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1.
Attach Hum Dev ; 26(2): 133-158, 2024 Apr.
Article En | MEDLINE | ID: mdl-38704613

METHODS: The systematic review and meta-analysis included 17 research articles from 1994 to 2022. Results were summarized by developmental periods. RESULTS: Attachment insecurity was associated with CU traits across development (r = .17). This association was marginally stronger for high-risk samples (e.g., clinical, justice) and for continuous attachment measures versus coding schemes. From early to middle childhood, attachment disorganization was associated with CU traits (r = .17). IMPLICATIONS: Research on attachment and CU traits in childhood is still in its infancy. Changes in attachment measures from childhood to adolescence make developmental comparisons difficult. Results suggest attachment as a potential developmental mechanism for youth with CU traits, however, the area requires more research.


Object Attachment , Humans , Adolescent , Child , Emotions , Child Development , Empathy
2.
Air Med J ; 43(3): 248-252, 2024.
Article En | MEDLINE | ID: mdl-38821707

OBJECTIVE: Accurate triage of children referred for tertiary pediatric critical care services is crucial to ensure optimal disposition and resource conservation. We aimed to explore the characteristics and level of care needs of children referred to tertiary pediatric critical care inpatient and transport services and the characteristics of referring physicians and hospitals to which these children present. METHODS: We conducted a 1-year retrospective cohort study of children (< 16 years) with documented referral to pediatric critical care and specialized transport services at a tertiary pediatric hospital from regional (24/7 pediatrician on-call coverage) and community (no pediatric specialty services) hospitals in Canada's Maritime provinces. RESULTS: We identified 205 documented referrals resulting in 183 (89%) transfers; 97 (53%) were admitted to the pediatric intensive care unit (PICU). Of 150 children transferred from centers with 24/7 pediatric specialist coverage, 45 (30%) were admitted to the tertiary hospital pediatric medical unit with no subsequent admission to the PICU. Of 20 children transferred from community hospitals and admitted to the tertiary hospital general pediatric medical unit, 9 (45%) bypassed proximate regional hospitals with specialist pediatric care capacity. The specialized pediatric critical care transport team performed 151 (83%) of 183 interfacility transfers; 83 (55%) were admitted to the PICU. CONCLUSION: One third of the children accepted for interfacility transfer after pediatric critical care referral were triaged to a similar level of care as could be provided at the sending or nearest regional hospital. Improved utilization of pediatric expertise in regional hospitals may reduce unnecessary pediatric transports and conserve valuable health care resources.


Critical Care , Referral and Consultation , Humans , Retrospective Studies , Child , Referral and Consultation/statistics & numerical data , Child, Preschool , Infant , Female , Male , Critical Care/statistics & numerical data , Adolescent , Canada , Tertiary Care Centers/statistics & numerical data , Intensive Care Units, Pediatric/statistics & numerical data , Patient Transfer/statistics & numerical data , Infant, Newborn , Triage/statistics & numerical data , Transportation of Patients/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Cohort Studies
3.
Sci Rep ; 14(1): 11361, 2024 05 18.
Article En | MEDLINE | ID: mdl-38762572

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human malignancies. Tissue microarrays (TMA) are an established method of high throughput biomarker interrogation in tissues but may not capture histological features of cancer with potential biological relevance. Topographic TMAs (T-TMAs) representing pathophysiological hallmarks of cancer were constructed from representative, retrospective PDAC diagnostic material, including 72 individual core tissue samples. The T-TMA was interrogated with tissue hybridization-based experiments to confirm the accuracy of the topographic sampling, expression of pro-tumourigenic and immune mediators of cancer, totalling more than 750 individual biomarker analyses. A custom designed Next Generation Sequencing (NGS) panel and a spatial distribution-specific transcriptomic evaluation were also employed. The morphological choice of the pathophysiological hallmarks of cancer was confirmed by protein-specific expression. Quantitative analysis identified topography-specific patterns of expression in the IDO/TGF-ß axis; with a heterogeneous relationship of inflammation and desmoplasia across hallmark areas and a general but variable protein and gene expression of c-MET. NGS results highlighted underlying genetic heterogeneity within samples, which may have a confounding influence on the expression of a particular biomarker. T-TMAs, integrated with quantitative biomarker digital scoring, are useful tools to identify hallmark specific expression of biomarkers in pancreatic cancer.


Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Tissue Array Analysis , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , High-Throughput Nucleotide Sequencing , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Retrospective Studies , Transcriptome , Male , Female , Middle Aged , Aged
4.
Nurs Rep ; 14(1): 428-443, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38391078

BACKGROUND: Incidence of disability secondary to Parkinson's disease is increasing faster globally than any other neurological condition. The diverse appearance of symptomatology associated with Parkinson's, and the degenerative nature and subsequent functional decline, often increase dependence on caregivers for assistance with daily living, most commonly within a care home setting. Yet, primary literature and evidence synthesis surrounding these unique and complex care needs, challenges and the lived experiences of this population living in long-term nursing or residential facilities remains sparce. The aim of this review is to synthesize qualitative literature about the lived experience of people with Parkinson's disease living in care home settings. METHODS: A systematic search of the literature was conducted in October 2023 across six different databases (CINAHL, Medline, EMBASE, PsycINFO, Scopus and Cochrane Library). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to guide this review. RESULTS: Five articles met the inclusion criteria. Four themes were identified following evidence synthesis: (1) Unique pharmacological challenges. (2) Transitioning and adapting to care home life and routines. (3) Dignified care within care homes. (4) Multidisciplinary care vacuum in care homes. CONCLUSION: This review revealed the significant and unique challenges for people with Parkinson's disease when transitioning into care homes. These are exacerbated by wider social care challenges such as staffing levels, skill mixes and attitudes as well as a lack of disease-specific knowledge surrounding symptomatology and pharmacology. The lack of multi-disciplinary working and risk-adverse practice inhibited person-centred care and autonomy and reduced the quality of life of people living with Parkinson's disease in care homes. Recommendations for practice highlight training gaps, the need for consistent and improved interdisciplinary working and better person-centred assessment and care delivery.

5.
BMC Public Health ; 24(1): 570, 2024 Feb 22.
Article En | MEDLINE | ID: mdl-38388909

BACKGROUND: Pancreatic cancer, ranking seventh in global cancer-related deaths, poses a significant public health challenge with increasing incidence and mortality. Most cases are diagnosed at an advanced stage, resulting in low survival rates. Early diagnosis significantly impacts prognosis, making symptom awareness crucial. Symptoms are often subtle, leading to delayed help-seeking behaviour. Patients and their carers prioritise increased public awareness, indicating a need for innovative approaches to promote awareness of the disease. METHODS: This study employed a quasi-experimental pre-test/post-test design to assess the relationship between a serious game and pancreatic cancer awareness. Members of the public (N = 727) were recruited internationally, via social media and with signposting by relevant organisations. Participants completed measures of symptom awareness and help-seeking intentions before and after playing the game. The serious game, co-designed with experts by lived experience, patient advocates and healthcare professionals, presented participants with a human anatomy diagram, with each section linked to a question about pancreatic cancer. RESULTS: The serious game demonstrated a statistically significant improvement on pancreatic cancer awareness based on matched paired t-tests. Due to missing data, paired comparisons were only possible for 489 cases. Symptom awareness scores exhibited a statistically significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.43). Help-seeking intentions also markedly improved, showing a significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.10). Independent-samples t-tests were also conducted to determine if there were any group differences on pre- to post-test changes based on age, gender, and previous knowledge and/or experience of pancreatic cancer. Participants overwhelmingly endorsed the game's usability and educational value, suggesting its potential as an effective tool for enhancing public awareness and proactive health-seeking behaviour. DISCUSSION: This study is the first to explore a serious game's utility in pancreatic cancer awareness. Results suggest that such interventions can effectively increase public awareness and influence help-seeking intentions. The co-design process ensured content relevance, and participant satisfaction was high. Findings highlight the game's potential as an accessible and convenient tool for diverse populations.


Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/diagnosis , Health Personnel , Health Behavior
6.
Comput Struct Biotechnol J ; 23: 174-185, 2024 Dec.
Article En | MEDLINE | ID: mdl-38146436

The immune response associated with oncogenesis and potential oncological ther- apeutic interventions has dominated the field of cancer research over the last decade. T-cell lymphocytes in the tumor microenvironment are a crucial aspect of cancer's adaptive immunity, and the quantification of T-cells in specific can- cer types has been suggested as a potential diagnostic aid. However, this is cur- rently not part of routine diagnostics. To address this challenge, we present a new method called True-T, which employs artificial intelligence-based techniques to quantify T-cells in colorectal cancer (CRC) using immunohistochemistry (IHC) images. True-T analyses the chromogenic tissue hybridization signal of three widely recognized T-cell markers (CD3, CD4, and CD8). Our method employs a pipeline consisting of three stages: T-cell segmentation, density estimation from the segmented mask, and prediction of individual five-year survival rates. In the first stage, we utilize the U-Net method, where a pre-trained ResNet-34 is em- ployed as an encoder to extract clinically relevant T-cell features. The segmenta- tion model is trained and evaluated individually, demonstrating its generalization in detecting the CD3, CD4, and CD8 biomarkers in IHC images. In the second stage, the density of T-cells is estimated using the predicted mask, which serves as a crucial indicator for patient survival statistics in the third stage. This ap- proach was developed and tested in 1041 patients from four reference diagnostic institutions, ensuring broad applicability. The clinical effectiveness of True-T is demonstrated in stages II-IV CRC by offering valuable prognostic information that surpasses previous quantitative gold standards, opening possibilities for po- tential clinical applications. Finally, to evaluate the robustness and broader ap- plicability of our approach without additional training, we assessed the universal accuracy of the CD3 component of the True-T algorithm across 13 distinct solid tumors.

7.
Healthcare (Basel) ; 11(24)2023 Dec 14.
Article En | MEDLINE | ID: mdl-38132056

Up to 26% of individuals residing in care homes are impacted by cancer. This underscores the importance of understanding the holistic needs of care home residents living with cancer to enhance the quality of their care. The primary objective of this integrative literature review was to consolidate the available evidence concerning the comprehensive needs of people living with cancer in care home settings, providing valuable insights into addressing their diverse needs. An integrative literature review was conducted using a systematic approach. Extensive searches were conducted in three databases, complemented by a thorough examination of grey literature and reference lists of relevant papers. The review focused on literature published between 2012 and 2022. The screening process involved two independent reviewers, with a third reviewer resolving any discrepancies. The review identified twenty research papers that met the eligibility criteria. These papers shed light on three primary themes related to the holistic needs of care home residents with cancer: physical, psychological, and end-of-life needs. Physical needs encompassed pain management, symptom control, and nutrition, while psychological needs involved social support, emotional well-being, and mental health care. End-of-life needs addressed end-of-life care and advance care planning. These themes highlight the multifaceted nature of cancer care in care homes and underscore the importance of addressing residents' holistic needs in a comprehensive and integrated manner. Improving care home education about cancer and integrating palliative and hospice services within this setting are vital for addressing the diverse needs of residents with cancer.

8.
Front Oncol ; 13: 1219111, 2023.
Article En | MEDLINE | ID: mdl-37781187

Background: The head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries. Methods: We used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data. Findings: Five-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan. Interpretation: Survival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors.

9.
Psychol Rep ; : 332941231201355, 2023 Sep 21.
Article En | MEDLINE | ID: mdl-37732514

Background: Public health measures (e.g., minimizing social interactions, social distancing, and mask wearing) have been implemented in Canada to reduce the transmission of COVID-19. Given that adolescents may be a high-risk demographic for spreading COVID-19, this study investigated adherence to and motivations for complying with public health measures among Canadian youth at two points of the COVID-19 pandemic. Methods: Adolescents (N = 1,484, 53% girls, Mage = 15.73 [SD = 1.41]) completed an online survey in either Summer 2020 (Cohort 1 [C1]; n = 809, 56% girls) or Winter 2020/2021 (Cohort 2 [C2]; n = 675, 50% girls). We investigated differences in adherence across cohorts using independent sample t-tests and predictors of adherence using a path analysis. Results: Youth engaged in similar levels of social interaction in C1 and C2. Relative to adolescents in C1, adolescents in C2 reported more mask wearing, but less social distancing. Social responsibility was associated with adherence to almost all public health measures across both cohorts, with one exception: it did not predict minimizing social interactions in C2. Not wanting to get sick predicted minimizing social interactions and mask wearing. Concern with population health predicted adherence to all public health measures in C1 and all but mask wearing in C2. Maintaining social ties was negatively associated with minimizing social interactions in both cohorts, and with social distancing in C1. Conclusions: Youth engaged in more mask wearing but less social distancing as the pandemic progressed. Social responsibility and not wanting to get sick were consistent predictors of adherence to most public health measures throughout the pandemic. Youth shifted away from adhering to mask wearing measures due to concern with population health over the course of the pandemic. These results can inform targeted campaigns to bolster compliance with public health measures among adolescents.

