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Despite the effectiveness of cancer screening (CS) in providing timely diagnoses and early treatments, the participation of citizens remains very low in particular in Southern Italy. This study aims to investigate the meanings that intervene in the relationship between the individual and their active participation in CSs within public healthcare. A total of 101 ad hoc semi-structured interviews were collected with CS users in public service of Campania Region, Italy. The interviews were analyzed through a qualitative-quantitative methodology by T-Lab software. A cluster analysis and multiple matching analysis were conducted. Findings show five clusters: prevention as a sensory and emotional burden; prevention as a strategy to manage the hereditary risk of death; individual's internal demand for health; the times and places of prevention; and the concreteness of doing prevention; and two factors: from the risk of disease diagnosis to preventive measures and from external healthcare settings to internal self-care settings. Findings shed light on how to construct better well-being promotion strategies and foster a subjective health and prevention demand accounting for the continuous experiences of those participating in CSs to encourage greater citizen engagement., (© 2024 The Author(s). Nursing & Health Sciences published by John Wiley & Sons Australia, Ltd.)

Potential traumatic events, such as breast cancer, can influence autobiographical memory (AM), interrupting the continuity of narrative identity. AM is based on a hierarchical search across different levels of specificity that are indexed from top to bottom when a memory is retrieved. In the breast cancer field, non-specific AMs are an observed clinical phenomenon. In particular, breast cancer survivors report issues related to self-defining memories (SDMs), specific and significant AMs that evoke strong emotions and sensory details at the time of memory. SDMs are linked to life goals and facilitate adaptation to critical experiences, preserving the continuity of identity. This study explored the narrative identity integration process of breast cancer survivors, analyzing themes, specificity, and integrative meaning in SDMs. Ten women participated in an online group support program centered on the integration of AMs linked to the cancer journey. Participants were asked to assess their body image perceptions, filling out an online survey three times, in which they had to report three SDMs each time. A reflexive thematic analysis of the SDMs identified three main themes: the onset of breast cancer; the labeling of negative emotions, and changes in the body. The results indicated inhibited retrieval of specific episodes, fostering a progressive failure in memory characterization and the concurrent meaning-making process. Participants struggled with connecting the memories to insights regarding their self and life, as well as relating the memories to external conditions and other individuals. Further studies might examine the impact of these difficulties on the psychological adjustment of BC long-term survivors. They could also explore cognitive reconstruction by reframing the memories and re-evaluating their traumatic meanings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martino, Sebri, Singer, Madow, Giudice, Mazzoni, Freda and Pravettoni.)

Following the One Health approach, designing multidimensional strategies to orient healthcare in promoting health and preventive processes has become paramount. In particular, in the prevention domain, cancer screening attendance is still unsatisfactory in many populations and requires specific consideration. To this end, following a research-intervention logic, this study aims to investigate the experiences and meanings that users of public cancer screening services associate with prevention, particularly participation in the screenings. The experiences of 103 users (96 females; M age = 54.0; SD = 1.24) of public cancer screening programs in the Campania region (Italy) were collected through interviews. The data collected were analysed following the Grounded Theory Methodology, supported by the software Atlas.ti 8.0. The text material was organised into eight macro-categories: Health and Body; Relationship with Cancer and Diseases; Health Facilities and Health Providers; The Affective Determinants of Cancer Screening Participation; Partners and Children; Physical Sensations and Emotions in the Course of Action; Protective Actions; Promotion and Dissemination. The core category was named Family and Familiarity. Respondents perceived prevention as an act of care for the family and themselves. Our findings support a shift from the idea of taking care of personal health as an individual matter toward considering it as a community issue, according to which resistance to act is overcome for and through the presence of loved ones. The results of this study contribute to a deeper understanding of the perspectives of southern Italian users on participation in cancer screening, and provide important insights to guide future actions to promote these public programmes based primarily on the emerging theme of family and familiarity related to screening programs.

Emotional forecasting, meaning how a person anticipates feeling as a consequence of their choices, drives healthcare decision-making. Research, however, suggests that people often do not fully anticipate or otherwise grasp the future emotional impacts of their decisions. Emotional reappraisal strategies, such as putting emotions into words and sharing emotions with others, may mitigate potential undesirable effects of emotions on decision-making. The use of such strategies is important for consequential decisions, such as obtaining timely mammography screening for breast cancer, whereby earlier diagnosis may impact the success of treatment. In this study, we explored the use of emotional reappraisal strategies for decision-making regarding breast cancer screening attendance among women aged 50-69 years. Data were collected through semi-structured interviews following mammography with a reflexive thematic methodological approach employed for analysis. Results shed light on how participants' emotional response narratives were reconstructed before the mammography, felt during the mammography, and forecasted while awaiting the results. Future research should consider how individuals experience and manage their emotions as they access breast screening services., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly., (© 2024. The Author(s).)

