Use of colonoscopy as a primary screening test for colorectal cancer in average risk people

The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. METHODS: The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. RESULTS: Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. CONCLUSIONS: Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscop

Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy

For colorectal cancer screening, the predictive value of distal findings in the ascertainment of proximal lesions is not fully established. The aims of this study were to assess distal findings as predictors of advanced proximal neoplasia and to compare the predictive value of endoscopy alone vs. combined endoscopic and histopathologic data. METHODS: Primary colonoscopy screening was performed in 2210 consecutive, average-risk adults. Age, gender, endoscopic (size, number of polyps), and histopathologic distal findings were used as potential predictors of advanced proximal neoplasms (i.e., any adenoma > or =1 cm in size, and/or with villous histology, and/or with severe dysplasia or invasive cancer). Polyps were defined as distal if located in the descending colon, the sigmoid colon, or the rectum. Those in other locations were designated proximal. RESULTS: Neoplastic lesions, including 11 invasive cancers, were found in 617 (27.9%) patients. Advanced proximal neoplasms without any distal adenoma were present in 1.3% of patients. Of the advanced proximal lesions, 39% were not associated with any distal polyp. Older age, male gender, and distal adenoma were independent predictors of advanced proximal neoplasms. The predictive ability of a model with endoscopic data alone did not improve after inclusion of histopathologic data. In multivariate logistic regression analysis, the predictive ability of models that use age, gender, and any combination of distal findings was relatively low. The proportion of advanced proximal neoplasms identified if any distal polyp was an indication for colonoscopy was only 62%. CONCLUSIONS: A strategy in which colonoscopy is performed solely in patients with distal colonic findings is not effective screening for the detection of advanced proximal neoplasms in an average-risk populatio

Gender Differences in Immune Reconstitution: A Multicentric Cohort Analysis in Sub-Saharan Africa

In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution

Depletion of Human Histone H1 Variants Uncovers Specific Roles in Gene Expression and Cell Growth

At least six histone H1 variants exist in somatic mammalian cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be actively involved in the regulation of gene expression. However, it is not well known whether the different variants have distinct roles or if they regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. Rapid inhibition of each H1 variant was not compensated for by changes of expression of other variants. Microarray experiments have shown a different subset of genes to be altered in each H1 knock-down. Interestingly, H1.2 depletion caused specific effects such as a cell cycle G1-phase arrest, the repressed expression of a number of cell cycle genes, and decreased global nucleosome spacing. On its side, H1.4 depletion caused cell death in T47D cells, providing the first evidence of the essential role of an H1 variant for survival in a human cell type. Thus, specific phenotypes are observed in breast cancer cells depleted of individual histone H1 variants, supporting the theory that distinct roles exist for the linker histone variants

Repressive LTR Nucleosome Positioning by the BAF Complex Is Required for HIV Latency

The SWI/SNF BAF chromatin remodeling complex generates a repressive nucleosome structure at the HIV LTR conducive to establishment and maintenance of HIV latency, while PBAF augments HIV transcription

Regulation of the 11beta-hydroxysteroid dehydrogenase type 2 promoter by steroid hormones in breast cancer cells. Convergence of progesterone receptor binding to DNA and JAK/START pathway activation

El gen humano 11-HSD2 es un modelo para investigar la contribución de los efectos de los receptores de esteroides en células de cáncer de mama. El análisis del promotor mostró que la región distal está implicada en la mayor parte de la activación dependiente de hormona. En respuesta a hormona, STAT5A se recluta a la región distal y PR a las regiones distal y proximal del promotor. El reclutamiento de PR se debe a dos mecanismos diferentes, la unión directa de PR a la región proximal, y la implicación vía JAK/STAT en el reclutamiento a la región distal. La inducción del gen 11-HSD2 por hormonas disminuye parcialmente por inhibidores de MAPK y PI3K/Akt y totalmente por inhibidores de JAK/STAT. Así, los efectos citoplasmáticos del PR están implicados en la inducción del gen progesterona. La forma activa de la ARN-polimerasa II es reclutada por la inducción con hormonas a la región distal del promotor 11-HSD2 y la región distal tiene respuesta a hormonas por sí misma, indicando que la inducción del gen por hormonas empieza antes del sitio de inicio de transcripción descrito previamente.The human 11-HSD2 gene is a model to investigate the contribution of steroid hormone receptors effects on a progesterone responsive promoter in breast cancer cells. Deletion analysis of the 11-HSD2 promoter showed that the distal region is involved in most of the hormone-dependent activation. ChIP showed hormone-dependent STAT5A-recruitment to the distal region and PR-recruitment to the distal and proximal promoter regions. Results suggest two different mechanisms of hormone-induced PR-recruitment, since cells stably expressing PR containing a mutated DNA-binding domain have affected hormone-dependent PR-recruitment to proximal promoter, and JAK/STAT pathway inhibition blocks PR-recruitment to distal promoter. Hormone-stimulated 11-HSD2 gene-expression was partially decreased by MAPK and PI3K/AKT pathway inhibitors and totally blocked by JAK/STAT pathways inhibitors, indicating that cytoplasmic PR effects involvement in progestin-induced 11-HSD2 expression. Importantly, upon hormone induction active RNA-polymerase II is recruited from the 11-HSD2 distal promoter region and the distal minimal promoter has hormone-responsiveness by itself, suggesting that progesterone-dependent 11-HSD2 expression starts upstream the previously characterized transcription start site

