. The data obtained were employed to calculate the thermal resistance to be used in compact models, such as the Stanford model, for circuit simulation. The thermal resistance extraction technique presented in this work is based on electrical and thermal measurements instead of being indirectly supported by a single fitting of the electrical response (using just I - V curves), as usual. Besides, the set and reset voltages were calculated from the complete I - V curve resistive switching series through different automatic numerical methods to assess the device variability. The series resistance was also obtained from experimental measurements, whose value is also incorporated into a compact model enhanced version., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Colloidal crystals have applications in water treatments, including water purification and desalination technologies. It is, therefore, important to understand the interactions between colloids as a function of electrolyte concentration. We study the assembly of DNA-grafted gold nanoparticles immersed in concentrated electrolyte solutions. Increasing the concentration of divalent Ca 2+ ions leads to the condensation of nanoparticles into face-centered-cubic (FCC) crystals at low electrolyte concentrations. As the electrolyte concentration increases, the system undergoes a phase change to body-centered-cubic (BCC) crystals. This phase change occurs as the interparticle distance decreases. Molecular dynamics analysis suggests that the interparticle interactions change from strongly repulsive to short-range attractive as the divalent-electrolyte concentration increases. A thermodynamic analysis suggests that increasing the salt concentration leads to significant dehydration of the nanoparticle environment. We conjecture that the intercolloid attractive interactions and dehydrated states favour the BCC structure. Our results gain insight into salting out of colloids such as proteins as the concentration of salt increases in the solution.

Electrostatic forces in solutions are highly relevant to a variety of fields, ranging from electrochemical energy storage to biology. However, their manifestation in concentrated electrolytes is not fully understood, as exemplified by counterintuitive observations of colloidal stability and long-ranged repulsions in molten salts. Highly charged biomolecules, such as DNA, respond sensitively to ions in dilute solutions. Here, we use non-base-pairing DNA-coated nanoparticles (DNA-NP) to analyze electrostatic interactions in concentrated salt solutions. Despite their negative charge, these conjugates form colloidal crystals in solutions of sufficient divalent cation concentration. We utilize small-angle X-ray scattering (SAXS) to study such DNA-NP assemblies across the full accessible concentration ranges of aqueous CaCl 2 , MgCl 2 , and SrCl 2 solutions. SAXS shows that the crystallinity and phases of the assembled structures vary with cation type. For all tested salts, the aggregates contract with added ions at low salinities and then begin expanding above a cation-dependent threshold salt concentration. Wide-angle X-ray scattering (WAXS) reveals enhanced positional correlations between ions in the solution at high salt concentrations. Complementary molecular dynamics simulations show that these ion-ion interactions reduce the favorability of dense ion configurations within the DNA brushes below that of the bulk solution. Measurements in solutions with lowered permittivity demonstrate a simultaneous increase in ion coupling and decrease in the concentration at which aggregate expansion begins, thus confirming the connection between these phenomena. Our work demonstrates that interactions between charged objects continue to evolve considerably into the high-concentration regime, where classical theories project electrostatics to be of negligible consequence., Competing Interests: Competing interests statement:The authors F.J.-Á. and M.O.d.l.C. participated in a Faraday Discussion meeting on iontronics in June 2023, at Edinburgh, UK, which the reviewer S.P. and her group also attended. F.J.-Á. presented an article [Felipe Jiménez-Ángeles, Ali Ehlen, and Monica Olvera de la Cruz, Faraday Discuss. 246, 576–591 (2023)], and a member of the group of S.P. also presented an article in this meeting [Y. K. Catherine Fung and Susan Perkin, Faraday Discuss. 246, 370–386 (2023)]. The questions and answers on the presentations during all the different session in the meting are also published in Faraday Discuss. 2023, Vol. 246, under manuscripts with titles such as “Ionotronic coupling: general discussion” and “Iontronics under confinement: general discussion”, where F.J.-Á. participated on pages 592–617 and 157–178 and M.O.d.l.C. on pages 592–617, 466–486, and 322–355. These manuscripts are only reports on the discussions among the participants concerning articles presented during the meeting; For example, F.J.-Á. answered a short question by S.P. (in addition to 5 more questions by others) published on Vol. 246, pages 592–617, and M.O.d.l.C. asked a question to Christian Holm in the same session. Both F.J.-Á. and M.O.d.l.C. declare no conflict of interest with S.P.

Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesize that environments of severe carotid atherosclerotic disease worsen endothelial dysfunction in stroke linked to enhanced risk of further cerebrovascular events. We mounted nonischemic common carotid arteries from 2- to 4-month-old male Oncins France 1 mice in tissue baths for isometric contraction force measurements and exposed them to serum from men with a recent ischemic stroke and different degrees of carotid stenosis: low- or moderate-grade stenosis (LMGS; < 70%) and high-grade stenosis (HGS; ≥ 70%). The results show that serum from stroke patients induced an impairment of acetylcholine relaxations in mice carotid arteries indicative of endothelium dysfunction. This effect was more pronounced after incubation with serum from patients with a recurrent stroke or vascular death within 1 year of follow-up. When patients were stratified according to the degree of stenosis, serum from HGS patients induced more pronounced carotid artery endothelial dysfunction, an effect that was associated with enhanced circulating levels of IL-1β. Mechanistically, endothelial dysfunction was prevented by both nonselective and selective COX blockade. Altogether, the present findings add knowledge on the understanding of the mechanisms involved in the increased risk of stroke in atherosclerosis and suggest that targeting COX in the carotid artery wall may represent a potential novel therapeutic strategy for secondary stroke prevention., (© 2022. The Author(s).)

Obesity is defined as having an excess of adipose tissue and is associated with the development of diabetes, hypertension, and atherosclerosis, which are the main causes of death worldwide. Research shows that probiotics and prebiotics reduce the metabolic alterations caused by high-fat diets. Therefore, this work evaluated the effect of the incorporation of Lactobacillus acidophilus (probiotic) and inulin (prebiotic) in the diet through obesity markers (biochemical, anthropometric, and molecular markers) in an obese murine model. Four treatments were administered: (1) hypocaloric diet (HD), (2) HD + L. acidophilus, (3) HD + inulin, and (4) DH supplemented with L. acidophilus + inulin for 8 weeks. After treatment, glucose, triglycerides, total cholesterol, HDL-C, and LDL-C in plasma were determined. In addition, the total body weight and adipose tissue were taken to calculate the body mass index. Following RNA extraction from adipose tissue, the expression of PPAR gamma, PPAR alpha, and transforming growth factor beta 1 (TGF1β) was evaluated by semiquantitative PCR. All treatments showed an improvement in biochemical markers compared to the values of the obese model (p < 0.05). Optimal values for blood glucose (133.2 ± 14.3 mg/dL), triglycerides (71 ± 4.6 mg/dL), total cholesterol (48.9 ± 6 mg/dL), HDL-C (40.9 ± 4.8 mg/dL), and LDL-C (8.4 ± 1.7 mg/dL) were obtained in the mixed treatment. Regarding fat mass index (FMI), prebiotic treatment caused the greatest reduction. On the other hand, mixed treatment increased the gene expression of PPARα and TGF1β in adipose tissue with DH with L. acidophilus and inulin treatment. This work demonstrates that the use of L. acidophilus and inulin as a complementary treatment is a viable alternative for prevention and action as a complementary treatment for obesity given the reduction in biochemical parameters and anthropometric indices; these reductions were greater than those found in the classic treatment of obesity due to the induction of the expression of genes related to lipid metabolism and anti-inflammatory cytokines, which contribute to reducing the high levels of glucose, triglycerides, and cholesterol caused by