Search

Bacteriophages (viruses of bacteria) play a pivotal role in shaping both the evolution and dynamics of bacterial populations. Bacteria employ arsenals of genetically encoded phage defense systems, but can alternatively achieve protection by changing the availability of cellular resources that phages rely on for propagation. These physiological changes are often adaptive responses to unique environmental signals. The facultative pathogen Vibrio cholerae adapts to both aquatic and intestinal environments with niche-specific physiological changes that ensure its evolutionary success in such disparate settings. In both niches, V. cholerae is susceptible to predation by lytic phages like ICP1. However, both phages and susceptible bacterial hosts coexist in nature, indicating that environmental cues may modulate V. cholerae cell state to protect against phage infection. This work explores one such modification in response to the intestine-specific signals of bile and anaerobicity. We found that V. cholerae grown in these conditions reduces O1-antigen decoration on its outer membrane lipopolysaccharide. Because the O1-antigen is an essential moiety for ICP1 phage infection, we investigated the effect of partial O1-antigen depletion as a mechanism of phage defense and observed that O1-depletion limits phage adsorption. We identified mechanistic contributions to O1-depletion, including the essentiality of a weak acid tolerance system for O1 production at low pH and alterations in transcriptional profiles indicating limitations in resources for O1-biosynthesis. This analysis illustrates a complex interplay between signals relevant to the intestinal environment and bacterial physiology that provides V. cholerae with protection from phage predation. IMPORTANCE Vibrio cholerae is the bacterial pathogen responsible for cholera, a diarrheal disease that impacts people in areas without access to potable water. In regions that lack such infrastructure, cholera represents a large proportion of disease outbreaks. Bacteriophages (phages, viruses that infect bacteria) have recently been examined as potential therapeutic and prophylactic agents to treat and prevent bacterial disease outbreaks like cholera due to their specificity and stability. This work examines the interaction between V. cholerae and vibriophages in consideration for a cholera prophylaxis regimen (M. Yen, L. S. Cairns, and A. Camilli, Nat Commun 8:14187, 2017, https://doi.org/10.1038/ncomms14187) in the context of stimuli found in the intestinal environment. We discover that common signals in the intestinal environment induce cell surface modifications in V. cholerae that also restrict some phages from binding and initiating infection. These findings could impact considerations for the design of phage-based treatments, as phage infection appears to be limited by bacterial adaptations to the intestinal environment.

Introduction The diagnosis of endometriomas in patients with endometriosis is of primary importance because it influences the management and prognosis of infertility and pain. Imaging techniques are evolving constantly. This study aimed to systematically assess the diagnostic accuracy of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) in detecting endometrioma using the surgical visualisation of lesions with or without histopathological confirmation as reference standards in patients of reproductive age with suspected endometriosis.Methods PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov databases were searched from their inception to 12 October 2022, using a manual search for additional articles. Two authors independently performed title, abstract and full-text screening of the identified records, extracted study details and quantitative data and assessed the quality of the studies using the ‘Quality Assessment of Diagnostic Accuracy Study 2’ tool. Bivariate random-effects models were used to determine the pooled sensitivity and specificity, compare the two imaging modalities and evaluate the sources of heterogeneity.Results Sixteen prospective studies (10 assessing TVUS, 4 assessing MRI and 2 assessing both TVUS and MRI) were included, representing 1976 participants. Pooled TVUS and MRI sensitivities for endometrioma were 0.89 (95% confidence interval ‘CI’, 0.86–0.92) and 0.94 (95% CI, 0.74–0.99), respectively (indirect comparison p-value of 0.47). Pooled TVUS and MRI specificities for endometrioma were 0.95 (95% CI, 0.92–0.97) and 0.94 (95% CI, 0.89–0.97), respectively (indirect comparison p-value of 0.51). These studies had a high or unclear risk of bias. A direct comparison (all participants undergoing TVUS and MRI) of the modalities was available in only two studies.Conclusion TVUS and MRI have high accuracy for diagnosing endometriomas; however, high-quality studies comparing the two modalities are lacking.

