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Introduction: Chimeric Antigen Receptor T-cell therapy (CAR-T) represents the most recent immunotherapy’s innovation to cure some refractory and/or relapsing haematological tumours. However, because of the life-threatening toxicities it might cause such as Cytokine Release Syndrome and Immune Cell Associated Neurotoxicity Syndrome, patients are closely monitored by nurses for the early identification of toxicities during the post-infusion phase of CAR-T cell therapy. Exploring the nurses’ experience with respect to any difficulties related to the monitoring is important since these issues can be perceived by patients and affect the nurse-patient’s caring relationship, considered as a shared lived experience between the patient and the nurse. Aim: This study aims to investigate haematology nurses’ lived experience with monitoring CAR-T’s induced toxicities. Materials and methods: A qualitative study following Cohen's phenomenological methodology will be conducted through semi-structured interviews in a sample of Italian nurses working in haematology units, who have had previous experience in the management of patients undergoing CAR-T therapy for at least two months and who have performed the monitoring for the same months of experience; the interviews will be audio-recorded and then transcribed verbatim. Two researchers will carry out the manual analysis and interpretation of the collected data independently, identifying themes and sub-themes. Conclusion: To explore the nurses’ experiences in this field could facilitate the identification of the educational needs, at individual and group level. Despite it is important to consider contextual variables, the findings of this study could contribute to develop evidence supporting advanced and specialized nursing care in the haematological setting.

Background:. The advent of artificial intelligence (AI) in microsurgery has tremendous potential in plastic and reconstructive surgery, with possibilities to elevate surgical precision, planning, and patient outcomes. This systematic review seeks to summarize available studies on the implementation of AI in microsurgery and classify these into subdomains where AI can revolutionize our field. Methods:. Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a meticulous search strategy was used across multiple databases. The inclusion criteria encompassed articles that explicitly discussed AI’s integration in microsurgical practices. Our aim was to analyze and classify these studies across subdomains for future development. Results:. The search yielded 2377 articles, with 571 abstracts eligible for screening. After shortlisting and reviewing 86 full-text articles, 29 studies met inclusion criteria. Detailed analysis led to the classification of 6 subdomains within AI applications in microsurgery, including information and knowledge delivery, microsurgical skills training, preoperative planning, intraoperative navigational aids and automated surgical tool control, flap monitoring, and postoperative predictive analytics for patient outcomes. Each subtheme showcased the multifaceted impact of AI on enhancing microsurgical procedures, from preoperative planning to postoperative recovery. Conclusions:. The integration of AI into microsurgery signals a new dawn of surgical innovation, albeit with the caution warranted by its nascent stage and application diversity. The authors present a systematic review and 6 clear subdomains across which AI will likely play a role within microsurgery. Continuous research, ethical diligence, and cross-disciplinary cooperation is necessary for its successful integration within our specialty.

This special issue examines representations and constructions of pregnancy, childbirth, and breastfeeding in contemporary Japanese fiction in a selection of literary texts from the 2010s to the 2020s. It thus joins ongoing conversations and existing studies concerned with the representation of reproduction and motherhood in modern and contemporary Japanese culture (Saito, 1994; Seaman, 2016; Castellini, 2017; Harada, 2021). However, the essays in this section focus on depictions of pregnancy, childbirth, and breastfeeding in terms of narrating bodies as a way to articulate women’s experiences of physical and psychological oppression within Japanese society and redefine new forms of mothering, fathering, and parenting. This research investigates the ambivalence and complexity around motherhood and embodiment in contemporary women’s fiction. At the same time, it explores the connections between literary studies and contemporary sociocultural dynamics of gender and family.

The “breast-is-best” ideology (bonyū shinwa), which is still firmly rooted in Japanese consciousness, can cause women stress and pain, becoming a source of anxiety and even depression. When used in fiction, we can read it as a topos that highlights the great pressure experienced by mothers as primary caregivers in contemporary Japanese society. In this paper, I analyze the representation of breastfeeding in relation to the concept of care in the novel Chibusa no kuni de (In the Country of Breasts, 2020) by Fukazawa Ushio. I argue that Fukazawa’s novel tackles the issue of “breast-is-best” discourse on several levels. On the one hand, this novel describes the discomfort that both the lack and overproduction of breastmilk can cause in women, and also depicts women who lack the so-called “maternal instinct.” On the other hand, the novel also questions the traditional view of care as something that should be performed at the individual level in the intimate sphere. My analysis of Fukazawa’s work will highlight the link between breastfeeding, care, and power, while shedding light on the interdependence between caregivers and care-receivers.

