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Prostate cancer is primarily hormone-dependent, and medical treatments have focused on inhibiting androgen biosynthesis or signaling through various approaches. Despite significant advances with the introduction of androgen receptor signalling inhibitors (ARSIs), patients continue to progress to castration-resistant prostate cancer (CRPC), highlighting the need for targeted therapies that extend beyond hormonal blockade. Chimeric Antigen Receptor (CAR) T cells and other engineered immune cells represent a new generation of adoptive cellular therapies. While these therapies have significantly enhanced outcomes for patients with hematological malignancies, ongoing research is exploring the broader use of CAR T therapy in solid tumors, including advanced prostate cancer. In general, CAR T cell therapies are less effective against solid cancers with the immunosuppressive tumor microenvironment hindering T cell infiltration, activation and cytotoxicity following antigen recognition. In addition, inherent tumor heterogeneity exists in patients with advanced prostate cancer that may prevent durable therapeutic responses using single-target agents. These barriers must be overcome to inform clinical trial design and improve treatment efficacy. In this review, we discuss the innovative and rationally designed strategies under investigation to improve the clinical translation of cellular immunotherapy in prostate cancer and maximise therapeutic outcomes for these patients.
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AIM: To describe popular diet content visible on #intermittentfasting, #keto, and #lowcarb on adolescent social media accounts. METHODS: An adolescent Instagram profile captured 200 'top' images from three popular diet hashtags (#intermittentfasting, #keto, and #lowcarb) across two timepoints. Images were coded using a pre-determined ontology as food (core or discretionary; common foods/food groups), people (group, individual, before/after), or informative. Descriptive statistics were used to summarise these categories across hashtags. RESULTS: At the time of first data collection, there were 3.8 million #intermittentfasting, 19 million #keto, and 22 million #lowcarb posts on Instagram. At the second timepoint there were 4.3 million #intermittentfasting, 21.5 million #keto, and 24.3 million #lowcarb posts. Images tagged #intermittentfasting were categorised as 44% food, 39% people, 10% information; #keto were 64% food, 28% people, 5% information; and #lowcarb were 69% food, 14% people, 16% information. Food images mostly depicted animal proteins (58.6% of #intermittentfasting; 62.9% of #keto; and 40.1% of #lowcarb). Images of people were individual (44%) or before/after (39%); mostly female (77%), of white (53%) ethnicity. Across all posts, 12.5% were linked to a commercial product/program, and 2.3% provided nutrition information. CONCLUSION: Diet-related images visible when adolescents search #intermittentfasting, #keto, and #lowcarb on Instagram promote animal-based foods with or without vegetables. These diet hashtags on Instagram do not provide nutrition information and are not helpful for young people searching for diet information online.
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The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Sobrepeso , Adulto , Adolescente , Humanos , Sobrepeso/complicaciones , Sobrepeso/terapia , Obesidad , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Terapia Conductista , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joined-up policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.