Objective: This study aimed to determine psychosocial differences between children with Long-COVID Syndrome (LCS) and two control groups (i.e., children who did not have COVID-19 and children who had previously had COVID-19 but did not develop LCS) from a bio-psycho-social and psychosomatic perspective. To classify children in these three groups, we examined the percentage of children meeting criteria for LCS, the type, frequency, perceived severity of symptoms, and their prevalence compared with children who never had SARS-CoV-2 infection., Methods: Data were collected from 198 Italian mothers of children aged 4 to 13 years using a cross-sectional web-based case-control survey. Of these, 105 were mothers of children who had contracted SARS-CoV-2 and 94 were mothers of children who had previously had COVID-19. Information was collected on the type and frequency of symptoms commonly referred to as "Long-COVID symptoms" and psychosocial dimensions (i.e., maternal and child health anxiety, COVID-19 anxiety, adjustment, and child deprivation). Descriptive analyses, chi-square tests, Student's T-Test, and analyses of variance were performed., Results: 29 children (15% of the total sample) developed LCS, mostly in the neurological/neuropsychiatric domain (59%), and of mild intensity. Regarding psychosocial and psychological dimensions, maternal health anxiety, child deprivation, and fear of SARS-CoV-2 infection differed between groups, with the first two dimensions higher in children with LCS than in controls and the latter lower in children with LCS than in controls., Conclusion: This study sheds light on the need of integrating a psychosocial approach into the medical care of children with LCS and their caregivers., Competing Interests: Declaration of Competing Interest The authors have no competing interests to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways., Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks., Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months., Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

The main aim of this paper is to discuss the socio-political meaning of the transnational literary production made by female migrant writers. Thus, it analyses their role in the framework of the 'hybrid' literary production of the 21st century in Europe, such as Spain and Italy. Moving away from the idea of national literatures, this paper investigates literature as a geographical and emotional inquiry point and friction between languages, ideas, practices, literary institutions, female authors, and female voices in today's markets. Hybrid literature written by first and second-generation migrants and displaced people is part of a huger concept of transnational literature, which breaks down with the idea of national identity and transiting towards a new conceptualization of hybridity in the literary production, also based on the translation of writings to other languages. The research question is about the relation between the transnational literary works, written by migrant women, and the social change. Based on the conceptualization of the Bhabha's 'third space', I will analyse the relation between the positioning of female migrant writers of 21st century and the role of hybridity. The preliminary findings show, firstly, the idea of reconceptualising it appears in light of the complexity of migrant people's realities and sex-gender differences. By adopting an intersectional lens, focused on the dialectic between gender and race/ethnicity and class, this paper analyses the tensions embedded in the re-positioning of four female migrant writers and their transnational experience (self)reflected in their writings. The present research contributes to the scientific knowledge in the field of cross-cultural literary studies, crossed with the migration study, through questioning the changing gender role and relations in transnational migrant literature. In addition, the findings show that today's reflection on 'third space' theory in the diasporic literature seems an idea to be refined when migrant women are involved., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Di Martino ML.)

An optimal bowel preparation for colonoscopy is essential to increasing the quality of the examination. Visual booklets have been proposed with conflicting results to enhance bowel preparation. A literature search was performed in March 2023 in the most important databases. Only RCTs were selected. We calculated odd ratios (OR) for dichotomous outcomes. Mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity with the Chi 2 and the I 2 statistics. In cases of high heterogeneity, a random effect model was used. Six studies were selected, enrolling 1755 patients overall. Adequate bowel preparation was observed in 86.7% of the booklet group versus 77.5% of the control group, with an OR = 2.31 in favor of the booklet. In studies using a 4-L PEG-based preparation, no difference compared to controls was observed, while in non-PEG formulations, preparation with booklets was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in an inpatient setting without any differences between booklets and controls, while outpatients receiving booklets had better results (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). The adenoma detection rate was similar between the two groups. In conclusion, booklets are useful to improve bowel preparation. Outpatient settings and preparations not containing PEG could benefit more from booklets.

Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates of this compound class. The analysis of thiol-containing metabolites is challenging due to the lack of specific tools, making these compounds difficult to investigate selectively. We have now developed a new methodology comprising bicyclobutane for chemoselective and irreversible capturing of this metabolite class. We utilized this new chemical biology tool immobilized onto magnetic beads for the investigation of human plasma, fecal samples, and bacterial cultures. Our mass spectrometric investigation detected a broad range of human, dietary and bacterial thiol-containing metabolites and we even captured the reactive sulfur species cysteine persulfide in both fecal and bacterial samples. The described comprehensive methodology represents a new mass spectrometric strategy for the discovery of bioactive thiol-containing metabolites in humans and the microbiome., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Research has identified a wide range of psychosocial factors associated to choosing to engage in ongoing cancer screenings. Nevertheless, a systematic review of the theoretical frameworks and constructs underpinning studies on breast, cervical, and colorectal cancer screening participation has yet to be conducted. As part of the action-research project "Miriade," the present study aims to identifying the main theoretical frameworks and constructs adopted in the literature over the past five years to explain cancer screening participation. According to the PRISMA guidelines, a search of the MEDLINE/PubMed and PsycINFO databases was made. Empirical studies conducted from 2017 to 2021 were included. The following keywords were used: breast OR cervical OR colorectal screening AND adhesion OR participation OR engagement AND theoretical framework OR conceptual framework OR theory . Overall, 24 articles met the inclusion criteria. Each theoretical framework highlighted clinical and psychosocial constructs of cancer screening participation, focusing on the individuals (psycho-emotional functioning and skills plan) and/or the health services perspectives. Findings from the present study acknowledge the plurality of the theoretical frameworks and constructs adopted to predict or promote breast, cervical, and colorectal cancer screening adhesion and the need for new research efforts to improve the effectiveness of cancer screening promotion interventions., (© 2022 The Authors.)

