A Broad Study to Develop Maternity Units Design Knowledge Combining Spatial Analysis and Mothers' and Midwives' Perception of the Birth Environment

Objectives: This article investigates how the physical birth environment is perceived by the users (women and midwives) in different settings, a midwife-led unit and an obstetric-led unit, placed in Italy. Background: In the field of birth architecture research, there is a gap in the description of the spatial and physical characteristics of birth environments that impact users' health, specifically for what concerns the perception by women. Methods: The study focuses on multi-centered mixed methods design, employing both quantitative and qualitative research methods (questionnaire, spatial analysis) and covering different disciplines (architecture, environmental psychology, and midwifery). Results: The results revealed significant differences between the two settings and some associations between perceived and spatial data concerning: calm atmosphere, greater intimacy, spacious birth room, clarity of service points, clarity in finding midwives, sufficient space for labor, noise, privacy, and the birth room adaptability. Conclusions: The findings confirm the importance of the spatial layout and indicate documented knowledge as an input to consider when designing birth spaces in order to promote user well-being

Low sodium and tolvaptan have opposite effects in human small cell lung cancer cells.

Abstract Purpose Hyponatraemia is frequently observed in cancer patients and can be due to the syndrome of inappropriate anti-diuresis (SIAD), related to ectopic vasopressin secretion, particularly in small cell lung cancer (SCLC). Hyponatraemia is associated with a worse outcome in cancer patients. The vasopressin receptor antagonist tolvaptan effectively corrects hyponatraemia secondary to SIAD and there is in vitro evidence that it has also an antiproliferative effect in cancer cells. The purpose of this study was i) to analyse the effect of low serum sodium concentrations ([Na+]) in SCLC cells and ii) to determine whether tolvaptan counteracts tumor progression. Methods We evaluated cell proliferation, cell cycle, apoptosis, oxidative stress, invasivity in low [Na+] as well as after exposure to tolvaptan. We also analysed the intracellular signalling pathways involved. Results In reduced [Na+] cell proliferation was significantly increased compared to normal [Na+] and cells were mostly distributed in the G2/M phase. Apoptosis appeared reduced. In addition, the ability to cross matrigel-coated membranes markedly increased. As observed in other cancer cell models, the expression of the heme-oxigenase-1 gene was increased. Finally, we found that in cells cultured in low [Na+] the RhoA/ROCK1/2 pathway, which is involved in the regulation of actin cytoskeleton, was activated. On the other hand, we found that tolvaptan effectively inhibited cell proliferation, anchorage-independent growth, invasivity and promoted apoptosis. Accordingly, the RhoA/ROCK-1/2 pathway was inhibited. Conclusions These findings demonstrate for the first time that low [Na+] favours tumor progression in SCLC cells, whereas tolvaptan effectively inhibits cell proliferation, survival and invasivity

Optimal settings for childbirth.

Many studies highlight how health is influenced by the settings in which people live, work, and receive health care. In particular, the setting in which childbirth takes place is highly influential. The physiological processes of women's labor and birth are enhanced in optimal ("salutogenic," or health promoting) environments. Settings can also make a difference in the way maternity staff practice. This paper focuses on how positive examples of Italian birth places incorporate principles of healthy settings. The "Margherita" Birth Center in Florence and the Maternity Home "Il Nido" in Bologna were purposively selected as cases where the physical-environmental setting seemed to reflect an embedded model of care that promotes health in the context of childbirth. Narrative accounts of the project design were collected from lead professional and direct inspections performed to elicit the key salutogenic components of the physical layout. Comparisons between cases with a standard hospital labor ward layout were performed. Cross-case similarities emerged. The physical characteristics mostly related to optimal settings were a result of collaborative design decisions with stakeholders and users, and the resulting local intention to maximize safe physiological birth, psychosocial wellbeing, facilitate movement and relaxation, prioritize space for privacy, intimacy, and favor human contact and relationships. The key elements identified in this paper have the potential to inform further investigations for the design or renovation of all birth places (including hospitals) in order to optimize the salutogenic component of any setting in any country

