Thyboruiz3645

RESULTS Overall, 7.3% of women delivered preterm infants. The presence of both anxiety and depression, but neither of these conditions alone, was significantly associated with PTB (OR 1.6, 95% CI 1.1 to 2.3) and had significant interaction with neighbourhood deprivation (p=0.004). The predicted probability of PTB for women with both anxiety and depression was 10.0%, which increased to 15.7% if they lived in the most deprived neighbourhoods and decreased to 1.4% if they lived in the least deprived neighbourhoods. CONCLUSIONS Effects of anxiety and depression on risk of PTB differ depending on where women live. This understanding may guide the identification of women at increased risk for PTB and allocation of resources for early identification and management of anxiety and depression. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Understanding podocyte-specific responses to injury at a systems level is difficult because injury leads to podocyte loss or an increase of extracellular matrix, altering glomerular cellular composition. Finding a window into early podocyte injury might help identify molecular pathways involved in the podocyte stress response. METHODS We developed an approach to apply proteome analysis to very small samples of purified podocyte fractions. To examine podocytes in early disease states in FSGS mouse models, we used podocyte fractions isolated from individual mice after chemical induction of glomerular disease (with Doxorubicin or LPS). We also applied single-glomerular proteome analysis to tissue from patients with FSGS. RESULTS Transcriptome and proteome analysis of glomeruli from patients with FSGS revealed an underrepresentation of podocyte-specific genes and proteins in late-stage disease. Proteome analysis of purified podocyte fractions from FSGS mouse models showed an early stress response that includes perturbations of metabolic, mechanical, and proteostasis proteins. U0126 Additional analysis revealed a high correlation between the amount of proteinuria and expression levels of the mechanosensor protein Filamin-B. Increased expression of Filamin-B in podocytes in biopsy samples from patients with FSGS, in single glomeruli from proteinuric rats, and in podocytes undergoing mechanical stress suggests that this protein has a role in detrimental stress responses. In Drosophila, nephrocytes with reduced filamin homolog Cher displayed altered filtration capacity, but exhibited no change in slit diaphragm structure. CONCLUSIONS We identified conserved mechanisms of the podocyte stress response through ultrasensitive proteome analysis of human glomerular FSGS tissue and purified native mouse podocytes during early disease stages. This approach enables systematic comparisons of large-scale proteomics data and phenotype-to-protein correlation. Copyright © 2020 by the American Society of Nephrology.OBJECTIVES The objective of this study was to evaluate the frequency of human papillomavirus (HPV) in the oral cavity of women with and without abnormal cervical cytology and to determine whether there is an association of oral HPV infection with infection of the cervix or with cervical cancer precursor lesions. METHODS The present study was conducted among 406 women, aged 18-82 years, who attended the Prevention Department of Barretos Cancer Hospital (HCB), Brazil due to a previous altered cervical cytology result. Oral rinse, cervical cytology and biopsy were collected at the same day. The participants also answered a questionnaire about socioeconomic characteristics and risk factors for cervical cancer. Molecular screening for HPV16, HPV18 and 12 other high-risk HPV types was performed on cervical and oral rinse specimens using Cobas 4800 (Roche Molecular Systems, USA). RESULTS HPV was detected in the oral rinse of 3.9% of participants. Infection of the oral cavity with a non-HPV16 or 18 type was most frequent (81.2%), followed by HPV16 (18.7%). Infection with HPV in the cervix and oral cavity was present in 11 (2.7%) of participants. There were no differences observed in the smoking status (p value 0.62), mean age of first sexual intercourse (p value 0.25), mean age of the first oral sex (p value 0.90) or mean lifetime number of sexual partners (p value 0.08) between the participants with oral HPV infection or not. CONCLUSION The presence of HPV infection in the oral cavity was low in the group of women with abnormal cervical cancer screening findings and a high rate of cervical HPV infection. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE Epigenetic deregulation is deeply implicated in the pathogenesis of bladder cancer. KDM6A (Lysine (K)-specific demethylase 6A) is a histone modifier frequently mutated in bladder cancer. However, the molecular mechanisms of how KDM6A deficiency contributes to bladder cancer development remains largely unknown. We hypothesized that clarification of the pathogenic mechanisms underlying KDM6A-mutated bladder cancer can help in designing new anticancer therapies. EXPERIMENTAL DESIGN We generated mice lacking Kdm6a in the urothelium and crossed them with mice heterozygous for p53, whose mutation/deletion significantly overlaps with the KDM6A mutation in muscle-invasive bladder cancer (MIBC). In addition, BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine), a cigarette smoke-like mutagen, was used as a tumor-promoting agent. Isolated urothelia were subjected to phenotypic, pathologic, molecular, and cellular analyses. The clinical relevance of our findings was further analyzed using genomic and clinical data of patients with MIBC. RESULTS We found that Kdm6a deficiency activated cytokine and chemokine pathways, promoted M2 macrophage polarization, increased cancer stem cells and caused bladder cancer in cooperation with p53 haploinsufficiency. We also found that BBN treatment significantly enhanced the expression of proinflammatory molecules and accelerated disease development. Human bladder cancer samples with decreased KDM6A expression also showed activated proinflammatory pathways. Notably, dual inhibition of IL6 and chemokine (C-C motif) ligand 2, upregulated in response to Kdm6a deficiency, efficiently suppressed Kdm6a-deficient bladder cancer cell growth. CONCLUSIONS Our findings provide insights into multistep carcinogenic processes of bladder cancer and suggest molecular targeted therapeutic approaches for patients with bladder cancer with KDM6A dysfunction. ©2020 American Association for Cancer Research.