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Non-urothelial bladder cancers make up a rare minority of all genitourinary (GU) tract histologic cancers since urothelial cancer (UC) makes up the most common histologic subtype. Bladder cancer variant histology (BCVH) or urothelial variants also occur rarely though distinction is important given aggressive presentation and natural history. While methods for diagnosis and treatment of typical urothelial cancers (UC) are well-established, there are no clear guidelines with regard to the diagnosis of non-urothelial bladder cancers, which often results in misdiagnosis and treatment delay. This review will focus on the clinicopathologic characteristics of the most common non-urothelial bladder cancers, to be distinguished from bladder cancer variant histology containing a UC component. The role of genomics in non-urothelial bladder cancers is evolving and the use of biomarkers to guide the diagnosis and treatment of these tumors remains a key area of unmet need. Treatment of these cancers will be discussed in a companion review.

Background: Health and Safety Executive data show that teachers are at heightened risk of mental health difficulties, yet few studies have attempted to address this. Poor teacher mental health may impact on the quality of support provided to young people, who also report increased mental health difficulties themselves. Objective: To test the effectiveness of an intervention aiming to improve secondary school teachers’ well-being through mental health support and training. Design: A cluster randomised controlled trial with embedded process and economic evaluations. Setting: Twenty-five mainstream, non-fee-paying secondary schools in the south-west of England and South Wales, stratified by geographical area and free school meal entitlement, randomly allocated to intervention or control groups following collection of baseline measures (n = 12, intervention; n = 13, control) between May and July 2016. Participants: All teachers in the study schools at any data collection. All students in year 8 (baseline) and year 10 (final follow-up). Intervention: Each intervention school received three elements: (1) a 1-day mental health first aid for schools and colleges training session delivered to 8% of all teachers; (2) a 1-hour mental health session delivered to all teachers; and (3) 8% of staff trained in the 2-day standard mental health first aid training course set up a confidential peer support service for colleagues. Control schools continued with usual practice. Main outcome measures: The primary outcome was teacher well-being (using the Warwick–Edinburgh Mental Wellbeing Scale). Secondary outcomes were teacher depression, absence and presenteeism, and student well-being, mental health difficulties, attendance and attainment. Follow-up was at 12 and 24 months. Data were analysed using intention-to-treat mixed-effects repeated-measures models. Economic evaluation: A cost–consequence analysis to compare the incremental cost of the intervention against the outcomes measured in the main analysis. Process evaluation: A mixed-methods study (i.e. qualitative focus groups and interviews, quantitative surveys, checklists and logs) to examine intervention implementation, activation of the mechanisms of change outlined in the logic model, intervention acceptability and the wider context. Results: All 25 schools remained in the study. A total of 1722 teachers were included in the primary analysis. We found no difference in mean teacher well-being between study arms over the course of follow-up (adjusted mean difference –0.90, 95% confidence interval –2.07 to 0.27). There was also no difference in any of the secondary outcomes (p-values 0.203–0.964 in the fully adjusted models). The average cost of the intervention was £9103 (range £5378.97–12,026.73) per intervention school, with the average cost to Welsh schools being higher because of a different delivery model. The training components were delivered with high fidelity, although target dosage was sometimes missed. The peer support service was delivered with variable fidelity, and reported usage by teachers was low (5.9–6.1%). The intervention had high acceptability, but participants reported low support from senior leadership, and minimal impact on school culture. Limitations: Participants and the study team were unblinded, self-report for the main outcome measures and inaccurate measurement of peer support service usage. Conclusions: The Wellbeing in Secondary Education (WISE) intervention was not effective at improving teacher or student well-being, or reducing mental health difficulties, possibly because of contextual barriers preventing it becoming embedded in school life. Future work: Identification of ways in which to achieve system-level change and sustained support from senior leaders is important for future school-based mental health interventions. Trial registration: Current Controlled Trials ISRCTN95909211. Funding: This project was funded by the National Institute for Health Research Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 12. See the NIHR Journals Library website for further project information. Intervention costs were met by Public Health Wales, Public Health England and Bristol City Council.

BackgroundTeachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention.Methods and findingsThe intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference -0.90, 95% CI -2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study's main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures.ConclusionsIn this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being.Trial registrationwww.isrctn.com ISRCTN95909211.

