Search

Teaching physiology can be challenging as students are initially required to understand basic and abstract concepts. Thus students typically view physiology as a "difficult" subject and place an emphasis on rote learning and memorization. Here, we attempted to address this knowledge gap by introducing a pedagogical intervention into the neurophysiology lesson plan of first-year medical and health physiology students at the University of La Reunion. This intervention aimed to better link abstract concepts (e.g., saltatory conduction) and a pathological disorder (multiple sclerosis), together with a discussion of a specific therapeutic intervention (fampridine). Students were required to complete readings (focused on neurophysiology aspects) and two online quizzes before two scheduled in-person lectures. They could also pose questions on a dedicated online forum. Thereafter, the in-person lectures discussed questions posted on the online forum, provided feedback on poorly answered questions (from the online quizzes), and dealt with questions posed by students attending classes. Student feedback regarding the pedagogic intervention was assessed by an anonymous online survey. This survey revealed that the pedagogical intervention was positively received. For example, 94% of respondents agreed the course was well developed, while 80% indicated that the pedagogical intervention was beneficial in terms of their understanding of basic and abstract neurophysiology concepts. Together, this pedagogical intervention was enthusiastically received by the students who better understood how basic nerve physiology concepts fit into the broader context and that such an understanding can result in the development and the roll-out of unique therapeutic interventions for multiple sclerosis.

This article adopts the perspective of Sen's capability approach to examine elite athletes' environment and their capability to plan and prepare a career transition out of sport. Interviews were conducted with 14 elite athletes in Canada and results from the thematic analysis reveal that discrepancies exist in the athletes' environment. Three types of environments emerged from the findings: enabling, restricting, or hindering athletes' capabilities to plan and prepare their transition out of sport to a career they value. The difficulties reside more specifically in the possibilities they have to prepare an education path of their choice while being part of the national team. The results highlight that even though support from family and teammates is essential, it is not sufficient, as the support of coaching staff was shown to be crucial. The role of Game Plan advisors varies according to athletes' type of environment and underline the importance of going beyond their role of individual counseling in certain types of environments.

Abstract Background Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. Methods Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. Results Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. Conclusions A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development. Graphical Abstract

Abstract Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition.

Un monstre humanoïde serait né à Cracovie en 1547. Il connaît une certaine célébrité et se retrouve dans des ouvrages naturalistes, de tératologie, de prodiges ou encore des cosmographies. Alors qu’il est souvent utilisé pour dénoncer les persécutions contre les protestants, le catholique intransigeant François de Belleforest l’insère dans sa Cosmographie universelle en 1575. Dans sa dénonciation du protestantisme, Belleforest est souvent radical, devient à l’occasion manichéen, voire violent, et utilise la nouvelle Imago Mundi au service de son combat. Son usage politique de la géographie est d’autant plus efficace que l’ouvrage touche un large public avide de découvrir une synthèse des récentes découvertes sur le monde. L’article procède à une archéologie de cette gravure, et étudie l’élaboration et la circulation des savoirs cosmographiques, ainsi que leurs usages confessionnels et politiques. Il apparaît que Belleforest dote cette gravure d’un sens nouveau qui met en évidence les angoisses eschatologiques et politiques en cette période charnière de passage du pouvoir de Charles IX à Henri III.

Abstract Selective KRASG12C inhibitors have been developed to covalently lock the oncogene in the inactive GDP-bound state. Two of these molecules, sotorasib and adagrasib, are approved for the treatment of adult patients with KRASG12C-mutated previously treated advanced non-small cell lung cancer. Drug treatment imposes selective pressures leading to the outgrowth of drug-resistant variants. Mass sequencing from patients’ biopsies identified a number of acquired KRAS mutations -both in cis and in trans- in resistant tumors. We demonstrate here that disease progression in vivo can also occur due to adaptive mechanisms and increased KRAS-GTP loading. Using the preclinical tool tri-complex KRASG12C-selective covalent inhibitor, RMC-4998 (also known as RM-029), that targets the active GTP-bound (ON) state of the oncogene, we provide a proof-of-concept that the clinical stage KRASG12C(ON) inhibitor RMC-6291 alone or in combination with KRASG12C(OFF) drugs can be an alternative potential therapeutic strategy to circumvent resistance due to increased KRAS-GTP loading.