10.
Br J Cancer ; 129(10): 1599-1607, 2023 11.
Article En | MEDLINE | ID: mdl-37758836

BACKGROUND: Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes. METHODS: A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months. RESULTS: Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model. CONCLUSIONS: This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication.


Carcinoma, Squamous Cell , Mouth Neoplasms , Precancerous Conditions , Humans , Mouth Neoplasms/pathology , Precancerous Conditions/pathology , Carcinoma, Squamous Cell/pathology , Mouth Mucosa/pathology , Prognosis , Cell Transformation, Neoplastic/pathology
11.
PLoS One ; 18(8): e0289355, 2023.
Article En | MEDLINE | ID: mdl-37527282

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS). METHODS: 25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method. RESULTS: Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034). CONCLUSIONS: High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.


Adenocarcinoma , Duodenal Neoplasms , Humans , B7-H1 Antigen/metabolism , Adenocarcinoma/pathology , Survival Analysis , Duodenal Neoplasms/pathology , Biomarkers, Tumor/metabolism , Intestine, Small/metabolism , Prognosis , Lymphocytes, Tumor-Infiltrating , Tumor Microenvironment
12.
BMC Med Educ ; 23(1): 555, 2023 Aug 07.
Article En | MEDLINE | ID: mdl-37550708

INTRODUCTION: Dementia awareness is a key priority of medical and nursing pre-registration education. The 'dementia friends' programme is an internationally recognised and accredited dementia awareness workshop that is led by a trained facilitator. While this programme has been associated with positive outcomes, few studies have examined how medical and nursing students apply their learning in practice after the workshop. The aim of his study was to explore how nursing and medical students apply the dementia friend's programme into practice when caring for people living with dementia. METHODS: Seven focus-group interviews were conducted with 36 nursing students and 14 medical students at one university in Northern Ireland (n = 50), following 'the dementia friends programme. Interview guides were co-designed alongside people living with dementia. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Ethical approval was granted for this study. RESULTS: Four themes emerged: 'reframing dementia', which highlighted how the education had enabled students to actively empower and support people living with dementia in practice; 'dementia friendly design', which focused on how students had modified their clinical environments when providing care for people living with dementia, 'creative communication', which considered how students had used their education to adapt their verbal and non-verbal communication with people living with dementia and 'realities of advanced dementia' which contemplated how students believed their dementia education could be improved within their current curriculum. DISCUSSION: The Dementia Friends programme has actively supported nursing and medical students to improve the lives of people with dementia in their care through environmental adaptions and creative approaches to communication. This study provides an evidence base that supports the provision of 'a dementia friends programme to healthcare professional students. The study also highlights how this education can actively influence how nursing and medical students support people living with dementia in their practice in the months and years after education.


Dementia , Education, Nursing , Students, Nursing , Humans , Curriculum , Dementia/therapy
13.
BMC Geriatr ; 23(1): 361, 2023 06 09.
Article En | MEDLINE | ID: mdl-37296393

BACKGROUND: The aim of this study is to 1) explore the experiences of people living with dementia interacting with DFCs and 2) identify factors that influence empower and support people living with dementia to live successfully in DFCs. The main elements of a DFC are related to people; communities; organisations and partnerships. There are over 200 organisations recognised as dementia-friendly in Northern Ireland (NI). This realist evaluation is to understand how DFCs work for people living with dementia, how positive outcomes are achieved, for whom and in what contexts do DFCs work best. METHODS: A realist evaluation using case study methodology. The process evaluation includes a realist review of the literature, non-participant observation of people living with dementia in their local communities, semi-structured interviews to explore the facilitators and barriers to living well in DFCs and focus groups comprised of people living with dementia, family caregivers and people working in DFCs to support Context- Mechanisms and Outcomes (CMOs). This four-stage realist assessment cycle is used, including iterative rounds of theory development, data gathering, and theory testing. In the end, analysis will reveal context mechanisms that influence how dementia-friendly communities operate and present an initial theory of how people think, which, if adopted, may be able to alter current contexts so that "key" mechanisms are activated to generate desired outcomes. DISCUSSION: To give confidence in moving from hypothetical constructions about how DFCs could function to explanations of possible or observable causal mechanisms, the realist evaluation of a complex intervention incorporates a variety of evidence and perspectives. Despite playing a significant role in a person with dementia's everyday life, it appears that little is known about how communities function to achieve intended results. Even though there has been a lot of work to pinpoint the fundamentals and crucial phases of building DFCs, it is still unclear how people living with dementia benefit the most from these communities. This study intends to advance our understanding of how outcomes are produced for people living with dementia by contributing to the underlying theory of DFCs as well as addressing the primary research objectives.


