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Down syndrome (DS) is a segmental progeroid genetic disorder associated with multi-systemic precocious aging phenotypes, which are particularly evident in the immune and nervous systems. Accordingly, people with DS show an increased biological age as measured by epigenetic clocks. The Ts65Dn trisomic mouse, which harbors extra-numerary copies of chromosome 21 (Hsa21)-syntenic regions, was shown to recapitulate several progeroid features of DS, but no biomarkers of age have been applied to it so far. In this pilot study, we used a mouse-specific epigenetic clock to measure the epigenetic age of hippocampi from Ts65Dn and euploid mice at 20 weeks. Ts65Dn mice showed an increased epigenetic age in comparison with controls, and the observed changes in DNA methylation partially recapitulated those observed in hippocampi from people with DS. Collectively, our results support the use of the Ts65Dn model to decipher the molecular mechanisms underlying the progeroid DS phenotypes., 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 Ravaioli, Stagni, Guidi, Pirazzini, Garagnani, Silvani, Zoccoli, Bartesaghi and Bacalini.)

Drivers must respond promptly to a wide range of possible road hazards, from trucks veering into their lane to pedestrians stepping onto the road. While drivers' vision is tested at the point of licensure, visual function can degrade, and drivers may not notice how these changes impact their ability to notice and respond to events in the world in a timely fashion. To safely examine the potential consequences of visual degradation on hazard detection, we performed two experiments examining the impact of simulated optical blur on participants' viewing duration thresholds in a hazard detection task, as a proxy for eyes-on-road duration behind the wheel. Examining this question with older and younger participants, across two experiments, we found an overall increase in viewing duration thresholds under blurred conditions, such that younger and older adults were similarly impacted by blur. Critically, in both groups, we found that the increment in thresholds produced by blur was larger for non-vehicular road hazards (pedestrians, cyclists and animals) compared to vehicular road hazards (cars, trucks and buses). This work suggests that blur poses a particular problem for drivers detecting non-vehicular road users, a population considerably more vulnerable in a collision than vehicular road users. These results also highlight the importance of taking into account the type of hazard when considering the impacts of blur on road hazard detection., (© 2024. The Author(s).)

Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman's needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.

The predatory mites of the Phytoseiidae family are crucial biological control agents widely utilized in biological pest management targeting phytophagous mites and insects. Key factors in these control strategies are that phytoseiids must be able to find their main target prey and to maintain high populations and efficacy. To reduce expenses and time-consuming production methods of mass rearing of phytoseiids, pollen and other factitious (i.e., non-natural/nontarget) hosts need to be present as an alternative food for predatory mite populations. The mass-rearing possibilities of these predators on alternative food sources, such as astigmatid mites (i.e., house and stored mites) and pollen, must be evaluated not only by the cost of rearing settings but on the basis of their efficiency maintenance in killing prey. The pest kill rate (km) is the average daily lifetime killing of the pest by the natural enemy under consideration and can represent a useful indicator for phytoseiids efficacy to rank them as BCAs on the basis of their effective killing/predation on target prey. In this study, we evidenced that 2 astigmatid mites, Glycyphagus domesticus (De Geer) and Lepidoglyphus destructor (Schrank), and Quercus ilex L. pollen can be successfully adopted as substitute food sources for mass rearing of the phytoseiid Neoseiulus californicus (MgGregor); then, we determined that these populations of BCAs maintained a consistent km at new/first impact on the main target pest, Tetranychus urticae Koch., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

