Repeated dermal application of the common preservative methylisothiazolinone triggers local inflammation, T cell influx, and prolonged mast cell-dependent tactile sensitivity in mice

als.fakia shared this article with you from Inoreader Repeated dermal application of the common preservative methylisothiazolinone triggers local inflammation, T cell influx, and prolonged mast cell-dependent tactile sensitivity in mice Via PLOS ONE Alerts: New Articles by Jaclyn M. Kline, Erica Arriaga-Gomez, Tenzin Yangdon, Beebie Boo, Jasmine Landry, Marietta Saldías-Montivero, Nefeli Neamonitaki, Hanna Mengistu, Sayira Silverio, Hayley Zacheis, Dogukan Pasha, Tijana Martinov, Brian T. Fife, Devavani Chatterjea Occupational exposure to toxic chemicals increases the risk of developing localized provoked vulvodynia—a prevalent, yet poorly understood, chronic condition characterized by sensitivity to touch and pressure, and accumulation of mast cells in painful tissues. Here, we topically sensitized female ND4 Swiss mice to the common household and industrial preservative methylisothiazolinone (MI) and subsequently challenged them daily with MI or acetone and olive oil vehicle on the labiar skin. MI-challenged mice developed significant, persistent tactile sensitivity and long-lasting local accumulation of mast cells alongside early, transient increases in CD4+ and CD8+ T cells, eosinophils, neutrophils, and increases in pro-inflammatory cytokines. Therapeutic administration of imatinib, a c-Kit inhibitor known to inhibit mast cell survival, led to reduced mast cell accumulation and alleviated tactile genital pain. We provide the first pre-clinical evidence of dermal MI -induced mast-cell dependent pain and lay the groundwork for detailed understanding of these intersections between MI-driven immunomodulation and chronic pain. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk factors for development of acute kidney injury in hospitalised adults

als.fakia shared this article with you from Inoreader Risk factors for development of acute kidney injury in hospitalised adults in Zimbabwe Via PLOS ONE Alerts: New Articles by Alexander Gilbert, Lindsey Robertson, Jack E. Heron, Steve Chadban, Chiratidzo Ndhlovu, Rumbi F. Dahwa, David M. Gracey Background Acute kidney injury (AKI) is predominantly a disease of low and middle-income countries. Despite this, there is a particular paucity of data regarding AKI in Africa. Most published studies were conducted prior to the most recent Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI. This prospective, observational, cohort study examines AKI amongst newly admitted acute medical inpatients in a large, urban, tertiary hospital in Harare, Zimbabwe. Methods All newly admitted, adult, medical patients in separate, randomly selected, 24-hour periods were included. Baseline demographic information, comorbidities, nephrotoxic medication use, and reason for admission were recorded on a standardised data capture record. A serum creatinine measurement was performed on all patients at the time of admission and again after 48 hours. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation a nd AKI was defined using the most recent KDIGO definition as an increase in the serum creatinine of greater than 26.5μmol/L within 48 hours, with admission creatinine used as a baseline measurement. Results 253 patients were included in the analysis; 137 patients (54.2%) were female; 100 patients (39.5%) had HIV infection. 36 patients (14.2%) met the KDIGO criteria for AKI during the 48-hour follow-up period. AKI was more common among males (19.8% vs 9.5%; p = 0.019). The AKI group had a higher serum creatinine at presentation than those without AKI (296.5μmol/L vs 91.0μmol/L; p Conclusions KDIGO-defined AKI was common in hospitalised patients in Sub-Saharan Africa and was predicted by male sex, a history of comorbid hypertension and a history of comorbid chronic kidney disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism

als.fakia shared this article with you from Inoreader Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism Via PLOS ONE Alerts: New Articles by Michael L. Goodson, Trina A. Knotts, Elsie L. Campbell, Chelsea A. Snyder, Briana M. Young, Martin L. Privalsky The NCoR corepressor plays critical roles in mediating transcriptional repression by both nuclear receptors and non-receptor transcription factors. Alternative mRNA splicing of NCoR produces a series of variants with differing molecular and biological properties. The NCoRω splice-variant inhibits adipogenesis whereas the NCoRδ splice-variant promotes it, and mice bearing a splice-specific knockout of NCoRω display enhanced hepatic steatosis and overall weight gain on a high fat diet as well as a greatly increased resistance to diet-induced glucose intolerance. We report here that the reciprocal NCoRδ splice-specific knock-out mice display the contrary phenotypes of reduced hepatic steatosis and reduced weight gain relative to the NCoRω-/- mice. The NCoRδ-/- mice also fail to demonstrate the strong resistance to diet-induced glucose intolerance exhibited by the NCoRω-/- animals. The NCoR δ and ω variants possess both unique and shared transcriptional targets, with expression of certain hepatic genes affected in opposite directions in the two mutants, others altered in one but not the other genotype, and yet others changed in parallel in both NCoRδ-/- and NCoRω-/- animals versus WT. Gene set expression analysis (GSEA) identified a series of lipid, carbohydrate, and amino acid metabolic pathways that are likely to contribute to their distinct steatosis and glucose tolerance phenotypes. We conclude that alternative-splicing of the NCoR corepressor plays a key role in the regulation of hepatic energy storage and utilization, with the NCoRδ and NCoRω variants exerting both opposing and shared functions in many aspects of this phenomenon and in the organism as a whole. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancer inpatients with COVID-19

