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Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and postharvest regulation), plant responses to environmental signals (endoplasmic-reticulum-associated degradation, chloroplast-associated degradation, drought tolerance, and the growth-defense trade-off), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.

Virtual reality has shown to have great potential as an educational tool when it comes to new learning methods. With the growth and dissemination of this technology, there is a massive opportunity for teachers to add this technology to their methods of teaching a second/foreign language, since students keep showing a growing interest in new technologies. This systematic review of empirical research aims at understanding whether the use of gaming strategies in virtual reality is beneficial for the learning of a second/foreign language or not. Results show that more than half of the articles proved that virtual reality technologies with gaming strategies can be used to learn a foreign language. It was also found that "learning" was the most evaluated dependent variable among the chosen records, augmented reality was the leading technology used, primary education and lower secondary was the most researched school stages, and the most used language to evaluate the use of gamified technology was by far the English language. Given the lack of directed investigation, it is recommended to use these technologies to support second language learning and not entirely replace traditional approaches. A research agenda is also proposed by the authors.

The widespread adoption of metformin as a primary therapeutic agent for type 2 diabetes has prompted inquiries into its potential impact on vitamin B 12 (cobalamin) levels and subsequent deficiency. This study aimed to elucidate this complex relationship and enhance the care provided to patients undergoing metformin treatment. A comprehensive search of meta-analyses , systematic reviews, randomised controlled trials and guidelines published between January 2010 and September 2021 was conducted. MeSH terms 'metformin' and 'vitamin B 12 ,' along with corresponding DeCS terms, guided the search. Varied recommendations from different scientific associations underscore the need for regular monitoring of vitamin B 12 levels in patients undergoing long-term metformin therapy. Different durations of metformin exposure, spanning from 6 weeks to 48 months, were associated with decreased vitamin B 12 concentrations. Observed decreases in B 12 concentrations ranged from 7.7 to 65.8 pmol/L, with percentage reductions ranging from 6.3 % to over 35 %. The evidence highlights a dosage-dependent correlation between higher metformin doses and an increased prevalence of B 12 deficiency. The results obtained highlight the association between metformin and B 12 deficiency. The prevalence of B 12 deficiency under metformin is of a greater magnitude than the one declared on the Summary of Product Characteristics approved by the medicine regulatory agencies. Thus, clinicians should be aware of this possible side effect when prescribing metformin, in order to prevent, monitor and treat if present.

Background/Aim: Metformin has been associated with vitamin B 12 (cobalamin) deficiency, pushing scientific societies such as the American Diabetes Association and the European Association for the Study of Diabetes to emphasise the need for screening B 12 levels, without specific metformin doses or exposure durations triggering this screening. Robust data regarding the prevalence of B 12 deficiency in metformin-treated patients in Portugal are currently lacking. Aim of this study was to identify the prevalence of B 12 deficiency in a sample of diabetic patients taking metformin. Secondary objectives were determining the minimum dose and minimum and median time exposure time leading to this deficiency and identifying the average duration of metformin use in the patients with this deficiency. Methods: Descriptive and cross-sectional observational study was performed on a sample of 79 users from a population of 714 diabetic patients on metformin. Inclusion criteria comprised individuals aged 18 or older, receiving metformin for at least 1 month and voluntarily participating in the study. Exclusion criteria included a history of gastrectomy or B 12 supplementation. Results: A prevalence of 25.3 % of vitamin B 12 deficiency was identified in the study sample. Minimum doses of 500 mg of metformin per day and a minimum exposure period of 1 year were associated with B 12 deficiency. An average exposure time of 5.33 years was identified. Conclusion: These results align with the prevalence described in the few international studies and should alert physicians to potential clinical manifestations of this deficiency, such as anaemia and neurological symptoms like neuropathy.

