SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from ...colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE‐1) and high (PE‐2) punicalagin:EA ratio were administered. Twenty‐three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC‐ESI‐QTOF‐MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE‐1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE‐2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE‐2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
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The therapeutic landscape for spinal muscular atrophy has changed in the last few years, encompassing respiratory/motor function and life expectancy benefits. However, physicians still have the ...challenge of tailoring individuals' treatment to therapeutic goals, disease progression, patient/caregiver's preferences, and personal experience to achieve an optimal risk/benefit balance. This study aims to provide insight into the preferred treatment choices of pediatric neurologists managing spinal muscular atrophy in their daily practice and to recognize behavioral factors that may influence decision-making.
This is a noninterventional, cross-sectional pilot study involving 50 pediatric neurologists managing spinal muscular atrophy in Spain. We designed an online platform that contains 13 simulated case scenarios of common presentations of patients with spinal muscular atrophy. The primary study outcome will be treatment preferences according to the percentages of participants who select treatment initiation when recommended, switch therapies when there is evidence of disease progression, and select treatment discontinuation when disease progression puts patients outside treatment recommendation (11 case scenarios). Secondary outcomes include therapeutic inertia prevalence (11 case scenarios), herding phenomenon prevalence (2 case scenarios), care-related regret prevalence (specific questions) and intensity (10-item Regret Intensity Scale), occupational burnout prevalence (nonproprietary single-item measure), and risk preferences (uncertainty test and risk aversion assessment).
The study findings will contribute to better understand relevant factors associated with therapeutic decisions of pediatric neurologists in spinal muscular atrophy, identifying treatment preferences and evaluating the role of behavioral aspects such as therapeutic inertia, herding, regret, and workplace burnout.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of ...polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5–35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We show that pure Ricardian trade can account for the empirical evidence that domestic growth is more affected by foreign growth than by trade openness. To do this, we develop a two‐country model ...involving a backward economy that exchanges intermediate goods with a faster growing country. We obtain three main results regarding growth and welfare of the backward economy: (i) the growth‐enhancing comparative advantage is facilitated by faster foreign growth; (ii) the growth rate may be negatively affected or unaffected by a domestic tariff, while it is always positively impacted by foreign growth; and (iii) a domestic tariff could be welfare‐improving.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, ODKLJ, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Promover la interacción del alumnado en las aulas universitarias es una preocupación frecuente del profesorado que precisa de más investigación. El objetivo de este artículo es identificar buenas ...prácticas que ayuden a fomentar la interacción en el aula. Para ello se realizó un estudio observacional en 90 clases de diferentes docentes de todas las áreas del conocimiento. Se identificaron 17 buenas prácticas, versátiles en cuanto a duración, tamaño del grupo y campo de aplicación, y se clasificaron en cuatro categorías. Todas las prácticas identificadas pueden ser inspiradoras para que el profesorado fomente la interacción en los diferentes campos del conocimiento de la docencia universitaria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We studied potential changes in the sub‐ventricular zone (SVZ) stem cell niche of the senescence‐accelerated mouse prone‐8 (SAM‐P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival ...revealed a lower number of label‐retaining stem cells in the SAM‐P8 SVZ compared with the SAM‐Resistant 1 (SAM‐R1) control strain. We also found that in SAM‐P8 niche signaling is attenuated and the stem cell pool is less responsive to the self‐renewal niche factor pigmented epithelium‐derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM‐P8 SVZ niche; however, SAM‐P8 stem cells present a significant expression decrease of patatin‐like phospholipase domain containing 2, a receptor for PEDF (PNPLA2‐PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR‐PEDF) receptor. We observed changes in self‐renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2 and report that although these genes are down‐regulated in SAM‐P8, differentiation genes (Pax6) are up‐regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down‐regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM‐P8 at young age periods. Differences between these 2 models, SAM‐P8 and SAM‐R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self‐renewal at a very young age, which could be involved in the premature senescence observed in the SAM‐P8 model.—Castro‐Garcia, P., Díaz‐Moreno, M., Gil‐Gas, C., Fernández‐Gómez, F. J., Honrubia‐Gómez, P., Álvarez‐Simón, C. B., Sánchez‐Sánchez, F., Cano. J. C. C., Almeida, F., Blanco. V., Jordán, J. Mira, H., Ramírez‐Castillejo, C. Defects in sub‐ventricular zone pigmented epithelium‐derived factor niche signaling in the senescence‐accelerated mouse prone‐8. FASEB J. 29, 1480‐1492 (2015). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Sperm capacitation involves biochemical and physiological changes that enable sperm to fertilize the oocyte. It can be induced in vitro under controlled conditions that simulate the environment of ...the oviduct. While extensively studied in mammals, its approach in lizards remains absent. Understanding the mechanisms that ensure reproduction is essential for advancing the implementation of assisted reproductive technologies in this group. We aimed to perform a sperm analysis to determine if capacitation-related changes were induced after incubation with capacitating media. Fifteen males of
