Investigating staff’s attitudes and willingness to support men and women with mild intellectual disabilities on matters relating to their sexuality

Background: This study explored residential support staff’s attitudes towards sexuality in men and women with an intellectual disability (ID), and whether their attitudes were linked to a willingness to support service users with sexual matters. Method: The Attitudes to Sexuality Questionnaire - Individuals with an Intellectual Disability was used to gather data on 34 support staff’s attitudes. This was supplemented with additional questions on risk issues developed by the author. A semi-structured interview examined staff’s experiences of supporting sexual matters. Result: Liberal attitudes were held, no statistically significant differences were found on attitudes to men and women. Nonetheless, trends were found with more liberal views expressed about men than women on sexual rights and non-reproductive sexual behaviour. Most staff were willing to support the sexuality of service users. A positive association was found between staff’s attitudes and their willingness to support sexuality. Willingness was not associated with feelings of confidence or comfort in dealing with sexual matters. Conclusions: Sexuality is an integral aspect of quality of life. Understanding staff’s values and attitudes towards the sexuality of people with ID is important, as this population of people rely on staff for support on this sensitive topic. Assisting the sexuality of people with ID is a complex and emotive subject worthy of further investigation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

ERCP in Total Situs Viscerum Inversus

A 69-year-old cholecystectomized female with known total situs viscerum inversus presented recurrent colicky pain in the left upper abdominal quadrant and jaundice. Laboratory parameters showed increased neutrophils and coniugated bilirubin of 5.53 mg/dl. US and MRCP confirmed total situs viscerum inversus and a dilatation of the intra- and extrahepatic ducts with a peripapillary 13 mm stone. ERCP, sphincterotomy and successful common bile duct stone extraction were performed in the conventional way. ERCP was carried out successfully despite situs inversus maintaining the patient in the prone position with the endoscopist on the right side of the table. Some authors have reported similar cases in whom ERCP was performed in other positions, while this report shows that an experienced endoscopist can achieve the same results in the conventional way as it is possible when anatomical changes, Billroth II or Roux-en-Y, or different positions of the patient, supine or on the left side, are present

Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus

Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph’s free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett’s esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05–0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well-defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity

Clinico-pathological associations and concomitant mutations of the RAS/RAF pathway in metastatic colorectal cancer

Background: Over the past few years, next-generation sequencing (NGS) has become reliable and cost-effective, and its use in clinical practice has become a reality. A relevant role for NGS is the prediction of response to anti-EGFR agents in metastatic colorectal cancer (mCRC), where multiple exons from KRAS, NRAS, and BRAF must be sequenced simultaneously. Methods: We optimized a 14-amplicon NGS panel to assess, in a consecutive cohort of 219 patients affected by mCRC, the presence and clinico-pathological associations of mutations in the KRAS, NRAS, BRAF, and PIK3CA genes from formalin-fixed, paraffin-embedded specimens collected for diagnostics and research at the time of diagnosis. Results: We observed a statistically significant association of RAS mutations with sex, young age, and tumor site. We demonstrated that concomitant mutations in the RAS/RAF pathway are not infrequent in mCRC, and as anticipated by whole-genome studies, RAS and PIK3CA tend to be concurrently mutated. We corroborated the association of BRAF mutations in right mCRC tumors with microsatellite instability. We established tumor side as prognostic parameter independently of mutational status. Conclusions: To our knowledge, this is the first monocentric, consecutively accrued clinical mCRC cancer cohort tested by NGS in a real-world context for KRAS, NRAS, BRAF, and PIK3CA. Our study has highlighted in clinical practice findings such as the concomitance of mutations in the RAS/RAF pathway, the presence of multiple mutations in single gene, the co-occurrence of RAS and PIK3CA mutations, the prognostic value of tumor side and possible associations of sex with specific mutations

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn\u2019s disease-associated small bowel carcinoma

Most Crohn\u2019s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies

Extrafollicular plasmablast present in the acute phase of infections express high levels of PD-L1 and are able to limit T cell respose

During infections with protozoan parasites or some viruses, T cell immunosuppression is generated simultaneously with a high B cell activation. It has been described that, as well as producing antibodies, plasmablasts, the differentiation product of activated B cells, can condition the development of protective immunity in infections. Here, we show that, in T. cruzi infection, all the plasmablasts detected during the acute phase of the infection had higher surface expression of PD-L1 than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in a BCR-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection expressed PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. In vitro experiments showed that PD-L1hi plasmablasts suppressed the T cell response, partially via PD-L1. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, whose peaks of response precede the peak of germinal center response, may have a modulatory function in infections, thus influencing T cell response.Fil: Gorosito Serran, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fiocca Vernengo, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Almada, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Beccaria, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gazzoni, Yamila Natali. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Canete, Pablo F.. Australian National University; ArubaFil: Roco, Jonathan A.. Australian National University; ArubaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Wehrens, Ellen. University of California; Estados UnidosFil: Cai, Yeping. Australian National University; ArubaFil: Zuniga, Elina Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cockburn, Ian A.. Australian National University; ArubaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Vinuesa, Carola G.. Australian National University; ArubaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Small bowel carcinomas in celiac or Crohn's disease: Distinctive histophenotypic, molecular and histogenetic patterns

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32 000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobactor pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagA− n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism

Outer Membrane Vesicles as a Candidate Vaccine against Edwardsiellosis

Infection with Edwardsiella tarda, a Gram-negative bacterium, causes high morbidity and mortality in both marine and freshwater fish. Outer membrane vesicles (OMVs) released from Gram-negative bacteria are known to play important roles in bacterial pathogenesis and host immune responses, but no such roles for E. tarda OMVs have yet been described. In the present study, we investigated the proteomic composition of OMVs and the immunostimulatory effect of OMVs in a natural host, as well as the efficacy of OMVs when used as a vaccine against E. tarda infection. A total of 74 proteins, from diverse subcellular fractions, were identified in OMVs. These included a variety of important virulence factors, such as hemolysin, OmpA, porin, GAPDH, EseB, EseC, EseD, EvpC, EvpP, lipoprotein, flagellin, and fimbrial protein. When OMVs were administrated to olive flounder, significant induction of mRNAs encoding IL-1β, IL-6, TNFα, and IFNγ was observed, compared with the levels seen in fish injected with formalin-killed E. tarda. In a vaccine trial, olive flounder given OMVs were more effectively protected (p<0.0001) than were control fish. Investigation of OMVs may be useful not only for understanding the pathogenesis of E. tarda but also in development of an effective vaccine against edwardsiellosis