One of the challenges in substituting dairy products by alternative proteins is that the properties of mixed protein gels cannot necessarily be predicted by those of single protein gels, whereas the need of mixing is often driven by nutritional aspects. However, mixing plant proteins could also open a door to new textures. The main goal of this study was to investigate the impact of binary mixing of hemp (H), yellow pea (P), and brown lentil (L) protein concentrates/isolates on their gel and water-holding properties. Dispersions of reconstituted proteins and mixtures thereof were gelled using glucono-δ-lactone (GDL), transglutaminase (TG), and temperature (T) at a protein content of 12% (w/w). Mixtures of pea and lentil proteins showed gel strengths for TG- and T-induced gels that are proportional to the ratio of the mixture constituents (linear mixing behavior), whereas synergistic effects were observed for GDL-induced gelation. In contrast, all mixtures containing hemp exhibited a non-linear mixing behavior for the three gelation methods, usually resulting in lower gel strengths compared to theoretically expected values. The study showed that mixing plant-based proteins of different protein sources can lead to very different mixing behaviors in terms of gel properties, showing either a reinforcing, an indifferent or a weakening effect compared to the theoretically expected properties. The results can help developing more targeted plant protein-based soft gel products such as yogurt alternatives with specific techno-functional properties, while adjusting the nutritional characteristics., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research has usually considered cyberbullying as a unitary phenomenon. Thus, it has been neglected to explore whether the specific online aggressive behaviours relate differentially to demographic features of the perpetrators of online aggressive actions, their personality characteristics, or to the ways in which they interact with the Internet. To bridge this gap, a study was conducted through a questionnaire administered online to 1228 Italian high-school students (Female: 61.1%; 14-15 yo: 48.%; 16-17 yo: 29.1%; 18-20 yo: 20.4%, 21-25 yo: 1.6%; Northern Italy: 4.1%; Central Italy: 59.2%; Southern Italy: 36.4%). The questionnaire, in addition to items about the use of social media, mechanisms of Moral Disengagement and personality characteristics of the participants in the study, also included a scale for the measurement of cyberbullying through the reference to six aggressive behaviours. The results indicate that cyberbullying can be considered as a non-unitary phenomenon in which the different aggressive behaviours can be related to different individual characteristics such as gender, personality traits and the different ways of interacting with social media. Moreover, the existence of two components of cyberbullying has been highlighted, one related to virtual offensive actions directly aimed at a victim, the other to indirect actions, more likely conducted involving bystanders. These findings open important perspectives for understanding, preventing, and mitigating cyberbullying among adolescents., Competing Interests: The authors have declared that no competing interests exist.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Multi-drug resistant organisms (MDRO) are an emerging health problem with an important impact on clinical outcome in Intensive Care Units (ICUs) and immunocompromised patients. Conversely, the role of MDRO colonization in Internal Medicine is less clear. The objective of our study is to evaluate the clinical impact (namely sepsis development, in-hospital and 30-days mortality, and re-hospitalization) of MDRO colonization in Internal Medicine. Methods : Patients admitted to our Internal Medicine Unit between January 2019 and March 2020 were potentially includible. Outcomes in patients with a positive rectal swab for MDRO (RS+) and in patients without a RS+ were compared. Results of the multivariate analyses were expressed as Odds Ratios (ORs) and the corresponding 95% Confidence Interval (CI). Results : In a cohort of 2147 patients, 77 patients with RS+ were consecutively identified; 377 patients with a rectal swab negative for MDRO were randomly selected from the same cohort (five for each patient with RS+). At the multivariate analysis, RS+ was associated with an increased risk of sepsis development during hospitalization (OR 4.18; 95% CI, 1.99-8.78) and with death or re-hospitalization at 30 days (OR 4.79; 95% CI, 2.79-8.23), whereas RS+ did not appear to be associated with death during hospitalization or need for ICU transfer. Conclusions: Our results suggest for the first time a prognostic role for RS+ in Internal Medicine. Thus, assessment of rectal swab at hospital admission appears useful even in this setting. However, larger prospective studies and a cost-benefit analysis are needed to confirm our preliminary findings.

This paper presents an experiment in which participants had to discriminate three mid-air haptic shapes (circle, square, point) by reporting whether the haptic stimulus (e.g. circle on the palm of the hand) was compatible with an image (e.g. a circle) or a word (e.g. 'circle') displayed on a screen. Results indicate that only the 'point' stimulus was appreciably recognised and discriminated in terms of accuracy and time needed for the identification. Accuracy increased with repetition, and response time decreased, suggesting a learning effect. The comparison between visual and textual labels shows that for the haptic point stimulus there is no significant difference but a tendency to have greater accuracy with images than with texts, while the opposite result is found for the circle stimulus. This outcome suggests the need for new experiments focussed of the effect of visual/textual labels to make the recognition/discrimination tasks of haptic stimuli easier. Practitioner Summary: Three haptic shapes were presented with images or texts, matching or not the stimuli. The point was easy to recognise, while the circle and the square were difficult to discriminate against each other. Visual/textual labels bring contradictory results for different shapes. Abbreviations: 1D: one-dimensional; 2D: two-dimensional; 3D: three-dimensional; API: application programming interface; cm: centimeter; GLMM: generalised linear mixed-effect model; HCI: human-computer interaction; Hz: hertz; LMM: linear mixed-effect model; MCC: Matthews' correlation coefficient; mm: millimeter; ms: millisecond; QQ-plot: Quantile-Quantile plot; SD: standard deviation.

With the spread of the pandemic and the introduction of measures aimed at its containment, it is necessary to understand in specific national contexts how home quarantine has affected the psychophysical well-being of academics, and their ability to maintain integrity. To this end we constructed an online questionnaire to investigate the levels of stress, well-being, and work-life balance in relationship with living and working conditions. Moreover, the questionnaire was designed to obtain information about the perceived occurrence, increase or decrease of misconduct in research (e.g., research misconduct by colleagues) and professional relationships (e.g., misbehaviors between colleagues, from students and toward students). The questionnaire was administered online by contacting faculty at three universities in Tuscany, Italy, asking them to relate their experience during the first lockdown (March-May 2020). Faculty members were invited to complete the questionnaire by their institutional e-mail account. The final sample consisted of 581 respondents. The results showed that inadequacies of the equipment, and particularly poor internet connection, were significantly correlated with main issues reported, such as relationships with students and research activities. Female teachers primarily suffered from stressful conditions, lacked well-being, and experienced work-life imbalance. Stress levels were related to perceptions of the frequency of misconduct and of an increase in their frequency during the period of home quarantine. Female professors, when compared to their male counterparts, perceived misconduct from students as increased and more frequent in the period of quarantine. Results point to a gender issue that is likely to arise from conditions of domestic activities imbalance and that increases stress and misconduct perception., (© 2022. The Author(s).)

Flavonoids have long been known to exert benefits in various health problems. Among them, the BDNF mimetic 7,8-Dihydroxyflavone (7,8-DHF) is emerging as a potential treatment for a constellation of brain and body pathologies. During the past 10 years, more than 180 preclinical studies have explored the efficacy of 7,8-DHF in animal models of different pathologies. The current review intends to be an exhaustive survey of these studies. By providing detailed information on the rationale of the experimental design and outcome of treatment, we will give the reader tools to critically interpret the achievement obtained so far. If we put together each individual piece of this complex mosaic, a picture emerges that is full of promise regarding the potential usefulness of 7,8-DHF for human treatment. Much has been done so far and we believe that the time is now ripe to move from the bench to the bedside, in order to establish whether supplementation with 7,8-DHF may serve as therapy or, at least, as adjuvant for the treatment of pathologies affecting brain and body functioning.