Bacteria can acquire mobile genetic elements (MGEs) to combat infection by viruses (phages). Satellite viruses, including the PLEs (phage-inducible chromosomal island-like elements) in epidemic Vibrio cholerae, are MGEs that restrict phage replication to the benefit of their host bacterium. PLEs parasitize the lytic phage ICP1, unleashing multiple mechanisms to restrict phage replication and promote their own spread. In the arms race against PLE, ICP1 uses nucleases, including CRISPR-Cas, to destroy PLE's genome during infection. However, through an unknown CRISPR-independent mechanism, specific ICP1 isolates subvert restriction by PLE. Here, we discover ICP1-encoded Adi that counteracts PLE by exploiting the PLE's large serine recombinase (LSR), which normally mobilizes PLE in response to ICP1 infection. Unlike previously characterized ICP1-encoded anti-PLE mechanisms, Adi is not a nuclease itself but instead appears to modulate the activity of the LSR to promote destructive nuclease activity at the LSR's specific attachment site, attP. The PLE LSR, its catalytic activity, and attP are additionally sufficient to sensitize a PLE encoding a resistant variant of the recombination module to Adi activity. This work highlights a unique type of adaptation arising from inter-genome conflicts, in which the intended activity of a protein can be weaponized to overcome the antagonizing genome.

Abstract The number of embryonic primordial germ cells in Drosophila is determined by the quantity of germ plasm, whose assembly starts in the posterior region of the oocyte during oogenesis. Here, we report that extending JAK-STAT activity in the posterior somatic follicular epithelium leads to an excess of primordial germ cells in the future embryo. We show that JAK-STAT signaling is necessary for the differentiation of approximately 20 specialized follicle cells maintaining tight contact with the oocyte. These cells define, in the underlying posterior oocyte cortex, the anchoring of the germ cell determinant oskar mRNA. We reveal that the apical surface of these posterior anchoring cells extends long filopodia penetrating the oocyte. We identify two JAK-STAT targets in these cells that are each sufficient to extend the zone of contact with the oocyte, thereby leading to production of extra primordial germ cells. JAK-STAT signaling thus determines a fixed number of posterior anchoring cells required for anterior-posterior oocyte polarity and for the development of the future germline.

The increase in coastal risks associated with rising sea levels calls for dynamic adaptation measures to reorganise coastal territory. The challenges of appropriating measures and putting them into practice are major. They are multi-level and at the crossroads of different policies: land use planning, tourism, risk management and so on. Faced with these challenges, this article reports on a co-construction process towards a policy of spatial integrated managed retreat in the context of the Occitanie region and its governance. In practice, this resulted in the co-construction of a shared regional framework, building a community of practice and adapting territorial governance arrangements. This article offers a reflective analysis of this co-construction. Firstly, the process (30 months in total) is transcribed by means of a chronicle, detailing the diversity and complementarity of methods and approaches that have been used. The main achievements (common definition, principles of action, scale of intervention, temporal typology of actions) and the choice of a governance framework are then presented and discussed on how they could contribute to gradually build a community of practice as well as the types of constraints encountered. The contributions towards the community of practice are analysed in terms of knowledge sharing, pooling and collective learning. This reflective analysis provides lessons for local stakeholders and, more broadly, for the transition of coastal territory.

This paper reports the results of a study aimed at understanding the processes governing the construction of educational inequalities in French classrooms, the French school system being particularly unequal. Traditional explanations have focused on the factors governing the production of inequalities but have not always shown how these factors translate into learning inequalities in class. Consistent with relational approaches, the study draws on ethnographic research conducted over an 18-month period in 6 socially contrasting Parisian schools. Both students from wealthy families considered to be 'high-achieving' and students from poor families viewed as being 'low-achieving' were observed over the course of full school days to understand the factors that lead them to develop different activities. The evidence suggests that children interpret teacher expectations very differently, although the same expectations were observed in all the classes observed during the study. These expectations point to an invisible curriculum operating alongside the formal curriculum and generally perceived only by high-achieving students, who are able to grasp and understand it through their prior socialization. A further characteristic of the invisible curriculum is that it is rarely made explicit by teachers. This finding highlights the need to further examine explicitation strategies in schools.