obesity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Antimicrobial stewardship programmes (ASPs) have resulted in antimicrobial consumption (AMC) reduction and quality of prescription (QOP) improvement. However, evidence of ASP impact in paediatrics is still limited. This study aims to assess a paediatric ASP long-term outcomes., Methods: A quality improvement study assessed by a interrupted time series analysis was conducted in a paediatric tertiary hospital. QOP expressed as proportion of adequate prescriptions, AMC measured by defined daily dose incidence per 1000 occupied bed days, incidence density of bloodstream infections (BSIs) and its related all-cause crude death rate (CDR) were compared between pre (from January 2013 to December 2015) and post (from January 2016 to December 2019) ASP activities intensification, which included a dedicated paediatric infectious diseases physician to actively perform educational interviews with prescribers., Results: Inappropriate prescribing showed a significant downward shift associated to the intervention with a -51.4% (-61.2% to -41.8%) reduction with respect to the expected values. Overall AMC showed no trend change after the intervention. For neonatology a28.8% (-36.8% to -20.9%) reduction was observed. Overall anti-pseudomonal cephalosporin use showed a -51.2% (-57.0% to -45.4%) reduction. Decreasing trends were observed for carbapenem use, with a quarterly per cent change (QPC) of -2.4% (-4.3% to -0.4%) and BSI-related CDR (QPC=-3.6%; -5.4% to -1.7%) through the study period. Healthcare-associated multi-drug-resistant BSI remained stable (QPC=2.1; -0.6 to 4.9)., Conclusions: Intensification of counselling educational activities within an ASP suggests to improve QOP and to partially reduce AMC in paediatric patients. The decreasing trends in mortality remained unchanged., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Transient receptor potential vanilloid 2 (TRPV2) channels are expressed in both smooth muscle and endothelial cells and participate in vascular mechanotransduction and sensing of high temperatures and lipids. Nevertheless, the impact of TRPV2 channel activation by agonists on the coordinated and cell-type specific modulation of vasoreactivity is unknown., Main Methods: Aorta from 2- to 4-months-old male Oncins France 1 mice was dissected and mounted in tissue baths for isometric tension measurements. TRPV2 channel expression was assessed by immunofluorescence and western blot in mice aortas and in cultured A7r5 rat aortic smooth muscle cells., Key Findings: TRPV2 channels were expressed in all three mouse aorta layers. Activation of TRPV2 channels with probenecid evoked endothelium-dependent relaxations through a mechanism that involved activation of smooth muscle K ir and K v channels. In addition, TRPV2 channel inhibition with tranilast increased endothelium-independent relaxations to probenecid and this effect was abrogated by the K ATP channel blocker glibenclamide, revealing that smooth muscle TRPV2 channels induce negative feedback on probenecid relaxations mediated via K ATP channel inhibition. Exposure to the NO donor sodium nitroprusside increased TRPV2 channel translocation to the plasma membrane in cultured smooth muscle cells and enhanced negative feedback on probenecid relaxations., Significance: In conclusion, we present the first evidence that TRPV2 channels may modulate vascular tone through a balance of opposed inputs from the endothelium and the smooth muscle leading to net vasodilation. The fact that TRPV2 channel-induced activity can be amplified by NO emphasizes the pathophysiological relevance of these findings., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

