Clinical characteristics and treatment modalities of vulvovaginal atrophy in genitourinary syndrome of menopause

Background: Genitourinary syndrome of menopause (GSM) causes symptoms such as vaginal dryness, dysuria, repetitive urinary tract infection and urinary urgency may affect daily activities, sexual relationships, and overall quality of life. The aim of the study was to provide the clinical characteristics of VVA patients in South Korea and the effectiveness as well as complications of the currently used low dose estrogen vaginal suppository.Methods: 52 women who has visited the outpatient gynecology clinic of the National Health Insurance Service Ilsan Hospital from January 2018 to December 2019 were recruited as study subjects. For the analysis of the clinical characteristics, subjective symptoms described by the patient’s own words such as vaginal dryness, pain, dysuria, dyspareunia, or no symptoms at all were included. Objective signs such as thinning of vaginal rugae, mucosal dryness, and mucosal fragility and the presence of petechiae were recorded.Results: Vaginal dryness was the most common complaint (92.3%). Thinning of the vaginal rugae was the most commonly noted objective sign (73.1%). Of the 52 subjects, 31 (59.6%) refrained from using the low dose estrogen vaginal suppository. The most common reason for not being able to use the suppository was the inability to insert the suppository (32.3%).Conclusions: Although patient-reported symptoms and clinical objectivity through physical examination are two components in diagnosing VVA, further study is warranted for a more objective and discriminatory diagnosis criteria for VVA. As the only available treatment modality was low dose vaginal estrogen suppository, comparison with other treatment modalities were not available

A case of idiopathic isolated hypoglossal nerve palsy in a Korean child

Hypoglossal nerve palsy (HNP) is an uncommon neurological abnormality that can provoke characteristic clinical signs, including unilateral atrophy of the tongue musculature. We present the case of a healthy 11-year-old Korean male who was admitted to the outpatient department of our institution with acute onset dysarthria, tongue fasciculations, and right-sided tongue weakness upon awakening. His evaluation included a virology work-up, neck magnetic resonance imaging (MRI), brain MRI, and otorhinolaryngological physical examination; all tests were normal and showed no evidence of inflammation. Fifteen days after the onset of symptoms, the patient recovered completely. Herein, we report a case of idiopathic isolated HNP in a Korean male

Effect of Pertussis Toxin and Herbimycin A on Proteinase-Activated Receptor 2-Mediated Cyclooxygenase 2 Expression in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of Gi protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection

Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation

Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity. Accordingly, negative regulation of the DDR is as critical as its activation. In this study, we have identified ring finger protein 126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing 53BP1. RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but also of RNF168, FK2, RAP80, and BRCA1. However, the iRIF formation of H2AX, MDC1, and RNF8 is maintained, indicating that RNF126 acts between RNF8 and RNF168 during the DDR. In addition, RNF126 overexpression consistently results in the loss of RNF168-mediated H2A monoubiquitination at lysine 13/15 and inhibition of the non-homologous end joining capability. Taken together, our findings reveal that RNF126 is a novel factor involved in the negative regulation of DDR, which is important for sustaining genomic integrity

Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery

Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization

Calcified Macroplastique Substance: A Rare Cause of Recurrent Gross Hematuria after Endoscopic Injection

Endoscopic subureteral injection for treatment of vesicoureteral reflux (VUR) is known to be safe and efficient due to its minimal invasive nature. Being non-migratory, non-antigenic, and biocompatible, Macroplastique (Polydimethylsiloxane) is likely to be stable over time. A 5-year-old boy with a past history of subureteral administration of Macroplastique for unilateral Grade V VUR 4 years ago presented with recurrent gross and microscopic hematuria, along with suprapubic pain. On computed tomography (CT) abdomen, calcified material, suspected to be a stone, was visualized in the bladder. On diagnostic cystoscopy, calcification was seen around the orifice site where Macroplastique injection had been performed. We removed the calcific material by Holmium laser. Endoscopic subureteric implantation has several advantages, but nevertheless, vigilance is needed to detect long-term complications, especially in patients with gross or microscopic hematuria

AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

Arthroscopic Treatment of Septic Arthritis of the Shoulder: Technical Pearls to Reduce the Rate of Reoperation

Background The aim of this study was to evaluate clinical experience with arthroscopic debridement for septic arthritis of the shoulder joint and to report on our patient outcomes. Methods The retrospective analysis included 36 shoulders (male:female, 15:21), contributed by 35 patients (mean age, 63.8 years) treated by arthroscopy for septic arthritis of the shoulder between November 2003 and February 2016. The mean follow-up period was 14.3 months (range, 12–33 months). An additional posterolateral portal and a 70º arthroscope was used to access the posteroinferior glenohumeral (GH) joint and posteroinferior subacromial (SA) space, respectively. Irrigation was performed with a large volume of fluid (25.1±8.1 L). Multiple suction drains (average, 3.3 drains) were inserted into the GH joint and SA space and removed 8.9±4.3 days after surgery. Intravenous antibiotics were administered for 3.9±1.8 weeks after surgery, followed by oral antibiotic treatment for another 3.6±1.9 weeks. Results Among the 36 shoulders, reoperation was required in two cases (5.6%). The average range of motion achieved was 150.0º for forward flexion and T9 for internal rotation. The mean simple shoulder test score was 7.9±3.6 points. Nineteen shoulders (52.8%) had acupuncture or injection history prior to the infection. Pathogens were identified in 15 shoulders, with Staphylococcus aureus being the most commonly identified pathogen (10/15). Both the GH joint and the SA space were involved in 21 shoulders, while 14 cases involved only the GH joint and one case involved only the SA space. Conclusions Complete debridement using an additional posterolateral portal and 70º arthroscope, a large volume of irrigation with >20 L of saline, and multiple suction drains may reduce the reoperation rate

Heterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cells.

Excessive mitochondrial fission is associated with the pathogenesis of neurodegenerative diseases. Dynamin-related protein 1 (Drp1) possesses specific fission activity in the mitochondria and peroxisomes. Various post-translational modifications of Drp1 are known to modulate complex mitochondrial dynamics. However, the post-transcriptional regulation of Drp1 remains poorly understood. Here, we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) regulates Drp1 expression at the post-transcriptional level. hnRNP A1 directly interacts with Drp1 mRNA at its 3'UTR region, and enhances translation potential without affecting mRNA stability. Down-regulation of hnRNP A1 induces mitochondrial elongation by reducing Drp1 expression. Moreover, depletion of hnRNP A1 suppresses 3-NP-mediated mitochondrial fission and dysfunction. In contrast, over-expression of hnRNP A1 promotes mitochondrial fragmentation by increasing Drp1 expression. Additionally, hnRNP A1 significantly exacerbates 3-NP-induced mitochondrial dysfunction and cell death in neuroblastoma cells. Interestingly, treatment with 3-NP induces subcellular translocation of hnRNP A1 from the nucleus to the cytoplasm, which accelerates the increase in Drp1 expression in hnRNP A1 over-expressing cells. Collectively, our findings suggest that hnRNP A1 controls mitochondrial dynamics by post-transcriptional regulation of Drp1.This research was supported by a grant of the Korea–UK Collaborative Alzheimer's Disease Research Project by Ministry of Health & Welfare, Republic of Korea (A120196, HI14C1913) and was supported by the Basic Science Research Program of the National Research Foundation, Republic of Korea (2014R1A2A1A11053431). We are grateful to Wellcome Trust, Principal Research Fellowship to DCR (095317/Z/11/Z)This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.bbagrm.2015.10.01