Abstract Background Implementing evidence-based healthcare practices (EBPs) is a complex endeavour and often lags behind research-informed decision processes. Understanding and systematically improving implementation using implementation theory can help bridge the gap between research findings and practice. This study aims to translate, pilot, and validate a German version of the English NoMAD questionnaire (G-NoMAD), an instrument derived from the Normalisation Process Theory, to explore the implementation of EBPs. Methods Survey data has been collected in four German research projects and subsequently combined into a validation data set. Two versions of the G-NoMAD existed, independently translated from the original English version by two research groups. A measurement invariance analysis was conducted, comparing latent scale structures between groups of respondents to both versions. After determining the baseline model, the questionnaire was tested for different degrees of invariance (configural, metric, scalar, and uniqueness) across samples. A confirmatory factor analysis for three models (a four-factor, a unidimensional, and a hierarchical model) was used to examine the theoretical structure of the G-NoMAD. Finally, psychometric results were discussed in a consensus meeting, and the final instructions, items, and scale format were consented to. Results A total of 539 health care professionals completed the questionnaire. The results of the measurement invariance analysis showed configural, partial metric, and partial scalar invariance indicating that the questionnaire versions are comparable. Internal consistency ranged from acceptable to good (0.79 ≤ α ≤ 0.85) per subscale. Both the four factor and the hierarchical model achieved a better fit than the unidimensional model, with indices from acceptable (SRMR = 0.08) to good (CFI = 0.97; TLI = 0.96). However, the RMSEA values were only close to acceptable (four-factor model: χ2164 = 1029.84, RMSEA = 0.10; hierarchical model: χ2166 = 1073.43, RMSEA = 0.10). Conclusions The G-NoMAD provides a reliable and promising tool to measure the degree of normalisation among individuals involved in implementation activities. Since the fit was similar in the four-factor and the hierarchical model, priority should be given to the practical relevance of the hierarchical model, including a total score and four subscale scores. The findings of this study support the further usage of the G-NoMAD in German implementation settings. Trial registration Both the AdAM project (No. NCT03430336, 06/02/2018) and the EU-project ImpleMentAll (No. NCT03652883, 29/08/2018) were registered on ClinicalTrials.gov. The ImplementIT study was registered at the German Clinical Trial Registration (No. DRKS00017078, 18/04/2019). The G-NoMAD validation study was registered at the Open Science Framework (No7u9ab, 17/04/2023).

BackgroundTherapist-guided exposure and response prevention (ERP) for the treatment of obsessive-compulsive disorder (OCD) is frequently conducted within clinical settings but rarely at places where patients are usually confronted with OCD symptom-provoking situations in daily life (eg, at home). ObjectiveThis study aimed to investigate patients’ views on 1 ERP session at home via videoconference and its impact on treatment outcome. MethodsA total of 64 inpatients with OCD received 1 session of therapist-guided videoconference-based ERP at home in adjunction to a multimodal inpatient treatment between 2015 and 2020. ResultsCompared with 64 age- and sex-matched controls who received a multimodal inpatient treatment without 1 session of videoconference-based ERP at home, patients who received 1 session of videoconference-based ERP in adjunction to a multimodal inpatient treatment showed stronger reductions in OCD symptom severity from admission to discharge. Before the videoconference-based ERP session, patients reported high rationale credibility and treatment expectancy. After the videoconference-based ERP session, patients reported medium-to-high positive mood as well as depth and smoothness of the session, and they perceived the working alliance as high. ConclusionsResults highlight the importance of administering therapist-guided ERP sessions in patients’ natural environment to enhance treatment response in OCD. Videoconference-based ERP as add-on to treatment as usual is, therefore, a promising approach to facilitate the application of ERP in patients’ natural environment and foster the generalization of ERP conducted in clinical settings.

Bacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven by mobile genetic elements (MGEs). One such MGE, a phage satellite in Vibrio cholerae called PLE, provides specific and robust defense against a pervasive lytic phage, ICP1. The interplay between PLE and ICP1 has revealed strategies for molecular parasitism allowing PLE to hijack ICP1 processes in order to mobilize. Here, we describe the mechanism of PLE-mediated transcriptional manipulation of ICP1 structural gene transcription. PLE encodes a novel DNA binding protein, CapR, that represses ICP1's capsid morphogenesis operon. Although CapR is sufficient for the degree of capsid repression achieved by PLE, its activity does not hinder the ICP1 lifecycle. We explore the consequences of repression of this operon, demonstrating that more stringent repression achieved through CRISPRi restricts both ICP1 and PLE. We also discover that PLE transduces in modified ICP1-like particles. Examination of CapR homologs led to the identification of a suite of ICP1-encoded homing endonucleases, providing a putative origin for the satellite-encoded repressor. This work unveils a facet of the delicate balance of satellite-mediated inhibition aimed at blocking phage production while successfully mobilizing in a phage-derived particle.