TRP channels are important pharmacological targets in physiopathology. TRPV2 plays distinct roles in cardiac and neuromuscular function, immunity, and metabolism, and is associated with pathologies like muscular dystrophy and cancer. However, TRPV2 pharmacology is unspecific and scarce at best. Using in silico similarity-based chemoinformatics we obtained a set of 270 potential hits for TRPV2 categorized into families based on chemical nature and similarity. Docking the compounds on available rat TRPV2 structures allowed the clustering of drug families in specific ligand binding sites. Starting from a probenecid docking pose in the piperlongumine binding site and using a Gaussian accelerated molecular dynamics approach we have assigned a putative probenecid binding site. In parallel, we measured the EC50 of 7 probenecid derivatives on TRPV2 expressed in Pichia pastoris using a novel medium-throughput Ca 2+ influx assay in yeast membranes together with an unbiased and unsupervised data analysis method. We found that 4-(piperidine-1-sulfonyl)-benzoic acid had a better EC50 than probenecid, which is one of the most specific TRPV2 agonists to date. Exploring the TRPV2-dependent anti-hypertensive potential in vivo, we found that 4-(piperidine-1-sulfonyl)-benzoic acid shows a sex-biased vasodilator effect producing larger vascular relaxations in female mice. Overall, this study expands the pharmacological toolbox for TRPV2, a widely expressed membrane protein and orphan drug target., Competing Interests: None., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Background: Maintaining a healthy lifestyle is crucial for safeguarding the well-being and quality of life perception, appropriate growth, and development of children and adolescents, while also mitigating the risk of future adult-onset diseases., Objective: To assess associations between perceived quality of life and healthy lifestyle and related outcomes in Spanish children and adolescents., Methods: Cross-sectional analysis of 8-16-year-old children and adolescents (n = 3534) were included in the nationwide study of Physical Activity, Sedentarism, and Obesity in Spanish Youth (PASOS). Data were collected through (1) questionnaires on health-related quality of life (HRQoL), healthy lifestyle outcomes (dietary intake, physical fitness, sleep, and screen time), and (2) anthropometric measurements for weight status assessment. Data were analysed by logistic regression, using the health-related quality of life (HRQoL) as the grouping variable., Results: Participants with a lower HRQoL were those with a lower adherence to the MedDiet and lower achievement of the recommended daily intake of fruit and vegetables. They were also less likely to follow the recommendations for screen time and sleep (with the exception of the weekend) compared to participants with a higher HRQoL. Participants with a lower HRQoL showed a lower healthy weight status and poorer physical fitness than those with a higher HRQoL., Conclusions: Healthy eating habits, healthy weight status (normal weight), appropriate sleep time, physical fitness, and limited screen time play a crucial role in the perceived quality of life in children and adolescents.

Peripheral nerve sheath tumors (PNST) comprise schwannomas and neurofibromas. The finding of increased adipose tissue around benign PNSTs has been described as the "split fat sign" on magnetic resonance imaging exams, which is suggestive of an intramuscular or intermuscular location of the tumor. However, few studies have described this sign as a salient ultrasound feature of PNSTs. The main purpose of this study was to retrospectively evaluate the presence of increased fatty tissue deposition around benign PNSTs diagnosed by high-resolution ultrasound. In addition, we aimed to corroborate the presence of vascularization around the affected area. A retrospective analysis of ten cases of PNSTs and two cases of post-traumatic neuromas diagnosed by high-resolution ultrasound was performed with a Logiq ® P8 ultrasound with a 2-11 MHz multifrequency linear probe L3-12-D (central frequency: 10 MHz). Localized types of neurofibromas and schwannomas in any location were seen as predominantly hypoechoic tumors with an oval or fusiform shape. Exiting and entering nerves (tail sign) were observed in six cases, showing localized lesions both in intermuscular and subcutaneous locations. The presence of increased hyperechoic tissue (the split fat sign) was noted in cases of solitary intermuscular and intramuscular peripheral nerve sheath tumors, mainly the schwannomas. Though small tumors did not demonstrate the tail sign, the increase in adipose tissue and vascularity on US was well demonstrated. In conclusion, the nerve in continuity forms the basis of the ultrasonographic diagnosis of PNSTs. However, high-resolution US can convincingly demonstrate the increased presence of fat in the upper and lower poles as well as circumferentially in intermuscular or intramuscular benign PNSTs.

The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium , and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus , and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches., 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 Galeana-Cadena, Gómez-García, Lopez-Salinas, Irineo-Moreno, Jiménez-Juárez, Tapia-García, Boyzo-Cortes, Matías-Martínez, Jiménez-Alvarez, Zúñiga and Camarena.)

Objectives: To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU)., Methods: We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy., Results: Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control., Conclusions: The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU., (© 2023. The Author(s).)