Breast cancer (BC) in younger age is a critical and potentially traumatic experience that can interrupt the continuity of self-narrative during a crucial phase. In the Narrative Identity framework the translation of memories into autobiographical narratives is an internal and external process that plays a key role in meaning-making, social relationships and self-coherence. The aim of this study is to examine the role and function that autobiographical memory narratives (AMN) play in the process of adaptation to BC medical treatment. Seventeen BC women below 50 years received prompts to provide autobiographical memory narratives at four phases during their treatment (pre-hospitalization-T1-post-surgery-T2-chemo-radio therapy-T3-follow-up-T4). The Emotional Processing Scale (EPS) was also administered. In all, 68 AMN were collected. A three step procedure of data analysis was conducted. The first one, an empirically-derived memory coding manual to analyze key dimensions of AMN was developed: Agency; Emotional Regulation and Interpersonal Relations. Findings show a particular vulnerability in narrative identity faced by BC women during the shift from T1-T3. In the second one, an emotional coping profile for each woman focusing on the shift from T1-T3 was created. For the third step, these profiles were compared with the EPS scores. The final results suggest the capacity of the AMNs to differentiate the women's emotional adaptation over the course of the BC treatment. Despite the study's limitations, it supports the use of AMN as clinical device to construct a deeper knowledge and profiling trajectory of how women have internalized and elaborated past encounters with illness and help providers, as well as their prior experience of bodily/psychological health and integrity. This information adds to an understanding of their current efforts at recovery and adaptation. In this way we believe that the recollection of narrative memories, not only at the end of the cancer treatment but also during its process, could help the women to mend the broken continuity of their narrative self, as they seek to maintain a healthy balance of internal resources across their past, present, and projected future.

Bacterial host cell invasion has routinely been investigated by gentamicin protection assays, which are laborsome and suffer from pronounced experimental noise. This chapter describes an internally controlled, medium- to high-throughput method that resolves the capacity of multiple Salmonella virulence factor mutant strains to bind and invade host cells. The method, widely applicable to also other pathogens, is based on the combination of consortia of genetically tagged isogenic bacterial strains and a modified gentamicin protection assay. These protocols provide a flexible tool box to stringently quantify host cell binding and invasive properties of different mutants. Moreover, the method can be applied to both infections of cultured host cells and in vivo animal models, providing a comparable genetic readout, which greatly facilitates comparisons across experimental models., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) stimulating the auricular branch of the vagus nerve along a well-defined neuroanatomical pathway, has promising therapeutic efficacy. Potentially, taVNS can modulate autonomic responses. Specifically, taVNS can induce more consistent parasympathetic activation and may lead to increased heart rate variability (HRV). However, the effects of taVNS on HRV remain inconclusive. Here, we investigated changes in HRV due to brief alteration periods of parasympathetic-vagal cardiac activity produced by taVNS on the cymba as opposed to control administration via the helix., Materials and Methods: We compared the effect of 10 min of active stimulation ( i.e ., cymba conchae) to sham stimulation ( i.e ., helix) on peripheral cardiovascular response, in 28 healthy young adults. HRV was estimated in the time domain and frequency domain during the overall stimulation., Results: Although active-taVNS and sham-taVNS stimulation did not differ in subjective intensity ratings, the active stimulation of the cymba led to vagally mediated HRV increases in both the time and frequency domains. Differences were significant between active-taVNS and both sham-taVNS and resting conditions in the absence of stimulation for various HRV parameters, but not for the low-frequency index of HRV, where no differences were found between active-taVNS and sham-taVNS conditions., Conclusion: This work supports the hypothesis that taVNS reliably induces a rapid increase in HRV parameters when auricular stimulation is used to recruit fibers in the cymba compared to stimulation at another site. The results suggest that HRV can be used as a physiological indicator of autonomic tone in taVNS for research and potential therapeutic applications, in line with the established effects of invasive VNS. Knowledge of the physiological effect of taVNS short sessions in modulating cardiovagal processing is essential for enhancing its clinical use., Competing Interests: Mariella Pazzaglia is an Academic Editor for PeerJ., (© 2022 Forte et al.)