ABSTRACTBacteriophages (viruses of bacteria) play a pivotal role in shaping both the evolution and dynamics of bacterial populations. Bacteria employ arsenals of genetically encoded phage defense systems, but can alternatively achieve protection by changing the availability of cellular resources that phages rely on for propagation. These physiological changes are often adaptive responses to unique environmental signals. The facultative pathogen Vibrio cholerae adapts to both aquatic and intestinal environments with niche-specific physiological changes that ensure its evolutionary success in such disparate settings. In both niches, V. cholerae is susceptible to predation by lytic phages like ICP1. However, both phages and susceptible bacterial hosts coexist in nature, indicating that environmental cues may modulate V. cholerae cell state to protect against phage infection. This work explores one such modification in response to the intestine-specific signals of bile and anaerobicity. We found that V. cholerae grown in these conditions reduces O1-antigen decoration on its outer membrane lipopolysaccharide. Because the O1-antigen is an essential moiety for ICP1 phage infection, we investigated the effect of partial O1-antigen depletion as a mechanism of phage defense and observed that O1-depletion limits phage adsorption. We identified mechanistic contributions to O1-depletion, including the essentiality of a weak acid tolerance system for O1 production at low pH and alterations in transcriptional profiles indicating limitations in resources for O1-biosynthesis. This analysis illustrates a complex interplay between signals relevant to the intestinal environment and bacterial physiology that provides V. cholerae with protection from phage predation.IMPORTANCEVibrio cholerae is the bacterial pathogen responsible for cholera, a diarrheal disease that impacts people in areas without access to potable water. In regions that lack such infrastructure, cholera represents a large proportion of disease outbreaks. Bacteriophages (phages, viruses that infect bacteria) have recently been examined as potential therapeutic and prophylactic agents to treat and prevent bacterial disease outbreaks like cholera due to their specificity and stability. This work examines the interaction between V. cholerae and vibriophages in consideration for a cholera prophylaxis regimen (M. Yen, L. S. Cairns, and A. Camilli, Nat Commun 8:14187, 2017, https://doi.org/10.1038/ncomms14187) in the context of stimuli found in the intestinal environment. We discover that common signals in the intestinal environment induce cell surface modifications in V. cholerae that also restrict some phages from binding and initiating infection. These findings could impact considerations for the design of phage-based treatments, as phage infection appears to be limited by bacterial adaptations to the intestinal environment.

Many viruses possess temporally unfolding gene expression patterns aimed at subverting host defenses, commandeering host metabolism, and ultimately producing a large number of progeny virions. High-throughput omics tools, such as RNA sequencing (RNA-seq), have dramatically enhanced the resolution of expression patterns during infection. Less studied have been viral satellites, mobile genomes that parasitize viruses. By performing RNA-seq on infection time courses, we have obtained the first time-resolved transcriptomes for bacteriophage satellites during lytic infection. Specifically, we have acquired transcriptomes for the lytic Vibrio cholerae phage ICP1 and all five known variants of ICP1's parasite, the phage inducible chromosomal island-like elements (PLEs). PLEs rely on ICP1 for both DNA replication and mobilization and abolish production of ICP1 progeny in infected cells. We investigated PLEs' impact on ICP1 gene expression and found that PLEs did not broadly restrict or reduce ICP1 gene expression. A major exception occurred in ICP1's capsid morphogenesis operon, which was downregulated by each of the PLE variants. Surprisingly, PLEs were also found to alter the gene expression of CTXΦ, the integrative phage that encodes cholera toxin and is necessary for virulence of toxigenic V. cholerae One PLE, PLE1, upregulated CTXΦ genes involved in replication and integration and boosted CTXΦ mobility following induction of the SOS response.IMPORTANCE Viral satellites are found in all domains of life and can have profound fitness effects on both the viruses they parasitize and the cells they reside in. In this study, we have acquired the first RNA sequencing (RNA-seq) transcriptomes of viral satellites outside plants, as well as the transcriptome of the phage ICP1, a predominant predator of pandemic Vibrio cholerae Capsid downregulation, previously observed in an unrelated phage satellite, is conserved among phage inducible chromosomal island-like elements (PLEs), suggesting that viral satellites are under strong selective pressure to reduce the capsid expression of their larger host viruses. Despite conserved manipulation of capsid expression, PLEs exhibit divergent effects on CTXΦ transcription and mobility. Our results demonstrate that PLEs can influence both their hosts' resistance to phage and the mobility of virulence-encoding elements, suggesting that PLEs can play a substantial role in shaping Vibrio cholerae evolution.