The sense of presence is an important aspect of virtual reality experiences, being increasingly researched in educational contexts for its potential association with learning outcomes. A panorama of how these investigations have been conducted could help researchers and practitioners to harness this potential and find new directions. A systematic literature review was conducted to contribute to this perspective, with a comprehensive analysis of 140 primary studies recovered from five worldwide databases. The results show an overview of 24 years of research, with a summarization of areas, factors, and methodological approaches that have been the focus of investigation when these three variables of interest (VR, sense of presence, and learning) are together. We conclude with a list of research gaps that need to be addressed and a research agenda, identifying current and emerging challenges. [ABSTRACT FROM AUTHOR]

To compare the effect of an intensity‐controlled exercise program (ICEP) and a nonintensity‐controlled exercise program (non‐ICEP) on the variables responsible for blood pressure regulation in hypertensive older adults. 95 hypertensive older adults (65.40 ± 7.48 years/22 males and 73 females) performed hemodynamic, functional fitness, and biochemical evaluations before and after 12 weeks of the multicomponent exercises which included walking, muscle strength, hydrogymnastics, Pilates, dynamic balance, agility, flexibility, and others. A significant improvement was observed in general functional fitness index (GFFI: p ≤ 0.000, d = 0.35), nitrite (NO2−: p ≤ 0.000, d = 0.49), systolic blood pressure (SBP: p ≤ 0.000, d = 0.65), diastolic blood pressure (DBP: p ≤ 0.013, d = 0.40), thiobarbituric acid reactive substances (TBARS: p ≤ 0.007, d = 0.78), activity of the endothelial superoxide dismutase enzyme (ecSOD: p ≤ 0.032, d = 0.41), double product (DP: p ≤ 0.015, d = 0.43), and waist‐hip ratio (WHR: p ≤ 0.000, d = 0.44) for ICEP. Only GFFI (p ≤ 0.047, d = 0.12), TBARS (p ≤ 0.000, d = 0.77), SOD (p ≤ 0.025, d = 0.25), DP (p ≤ 0.046, d = 0.26), and BMI (p ≤ 0.018, d = 0.02) presented better results in non‐ICEP. When the effect of the groups (controlled by age, BMI, and sex) was evaluated, an increase was observed in the NO2−, TBARS, and SOD and a reduction in the SBP and WHR variables in the ICEP group compared to the non‐ICEP group. Twelve weeks of engagement in a controlled‐intensity exercise program was enough to improve the level of functional fitness and variables regarding blood pressure regulation in hypertensive older adults. Conversely, physical exercise performed without intensity control was related to the limited effect on such variables. [ABSTRACT FROM AUTHOR]

This article provides an overview of the potential impact of metformin, a medication commonly used for type 2 diabetes, on vitamin B12 levels and deficiency. The authors conducted a comprehensive review of various studies and guidelines published between 2010 and 2021. The evidence suggests that long-term use of metformin is associated with decreased vitamin B12 concentrations, and higher doses of metformin may increase the risk of B12 deficiency. The authors recommend regular monitoring of vitamin B12 levels in patients taking metformin to prevent and treat deficiency. The article also discusses the prevalence of B12 deficiency in patients on metformin therapy and highlights the importance of managing this side effect to improve patients' quality of life. The document includes a list of references that can be helpful for library patrons researching the effects of metformin on vitamin B12 levels and related health conditions. [Extracted from the article]

Objective: Recently, there has been a growing interest in operationalizing and measuring cognitive reserve (CR) for clinical and research purposes. This umbrella review aims to summarize the existing systematic and meta-analytic reviews about measures of CR. Method: A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the guidelines of Aromataris et al. (2015) to identify the systematic reviews and meta-analysis involving the assessment of CR. The methodological quality of the papers included in this umbrella review was assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) and Specialist Unit for Review Evidence (SURE). Results: Thirty-one reviews were identified, sixteen of which were systematic reviews, and fifteen were meta-analyses. Most of the reviews had a critically low quality, according to AMSTAR-2. The reviews included between two and 135 studies. Most of the papers focused on older adults, mainly those with dementia. CR was measured using one to six proxies, but most considered each proxy separately. The most assessed proxies of CR were education on its own, combined with occupation and/or engagement in activities or combined with parental education, bilingualism, and engagement in activities when four CR proxies were studied. Most of the studies included in higher quality reviews focused on three proxies, with education and engagement in activities being the most evaluated using CR questionnaires. Conclusion: Despite the growing interest in measuring CR, its operationalization did not improve since the last umbrella review in this field. [ABSTRACT FROM AUTHOR]