Dementia , Humans , Dementia/diagnosis , Dementia/epidemiology , Dementia/therapy , Northern Ireland/epidemiology , Caregivers , Focus Groups , Review Literature as Topic
14.
BMC Nurs ; 22(1): 177, 2023 May 22.
Article En | MEDLINE | ID: mdl-37217937

INTRODUCTION: Although it is possible to live well with dementia and many individuals with dementia lead active lives with the help of family, friends, and communities, the general impression of dementia is frequently negative. Dementia is a global health issue. Despite this, little research has been done on the effects of innovative dementia education strategies among undergraduate nursing students. The aim of this study was therefore to assess if this serious digital game, originally intended for the public, could increase knowledge about dementia in first-year nursing students. METHODS: The intervention was a digital serious game called "The Dementia Game", which was available to students throughout February 2021, to a convenience sample of first-year undergraduate nursing students (n = 560) completing a BSc Honours Nursing Degree programme in one university in Northern Ireland. The game was evaluated using a pretest-posttest design. The questionnaire comprised of a 30- item true- false Alzheimer's Disease Knowledge Scale (ADKS), which covers risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving and treatment and management. Data were analysed using paired t-tests and descriptive statistics. RESULTS: Overall dementia knowledge increased significantly after playing the game. Pre-test to post-test increases were observed across a range of seven categories of dementia knowledge (life impact, risk factors, symptoms, treatment, assessment, caregiving and trajectory), with particularly large increases in knowledge of trajectory and risk factors, as shown using paired t-tests. All pre-test to post-test comparisons were significant at the p < 0.001 level. CONCLUSIONS: A short serious digital game on dementia improved first-year student's knowledge about dementia. Undergraduate students also expressed that this approach to dementia education was effective in improving their knowledge about the disease.

15.
Cancers (Basel) ; 15(6)2023 Mar 20.
Article En | MEDLINE | ID: mdl-36980751

New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4+ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3+ (p < 0.001) and ICOS+ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8+ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an 'immune cold' tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC.

16.
J Clin Pathol ; 76(6): 418-423, 2023 Jun.
Article En | MEDLINE | ID: mdl-36717223

Interrogation of immune response in autopsy material from patients with SARS-CoV-2 is potentially significant. We aim to describe a validated protocol for the exploration of the molecular physiopathology of SARS-CoV-2 pulmonary disease using multiplex immunofluorescence (mIF).The application of validated assays for the detection of SARS-CoV-2 in tissues, originally developed in our laboratory in the context of oncology, was used to map the topography and complexity of the adaptive immune response at protein and mRNA levels.SARS-CoV-2 is detectable in situ by protein or mRNA, with a sensitivity that could be in part related to disease stage. In formalin-fixed, paraffin-embedded pneumonia material, multiplex immunofluorescent panels are robust, reliable and quantifiable and can detect topographic variations in inflammation related to pathological processes.Clinical autopsies have relevance in understanding diseases of unknown/complex pathophysiology. In particular, autopsy materials are suitable for the detection of SARS-CoV-2 and for the topographic description of the complex tissue-based immune response using mIF.


COVID-19 , Humans , COVID-19/diagnosis , COVID-19/pathology , SARS-CoV-2 , Autopsy , Lung/pathology , COVID-19 Testing
17.
Child Psychiatry Hum Dev ; 54(2): 582-596, 2023 04.
Article En | MEDLINE | ID: mdl-34687405

There is growing evidence of diverse etiological pathways to the development of callous-unemotional (CU) traits, known as primary and secondary CU variants. The purpose of the present study was to extend previous cross-sectional research and examine theoretical predictors of CU variants prospectively from childhood to adolescence. Participants included high-risk control and normative samples from the Fast Track project (N = 754, male = 58%, Black = 46%). Using structural equation modelling, primary CU traits, identified in early adolescence, were associated with higher levels of childhood emotion regulation and lower levels of prosocial behavior. Secondary CU traits were associated with lower levels of childhood emotion regulation and low parental warmth, but not prosocial behaviour. Neither CU variant was related to harsh parenting. Parental warmth moderated emotion regulation and prosocial behavior on secondary CU traits. Results were not moderated by sex. A greater understanding of theoretical developmental precursors of CU variants may better guide intervention efforts.