Background:. Achieving optimal aesthetic outcomes in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction remains a challenge, often necessitating additional procedures for refinement. This study presents two innovative techniques (the hug flap and Hamdi hammock) aimed at enhancing breast projection and inframammary fold (IMF) definition in DIEP flap reconstruction. Methods:. The hug flap technique uses de-epithelialized caudal mastectomy skin to augment breast projection, whereas the Hamdi hammock uses a percutaneous purse-string suture to define the IMF. A retrospective review of 782 patients who underwent DIEP flap breast reconstruction between 2007 and 2023 was conducted. Results:. The hug flap group required significantly less additional fat grafting compared to other techniques (11% versus 27% and 22%). No total flap losses occurred in the hug flap group, and fat necrosis rates were low. The Hamdi hammock was used in 405 patients with a mean of two lipofilling sessions. Complications were minor and no stitches required removal. Conclusions:. The hug flap and Hamdi hammock techniques offer effective and safe methods for enhancing breast projection and IMF definition in DIEP flap reconstruction. These techniques may reduce the need for additional procedures and improve aesthetic outcomes.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis. As we age, the efficiency of the NRF2 pathway declines due to several factors including increased activity of its repressors, impaired NRF2-mediated antioxidant and cytoprotective gene expression, and potential epigenetic changes, though the precise mechanisms remain unclear. This leads to diminished antioxidant defenses, increased oxidative damage, and exacerbated metabolic dysregulation and inflammation—key contributors to age-related diseases. Given NRF2’s role in mitigating proteotoxic stress, the pharmacological modulation of NRF2 has emerged as a promising therapeutic strategy, even in aged preclinical models. By inducing NRF2, it is possible to mitigate the damaging effects of oxidative stress, metabolic dysfunction, and inflammation, thus reducing protein misfolding. The review highlights NRF2’s therapeutic implications for neurodegenerative diseases and cardiovascular conditions, emphasizing its role in improving proteostasis and redox homeostasis Additionally, it summarizes current research into NRF2 as a therapeutic target, offering hope for innovative treatments to counteract the effects of aging and associated diseases.

Background: Vascular calcification (VC) is a dynamic, tightly regulated process driven by cellular activity and resembling the mechanisms of bone formation, with specific molecules playing pivotal roles in its progression. We aimed to investigate the involvement of the bone morphogenic proteins (BMP-2, BMP-4, BMPR-1a/1b, and BMPR-2) system in this process. Our study used an advanced in vitro model that simulates the biological environment of the vascular wall, assessing the ability of a phosphate mixture to induce the osteoblastic switch in human coronary artery smooth muscle cells (HCASMCs). Methods: HCASMCs were grown in mono- and co-culture with human coronary artery endothelial cells (HCAECs) in a double-flow bioreactor (LiveBox2 and IVTech), allowing static and dynamic conditions through a peristaltic pump. The VC was stimulated by incubation in a calcifying medium for 7 days. A BMP system Real-Time PCR was performed at the end of each experiment. Results: In monocultures, BMP-2 expression increased in calcified HCASMCs in static (p = 0.01) and dynamic conditions. BMP-4 and the biological receptors were expressed in all the experimental settings, increasing mainly in dynamic flow conditions. In co-cultures, we observed a marked increase in BMP-2 and BMP-4, BMPR-1a (p = 0.04 and p = 0.01, respectively), and BMPR-2 (p = 0.001) in the calcifying setting mostly in dynamic conditions. Conclusions: The increase in BMP-2/4 in co-culture suggests that these genes might promote the switch towards an osteogenic-like phenotype, data also supported by the rise of both BMPR-1a and BMPR-2. Thus, our findings provide insights into the mechanisms by which dynamic co-culture modulates the BMP system activation in an environment mimicking in vivo VC’s cellular and mechanical characteristics.

The discovery of a multi-target scaffold in medicinal chemistry is an important goal for the development of new drugs with different biological effects. Azobenzene is one of the frameworks in medicinal chemistry used for its simple synthetic methods and for the possibility to obtain a great variety of derivatives by simple chemical modifications or substitutions. Phenyldiazenyl-containing compounds show a wide spectrum of pharmacological activities, such as antimicrobial, anti-inflammatory, anti-neurodegenerative, anti-cancer, and anti-enzymatic. The aim of this review is to highlight the importance of azobenzene as a scaffold in medicinal chemistry, with particular attention to the chemical modifications and structure–activity relationships (SARs). This review emphasizes the main therapeutic applications of phenyldiazenyl derivatives, with a particular focus on structural modification and its influence on activity, with the aim of inspiring medicinal chemists to obtain new, increasingly powerful azobenzenes useful in therapy.

