Come Out To Play : the sports experiences of lesbian, gay, bisexual and transgender (LGBT) people in Victoria

Despite extensive changes in social attitudes to lesbian, gay, bisexual and transgender (LGBT) Australians over the last decade, research shows they still experience significant levels of discrimination and abuse. There is very little direct empirical research on the sport experience of LGBT Australians. Whilst other disadvantaged groups in the Australian sport context have been recognised in the research and policy agenda, the existence, experiences and needs of LGBT peoples within sport have largely been ignored. Both implicit discrimination that results from ‘heteronormative’ attitudes and explicit discrimination that causes LGBT sports-people to remain in the closet, become isolated and essentially silenced, have shaped a circle of silence on this topic. Sport plays a significant role in Australian society; however, it is a place where LGBT Australians are largely silent and invisible. Come Out To Play is the first comprehensive survey of the LGBT sport experience in Australia and provides rich insight through closed and open ended responses into the sporting lives, passions, rewards and challenges of these sports participants, supporters, volunteers and workers

Exploring Lesbian, Gay, Bisexual and Transgender (LGBT) Inclusion in Australian Cricket

Cricket Australia and Cricket Victoria commissioned the Institute of Sport, Exercise and Active Living (ISEAL) at Victoria University to examine the current climate, attitudes and initiatives towards LGBT inclusion within Australian cricket. The aims of this research were to explore: The current attitudes towards the inclusion of LGBT players, coaches, volunteers and employees in Australian cricket; The experiences of LGBT people in Australian cricket, including both professional and community players, coaches, volunteers and employees; The beliefs and attitudes of cricket leaders (i.e. coaches and officials) from clubs, leagues and associations towards LGBT inclusion; How LGBT inclusion can be improved and promoted effectively within Australian cricket

Beware of Histiocytes: Whipple Adenopathy and its Mimics

Histiocytic proliferations are heterogeneous lesions with distinct pathogenic and clinical-pathological features. While many of these conditions are nonspecific immune responses to variable causes, a minority of them is associated with specific etiological factors and unique clinical-pathological pictures. By presenting a rare case of Whipple adenopathy, we address the peculiar histological features of this condition and the differential diagnosis of nodal histiocytosis in general

Effect of Exercise Training on Left Ventricular Remodeling in Diabetic Patients with Diastolic Dysfunction: Rationale and Design

This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction

Muscle atrophy in patients with Type 2 Diabetes Mellitus : roles of inflammatory pathways, physical activity and exercise

Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin-proteasome, lysosomal-proteasome and caspase 3-mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor. B (NF-kappa B) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-kappa B, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions

Feasibility of multiple immunoexpression assay for immune tumor micrornvironment (I-TME) on matched metastatic and primary renal cell carcinoma (RCC) for patient prognostication and predictiveness to immunotherapy (preliminary analyses of the Meet URO 18 study).

Background: The Meet-URO 18 study is ongoing to assess the prognostic role of I-TME in advanced RCC patients treated with 65second line nivolumab divided into two cohorts according to clinical benefit [progression-free survival 65 12 and 64 3 months]. We primarily assessed the feasibility of multiple antibody testing related to I-TME on matched metastases and primary tumor. Methods: Immunohistochemical analyses were used for the TME assessment of T-lineage (CD3, CD4, CD8), FOXP-3, granulocytes (CD15), macrophage-lineage (CD68), natural killer (NK)-cells (CD56), tumor cells (TCs) (CD56), B-lineage (CD20) and phosphorylated mTOR (phmTOR). TCs were quantitatively assessed for CD15, CD56 and phmTOR positivity. For T-, B- and CD68 cells within TC nests, the number of immunoreactive cells were counted with a microscopic field of x200 (0.933 mm2). Results: Overall, 42 tumor tissue samples (primary tumors, metastases) were available and for 17 patients both metastatic and primary tumor tissues were assessable for matched analyses. Among these patients, 12 had clear cell, 1 papillary and 4 mucinous tubular and spindle cell histotype according to WHO 2016 classification. Intratumoral T/CD8 cells ranged from 32 to >400 spots (mean 240; >400 in 7 samples) and intratumoral T/CD4 cells from 4 to >400 spots (mean 168; >400 in 5 samples). Nine samples showed absence of phmTOR expression, while 8 ranged from 10% to 90% of positive TCs. We did not observe countable NK-cells, whereas CD56 was visible in 5 samples (mean 55% of positive TCs). Intratumoral CD68 cells ranged from 34 to >400 spots (mean 175, >400 in 3 patients). Agreement of CD15 method of reporting granulocytic presence was high, thus only CD15 neoplastic expression was reported and ranged from 12% to 55% (mean 30%) in 15 patients. TME multiple analysis resulted equally clustered in 8 patients (<20% variability of single immuno-test) whereas the remaining 9 patients showed significant differences as percentage of immuno-tissue expression in at least one of the 5 immuno-indicators (T/CD8-CD4, C15, CD68, CD56, phmTOR). The remaining 8 samples of patients without matched analyses were used to test the feasibility of multiple analyses; among all antibodies exclusion of the CD20 and FOXP-3 final evaluation was needed, due to technical standardization. According to the 5 immuno-indicators, double-triple positive or penta-positive TME indicators may be identified and graded. Conclusions: Providing multiple immunoexpression platforms on a single specimen may be used as routine workflow. Profiling I-TME, especially CD56, CD15 on TCs and CD68 cells and phmTOR, deserves investigation with extensive control groups. A validation cohort will be tested at tissue level and in correlation with peripheral blood markers

Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study

76siWe aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.noneBrunelli, Matteo; Martignoni, Guido; Malpeli, Giorgio; Volpe, Alessandro; Cima, Luca; Raspollini, Maria Rosaria; Barbareschi, Mattia; Tafuri, Alessandro; Masi, Giulia; Barzon, Luisa; Ammendola, Serena; Villanova, Manuela; Cerruto, Maria Angela; Milella, Michele; Buti, Sebastiano; Bersanelli, Melissa; Fornarini, Giuseppe; Rebuzzi, Sara Elena; Vellone, Valerio Gaetano; Gaggero, Gabriele; Procopio, Giuseppe; Verzoni, Elena; Bracarda, Sergio; Fanelli, Martina; Sabbatini, Roberto; Passalacqua, Rodolfo; Perrucci, Bruno; Giganti, Maria Olga; Donini, Maddalena; Panni, Stefano; Tucci, Marcello; Prati, Veronica; Ortega, Cinzia; Caliò, Anna; Eccher, Albino; Alongi, Filippo; Pappagallo, Giovanni; Iacovelli, Roberto; Mosca, Alessandra; Umari, Paolo; Montagnani, Ilaria; Gobbo, Stefano; Atzori, Francesco; Munari, Enrico; Maruzzo, Marco; Basso, Umberto; Pierconti, Francesco; Patriarca, Carlo; Colombo, Piergiuseppe; Lapini, Alberto; Conti, Giario; Salvioni, Roberto; Bollito, Enrico; Cossarizza, Andrea; Massari, Francesco; Rizzo, Mimma; Franco, Renato; Zito-Marino, Federica; Aberasturi Plata, Yoseba; Galuppini, Francesca; Sbaraglia, Marta; Fassan, Matteo; Dei Tos, Angelo Paolo; Colecchia, Maurizio; Moch, Holger; Scaltriti, Maurizio; Porta, Camillo; Delahunt, Brett; Giannarini, Gianluca; Bortolus, Roberto; Rescigno, Pasquale; Banna, Giuseppe Luigi; Signori, Alessio; Obispo, Miguel Angel Llaja; Perris, Roberto; Antonelli, AlessandroBrunelli, Matteo; Martignoni, Guido; Malpeli, Giorgio; Volpe, Alessandro; Cima, Luca; Raspollini, Maria Rosaria; Barbareschi, Mattia; Tafuri, Alessandro; Masi, Giulia; Barzon, Luisa; Ammendola, Serena; Villanova, Manuela; Cerruto, Maria Angela; Milella, Michele; Buti, Sebastiano; Bersanelli, Melissa; Fornarini, Giuseppe; Rebuzzi, Sara Elena; Vellone, Valerio Gaetano; Gaggero, Gabriele; Procopio, Giuseppe; Verzoni, Elena; Bracarda, Sergio; Fanelli, Martina; Sabbatini, Roberto; Passalacqua, Rodolfo; Perrucci, Bruno; Giganti, Maria Olga; Donini, Maddalena; Panni, Stefano; Tucci, Marcello; Prati, Veronica; Ortega, Cinzia; Caliò, Anna; Eccher, Albino; Alongi, Filippo; Pappagallo, Giovanni; Iacovelli, Roberto; Mosca, Alessandra; Umari, Paolo; Montagnani, Ilaria; Gobbo, Stefano; Atzori, Francesco; Munari, Enrico; Maruzzo, Marco; Basso, Umberto; Pierconti, Francesco; Patriarca, Carlo; Colombo, Piergiuseppe; Lapini, Alberto; Conti, Giario; Salvioni, Roberto; Bollito, Enrico; Cossarizza, Andrea; Massari, Francesco; Rizzo, Mimma; Franco, Renato; Zito-Marino, Federica; Aberasturi Plata, Yoseba; Galuppini, Francesca; Sbaraglia, Marta; Fassan, Matteo; Dei Tos, Angelo Paolo; Colecchia, Maurizio; Moch, Holger; Scaltriti, Maurizio; Porta, Camillo; Delahunt, Brett; Giannarini, Gianluca; Bortolus, Roberto; Rescigno, Pasquale; Banna, Giuseppe Luigi; Signori, Alessio; Obispo, Miguel Angel Llaja; Perris, Roberto; Antonelli, Alessandr

Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity