Sawyerwhitley1698

Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4 Gy non-myeloablative irradiation, 8 Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8 Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase in MECA32 and ZO-1 was detected in the 4 Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK mitogen-activated protein kinase (MAPK) but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4 Gy irradiation mice at day 10 compared with other groups. Both 8 Gy myeloablative and 4 Gy non-myeloablative irradiation disturbed the levels of short-chain fatty acids (SCFAs) in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and SCFAs metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells (MNCs) of gut, disturbed intestinal bacterial community and SCFAs level.

To evaluate the proportion of patients with early RA (ERA) who had or had not initiated glucocorticoids, to analyse the baseline characteristics, and to assess the clinical benefit and side effects of glucocorticoids during 5 years of follow-up.

We included patients with ERA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria and were naïve to conventional DMARDs (cDMARDs). We retrospectively collected patient characteristics prior to the introduction of cDMARDs with or without glucocorticoids. Efficiency and serious adverse events were analysed at 6, 12, 36 and 60 months.

Data from 474 eligible ERA patients were collected; 180 patients initiated glucocorticoids compared with 294 who did not. At baseline, the increased CRP was the main factor that favoured the initiation of glucocorticoids followed by smoking, absence of ACPA, prescription of MTX as a monotherapy and age. Five years' follow-up of DAS28-CRP, HAQ or visual analog score (VAS) pain values did not differ between the two groups. We also analysed a subgroup of 139 patients who received >1 g of prednisolone during the 5-year period. We confirmed the same baseline differences and observed in addition more men and higher DAS-28CRP values. During the 5 years' follow-up, DAS-28CRP, VAS pain and HAQ remained significantly higher in this subgroup. More severe infections were also reported.

In our ERA cohort, the initiation of glucocorticoid treatment did not bring additional benefit for the short- and long-term control of the disease. Glucocorticoid was more prescribed in seronegative RA patients with a higher level of inflammation.

In our ERA cohort, the initiation of glucocorticoid treatment did not bring additional benefit for the short- and long-term control of the disease. Glucocorticoid was more prescribed in seronegative RA patients with a higher level of inflammation.

To describe how many people with RA reduce their baseline physical activity level over the first year of MTX treatment, and which factors predict this.

Data came from the Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of people with early RA starting MTX. see more Participants reported demographics and completed questionnaires at baseline, and 6 and 12 months, including reporting the number of days per week they performed ≥20 min of physical activity, coded as none, low (1-3 days) or high (4-7 days). The physical activity levels of participants over 12 months are described. Predictors of stopping physical activity were assessed using multivariable logistic regression.

In total, 1468 participants were included [median (interquartile range) age 60 (50, 69) years; 957 (65.2%) women]. At baseline, the physical activity levels of the people with RA were none = 408 (27.8%), low = 518 (35.3%) and high = 542 (36.9%). Eighty percent of participants maintained some physical activity or began physical aactivity participation.

The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment.

Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45mg/kg intracoronary (IC) doxorubicin per injection] and follow-up control (no doxorubicin); single injection and sacrifice either at 48h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3e defects.The presence of adherens junctions and the associated protein β-catenin are requirements for the development of glucose-stimulated insulin secretion (GSIS) in β-cells. Evidence indicates that modulation of β-catenin function in response to changes in glucose levels can modulate the levels of insulin secretion from β-cells but the role of β-catenin phosphorylation in this process has not been established. We find that a Ser552Ala version of β-catenin attenuates glucose-stimulated insulin secretion indicating a functional role for Ser552 phosphorylation of β-catenin in insulin secretion. This is associated with alterations F/G actin ratio but not the transcriptional activity of β-catenin. Both glucose and GLP-1 stimulated phosphorylation of the serine 552 residue on β-catenin. We investigated the possibility that an EPAC-PAK1 pathway might be involved in this phosphorylation event. We find that reduction in PAK1 levels using siRNA attenuates both glucose and GLP-1 stimulated phosphorylation of β-catenin Ser552 and the effects of these on insulin secretion in β-cell models.