Despite the proven effectiveness of cancer prevention, the literature highlights numerous obstacles to the adoption of screening, even at a young age. In cancer discourse, the metaphor of war is omnipresent and reflects an imperative demand to win the war against disease. From the psychodynamic perspective, the risk of cancer forecasts an emotionally critical experience for which it is important to study mental representations concerning illness and health care. Through the creation of an invented story that offers a framework for imagination, our aim is to understand what the relationship with preventive practices in oncology means for young women and how this relationship is revealed by their metaphors. A total of 58 young women voluntarily participated in the present research, answering a narrative prompt. The stories written by the participants were analyzed using qualitative methodology to identify construct, themes and metaphors. Our findings identify four constructs: the construction of a defense: youth as protection; the attribution of blame about cancer risk; learning from experience as a prevention activator; and from inaccessibility to access to preventive practices: the creation of engagement. The construction of an invented story allows us to promote a process of prefiguration on the bodily, affective and thought planes invested in preventive practice and brings out the use of metaphors to represent cancer risk and self-care. The results allow us to think about the construction of interventions to promote engagement processes in prevention from an early age.

Objective: The present study aims at systematically reviewing research conducted on factors promoting breast, cervical and colorectal cancer screenings participation., Methods: A literature search in MEDLINE/PubMed and PsycInfo from January 2017 to October 2021 was performed. Data extraction, researchers' full agreement and the inclusion criteria produced 102 eligible studies. Data were narratively synthesized and critically interpreted., Results: Multiple factors favoring or hindering breast, cervical and colorectal cancer screenings were identified and summarized as factors operating at the individual level (background information, individual characteristics, emotions related to screening procedure and to cancer, knowledge and awareness), at the relational level (relationships with healthcare staff, significant others, community members), and at the healthcare system level (systems barriers/policy, lack of staff). A critical appraisal of studies revealed a fragmentation in the literature, with a compartmentalization of studies by type of cancer screening, country and specific populations of destination., Conclusions: Overall findings indicated that greater integration of research results obtained independently for each cancer diagnosis and within the different countries/populations could foster a more comprehensive understanding of factors potentially enhancing the participation in breast, cervical and colorectal cancer screenings worldwide. This review, which is grounded in the current context of globalization and superdiversification in population, can help to enhance a better integration between research and practices, by supporting the development of more effective and inclusive evidence-based interventions and health-promotion campaigns worldwide. Research and practical implications are highlighted and discussed., (© 2022 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Cancer screening programs are public health interventions beneficial to early diagnoses and timely treatments. Despite the investment of health policies in this area, many people in the recommended age groups do not participate. While the literature is mainly focused on obstacles and factors enabling access to health services, a gap from the point of view of the target population concerns healthcare providers. Within the "Miriade" research-action project, this study aims to explore the dimensions that mediate the relationship between healthcare providers and preventive practices through the narrations of 52 referents and healthcare providers involved in breast, cervical and colorectal cancer screening. We conducted ad hoc narrative interviews and used theory-driven analysis based on Penchansky and Thomas' conceptualization and Saurman's integration of six dimensions of healthcare access: affordability, availability, accessibility, accommodation, acceptability and awareness. The results show that 21 thematic categories were representative of the access dimensions, and 5 thematic categories were not; thus, we have classified the latter as the dimension of affection. The results suggest trajectories through which psychological clinical intervention might be constructed concerning health, shared health decisions and access to cancer screening.

Shigella spp, the etiological agents of bacillary dysentery in humans, have evolved an intricate regulatory strategy to ensure fine-tuned expression of virulence genes in response to environmental stimuli. A key component in this regulation is VirF, an AraC-like transcription factor, which at the host temperature (37°C) triggers, directly or indirectly, the expression of > 30 virulence genes important for invasion of the intestinal epithelium. Previous work identified two different forms of VirF with distinct functions: VirF30 activates virulence gene expression, while VirF21 appears to negatively regulate virF itself. Moreover, VirF21 originates from either differential translation of the virF mRNA or from a shorter leaderless mRNA (llmRNA). Here we report that both expression of the virF21 llmRNA and the VirF21:VirF30 protein ratio are higher at 30°C than at 37°C, suggesting a possible involvement of VirF21 in minimizing virulence gene expression outside the host (30°C). Ectopic elevation of VirF21 levels at 37°C indeed suppresses Shigella´s ability to infect epithelial cells. Finally, we find that the VirF21 C-terminal portion, predicted to contain a Helix-Turn-Helix motif (HTH2), is required for the functionality of this negative virulence regulator., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