Conduct Disorder , Humans , Male , Adolescent , Conduct Disorder/psychology , Emotions/physiology , Cross-Sectional Studies , Parenting/psychology
18.
Dev Psychopathol ; 35(1): 274-289, 2023 02.
Article En | MEDLINE | ID: mdl-34009113

While phenotypically indistinguishable with respect to callousness, individuals with primary and secondary callous-unemotional (CU) traits may show different developmental outcomes. This research predominantly comprised cross-sectional studies of male participants with a focus on maladaptive correlates. Thus, the present study examined whether youth with primary and secondary CU traits identified in Grade 7 reported distinct maladaptive outcomes (internalizing, externalizing, and substance use problems; criminal offenses; and sexual and partner experiences) and adaptive outcomes (health and wellbeing, education, and employment) in adulthood at age 25. We also examined sex differences. Participants included the high-risk control and normative samples from the Fast Track project (N = 754, male = 58%, Black = 46%). Youth with secondary CU traits reported higher levels of adult internalizing and externalizing psychopathology, a greater number of sexual partners and risky sexual behavior, and a greater number of violent offenses, compared with individuals with primary CU traits and those with low CU and anxiety symptoms. Conversely, youth with primary CU traits and low symptoms had higher wellbeing and happiness scores than those with secondary CU traits. Finally, there was differentiation on outcomes between female primary and secondary CU variants and male primary and secondary CU variants.


Conduct Disorder , Adult , Humans , Male , Adolescent , Female , Conduct Disorder/psychology , Cross-Sectional Studies , Anxiety , Aggression/psychology , Emotions
19.
J Child Health Care ; 27(4): 693-706, 2023 12.
Article En | MEDLINE | ID: mdl-35499965

Repression has been linked to greater illness, somatic symptoms, and poorer physical health, both in adult and pediatric populations. The current study examined psychological and pain profiles of children with chronic pain who may under-report levels of psychological distress at a first interdisciplinary chronic pain assessment. Children and their caregiver completed measures of psychopathology and pain intensity, while clinicians rated their levels of disability. Based on self-report measures, children were classified as "repressors" (low anxiety/high social desirability) or as "true low anxious" (low anxiety/low social desirability). Groups were then compared on psychological and pain characteristics. Compared to children with true low anxiety, repressors reported lower levels of depressive and somatic symptoms but provided higher ratings on pain intensity, pain-unpleasantness, and self-oriented perfectionism. Caregivers of repressors rated their children as having higher levels of adaptability compared to caregivers of children in the true low anxious group. Groups did not differ on clinician-rated level of disability. Children classified as repressors exhibited different profiles than children classified as having true low anxiety on both psychological outcomes and pain characteristics. Repression may be an important factor to consider for those assessing and treating children with chronic pain.


Chronic Pain , Medically Unexplained Symptoms , Adult , Child , Humans , Self Report , Repression, Psychology , Adaptation, Psychological , Anxiety/psychology
20.
J Res Adolesc ; 33(1): 344-360, 2023 03.
Article En | MEDLINE | ID: mdl-35699159

The Affect Regulation Checklist (ARC) was designed to capture affect dysregulation, suppression, and reflection. Importantly, affect dysregulation has been established as a transdiagnostic mechanism underpinning many forms of psychopathology. We tested the ARC psychometric properties across clinical and community samples and through both parent-report and youth self-report information. Clinical sample: Participants included parents (n = 814; Mage = 43.86) and their child (n = 608; Mage = 13.98). Community sample: Participants included independent samples of parents (n = 578; Mage = 45.12) and youth (n = 809; Mage = 15.67). Exploratory structural equation modeling supported a three-factor structure across samples and informants. Dysregulation was positively associated with all forms of psychopathology. In general, suppression was positively associated with many forms of psychopathology, and reflection was negatively associated with externalizing problems and positively associated with internalizing problems.


Checklist , Psychopathology , Child , Humans , Adolescent , Adult , Middle Aged , Self Report , Psychometrics , Parents
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