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.

Abstract Hepatitis B Virus (HBV) is a hepadnavirus that is the principal pathogen underlying viral liver disease in human populations. In this study, we describe the isolation and characterization of a fully human monoclonal antibody for HBV. This HuMab was isolated by a combinatorial screen of the memory B-cell repertoire from an acute/recovered HBV-infected patient. Lead candidate selection was based upon strong binding and neutralizing activity for live HBV. We provide a detailed biochemical/biophysical, and subclass characterization of its specificity and affinity against all of the principal HBV genotypes combined with a functional analysis of its in vitro activity. We also demonstrate its potential as a prophylaxis/therapy in vivo using human liver chimeric mouse models for HBV infection. These data have important implications for our understanding of natural human immunity to HBV and suggest that this potentially represents a new antibody-based anti-viral candidate for prophylaxis and/or therapy for HBV infection.

With the transition to teleworking imposed by the 2020 shutdown to the whole French primary education system, school teachers have experienced a profound change in the way they practice their profession. A study carried out in three French regions revealed four fracture lines among them. (1) Their unequal resources in terms of time and disposition to use digital technology, (2) the characteristics of the public they teach, (3) the way they conceive their profession, and (4) their ability to deal with these transformations lead to reactions to the situation that converge or compensate to explain the transformations in their practices and the judgement they express about the period.

Abstract Importance There is an abundance of research demonstrating the growing challenge of burnout in healthcare professionals. This has been further exacerbated by the COVID‐19 pandemic. The use of meditation using various techniques has shown promising results in the reduction of stress and its sequelae. Objective To determine the efficacy of a mantra‐based meditation protocol developed by the American Meditation Institute to reduce caregiver stress by evaluating changes in burnout and secondary traumatic stress (components of compassion fatigue) and compassion satisfaction with the application of the meditation protocol. Design, Setting, and Participation This pre–post cohort analysis was conducted on prospective enrollees of the Continuing Medical Education (CME)‐accredited American Meditation Institute's annual Heart and Science of Yoga® Conference, a comprehensive training in Yoga Science as Holistic Mind/Body Medicine for physicians and other healthcare providers held in October in Lenox, Massachusetts. Enrollees were trained in mantra‐based AMI Meditation at the conference and monitored during the 6‐month period following the conference. Interventions The mantra‐based AMI Meditation intervention included a 5‐day in‐person training, a daily practice of a guided mantra‐based AMI Meditation using a 20‐min CD or MP3 recording, and receipt of a monthly motivational letter. Study participants completed the Professional Quality of Life (ProQOL) Measure (a survey) and a demographic survey at baseline, and the ProQOL Measure and an informational survey at 3 and 6 months. Main Outcomes and Measures The primary outcome was a change from baseline in participants’ level of burnout using the ProQOL assessed at baseline and 3 and 6 months. Secondary outcomes included change from baseline in participants’ level of secondary traumatic stress and compassion satisfaction assessed at 3 and 6 months using the ProQOL Measure. Qualitative data were also collected from participant feedback, via the informational surveys, at 3 months and after completion of the program at 6 months. Results Of the 54 participants who enrolled and completed a baseline survey, 30 completed the follow‐up at 3 months and 21 participants completed the follow‐up at 6 months. From baseline to 6 months, there were statistically significant improvements in the scores for all three ProQOL scales. Using paired t‐test, burnout scores were reduced by 23.2% (p

Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL is removed. Conversely, Cbl-/- macrophages are resistant to viral infection, indicating that CBL regulates cell-intrinsic polarization between antibacterial and antiviral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map for developing a deeper understanding of the intricate interactions between Mtb and its host.

