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Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5]; P = .0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8]; P = .0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low-hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P < .0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT01564784.

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.

ImportanceEarly-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.ObjectiveTo report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.Data sourcesPubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023.Study selectionStudies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included.Data extraction and synthesisData extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model.Main outcomes and measuresOutcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis.ResultsOf the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies).Conclusions and relevanceIn this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Abstract A substantial amount of research, resources, and effort has been invested in the search for a 'holy grail' of twenty-first century leadership competencies. Ironically, despite the increasing significance of leadership and the substantial investments in uncovering the attributes of successful leaders, concerns persist regarding the quality of leadership worldwide. While the literature extensively outlines 'what' twenty-first century-ready leaders should embody, there remains a gap in outlining 'how' to nurture such leaders. We contrast existing practices that have focused on teaching functional content and relying on retrospective and deficit-based competency models by advocating for a strengths-based perspective. While there has been an increasing interest in positive psychology, which promotes a shift away from prevalent deficit correction approaches towards a framework that emphasises social-emotional and meta-cognitive strengths, character strengths have received little attention in corporate leader development programmes. We argue that nurturing character strengths offers a more sustainable, self-reinforcing process for twenty-first century leader development to overcome the limitations of short-lived leadership training results that fade over time. The Values in Action Classification of Character Strengths and Virtues provides a robust framework for identifying and nurturing these strengths. However, character strengths have traditionally been viewed as personal attributes, rather than leadership competencies. We challenge traditional views on leader development by arguing that character strengths reflect the competencies required of twenty-first century-ready leaders, as these more 'humane' characteristics remain relevant over time and valued across cultures because they represent qualities that are universally appreciated in defining 'what makes a good person'.

Catherine H Yu,1,2 Giuliana Guarna,1 Pamela Tsao,3 Jude R Jesuthasan,1 Adrian NC Lau,3,4 Ferhan S Siddiqi,1 Julie Anne Gilmour,3 Danyal Ladha,1 Henry Halapy,5 Andrew Advani1–3 1Li Ka Shing Knowledge Institute, St Michael’s Hospital, 2Division of Endocrinology and Metabolism, Department of Medicine, St Michael’s Hospital, University of Toronto, 3Department of Medicine, Faculty of Medicine, University of Toronto, 4Division of Endocrinology, Department of Medicine, University Health Network, 5Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada Purpose: For emerging adults with chronic medical diseases, the transition from pediatric to adult health care is often a time of great upheaval, commonly associated with unhealthy self-management choices, loss to follow-up, and adverse outcomes. We conducted a systematic review to examine the use of incentive strategies to promote positive health-related behaviors in young adults with chronic medical diseases.Methods: The Medline, CINAHL, Embase, PsycInfo, and Cochrane databases were searched through June 2014. Studies of any design where an incentive was used to achieve a target behavior or outcome in a pediatric or emerging adult population (age

The possible association of Cytomegalovirus (CMV) with human colorectal adenocarcinomas was first reported in 1978 by Huang and Roche, who detected CMV DNA in 4 of 7 colonic adenocarcinomas by membrane complementary Ribonucleic Acid-Deoxyribonucleic Acid (RNA-DNA) hybridisation. CMV earns its name from the characteristic cytomegalic appearance of intranuclear inclusions in infected cells, which include endothelial cells, histiocytes, macrophages, and epithelial cells. The most common site of CMV infection in the gastrointestinal tract is the colon (55%), followed by the sigmoid colon and rectum (35%) and the gastric antrum (25%). Here, a middle-aged female presenting with pain in the lower abdomen, which was insidious in onset and gradually progressive. Ultrasonography revealed a large intestine dilated and filled with multiple air-fluid levels, indicating bowel obstruction. Multidetector Computed Tomography (MDCT) showed circumferential wall thickening involving the distal half of the transverse colon and descending colon. The case was subjected to laparotomy. The resected segment of the colon was sent for histopathological evaluation, and microscopic examination showed adenocarcinoma and many mucosal ulcers, which on keen observation revealed viral inclusions. The diagnosis of colon adenocarcinoma, with a pathological staging of pT2N0Mx with CMV infection, was rendered. CMV infection was confirmed by immunohistochemistry. The patient was on post-surgery chemotherapy and receiving ganciclovir. On follow-up, the patient was recovering fine. Histopathology examination and IHC remain the gold standard in diagnosing CMV, and the concurrent occurrence of colitis and carcinoma should be kept in mind to assist in proper management.