Down syndrome (DS), which is due to triplication of chromosome 21, is constantly associated with intellectual disability (ID). ID can be ascribed to both neurogenesis impairment and dendritic pathology. These defects are replicated in the Ts65Dn mouse, a widely used model of DS. While neurogenesis impairment in DS is a fetal event, dendritic pathology occurs after the first postnatal months. Neurogenesis alterations across the life span have been extensively studied in the Ts65Dn mouse. In contrast, there is scarce information regarding dendritic alterations at early life stages in this and other models, although there is evidence for dendritic alterations in adult mouse models. Thus, the goal of the current study was to establish whether dendritic alterations are already present in the neonatal period in Ts65Dn mice. In Golgi-stained brains, we quantified the dendritic arbors of layer II/III pyramidal neurons in the frontal cortex of Ts65Dn mice aged 2 (P2) and 8 (P8) days and their euploid littermates. In P2 Ts65Dn mice, we found a moderate hypotrophy of the apical and collateral dendrites but a patent hypotrophy of the basal dendrites. In P8 Ts65Dn mice, the distalmost apical branches were missing or reduced in number, but there were no alterations in the collateral and basal dendrites. No genotype effects were detected on either somatic or dendritic spine density. This study shows dendritic branching defects that mainly involve the basal domain in P2 Ts65Dn mice and the apical but not the other domains in P8 Ts65Dn mice. This suggests that dendritic defects may be related to dendritic compartment and age. The lack of a severe dendritic pathology in Ts65Dn pups is reminiscent of the delayed appearance of patent dendritic alterations in newborns with DS. This similarly highlights the usefulness of the Ts65Dn model for the study of the mechanisms underlying dendritic alterations in DS and the design of possible therapeutic interventions., (© 2021 S. Karger AG, Basel.)

Background: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients., Methods: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit., Results: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count., Conclusion: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.

Down syndrome (DS), a major genetic cause of intellectual disability, is characterized by numerous neurodevelopmental defects. Previous in vitro studies highlighted a relationship between bioenergetic dysfunction and reduced neurogenesis in progenitor cells from the Ts65Dn mouse model of DS, suggesting a critical role of mitochondrial dysfunction in neurodevelopmental alterations in DS. Recent in vivo studies in Ts65Dn mice showed that neonatal supplementation (Days P3-P15) with the polyphenol 7,8-dihydroxyflavone (7,8-DHF) fully restored hippocampal neurogenesis. The current study was aimed to establish whether brain mitochondrial bioenergetic defects are already present in Ts65Dn pups and whether early treatment with 7,8-DHF positively impacts on mitochondrial function. In the brain and cerebellum of P3 and P15 Ts65Dn pups we found a strong impairment in the oxidative phosphorylation apparatus, resulting in a deficit in mitochondrial ATP production and ATP content. Administration of 7,8-DHF (dose: 5 mg/kg/day) during Days P3-P15 fully restored bioenergetic dysfunction in Ts65Dn mice, reduced the levels of oxygen radicals and reinstated the hippocampal levels of PGC-1α. No pharmacotherapy is available for DS. From current findings, 7,8-DHF emerges as a treatment with a good translational potential for improving mitochondrial bioenergetics and, thus, mitochondria-linked neurodevelopmental alterations in DS.

Study Objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs., Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls., Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS., Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Granulosa cell tumors are rare ovarian tumors that can arise during pregnancy. We present a new case of recurrent adult granulosa cell tumor (AGCT) in pregnancy and a systematic review of the literature. The new case described is a 41-year-old woman G5P1122 with a prior history of AGCT that was referred to our center at 29 weeks because of a symptomatic abdominal mass, compatible with a possible recurrence of AGCT. At 36 + 3 weeks, she underwent a cesarean delivery for preterm labor and a total hysterectomy with a radical surgical staging. A healthy female infant was delivered. The patient received a platinum-based chemotherapy, with a 26-month follow-up negative for recurrence. Analyzing our case with the four identified by the literature review, three were recurrent and two were primary AGCT. Only one required surgery for AGCT at 15 weeks, while another underwent chemotherapy in pregnancy. In the other three cases, surgery for AGCT was done at the time of cesarean delivery. There were three cases of preterm delivery. All five pregnancies resulted in the birth of live babies with weight adequate for gestational age. In conclusion, AGCT diagnosed in pregnancy is rare, reported in only five cases. All gave birth to live babies in the third trimester, and maternal outcome at up to 18 months showed no recurrence.