MS4A1 Dysregulation in Asbestos-Related Lung Squamous Cell Carcinoma Is Due to CD20 Stromal Lymphocyte Expression

Asbestos-related lung cancer accounts for 4–12% of lung cancers worldwide. We have previously identified ADAM28 as a putative oncogene involved in asbestos-related lung adenocarcinoma (ARLC-AC). We hypothesised that similarly gene expression profiling of asbestos-related lung squamous cell carcinomas (ARLC-SCC) may identify candidate oncogenes for ARLC-SCC. We undertook a microarray gene expression study in 56 subjects; 26 ARLC-SCC (defined as lung asbestos body (AB) counts >20AB/gram wet weight (gww) and 30 non-asbestos related lung squamous cell carcinoma (NARLC-SCC; no detectable lung asbestos bodies; 0AB/gww). Microarray and bioinformatics analysis identified six candidate genes differentially expressed between ARLC-SCC and NARLC-SCC based on statistical significance (p<0.001) and fold change (FC) of >2-fold. Two genes MS4A1 and CARD18, were technically replicated by qRT-PCR and showed consistent directional changes. As we also found MS4A1 to be overexpressed in ARLC-ACs, we selected this gene for biological validation in independent test sets (one internal, and one external dataset (2 primary tumor sets)). MS4A1 RNA expression dysregulation was validated in the external dataset but not in our internal dataset, likely due to the small sample size in the test set as immunohistochemical (IHC) staining for MS4A1 (CD20) showed that protein expression localized predominantly to stromal lymphocytes rather than tumor cells in ARLC-SCC. We conclude that differential expression of MS4A1 in this comparative gene expression study of ARLC-SCC versus NARLC-SCC is a stromal signal of uncertain significance, and an example of the rationale for tumor cell enrichment in preparation for gene expression studies where the aim is to identify markers of particular tumor phenotypes. Finally, our study failed to identify any strong gene candidates whose expression serves as a marker of asbestos etiology. Future research is required to determine the role of stromal lymphocyte MS4A1 dysregulation in pulmonary SCCs caused by asbestos

Ontogeny and thermogenic role for sternal fat in female sheep

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat. In adult sheep, implanted temperature probes were used to characterise the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant within sternal than retroperitoneal fat and was only retained in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the post-prandial rise in temperature was greater and more prolonged in sternal than retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood when it shows a greater thermogenic response to feeding than muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals

How do women at increased, but unexplained, familial risk of breast cancer perceive and manage their risk? A qualitative interview study

<p>Abstract</p> <p>Background</p> <p>The perception of breast cancer risk held by women who have not had breast cancer, and who are at increased, but unexplained, familial risk of breast cancer is poorly described. This study aims to describe risk perception and how it is related to screening behaviour for these women.</p> <p>Methods</p> <p>Participants were recruited from a population-based sample (the Australian Breast Cancer Family Study - ABCFS). The ABCFS includes women diagnosed with breast cancer and their relatives. For this study, women without breast cancer with at least one first- or second-degree relative diagnosed with breast cancer before age 50 were eligible unless a <it>BRCA1 </it>or <it>BRCA2 </it>mutation had been identified in their family. Data collection consisted of an audio recorded, semi-structured interview on the topic of breast cancer risk and screening decision-making. Data was analysed thematically.</p> <p>Results</p> <p>A total of 24 interviews were conducted, and saturation of the main themes was achieved. Women were classified into one of five groups: don't worry about cancer risk, but do screening; concerned about cancer risk, so do something; concerned about cancer risk, so why don't I do anything?; cancer inevitable; cancer unlikely.</p> <p>Conclusions</p> <p>The language and framework women use to describe their risk of breast cancer must be the starting point in attempts to enhance women's understanding of risk and their prevention behaviour.</p

Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis

Animación sociocultural mediante el deporte en la Unidad de Salud Mental del establecimiento carcelario La Modelo de Bogotá

Servicio Social ComunitarioInvestigación realizada tuvo como objetivo la realización de una animación sociocultural en el establecimiento carcelario la Modelo ubicado en la ciudad de Bogotá- Colombia, específicamente en la unidad de salud mental, a través de metodologías participativas y alternativas de intervención como el Aprendizaje Servicio Solidario (ASS); de esta manera fue posible identificar en un primer momento algunas de las necesidades sentidas, percibidas e inferidas, tanto de la institución, como de las personas privadas de la libertad (PPL), a través del arte y el deporte. En un segundo momento se desarrolló una intervención a través de las metodologías ya mencionadas, utilizando el deporte como herramienta principal, buscando potencializar en los internos diferentes alternativas para la solución de problemas y la transformación de las necesidades evaluadas. En cuanto a este último objetivo de la intervención no todas las necesidades pudieron tener alguna modificación, puesto que algunas de ellas se encuentran vinculadas con lineamientos institucionales fuera del alcance de esta investigación. Para este estudio no se contó con una muestra estable, ya que para cada sesión los PPL podían elegir su participación de manera voluntaria y en casos particulares se evidenciaban traslados de patio o de establecimiento carcelario y, además, se presentaron situaciones de inseguridad en el patio, que no permitieron el desarrollo adecuado de las últimas sesiones de intervención.140 p.1. Marco Teórico 2. Marco Metodológico 3. Diseño Metodológico de la Intervención 4. Categorías de Análisis 5. Análisis de Contenido 6. Matriz Operativa del Proyecto 7. Análisis de Procesos 8. ReferenciasPregradoPsicólog