Abstract Background Autosomal recessive renal polycystic kidney disease occurs in 1 in 20,000 live births. It is caused by mutations in both alleles of the PKHD1 gene. Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease is rarely discussed, and literature concerning abdominal dystocia is extremely scarce. We present a case of a patient with autosomal recessive renal polycystic kidney disease whose delivery was complicated by abdominal dystocia, and we discuss the factors that determined the route and timing of delivery. Case presentation A 23-year-old Caucasian woman, G2 P0, with a prior unremarkable pregnancy was referred to our tertiary center at 31 weeks of gestation because of severe oligoamnios (amniotic fluid index = 2) and hyperechogenic, dedifferentiated, and enlarged fetal kidneys. She had no other genitourinary anomaly. Fetal magnetic resonance imaging showed enlarged, hypersignal kidneys and severe pulmonary hypoplasia. We had a high suspicion of autosomal recessive renal polycystic kidney disease, and after discussion with our multidisciplinary team, the parents opted for conservative care. Ultrasound performed at 35 weeks of gestation showed a fetal estimated weight of 3550 g and an abdominal circumference of 377 mm, both above the 90th percentile. Because of the very rapid kidney growth and suspected risk of abdominal dystocia, we proposed induction of labor at 36 weeks of gestation after corticosteroid administration for fetal lung maturation. Vaginal delivery was complicated by abdominal dystocia, which resolved by continuing expulsive efforts and gentle fetal traction. A 3300-g (P50–90) male infant was born with Apgar scores of 1-7-7 at 1, 5, and 10 minutes, respectively, and arterial and venous umbilical cord pH values of 7.23–7.33. Continuous peritoneal dialysis was started at day 2 of life because of anuria. Currently, the infant is 1 year old and is waiting for kidney transplant that should be performed once he reaches 10 kg. Molecular analysis of PKHD1 performed on deoxyribonucleic acid (DNA) from the umbilical cord confirmed autosomal recessive renal polycystic kidney disease. Conclusions Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease needs to be discussed because of the risk of abdominal dystocia. The route and timing of delivery depend on the size of the fetal abdominal circumference and the gestational age. The rate of kidney growth must also be taken into account.

This community case study describes the process of developing a strategy for community-university engagement, as an example of co-production, and presents the strategy and early outcomes of the work. Based in London, the strategy and the process of co-production are of international relevance in supporting more productive relationships between universities and their cities, as a foundation for repurposing universities for sustainable human progress. The case study is presented in the context of literature related to community engagement with universities and co-production, an area of growing concern as universities seek to strengthen relationships and contribution to sustainable human progress in their home cities. London is one of the world's great university cities, with more than 40 higher education institutions contributing ground-breaking research and educating students from across the globe. London is also home to vibrant local communities, with a strong tradition of grassroots action, community organization and citizen participation. Community groups and universities have a strong history of working together, often without formal recognition or resources. The Community university Knowledge Strategy for London, known as Collaborate!, was a collaboration between universities and grassroots community groups in London, co-convened by Just Space and University College London (UCL). A series of workshops, guided by two steering committees of community and university members, explored principles for working together, cultural and institutional barriers, decolonization, industrial strategies, community spaces and case studies of good practice. The final conference outlined the basis for a London-wide strategy to enable better engagement between universities and grassroots community groups. The strategy addresses core principles, curriculum, evaluation and evidence, resources, relationship building, governance and structures to support collaboration. Co-production ensured high levels of trust between participants and commitment to the outcomes. Implementation of the strategy actions requires ongoing resources to support intermediary structures to overcome misalignment between universities as large, hierarchical institutions and community groups as dynamic, informal, social organizations.