BackgroundIn modern society, achieving high-quality sleep is increasingly challenging. We conducted a study to explore the potential benefits of daytime physical activity and balneotherapy, including mud application and thermal-water bathing, on sleep quality.MethodsTo assess daytime physical activity and sleep parameters, we actigraphically monitored 127 healthy participants (34.6% male, average age 64.61 ± 0.89 years) during a one-week stay at a spa resort, where they received mud application and thermal-water bathings.ResultsParticipants were divided into three groups based on the timing of mud application. Those receiving mud application before 8:30 a.m. tended to have shorter sleep durations compared to those with later application, especially if it occurred before 7:45 a.m. However, mud application did not significantly affect sleep quality. Three-way ANCOVA revealed a significant effect of daytime physical activity on delta Sleep Efficiency, but post-hoc tests were insignificant. Furthermore, analyzing the duration of daily thermal-water bathings, individuals bathing for over 75 min per day experienced a noteworthy improvement in sleep quality, particularly in terms of delta Sleep Efficiency (2.15 ± 0.9% vs. −0.34 ± 0.31%, p = 0.007).ConclusionOur findings suggest that extended thermal-water bathing may enhance objective aspects of sleep quality. Since balneotherapy is mainly prescribed for individuals with musculoskeletal pathologies or psychological disorders, these findings may encourage doctors to recommend bathing in thermal water also to healthy subjects. Future researchers need to investigate the role of daytime physical activity in depth.

Social jetlag (SJL), resulting from misalignment between biological rhythms and social schedules, has emerged as a prevalent phenomenon in modern society, particularly among young athletes. However, the effect of SJL on performance is poorly studied. Jump and dynamic balance are two key skills in volleyball, as the first allows the player to perform better both during the offense and defense phase, and the second is fundamental in landing and in injury prevention. Therefore, our aim was to investigate the effect of SJL on jump skill performance and balance in female volleyball players. Thirty female volleyball players (mean age: 17.3 ± 0.88 years) participated in the study. SJL was assessed using the Munich ChronoType Questionnaire (MCTQ), integrated with Jankowsky's sleep-corrected formula. Jump skill performance was evaluated using a standardized jump test, the Vertec Jump Test, while balance was assessed with the Y Balance Test. The tests were performed at 09:00 a.m. and at 06:00 p.m. The results revealed that players with greater SJL exhibited decreased jump performance, characterized by lower vertical jump height (p = 0.02). Furthermore, players with lower SJL showed the typical difference between morning and afternoon performance (p = 0.001), demonstrating their synchronization between biological rhythms and social commitments, while no statistically significant difference between the two sessions was shown in players with higher SJL. Regarding balance, no significant association with SJL was found, but the morning session yielded lower results than the afternoon one (p = 0.01). These findings highlight the detrimental impact of SJL on jump skill performance, underscoring the importance of optimizing sleep-wake schedules and circadian alignment to enhance athletic performance. Future research should explore targeted interventions, such as sleep hygiene education, to minimize social jetlag and promote optimal performance in adolescent athletes.

Introduction: ctDNA is a useful tool for NGS molecular profiling in advanced NSCLC patients. Its clinical applicability in patients with gene rearrangements is still limited due to a lower detection rate of these types of alterations compared to single SNVs or small indels. To this purpose, we performed a study in two Italian centers to assess the concordance between tissue and plasma samples in the detection of genes fusions (ALK, ROS, RET) and METexon14 mutations in advanced NSCLC patients. Methods: Patients with a histological diagnosis of oncogene addicted (ALK, ROS1, RET positive or METexon14 mutated) advanced NSCLC were enrolled at the time of first line of TKI treatment. Plasma samples were harvested before the start of TKI treatment and NGS analysis on ctDNA samples using the AVENIO ctDNA Expanded kit was performed. The Positive Percent Agreement (PPA) between tissue and plasma was calculated. Results: Fifty-eight rearranged or METexon14 mutated NSCLC patients were included and 57 ctDNA samples were successfully sequenced. An overall PPA of 37% (21/57) was obtained, with a best performance for RET fusion (80%), intermediate for METexon14 skipping mutations (40%) and ALK rearranged (36%) and a worst one for ROS1 rearranged samples (18%). We found TP53, APC and SMAD4 as most prevalent co-mutated genes (21%, 12% and 10% of patients, respectively). Among different factors considered, increased driver detection rate in patients with extra-thoracic metastases (p = 0.0049) was observed. Significantly shorter survival was observed in patients harboring co-occurring KRAS/NRAS mutations in ctDNA. Conclusions: ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

Chronobiology is the field of study focused on understanding the temporal patterns of biological functions, specifically examining the regular cycles or oscillations in these processes [...]

Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. β+- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and β−-emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are 68Ga, 44Sc, 18F, 64Cu, 99mTc, and 125I for diagnostic imaging.

Background Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. Aims We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. Method The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. Results We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = −3.19, 95% CI: −5.30 to −1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = −1.57, 95% CI: −2.88 to −0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. Conclusions Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.