Psychiatric and medical comorbidities of eating disorders : findings from a rapid review of the literature

Background: Eating disorders (EDs) are potentially severe, complex, and life-threatening illnesses. The mortality rate of EDs is signifcantly elevated compared to other psychiatric conditions, primarily due to medical complications and suicide. The current rapid review aimed to summarise the literature and identify gaps in knowledge relating to any psychiatric and medical comorbidities of eating disorders. Methods: This paper forms part of a rapid review) series scoping the evidence base for the feld of EDs, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021–2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/Medline were searched for English-language studies focused on the psychiatric and medical comorbidities of EDs, published between 2009 and 2021. High-level evidence such as meta-analyses, large population studies and Randomised Control Trials were prioritised. Results: A total of 202 studies were included in this review, with 58% pertaining to psychiatric comorbidities and 42% to medical comorbidities. For EDs in general, the most prevalent psychiatric comorbidities were anxiety (up to 62%), mood (up to 54%) and substance use and post-traumatic stress disorders (similar comorbidity rates up to 27%). The review also noted associations between specifc EDs and non-suicidal self-injury, personality disorders, and neurodevelopmental disorders. EDs were complicated by medical comorbidities across the neuroendocrine, skeletal, nutritional, gastrointestinal, dental, and reproductive systems. Medical comorbidities can precede, occur alongside or emerge as a complication of the ED. Conclusions: This review provides a thorough overview of the comorbid psychiatric and medical conditions cooccurring with EDs. High psychiatric and medical comorbidity rates were observed in people with EDs, with comorbidities contributing to increased ED symptom severity, maintenance of some ED behaviours, and poorer functioning as well as treatment outcomes. Early identifcation and management of psychiatric and medical comorbidities in people with an ED may improve response to treatment and overall outcomes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. Results Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. Conclusions For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making

Array-Comparative Genomic Hybridization Reveals Loss of SOCS6 Is Associated with Poor Prognosis in Primary Lung Squamous Cell Carcinoma

BACKGROUND: Primary tumor recurrence commonly occurs after surgical resection of lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC recurrence. METHODS: We used array comparative genomic hybridization (aCGH) to identify genes affected by copy number alterations that may be involved in SCC recurrence. Training and test sets of resected primary lung SCC were assembled. aCGH was used to determine genomic copy number in a training set of 62 primary lung SCCs (28 with recurrence and 34 with no evidence of recurrence) and the altered copy number of candidate genes was confirmed by quantitative PCR (qPCR). An independent test set of 72 primary lung SCCs (20 with recurrence and 52 with no evidence of recurrence) was used for biological validation. mRNA expression of candidate genes was studied using qRT-PCR. Candidate gene promoter methylation was evaluated using methylation microarrays and Sequenom EpiTYPER analysis. RESULTS: 18q22.3 loss was identified by aCGH as being significantly associated with recurrence (p = 0.038). Seven genes within 18q22.3 had aCGH copy number loss associated with recurrence but only SOCS6 copy number was both technically replicated by qPCR and biologically validated in the test set. SOCS6 copy number loss correlated with reduced mRNA expression in the study samples and in the samples with copy number loss, there was a trend for increased methylation, albeit non-significant. Overall survival was significantly poorer in patients with SOCS6 loss compared to patients without SOCS6 loss in both the training (30 vs. 43 months, p = 0.023) and test set (27 vs. 43 months, p = 0.010). CONCLUSION: Reduced copy number and mRNA expression of SOCS6 are associated with disease recurrence in primary lung SCC and may be useful prognostic biomarkers

MicroRNA-218 Is Deleted and Downregulated in Lung Squamous Cell Carcinoma

MicroRNAs (miRNAs) are a family of small, non-coding RNA species functioning as negative regulators of multiple target genes including tumour suppressor genes and oncogenes. Many miRNA gene loci are located within cancer-associated genomic regions. To identify potential new amplified oncogenic and/or deleted tumour suppressing miRNAs in lung cancer, we inferred miRNA gene dosage from high dimensional arrayCGH data. From miRBase v9.0 (http://microrna.sanger.ac.uk), 474 human miRNA genes were physically mapped to regions of chromosomal loss or gain identified from a high-resolution genome-wide arrayCGH study of 132 primary non-small cell lung cancers (NSCLCs) (a training set of 60 squamous cell carcinomas and 72 adenocarcinomas). MiRNAs were selected as candidates if their immediately flanking probes or host gene were deleted or amplified in at least 25% of primary tumours using both Analysis of Copy Errors algorithm and fold change (≥±1.2) analyses. Using these criteria, 97 miRNAs mapped to regions of aberrant copy number. Analysis of three independent published lung cancer arrayCGH datasets confirmed that 22 of these miRNA loci showed directionally concordant copy number variation. MiR-218, encoded on 4p15.31 and 5q35.1 within two host genes (SLIT2 and SLIT3), in a region of copy number loss, was selected as a priority candidate for follow-up as it is reported as underexpressed in lung cancer. We confirmed decreased expression of mature miR-218 and its host genes by qRT-PCR in 39 NSCLCs relative to normal lung tissue. This downregulation of miR-218 was found to be associated with a history of cigarette smoking, but not human papilloma virus. Thus, we show for the first time that putative lung cancer-associated miRNAs can be identified from genome-wide arrayCGH datasets using a bioinformatics mapping approach, and report that miR-218 is a strong candidate tumour suppressing miRNA potentially involved in lung cancer