Evolutionary relationships amongst Chlorobia and Ignavibacteria species/strains were examined using phylogenomic and comparative analyses of genome sequences. In a phylogenomic tree based on 282 conserved proteins, the named Chlorobia species formed a monophyletic clade containing two distinct subclades. One clade, encompassing the genera Chlorobaculum, Chlorobium, Pelodictyon, and Prosthecochloris, corresponds to the family Chlorobiaceae, whereas another clade, harboring Chloroherpeton thalassium, Candidatus Thermochlorobacter aerophilum, Candidatus Thermochlorobacteriaceae bacterium GBChlB, and Chlorobium sp. 445, is now proposed as a new family (Chloroherpetonaceae fam. nov). In parallel, our comparative genomic analyses have identified 47 conserved signature indels (CSIs) in diverse proteins that are exclusively present in members of the class Chlorobia or its two families, providing reliable means for identification. Two known Ignavibacteria species in our phylogenomic tree are found to group within a larger clade containing several Candidatus species and uncultured Chlorobi strains. A CSI in the SecY protein is uniquely shared by the species/strains from this “larger Ignavibacteria clade”. Two additional CSIs, which are commonly shared by Chlorobia species and the “larger Ignavibacteria clade”, support a specific relationship between these two groups. The newly identified molecular markers provide novel tools for genetic and biochemical studies and identification of these organisms.

Psoriasis is a chronic inflammatory skin disease mainly characterized by the hyperproliferation and abnormal differentiation of the epidermal keratinocytes. An interesting phenolic compound, namely quebecol (2,3,3-tri-(3-methoxy-4-hydroxyphenyl)-1-propanol) (compound 1, CPD1), was isolated from maple syrup in 2011 and was recently synthesized. Quebecol and its derivatives ethyl 2,3,3-tris(3-hydroxy-4-methoxyphenyl)propenoate (compound 2, CPD2) and bis(4-hydroxy-3-methoxyphenyl)methane (compound 3, CPD3) have shown antiproliferative and anti-inflammatory potential, making them promising candidates for the treatment of psoriasis. This study aimed to evaluate the antipsoriatic potential of quebecol and its derivatives on psoriatic skin substitutes produced according to the self-assembly method. A sulforhodamine B (SRB) assay determining the concentration that inhibits 20% of cell growth (IC20) was performed for CPD1, CPD2 and CPD3, and their IC20 values were 400, 150 and 350 μM, respectively. At these concentrations, cell viability was 97%, 94% and 97%, respectively. The comparative control methotrexate (MTX) had a cell viability of 85% at a concentration of 734 μM. Histological analyses of psoriatic skin substitutes treated with CPD1, CPD2 and CPD3 exhibited significantly reduced epidermal thickness compared with untreated psoriatic substitutes, which agreed with a decrease in keratinocyte proliferation as shown by Ki67 immunofluorescence staining. The immunofluorescence staining of differentiation markers (keratin 14, involucrin and loricrin) showed improved epidermal differentiation. Taken together, these results highlight the promising potential of quebecol and its derivatives for the treatment of psoriasis.

Background: Individuals with cerebral palsy (CP) manifest skeletal fragility problems early in life, are vulnerable to non-trauma fracture (NTFx), and have a high burden of premature mortality. No studies have examined the contribution of NTFx to mortality among adults with CP. The purpose of this study was to determine if NTFx is a risk factor for mortality among adults with CP and if NTFx exacerbates mortality risk compared to adults without CP. Methods: Data from 2011 to 2016 Optum Clinformatics® Data Mart and a random 20% sample Medicare fee-for-service were used for this retrospective cohort study. Diagnosis codes were used to identify adults (18+ years) with and without CP, NTFx, and pre-NTFx comorbidities. Crude mortality rates per 100 person years were estimated. Cox regression estimated hazard ratios (HR and 95% confidence interval [CI]) for mortality, comparing: (1) CP and NTFx (CP + NTFx; n = 1777); (2) CP without NTFx (CP w/o NTFx; n = 12,933); (3) without CP and with NTFx (w/o CP + NTFx; n = 433,560); and (4) without CP and without NTFx (w/o CP w/o NTFx; n = 6.8 M) after adjusting for demographics and pre-NTFx comorbidities. Results: The 3-, 6-, and 12-month crude mortality rates were highest among CP + NTFx (12-month mortality rate = 6.80), followed by w/o CP + NTFx (12-month mortality rate = 4.91), CP w/o NTFx (12-month mortality rate = 2.15), and w/o CP w/o NTFx (12-month mortality rate = 0.49). After adjustments, the mortality rate was elevated for CP + NTFx for all time points compared to CP w/o NTFx (e.g., 12-month HR = 1.61; 95%CI = 1.29–2.01), w/o CP + NTFx (e.g., 12-month HR = 1.49; 95%CI = 1.24–1.80), and w/o CP w/o NTFx (e.g., 12-month HR = 5.33; 95%CI = 4.42–6.44). There were site-specific effects (vertebral column, lower extremities) on 12-month mortality. Conclusions: NTFx is associated with an increase of 12-month mortality risk among adults with CP and compared to adults without CP. Findings suggest that NTFx may be a robust risk factor for mortality among adults with CP.

Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models’ usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model’s parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.

We describe the case of a 7-year-old child, victim of ocular trauma causing a corneal wound that was sutured urgently. The child has been regularly monitored in our department. Few months later, he consults for a painful red eye evolving within two weeks. The use of Voriconazole as an intracameral injection has shown its superiority in treating fungal endophtalmitis. Further studies should be underwent to learn more about better injection strategies and so as to consider better its benefits and side effects.

Abstract Background Secondary school teachers have low levels of wellbeing and high levels of depression compared with the general population. Teachers are in a key position to support students, but poor mental health may be a barrier to doing so effectively. The Wellbeing in Secondary Education (WISE) project is a cluster randomised controlled trial (RCT) of an intervention to improve the mental health support and training available to secondary school teachers through delivery of the training package Mental Health First Aid and a staff peer support service. We will conduct a process evaluation as part of the WISE trial to support the interpretation of trial outcomes and refine intervention theory. The domains assessed will be: the extent to which the hypothesised mechanisms of change are activated; system level influences on these mechanisms; programme differentiation and usual practice; intervention implementation, including any adaptations; intervention acceptability; and intervention sustainability. Methods Research questions will be addressed via quantitative and qualitative methods. All study schools (n = 25) will provide process evaluation data, with more detailed focus group, interview and observation data being collected from a subsample of case study schools (4 intervention and 4 control). Mechanisms of change, as outlined in a logic model, will be measured via teacher and student surveys and focus groups. School context will be explored via audits of school practice that relate to mental health and wellbeing, combined with stakeholder interviews and focus groups. Implementation of the training and peer support service will be assessed via training observations, training participant evaluation forms, focus groups with participants, interviews with trainers and peer support service users, and peer supporter logs recording help provided. Acceptability and sustainability will be examined via interviews with funders, head teachers, trainers and peer support services users, and focus groups with training participants. Discussion The process evaluation embedded within the WISE cluster RCT will illuminate how and why the intervention was effective, ineffective or conferred iatrogenic effects. It will contribute to the refinement of the theory underpinning the intervention, and will help to inform any future implementation. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN95909211 registered on 24 March 2016.

In this study we used 3-methylphenol (3MP) as a pollutant model of phenols to study the effectiveness of the photo-Fenton Fe(III)Ox system. The preliminary study of the mixture 3MP-Fe(III)Ox-H2O2 in the absence of light and at room temperature allowed us to confirm the absence of interaction under our experimental conditions. However, the same system was studied in the presence of light (365 nm) in order to study the photo-Fenton process. Various parameters (H2O2 concentrations and pH) were tested in order to optimize the efficiency of the system in terms of degradation of 3MP. In order to understand the mechanism involved in radical inhibition experiments (•OH and HO2• / O2•-) have been carried out. One of the important conclusions of this work is that the Fe(III)Ox complex plays a very positive role in the degradation of 3MP. In addition, we have also shown that this process is very efficient in the neutral pH range. This complex is really a very promising source of iron in the photo-Fenton processes.