Mental health in hospitals: A cross-sectional study of the representations of professionals in a French university hospital: Considering mental health is essential for the individual and society. Healthcare professionals are at risk of poor mental health. On the occasion of WHO World Mental Health Day on October 10th, 2021, a survey was conducted by the Occupational Health Service and the Direction of quality in Healthcare of the University Hospital of Lyon (Hospices civils de Lyon, HCL). The aim of the study was to collect the representations and beliefs of hospital staff on the/their mental health. Methods: A short and anonymous questionnaire was sent electronically to the 22,904 HCL professionals, with a link towards a short educational video. Results: Seven hundred and sixty-six responses were collected. Representations of mental health were generally positive among professionals, with a transactional vision including known determinants such as living and working conditions. The most chosen words related to mental health were ?equilibrium? and ?well-being?. The measures considered to be the most relevant by professionals to promote mental health were the establishment of rest ?bubble? times, times for discussions (colleagues and management), prevention programs, easier access to a ?psy? and to the occupational health service. Conclusion: This survey contributed to a better understanding of the representations of HCL professionals regarding mental health and to their awareness in this field. These results can be used to develop a mental health promotion plan in the workplace, adapted to hospital professionals.

Considering mental health is essential for the individual and society. Healthcare professionals are at risk of poor mental health. On the occasion of WHO World Mental Health Day on October 10th, 2021, a survey was conducted by the Occupational Health Service and the Direction of quality in Healthcare of the University Hospital of Lyon (Hospices civils de Lyon, HCL). The aim of the study was to collect the representations and beliefs of hospital staff on the/their mental health.La prise en considération de la santé mentale est essentielle pour l'individu et la société. Les professionnels de santé sont à risque d'une santé mentale dégradée. À l'occasion de la Journée mondiale de la santé mentale de l'OMS le 10 octobre 2021, une enquête a été conduite par le Service de médecine et santé au travail (SMST) et la Direction qualité usagers et santé populationnelle (DQUSP) des Hospices civiles de Lyon (HCL). L'objectif était de recueillir les représentations et croyances des personnels hospitaliers sur la/leur santé mentale. Méthode: Un questionnaire court et anonyme a été adressé par voie électronique aux 22 904 professionnels des HCL, accompagné d'une courte vidéo pédagogique. Résultats: Au total, 766 réponses ont été recueillies. Les représentations de la santé mentale étaient globalement positives parmi les professionnels, avec une vision transactionnelle incluant les déterminants connus comme les conditions de vie et de travail. Les mots les plus choisis en lien avec la santé mentale étaient « équilibre » et « bien-être ». Les mesures considérées comme les plus pertinentes pour promouvoir la santé mentale par les professionnels étaient la mise en place de temps de « bulle » de repos, des temps d'échanges (collègues et encadrement), des programmes de prévention, l'accès facilité à un(e) « psy » et au service de médecine et santé au travail. Conclusion: Cette enquête a contribué à mieux connaître les représentations des professionnels des HCL quant à la/leur santé mentale, et a participé à leur sensibilisation dans ce domaine. Ces résultats pourront participer à élaborer un plan de promotion de la santé mentale au travail adapté aux professionnels hospitaliers

Associations between gender and other factors and mean CD4 response to ART.

<p>*<i>P</i> value from Wald test for association model adjusted for all variables included in the table.</p><p>**<i>P</i> value from likelihood ratio test for association from the multivariable linear mixed model adjusted for all variables included in the table.</p>‡<p>214 cells/µL (95% CI 195–233) represents the mean CD4 count after 1 year of ART predicted by the multivariable linear mixed model for the reference level of all the variables included in the table.</p><p>BMI, body mass index.</p

Predicted female mean CD4 count after ART start by initial CD4 level, Uganda, Kenya, and Malawi.

<p>N = 8,878; mixed multivariate polynomial model.</p