Glucocorticoid hormones affect gene expression via activation of glucocorticoid receptor NR3C1, causing modulation of inflammation and autoimmune activation. The glucocorticoid Dexamethasone is an important pharmaceutical for the treatment of colitis and other inflammatory bowel diseases. While suppressive effects of glucocorticoids on activated immune cells is significant, their effects upon epithelial cells are less well studied. Previous research shows that the effects of Dexamethasone treatment on polarized Caco-2 cell layer permeability is delayed for >10 treatment days (as measured by transepithelial electrical resistance). In vivo intestinal epithelial cells turn over every 3–5 days; we therefore hypothesized that culture age may produce marked effects on gene expression, potentially acting as a confounding variable. To investigate this issue, we cultured polarized Caco-2 monolayers during a 30-day timecourse with ~15 days of continuous Dexamethasone exposure. We collected samples during the timecourse and tested differential expression using a 250-plex gene expression panel and Nanostring nCounter® system. Our custom panel was selectively enriched for KEGG annotations for tight-junction, actin cytoskeleton regulation, and colorectal cancer-associated genes, allowing for focused gene ontology-based pathway enrichment analyses. To test for confounding effects of time and Dexamethasone variables, we used the Nanostring nSolver differential expression data model which includes a mixturenegative binomial modelwith optimization. We identified a time-associated “EMT-like” signature with differential expression seen in important actomyosin cytoskeleton, tight junction, integrin, and cell cycle pathway genes. Dexamethasone treatment resulted in a subtle yet significant counter-signal showing suppression of actomyosin genes and differential expression of various growth factor receptors.
Persons living with human immunodeficiency virus (HIV) are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL) than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Cleary’s model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease) using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts), symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV) mental function), functional status (missed appointments and MOS-HIV physical function), general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition), and overall quality of life (QOL) (Satisfaction with Life Scale and MOS-HIV overall QOL). The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease.
Addison's Knowledge of Shakspeare Get access W. A. Henderson W. A. Henderson 1Dublin Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume s8-IV, Issue 86, 19 August 1893, Page 147, https://doi.org/10.1093/nq/s8-IV.86.147b Published: 19 August 1893
Introduction: Successful strategy for bowel preparation (prep) for colonoscopy aims at administering small–volume oral cathartics coupled with restricted solid food intake. An effective, safe, and standardized bowel preparation in children that is easily administered and acceptable has not yet been determined for children undergoing colonoscopy. Methods: This study compared the efficacy and acceptability of oral sodium phosphate (NaP) regimen 1 day prior to the examination at 1 mL/kg/day with a maximum 90 mL (2/3 dose in the morning, a maximum 45 mL, the remainder in the evening) (regimen A) to our standard prep regimen magnesium citrate 4 mL/kg/day in the morning (maximum 240 mL) for 3 days prior to, and a NaP enema the morning of the colonoscopy (regimen B). Both groups were only allowed clear liquids on prep days and nothing by mouth after midnight. After informed consent, 45 children (22 females) were randomized. Weight, vital signs, electrolytes, calcium, phosphorus and magnesium were taken at screening and on the day of the colonoscopy. Questionnaires were given to the subjects to assess acceptability and 10 possible side effects with intensity rating at none, mild, moderate or severe. An endoscopist blinded to the medication rated the bowel prep on a 4-level scale of excellent, good, fair or poor for overall quality of the colon prep and within each of its 5 segments. Results: Median [range] age (yr) and weight (kg) at screening was 13 [9–17], 53 [27–88], and 15 [8–18], 51 [28–109] in A and B, respectively. Mean weight loss of 0.88 and 1.05, SD ± 1.04 kg for A and B, respectively was not significantly different between groups. The mean increase in serum magnesium (mEq/L) was −0.01 vs 0.14 (p=0.001), and the mean increase in serum phosphorus (mg/dL) was 0.40 vs 0.33 (p=NS) in A vs B, respectively. No statistically significant difference was observed in other electrolytes between both groups. There were no serious adverse events reported from both regimens. The side effects were not statistically significant between both regimens, apart from higher nausea intensity in regimen A (p=0.012). Bowel cleansing was similar between the groups; 71% were rated excellent or good. Willingness to repeat the prep was higher in A vs B (77% vs 32%, p<0.006). Ten subjects in regimen A had prior colonoscopies using regimen B; 9 rated A better, 1 rated A the same. Conclusion: Oral NaP is safe and effective for bowel cleansing prior to colonoscopy in children and adolescents. It has a shorter prep time, comparable side effects and is more acceptable than our standard magnesium citrate regimen.
Cock-fighting Get access W. A. Henderson W. A. Henderson 1Dublin Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume s8-VII, Issue 181, 15 June 1895, Page 474, https://doi.org/10.1093/nq/s8-VII.181.474d Published: 15 June 1895
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