Abstract Background Many young people who receive psychiatric care in inpatient or residential settings in North America have experienced various forms of emotional trauma. Moreover, these settings can exacerbate trauma sequelae. Common practices, such as seclusion and restraint, put young people at risk of retraumatization, development of comorbid psychopathology, injury, and even death. In response, psychiatric and residential facilities have embraced trauma-informed care (TIC), an organizational change strategy which aligns service delivery with treatment principles and discrete interventions designed to reduce rates of retraumatization through responsive and non-coercive staff-client interactions. After more than two decades, a number of TIC frameworks and approaches have shown favorable results. Largely unexamined, however, are the features that lead to successful implementation of TIC, especially in child and adolescent inpatient psychiatric and residential settings. Methods Using methods proposed by Pawson et al. (J Health Serv Res Policy 10:21–34, 2005), we conducted a modified five-stage realist systematic review of peer-reviewed TIC literature. We rigorously searched ten electronic databases for peer reviewed publications appearing between 2000 and 2015 linking terms “trauma-informed” and “child*” or “youth,” plus “inpatient” or “residential” plus “psych*” or “mental.” After screening 693 unique abstracts, we selected 13 articles which described TIC interventions in youth psychiatric or residential settings. We designed a theoretically-based evaluative framework using the active implementation cycles of the National Implementation Research Network (NIRN) to discern which foci were associated with effective TIC implementation. Excluded were statewide mental health initiatives and TIC implementations in outpatient mental health, child welfare, and education settings. Interventions examined included: Attachment, Self-Regulation, and Competency Framework; Six Core Strategies; Collaborative Problem Solving; Sanctuary Model; Risking Connection; and the Fairy Tale Model. Results Five factors were instrumental in implementing trauma informed care across a spectrum of initiatives: senior leadership commitment, sufficient staff support, amplifying the voices of patients and families, aligning policy and programming with trauma informed principles, and using data to help motivate change. Conclusions Reduction or elimination of coercive measures may be achieved by explicitly targeting specific coercive measures or by implementing broader therapeutic models. Additional research is needed to evaluate the efficacy of both approaches.

Recently, several promising treatments for high-grade gliomas (HGGs) failed to provide significant benefit when translated from the preclinical setting to patients. Improving the animal models is fundamental to overcoming this translational gap. To address this need, we developed and comprehensively characterized a new in vivo model based on the orthotopic implantation of CT-2A cells cultured in neurospheres (NS/CT-2A). Murine CT-2A methylcholanthrene-induced HGG cells (C57BL/6 background) were cultured in monolayers (ML) or NS and orthotopically inoculated in syngeneic animals. ML/CT-2A and NS/CT-2A tumors' characterization included the analysis of tumor growth, immune microenvironment, glioma stem cells (GSCs), vascularization and metabolites. The immuno-modulating properties of NS/CT-2A and ML/CT-2A cells on splenocytes were tested in vitro. Mice harboring NS/CT-2A tumors had a shorter survival than those harboring ML/CT-2A tumors (P=0.0033). Compared to standard ML/CT-2A tumors, NS/CT-2A tumors showed more abundant GSCs (P=0.0002 and 0.0770 for Nestin and CD133, respectively) and regulatory T cells (Tregs, P=0.0074), and a strong tendency towards an increased vascularization (P=0.0503). There were no significant differences in metabolites' composition between NS/ and ML/CT-2A tumors. In vitro, NS were able to drive splenocytes towards a more immunosuppressive status by reducing CD8+ T cells (P=0.0354) and by promoting Tregs (P=0.0082), macrophages (MF, P=0.0019) and their M2 subset (P=0.0536). Compared to standard ML/CT-2A tumors, NS/CT-2A tumors show a more aggressive phenotype with increased immunosuppression and GSCs proliferation. Because of these specific features, the NS/CT-2A model represents a clinically relevant platform in the search for new HGG treatments aimed at reducing immunosuppression and eliminating GSCs.

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.

Atherosclerosis represents an ever-present global concern, as it is a leading cause of cardiovascular disease and an immense public welfare issue. Macrophages play a key role in the onset of the disease state and are popular targets in vascular research and therapeutic treatment. Carbon nanodots (CNDs) represent a type of carbon-based nanomaterial and have garnered attention in recent years for potential in biomedical applications. This investigation serves as a foremost attempt at characterizing the interplay between macrophages and CNDs. We have employed THP-1 monocyte-derived macrophages as our target cell line representing primary macrophages in the human body. Our results showcase that CNDs are non-toxic at a variety of doses. THP-1 monocytes were differentiated into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and co-treatment with 0.1 mg/mL CNDs. This co-treatment significantly increased the expression of CD 206 and CD 68 (key receptors involved in phagocytosis) and increased the expression of CCL2 (a monocyte chemoattractant and pro-inflammatory cytokine). The phagocytic activity of THP-1 monocyte-derived macrophages co-treated with 0.1 mg/mL CNDs also showed a significant increase. Furthermore, this study also examined potential entrance routes of CNDs into macrophages. We have demonstrated an inhibition in the uptake of CNDs in macrophages treated with nocodazole (microtubule disruptor), N-phenylanthranilic acid (chloride channel blocker), and mercury chloride (aquaporin channel inhibitor). Collectively, this research provides evidence that CNDs cause functional changes in macrophages and indicates a variety of potential entrance routes.