Abstract As a vital source of nutrition, cultural identity, and economic activity, seafood has become one of the most globally traded commodities worldwide. However, increased concerns about food security, coupled with the disruptive effects of climate change, contagious diseases, and geopolitical conflict, are bringing acute attention to the need for food system transformation at multiple scales. Here, we investigate the United States’ potential to achieve seafood “independence” and maximize health benefits to the nation by integrating production, utilization, yield, and consumption data across seven regions of the United States and nationally over 50 years (1970–2021). Although the United States is the second largest importer of seafood worldwide, findings from this study show that self-reliance at the national level is achievable, though the ability of different subregions to meet demand is variable. Achieving greater seafood independence would require shifts in consumer behavior, investments in infrastructure, and continual adaptation in the face of climate change.

Abstract Background Bangladesh has a shortfall of health professionals. The World Health Organization states that improving education will increase recruitment and retention of health workers. Traditional learning approaches, in medical education particularly, focus on didactic teaching, teaching of subjects and knowledge testing. These approaches have been superseded in some programmes, with a greater focus on active learning, integrated teaching and learning of knowledge, application, skills and attitudes or values and associated testing of competencies as educational outcomes. In addition, some regions do not have continuous professional development or clinical placements for health worker students, contributing to difficulties in retention of health workers. This study aims to explore the experiences of health professional education in Bangladesh, focusing on what is through observation of health professional education sessions and experiences of educators. Methods This mixed method study included 22 observations of teaching sessions in clinical and educational settings, detailed analysis of 8 national curricula documents mapped to Global Competency and Outcomes Framework for Universal Health Coverage and 15 interviews of professionals responsible for health education. An observational checklist was created based on previous literature which assessed training of within dimensions of basic clinical skills; diagnosis and management; professionalism; professional development; and effective communication. Interviews explored current practices within health education in Bangladesh, as well as barriers and facilitators to incorporating different approaches to learning. Results Observations revealed a variety of approaches and frameworks followed across institutions. Only one observation included all sub-competencies of the checklist. National curricula documents varied in their coverage of the Global Competency and Outcomes Framework domains. Three key themes were generated from a thematic analysis of interview transcripts: (1) education across the career span; (2) challenges for health professional education; (3) contextual factors and health professional education. Opportunities for progression and development post qualification are limited and certain professions are favoured over others. Conclusion Traditional approaches seem to predominate but there is some enthusiasm for a more clinical focus to education and for more competency based approaches to teaching, learning and assessment.

Novel treatment strategies are needed for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell-engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.

Craig A Portell, Candice M Wenzell, Anjali S Advani Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Acute lymphoblastic leukemia (ALL) in adults remains a challenging disease to treat, and novel therapies are needed. Precursor-B ALL comprises 80% of cases, and the CD19 antigen is expressed in nearly all precursor-B ALL patients. Bispecific T-cell-engaging antibodies are novel bioengineered proteins. The bispecific T-cell-engaging antibody blinatumomab engages polyclonal T cells to CD19-expressing B cells. By binding to both CD3 and CD19, blinatumomab physically brings these T cells in close proximity to malignant B cells and potentiates T-cell-induced cytotoxic cell kill. Blinatumomab requires continuous intravenous infusion due to its short half-life, the need for continuous exposure for the drug to exert sufficient efficacy, and lessened toxicity. A phase II trial of B-cell ALL patients with persistent or relapsed minimal residual disease demonstrated an 80% rate of complete molecular remission. Cytokine-release syndrome and central nervous system events, such as seizures and encephalopathy, are reversible toxicities. Promising results in B-cell ALL with minimal residual disease have led to further evaluation of this drug in newly diagnosed and relapsed B-cell ALL. Keywords: blinatumomab, B-cell acute lymphoblastic leukemia, CD19, BiTE antibodies