Magnetically Driven Bioreactors as new Tools in Drug Delivery

The pharmacological properties of many drugs can be improved by drug delivery systems able to drive therapeutic agents to target regions. The use of carriers, in fact, may reduce possible cytotoxic effects of drugs and increase their bioavailability at the site of action, thus improving the efficacy and the safety of treatments. Therefore, we have developed an erythrocyte-based drug delivery system (erythro-magneto-HA virosome), which has the potential to be magnetically guided to specific sites and to fuse with target cells. These engineered erythrocytes have demonstrated in previous work a very high in vitro capability to release anticancer drugs directly inside target cells. Because the erythro-magneto-HA virosomes (EMHVs) proved to be promising carriers, we decided to investigate in more details the effectiveness and safety of this erythrocyte-based drug delivery system. We evaluated the ability of the EMHVs to be specifically localized in vivo to desired sites by means of an external magnetic field and to protect an anticancer drug such as 5-Aza-2\u27-deoxycytidine from degradation. Additionally we have assessed the ability of the EMHVs to act as bioreactors and to convert the pro-drug 5-Aza-2\u27-deoxycytidine into an active drug. Finally, we have studied the interaction of the EMHVs with the host immune system. The pro-drug 5-Aza-2\u27-deoxycytidine has short half-life when systemically injected and needs to be phosphorylated to become an active drug. We found that when inside the engineered erythrocytes it is protected by degradation and is transformed in its active form thus becoming readily available for uptake by the targeted cells. Moreover, we have observed that the EMHVs used didn\u27t cause either a cell-mediated or a humoral immune response in host mice having the same haplotype of the donors. These findings suggest that erythro-magneto-HA virosomes are a safe and useful drug delivery system that may offer numerous advantages for several clinical application

Exploring the Role of Birth Environment on Italian Mothers' Emotional Experience during Childbirth.

The physical environment is one of the factors that affect mother's experience of childbirth and psychological health. A woman's childbirth experience has been found to influence not only the mother's own health and future births but also the well-being of her child and family. The present study's objective was to investigate mothers' perceptions of spatial-physical humanization, affective quality of place, and emotions during childbirth. To achieve this goal, the first part of our work was dedicated to selecting two birth environments (hospital and birth center) with different degrees of humanization. The methods include observations and field survey which mainly concerned the environmental quality of the spaces and the layout of the birth unit, and self-report questionnaire about perceived environment, affective quality attributed to place, and delivery experience. Participants are 66 low-risk women, choosing hospital or birth center. The findings indicate an enhanced perception of both the spatial-physical aspects and the social and functional aspects of the care unit among mothers who give birth at the birth center. These same mothers also report a more positive perception of the childbirth experience. In conclusion, this study contributes to the understanding of the role of birth environments in shaping mothers' emotional experiences during childbirth

Sleep-related hypermotor epilepsy: Long-term outcome in a large cohort

To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE)

From virtual screening hits targeting a cryptic pocket in BACE-1 to a nontoxic brain permeable multitarget anti-Alzheimer lead with disease-modifying and cognition-enhancing effects

Starting from six potential hits identified in a virtual screening campaign directed to a cryptic pocket of BACE-1, at the edge of the catalytic cleft, we have synthesized and evaluated six hybrid compounds, designed to simultaneously reach BACE-1 secondary and catalytic sites and to exert additional activities of interest for Alzheimer's disease (AD). We have identified a lead compound with potent in vitro activity towards human BACE-1 and cholinesterases, moderate Ab42 and tau antiaggregating activity, and brain permeability, which is nontoxic in neuronal cells and zebrafish embryos at concentrations above those required for the in vitro activities. This compound completely restored short- and long-term memory in a mouse model of AD (SAMP8) relative to healthy control strain SAMR1, shifted APP processing towards the non-amyloidogenic pathway, reduced tau phosphorylation, and increased the levels of synaptic proteins PSD95 and synaptophysin, thereby emerging as a promising disease-modifying, cognitionenhancing anti-AD lead

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.Peer Reviewe