Jessica L Bourdon,1 Sidney Judson,1 Taylor Fields,1 Sabrina Verdecanna,1 Nehal P Vadhan,2 Jon Morgenstern3 1Wellbridge Addiction Treatment and Research, Calverton, NY, USA; 2Institute of Behavioral Science, Feinstein Institutes for Medical Research. Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USA; 3Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USACorrespondence: Jessica L Bourdon, Email jbourdon@wellbridge.orgBackground: There is a lack of consensus in the addiction field as to how to refer to alumni of residential treatment who no longer use substances or who reduce their use. In the literature, this label and broader identity are typically discussed in technical (amount and frequency of use) or social terms (environment and social network changes).Objective: The current paper seeks to simplify the discussion by focusing on personal labels without complex technical or social considerations. Alumni of an inpatient addiction treatment facility were asked how they refer to themselves regarding their sobriety status post-discharge.Methods: Forty-nine patients were contacted 3 months post-discharge from a residential inpatient addiction treatment (men = 67%; Mage = 47.75 years). The patients completed a post-discharge assessment that was conducted by a trained research assistant over a 20-minute video call. The current study focused on a “sobriety label” measure in which patients indicated what they want to be called. Patients also explained why they chose their answer in an open-ended question.Results: Most patients identified as in recovery (n = 29; 59.18%) followed by a sober person (n = 7; 14.29%) and four other responses. No alum selected the in remission option, which is notably a common way to refer to patients who no longer use substances.Conclusion: The current study adds a critical patient/alumni perspective to the existing body of literature and serves as a call to action for researchers to add a similar “sobriety label” measure to future assessments, studies, and batteries in effort to bring consistency to the labels, definitions, and identities that are published. This methodology of understanding how this population identifies will create uniformity in future literature and decrease the stigma surrounding addiction.Plain Language Summary: There is a history of inconsistent use of labels, definitions, and identities in the addiction treatment field. Few past studies have directly asked patients how they self-label, and it is important to ask those who use substances or who have reduced their use what they preferred to be called. This study asked a simple question to alumni of an inpatient treatment facility what they want to be called. We then asked them to explain why they chose that answer. Most alumni identified as “in recovery” or “a sober person”. This simple tool can be utilized by other facilities and also highlights that many research studies are referring to individuals by terms they do not prefer (eg, “in remission”).Keywords: sobriety, identity, label, addiction, discharge, recovery, sober person, inpatient

Abstract Our objective was to capture subgroups of soft-tissue sarcoma (STS) using handcraft and deep radiomics approaches to understand their relationship with histopathology, gene-expression profiles, and metastatic relapse-free survival (MFS). We included all consecutive adults with newly diagnosed locally advanced STS (N = 225, 120 men, median age: 62 years) managed at our sarcoma reference center between 2008 and 2020, with contrast-enhanced baseline MRI. After MRI postprocessing, segmentation, and reproducibility assessment, 175 handcrafted radiomics features (h-RFs) were calculated. Convolutional autoencoder neural network (CAE) and half-supervised CAE (HSCAE) were trained in repeated cross-validation on representative contrast-enhanced slices to extract 1024 deep radiomics features (d-RFs). Gene-expression levels were calculated following RNA sequencing (RNAseq) of 110 untreated samples from the same cohort. Unsupervised classifications based on h-RFs, CAE, HSCAE, and RNAseq were built. The h-RFs, CAE, and HSCAE grouping were not associated with the transcriptomics groups but with prognostic radiological features known to correlate with lower survivals and higher grade and SARCULATOR groups (a validated prognostic clinical-histological nomogram). HSCAE and h-RF groups were also associated with MFS in multivariable Cox regressions. Combining HSCAE and transcriptomics groups significantly improved the prognostic performances compared to each group alone, according to the concordance index. The combined radiomic-transcriptomic group with worse MFS was characterized by the up-regulation of 707 genes and 292 genesets related to inflammation, hypoxia, apoptosis, and cell differentiation. Overall, subgroups of STS identified on pre-treatment MRI using handcrafted and deep radiomics were associated with meaningful clinical, histological, and radiological characteristics, and could strengthen the prognostic value of transcriptomics signatures.

