The impact of cultural identity, parental communication, and peer influence on substance use among Indigenous youth in Canada.

Heavy drinking and smoking have been found to be among the leading causes of morbidity and mortality within Indigenous youth in North America. The focus of this study was to examine the relative roles of cultural identity, parent-child communication about the harms of substance use (SU), and perception about peers' opinions on heavy drinking and cigarette smoking among Indigenous youth. Strong Indigenous cultural identity, parent-child communication about SU, and affiliation with peers who do not use and/or who disapprove of substance use were all expected to reduce risk for heavy drinking and smoking. Substance use beliefs were hypothesized to mediate these effects. Youth (N = 117; Mage = 14.07; grades 6-11) from two Indigenous communities in Quebec completed self-reports. Consistent with the hypotheses, strong cultural identity predicted increased negative beliefs about substance use, which predicted reduced drinking and smoking. Similarly, affiliating with peers who did not use alcohol predicted decreased positive beliefs about alcohol use, which predicted reduced drinking. Affiliating with peers who did not smoke cigarettes predicted reduced cigarette smoking. Parental influences were not supported in this model. Intervention strategies may benefit from targeting cultural identity, peer groups, and substance use beliefs among Indigenous youth.

Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1.

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.

Circulating tumour cells: The Good, the Bad and the Ugly.

This review is an overview of the current knowledge regarding circulating tumour cells (CTCs), which are potentially the most lethal type of cancer cell, and may be a key component of the metastatic cascade. The clinical utility of CTCs (the "Good"), includes their diagnostic, prognostic, and therapeutic potential. Conversely, their complex biology (the "Bad"), including the existence of CD45+/EpCAM+ CTCs, adds insult to injury regarding their isolation and identification, which in turn hampers their clinical translation. CTCs are capable of forming microemboli composed of both non-discrete phenotypic populations such as mesenchymal CTCs and homotypic and heterotypic clusters which are poised to interact with other cells in the circulation, including immune cells and platelets, which may increase their malignant potential. These microemboli (the "Ugly") represent a prognostically important CTC subset, however, phenotypic EMT/MET gradients bring additional complexities to an already challenging situation.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

The Role of HPV in Determining Treatment, Survival, and Prognosis of Head and Neck Squamous Cell Carcinoma.

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.

Developing and testing the effectiveness of a novel online integrated treatment for problem gambling and tobacco smoking: a protocol for an open-label randomized controlled trial.

BACKGROUND: Gambling and tobacco smoking are highly comorbid among North American adults. However, there is a paucity of treatment options that are integrated (i.e. targeting both gambling and tobacco smoking simultaneously), accessible, and evidence based. METHODS: The aim of this two-arm open-label randomized controlled trial is to examine the effectiveness of an online, self-guided integrated treatment for problem gambling and tobacco smoking. A target sample of 214 participants will be recruited and be randomized into either an 8-week integrated or gambling only control condition. Both conditions will consist of seven online modules following cognitive behavioural therapy and motivational interviewing principles. Our three primary outcomes are (1) the number of days gambled, (2) money spent on gambling activities, and (3) time spent in gambling activities. Secondary outcomes include gambling disorder symptoms, cigarette use, and nicotine dependence symptoms. Assessments will be completed at baseline, at completion (i.e. 8 weeks from baseline), and at follow-up (i.e. 24 weeks from baseline). Generalized linear mixed modelling will be used to evaluate our primary and secondary outcomes. We expect that participants receiving online integrated treatment will show larger reductions in gambling relative to those receiving a control gambling only intervention. We further hypothesize that reductions in smoking will mediate these group differences. DISCUSSION: The rates of problem gambling and tobacco smoking are high in North America; yet, the treatment options for both are limited, with no integrated treatments available. If supported, our pilot study will be a cost-effective and accessible way to improve treatments for co-occurring problem gambling and tobacco use. TRIAL REGISTRATION: ClinicalTrials.gov NCT03614884 . Registered on August 3, 2019.

Follicular dendritic cell sarcoma of the duodenum: an extremely rare entity.

Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare tumour, only reported in case reports and case series. It poses diagnostic and management challenge both to the clinician and pathologist. We present such a rare case of duodenal FDCS in a 56-year-old woman who was recently managed in our institution. Repeated pre surgical biopsies were non-diagnostic and the final diagnosis was made only after surgical excision of the tumour and with the help of histopathological and immunohistochemical studies. The patient had a complete en block resection of the tumour and was discharged home well 5 days postsurgery. To the best of our knowledge, this is the first case of FDCS reported arising from the duodenum.

Implicit cognition and substance use: the role of controlled and automatic processes in children.