Serological diagnostic assays are essential tools for determining an individual’s protection against viruses like SARS-CoV-2, tracking the spread of the virus in the community, and evaluating population immunity. To assess the diversity and quality of the anti-SARS-CoV-2 antibody response, we have compared the antibody profiles of people with mild, moderate, and severe COVID-19 using a dot blot assay. The test targeted the four major structural proteins of SARS-CoV-2, namely the nucleocapsid (N), spike (S) protein domains S1 and S2, and receptor-binding domain (RBD). Serum samples were collected from 63 participants at various time points for up to 300 days after disease onset. The dot blot assay revealed patient-specific differences in the anti-SARS-CoV-2 antibody profiles. Out of the 63 participants with confirmed SARS-CoV-2 infections and clinical COVID-19, 35/63 participants exhibited diverse and robust responses against the tested antigens, while 14/63 participants displayed either limited responses to a subset of antigens or no detectable antibody response to any of the antigens. Anti-N-specific antibody levels decreased within 300 days after disease onset, whereas anti-S-specific antibodies persisted. The dynamics of the antibody response did not change during the test period, indicating stable antibody profiles. Among the participants, 28/63 patients with restricted anti-S antibody profiles or undetectable anti-S antibody levels in the dot blot assay also exhibited weak neutralization activity, as measured by a surrogate virus neutralization test (sVNT) and a microneutralization test. These results indicate that in some cases, natural infections do not lead to the production of neutralizing antibodies. Furthermore, the study revealed significant serological variability among patients, regardless of the severity of their COVID-19 illness. These differences need to be carefully considered when evaluating the protective antibody status of individuals who have experienced primary SARS-CoV-2 infections.

BackgroundThe Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is an empirically supported psychotherapeutic treatment developed specifically for persistent depressive disorder. However, given the high rates of nonresponse and relapse, there is a need for optimization. Studies suggest that outcomes can be improved by increasing the treatment dose via, for example, the continuous web-based application of therapy strategies between sessions. The strong emphasis in CBASP on the therapeutic relationship, combined with limited therapeutic availabilities, encourages the addition of web-based interventions to face-to-face therapy in terms of blended therapy. ObjectiveThe aim of this study was to test an app-based intervention called CBASPath, which was designed to be used as a blended therapy tool. CBASPath offers 8 sequential modules with app-based exercises to facilitate additional engagement with the therapy content and a separate exercise to conduct situational analyses within the app at any time. MethodsCBASPath was tested in an open pilot study as part of routine outpatient CBASP treatment. Participating patients were asked to report their use patterns and blended use (integrated use of the app as part of therapy sessions) at 3 assessment points over the 6-month test period and rate the usability and quality of and their satisfaction with CBASPath. ResultsThe results of the pilot trial showed that 93% (12/13) of participants used CBASPath as a blended tool during their therapy and maintained this throughout the study period. Overall, they reported good usability and quality ratings along with high user satisfaction. All participants showed favorable engagement with CBASPath; however, the frequency of use differed widely among the participants and assessment points. Situational analysis was used by all participants, and the number of completed modules ranged from 1 to 7. All participants reported blended use, although the frequency of integration in the face-to-face sessions varied widely. ConclusionsOur findings suggest that the digital augmentation of complex and highly interactive CBASP therapy in the form of blended therapy with CBASPath is feasible in routine outpatient care. Therapeutic guidance might contribute to high adherence and increase patient self-management. A few adjustments, such as saving entries directly in the app, could facilitate higher user engagement. A randomized controlled trial is now needed to investigate the efficacy and added value of this blended approach. In the long term, CBASPath could help optimize persistent depressive disorder treatment and reduce relapse by intensifying therapy and providing long-term patient support through the app.