Immunologic thrombocytopenic purpura (ITP) is a condition that affects four to 18 per 100 000 children every year. In most cases, spontaneous remission occurs, but splenectomy may be proposed. Exploring the site of platelet sequestration can help to better predict potential poor responders to splenectomy, but 111 In-radiolabeled platelet scintigraphy (IPS) can be difficult to perform in children with very few platelets. A 12-year-old boy suffering from refractory ITP was referred for evaluation of platelet survival and sequestration and consideration of splenectomy. His platelet count consistently remained below 10 000/mm 3 . An exceptional procedure was set up to use homologous platelets to perform the IPS. Splenectomy was ruled out based on the results of 111 In-radiolabeled homologous platelet scintigraphy. The attending pediatrician intensified medical treatments, resulting in a significant improvement in platelet count. This increase in platelet levels allowed for 111 In-radiolabeled autologous platelet scintigraphy, which confirmed the absence of splenic sequestration. This allowed us to reject splenectomy in this child. Homologous IPS could help clinicians to choose splenectomy as a treatment option for ITP in children with a very low platelet count, and its use should be promoted after failed thrombopoietin receptor agonist (TPO-RA) treatment. More systematic studies are needed to confirm the predictive response to splenectomy of homologous IPS.

The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the Trp53 alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in Trp53+/+Eμ-Myc males compared to Trp53ΔAS/ΔAS Eμ-Myc males, but also compared to Trp53+/+Eμ-Myc and Trp53ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenic cells from Trp53+/+Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We identified Ackr4 as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of ACKR4 increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.

Most research on dual language learners (DLLs) in preschool has focused on language and literacy development. Less work has been done on their play and social interactions, in spite of the importance of these for development and learning. Although DLLs possess many social strengths, they also face challenges, particularly in an English-dominant classroom. In the present investigation we examined the influence of three factors on DLLs play interactions with peers in preschool: teacher support, peer interactions, and play materials. We recorded the free play of 12 DLLs who were of low English proficiency in English-dominant classrooms and coded aspects of these three factors. Using multiple regression analysis we identified four variables that predicted the frequency of DLLs' interactions with their peers. Teacher interactions in play that included a child's home language--though not overall teacher contact, alone--verbal and positive play behaviors by peers, and the availability of blocks and replica play toys. Implications of our findings for classroom practice are offered.

Abstract Despite abundant evidence demonstrating that platelets foster metastasis, anti-platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subject syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the glycoprotein VI (GPVI) platelet-specific receptor in humanized mouse models efficiently reduce the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study demonstrates therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as a molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.

