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Kring Buckley posted an update 6 months, 4 weeks ago
Myofascial pelvic pain is a common, nonarticular musculoskeletal disorder characterized by the presence of myofascial trigger points in the lower abdominal wall and/or pelvic floor muscles. Myofascial pelvic pain is involved in an estimated 22% to 94% of cases of chronic pelvic pain, which is one of the most common gynecologic conditions in the United States. Myofascial pelvic pain may exist independently or in conjunction with disorders such as vaginismus, dysmenorrhea, and endometriosis and is frequently a causative factor in sexual pain or dyspareunia. This article reviews the pathophysiology, assessment, and treatment options for myofascial pelvic pain, with a particular focus on trigger point injections. Increased recognition and treatment of this commonly overlooked diagnosis has the potential to improve care and outcomes for many patients suffering from chronic pelvic pain.Uromodulin (UMOD) can bind complement factor H (cFH) and inhibit the activation of complement alternative pathway (AP) by enhancing the cofactor activity of cFH on degeneration of C3b. UMOD, an N-glycans-rich glycoprotein, is expressed in thick ascending limb of Henle’s loop where the epithelia need to adapt to gradient change of pH and ion concentration. ELISA-based cofactor activity of cFH and erythrocytes haemolytic assay was used to measure the impact of native and de-glycosylated UMOD on the functions of cFH. The binding assay was performed under different pH and ion concentrations, using ELISA. The levels of sialic acid on UMOD, from healthy controls and patients with chronic kidney disease (CKD), were also detected by lectin-ELISA. It was shown that removal of glycans decreased the binding between UMOD and cFH and abolished the ability of enhancing C3b degradation. In acidic condition, the binding became stronger, but it reduced as sodium concentration increased. A significant decrease of α-2,3 sialic acids on UMOD was observed in CKD patients compared with that of healthy individuals. The sialic acids on UMOD, local pH and sodium concentration could impact the binding capacity between UMOD and cFH and thus regulate the activation of complement AP.
This study aimed to assess and compare the effects of the GLP-1 analog liraglutide and the PPARα/δ agonist elafibranor on liver histology and their impact on hepatic lipidome, metabolome, Kupffer and hepatic stellate cell activation in a model of advanced non-alcoholic fatty liver disease (NAFLD).
Male C57BL/6JRj mice with biopsy-confirmed hepatosteatosis and fibrosis induced by 36-week Amylin liver NASH (AMLN) diet (high-fat, fructose and cholesterol) were randomized to receive for 12weeks (a) liraglutide (0.4mg/kg/day s.c.), (b) elafibranor (30mg/kg/day p.o.) and (c) vehicle. Metabolic status, liver pathology, markers of inflammation, Kupffer and stellate cell activation, and metabolomics/lipidomics were assessed at study completion.
Elafibranor and liraglutide improved weight, insulin sensitivity, glucose homeostasis and NAFLD activity score (pre-to-post biopsy). NRL-1049 cost Elafibranor had a profound effect on hepatic lipidome, demonstrated by reductions in glycerides, increases in phospholipids, and by beneficmechanisms of action and support the notion for their evaluation as combination therapies in the future.NELF-mediated pausing of RNA polymerase II (RNAPII) constitutes a crucial step in transcription regulation. However, it remains unclear how control release of RNAPII pausing can affect the epigenome and regulate important aspects of animal physiology like aging. We found that NELF-A dosage regulates Drosophila healthspan Halving NELF-A level in the heterozygous mutants or via neuronal-specific RNAi depletion improves their locomotor activity, stress resistance, and lifespan significantly. Conversely, NELF-A overexpression shortens fly lifespan drastically. Mechanistically, lowering NELF-A level facilitates the release of paused RNAPII for productive transcription of the heat-shock protein (Hsp) genes. The elevated HSPs expression in turn attenuates the accumulation of insoluble protein aggregates, reactive oxidative species, DNA damage and systemic inflammation in the brains of aging NELF-A depleted flies as compared to their control siblings. This pro-longevity effect is unique to NELF-A due to its higher expression level and more efficient pausing of RNAPII than other NELF subunits. Importantly, enhanced resistance to oxidative stress in NELF-A heterozygous mutants is highly conserved such that knocking down its level in human SH-SY5Y cells attenuates hydrogen peroxide-induced DNA damage and apoptosis. Depleting NELF-A reconfigures the epigenome through the maintenance of H3K9me2-enriched heterochromatin during aging, leading to the repression of specific retrotransposons like Gypsy-1 in the brains of NELF-A mutants. Taken together, we showed that the dosage of neuronal NELF-A affects multiple aspects of aging in Drosophila by regulating transcription of Hsp genes in the brains, suggesting that targeting transcription elongation might be a viable therapeutic strategy against age-onset diseases like neurodegeneration.
Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen that comprises two cycles of a total of 800mg/m
of thiotepa and a total of 280mg/m
of melphalan is widely utilized.
To evaluate the safety and efficacy of this thiotepa-melphalan high-dose therapy for high-risk neuroblastoma, we reviewed the medical records of 41 patients with high-risk neuroblastoma who underwent this regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point.
The median follow-up duration for living patients was 9.2years (range 5.5-14.0years). The 5-year event-free survival (EFS) and overall survival from treatment initiation were 41.5±7.7% and 56.1±7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.
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