The behaviors of infectious bacteria are commonly studied in bulk. This is effective to define the general properties of a given isolate, but insufficient to resolve subpopulations and unique single-microbe behaviors within the bacterial pool. We here employ microscopy to study single-bacterium characteristics among Salmonella enterica serovar Typhimurium (S.Tm), as they prepare for and launch invasion of epithelial host cells. We find that during the bacterial growth cycle, S.Tm populations switch gradually from fast planktonic growth to a host cell-invasive phenotype, characterized by flagellar motility and expression of the Type-three-secretion-system-1. The indistinct nature of this shift leads to the establishment of a transient subpopulation of S.Tm "doublets"-waist-bearing bacteria anticipating cell division-which simultaneously express host cell invasion machinery. In epithelial cell culture infections, these S.Tm doublets outperform their "singlet" brethren and represent a hyperinvasive subpopulation. Atop both glass and enteroid-derived monolayers, doublets swim along markedly straighter trajectories than singlets, thereby diversifying search patterns and improving the surface exploration capacity of the total bacterial population. The straighter swimming, combined with an enhanced cell-adhesion propensity, suffices to account for the hyperinvasive doublet phenotype. This work highlights bacterial cell length heterogeneity as a key determinant of target search patterns atop epithelia., (© 2022 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Background: Sex differences are widely reported in clinical psychology but are rarely examined in interventions., Method: This mixed-method explorative study examined sex differences in 13 mothers and 10 fathers of children in the off-therapy phase of acute lymphoblastic leukaemia. Parents underwent an expressive writing intervention using the guided written disclosure protocol (GWDP)., Results: Mothers had more negative mood profiles than fathers but improved more during the intervention., Conclusion: Though preliminary, our findings highlight the importance of sex as a potential moderator of intervention and treatment outcome that could be of great clinical significance., Competing Interests: The authors have declared that no competing interests exist.

Breast cancer (BC) in women under 50 is a potentially traumatic experience that can upset a woman's life during a crucial phase of her lifespan. Anticipatory mourning linked to the diagnosis of BC can produce a series of inevitable losses similar to those of the bereaved. Narration can be one tool to construct meaning, to grow through the experience, and reconfigure time perspectives during and after the illness. The aim of this study was to apply the Meaning of Loss Codebook (MLC) to the narrative context of young women with BC. An ad hoc narrative interview was administered to 17 women at four times during the first year of treatment. A thematic analysis was performed using the MLC, adopting a bottom-up and top-down methodology. The results highlight the MLC's usefulness in capturing the experiences of the women, allowing for a greater appreciation of the nuances of the meanings embodied in their narratives. The thematic categories grounded in the MLC cover the whole experience of BC during the first year of treatment, attesting to the possibility of extending the use of the MLC to observe the longitudinal elaboration of the psychic experience of BC in addition to its established validity in the context of bereavement and loss.

Spinal cord injuries (SCI) are disruptive neurological events that severly affect the body leading to the interruption of sensorimotor and autonomic pathways. Recent research highlighted SCI-related alterations extend beyond than the expected network, involving most of the central nervous system and goes far beyond primary sensorimotor cortices. The present perspective offers an alternative, useful way to interpret conflicting findings by focusing on the deafferented and deefferented body as the central object of interest. After an introduction to the main processes involved in reorganization according to SCI, we will focus separately on the body regions of the head, upper limbs, and lower limbs in complete, incomplete, and deafferent SCI participants. On one hand, the imprinting of the body's spatial organization is entrenched in the brain such that its representation likely lasts for the entire lifetime of patients, independent of the severity of the SCI. However, neural activity is extremely adaptable, even over short time scales, and is modulated by changing conditions or different compensative strategies. Therefore, a better understanding of both aspects is an invaluable clinical resource for rehabilitation and the successful use of modern robotic technologies.

A breast cancer diagnosis is a critical event with a potentially traumatic nature. In recent years there has been an increase of this illness in women aged under-fifty, a group of particular scientific interest. In this article the authors review the recent scientific literature on psychological impact of breast cancer experiences in under-50 women. Our results highlight three trajectories: clinical psychological risks; feminine-specific concerns; resources between individual and relational aspects. This overview illustrates the complexity of the effects of breast cancer in under-50women allowing to think about theoretical and psychosocial models to provide support for under-50 women during the illness experience.

Spinal cord injuries (SCIs) exert devastating effects on body awareness, leading to the disruption of the transmission of sensory and motor inputs. Researchers have attempted to improve perceived body awareness post-SCI by intervening at the multisensory level, with the integration of somatic sensory and motor signals. However, the contributions of interoceptive-visceral inputs, particularly the potential interaction of motor and interoceptive signals, remain largely unaddressed. The present perspective aims to shed light on the use of interoceptive signals as a significant resource for patients with SCI to experience a complete sense of body awareness. First, we describe interoceptive signals as a significant obstacle preventing such patients from experiencing body awareness. Second, we discuss the multi-level mechanisms associated with the homeostatic stability of the body, which creates a unified, coherent experience of one's self and one's body, including real-time updates. Body awareness can be enhanced by targeting the vagus nerve function by, for example, applying transcutaneous vagus nerve stimulation. This perspective offers a potentially useful insight for researchers and healthcare professionals, allowing them to be better equipped in SCI therapy. This will lead to improved sensory motor and interoceptive signals, a decreased likelihood of developing deafferentation pain, and the successful implementation of modern robotic technologies.