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Diabetes Mellitus Tipo 2 , Obesidad Infantil , Niño , Adolescente , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Obesidad Infantil/psicología , Calidad de Vida , Dieta , ComorbilidadRESUMEN
This study aimed to understand clinician, researcher and consumer views regarding factors which influence eating disorder (ED) risk during behavioral weight management, including individual risk factors, intervention strategies and delivery features. Eighty-seven participants were recruited internationally through professional and consumer organizations and social media and completed an online survey. Individual characteristics, intervention strategies (5-point scale) and delivery features (important/unimportant/unsure) were rated. Participants were mostly women (n = 81), aged 35-49 y, from Australia or United States, were clinicians and/or reported lived experience of overweight/obesity and/or ED. There was agreement (64% to 99%) that individual characteristics were relevant to ED risk, with history of ED, weight-based teasing/stigma and weight bias internalization having the highest agreement. Intervention strategies most frequently rated as likely to increase ED risk included those with a focus on weight, prescription (structured diets, exercise plans) and monitoring strategies, e.g., calorie counting. Strategies most frequently rated as likely to decrease ED risk included having a health focus, flexibility and inclusion of psychosocial support. Delivery features considered most important were who delivered the intervention (profession, qualifications) and support (frequency, duration). Findings will inform future research to quantitatively assess which of these factors predict eating disorder risk, to inform screening and monitoring protocols.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Obesidad , Sobrepeso , Adulto , Persona de Mediana Edad , Control de la Conducta , Consenso , Obesidad/psicología , Sobrepeso/psicología , Estigma Social , Encuestas y Cuestionarios , Humanos , Mantenimiento del Peso Corporal , Masculino , FemeninoRESUMEN
This systematic review examined change in eating disorder risk during weight management interventions. Four databases and clinical trials registries were searched in March and May 2022, respectively, to identify behavioral weight management intervention trials in adults with overweight/obesity measuring eating disorder symptoms at pre- and post-intervention or follow-up. Random effects meta-analyses were conducted examining within group change in risk. Of 12,023 screened, 49 were eligible (n = 6337, mean age range 22.1 to 59.9 years, mean (SD) 81(20.4)% female). Interventions ranged from 4 weeks to 18 months, with follow-up of 10 weeks to 36 months post-intervention. There was a within group reduction in global eating disorder scores (20 intervention arms; Hedges' g = -0.27; 95% CI -0.36, -0.17; I2 67.1%) and binge eating (49 intervention arms; -0.66; 95% CI -0.76, -0.56; I2 82.7%) post-intervention, both maintained at follow-up. Of 14 studies reporting prevalence or episodes of binge eating, all reported a reduction. Four studies reported eating disorder symptoms, not present at baseline, in a subset of participants (0%-6.5%). Overall, behavioral weight management interventions do not increase eating disorder symptoms for most adults; indeed, a modest reduction is seen post-intervention and follow-up. A small subset of participants may experience disordered eating; therefore, monitoring for the emergence of symptoms is important.
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Trastorno por Atracón , Trastornos de Alimentación y de la Ingestión de Alimentos , Adulto , Femenino , Humanos , Adulto Joven , Persona de Mediana Edad , Masculino , Sobrepeso/complicaciones , Sobrepeso/terapia , Obesidad/complicaciones , Obesidad/terapia , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Terapia Conductista , Trastorno por Atracón/terapiaRESUMEN
INTRODUCTION: People with obesity are vulnerable to eating disorders. It has been suggested that screening for eating disorder risk be part of obesity care. However, it is unclear what current practice entails. OBJECTIVE: To explore considerations of eating disorder risk during treatment of obesity, including assessment and intervention strategies used in clinical practice. MATERIALS AND METHODS: An online (REDCap) cross-sectional survey was distributed to health professionals working with individuals with obesity in Australia through professional societies and social media. The survey had three sections: 1. Characteristics of Clinician/Practice, 2. Current Practice, 3. Attitudes. Data were summarised using descriptive statistics and free-text comments were independently coded in duplicate to identify themes. RESULTS: 59 health professionals completed the survey. Most were dietitians (n = 29), identified as women (n = 45) and worked within a public hospital (n = 30) and/or private practice (n = 29). Overall, 50 respondents reported assessing for eating disorder risk. Most reported that having a history of, or risk factors of eating disorders should not preclude obesity care but emphasised the importance of treatment modification including using a patient-centred approach involving a multidisciplinary team and promoting healthy eating behaviours, with less emphasis on calorie restriction or bariatric surgery. Management approaches did not differ for those with eating disorder risk factors or a diagnosed eating disorder. Clinicians identified the need for additional training and clear referral pathways. CONCLUSION: Individualised care, balancing models of care for eating disorders and obesity and further access to training and services will be important in improving care of patients with obesity.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Obesidad , Humanos , Femenino , Estudios Transversales , Australia/epidemiología , Obesidad/terapia , Obesidad/prevención & control , Factores de Riesgo , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/terapiaRESUMEN
(1) Background: weight-management interventions vary in their delivery features and intervention strategies. We aimed to establish a protocol to identify these intervention components. (2) Methods: a framework was developed through literature searches and stakeholder consultation. Six studies were independently coded by two reviewers. Consensus included recording conflict resolutions and framework changes. (3) Results: more conflicts occurred for intervention strategies compared to delivery features; both required the updating of definitions. The average coding times were 78 min (SD: 48) for delivery features and 54 min (SD: 29) for intervention strategies. (4) Conclusions: this study developed a detailed framework and highlights the complexities in objectively mapping weight-management trials.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Obesidad , Humanos , Obesidad/terapia , Ejercicio Físico , Dieta Reductora , Trastornos de Alimentación y de la Ingestión de Alimentos/terapiaRESUMEN
The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.