Background: Youth is a vulnerable period. To classify lifestyle behaviors and its relationship with health-related outcomes of Spanish children and adolescents., Methods: Cross-sectional study including 3261 children aged 7.5-17.5 y (52.8% females). Physical activity (PA), screen-time, sleep time, adherence to Mediterranean diet (MD), weight status (WS) by validated methods. Cluster analysis was run considering chronological age., Results: Six clusters were identified: C1: high screen time, low adherence to MD and sleep time (n = 431,13.20%); C2: high WS, medium adherence to MD,high sleep time, and low screen time (n = 466,14.30%); C3: young group with low screen time and high PA, adherence to MD and sleep (n = 537,16.40%); C4: worst profile regarding adherence to MD, PA, WS and sleep time (n = 609,18.70%); C5: low screen time and PA, high sleep time (n = 804,24.70%); C6: high PA and screen time, low WS (n = 414,12.70%). Mean absolute values were statistically different among PA levels, screen and sleep time, adherence to MD, age, and WS (all p < 0.001)., Conclusions: The most prevalent pattern was low levels of PA, MD, and screen time, and high sleep time. The second most prevalent was characterized by very low levels of PA, sleep time, and adherence to MD, and high screen time, and WS in adolescents., Impact Statement: The main identified lifestyle behavior was poor physical activity, low adherence to Mediterranean Diet and high screen and sleep time. Children should increase physical activity levels, adherence to Mediterranean diet, decrease screen and sleep the appropriate hours per day. Families, schools, and medical communities must work together to gloss over present and future diseases. Sleep time had not been previously included in cluster analysis with physical activity, sedentary behaviors, obesity, and nutritional status, thus the present data open a new perspective in Spanish population. Health policies should focus on promoting physical activity, Mediterranean diet, adequate sleep and reducing screen time., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The technical and intellectual capabilities of past societies are reflected in the monuments they were able to build. Tracking the provenance of the stones utilised to build prehistoric megalithic monuments, through geological studies, is of utmost interest for interpreting ancient architectures as well as to contribute to their protection. According to the scarce information available, most stones used in European prehistoric megaliths originate from locations near the construction sites, which would have made transport easier. The Menga dolmen (Antequera, Malaga, Spain), listed in UNESCO World Heritage since July 2016, was designed and built with stones weighting up to nearly 150 tons, thus becoming the most colossal stone monument built in its time in Europe (c. 3800-3600 BC). Our study (based on high-resolution geological mapping as well as petrographic and stratigraphic analyses) reveals key geological and archaeological evidence to establish the precise provenance of the massive stones used in the construction of this monument. These stones are mostly calcarenites, a poorly cemented detrital sedimentary rock comparable to those known as 'soft stones' in modern civil engineering. They were quarried from a rocky outcrop located at a distance of approximately 1 km. In this study, it can be inferred the use of soft stone in Menga reveals the human application of new wood and stone technologies enabling the construction of a monument of unprecedented magnitude and complexity., (© 2023. The Author(s).)

Abstract: Osteonecrosis after COVID-19 infection is a complex pathology with multifactorial origin. Factors such as infection itself with associated coagulopathy, as well as genetic mechanisms, and medications used for its treatment such as corticosteroids, may also be involved. The variability in the presentation makes diagnosis difficult, which, if done soon, can help delay progression and reduce morbidity and the need for surgery.This report presents a case of knee osteonecrosis in a female patient who did not have previous knee pathology on imaging tests. She was diagnosed by magnetic resonance imaging months after hospital admission for SARS-CoV-2 pneumonia, which required high-dose corticosteroid treatment., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Canine monocytic ehrlichiosis (CME) is a disease caused by the Gram-negative bacteria Ehrlichia canis, a bacterium that affects domestic dogs but can also infect humans. The diagnosis implies a challenge due to its diversity in clinical manifestations., Methodology: The frequency of E. canis infection, risk factors, and clinical-pathological parameters associated with seropositivity were calculated with the PROC FREQ TABLES and PROC LOGISTIC procedures of the SAS statistical software., Results: The study showed a seroprevalence of 26.62% (156/586). Association between seropositivity and risk factors was found. The age and the presence of ticks including clinical signs such as anorexia, seizures, cough, petechiae, epistaxis, and hematochezia, as well as multiple blood and biochemical alterations were analyzed. The logistic regression analysis showed a high predictive power (c = 0.98) for CME for thrombocytopenia, leukopenia, and anemia., Conclusions: The high prevalence of E. canis in endemic areas makes its diagnosis difficult. Thus, clinical signs must be considered, along with blood and biochemical alterations, as a possible predictor of the disease., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Gerardo Pavel Espino-Solís, Erika Astrid Flores-Lira, Alberto Barreras-Serrano, Issa Carolina García-Reynoso, Antonio de la Mora Covarrubias, Florinda Jiménez Vega, Angélica Escárcega-Ávila.)