Virus-like particles (VLPs) constitute large, polyvalent platforms onto which a wide variety of functional units can be grafted. Their use in biological settings often depends on their specific binding to cells or receptors of interest; this can be compromised by excessive nonspecific association with other cells. We found that lysine residues mediate such nonspecific interactions, presumably by virtue of protonation and interaction with anionic membrane lipid headgroups and/or complementary residues of cell surface proteins and polysaccharides. Chemical acylation of surface-exposed amines of the Qβ VLP led to a significant reduction in the association of particles with mammalian cells. Single-point mutations of particular lysine residues to either glutamine, glutamic acid, tryptophan, or phenylalanine were mostly well-tolerated and formed intact capsids, but the introduction of double and triple mutants was far less forgiving. Introduction of glutamic acid at position 13 (K13E) led to a dramatic increase in cellular binding, whereas removal of the lysine at position 46 (K46Q) led to an equally striking reduction. Several plasma membrane components were found to specifically interact with the Qβ capsid irrespective of surface charge. These results suggest that specific cellular interactions are engaged or obviated by such mutations and provide us with more "benign" particles to which can be added binding functionality for targeted delivery applications.

Background: Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification., Design and Methods: In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots' scanning by SEM. Images acquired with SEM were then analyzed with the MATLAB software with the "Texture Analysis" methods to perform classification. Among the various texture parameters, we reported Contrast and Energy., Results: Significant differences among healthy subjects, patients with AHA and those treated with VKAs were detected for the coagulative parameters. We found no differences between VKAs and AHA patients. Contrast and energy highlighted a significant difference among the three groups in agreement with the laboratory's parameters. We found no significant differences between VKAs and AHA patients., Conclusions: The use of SEM, CWA and thrombin generation parameters may be a starting point for studies aimed to demonstrate the general characteristics of clot formation in different clinical conditions with a multiparametric approach.

The gut epithelium is a critical protective barrier. Its NAIP/NLRC4 inflammasome senses infection by Gram-negative bacteria, including Salmonella Typhimurium (S.Tm) and promotes expulsion of infected enterocytes. During the first ~12-24 h, this reduces mucosal S.Tm loads at the price of moderate enteropathy. It remained unknown how this NAIP/NLRC4-dependent tradeoff would develop during subsequent infection stages. In NAIP/NLRC4-deficient mice, S.Tm elicited severe enteropathy within 72 h, characterized by elevated mucosal TNF (>20 pg/mg) production from bone marrow-derived cells, reduced regeneration, excessive enterocyte loss, and a collapse of the epithelial barrier. TNF-depleting antibodies prevented this destructive pathology. In hosts proficient for epithelial NAIP/NLRC4, a heterogeneous enterocyte death response with both apoptotic and pyroptotic features kept S.Tm loads persistently in check, thereby preventing this dire outcome altogether. Our results demonstrate that immediate and selective removal of infected enterocytes, by locally acting epithelium-autonomous NAIP/NLRC4, is required to avoid a TNF-driven inflammatory hyper-reaction that otherwise destroys the epithelial barrier.

The gut epithelium serves to maximize the surface for nutrient and fluid uptake, but at the same time must provide a tight barrier to pathogens and remove damaged intestinal epithelial cells (IECs) without jeopardizing barrier integrity. How the epithelium coordinates these tasks remains a question of significant interest. We used imaging and an optical flow analysis pipeline to study the dynamicity of untransformed murine and human intestinal epithelia, cultured atop flexible hydrogel supports. Infection with the pathogen Salmonella Typhimurium ( S Tm) within minutes elicited focal contractions with inward movements of up to ∼1,000 IECs. Genetics approaches and chimeric epithelial monolayers revealed contractions to be triggered by the NAIP/NLRC4 inflammasome, which sensed type-III secretion system and flagellar ligands upon bacterial invasion, converting the local tissue into a contraction epicenter. Execution of the response required swift sublytic Gasdermin D pore formation, ion fluxes, and the propagation of a myosin contraction pulse across the tissue. Importantly, focal contractions preceded, and could be uncoupled from, the death and expulsion of infected IECs. In both two-dimensional monolayers and three-dimensional enteroids, multiple infection-elicited contractions coalesced to produce shrinkage of the epithelium as a whole. Monolayers deficient for Caspase-1(-11) or Gasdermin D failed to elicit focal contractions but were still capable of infected IEC death and expulsion. Strikingly, these monolayers lost their integrity to a markedly higher extent than wild-type counterparts. We propose that prompt NAIP/NLRC4/Caspase-1/Gasdermin D/myosin-dependent contractions allow the epithelium to densify its cell packing in infected regions, thereby preventing tissue disintegration due to the subsequent IEC death and expulsion process., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Endothelial damage and fibro-proliferative vasculopathy of small vessels are pathological hallmarks of systemic sclerosis (SSc). The consequence is the detachment of resident elements that become circulating endothelial cells (CECs). The aim of our study was to evaluate the potential of CECs as biomarker in SSc. We enrolled 50 patients with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subset of SSc, who underwent clinical evaluation to establish the organ involvement. CECs were measured by flow-cytometry utilizing a polychromatic panel. An evident difference was observed in CEC counts comparing controls to SSc patients (median 10.5 vs. 152 cells/ml, p < 0.0001) and for the first time, between the two subsets of disease (median lcSSc 132 vs. dcSSc 716 CEC/ml, p < 0.0001). A significant correlation was established between CECs and some SSc clinical parameters, such as digital ulcers, skin and pulmonary involvement, presence of Scl-70 antibodies, nailfold videocapillaroscopy patterns and EUSTAR activity index. After 12 months, CECs correlated with clinical worsening of patients, showing that a number higher than 414 CEC/ml is a strong negative prognostic factor (RR 5.70). Our results indicate that CECs are a direct indicator of systemic vascular damage. Therefore, they can be used as a reliable marker of disease severity.

