The Impact of the COVID-19 Pandemic on Perinatal Loss Experienced by the Parental Couple: Protocol for a Mixed Methods Study

Background: At the beginning of 2020, mothers and fathers who experienced perinatal events (from conception to pregnancy and postpartum period) found themselves facing problems related to the emergency caused by the COVID-19 pandemic and the associated difficulties for health care centers in providing care. In the unexpected and negative event of perinatal loss (ie, miscarriage, stillbirth, and neonatal death) more complications occurred. Perinatal loss is a painful and traumatic life experience that causes grief and can cause affective disorders in the parental couple—the baby dies and the couple’s plans for a family are abruptly interrupted. During the COVID-19 pandemic, limited access to perinatal bereavement care, due to the lockdown measures imposed on medical health care centers and the social distancing rules to prevent contagion, was an additional risk factor for parental mental health, such as facing a prolonged and complicated grief. Objective: The main aims of this study are as follows: to investigate the impact of COVID-19 on mothers and fathers who experienced perinatal loss during the pandemic, comparing their perceptions; to evaluate their change over time between the first survey administration after bereavement and the second survey after 6 months; to examine the correlations between bereavement and anxiety, depression, couple satisfaction, spirituality, and sociodemographic variables; to investigate which psychosocial factors may negatively affect the mourning process; and to identify the potential predictors of the development of complicated grief. Methods: This longitudinal observational multicenter study is structured according to a mixed methods design, with a quantitative and qualitative section. It will include a sample of parents (mothers and fathers) who experienced perinatal loss during the COVID-19 pandemic from March 2020. There are two phases—a baseline and a follow-up after 6 months. Results: This protocol was approved by the Ethics Committee of Psychological Research, University of Padova, and by the Institutional Ethics Board of the Spedali Civili of Brescia, Italy. We expect to collect data from 34 or more couples, as determined by our sample size calculation. Conclusions: This study will contribute to the understanding of the psychological processes related to perinatal loss and bereavement care during the COVID-19 pandemic. It will provide information useful to prevent the risk of complicated grief and psychopathologies among bereaved parents and to promote perinatal mental health. International Registered Report Identifier (IRRID): DERR1-10.2196/3886

The impact of the COVID-19 pandemic on perinatal loss among Italian couples: A mixed-method study

Background: Perinatal bereavement is an event that greatly impacts the emotional, psychological, and psychosocial aspects of those who want to have a child. Objectives: Since there are few studies on the psychological impact of the COVID-19 pandemic on couples grieving for perinatal loss, this research aimed to survey this experience. Participants: Between 2020 and 2021, in Italian provinces highly affected by the COVID-19 pandemic, 21 parents participated: 16 mothers (76%; mean age 36.2; SD: 3.1) and 5 fathers (24%; mean age 40.2; SD: 3.4), among which there were 4 couples. Methods: A mixed-method design was used through self-report questionnaires and in-depth interviews. Accompanied by a sociodemographic form, the following questionnaires were administered: Prolonged Grief-13, the Parental Assessment of Paternal Affectivity (PAPA) (to fathers), the Parental Assessment of Maternal Affectivity (PAMA) (to mothers), the Dyadic Adjustment Scale short version, the Daily Spiritual Experiences Scale, and the Impact of Event Scale-Revised. The texts obtained through the in-depth interviews underwent thematic analysis. Results: Fifty per cent of participants suffered from Post-Traumatic Stress Disorders (PTSD) symptoms and 20% suffered from relational dyadic stress. Four areas of thematic prevalence emerged: psychological complexity of bereavement, the impact of the COVID-19, disenfranchisement vs. support, and spirituality and contact with the lost child. Participants interpreted their distress as related to inadequate access to healthcare services, and perceiving the pandemic restrictions to be responsible for less support and lower quality of care. Furthermore, they needed psychological help, and most of them were unable to access this service. Spirituality/religiosity did not help, while contact with the fetus and burial did. Conclusion: It is important to implement psychological services in obstetrics departments to offer adequate support, even in pandemic situations

Ozone activates the Nrf2 pathway and improves preservation of explanted adipose tissue in vitro

In clinical practice, administration of low ozone (O3) dosages is a complementary therapy for many diseases, due to the capability of O3 to elicit an antioxidant response through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-dependent pathway. Nrf2 is also involved in the adipogenic differentiation of mesenchymal stem cells, and low O3 concentrations have been shown to stimulate lipid accumulation in human adipose-derived adult stem cells in vitro. Thus, O3 treatment is a promising procedure to improve the survival of explanted adipose tissue, whose reabsorption after fat grafting is a major problem in regenerative medicine. In this context, we carried out a pilot study to explore the potential of mild O3 treatment in preserving explanted murine adipose tissue in vitro. Scanning and transmission electron microscopy, Western blot, real-time polymerase chain reaction and nuclear magnetic resonance spectroscopy were used. Exposure to low O3 concentrations down in the degradation of the explanted adipose tissue and induced a concomitant increase in the protein abundance of Nrf2 and in the expression of its target gene Hmox1. These findings provide a promising background for further studies aimed at the clinical application of O3 as an adjuvant treatment to improve fat engraftment

