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.

Relationship between sedentary behaviour and anxiety symptoms among youth in 24 low- and middle-income countries

als.fakia shared this article with you from Inoreader Relationship between sedentary behaviour and anxiety symptoms among youth in 24 low- and middle-income countries Via PLOS ONE Alerts: New Articles by Ming-Hui Wang, Dian-Min Xiao, Ming-Wei Liu, Yuan-An Lu, Qi-Qiang He Background Anxiety is burdensome and common in youth. Sedentary behaviour has been identified as potentially modifiable dangerous factors for many diseases. Nevertheless, little is known about the relationship between sedentary behaviour and the risk of anxiety symptoms in youth. Therefore, we aimed to examine the association among youth in 24 low- and middle-income countries (LMICs). Methods Data from the Global School-based Student Health Survey (GSHS) were analyzed in 59587 youth aged 12–15 years. Most of the country-wide data were nationally representative. Anxiety symptoms were self-reported. Multivariable logistic regression and meta-analyses of country-wise estimates were conducted. Results The prevalence of anxiety symptoms was 10.3%. Countrywide meta-analysis demonstrated that sedentary behaviour of >2 h/day (vs.≤2 h/day) was associated with an increased risk of anxiety symptoms (OR = 1.22; 95% CI = 1.10–1.37). Conclusions This study provides multi-national evidence of the dangerous effect of sedentary behaviour against anxiety symptoms among youth in LMICs. Decreasing the level of sedentary behaviour during adolescence could be an important target for reducing the prevalence of anxiety. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exposure to small molecule cocktails allows induction of neural crest lineage cells from human adipose-derived mesenchymal stem cells

als.fakia shared this article with you from Inoreader Exposure to small molecule cocktails allows induction of neural crest lineage cells from human adipose-derived mesenchymal stem cells Via PLOS ONE Alerts: New Articles by Yuzo Takayama, Yuka Akagi, Yoichiro Shibuya, Yasuyuki S. Kida Neural crest cells (NCCs) are a promising source for cell therapy and regenerative medicine owing to their multipotency, self-renewability, and capability to secrete various trophic factors. However, isolating NCCs from adult organs is challenging, because NCCs are broadly distributed throughout the body. Hence, we attempted to directly induce NCCs from human adipose-derived mesenchymal stem cells (ADSCs), which can be isolated easily, using small molecule cocktails. We established a controlled induction protocol with two-step application of small molecule cocktails for 6 days. The induction efficiency was evaluated based on mRNA and protein expression of neural crest markers, such as nerve growth factor receptor (NGFR) and sex-determining region Y-box 10 (SOX10). We also found that various trophic factors were significantly upregulated following treatment with the small molecule cocktails. Therefore, we performed global profiling of cell surface makers and identified distinctly upre gulated markers, including the neural crest-specific cell surface markers CD271 and CD57. These results indicate that our chemical treatment can direct human ADSCs to developing into the neural crest lineage. This offers a promising experimental platform to study human NCCs for applications in cell therapy and regenerative medicine. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trace metals contamination

als.fakia shared this article with you from Inoreader Trace metals contamination potential and health risk assessment of commonly consumed fish of Perak River, Malaysia Via PLOS ONE Alerts: New Articles by Mohammed Abdus Salam, Shujit Chandra Paul, Rabiatul Adawiyah M. Mohamad Zain, Snahasish Bhowmik, Mithun Rani Nath, Sadia Afrin Siddiqua, Tutun Das Aka, Muhammad Anwar Iqbal, Wan Rashidah Kadir, Rozita Binti Ahamad, Md. Abdul Khaleque, Aweng Eh Rak, Mohamad Faiz Mohd Amin The rapid growth of industrial and agricultural activities in Malaysia are leading to the impairment of most of the rivers in recent years through realising various trace metals. This leads to toxicity, particularly when the toxic has entered the food chain. Perak River is one of the most dynamic rivers for the Malaysian population. Therefore, in consideration of the safety issue, this study was conducted to assess the concentration of such metals (Cd, Cu, Zn, Fe, and Pb) in the muscles of most widely consumed fish species (Barbonymus schwanenfeldii, Puntius bulum, Puntius daruphani, Hexanematichthys sagor, Channa striatus, Mystacoleucus marginatus, and Devario regina) from different locations of Perak River, Malaysia by employing inductively coupled plasma optical emission spectroscopy (ICP-OES). Among the trace metals, Fe and Cd were found to be the highest (29.33–148.01 μg/g) and lowest (0.16–0.49 μg/g) concentration in all of the studied species, respectively. Although the estimated daily intakes (μg/kg/day) of Cd (0.65–0.85), Fe (79.27–352.00) and Pb (0.95–12.17) were higher than their reference, the total target hazard quotients values suggested that the local residents would not experience any adverse health effects from its consumption. In contrast, the target cancer risk value suggested that all fish species posed a potential cancer risk due to Cd and cumulative cancer risk values, strongly implying that continuous consumption of studied fish species would cause cancer development to its consumers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio

als.fakia shared this article with you from Inoreader Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio Via PLOS ONE Alerts: New Articles by Yu Nishida, Shuhei Hosomi, Hirokazu Yamagami, Koji Fujimoto, Rieko Nakata, Shigehiro Itani, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Yasuaki Nagami, Koichi Taira, Noriko Kamata, Toshio Watanabe, Yasuhito Iseki, Tatsunari Fukuoka, Masatsune Shibutani, Hisashi Nagahara, Satoko Ohfuji, Yasuhiro Fujiwara Objectives Pouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients. Materials and methods UC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment w eighting (IPTW). Results Forty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7–47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01–1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31 –9.89; P = 0.01). Conclusions NLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.