Abstract Background Teachers are reported to be at increased risk of common mental health disorders compared to other occupations. Failure to support teachers adequately may lead to serious long-term mental disorders, poor performance at work (presenteeism), sickness absence and health-related exit from the profession. It also jeopardises student mental health, as distressed staff struggle to develop supportive relationships with students, and such relationships are protective against student depression. A number of school-based trials have attempted to improve student mental health, but these have mostly focused on classroom based approaches and have failed to establish effectiveness. Only a few studies have introduced training for teachers in supporting students, and none to date have included a focus on improving teacher mental health. This paper sets out the protocol (version 4.4 20/07/16) for a study aiming to address this gap. Methods Cluster randomised controlled trial with secondary schools as the unit of randomisation. Intervention schools will receive: i) Mental Health First Aid (MHFA) training for a group of staff nominated by their colleagues, after which they will set up a confidential peer support service for colleagues ii) training in MHFA for schools and colleges for a further group of teachers, which will equip them to more effectively support student mental health iii) a short mental health awareness raising session and promotion of the peer support service for all teachers. Comparison schools will continue with usual practice. The primary outcome is teacher wellbeing measured using the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS). Secondary outcomes are teacher depression, absence and presenteeism, and student wellbeing, mental health difficulties, attendance and attainment. Measures will be taken at baseline, one year follow up (teachers only) and two year follow up. Economic and process evaluations will be embedded within the study. Discussion This study will establish the effectiveness and cost-effectiveness of an intervention that supports secondary school teachers’ wellbeing and mental health, and improves their skills in supporting students. It will also provide information regarding intervention implementation and sustainability. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN95909211 registered 24/03/16

Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs) have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc) and the human sodium iodide transporter (hNIS) to allow cell monitoring via bioluminescence imaging (BLI) and small-animal positron emission tomography (PET). Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells.

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease. Human motor neurons generated from induced pluripotent stem cells (iPSc) offer new perspectives for disease modeling and drug testing in ALS. In standard iPSc-derived cultures, however, the two major phenotypic alterations of ALS—degeneration of motor neuron cell bodies and axons—are often obscured by cell body clustering, extensive axon criss-crossing and presence of unwanted cell types. Here, we succeeded in isolating 100% pure and standardized human motor neurons by a novel FACS double selection based on a p75NTR surface epitope and an HB9::RFP lentivirus reporter. The p75NTR/HB9::RFP motor neurons survive and grow well without forming clusters or entangled axons, are electrically excitable, contain ALS-relevant motor neuron subtypes and form functional connections with co-cultured myotubes. Importantly, they undergo rapid and massive cell death and axon degeneration in response to mutant SOD1 astrocytes. These data demonstrate the potential of FACS-isolated human iPSc-derived motor neurons for improved disease modeling and drug testing in ALS and related motor neuron diseases.

Objective: To identify factors to consider for developing and implementing a community-based exercise (CBE) program for people living with HIV (PLWH). Methods: We conducted a qualitative descriptive study using semi-structured interviews with PLWH, rehabilitation professionals, and recreation providers from Canada and the United Kingdom. We asked participants to describe their experience with exercise, facilitators, and barriers to accessing and participating in exercise, and factors to consider in developing a CBE program for PLWH. Interviews were analyzed using content analytical techniques. Results: We developed a Framework of CBE in the Context of HIV that describes (1) exercise experiences of PLWH (nature of exercise, motivators for initiating or sustaining exercise, perceived benefits, and barriers and facilitators to exercise) and (2) 11 factors to consider in developing and implementing a CBE program for PLWH. Conclusion: Recommendations for the development and implementation of an accessible and feasible CBE program may enhance exercise participation among PLWH.