Enterobacterial pathogens infect the gut by a multistep process, resulting in colonization of both the lumen and the mucosal epithelium. Due to experimental constraints, it remains challenging to address how luminal and epithelium-lodged pathogen populations cross-feed each other in vivo Enteroids are cultured three-dimensional miniature intestinal organs with a single layer of primary intestinal epithelial cells (IECs) surrounding a central lumen. They offer new opportunities to study enterobacterial infection under near-physiological conditions, at a temporal and spatial resolution not attainable in animal models, but remain poorly explored in this context. We employed microinjection, time-lapse microscopy, bacterial genetics, and barcoded consortium infections to describe the complete infection cycle of Salmonella enterica serovar Typhimurium in both human and murine enteroids. Flagellar motility and type III secretion system 1 (TTSS-1) promoted Salmonella Typhimurium targeting of the intraepithelial compartment and breaching of the epithelial barrier. Strikingly, however, TTSS-1 also potently boosted colonization of the enteroid lumen. By tracing the infection over time, we identified a cycle(s) of TTSS-1-driven IEC invasion, intraepithelial replication, and reemergence through infected IEC expulsion as a key mechanism for Salmonella Typhimurium luminal colonization. These findings suggest a positive feed-forward loop, through which IEC invasion by planktonic bacteria fuels further luminal population expansion, thereby ensuring efficient colonization of both the intraepithelial and luminal niches. IMPORTANCE Pathogenic gut bacteria are common causes of intestinal disease. Enteroids-cultured three-dimensional replicas of the mammalian gut-offer an emerging model system to study disease mechanisms under conditions that recapitulate key features of the intestinal tract. In this study, we describe the full life cycle of the prototype gut pathogen Salmonella enterica serovar Typhimurium within human and mouse enteroids. We map the consecutive steps and define the bacterial virulence factors that drive colonization of luminal and epithelial compartments, as well as breaching of the epithelial barrier. Strikingly, our work reveals how bacterial colonization of the epithelium potently fuels expansion also in the luminal compartment, through a mechanism involving the death and expulsion of bacterium-infected epithelial cells. These findings have repercussions for our understanding of the Salmonella infection cycle. Moreover, our work provides a comprehensive foundation for the use of microinjected enteroids to model gut bacterial diseases., (Copyright © 2021 Geiser et al.)

Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial cell invasion. According to this model, the Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia- and filopodia-containing ruffles and cooperative S.Tm uptake. However, cell line experiments poorly recapitulate many of the cell and tissue features encountered in the host's gut mucosa. Here, we employed bacterial genetics and multiple imaging modalities to compare S.Tm invasion of cultured epithelial cell lines and the gut absorptive epithelium in vivo in mice. In contrast to the prevailing ruffle-model, we find that absorptive epithelial cell entry in the mouse gut occurs through "discreet-invasion". This distinct entry mode requires the conserved TTSS-1 effector SipA, involves modest elongation of local microvilli in the absence of expansive ruffles, and does not favor cooperative invasion. Discreet-invasion preferentially targets apicolateral hot spots at cell-cell junctions and shows strong dependence on local cell neighborhood. This proof-of-principle evidence challenges the current model for how S.Tm can enter gut absorptive epithelial cells in their intact in vivo context., Competing Interests: The authors have declared that no competing interests exist.