Abstract Background The Live Birth Rate (LBR) after day 5 (D5) blastocyst transfer is significantly higher than that with D6 embryos in both fresh and frozen-vitrified embryo transfer cycles, according to the most recently published meta-analyses. Therefore, for women obtaining only D6 blastocysts, the chances of pregnancy may be lower but nonetheless sufficient to warrant transferring such embryos. The best strategy for transfer (i.e., in fresh versus frozen cycles) remains unclear and there is a paucity of data on this subject. Methods A total of 896 couples with D6 single blastocyst transfers were retrospectively analyzed: patients receiving a fresh D6 embryo transfer (Fresh D6 transfer group, n = 109) versus those receiving a frozen-thawed D6 embryo transfer (Frozen D6 transfer group, n = 787). A subgroup comprising a freeze-all cycle without any previous fresh or frozen D5 embryo transfers (Elective frozen D6, n = 77) was considered and also compared with the Fresh D6 transfer group. We compared LBR between these two groups. Correlation between D6 blastocyst morphology according to Gardner’s classification and live birth occurrence was also evaluated. Statistical analysis was carried out using univariate and multivariate logistic regression models. Results The LBR was significantly lower after a fresh D6 blastocyst transfer compared to the LBR with a frozen-thawed D6 blastocyst transfer [5.5% (6/109) vs. 12.5% (98/787), p = 0.034]. Comparison between LBR after Elective frozen D6 group to the Fresh D6 blastocyst transfers confirmed the superiority of frozen D6 blastocyst transfers. Statistical analysis of the blastocyst morphology parameters showed that both trophectoderm (TE) and inner cell mass (ICM) grades were significantly associated with the LBR after D6 embryo transfer (p

Abstract Background Meta-analysis show the diagnostic performance of cardiac dedicated multi-pinhole cadmium-zinc-telluride myocardial perfusion imaging (MPI) with a sensibility around 0.9 and a specificity around 0.7. The aim of the present study is to explore a simple method to generate less artefact on MPI using single photon emission computed tomography (SPECT) and to enhance specificity without changing sensibility. Results From October 2018 to March 2019, 200 patients who underwent SPECT with [99mTc]Tc-tetrofosmin were prospectively recruited: 100 patients with ischemia or necrosis diagnosis (first arm), and 100 patients with myocardial reversible SPECT artefact (second arm). Each SPECT was explored using two image process based on a Butterworth prefilter and post-filter: the original image processing (reconstruction A) with a cut-off frequency equals to 37% of the Nyquist frequency and order equals to 7, and a second image processing (reconstruction B) with a cut-off frequency equals to 25% of the Nyquist frequency and order equals to 5. For each patient, sum stress or rest score with and without septum (SSRS and SSRSws) were calculated with the two reconstructions. No significant statistical difference between SSRSa and SSRSb was identified for the first arm (P = 0.54) and the relative difference ∆r was − 0.5 ± 11.1% (95% CI − 2.7 to 1.7). We found a significant statistical difference between SSRSa and SSRSb for the second arm (p

The authentic teaching and learning approach introduces real-world scenarios into the classroom to better engage Generation Z students. Considering this, we introduced an authentic learning practical exercise (breakfast meal and glycemic variation) to undergraduate biology students at the University of La Reunion (France). Here, students were initially briefed regarding the practical and subsequently determined their baseline glucose values (glucometer). They then consumed 200 mL of fruit juice together with a pain au chocolat (chocolate pastry) and subsequently recorded their glucose values at regular intervals. The last reading was done after 150 min, and they thereafter plotted such data to reveal temporal glycemic variations. During this time, the students also worked on a report to document information collected and began to supply responses to several listed questions. Three weeks after completion of the practical, we evaluated whether this intervention would lead to changes in their views regarding the nature and regularity of breakfast meal intake (employing survey questions). Our findings show that a reasonable proportion of the students indicated that the intervention did change their dietary habits, with 50% sometimes opting for an improved breakfast, whereas 10% also changed their habits albeit for only a small while. Of note, >60% of students indicated that they changed their breakfast intake habits by the end of the endocrinology module. These findings show that the beneficial effects of authentic teaching approaches may elicit relatively long-lasting changes in terms of breakfast behavioral patterns in young people and that such effects may also impact the broader society. New & Noteworthy: This study introduced an authentic learning exercise (endocrinology practical exercise) to undergraduate biology students and ascertained whether it changed their views regarding the nature and regularity of breakfast meals. Here, many altered their breakfast dietary habits, which persisted even after the completion of their module. Authentic teaching approaches can therefore trigger relatively long-lasting changes in terms of breakfast behavioral patterns in young people and may also impact the broader society.