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In adolescents and adults, the co-occurrence of eating disorders and overweight or obesity is continuing to increase, and the prevalence of eating disorders is higher in people with higher weight compared to those with lower weight. People with an eating disorder with higher weight are more likely to present for weight loss than for eating disorder treatment. However, there are no clinical practice guidelines on how to screen, assess, and monitor eating disorder risk in the context of obesity treatment. In this article, we first summarize current challenges and knowledge gaps related to the identification and assessment of eating disorder risk and symptoms in people with higher weight seeking obesity treatment. Specifically, we discuss considerations relating to the validation of current self-report measures, dietary restraint, body dissatisfaction, binge eating, and how change in eating disorder risk can be measured in this setting. Second, we propose avenues for further research to guide the development and implementation of clinical and research protocols for the identification and assessment of eating disorders in people with higher weight in the context of obesity treatment. PUBLIC SIGNIFICANCE: The number of people with both eating disorders and higher weight is increasing. Currently, there is little guidance for clinicians and researchers about how to identify and monitor risk of eating disorders in people with higher weight. We present limitations of current research and suggest future avenues for research to enhance care for people living with higher weight with eating disorders.
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Trastorno por Atracón , Bulimia , Trastornos de Alimentación y de la Ingestión de Alimentos , Adulto , Adolescente , Humanos , Obesidad/terapia , Sobrepeso , Pérdida de Peso , Trastorno por Atracón/terapiaRESUMEN
AIM: This systematic review explored the feasibility, acceptability and effect on health outcomes of weight-neutral interventions in health improvement-seeking young people with overweight/obesity. METHODS: Six databases were searched to March 2021 for health, but not weight, focused interventions (PROSPERO, CRD42020152671). Eligible studies recruited young people (10-24 years) with overweight/obesity. The studies were described using narrative synthesis, with numerical results summarised. The quality of included studies was assessed using the Joanna Briggs Institute critical appraisal tools. RESULTS: Six articles were included, representing three pilot studies. Study 1 (n = 37, 14-17 years) compared a 6-week mindful eating program with single-session lifestyle education; Study 2 (n = 35, 14-17 years) compared 12-week weight-neutral lifestyle education focused on intuitive eating and carbohydrate quality, with/without guided imagery; and Study 3 (n = 33, 12-17 years) compared a 6-week mindfulness intervention with cognitive behavioural therapy in adolescents with depressive symptoms at risk of type 2 diabetes. All interventions explored feasibility (intervention group retention 57%-88%, attendance >80%) and reported interventions were acceptable. Studies 1 and 3 reported no change in mindfulness. Study 2 reported an increase (p < 0.05) in intuitive eating following weight-neutral plus guided imagery (0.32 ± 0.36, Hawks' Scale, score 1-4), compared with weight-neutral alone (0.15 ± 0.29). Study 1 reported decreased body mass index (p < 0.001) following mindful eating (-1.1 kg/m2 ), compared with single-session lifestyle education (+0.7 kg/m2 ); Studies 2 and 3 found no change in body mass index or body mass index z-score. CONCLUSIONS: Weight-neutral interventions may be feasible and acceptable in adolescents with overweight/obesity in the short term (≤12 weeks), but data are limited.