Research into novel anti-Helicobacter pylori agents represents an important approach for the identification of new treatments for chronic gastritis and peptic ulcers, which are associated with a high risk of developing gastric carcinoma. In this respect, two series of azobenzenesulfonamides were designed, synthesized, and tested against a large panel of human and bacterial CAs to evaluate their inhibitory activity. In addition, computational studies of the novel primary benzenesulfonamides (4a–j) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus H. pylori of the two series was also studied. The best-in-class compounds were found to be 4c and 4e among the primary azobenzenesulfonamides and 5c and 5f belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti-H. pylori activity, with MIC values of 4–8 μg/mL and MBCs between 4 and 16 μg/mL. Moreover, the evaluation of their toxicity on a G. mellonella larva in vivo model indicated a safe profile for 4c,e and 5c,f. The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti-H. pylori agents.

Sex differences may play a role in the etiopathogenesis and severity of metabolic dysfunction-associated steatotic liver disease (MASLD), a disorder characterized by excessive fat accumulation associated with increased inflammation and oxidative stress. We previously observed the development of steatosis specifically in female rats fed a high-fat diet enriched with liquid fructose (HFHFr) for 12 weeks. The aim of this study was to better characterize the observed sex differences by focusing on the antioxidant and cytoprotective pathways related to the KEAP1/NRF2 axis. The KEAP1/NRF2 signaling pathway, autophagy process (LC3B and LAMP2), and endoplasmic reticulum stress response (XBP1) were analyzed in liver homogenates in male and female rats that were fed a 12-week HFHFr diet. In females, the HFHFr diet resulted in the initial activation of the KEAP1/NRF2 pathway, which was not followed by the modulation of downstream molecular targets; this was possibly due to the increase in KEAP1 levels preventing the nuclear translocation of NRF2 despite its cytosolic increase. Interestingly, while in both sexes the HFHFr diet resulted in an increase in the levels of LC3BII/LC3BI, a marker of autophagosome formation, only males showed a significant upregulation of LAMP2 and XBP1s; this did not occur in females, suggesting impaired autophagic flux in this sex. Overall, our results suggest that males are characterized by a greater ability to cope with an HFHFr metabolic stimulus mainly through an autophagic-mediated proteostatic process while in females, this is impaired. This might depend at least in part upon the fine modulation of the cytoprotective and antioxidant KEAP1/NRF2 pathway resulting in sex differences in the occurrence and severity of MASLD. These results should be considered to design effective therapeutics for MASLD.

The purpose of this article is to analyse how the concept of choreography developed in the post-digital era. The modern term choreography indicates the making process of a 'relational performance architecture' consisting of the hybridisation of kinaesthetic and mediatic presences (Birringer 2004). Accordingly, the paper aims to discuss recent the decline of digital performance based on the migration (Bishop 2018; Monda 2020) of the kinaesthetic experience in choreographic artifacts. By considering three artworks performed in the context of the DRHA Conference Exhibition 2023 – a demo in Extended Reality, a performance in Virtual Reality, and a digital installation with the application of Artificial Intelligence. The subject will be discussed, going through three definitions of choreography. Firstly, choreography is examined as the transcodification of the movement qualities into a 'liquid architecture' (Novack 2010) planned to transmit and translate somatic information throughout digital circuits. Secondly, the paper explores the concept of 'mobile architecture' (Manning 2013), which underlined a conception of choreography as an event for the ontogenetic architecture of environments in movement (Manning & Massumi 2014). A third approach considers the multiple ways of writing/coding/designing computer-generated movements by transmedia strategies (Jürgon 2016). The term transmedia choreography is investigated taking into consideration how the knowledge embodied by experiencing movement, can shape the dialogue between several media choreographed together to establish a ‘kinesfield’ (Shiller 2003), an interactive platform designed for disseminating intangible cultural heritage (Monda 2022).

Abstract Birt‐Hogg‐Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss‐of‐function pathogenic variants in the gene encoding the tumor‐suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney‐specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb and Tfe3 contribute, in a differential and cooperative manner, to kidney cystogenesis. Remarkably, the analysis of BHD patient‐derived tumor samples revealed increased activation of TFEB/TFE3‐mediated transcriptional program and silencing either of the two genes rescued tumorigenesis in human BHD renal tumor cell line‐derived xenografts (CDXs). Our findings demonstrate in disease‐relevant models that both TFEB and TFE3 are key drivers of renal tumorigenesis and suggest novel therapeutic strategies based on the inhibition of these transcription factors.

