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Physical exercise is a robust lifestyle intervention known for its enhancement of cognitive abilities. Nevertheless, the extent to which these benefits can be transmitted across generations (intergenerational inheritance to F1, and transgenerational to F2 and beyond) remains a topic of limited comprehension. We have already shown that cognitive improvements resulting from physical exercise can be inherited from parents to their offspring, proving intergenerational effects. So, we set out to explore whether these enhancements might extend transgenerationally, impacting the F2 generation. In this study, we initially examined the behavioral traits of second generation (F2) male mice, whose grandfathers (F0) had an exercise intervention. Our findings revealed that F2 mice with physically active grandpaternal F0 progenitors displayed significantly improved memory recall, encompassing both spatial and non-spatial information when compared to their counterparts from sedentary F0 progenitors, and proving for the first time the transgenerational inheritance of physical exercise induced cognitive enhancement. Surprisingly, while F2 memory improved (as was the case with F1), adult hippocampal neurogenesis remained unchanged between experimental and control groups (unlike in F1). Additionally, our analysis of small RNA sequences in the hippocampus identified 35 differentially expressed miRNAs linked to important brain function categories. Notably, two of these miRNAs, miRNA-144 and miRNA-298, displayed a robust negative correlation with cognitive performance. These findings highlight the enduring transgenerational transmission of cognitive benefits associated with exercise, even after two generations, suggesting that moderate exercise training can have lasting positive effects, possibly orchestrated by a specific set of miRNAs that exert their influence across multiple generations., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The fruits of Arbutus unedo L. have a crimson colour and are enriched with remarkable concentrations of bioactive compounds such as anthocyanins and polyphenols. These fruits are commonly used in the production of a Portuguese Protected Geographical Indication distillate called "Aguardente de Medronho". During this process, a solid pomace is generated and presently discarded without valuable applications. In this work, two strategies have been developed for the valorisation of A. unedo pomace. The first approach considers the extraction of polyphenols from this by-product through the optimization of an ultrasound-assisted method using a Box-Behnken design coupled with response surface methodology. The results indicate that the temperature and the percentage of methanol, along with their interaction, significantly influence the total concentration of polyphenols and the antioxidant activity of the extracts obtained. The optimal conditions identified consider the extraction of 0.5 g of sample with 20 mL of a solvent containing 74% MeOH (aq), at a pH of 4.8, maintained at 70 °C for 15 min. On the other hand, the second valorisation strategy considered the use of A. unedo pomace in the development of functional cookies. The incorporation of 15-20% pomace in the cookie formulation was well-received by consumers. This incorporation results in an intake of ca. 6.55 mg of polyphenols per gram of cookie consumed, accompanied by an antioxidant activity of 4.54 mg Trolox equivalents per gram of cookie consumed. Overall, these results encourage the employment of A. unedo pomace either as a reliable source of extracts enriched in polyphenols or as a nutraceutical active ingredient in functional cookies, thereby positively impacting human health.