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Diabetes Mellitus Tipo 2 , Sobrepeso , Adolescente , Humanos , Índice de Masa Corporal , Sobrepeso/terapia , Ejercicio Físico , ObesidadRESUMEN
Non-dieting approaches, including mindful/intuitive eating, to health improvement are of increasing interest, yet little is known about young adults' social media exposure to them. Therefore, this study aimed to describe the imagery related to mindful/intuitive eating which is visible to young adult Instagram users. Images categorized under the hashtags 'mindfuleating' and 'intuitiveeating' were searched in September 2021 using the 'top posts' view. Screen captures of 1200 grid-view images per hashtag were used to construct coding frameworks and to determine saturation. Sample sizes for #mindfuleating and #intuitiveeating were 405 and 495 images, respectively. Individual images were coded collaboratively. Almost half of each sample depicted food or drink, of which 50-60% were healthy foods. Approximately 17% were single-person images, of which the majority were young, female adults with healthy weight. Approximately one-third of text suggested credibility through credentials, profession, or evidence. Messaging was similar for both hashtags, encompassing mindful/intuitive eating (~40%), nutrition/eating behaviours (~15%), physical/mental health (~20%), disordered eating (~12%), and body-/self-acceptance (~12%). Differences were observed between hashtags for weight-related concepts (20%/1%) and anti-diet/weight-neutral approaches (10%/35%). The representation on Instagram of mindful and intuitive eating portrays healthy lifestyles without a focus on weight but lacks demographical and body-type diversity. Instagram holds the potential for health professionals to disseminate culturally/demographically inclusive, evidence-based health/nutrition information to youth.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Atención Plena , Adolescente , Dieta/psicología , Conducta Alimentaria/psicología , Femenino , Alimentos , Humanos , Adulto JovenRESUMEN
Understanding the imagery on social media targeting postpartum women is an important step in determining the utility of Instagram as a potential avenue for targeting public health messages to this group. This study (1) describes the content of images on Instagram tagged with #postpartumbody and; (2) compares images from 'Top' posts ('trending' or 'popular') with 'Recent' posts. 600 images tagged with #postpartumbody (300 'Top' and 300 'Recent') were systematically captured from Instagram and coded using a predefined framework. Images of women were coded for adiposity, muscularity, pose and attire. Chi-square tests were used to compare 'Top' and 'Recent' posts. Most (n = 409) images were of a woman who generally had low/average adiposity (91%) and little-to-none/some visible muscle definition (93%). Most women (52%) were posing in a non-specific manner, 5% were posing to accentuate a postpartum body feature and 40% were wearing fitness attire. Compared with 'Recent', 'Top' posts were less likely to be text-focused (p < 0.001), photos of food (p < 0.001) or linked to a product/program (p < 0.001). Women of lower adiposity are more likely to post images of themselves on Instagram tagged with #postpartumbody than women of higher adiposity, which may reflect increased body pride in this group, but could reduce body satisfaction for some viewers. Conveying health information on Instagram may be necessary to interrupt potentially harmful content.
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OBJECTIVE: This review aimed to examine the validity of self-report screening questionnaires for identifying eating disorder (ED) risk in adults and adolescents with overweight/obesity. METHOD: Five databases were searched from inception to September 2020 for studies assessing validation of self-report ED screening questionnaires against diagnostic interviews in adolescents and adults with overweight/obesity. The review was registered with PROSPERO (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=220013). RESULTS: Twenty-seven papers examining 15 questionnaires were included. Most studies validated questionnaires for adults (22 of 27 studies), and most questionnaires (12 of 15) screened for binge eating or binge-eating disorder (BED). The Eating Disorder Examination Questionnaire (sensitivity = .16-.88, specificity = .62-1.0) and Questionnaire on Eating and Weight Patterns (sensitivity = .07-1.0, specificity = .0-1.0) were most frequently validated (six studies each). Five studies of three questionnaires were in adolescents, with the Adolescent Binge-Eating Disorder Questionnaire having highest sensitivity (1.0) but lower specificity (.27). Questionnaires designed to screen for BED generally had higher diagnostic accuracy than those screening for EDs in general. DISCUSSION: Questionnaires have been well validated to identify BED in adults with overweight/obesity. Validated screening tools to identify other EDs in adults and any ED in adolescents with overweight/obesity are lacking. Thus, clinical assessment should inform the identification of patients with co-morbid EDs and overweight/obesity. PUBLIC SIGNIFICANCE: Individuals with overweight/obesity are at increased risk of EDs. This review highlights literature gaps regarding screening for ED risk in this vulnerable group. This work presents possibilities for improving care of individuals with overweight/obesity by reinventing ED screening tools to be better suited to diverse populations.