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe3O4@Al(OH)3, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)3 phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe3O4), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r2) (83.6 mM−1 s−1) and rapid uptake of 18F-labeled fluoride ions as a PET tracer. The loading stability with 18F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the 18F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe3O4@Al(OH)3 nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI).

La kératoplastie transfixiante est l'une des plus fréquentes des greffes de tissus et transplantations d'organes. Le but de notre travail est de rapporter notre expérience en matière de greffe de cornée. C'est une étude prospective de 195 patients ayant bénéficié d'une greffe de cornée sur une période allant d'aout 2009 à Août 2015. Le recul moyen est de 21 mois. Les indications de la greffe étaient le kératocône 33.8%, les séquelles de traumatisme 10.7%, la kératopathie bulleuse 19.5%, les dystrophies héréditaires 10.7%, et les kératites herpétiques 9.2%. L'acuité visuelle initiale était inférieure à 1/10 dans 90% des cas. Nous avons observé une réaction de rejet dans 19 yeux dont 14 étaient récupérables, 33 hypertonies oculaires, 20cataracte, et 2 décollements descmetiques. La greffe de cornée apparaît comme une intervention donnant de bons résultats anatomiques et fonctionnels. Les résultats ne doivent pas occulter une surveillance post opératoire étroite et régulière pour dépister à temps d'éventuelles complications, en particulier le rejet de greffe.

Les cellulites orbitaires est une affection grave par ses complications aussi bien locales, locorégionales que générales, pouvant engager le pronostic vital et fonctionnel, surtout lorsque le diagnostic est tardif et la prise en charge inappropriée. Le but de cette étude est de décrire les aspects épidémiologiques, cliniques, thérapeutiques et évolutifs des cellulites orbitaires et d'insister sur la nécessité d'un diagnostic et d'un traitement précoces, afin d'éviter ses complications. Il s'agit d'une étude prospective concernent 75 patients présentant une cellulite orbitaire, menée au service d'Ophtalmologie et d'ORL au CHU Mohammed VI de Marrakech, de Septembre 2010 au Avril 2014. L'âge moyen des patients était de 24 ans allant de 2 ans à 70 ans. La porte d'entrée était dominée par l'atteinte sinusienne retrouvée chez 43 malades. L'examen ophtalmologique a montré une BAV chez 20% des patients avec une cécité bilatérale chez un patient et unilatérale chez 3, un chémosis (82%), une exophtalmie (85,71%), un ptosis (30%), une ophtalmoplégie (66%), une fistule orbitaire (4 cas), et une kératite d'exposition chez 8 cas. L'analyse des résultats tomodensitométriques a noté: 24 cas de cellulite pré septale (45%), 20 cas de cellulite orbitaire (15%), 2 cas d'abcès sous périosté (5%) et 14 cas d'abcès orbitaire (35%). 20 patients ont bénéficié d'un traitement chirurgical associé au traitement médical, ayant consisté en un drainage de l'abcès orbitaire dans 24 cas, une ethmoidectomie antérieure par voie endoscopique avec drainage d'un abcès sous-périosté dans 2 cas à et un drainage d'une collection abcédée des parties molles dans 6 cas. La cellulite orbitaire est une urgence thérapeutique qui met en jeu le pronostic visuel et vital. Causés le plus fréquemment par les traumatismes oculaires post chirurgicale ou AVP, les sinusites, les fractures orbitaires, et les corps étrangers intraoculaires. Les infections rétro-septales sont les plus graves, nécessitant une exploration par imagerie en coupes. L'évolution de la cellulite orbitaire est toujours grave en l'absence d'un traitement médical et chirurgical strict. Le traitement précoce et adapté représente un élément pronostique très important. Les cellulites orbitaires est une affection grave pouvant engager le pronostic vital et fonctionnel, surtout lorsque le diagnostic est tardif et la prise en charge inappropriée.