Background: Human scalp hair follicles (HFs) engage in olfactory receptor (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® up-regulated HF antimicrobial peptide expression of dermcidin (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands., Objectives: To understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner., Methods: DCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this treatment affected the HF microbiome., Results: Synthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs ex vivo. Combined antibiotic and odorant treatment, during an ex vivo dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured Staphylococcus epidermidis and Malassezia restricta over S. aureus and M. globosa, while exhibiting antimicrobial activity against Cutibacterium acnes. These effects were reversed by co-administration of Phenirat®., Conclusions: We provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases., Competing Interests: Declaration of Competing Interest JE, MBL, MB and RP are employees of Monasterium Laboratory, for which JC and FJ consult. DP and FR are employees of Giuliani S.p.a, which has filed a patent on the technology reported here (WO2019224211A1 and IT102018000005585, June 2020), for which RP consults. All remaining authors have no conflicts of interest to declare., (Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

During the Roman domain of the Iberian Peninsula (from 201 BCE to 460 CE) water management infrastructures were built to satisfy high water demand. However, whether the Roman activities affected the hydrological balance of Iberian wetlands remains unclear. Here, we investigate the paleo-hydrology of Lake Zóñar (southern Iberia) by using the stable isotopes ( 16 O, 17 O, 18 O, 1 H and 2 H) of its gypsum (CaSO 4 ·2H 2 O) sediments and reconstruct the isotopic composition of the lake water during Roman times. A period of recurrent lake low stand occurred between 2120 and 1890 cal. yr BP (ca. 170 BCE to 60 CE), coinciding with a relatively dry climate stage recorded by most regional paleoclimate archives. The stable isotopes and hydrochemistry of the lake water during gypsum precipitation are consistent with a shallow saline lake that evaporated under relative humidity ~ 10% lower than the present annual mean and at least 20% less rainfall amount. Our analytical and archeological findings support lake level lowering during the Roman period was probably caused by combined arid climate conditions and diversion of the inlets feeding the lake. Spring capturing was likely necessary to satisfy the high water demand of nearby Roman settlements, in the framework of a period of persistent droughts., (© 2023. The Author(s).)

The fruits of the native tree Cryptocarya alba Mol. (Lauraceae), known as "peumo" were consumed by the Mapuche Amerindians in Chile both raw and after boiling. The aim of this work was to compare the content of phenolic, procyanidins, antioxidant capacity and inhibition of enzymes related with metabolic syndrome (α-glucosidase, α-amylase and pancreatic lipase) from the phenolic enriched extracts (PEEs) of peumo fruits. Fruits were collected during two years in three different places in central Chile and were investigated raw, boiled, and after separation into cotyledons and peel. The water resulting from the fruit decoction was also analyzed. The composition of the PEE was assessed by HPLC-DAD-MS/MS and the main compounds were quantified by HPLC. The strong inhibitory effect on α-glucosidase, with IC 50 values below 1 µg/mL for several samples, was related, at least in part, to the content of 3-caffeoylquinic acid, 5-caffeoylquinic acid and (-)-epicatechin. The effect of the PEE on pancreatic lipase is of interest and can be partially explained by the (-)-epicatechin content. PCA analyses showed a clear separation of the samples according to the fruit parts and processing. However, no differences by geographic origin were observed. The activity of peumo PEEs on enzymes related to metabolic syndrome and its antioxidant capacity support further studies on the health promoting properties of this native Chilean food plant., 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 Elsevier Ltd. All rights reserved.)

Layered materials that perform mixed electron and ion transport are promising for energy harvesting, water desalination, and bioinspired functionalities. These functionalities depend on the interaction between ionic and electronic charges on the surface of materials. Here we investigate ion transport by an external electric field in an electrolyte solution confined in slit-like channels formed by two surfaces separated by distances that fit only a few water layers. We study different electrolyte solutions containing monovalent, divalent, and trivalent cations, and we consider walls made of non-polarizable surfaces and conductors. We show that considering the surface polarization of the confining surfaces can result in a significant increase in ionic conduction. The ionic conductivity is increased because the conductors' screening of electrostatic interactions enhances ionic correlations, leading to faster collective transport within the slit. While important, the change in water's dielectric constant in confinement is not enough to explain the enhancement of ion transport in polarizable slit-like channels.