The transcriptional profile of adipose-derived stromal cells (ASC) mirrors the whitening of adipose tissue with age

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear. Herein, we show that inguinal adipose tissue in mice turns from brown/beige- to white-like with age and resident ASC readily mirror these changes both at mRNA and microRNA transcriptional level. Mechanistically, our data suggest that these brown/age-related changes in ASC transcription rely on changes in the activity of E2F1 and NFkB transcription factors

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein \u3b1 subunit (G\u3b1olf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain

Interferon Regulatory Factor 7 (IRF7) inhibition reverts age induced transcriptional and metabolic derangement

Aging relies on incremental alterations of cell and tissue which contribute to deteriorate organ functions and progressively drives to death. We show herein that midlife brings about a massive transcriptional/metabolic reprogramming, reminiscent of a cell-autonomous activation of an ectopic anti-viral response, which impairs the biological functions on the basis of cell homeostasis and longevity, namely mitochondrial and amino acid biogenesis. Integrated transcriptional analyses indicate IRF7 to be the major driver of these changes reveling an unprecedented, cell-autonomous role of Interferon Regulatory Factor 7 (IRF7) in leading transcriptional, mitochondrial and amino acid alterations with age. We found that the inhibition of IRF7 is sufficient to revert the transcriptional profiling of \u201cold cell\u201d, determining diminished interferon signaling, reverted transcriptional derangement, restored mitochondrial function and partially reestablish the amino acid pool. Our results reveal IRF7 as a major regulator of aging-related transcriptional and metabolic alterations and point it out as an ideal candidate for the development of effective therapies against aging and aging-related diseases

Prevalence and types of video gaming and gambling activities among adolescent public school students: findings from a cross-sectional study in Italy

Abstract Adolescence is characterized by emotional instability and risk-taking behaviours that can lead to, among other things, an increased risk of developing pathological video-gaming and gambling habits. The aim of this Study is to assess the prevalence and type of video gaming and gambling habits in adolescent students attending Italian upper-secondary schools. The cross-sectional study was conducted via an online survey using validated questionnaires. The primary outcome measures were the prevalence of past-year video gaming and gambling activities. The sample consisted of 502 adolescent students from frst- and second-grade secondary schools. A total of 40.8% of participants were video gamers, 4.8% were gamblers, 17.8% were both video gamers and gamblers, and the remaining 36.6% were not players. Among participants who reported video gaming activity (n=294), 68.0% were classifed as nonproblem gamers, 24.5% as at-risk gamers, and 7.5% as disordered video gamers. Among the participants who reported gambling activity (n=113), 85.8% were not problematic gamblers, 8.9% were at-risk gamblers, and 5.3% were pathological gamblers. Only 0.2% of all subjects met the criteria for both pathological gambling and pathological video game use. The fndings indicate that video gaming and gambling are common leisure times among adolescent students. However, a small but signifcant minority of these adolescents met the criteria for either severe problem gaming or gambling or bot

Late open conversion after endovascular repair of abdominal aneurysm failure: Better and easier option than complex endovascular treatment

Aim: Conversion to open repair becomes the last option in case of endovascular repair of abdominal aneurysm failure, when radiological interventional procedures are unfeasible. While early conversion to open repair generally derives from technical errors, aetiopathogenesis and results of late conversion to open repair often remain unclear. Methods: We report data from our Institute’s experience on late conversion to open repair. Twenty-two late conversion to open repairs out of 435 consecutive patients treated during a 18 years period, plus two endovascular repair of abdominal aneurysms performed in other centres, are analysed. The indication for conversion to open repair was aneurysm enlargement because of type I, type III, type II endoleak and endotension. Even if seven cases (23%) had shown an initial aneurysmal shrinkage, in a later phase, the sac began to enlarge again. In 12 patients, conversion to open repair was the last chance after unsuccessful secondary endovascular procedures. Results: Three cases (12.5%) were treated in emergency. Aortic cross-clamping was only infrarenal in 10 cases, only or temporarily suprarenal in 14 and temporarily supraceliac in 9 cases, for 19 total and 5 partial endograft excisions. Two patients died for Multiple Organ Failure (MOF), on 42nd (endovascular repair of abdominal aneurysm infection) and 66th postoperative day. No other conversion to open repair-related deaths or major complications were revealed by followup post-conversion to open repair (mean: 68 months ranging from 24 to 180 months). Conclusion: Late conversion to open repair is often an unpredictable event. It represents a technical challenge: specifically, the most critical point is the proximal aortic clamping that often temporarily excludes the renal circulation. In our series, conversion to open repair can be performed with a low rate of complications. In response to an endovascular repair of abdominal aneurysm failure, before applying complex procedures of endovascular treatment, conversion to open repair should be taken into account