Silicosis is associated with preventable but irreversible lung damage. Early quantifiable assessment of silicosis workers would promote early interventional steps to reduce health deterioration. The objectives of this study were to correlate spirometry findings and post-six-minute walk test oxygen desaturation (post-6MWT OD) in chronic simple silicosis with age, duration of silica exposure (DSE), smoking pack years (SPY), occupation, and mean pulmonary artery pressure. Based on occupational exposure to silica and radiologic confirmation of chronic simple silicosis, 104 patients (all males) were enrolled and grouped based on SPY (nil, 1-10, 11-20, and >20) and occupation (drillers and dressers). They were further investigated with spirometry, post-6MWT OD, and transthoracic echocardiography (TTE), and findings were statistically analyzed. Abnormal spirometry findings were seen in 62.5% of total cases (65/104), with the highest percentage in the >20 SPY group (84%; 21/25) and drillers (68.3%; 28/41). The post-6MWT OD was seen in 50.96% of cases (53/104) with the highest percentage in the >20 SPY group (56%; 14/25) and drillers (63.4%; 26/41). Normal and restrictive patterns were predominant among 20 SPY group. Normal, obstructive, and restrictive patterns were predominant among dressers, while mixed patterns were in drillers. Mean age and mean DSE were higher for >20 SPY group and dressers; obstructive and mixed patterns; and patients with post-6MWT OD. Pulmonary hypertension was significantly associated with the presence of abnormal spirometry patterns (69.3%; 45/65) and post-6MWT OD (79.3%; 42/53). Mean forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was significantly lower for the >20 SPY group. Mean FEV1 had an inverse relation with SPY, and mean FVC was lower for drillers than dressers. Spirometry, post-6MWT OD, and TTE assessment give a complete overview of the cardiopulmonary exercise capacity of chronic silicosis patients and facilitate early interventions with special consideration for workers involved in machine-based mining activity.

Introduction New treatments and technologies have advanced diabetes care; however, diabetes continues to have a major impact on the daily lives of affected individuals, especially among equity-deserving groups. Evidence from patient engagement literature suggests that involving diverse patients in healthcare can create cost-effective improvements and enhanced efficiency in care that has high patient acceptability and numerous health benefits, as well as improved provider satisfaction. A scoping review will be conducted to provide a cohesive and comprehensive understanding of patient engagement practices and the resulting outcomes.Methods and analysis The review will follow the recommendations for the conduct of scoping reviews developed by the Joanna Briggs Institute (JBI) Scoping Review Methodology Group. The review will include English-language literature published between 1 January 1990 and the present, searched through MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), International Bibliography of the Social Sciences (IBSS), Sociological Abstracts, Applied Social Sciences Index and Abstracts (ASSIA), Scopus, Social Sciences Citation Index and Campbell Collaboration; hand searches; and grey literature. Literature that describes conceptualisations of engagement, methods/strategies for engagement and/or evaluations of engagement across different levels of diabetes care, including direct care, organisational design and governance and policymaking will be included. The review will encompass quantitative, qualitative and mixed-methods studies. Research that is secondary, published in languages other than English, or not specifically focused on patient engagement will be excluded. Screening and extraction will be completed by two independent reviewers and conflicts will be resolved by discussion or a third reviewer, with piloting at each step. Studies will be analysed through descriptive numerical summary and content analysis.Ethics and dissemination No ethical or safety considerations are pertinent to this work. The results will be disseminated to patients/patient advocacy groups, diabetes organisations, clinicians, researchers, decision-makers and policymakers by way of summary documents, infographics, meeting presentations and through peer-reviewed publications.Trial registration number The protocol has been registered with Open Science Framework: https://doi.org/10.17605/OSF.IO/KCD7Z.

Abstract DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype–environment interaction in retina.

Abstract Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.