Most phenotypic screens aiming to discover new antimalarial chemotypes begin with low cost, high-throughput tests against the asexual blood stage (ABS) of the malaria parasite life cycle. Compounds active against the ABS are then sequentially tested in more difficult assays that predict whether a compound has other beneficial attributes. Although applying this strategy to new chemical libraries may yield new leads, repeated iterations may lead to diminishing returns and the rediscovery of chemotypes hitting well-known targets. Here, we adopted a different strategy to find starting points, testing ∼70,000 open source small molecules from the Global Health Chemical Diversity Library for activity against the liver stage, mature sexual stage, and asexual blood stage malaria parasites in parallel. In addition, instead of using an asexual assay that measures accumulated parasite DNA in the presence of compound (SYBR green), a real time luciferase-dependent parasite viability assay was used that distinguishes slow-acting (delayed death) from fast-acting compounds. Among 382 scaffolds with the activity confirmed by dose response (<10 μM), we discovered 68 novel delayed-death, 84 liver stage, and 68 stage V gametocyte inhibitors as well. Although 89% of the evaluated compounds had activity in only a single life cycle stage, we discovered six potent (half-maximal inhibitory concentration of <1 μM) multistage scaffolds, including a novel cytochrome bc1 chemotype. Our data further show the luciferase-based assays have higher sensitivity. Chemoinformatic analysis of positive and negative compounds identified scaffold families with a strong enrichment for activity against specific or multiple stages.

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential., Competing Interests: The support of Becton Dickinson does not alter our adherence to PLOS ONE policies on sharing data and materials.

The sense of agency is an ongoing process of semiotic construction of the action starting from the affective, cognitive, intersubjective and cultural matrix of experience. A person narratively constructs the sense of her agentive experience and in doing so does not refer exclusively to the "what", but also to the "how". There is always a specific "modus" to experience one's own action. We present the psychological notion of the Modal Articulation Process (MAP), namely the way through which a person orients and configures in a contextual frame the sense of her actions by means of modal operators of necessity, possibility, impossibility, contingency, but also knowledge, will, capability, constrain and opportunity. The notion of Modal Articulation Process is proposed as a semiotic, dynamic and recursive process that articulates narratively many aspects of the agency: the relational positionings and the way of experiencing them, the constraints and the resources present in the socio-symbolic context, the inherent temporality of every human phenomenon. Although the study of modal operators has an ancient and solid tradition of research in the fields of modal logics, analytical philosophy and narrative semiotic disciplines as well, yet in the field of the psychological sciences - except for a few authoritative isolated cases (Kurt Lewin, Rom Harrè, Jaan Valsiner) - there is not a great deal of attention on the relevance of these symbolic devices and their function in constructing the sense of action in a narrative way. Indeed modal articulation processes are at stake both during daily common routines and during exceptional turning point experiences that request a reconfiguration of the sense of one's own agency (e.g. the experiences of illness demand a new modal re-articulation). Our discussion is aimed at deepening and developing the notion of modal articulation, its functions and its specificities.

Bacterial host cell invasion mechanisms depend on the bacterium's virulence factors and the properties of the target cell. The enteropathogen Salmonella enterica serovar Typhimurium ( S Tm) invades epithelial cell types in the gut mucosa and a variety of immune cell types at later infection stages. The molecular mechanism(s) of host cell entry has, however, been studied predominantly in epithelial cell lines. S Tm uses a type three secretion system (TTSS-1) to translocate effectors into the host cell cytosol, thereby sparking actin ruffle-dependent entry. The ruffles also fuel cooperative invasion by bystander bacteria. In addition, several TTSS-1-independent entry mechanisms exist, involving alternative S Tm virulence factors, or the passive uptake of bacteria by phagocytosis. However, it remains ill-defined how S Tm invasion mechanisms vary between host cells. Here, we developed an internally controlled and scalable method to map S Tm invasion mechanisms across host cell types and conditions. The method relies on host cell infections with consortia of chromosomally tagged wild-type and mutant S Tm strains, where the abundance of each strain can be quantified by qPCR or amplicon sequencing. Using this methodology, we quantified cooccurring TTSS-1-dependent, cooperative, and TTSS-1-independent invasion events in epithelial, monocyte, and macrophage cells. We found S Tm invasion of epithelial cells and monocytes to proceed by a similar MOI-dependent mix of TTSS-1-dependent and cooperative mechanisms. TTSS-1-independent entry was more frequent in macrophages. Still, TTSS-1-dependent invasion dominated during the first minutes of interaction also with this cell type. Finally, the combined action of the SopB/SopE/SopE2 effectors was sufficient to explain TTSS-1-dependent invasion across both epithelial and phagocytic cells. IMPORTANCE Salmonella enterica serovar Typhimurium ( S Tm) is a widespread and broad-host-spectrum enteropathogen with the capacity to invade diverse cell types. Still, the molecular basis for the host cell invasion process has largely been inferred from studies of a few selected cell lines. Our work resolves the mechanisms that Salmonellae employ to invade prototypical host cell types, i.e., human epithelial, monocyte, and macrophage cells, at a previously unattainable level of temporal and quantitative precision. This highlights efficient bacterium-driven entry into innate immune cells and uncovers a type III secretion system effector module that dominates active bacterial invasion of not only epithelial cells but also monocytes and macrophages. The results are derived from a generalizable method, where we combine barcoding of the bacterial chromosome with mixed consortium infections of cultured host cells. The application of this methodology across bacterial species and infection models will provide a scalable means to address host-pathogen interactions in diverse contexts., (Copyright © 2019 Di Martino et al.)