Ozone treatment induces antioxidant stress response through Keap1/Nrf2 dependent pathway

Recently ozone therapy has been applied successfully as adjuvant therapy in the treatment of several disorders such as rheumatoid arthr\u131tis, heart and vascular disease, asthma emphysema and multiple sclerosis. Positive effects of ozone therapy have been hypothesized to rely on the capability of mild acute oxidative stress to induce antioxidant response. Nevertheless, molecular mechanisms behind those beneficial effects remain unclear. Some evidence suggests that mild oxidative stress induced by ozone treatments leads to activation of the transcription factor Nrf2 (nuclear factor erythroid-derived-like2). Nrf2 regulates the expression of genes under the control of antioxidant response element (ARE) enhancer. These genes include drug metabolizing enzymes, such as glutathione s-transferases (GSTs) and NAD(P)H-quinone Oxidoreductase 1 (NQO1), and antioxidant genes, such as heme oxygenase-1 (OH-1), the subunit of \u3b3-glutamylcysteine synthetase (\u3b3-GCS) and thioredoxin. Under basal conditions, Nrf2 is sequestered in the cytoplasm by its specific inhibitor Keap1 (Kelch-like ECH associated protein), which promotes Nrf2 ubiquitination and proteasomal degradation within a few minutes after its transcription. Under specific stimuli, Nrf2 dissociates from Keap1 and is preserved from degradation. Then, Nrf2 translocates into the nucleus, heterodimerizes with Maf proteins and trans-activates ARE-mediated genes. The current study was designed to investigate whether ozone therapy might induce ARE activation via Nrf2-dependent mechanisms. First, we established a HeLa cell line engineered to express NanoLuc Luciferase under the control of ARE promoter. We show that the treatment with different concentrations of ozone increased ARE-driven expression of NanoLuc in a dose- 413 dependent manner (Figure 1a). Ultrastructural immunocytochemistry showed Nrf2 to be associated to perichromatin fibrils, which are sites of active transcription (Figure 1b). Hela cells were transiently transfected with Nrf2-GFP and/or Keap1-dsRed fusion proteins to enable microscopy visualization of Nfr2 and Keap1 subcellular localization (Figure 2a). As expected, in untreated cells Nrf2-GFP disappeared when co-transfected with Keap1-dsRed. In contrast, ozone treatment induced persistence of Nrf2-GFP fluorescence and its massive nuclear translocation, suggesting that ozone might prevent Keap1-mediated Nrf2 degradation. In line with this conclusion we found an increased amount of Nrf2 protein compared to controls over 30 minutes after ozone treatment (Figure 2b), likely due to an increased Nrf2 stability. Finally, Keap1 transient overexpression partially reverted ARE-Luc activation in ozone treated cells (Figure 2c), thus providing further evidence that ozone treatment is able to induce an antioxidant stress response through a Keap1/Nrf2-dependent pathway

Safety performance models for urban intersections in Brazil

This paper presents a modeling effort for developing safety performance models (SPM) for urban intersections for three major Brazilian cities. The proposed methodology for calibrating SPM has been divided into the following steps: defining the safety study objective, choosing predictive variables and sample size, data acquisition, defining model expression and model parameters and model evaluation. Among the predictive variables explored in the calibration phase were exposure variables (AADT), number of lanes, number of approaches and central median status. SPMs were obtained for three cities: Fortaleza, Belo Horizonte and Brasilia. The SPM developed for signalized intersections in Fortaleza and Belo Horizonte had the same structure and the most significant independent variables, which were AADT entering the intersection and number of lanes, and in addition, the coefficient of the best models were in the same range of values. For Brasilia, because of the sample size, the signalized and unsignalized intersections were grouped, and the AADT was split in minor and major approaches, which were the most significant variables. This paper also evaluated SPM transferability to other jurisdiction. The SPM for signalized intersections from Fortaleza and Belo Horizonte have been recalibrated (in terms of the COx) to the city of Porto Alegre. The models were adjusted following the Highway Safety Manual (HSM) calibration procedure and yielded C-x of 0.65 and 2.06 for Fortaleza and Belo Horizonte SPM respectively. This paper showed the experience and future challenges toward the initiatives on development of SPMs in Brazil, that can serve as a guide for other countries that are in the same stage in this subject. (C) 2014 Elsevier Ltd. All rights reserved