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Prolonged high-fat diets have been shown to affect an organism's stress responsiveness at the neuroendocrine level. In the present study, the authors used a 7-day protocol of fat administration in adult rats of both sexes to investigate the early behavioral impact of a moderately fat (20%) diet, often used by Western societies, on rats' reaction to acute stress and novelty. Their results show that this diet can reduce the rats' active behavioral responses to subsequent stressors and influence their corticosterone secretion. Fat-fed male rats adopted a less active behavior to cope with forced swimming stress, whereas their exploratory behavior in the open field environment was rather increased compared with chow-fed males. Fat-fed female rats exhibited a less active behavioral response to both stress paradigms compared with their chow-fed counterparts. Fat diet abolished facilitation in corticosterone secretion following a subsequent stressor in both sexes. However, only in males did fat diet exaggerate corticosterone response to novelty, irrespective of the previous stress history of the rat. These data indicate that a short-term metabolic stress can modify the rats' stress coping strategy in interaction with the gender.

We would like to thank Chen et al. for their comments on our recently published paper in Ageing Research Reviews (Veronese et al., 2021). In this reply we would like to answer to the points raised in their letter. Regarding the first question, we decided to run our search only in PubMed/Medline and ClinicalTrials.gov since the phase II-III randomized controlled trials of SARS-CoV 2 vaccines, considering the urgency for interventions to ameliorate the pandemic situation, received a great deal of interest. Therefore, they were usually published in high impact factor journals, reported in PubMed, and their protocols were usually reported in clinicaltrials.gov. However, following the suggestion of Chen et al., we did run a similar search in Web of Science (n = 150 articles) and Embase (n = 121 articles), without finding any possible eligible paper. We also searched, as suggested, the WHO ICTRP registry, which includes also the Chinese clinical trial registry, finding 36 ongoing trials, with two eligible out of them (https://trialsearch.who.int/Trial2.aspx? TrialID=ISRCTN79815558; https://trialsearch.who.int/Trial2.aspx? TrialID=RPCEC00000354). However, since both trials are still undergoing, it is not possible to know which percentage of older people will be eventually enrolled, therefore there is no need to modify what was already reported in our systematic review. With regard to the concern related to the language limitation, it should be pointed out that, among the completed trials, four out of ten were performed in China, but still they were published in an English language journal (Xia et al., 2020, 2021; Zhang et al., 2021; Zhu et al., 2020). Furthermore, we added the keywords suggested in the second point of the comments to our article: in this case, limiting the search to the 01st May 2021 as done in our systematic review, we found 547 possible eligible papers, but again, no new work was eligible for our analyses. Even if we recognize that adding these specific keywords might increase sensitivity of the search, they are probably of poor specificity in finding out papers that did not use randomized clinical trial as filter, particularly considering that practically all the papers reporting phase II-III trials on vaccination were published in widely known scientific journals. We also appreciate the comments regarding risk of bias and assessment of the quality of the study, which are a mandatory step in a systematic review. However, we would like to point out that the aim of our systematic review was not to investigate the efficacy/safety of COVID-19 vaccination in older people, but to highlight that older people were usually excluded from these studies. Therefore, this evaluation was not necessary, as we did not want to evaluate the quality of the results provided by the studies, but we aimed only at verifying the inclusion of older people. Finally, we are also grateful for the comments regarding the registration of the protocol and the statistical analysis. Regarding the first point, we agree that pre-publishing the protocol is an essential step in publishing a paper, but at the same time we also believe that the protocol structure is so simple in this case (we practically only extracted data regarding age range, asking to the corresponding authors further information when needed) that pre-publishing of the protocol would have not changed anything in the final results. However, we enclose to this letter as supplementary material the protocol. Moreover, the statistical analyses were so elementary that creating a specific paragraph would not represent an added value and we believe that keeping them in the outcomes section is enough for providing the necessary information to the readers to completely understand our work. In conclusion, we would like to thank Chen et al. for their comments that allowed us to confirm the methodological strengths of our paper. Indeed, as reported in this reply, addressing the points raised did not significantly change our results indicating that our work, even if simple, is correct and the conclusions are sound.

During the COVID-19 pandemic older subjects have been disproportionately affected by the disease. Vaccination is a fundamental intervention to prevent the negative consequences of COVID-19, but it is not known if the needs and vulnerabilities of older people are adequately addressed by their inclusion in randomized clinical trials (RCTs) evaluating the efficacy of vaccines for COVID-19. Given this background, we aimed to evaluate if current and ongoing phase II-III RCTs evaluating the efficacy of COVID-19 vaccines included a representative sample of older people. A systematic literature search in PubMed and Clinicaltrials.gov was performed until May 01st, 2021. Among 474 abstracts initially retrieved, 20 RCTs (ten already published, ten ongoing) were included. In the ten studies already published, the mean age of participants was 45.2 ± 11.9 years and only 9.83% of the participants were more than 65 years, 1.66% more than 75 years and less than 1% (0.55%) more than 85 years. In the ten ongoing RCTs, many of the studies aimed at including participants older than 18 years, with one study including participants between 18 and 84 years, and two between 21 and 100 years. In conclusion, our systematic review demonstrates that in published and ongoing phase II-III randomized clinical trials evaluating the efficacy of COVID-19 vaccines only a tiny fraction of the most vulnerable group of older people was included, although they clearly were the first population that had to be vaccinated. © 2021 Elsevier B.V.

OBJECTIVE: Advanced glycation end-products (AGEs) and pulse wave velocity (PWV) are pivotal indices of the processes of arterial ageing and damage accumulation. The aim of the present study was to investigate the impact of AGEs, as measured by a non-invasive skin autofluorescence method, on arterial stiffness, estimated by PWV, in two different age groups of non-diabetic subjects. METHODS AND PATIENTS: A total of 116 non-diabetic subjects were classified into two groups, with 55 subjects in the group aged