Abstract The objective of this study was to explore and describe the specificities of the occupational life of infertile endometriotic women treated by in vitro fertilization. We conducted a qualitative monocentric study between December 2020 and June 2021. Twelve semi-structured in-depth interviews using a theme-based interview guide with open questions were undertaken with infertile women with deep infiltrating endometriosis. Data analysis was conducted using an inductive approach according to the grounded theory method. Three main themes emerged from the interviews: (i) barriers to reconciling illness and work life, (ii) facilitating factors for well-being at work, and (iii) consequences and outlooks. It appeared that the time of infertility treatment represents a particular period of change in the working lives of women with endometriosis. For most women, these changes are experienced negatively, often with a renunciation of goals. For others, this is the time to communicate the difficulties linked to their illness to their professional entourage. There is a long path ahead to finally achieving recognition of endometriosis in the context of professional life.

La ricerca intende riscoprire la figura di Françoise Cachin, prima direttrice del Musée d’Orsay e dei Musées de France, per evidenziare come la sua peculiare metodologia di ricerca e pratica curatoriale abbiano contribuito in maniera determinante allo sviluppo della storia dell’arte internazionale. Per questo motivo è stato necessario in primis ricostruire il suo percorso professionale, attraverso lo spoglio di quotidiani e riviste, presso biblioteche e archivi romani e parigini, che ha permesso di comprendere come il modello dirigenziale da lei proposto sia stato di grande innovazione per le istituzioni francesi. Parallelamente alla consultazione dei cataloghi delle mostre da lei curate tra il 1986 e il 1994, si è svolta un’analisi approfondita del materiale archivistico conservato presso la Documentation del Musée d’Orsay: è stato, così, possibile rivalutare i caratteri di unicità e modernità di due dei suoi ultimi progetti curatoriali, in particolare "1893. L'Europe des peintres", mostra che ha problematizzato i processi di formazione dell'identità culturale europea e i criteri della periodizzazione storiografica artistica. This essay aims at rediscovering the figure of Françoise Cachin, as the first female director of the Musée d'Orsay (1986) and Musées de France (1994). It points out how her peculiar curatorial practice and research methodology have decisively contributed to the development of international art history. Firstly, the main stages of her professional career were reconstructed through the examination of newspapers and magazines, in Roman and Parisian libraries and archives. This allowed to understand how her conception of managerial roles has innovated French institutions. Then, the catalogues of the exhibitions she curated between 1986 and 1994 were analysed in parallel with the in-depth investigation of the archival material of the Documentation du Musée d'Orsay. Thus, it has become possible to re-evaluate the uniqueness and modernity of two of her last curatorial projects, in particular, "1893. L'Europe des peintres", which problematized the formation processes of the European cultural identity and the criteria of the artistic historiographical periodization.

Impaired sleep and low daily activity levels increase the risk of developing metabolic syndrome (MS). Metformin (MET), an insulin sensitizer drug, is effective in regressing MS and has been recently studied as an adjuvant agent for managing sleep disorders. The present study aimed to assess whether 1,700 mg/day of MET treatment modifies sleep and daily activity levels in people with MS evaluated by Rest-Activity circadian Rhythm (RAR), which is the expression of 24 h of spontaneous activity parameters. A total of 133 subjects with MS, randomized into the MET (n = 65) or placebo (PLA, n = 68) group, underwent a clinical/anthropometric examination and carried out a continuous 7-day actigraphic monitoring to investigate sleep and RAR parameters at baseline and after 1 year of intervention. After 1 year of intervention, 105 subjects were analyzed. The MET group showed greater anthropometric and metabolic improvements compared with placebo, with a significant reduction in weight (p = 0.01), body mass index (p = 0.01), waist circumference (p = 0.03), and glucose (p < 0.001). With regard to sleep parameters, the MET group showed a significant increase in actual sleep time (p = 0.01) and sleep efficiency (p = 0.04) compared with placebo. There were no significant changes reported in the RAR parameters. Our study suggests that MET might be used as an adjuvant treatment for sleep disorders in people with MS.

This paper aims to draw attention to the relationship between dance and architecture. After a historical and conceptual contextualisation, it sheds light on how the term choreography evolved its meaning along the twentieth century, indicating a dispositif for building a new ecology of the participative performance experience. In these terms, choreographic architectures can be recognised when in real and metaphysic spaces, movement strategies are planned to activate processes through which human dancing engages with the surrounding environment. This phenomenon is studied by comparing William Forsythe’s theory of the “choreographic object” with some installations performed in urban environments. Finally, to provide an enlarged vision of how a choreographic strategy can cooperate in building a performative ecology to regenerate the inhabiting contexts with the acting presences of socially empowered citizens, my analysis ends with the description of Asingeline and Garden State, two emblematic works by MaMaZa, a Frankfurt-based group of artists.