Background Participating in surveys can shape the perception of participants related to the study topic. Administering a vaccine hesitancy questionnaire can have negative impacts on participants’ vaccine confidence. This is particularly true for online and cross-cultural data collection because culturally safe health education to correct misinformation is typically not provided after the administration of an electronic survey. Objective To create a culturally safe, online, COVID-19 vaccine confidence survey for Indigenous youth designed to collect authentic, culturally relevant data of their vaccine experiences, with a low risk of contributing to further vaccine confusion among participants. Methods Using the Aboriginal Telehealth Knowledge Circle consensus method, a team of academics, health care providers, policy makers, and community partners reviewed COVID-19 vaccine hesitancy surveys used in public health research, analyzed potential risks, and created a framework for electronic Indigenous vaccine confidence surveys as well as survey items. Results The framework for safer online survey items is based on 2 principles, a first do-no-harm approach and applying a strengths-based lens. Relevant survey domains identified in the process include sociodemographic information, participants’ connection to their community, preferred sources for health information, vaccination uptake among family members and peers, as well as personal attitudes toward vaccines. A total of 44 survey items were developed, including 5 open-ended items to improve the authenticity of the data and the analysis of the experiences of Indigenous youth. Conclusions Using an Indigenous consensus method, we have developed an online COVID-19 vaccine confidence survey with culturally relevant domains and reduced the risk of amplifying misinformation and negative impacts on vaccine confidence among Indigenous participants. Our approach can be adapted to other online survey development in collaboration with Indigenous communities.

Summary: Background: Children in low and middle-income countries remain vulnerable following hospital-discharge. We estimated the incidence and correlates of hospital readmission among young children admitted to nine hospitals in sub-Saharan Africa and South Asia. Methods: This was a secondary analysis of the CHAIN Network prospective cohort enrolled between 20th November 2016 and 31st January 2019. Children aged 2–23 months were eligible for enrolment, if admitted for an acute illness to one of the study hospitals. Exclusions were requiring immediate resuscitation, inability to tolerate oral feeds in their normal state of health, had suspected terminal illness, suspected chromosomal abnormality, trauma, admission for surgery, or their parent/caregiver was unwilling to participate and attend follow-up visits. Data from children discharged alive from the index admission were analysed for hospital readmission within 180-days from discharge. We examined ratios of readmission to post-discharge mortality rates. Using models with death as the competing event, we evaluated demographic, nutritional, clinical, and socioeconomic associations with readmission. Findings: Of 2874 children (1239 (43%) girls, median (IQR) age 10.8 (6.8–15.6) months), 655 readmission episodes occurred among 506 (18%) children (198 (39%) girls): 391 (14%) with one, and 115 (4%) with multiple readmissions, with a rate of: 41.0 (95% CI 38.0–44.3) readmissions/1000 child-months. Median time to readmission was 42 (IQR 15–93) days. 460/655 (70%) and 195/655 (30%) readmissions occurred at index study hospital and non-study hospitals respectively. One-third (N = 213/655, 33%) of readmissions occurred within 30 days of index discharge. Sites with fewest readmissions had the highest post-discharge mortality. Most readmissions to study hospitals (371/450, 81%) were for the same illness as the index admission. Age, prior hospitalisation, chronic conditions, illness severity, and maternal mental health score, but not sex, nutritional status, or physical access to healthcare, were associated with readmission. Interpretation: Readmissions may be appropriate and necessary to reduce post-discharge mortality in high mortality settings. Social and financial support, training on recognition of serious illness for caregivers, and improving discharge procedures, continuity of care and facilitation of readmission need to be tested in intervention studies. We propose the ratio of readmission to post-discharge mortality rates as a marker of overall post-discharge access and care. Funding: The Bill & Melinda Gates Foundation (OPP1131320).