Background: The search for alternatives to sulfur dioxide (SO 2 ) in white wine production is a tough challenge for the oenological industry. The current article investigates the effectiveness of several preservatives in protecting Verdejo white wines. The following wines were elaborated: without preservative (CT wines), with SO 2 (SO 2 wines), with stilbene-enriched extract (ST99 wines), with glutathione (GSH wines) and finally with the combination stilbene extract plus glutathione (ST99-GSH wines)., Results: ST99 extract preserved the wines from malolactic fermentation (MLF), maintained the quality parameters of the wines, but affected their color from the beginning of the process. Synergistic effects between ST99 and GSH were found for oxygen consumption rates, related to oxidation processes. The content of amino acids and biogenic amines was slightly affected by the treatments, but the quality or safety of the wines was not compromised. However, after 12 months of ageing in bottle, the SO 2 wines showed the highest score in the sensory analysis. The reasons for the evolution of treated wines and the implications of this study for maintaining the quality of free SO 2 white wines are discussed., Conclusion: ST99 may be proposed as an alternative to SO 2 in wines to be consumed in the short term. Its combination with GSH does not prolong its shelf-life. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Controlled inoculations of non- Saccharomyces yeasts are becoming increasingly used to produce high-quality wines due to their enological potential. In this study, we evaluated the impact of sequential inoculation with the commercial non- Saccharomyces yeasts ( Torulaspora delbrueckii and Metschnikowia pulcherrima ) in combination with Saccharomyces cerevisiae on the chemical and sensory profile of rosé wines. Sequential inoculation with T. delbrueckii produced wines with an overall reduction in esters, mainly explained by the lower concentrations of ethyl esters of medium-chain fatty acids and isoamyl acetate. The lower ester concentrations of these wines were related to a reduction in fruity descriptors. An increase was observed, however, in other minor esters such as cinnamates and ethyl esters of branched acids. Zinc, ethyl isobutyrate, and ethyl dihydrocinnamate were selected as potential markers for this fermentation strategy. Sequential inoculation with M. pulcherrima resulted in rosé wines with an enhanced ester profile, reduced acetaldehyde, and increased anthocyans and tannins. Compared to the control wines fermented with S. cerevisiae , the changes observed in these wines were far subtler, especially for the volatile profile, sensory characteristics, and color parameters, with isobutyl hexanoate and isoamyl butyrate being selected as potential markers.

Background: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer's disease (AD) might predispose to cognitive deterioration after surgery., Objective: To analyze the effect of amyloid-β on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects., Methods: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers., Results: Cumulative incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-β was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A+) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A + group showed a notable worsening on memory performance., Conclusion: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-β deposits.

The simple protocol described in this article aims to provide all required information, as a comprehensive, easy-to-follow step-by-step method, to ensure the generation of the expected genome-edited mice. Here, we provide protocols for the preparation of CRISPR-Cas9 reagents for microinjection and electroporation into one-cell mouse embryos to create knockout or knock-in mouse models, and for genotyping the resulting offspring with the latest innovative next-generation sequencing methods. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Designing the best RNA guide for your gene disruption/editing strategy Basic Protocol 2: Preparing and validating CRISPR-Cas9 reagents Basic Protocol 3: Preparing and injecting CRISPR-Cas9 compounds into fertilized mouse oocytes Basic Protocol 4: Genotyping genome-edited mice Support Protocol: Genotyping for CRISPR-generated "indel" mutations., (© 2020 John Wiley & Sons, Inc.)

Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide and the fourth cause of cancer-related death. From Vogelstein's initial model, new molecular knowledge has been incorporated which includes an elevated number of genetic mutations, many of them located in the Wnt pathway, which affect its principle effector: β-catenin. Additionally, it is necessary to keep the heterogeneity of CRCs in mind, both in terms of morphology and biology. The aim of this work is to study the interaction between the Wnt molecular pathway, by means of immunoexpression of β-catenin, in CRC and other molecular mechanisms, such as the p53 pathway, in order to determine the pattern - if one exists - of different immunohistochemical expression of β-catenin and p53 in the superficial and deep tumor components, and lastly, to determine the impact of these markers on prognosis. Our cases showed an increasing gradient of β-catenin immunoexpression that parallels depth in the tumor, with a greater degree of nuclear immunoexpression in the deep compartment. We observe that in those cases with positivity for nuclear p53 and an absence of immunostaining of β-catenin show higher rates of survival, whereas one of the lowest rates was observed in patients who co-expressed p53 and β-catenin. We conclude that a combined analysis of β-catenin and p53 could have prognostic importance as markers for predicting the disease's progression and contribute to the identification of patients with a high risk of mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This paper examines health care expenditure (HCE) disparities between the European Union countries over the period 1995-2010. By means of using a continuous version of the distribution dynamics approach, the key conclusions are that the reduction in disparities is very weak and, therefore, persistence is the main characteristic of the HCE distribution. In view of these findings, a preliminary attempt is made to add some insights into potentially main factors behind the HCE distribution. The results indicate that whereas per capita income is by far the main determinant, the dependency ratio and female labour participation do not play any role in explaining the HCE distribution; as for the rest of the factors studied (life expectancy, infant mortality, R&D expenditure and public HCE expenditure share), we find that their role falls somewhat in between.