Abstract The aim of the present study is to explore the potential association between sleep quality and physical activity (PA) in women carriers of BRCA1/2 mutations. 63 women completed the Pittsburgh Sleep Quality Index (PSQI) and Godin Shepard Leisure-Time Physical Activity Questionnaire (GSL-TPAQ) and were included in the present cross-sectional analysis. Globally, women showed a PSQI score of 7.0 ± 3.6 and a GSL-TPAQ score of 22.8 ± 18.3. Good sleepers (PSQI score ≤ 5) showed significantly higher PA levels compared to bad sleepers (PSQI score > 5). Women in the higher tertile of GSL-TPAQ total score (≥ 27 METs/week) have a prevalence ratio (PR) of being a good sleeper of 2.85 (1.25–6.52, 95% confidence intervals) compared to women in the lower tertile (≤ 11 METs/week). These results were consistent in BRCA1 and BRCA2 women. Considering each single question of PA intensity, the PR of being a good sleeper by unit of increase of MET/week was higher and significant in women engaged in strenuous and moderate intensity PA. These results suggests a direct association between PA and sleep quality in women carriers of BRCA mutations.

Risk assessment and management during the entire production process of a radiopharmaceutical are pivotal factors in ensuring drug safety and quality. A methodology of quality risk assessment has been performed by integrating the advice reported in Eudralex, ICHQ, and ISO 9001, and its validity has been evaluated by applying it to real data collected in 21 months of activities of 18F-FDG production at Officina Farmaceutica, CNR-Pisa (Italy) to confirm whether the critical aspects that previously have been identified in the quality risk assessment were effective. The analysis of the results of the real data matched the hypotheses obtained from the model, and in particular, the most critical aspects were those related to human resources and staff organization with regard to management risk. Regarding the production process, the model of operational risk had predicted, as later confirmed by real data, that the most critical phase could be the synthesis and dispensing of the radiopharmaceuticals. So, the proposed method could be used by other similar radiopharmaceutical production sites to identify the critical phases of the production process and to act to improve performance and prevent failure in the entire cycle of radiopharmaceutical products.

The preparation of antiblastic and parental drugs should be carried out by ensuring an aseptic condition and minimizing exposure to toxic drugs. The aim of this study is to evaluate the quality and qualification of these features of an automated dispensing system, called PHARMODUCT®, built by Bioduct s.r.l, part of the Dedalus group. Three antiblastic drugs (cyclophosphamide (powder), 5-fluorouracil and paclitaxel) were used and three preparation and dispensing sessions were carried out for each drug, using PHARMODUCT®. Some of the infusion bags, prepared for each type of antiblastic, were sent to an external laboratory to perform the quantitative dosage analysis and compare it with the quantitative concentration, set on the automatic dispensing equipment, which was found to meet the acceptance criteria of 10%. In addition, to assess the safety of the process for operator exposure to toxic drugs, the differential pressure value between the main chamber and the clean room was measured to be ˂0 Pa, with an hourly leakage rate of ˂2.5 × 10−3 h−1. Media fill tests showed no microbiological growth after a 14-day incubation period. The PHARMODUCT® system meets the requirements of safety and repeatability for the dispensation of parenteral antiblastic drugs.

This study aimed to translate and adapt the English version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children and for parents into the Italian language; validate SSQ for hearing children and their parents; and evaluate the discriminant validity of the instrument. A group of 102 normal-hearing Italian children, aged between 9 and 16 years, and their parents were included in this study. A group of 31 parents of normal-hearing Italian children aged between 6 and 8 years was also included. A group of 57 hearing-impaired Italian children aged between 9 and 16 years, and their parents were also included, as well as a group of 30 parents of hearing-impaired Italian children aged between 6 and 8 years. Cronbach’s alpha in the SSQ for parents was 0.92; it was 0.95 in the SSQ for children. Guttmann’s split-half coefficient in SSQ for children for both λ4 and λ6 was 0.98; in SSQ for parents in λ4 was 0.96 and λ6 was 0.95. These data provide evidence for the discriminant validity of the SSQ scale (p-value < 0.001). Italian SSQ scales for children and for parents are now available.

People can be classified into three chronotypes (CT): morning-type (M-type), Neither-type (N-type) and Evening-type (E-type). M-types perform better in the morning, E-types in the evening. It seems that bad sleep worsens physical performance. The impact of sleep and CT on specific sports and populations is unclear. Therefore, we wanted to assess agility, strength and endurance in young soccer players in relation to their sleep and chronotype. 58 players (13–19 years) were recruited. Sleep and CT were assessed by questionnaires. The physical trial was performed at 8:30 a.m. and 6:00 p.m., and included three tests to determine agility, strength and endurance. The sample was classified by CT as M-types (n = 11), N-types (n = 29) and E-types (n = 18). Furthermore, they were categorized as people with Good Sleep/Wake quality (GSW, n = 28) and people with Bad Sleep/Wake quality (BSW, n = 30). Comparing the three CTs in the aerobic test, M-types performed better in the morning (p = 0.01), while E-types in the evening (p < 0.001). GSW performed better than BSW (p = 0.019) in the aerobic test in the p.m. session. These results underline the difference in aerobic power between M-and E-types during the morning and evening session; moreover, they show a difference in p.m. aerobic performance according to sleep quality.