OBJETIVO: Esta revisión tuvo como objetivo examinar la validez de los cuestionarios de detección de autorreporte para identificar el riesgo de trastorno de la conducta alimentaria (TCA) en adultos y adolescentes con sobrepeso/obesidad. MÉTODO: Se realizaron búsquedas en cinco bases de datos desde su inicio hasta septiembre de 2020 para obtener estudios que evaluaran la validación de los cuestionarios de autorreporte de detección de TCA frente a entrevistas diagnósticas en adolescentes y adultos con sobrepeso/obesidad. La revisión se registró en PROSPERO (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=220013). RESULTADOS: Se incluyeron veintisiete artículos que examinaron 15 cuestionarios. La mayoría de los estudios validaron cuestionarios para adultos (22 de 27 estudios) y la mayoría de los cuestionarios (12 de 15) detectaban atracones o trastorno por atracón (BED, en sus siglas en inglés). El Cuestionario de Examen de Trastornos alimentarios (Eating Disorder Examination Questionnaire) (sensibilidad = 0.16-0.88, especificidad = 0.62-1.0) y el Cuestionario sobre patrones de alimentación y peso (Questionnaire on Eating and Weight Patterns) (sensibilidad = 0.07-1.0, especificidad = 0.0-1.0) se validaron con mayor frecuencia (seis estudios cada uno). Cinco estudios de tres cuestionarios fueron en adolescentes, y el Cuestionario de Trastorno por Atracón en Adolescentes (Adolescent Binge-eating Disorder Questionnaire) tuvo la mayor sensibilidad (1,0) pero una menor especificidad (0,27). Los cuestionarios diseñados para detectar BED generalmente tuvieron una mayor precisión diagnóstica que los que detectaron TCA en general. DISCUSIÓN: Los cuestionarios han sido bien validados para identificar BED en adultos con sobrepeso/obesidad. Faltan herramientas de detección validadas para identificar otros TCA en adultos y cualquier tipo de trastorno de la conducta alimentaria en adolescentes con sobrepeso / obesidad. Por lo tanto, la evaluación clínica debe informar la identificación de pacientes con comorbilidad de TCA y sobrepeso/obesidad.
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Trastorno por Atracón , Bulimia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Adulto , Trastorno por Atracón/diagnóstico , Bulimia Nerviosa/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Humanos , Obesidad/complicaciones , Obesidad/diagnóstico , Sobrepeso/diagnóstico , Encuestas y CuestionariosRESUMEN
Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.
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Evaluación Preclínica de Medicamentos/métodos , Organoides/patología , Neoplasias de la Próstata/patología , Animales , Modelos Animales de Enfermedad , Genoma , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Mutación , Metástasis de la Neoplasia , Organoides/metabolismo , Estudios Prospectivos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Bancos de Tejidos , Transcriptoma , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. RESULTS: In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. CONCLUSIONS: This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.