Background and Purpose: Mitochondrial dysfunction and inflammation contribute to a myriad of cardiovascular diseases. Deleterious crosstalk of mitochondria and persistent endoplasmic reticulum (ER) stress triggers oxidative stress, which is involved in the development of vascular diseases. This study determined if inhibition of mitochondrial stress reduces aneurysm development in angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE -/- ) mice and its effect on ER stress., Experimental Approach: The mitochondria-targeted tetrapeptide, Szeto-Schiller 31 (SS31), ameliorated mitochondrial dysfunction and the enhanced expression of ER stress markers triggered by Ang II in ApoE -/- mice, and limited plasmatic and vascular reactive oxygen species (ROS) levels. Interestingly, SS31 improved survival, reduced the incidence and severity of abdominal aortic aneurysm (AAA), and the Ang II-induced increase in aortic diameter as evaluated by ultrasonography, resembling the response triggered by the classic ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (PBA)., Key Results: Disorganization of the extracellular matrix, increased expression of metalloproteinases and pro-inflammatory markers and infiltration of immune cells induced by Ang II in the abdominal aorta were effectively reduced by SS31 and ER inhibitors. Further, C/EBP homologous protein (CHOP) deficiency in ApoE -/- mice attenuated Ang II-mediated increase in vascular diameter and incidence of AAA, suggesting its contribution to the favourable response induced by ER stress inhibition., Conclusions and Implications: Our data demonstrate that inhibition of mitochondrial stress by SS31 limits AAA formation and increases survival through a reduction of vascular remodelling, inflammation and ROS, and support that attenuation of ER stress contributes to the favourable response elicited by SS31., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Pseudomonas aeruginosa biofilms are common in chronic wound infections and recalcitrant to treatment. Survival of cells within oxygen-limited regions in these biofilms is enabled by extracellular electron transfer (EET), whereby small redox active molecules act as electron shuttles to access distal oxidants. Here, we report that electrochemically controlling the redox state of these electron shuttles, specifically pyocyanin (PYO), can impact cell survival within anaerobic P. aeruginosa biofilms and can act synergistically with antibiotic treatment. Prior results demonstrated that under anoxic conditions, an electrode poised at sufficiently oxidizing potential (+100 mV vs Ag/AgCl) promotes EET within P. aeruginosa biofilms by re-oxidizing PYO for reuse by the cells. Here, when a reducing potential (-400 mV vs Ag/AgCl) was used to disrupt PYO redox cycling by maintaining PYO in the reduced state, we observed a 100-fold decrease in colony forming units within these biofilms compared with those exposed to electrodes poised at +100 mV vs Ag/AgCl. Phenazine-deficient Δ phz * biofilms were unaffected by the potential applied to the electrode but were re-sensitized by adding PYO. The effect at -400 mV was exacerbated when biofilms were treated with sub-MICs of a range of antibiotics. Most notably, addition of the aminoglycoside gentamicin in a reductive environment almost completely eradicated wild-type biofilms but had no effect on the survival of Δ phz * biofilms in the absence of phenazines. These data suggest that antibiotic treatment combined with the electrochemical disruption of PYO redox cycling, either through the toxicity of accumulated reduced PYO or the disruption of EET, or both, can lead to extensive killing. IMPORTANCE Biofilms provide a protective environment but also present challenges to the cells living within them, such as overcoming nutrient and oxygen diffusion limitations. Pseudomonas aeruginosa overcomes oxygen limitation by secreting soluble redox active phenazines, which act as electron shuttles to distal oxygen. Here, we show that electrochemically blocking the re-oxidation of one of these electron shuttles, pyocyanin, decreases cell survival within biofilms and acts synergistically with gentamicin to kill cells. Our results highlight the importance of the role that the redox cycling of electron shuttles fulfills within P. aeruginosa biofilms., Competing Interests: The authors declare no conflict of interest.