This study explores the limitations and benefits of different approaches to conducting online focus groups and illustrates an online focus group protocol used within the Value for Schools project in Italy. According to the project evaluation design, 13 online focus groups were organized, with the participation of 101 teachers and 37 school principals. The protocol setup, incorporation, and reorganization of the indications have been discussed in the literature, addressing the methodological and practical issues, such as the selection of participants and preliminary communication with them; the web conference platform (Zoom Business); timing, as well as access times and mode; the roles of the researchers involved (moderator, co-host technical assistant, co-host-observer, co-host-animator) and their integration spaces; technological support; and animation tools. The recording and transcription tools and subsequent analysis of the textual corpus are presented. Finally, the authors discuss the validation and reliability of online focus group protocols.

IntroductionThe Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab.MethodsImmunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor.ResultsA positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823).DiscussionThese results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

Tadalafil is an inhibitor of the enzyme human cyclic guanosine monophosphate–specific phosphodiesterase, type 5 (PDE-5). A mild vasodilator, it is primarily used for the treatment of erectile dysfunction (ED), an increasingly common condition. Other clinical uses include benign prostatic hyperplasia and pulmonary arterial hypertension. Adverse events are rare. Absolute contraindications include serious cardiac disease. Despite the widespread use of tadalafil, very little is known about any associations with lethal cases in forensic pathology, with related post-mortem redistribution phenomena and toxicology. This study presents a forensic case with possible contribution of tadalafil to the cause of death. Furthermore, an overview of tadalafil and a discussion on its relevance in the forensic practice are discussed. The administration of tadalafil might act as a concurrent cause, or contributing factor, to lethal cardiogenic shock in subjects with cardiac disease.

Tadalafil is an inhibitor of the enzyme human cyclic guanosine monophosphate–specific phosphodiesterase, type 5 (PDE-5). A mild vasodilator, it is primarily used for the treatment of erectile dysfunction (ED), an increasingly common condition. Other clinical uses include benign prostatic hyperplasia and pulmonary arterial hypertension. Adverse events are rare. Absolute contraindications include serious cardiac disease. Despite the widespread use of tadalafil, very little is known about any associations with lethal cases in forensic pathology, with related post-mortem redistribution phenomena and toxicology. This study presents a forensic case with possible contribution of tadalafil to the cause of death. Furthermore, an overview of tadalafil and a discussion on its relevance in the forensic practice are discussed. The administration of tadalafil might act as a concurrent cause, or contributing factor, to lethal cardiogenic shock in subjects with cardiac disease.

Background: MicroRNA-33 may control a wide range of different metabolic functions. Methods: This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In a subset of subjects, we compared circulating miR-33a with exosomal miR-33a. Results: Metabolic parameters were altered in O, with initial hyperinsulinemia. Circulating miR-33a was significantly higher in O than in N (p = 0.0002). Significant correlations between miR-33a and auxological and metabolic indices (Insulin p = 0.01; Cholesterol p = 0.01; LDL p = 0.01; HbA1c p = 0.01) were found. Splitting our population (O + N) into two groups, according to the median value of mRNA expression miR-33a levels (0.701), irrespective of the presence or absence of obesity, we observed that those having a higher expression of miR-33a were more frequently obese (87.5% vs. 12.5%; p < 0.0001) and had significantly increased values of auxological and metabolic parameters. Exosomes extracted from plasma of N and O carried miR-33a, and its expression was lower in O (p = 0.026). No correlations with metabolic parameters were observed. Conclusion: While exosome miR-33a does not provide any advantage, circulating miR-33a can provide important indications in an initial phase of metabolic dysfunction, stratifying obese adolescents at higher cardiometabolic risk.

The cardiovascular and metabolic disorders, collectively known as cardiometabolic disease (CMD), are high morbidity and mortality pathologies associated with lower quality of life and increasing health-care costs. The influence of the gut microbiota (GM) in dictating the interpersonal variability in CMD susceptibility, progression and treatment response is beginning to be deciphered, as is the mutualistic relation established between the GM and diet. In particular, dietary factors emerge as pivotal determinants shaping the architecture and function of resident microorganisms in the human gut. In turn, intestinal microbes influence the absorption, metabolism, and storage of ingested nutrients, with potentially profound effects on host physiology. Herein, we present an updated overview on major effects of dietary components on the GM, highlighting the beneficial and detrimental consequences of diet–microbiota crosstalk in the setting of CMD. We also discuss the promises and challenges of integrating microbiome data in dietary planning aimed at restraining CMD onset and progression with a more personalized nutritional approach.