The JAK-STAT pathway is evolutionary conserved. The simplicity of this signaling in Drosophila, due to the limited redundancy between pathway components, makes it an ideal model for investigation. In the Drosophila follicular epithelium, highly stereotyped functions of JAK-STAT signaling have been well characterized, but how signaling activity is regulated precisely to allow the different outcomes is not well understood. In this tissue, the ligand is secreted by the polar cells positioned at each follicle extremity, thus generating a gradient of JAK-STAT activity in adjacent cells. One way to control the delivered quantity of ligand is by regulating the number of polar cells, which is reduced by apoptosis to exactly two at each pole by mid-oogenesis. Hence, JAK-STAT activity is described as symmetrical between follicle anterior and posterior regions. Here, we show that JAK-STAT signaling activity is actually highly dynamic, resulting in asymmetry between poles by mid-oogenesis. Interestingly, we found similar temporal dynamics at follicle poles in the accumulation of the adherens junction E-cadherin protein. Remarkably, E-cadherin and JAK-STAT signaling not only display patterning overlaps but also share functions during oogenesis. In particular, we show that E-cadherin, like JAK-STAT signaling, regulates polar cell apoptosis non-cell-autonomously from follicle cells. Finally, our work reveals that E-cadherin is required for optimal JAK-STAT activity throughout oogenesis and that E-cadherin and Stat92E, the transcription factor of the pathway, form part of a physical complex in follicle cells. Taken together, our study establishes E-cadherin as a new positive regulator of JAK-STAT signaling during oogenesis.

Abstract A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver of infected individuals to reduce their risk of developing liver cancer. A strategy to deliver such a therapy could utilize the ability to target and promote apoptosis of infected hepatocytes. Presently there is no clinically relevant strategy that has been shown to effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) from the nucleus of hepatocytes. We used linearized single genome length HBV DNA of various genotypes to establish a cccDNA-like reservoir in immunocompetent mice and showed that clinical-stage orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins can eliminate HBV replication and episomal HBV genome in the liver. Primary human liver organoid models were used to confirm the clinical relevance of these results. This study underscores a clinically tenable strategy for the potential elimination of chronic HBV reservoirs in patients.

The distance learning implemented during the spring 2020 lockdown resulted in an increase in educational ine-qualities in French primary schools. A sociologically oriented ethnographic research conducted before, during and since the confinement with primary school teachers in Seine-Saint-Denis allows us to grasp the forced transfor-mations of teachers’ practices that could explain, at least to some degree, such an increase. The difficulty of main-taining the construction of shared meanings, the transformation of the systems of signs used for interactions with pupils, the fragility of the 'autonomy' required of pupils and the inequality of their parents in terms of supervision of personal work, and the difficulties in maintaining learning assistance are all phenomena that have sometimes ac-cumulated, making the benefit of work situations uncertain for some students.

Municipal activity leaders are, after teachers, the second largest category of supervisors in French primary schemes, both in terms of their population size and also with respect to the amount of time they spend with children. The article, based on an ethnographically-oriented sociological study conducted in seven Parisian schools, sheds light on activity leaders’ role in division of labour by analysing their contribution to children's education. It draws a picture of activity leaders’ practices, one centring on “playfulness”, the group, negotiations, commitment and a disdain for academic competition. It then reveals how said practices translate into specific forms of activity for children, generating new possibilities for some but disarming others in the face of certain very specific situations.

Sargen and Helaine discover a prophage competition element in Salmonella that inhibits the lytic cycle of co-resident prophages by cleaving a subset of cellular tRNAs. During Salmonella pathogenesis in macrophages, a persister subset experiences prophage induction and competition, reducing release of immunogenic cellular components and altering macrophage response to infection. [ABSTRACT FROM AUTHOR]

Background: Joint damage is the most frequent extraintestinal manifestation in inflammatory bowel disease (IBD). Aims: The aim of the study was to assess the value of low back pain (LBP) associated with sacroiliitis on abdominal imaging for the diagnosis of spondyloarthritis (SpA) in IBD. Methods: We used a questionnaire assessing rheumatological symptoms for all patients with abdominal computed tomography (CT) and magnetic resonance enterography (MRE). Sacroiliitis was assessed on available CT and MRE. Patients were classified as axial SpA according to the Assessment of SpondyloArthritis International Society criteria. Results: Fifty-one patients completed the questionnaire and performed both exams. LBP was present in 27 patients (52.9%), and 10 (19.6%) had an inflammatory component. Sacroiliitis was reported in 12 patients (23.5%), and 6 of them suffered from LBP. Among the 20 patients referred to the rheumatologist, 11 patients suffered from LBP. One patient was HLA-B27 positive and presented sacroiliitis. For the last 10 patients, none of them had a sacroiliitis, and 2 patients were negative for HLA-B27. Conclusion: An axial SpA has been diagnosed in 11.8% of IBD patients undergoing cross-sectional imaging, whereas one-fifth had inflammatory LBP, and sacroiliitis was observed in one-quarter of them. To optimize the diagnosis of axial SpA, HLA-B27 testing might be required for patients with both IBD and LBP, but this will require further investigation before its implementation in routine practice.