OBJECTIVE: Most cognitive models of substance abuse and dependence posit that controlled and automatic processes are central to substance use. Tests of these models rely on methods that are interpreted to measure one or the other of these processes. There has been growing interest in the use of implicit substance use tasks, which are posited to reflect automatic processes. Recent model advancements suggest that behavior is determined by multiple cognitive processes and that dual-process models may provide an overly simplistic account of the cognitive process involved in the assessment of implicit cognition. The goal of the current study was to apply the Quad Model to children's performance on implicit substance use tasks and consider associations with early substance use. METHOD: Children (N = 378; 52% girls) ranging from 10 to 12 years old completed alcohol and cigarette Single Category Implicit Association Tests (SC-IATs) and self-reports of substance use. RESULTS: Four distinct cognitive processes were found to influence SC-IAT performance, one of which reflected automatic activation, the process typically viewed as central to IAT performance. Differences across drinking status revealed weaker automatic activation of negative alcohol associations for those who had (vs. had not) initiated drinking, and a strong likelihood to overcome biased attitudes was supported for all children. The low prevalence of cigarette use in our young sample prohibited examination of the model across smoking status. CONCLUSIONS: Findings suggest that performance on implicit substance use tasks is not process pure. Quantifying and interpreting the multiple influencing processes are crucial for further development and evaluation of cognitive risk models of substance use.

Conjugated linoleic acid suppresses the migratory and inflammatory phenotype of the monocyte/macrophage cell.

OBJECTIVE: We have previously shown that conjugated linoleic acid (CLA) regresses pre-established murine atherosclerosis. Although the exact underlying mechanisms are unclear, accumulation of macrophages and expression of inflammatory markers were reduced in atherosclerotic plaques of CLA-fed mice, implicating the monocyte/macrophage as a target through which CLA may mediate anti-atherosclerotic effects. CLA mediates its effect at least in part via activation of the nuclear receptor, peroxisome proliferator activator receptor-gamma (PPARgamma). In this study we investigate if CLA mediates anti-atherogenic effects via modulation of monocyte/macrophage function and provide evidence for an additional PPARgamma-independent mechanism for CLA. METHODS AND RESULTS: Migration of the human monocyte cell line THP-1, and primary blood monocytes (HPBMCs) was assessed using transwell migration assays. Monocyte chemoattractant protein-1 (MCP-1) mediates chemotaxis via interaction with the chemokine (C-C motif)-2 receptor (CCR-2), which is expressed on the monocyte cell surface, and is negatively regulated by PPARgamma agonists. Incubation of THP-1 monocytes with CLA-isomers and a PPARgamma agonist inhibited MCP-1-induced monocyte migration. Prior to monocyte recruitment, activated platelets accumulate and release the contents of their secretory granules ("platelet-releasate"). Here we demonstrate that platelet-releasate is a monocyte chemoattractant, and CLA, but not the PPARgamma agonist, inhibits platelet-releasate-induced migration of THP-1 and HPBMC monocytes. CLA-treatment also suppressed the inflammatory macrophage phenotype, demonstrated by decreased induction of monocyte migration by CLA-treated macrophage-conditioned-media, as well as by decreased cyclooxygenase (COX)-2 and cytosolic phospholipase-A2 (cPLA2) expression and MCP-1, prostaglandin E2 (PGE2) and matrix metalloprotease (MMP)-9 generation. CONCLUSIONS: CLA-isomers inhibit monocyte migration and reduce the inflammatory output of the macrophage. These mechanisms may contribute to the potent anti-atherosclerotic effects of CLA in vivo.

Children's beliefs about substance use: an examination of age differences in implicit and explicit cognitive precursors of substance use initiation.

Cognitive models conceptualize attitudes and beliefs about substance use (SU) as proximal mediators of a variety of risk and protective factors for SU. Researchers have distinguished implicit and explicit cognition, but limited research has examined this distinction in the early stages of SU. The authors' goal was to examine age differences in implicit and explicit SU cognitions to clarify proximal cognitive processes that may be involved in early SU. Alcohol- and cigarette-naive children (N=76; 69.7% male; M age=11.8 years) completed the laboratory-based experiment. Likelihood ratings of costs and benefits of use assessed explicit cognitions, and a priming task assessed implicit cognitions. Regardless of age, children perceived costs of drinking alcohol and smoking as more likely than benefits. This discrepancy was smaller for older children, although this age difference was weaker for costs and benefits of cigarette use. Strong positive implicit alcohol use cognitions were apparent regardless of age. However, age differences were found for implicit cigarette use cognition. Older children were more positive about cigarette use. Findings suggest the importance of distinguishing explicit and implicit cognition for etiological models of early SU.