Classical HDACs in the regulation of neuroinflammation

Given the potentially devastating consequence of a single attack of NMOSD, caution is advised with IST discontinuation, particularly in patients with severe attack before IST.
IST discontinuation may increase the risk of relapse in seropositive patients with NMOSD even after 5 years of remission. Given the potentially devastating consequence of a single attack of NMOSD, caution is advised with IST discontinuation, particularly in patients with severe attack before IST.
To analyse the impact of the COVID-19 pandemic on rheumatic patients' and rheumatologists' usage, preferences and perception of digital health applications (DHAs).
A web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media (Twitter, Instagram and Facebook), QR code and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.
We analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of rheumatic and musculoskeletal diseases (RMDs) and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%). The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists). Only a minority (<10% in both groups) believed that digitalisation has a negative impact on the patient-doctor relationship.
The COVID-19 pandemic instigated an increase in patients' and rheumatologists' acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.
The COVID-19 pandemic instigated an increase in patients' and rheumatologists' acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.
The incubation of airway epithelia cells at low temperatures is a common in vitro experimental approach used in the field of cystic fibrosis (CF) research to thermo-stabilise F508del-CFTR and increase its functional expression. Given that the airway epithelium includes numerous ion transporters other than CFTR, we hypothesised that there was an impact of low temperature incubation on CFTR-independent ionoregulatory mechanisms in airway epithelia derived from individuals with and without CF.
After differentiation at the air-liquid interface, nasal epithelia were incubated at either 37°C or 29°C (low temperature) for 48 hours prior to analysis in an Ussing chamber.
While F508del-CFTR activity was increased after low temperature incubation, activity of CFTR in non-CF epithelia was unchanged. Importantly, cultures incubated at 29°C demonstrated decreased transepithelial potential difference (TEPD) and short-circuit currents (Isc) at baseline. The predominant factor contributing to the reduced baseline TEPD and Isc in 29°C cultures was the reduced activity of the epithelial sodium channel (ENaC), evidenced by a reduced responsiveness to amiloride. This effect was observed in cells derived from both non-CF and CF donors.
Significant transcriptional downregulation of ENaC subunits β and γ were observed, which may partially explain the decreased ENaC activity. We speculate that low temperature incubation may be a useful experimental paradigm to reduce ENaC activity in in vitro epithelial cultures.
Significant transcriptional downregulation of ENaC subunits β and γ were observed, which may partially explain the decreased ENaC activity. We speculate that low temperature incubation may be a useful experimental paradigm to reduce ENaC activity in in vitro epithelial cultures.
The influence of sex hormone and insulin/insulin-like growth factor (IGF) axis signaling on endometrial cancer recurrence is unknown. We evaluated these pathways in a prospective cohort of Gynecologic Oncology Group (GOG)0210 trial endometrial adenocarcinoma patients.
Stage II-IV patients (
= 816) were included in this study. Resiquimod clinical trial Pretreatment specimens were tested for tumor mRNA and protein expression of
, IGF-binding proteins (
)
and
, insulin (IR) and IGF-I receptors (IGF1R), phosphorylated IR/IGF1R (pIGF1R/pIR), and estrogen (ER) and progesterone receptors (PR) using qPCR and IHC. Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone, and sex hormone binding globulin were measured. HRs and 95% confidence intervals (CI) for progression-free survival were calculated from Cox models adjusting for age, stage, and grade.
Recurrence occurred in 280 (34%) cases during a median of 4.6 years of follow-up. ER positivity (HR, 0.67; 95% CI, 0.47-0.95), IR positivity (HR, 0.53; 95% CI, 0.29-0.98), and circulating IGF-I (highest vs. lowest quartile HR, 0.66; 95% CI, 0.47-0.92) were inversely associated with recurrence risk. Circulating estradiol (highest vs. lowest tertile HR, 1.55; 95% CI, 1.02-2.36) and pIGF1R/pIR positivity (HR, 1.40; 95% CI, 1.02-1.92) were associated with increased recurrence risk.
Circulating estradiol and tumor tissue phosphorylated (activated) IGR1R/IR were independently associated with higher risk of recurrence in patients with endometrial cancer.
This study may inform future clinical trials of endocrine-targeted adjuvant therapies in patients with endometrial cancer that could include baseline assessment of serum and tissue biomarkers of estradiol and insulin signaling pathways.
This study may inform future clinical trials of endocrine-targeted adjuvant therapies in patients with endometrial cancer that could include baseline assessment of serum and tissue biomarkers of estradiol and insulin signaling pathways.