The spring 2020 lockdown saw the disappearance of the physical co-presence that characterized classroom teaching, leading teachers to change their practices in supporting students’ work. The article, based on an ethnographic study combining observations of virtual synchronous classrooms, retrospective interviews and a framing questionnaire, reveals the rise during this period of indirect support aimed at facilitating the work of students alone at home or with their parents. It shows that, in parallel with the development of these new practices, some teachers tried to restore direct support, in particular to accompany the most fragile students. This support, constrained by the new use of digital tools, has come up against unforeseen limits such as the lack of overview of the students’ activity or the difficulty in using gestures, which have led teachers to make permanent adjustments and to test previously unexplored possibilities of these tools. Paradoxically, containment may have contributed to convince them of the need to work on students’ difficulties.

The objective of this study was to investigate the feelings and experiences of infertile women with deep infiltrating endometriosis during and after a first pregnancy achieved by in-vitro fertilization (IVF). We conducted a qualitative monocentric study between May and November 2020. Semi-structured interviews were undertaken with infertile women with deep infiltrating endometriosis who achieved a first pregnancy by IVF and delivered at least two years prior to the interview. Data analysis was performed using an inductive approach to identify recurrent categories and themes. Fifteen interviews were conducted to reach data saturation. Pregnancy appeared to improve all components of the experience of endometriosis that were explored (psychological and physical well-being, social relationships, professional life, and sexuality). This improvement was only temporary and all symptoms and negative aspects of the women's quality of life reappeared after a variable period.

Introduction: Access in France to early diagnosis and care for the most severe, but infrequent, Neurodevelopmental Disorders (NDD), autism spectrum disorder and global developmental delay, in children aged 0–7 was improved through measures implemented in 2019. However, there are no such measures for specific learning disorders (SLD), attention, motricity and language disorders (SLDD), despite their annual incidence of between 5 and 8%.Method: We describe the design of a new type of organization and financing of care for SLDD including evaluation procedure, as well as other factors, mainly at the prevention level that will contribute to local and national policy for this frequent health problem. This in response to a national call for projects, commonly called Article 51, targeted innovation in healthcare delivery and funding in the context of medium-term national reform. This provides project stakeholders with the opportunity to set up and implement “bottom-up” projects, mainly using local professionals. A joint initiative by the regional Health Authorities of the Occitanie region, the French Social Security system and a non-profit Association (Occitadys) proposed an experimental new structure of NDD care and funding.Discussion: We here discuss the design of this experiment that aims, over two to three years, to alleviate families' financial burden of care and establish a regional three-tier care system with respect to evaluation, re-education and rehabilitation care. Our approach may benefit SLDD health-care planning, and addresses the questions of prevention, early detection and care-design for families, taking local and socioeconomic disparities into account.

Virus-like particles (VLPs), composed of the small hepatitis B virus surface antigen (HBsAgS), are the antigenic components of the hepatitis B virus (HBV) vaccine and represent the backbones for a chimeric anti-malaria vaccine and various vaccine candidates. Biological vectors have to face pre-existing anti-vector immune responses due to previous immune exposure. Vector recognition after natural infections or vaccinations can result in unwarranted outcomes, with compromising effects on clinical outcomes. In order to evaluate the impact of a pre-existing anti-HBsAgS immune response, we developed mutant VLPs composed of subunits with reduced HBsAgS-specific antigenicity. The insertion of a Plasmodium falciparum circumsporozoite protein (CSP)-derived epitope as a read-out allowed the assessment of wild type (wt) and mutant VLPs in the context of a pre-existing immune response. Mutant and wt VLP platforms with a CSP-epitope insert are immunogenic and have the ability to generate anti-CSP antibody responses in both naïve BALB/c mice and mice with a pre-existing anti-HBsAgS immune response, but with superior anti-CSP responses in mice with a pre-existing immunity. The data indicate that previous HBsAgS exposure facilitates enhanced antibody responses against foreign epitopes delivered by the HBsAgS platform, and, in this context, the state of immune sensitization alters the outcome of subsequent vaccinations.