Balneotherapy and exercise are potential factors influencing sleep through several physiological pathways and relaxing effects. This review aims to assess whether balneotherapy can improve sleep quality in concomitance or not with exercise. The research was conducted on Medline, Scopus, PubMed, Web of Science, and Cochrane Library databases. The current review followed PRISMA reporting guidelines and involves twenty-one articles grouped into four sections based on the characteristics of the balneotherapy protocol: 1.a Balneotherapy–thermal water immersion alone (five studies); 1.b Balneotherapy–thermal water immersion with other spa treatments (six studies); 2.a Balneotherapy and physical exercise–balneotherapy and out-of-the-pool physical exercise (eight studies); 2.b Balneotherapy and physical exercise–balneotherapy and in-pool physical exercise (three studies). Apart from healthy or sub-healthy subjects, patients recruited in the studies were affected by fibromyalgia, ankylosing spondylitis, osteoarthritis, musculoskeletal pain, subacute supraspinatus tendinopathy, and mental disorders. Duration, number of sessions, and study protocols are very different from each other. Only one study objectively evaluated sleep, whereas the others used subjective sleep assessment methods. Eight studies considered sleep as a primary outcome and ten as secondary. Sixteen out of twenty-one studies described improvements in self-perceived sleep quality. Thus, balneotherapy associated with other spa treatments and physical exercise seems to be effective in improving self-perceived sleep quality. However, the miscellany of treatments makes it difficult to discern the isolated effects of balneotherapy and physical exercise. Future studies should consider using an objective sleep assessment method and describing the pathways and physiological mechanisms that could provoke sleep changes during balneotherapy treatments.

Personal budgets (PBs) may improve the lives of people with mental health conditions and people with intellectual disability (ID). However, a clear definition of PB, benefits, and challenges is still faded. This work aims to systematically review evidence on PB use in mental health and ID contexts, from both a qualitative and quantitative perspective, and summarize the recent research on interventions, outcomes, and cost-effectiveness of PBs in beneficiaries with mental health conditions and/or ID. The present systematic review is an update of the existing literature analyzed since 2013. We performed a systematic search strategy of articles using the bibliographic databases PubMed and PsycINFO. Six blinded authors screened the works for inclusion/exclusion criteria, and two blinded authors extracted the data. We performed a formal narrative synthesis of the findings from the selected works. A total of 9,800 publications were screened, and 29 were included. Improvement in responsibility and awareness, quality of life, independent living, paid work, clinical, psychological, and social domains, and everyday aspects of the users’ and their carers’ life have been observed in people with mental health conditions and/or ID. However, the PBs need to be less stressful and burdensome in their management for users, carers, and professionals. In addition, more quantitative research is needed to inform PBs’ policymakers.Systematic Review Registration[www.crd.york.ac.uk/prospero/], identifier [CRD42020172607].

The emphasis on graduates’ employability is a significant challenge for universities to support their transitions to the labour market, especially in countries with high youth unemployment rates. The concept of employability and its main definitions constitute the framework of this paper, according to which its influence on higher education policies and practices is considered. In the context of knowledge economies and high-skilled labour demands, employability acts as an educational process that supports the transition from university to work. In this regard, the study directly addresses adult education studies, their impact on career pathways and resourcefulness in the development of a life plan. Based on this framework, the paper illustrates a comparative analysis of employability policies that influence higher education strategies in in Italy, Nigeria and Palestine.

Abstract The comet assay is an electrophoretic technique used to assess DNA damage, as a marker of genotoxicity and oxidative stress, in tissues and biological samples including peripheral blood mononuclear cells (PBMCs) and whole blood (WB). Although numerous studies are performed on stored samples, the impact of cryopreservation on artifactual formation of DNA damage is not widely considered. The present study aims to evaluate the impact of storage at different time-points on the levels of strand breaks (SBs) and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites in isolated PBMCs and WB. Samples were collected, aliquoted and stored at − 80 °C. DNA damage was analyzed on fresh samples, and subsequently on frozen samples every 2 months up to a year. Results have shown no changes in DNA damage in samples of PBMCs and WB stored for up to 4 months, while a significant increase in SBs and Fpg-sensitive sites was documented starting from 6-month up to 12-month storage of both the samples. In addition, fresh and frozen WB showed higher basal levels of DNA damage compared to PBMCs. In conclusion, WB samples show high levels of DNA damage compared to PBMCs. One-year of storage increased the levels of SBs and Fpg-sensitive sites especially in the WB samples. Based on these findings, the use of short storage times and PBMCs should be preferred because of low background level of DNA damage in the comet assay.