were collected during the early stage of the reproductive season. The sperm were isolated from the seminal plasma and then diluted up to a volume of 150 μL using BWW medium to incubate with 5% CO
at 30 °C for a maximum duration of 3 h. A fraction was retrieved hourly for ongoing sperm assessment. The sperm analysis included assessments of its motility, viability, the capacitation status using the chlortetracycline (CTC) assay, and the acrosome integrity with the lectin binding assay to detect changes during incubation. We found that total motility was maintained up to 2 h post incubation, after which it decreased. However, sperm viability remained constant. From that moment on, we observed a transition to a deeper and less symmetrical flagellar bending in many spermatozoa. The CTC assay indicated a reduction in the percentage of sperm showing the full (F) pattern and an increase in those exhibiting the capacitated (B) and reactive (RA) patterns, accompanied by an elevation in the percentage of damaged acrosomes as revealed by the lectin binding assay. In mammals, these changes are often associated with sperm capacitation. Our observations support the notion that this process may also occur in saurian. While sperm analysis is a valuable method for assessing certain functional changes, additional approaches are required to validate this process.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Epidemiology supports the important role of nutrition in prostate cancer (PCa) prevention. Pomegranate juice (PJ) exerts protective effects against PCa, mainly attributed to PJ ellagitannins (ETs). ...Our aim was to assess whether ETs or their metabolites ellagic acid and urolithins reach the human prostate upon consumption of ET-rich foods and to evaluate the effect on the expression of three proliferation biomarkers. Sixty-three patients with BPH or PCa were divided into controls and consumers of walnuts (35 g walnuts/day) or pomegranate (200 mL PJ/day) for 3 days before surgery. Independently of the ETs source, the main metabolite detected was urolithin A glucuronide, (3,8-dihydroxy-6H-dibenzob,dpyran-6-one glucuronide) (up to 2 ng/g) together with the traces of urolithin B glucuronide, (3-hydroxy-6H-dibenzob,dpyran-6-one glucuronide) and dimethyl ellagic acid. The small number of prostates containing metabolites was likely caused by clearance of the compounds during the fasting. This was corroborated in a parallel rat study and thus the presence of higher quantities of metabolites at earlier time points cannot be discarded. No apparent changes in the expression of CDKN1A, MKi-67 or c-Myc were found after consumption of the walnuts or PJ. Our results suggest that urolithin glucuronides and dimethyl ellagic acid may be the molecules responsible for the beneficial effects of PJ against PCa.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Attitudes play a central role in intimate partner violence against women and are related to its origin, to the responses of women who suffer violence, and to the settings where it occurs. In fact, ...these attitudes are recognized as one of the risk factors linked to violent perpetration and to public, professional, and victim responses to this type of violence. However, even though available research generally shows a broad rejection of this violence, it remains a serious social and health problem that has reached epidemic proportions. This suggests that the information available about these attitudes (obtained through explicit and direct measures, i.e., self-reports) may be distorted or influenced by factors such as social desirability. In this context, the overall objective of our research project is to provide multi-method measures (explicit and implicit) of attitudes toward intimate partner violence against women, and the main goal of this paper is to propose an instrument for the implicit measurement of these attitudes. In this regard, the Implicit Association Test (IAT) is the most common procedure used, providing a superior predictive validity compared to explicit measures for socially sensitive topics. We will present an exploratory study that describes its adaptation for our purposes, and the development of the Gender Violence - Implicit Association Test (GV-IAT) to use among Spanish-speaking populations, and discuss the strengths and limitations of this proposal.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Some attitudes serve to justify violence against women, to blame women for the violence they experience, and to perpetuate levels of this violence. These attitudes often stem from traditional norms ...and beliefs which are important to identify. The purpose of this study is to compare beliefs about intimate partner violence against women (IPVAW) between two time points, examining the effect of the respondents- sex and previous academic-training.
Two opportunity samples of undergraduates took part in this study: 1,392 in 2006 (34.4% men and 65.6% women) and 730 in 2018 (36.3% men and 63.7% women). A four-factor model from the Inventory of Distorted Thoughts on Women and Violence (IPDMV) was used after assessing fit through CFA.
Significant differences between 2006 and 2018 in all factors were found using MANCOVA (covariable: age). Differences were also found by sex and previous academic-training, and effects of interaction in the first factor between these variables and the time point.
The beliefs and distorted thoughts about women and violence fell between the two time points analysed, with less acceptance of these beliefs among women and people with prior IPVAW academic-training.
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