Notre étude consistera en l'évaluation du pronostic des patients porteurs d'un adénocarcinome gastrique opérés et traités par radio-chimiothérapie adjuvante en technique conformationnelle. Entre Janvier 2007 et Décembre 2011, 34 patients ont reçu après une chirurgie radicale (R0 ou R1), un à trois cycles de 5-Fluoro-uracile associé à de l'Elvorine en adjuvant, suivi d'une radio-chimiothérapie selon le même protocole à la dose de 45Gy, puis de deux cycles de chimiothérapie à un mois d'intervalle après la radio-chimiothérapie concomitante. Dans le groupe d'étude, il y avait 34 patients d'âge médian 50 ans (47-58), avec un sexe ratio (H/F) de 2,4. Une chirurgie de type R1 a été réalisée dans 26,5% des cas, et 53% des patients étaient de stade III-IV. Le rapport nombres de ganglions positifs, sur nombre de ganglions prélevés étaient 0,4 dans 26,5% des cas. Durant le traitement mené à terme, une neutropénie de grade III a été observée chez quatre patients, avec des troubles digestifs (nausées, vomissement, ou diarrhée) de grade I/II dans la majorité des cas. Après un suivi médian de 20 mois, 70,6% des patients étaient en survie sans rechute, et 29,4% ont présenté une récidive métastatique; la survie globale à 5 ans était de 35,4% et la survie sans progression de 58,7%. La radio-chimiothérapie concomitante postopératoire pourrait être un régime efficace et sûre chez les patients ayant bénéficié d'une gastrectomie à visée curative dans le cancer de l'estomac localement avancé.

The vast majority of meiotic recombination events (crossovers (COs) and non-crossovers (NCOs)) cluster in narrow hotspots surrounded by large regions devoid of recombinational activity. Here, using a new molecular approach in plants, called "pollen-typing", we detected and characterized hundreds of CO and NCO molecules in two different hotspot regions in Arabidopsis thaliana. This analysis revealed that COs are concentrated in regions of a few kilobases where their rates reach up to 50 times the genome average. The hotspots themselves tend to cluster in regions less than 8 kilobases in size with overlapping CO distribution. Non-crossover (NCO) events also occurred in the two hotspots but at very different levels (local CO/NCO ratios of 1/1 and 30/1) and their track lengths were quite small (a few hundred base pairs). We also showed that the ZMM protein MSH4 plays a role in CO formation and somewhat unexpectedly we also found that it is involved in the generation of NCOs but with a different level of effect. Finally, factors acting in cis and in trans appear to shape the rate and distribution of COs at meiotic recombination hotspots.

Neurofibromatosis type 2 protein (NF2) has been shown to act as tumor suppressor primarily through its functions as a cytoskeletal scaffold. However, NF2 can also be found in the nucleus, where its role is less clear. Previously, our group has identified JC virus (JCV) tumor antigen (T-antigen) as a nuclear binding partner for NF2 in tumors derived from JCV T-antigen transgenic mice. The association of NF2 with T-antigen in neuronal origin tumors suggests a potential role for NF2 in regulating the expression of the JCV T-antigen. Here, we report that NF2 suppresses T-antigen protein expression in U-87 MG human glioblastoma cells, which subsequently reduces T-antigen-mediated regulation of the JCV promoter. When T-antigen mRNA was quantified, it was determined that increasing expression of NF2 correlated with an accumulation of T-antigen mRNA; however, a decrease in T-antigen at the protein level was observed. NF2 was found to promote degradation of ubiquitin bound T-antigen protein via a proteasome dependent pathway concomitant with the accumulation of the JCV early mRNA encoding T-antigen. The interaction between T-antigen and NF2 maps to the FERM domain of NF2, which has been shown previously to be responsible for its tumor suppressor activity. Co-immunoprecipitation assays revealed a ternary complex among NF2, T-antigen, and the tumor suppressor protein, p53 within a glioblastoma cell line. Further, these proteins were detected in various degrees in patient tumor tissue, suggesting that these associations may occur in vivo. Collectively, these results demonstrate that NF2 negatively regulates JCV T-antigen expression by proteasome-mediated degradation, and suggest a novel role for NF2 as a suppressor of JCV T-antigen-induced cell cycle regulation.

Within the field of the social and cultural anthropology, the objective of the doctoral research is to understand the process of encountering (and especially misunderstandings) between Kanak tourism providers and French tourists in New Caledonia. On the one hand, the ethnographic survey demonstrates that culture is not responsible for misunderstandings. On the other hand, it demonstrates that the capacity for reflection and resilience of actors asserts the productivity of misunderstandings. Finally, it considers the meaning of tourism as an ambivalent topic, beyond the context of New Caledonia.