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Perfilación de la Expresión Génica , Monocitos/metabolismo , Monocitos/patología , Neoplasias de la Próstata/genética , Transcriptoma , Microambiente Tumoral/genética , Biología Computacional/métodos , Progresión de la Enfermedad , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Inmunofenotipificación , Estimación de Kaplan-Meier , Masculino , Anotación de Secuencia Molecular , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/mortalidadRESUMEN
Adolescent obesity is increasing and a range of treatment approaches are needed. Provision of tailored treatment options accounting for individual and family needs, preferences, and capacity may encourage adolescents with obesity to seek treatment, and/or improve treatment outcomes. Delivered by trained health care professionals, novel dietary interventions may have utility for adolescents not responding to conventional diets, adolescents with comorbidities or severe obesity, and/or when rapid or substantial weight loss is required. This review describes current evidence and clinical considerations relating to the use of very low energy diets, low carbohydrate diets, and intermittent energy restriction in the treatment of adolescent obesity. Emerging evidence on the use of these novel dietary interventions demonstrates short-term weight-related and cardiometabolic improvements. While the evidence is encouraging, and no serious adverse effects have been reported, monitoring of intervention safety is essential. Considerations for health care professionals providing care to adolescents include nutritional adequacy, psychosocial health and social relationships during the intervention. Furthermore, long-term weight-related, cardiometabolic and psychological health outcomes of these dietary interventions are not well understood. Large randomised controlled trials are warranted to inform clinical practice and future guidelines for the use of novel dietary interventions in adolescents with obesity.
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Obesidad Mórbida , Obesidad Infantil , Adolescente , Dieta Baja en Carbohidratos , Ejercicio Físico , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Pérdida de PesoRESUMEN
PURPOSE OF REVIEW: Eating disorders are complex mental health conditions that share risk factors with obesity. This review outlines the context for concerns that paediatric obesity treatment presents a risk for eating disorder development. RECENT FINDINGS: Most children and adolescents undergoing professionally supervised obesity treatment will have improvements or no change to eating disorder risk profiles. However, some may subsequently develop a clinical eating disorder, and this is proposed to relate to weight-focussed dietary interventions that are standard in paediatric obesity treatment. Nevertheless, dietary restraint may not be a strong predictor of eating disorder risk in the context of paediatric obesity treatment. Most international guidelines recommend weight maintenance or weight loss as a treatment goal, and weight loss is related to improvements in cardiometabolic health but not eating disorder risk in the short term. The risk of inducing or exacerbating an eating disorder during paediatric weight management is likely to be low; however, the serious consequences combined with increasing scale of obesity treatment, and lack of empirical evidence, are of concern. There is a need for further research to identify long-term predictors of eating disorder development for children and adolescents who seek treatment for their obesity.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Obesidad Infantil , Adolescente , Niño , Dieta , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/terapia , Factores de Riesgo , Pérdida de PesoRESUMEN
Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.
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Background: Social media is a source of weight loss information for adolescents. However, engagement with image-based social media has been associated with reduced body image. This study describes weight loss imagery visible on an adolescent Instagram account. Methods: The "top" 600 images were captured from "#weightloss" on an adolescent (16 years, gender not specified) Instagram account in August 2020. Images were categorized and coded based on a predetermined ontology as food (nutrient-dense, energy-dense), people (group, individual, before/after), or text-focused by one coder (20% in duplicate, 90% agreement). Images of people were coded for sex and ethnicity and images of individuals coded for adiposity, muscularity, and pose. Results: Of 600 images, 208 (34.7%) were of individuals, predominantly females (83%) with white (37%), non-white (23%), or unclear (41%) ethnicity. Body types were thin (31%), average (43%), or higher weight (6%) with little-to-none (25%), visible (26%), or high (7%) muscularity. Almost half of images accentuated body features with a fitness/muscle accentuating (21%) or sexualized (21%) pose or both (3%). From 165 (27.5%) food images, 71% were nutrient-dense and 29% energy-dense. Of 107 (17.8%) before/after images, 90% depicted weight loss, 4% muscle building with 85% in females. From 93 (15.5%) text-focused images, 46% related to weight loss programs/products and few provided nutrition (n = 12, 13%) or exercise (n = 2, 2%) information. Conclusions: Most "#weightloss" imagery visible to adolescents on Instagram were of people, frequently females, with almost half of body-focused poses or before/after weight loss images. Few provide nutrition and exercise-related content.