Neural correlates of ‘pessimistic' attitude in depression

Background Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that ‘pessimism'-related emotion processing would characterize brain activity in major depression. Method During functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences - pleasant, unpleasant and neutral - and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the ‘unknown' expectation was compared with the ‘known' expectation conditions. Results While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. Conclusions Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a ‘pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depressio

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis : an international, multidisciplinary Delphi-based consensus

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.Peer reviewe

The effectiveness of technology-supported personalised learning in low- and middle-income countries: A meta-analysis

AbstractDigital technology offers the potential to address educational challenges in resource‐poor settings. This meta‐analysis examines the impact of students' use of technology that personalises and adapts to learning level in low‐ and middle‐income countries. Following a systematic search for research between 2007 and 2020, 16 randomised controlled trials were identified in five countries. Studies involved 53,029 learners aged 6–15 years. Coding examined learning domain (mathematics and literacy); personalisation level and delivery; technology use; and intervention duration and intensity. Overall, technology‐supported personalised learning was found to have a statistically significant—if moderate—positive effect size of 0.18 on learning (p = 0.001). Meta‐regression reveals how more personalised approaches which adapt or adjust to learners' level led to significantly greater impact (an effect size of 0.35) than those only linking to learners' interests or providing personalised feedback, support, and/or assessment. Avenues for future research include investigating cost implications, optimum programme length, and teachers' role in making personalised learning with technology effective. Practitioner notesWhat is already known about this topic? Promoting personalised learning is an established aim of educators. Using technology to support personalised learning in low‐ and middle‐income countries (LMICs) could play an important role in ensuring more inclusive and equitable access to education, particularly in the aftermath of COVID‐19. There is currently no rigorous overview of evidence on the effectiveness of using technology to enable personalised learning in LMICs. What this paper adds? The meta‐analysis is the first to evaluate the effectiveness of technology‐supported personalised learning in improving learning outcomes for school‐aged children in LMICs. Technology‐supported personalised learning has a statistically significant, positive effect on learning outcomes. Interventions are similarly effective for mathematics and literacy and whether or not teachers also have an active role in the personalisation. Personalised approaches that adapt or adjust to the learner led to significantly greater impact, although whether these warrant the additional investment likely necessary for implementation at scale needs to be investigated. Personalised technology implementation of moderate duration and intensity had similar positive effects to that of stronger duration and intensity, although further research is needed to confirm this. Implications for practice and/or policy: The inclusion of more adaptive personalisation features in technology‐assisted learning environments can lead to greater learning gains. Personalised technology approaches featuring moderate personalisation may also yield learning rewards. While it is not known whether personalised technology can be scaled in a cost‐effective and contextually appropriate way, there are indications that this is possible. The appropriateness of teachers integrating personalised approaches in their practice should be explored given ‘supplementary’ uses of personalised technology (ie, additional sessions involving technology outside of regular instruction) are common. </jats:sec

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments

Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients

Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of the widely used antineoplastic agent 5-fluorouracil (5FU), thereby limiting the efficacy of the therapy. To identify patients suffering from a complete or partial DPD deficiency, the activity of DPD is usually determined in peripheral blood mononuclear cells (PBM cells). In this study, we demonstrated that the highest activity of DPD was found in monocytes followed by that of lymphocytes, granulocytes and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in PBM cells proved to be intermediate compared with the DPD activity observed in monocytes and lymphocytes. The mean percentage of monocytes in the PBM cells obtained from cancer patients proved to be significantly higher than that observed in PBM cells obtained from healthy volunteers. Moreover, a profound positive correlation was observed between the DPD activity of PBM cells and the percentage of monocytes, thus introducing a large inter- and intrapatient variability in the activity of DPD and hindering the detection of patients with a partial DPD deficiency. © 1999 Cancer Research Campaig

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN

Updates in SJS/TEN: collaboration, innovation, and community

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15–20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1–5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28–29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper

Assessing the Advantages, Limitations and Potential of Human Primary Prostate Epithelial Cells as a Pre-clinical Model for Prostate Cancer Research

Choosing an appropriate cell model(s) is the first decision to be made before starting a new project or programme of study. Here, we address the rationale that can be behind this decision and we summarize the current cell models that are used to study prostate cancer. Researchers face the challenge of choosing a model that recapitulates the complexity and heterogeneity of prostate cancer. The use of primary prostate epithelial cells cultured from patient tissue is discussed, and the necessity for close clinical-academic collaboration in order to do this is highlighted. Finally, a novel quantitative phase imaging technique is described, along with the potential for cell characterization to not only include gene expression and protein markers but also morphological features, cell behaviour and kinetic activity