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Abstract 17β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women’s health.

This research is realised in the framework of a project recently funded as part of the PNRR (National Recovery and Resilience Plan) in the Accessibility sector. The working team has been established in the framework of the scientific agreement between the Museum of Villa della Regina in Turin, the Department of Architecture and Design at Politecnico di Torino, and the Department of History, Drawing and Restoration of Architecture at Sapienza Università di Roma, and includes knowledge from art history, digital surveying, 3D modelling, and digital solutions for cultural heritage. The research involves the reconstructive 3D modelling of Piffetti’s Library, once placed in the cabinet toward midnight and west inside the Villa della Regina and today in the Palazzo del Quirinale, and its interactive visualisation through augmented reality (AR) and virtual reality (VR) aimed at accessibility.

Background Cyber dating abuse (CDA) refers to physical, verbal, and psychological violence perpetrated towards a romantic part-ner via technology and social media. Another emerging form of online abuse is ghosting, a silent strategy to dissolve undesired relationships without openly having to break them up. The aims of the current study were (i) to explore the relationship between CDA and ghosting behaviours in romantic relationships and (ii) to investigate the roles of gender and personality traits (conscientiousness, agreeableness, extraversion, emotional stability, openness) in pre-diction of CDA (perpetration and victimization) Material and methods A sample of 409 participants (64.8% females), aged between 18 and 53 years (Mage = 26.40, SD = 6.06), took part in the study. Results CDA and ghosting behaviours are interrelated, and women were more prone than men were to use ghosting strate-gies, such as stopping messages abruptly and punishing the partner through silence. Moreover, gender and personal-ity traits differently predicted direct aggression and control/monitoring perpetration and direct aggression victimiza-tion, but they were not significant predictors of control/monitoring victimization. Conclusions The findings are discussed in light of gender differences to improve our understanding of the psychological factors involved in cyber dating violence.

Healthcare systems contribute significantly to climate change, leading to an increase in global morbidity and mortality. The operating theatre, in particular, is the most polluting area in the hospital environment; fortunately, there are numerous aspects on which action can be taken to reduce surgery-related emissions. [ABSTRACT FROM AUTHOR]

The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or phospho-threonine or phospho-serine residues. To better understand protein interactor recognition mechanisms across the Nedd4 family, we report the development and implementation of a python-based tool, PxYFinder, to identify PY motifs in the primary sequences of previously identified interactors of Nedd4 and related ligases. Using PxYFinder, we find that, on average, half of Nedd4 family interactions are likely PY-motif mediated. Further, we find that PPxY motifs are more prevalent than LPxY motifs and are more likely to occur in proline-rich regions and that PPxY regions are more disordered on average relative to LPxY-containing regions. Informed by consensus sequences for PY motifs across the Nedd4 interactome, we rationally designed a focused peptide library and employed a computational screen, revealing sequence- and biomolecular interaction-dependent determinants of WW-domain/PY-motif interactions. Cumulatively, our efforts provide a new bioinformatic tool and expand our understanding of sequence and structural factors that contribute to PY-motif mediated interactor recognition across the Nedd4 family.

[This corrects the article DOI: 10.1371/journal.pone.0185926.].

After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's

This research is realised in the framework of a project recently funded as part of the PNRR (National Recovery and Resilience Plan) in the Accessibility sector. The working team has been established in the framework of the scientific agreement between the Museum of Villa della Regina in Turin, the Department of Architecture and Design at Politecnico di Torino, and the Department of History, Drawing and Restoration of Architecture at Sapienza Università di Roma, and includes knowledge from art history, digital surveying, 3D modelling, and digital solutions for cultural heritage. The research involves the reconstructive 3D modelling of Piffetti's Library, once placed in the cabinet toward midnight and west inside the Villa della Regina and today in the Palazzo del Quirinale, and its interactive visualisation through augmented reality (AR) and virtual reality (VR) aimed at accessibility. [ABSTRACT FROM AUTHOR]

Despite epidemiological findings of improvements in cardiovascular risk factors with a light-to-moderate intake of alcohol, many misconceptions remain regarding alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Argentine physicians and to establish their sources of knowledge. An online national survey was distributed through the Argentine Federation of Cardiology (FAC) to cardiologists, internal medicine specialists, general and other subspecialty physicians in Argentina. The survey was completed by 745 physicians, of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate alcohol intake to be beneficial for cardiovascular health, 36% believed only wine offered such benefits, 24% viewed any intake to be harmful, and 5% had other opinions. More than half (57%) self-reported their knowledge came from academic sources. Regarding knowledge of drinking guidelines, only 41% of physicians were aware of the concept of “standard drink”. Physicians were generally not comfortable converting standard drinks into other metric units, however men tended to be more comfortable than women (p = 0.052). Physicians were not satisfied with their knowledge of drinking guidelines (3.01 ± 2.73, on a 0–10 scale). Physicians were generally comfortable in counselling patients regarding safe limits of consumption (6.22 ± 3.20, on a 0–10 scale). Argentine physicians were not satisfied with their knowledge of alcohol consumption guidelines or their understanding of the reported metrics. Only one-third of study participants viewed moderate alcohol intake as beneficial for cardiovascular health. This study shows the necessity to optimize the sources of knowledge.

Abstract After advanced age, having a parent affected with Alzheimer's disease (AD) is the most significant risk factor for developing AD among cognitively normal (NL) individuals. Although rare genetic mutations have been identified among the early-onset forms of familial AD (EOFAD), the genetics of the more common forms of late-onset AD (LOAD) remain elusive. While some LOAD cases appear to be sporadic in nature, genetically mediated risk is evident from the familial aggregation of many LOAD cases. The patterns of transmission and biological mechanisms through which a family history of LOAD confers risk to the offspring are not known. Brain imaging studies using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) have shown that NL individuals with a maternal history of LOAD, but not with a paternal family history, express a phenotype characterised by a pattern of progressive reductions of brain glucose metabolism, similar to that in AD patients. As maternally inherited AD may be associated with as many as 20 per cent of the total LOAD population, understanding the causes and mechanisms of expression of this form of AD is of great relevance. This paper reviews known genetic mutations implicated in EOFAD and their effects on brain chemistry, structure and function; epidemiology and clinical research findings in LOAD, including in vivo imaging findings showing selective patterns of hypometabolism in maternally inherited AD; possible genetic mechanisms involved in maternal transmission of AD, including chromosome X mutations, mitochondrial DNA and imprinting; and genetic mechanisms involved in other neurological disorders with known or suspected maternal inheritance. The review concludes with a discussion of the potential role of brain imaging for identifying endophenotypes in NL individuals at risk for AD, and for directing investigation of potential susceptibility genes for AD.