als.fakia shared this article with you from Inoreader Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute Via PLOS ONE Alerts: New Articles by Andreia C. de Melo, Luiz C. S. Thuler, Jesse L. da Silva, Lucas Z. de Albuquerque, Ana C. Pecego, Luciana de O. R. Rodrigues, Magda S. da Conceição, Marianne M. Garrido, Gelcio L. Quintella Mendes, Ana Cristina P. Mendes Pereira, Marcelo A. Soares, João P. B. Viola, on behalf of the Brazilian National Cancer Institute COVID-19 Task Force Objective This study aimed to describe the demographic and clinical characteristics of cancer inpatients with COVID-19 exploring clinical outcomes. Methods A retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR. Results The mean age was 55.3 years (SD ± 21.1). Comorbidities were present in 110 (60.8%) cases. The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. Metastatic disease accounted for 90 (49.7%) cases. In total, 63 (34.8%) had recently received cytotoxic chemotherapy. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. For solid tumors, the COVID-19-specific mortality rate was 37.7% (52 out of 138 patients) and for hematological malignancies, 23.5% (8 out of 34). According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p Conclusion This is the first Brazilian cohort of cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Maintaining resting cardiac fibroblasts in vitro by disrupting mechanotransduction

als.fakia shared this article with you from Inoreader Maintaining resting cardiac fibroblasts <i>in vitro</i> by disrupting mechanotransduction Via PLOS ONE Alerts: New Articles by George Gilles, Andrew D. McCulloch, Cord H. Brakebusch, Kate M. Herum Mechanical cues activate cardiac fibroblasts and induce differentiation into myofibroblasts, which are key steps for development of cardiac fibrosis. In vitro, the high stiffness of plastic culturing conditions will also induce these changes. It is therefore challenging to study resting cardiac fibroblasts and their activation in vitro. Here we investigate the extent to which disrupting mechanotransduction by culturing cardiac fibroblasts on soft hydrogels or in the presence of biochemical inhibitors can be used to maintain resting cardiac fibroblasts in vitro. Primary cardiac fibroblasts were isolated from adult mice and cultured on plastic or soft (4.5 kPa) polyacrylamide hydrogels. Myofibroblast marker gene expression and smooth muscle α-actin (SMA) fibers were quantified by real-time PCR and immunostaining, respectively. Myofibroblast differentiation was prevented on soft hydrogels for 9 days, but had occurred after 15 days on hydrogels. Transferring myofibr oblasts to soft hydrogels reduced expression of myofibroblast-associated genes, albeit SMA fibers remained present. Inhibitors of transforming growth factor β receptor I (TGFβRI) and Rho-associated protein kinase (ROCK) were effective in preventing and reversing myofibroblast gene expression. SMA fibers were also reduced by blocker treatment although cell morphology did not change. Reversed cardiac fibroblasts maintained the ability to re-differentiate after the removal of blockers, suggesting that these are functionally similar to resting cardiac fibroblasts. However, actin alpha 2 smooth muscle (Acta2), lysyl oxidase (Lox) and periostin (Postn) were no longer sensitive to substrate stiffness, suggesting that transient treatment with mechanotransduction inhibitors changes the mechanosensitivity of some fibrosis-related genes. In summary, our results bring novel insight regarding the relative importance of specific mechanical signaling pathways in regulating different myofibroblas t-associated genes. Furthermore, combining blocker treatment with the use of soft hydrogels has not been tested previously and revealed that only some genes remain mechano-sensitive after phenotypic reversion. This is important information for researchers using inhibitors to maintain a "resting" cardiac fibroblast phenotype in vitro as well as for our current understanding of mechanosensitive gene regulation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A comparison of the corneal biomechanics in pseudoexfoliation glaucoma, primary open-angle glaucoma and healthy controls using Corvis ST

als.fakia shared this article with you from Inoreader A comparison of the corneal biomechanics in pseudoexfoliation glaucoma, primary open-angle glaucoma and healthy controls using Corvis ST Via PLOS ONE Alerts: New Articles by Zia Sultan Pradhan, Sujit Deshmukh, Shivani Dixit, Shruthi Sreenivasaiah, Sujani Shroff, Sathi Devi, Carroll A. B. Webers, Harsha Laxmana Rao Purpose To compare the corneal biomechanical parameters between pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG) and healthy controls using Corvis ST. Methods A prospective, cross-sectional study was conducted which included 132 treatment-naïve eyes which underwent Corvis ST. The study cohort comprised of 44 eyes with PXG, 42 eyes with POAG and 46 healthy controls. Corneal biomechanical parameters, which included corneal velocities, length of corneal applanated surface, deformation amplitude (DA), peak distance and radius of curvature, were compared between the groups using analysis of variance models. Results The 3 groups were demographically similar. The mean IOP was 15.7 ±3 mmHg in the control group, 21.3 ±5 mmHg in the POAG group and 25.8 ±7 mmHg in the PXG group (p Conclusion Corneal biomechanical parameters measured on Corvis ST are not different between eyes with PXG, POAG and healthy controls after adjusting for IOP. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis

als.fakia shared this article with you from Inoreader Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis Via PLOS ONE Alerts: New Articles by Chia-Yu Lin, Jen-Ai Lee, Po-Yeh Lin, Shih-Chun Hua, Pei-Yun Tsai, Bi-Li Chen, Chia-En Lin, Tzong-Huei Lee, Shih‐Ming Chen The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, pppp View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.