Endothelial dysfunction in subfertile women with polycystic ovary syndrome.

RESEARCH QUESTION: Is there an association between post-occlusive reactive hyperaemia (PORH) and ovarian stimulation in women with normoandrogenaemic polycystic ovary syndrome (PCOS)? DESIGN: Women eligible for IVF at an academic fertility centre were invited to join this prospective study. Microvascular endothelial function was measured as PORH by laser Doppler flowmetry (LDF) before and after ovarian stimulation. Metabolic characteristics, hormone profiles and biochemical markers were analysed. RESULTS: Thirty-four normoandrogenaemic women with PCOS and 36 normoandrogenaemic women without PCOS were included. The PCOS group displayed higher C-reactive protein levels and insulin resistance (P = 0.048 and P = 0.025, respectively). No significant difference was found in microcirculatory function between the groups at baseline. After ovarian stimulation, PORH was enhanced in the control group (slope 7.1 ± 3.3 versus 9.7 ± 4.5; P = 0.007; peak flow 30.7 ± 16.3 versus 43.5 ± 17.3, P = 0.008; however, the PCOS group experienced a blunting response to supraphysiological hormone status (slope 8.2 ± 5.1 versus 7.2 ± 4.3, P = 0.212; peak flow, 38.8 ± 19.4 versus 37.0 ± 21.8, P = 0.895). CONCLUSIONS: Impaired microcirculatory function could be found using a non-invasive LDF technique in normoandrogenaemic women with PCOS undergoing IVF, indicating early changes in vascular endothelial dysfunction. Future observational studies should clarify whether PORH measurement might help predict IVF prognosis or obstetric complications.

Mid-term survival of patients with chronic kidney disease after extracorporeal membrane oxygenation.

OBJECTIVES: Chronic kidney disease (CKD) impairs the elimination of fluids, electrolytes and metabolic wastes, which can affect the outcomes of extracorporeal membrane oxygenation (ECMO) treatment. This study aimed to elucidate the impact of CKD on in-hospital mortality and mid-term survival of adult patients who received ECMO treatment. METHODS: Patients who received first-time ECMO treatment between 1 January 2003 and 31 December 2013 were included. Those with CKD were identified and matched to patients without CKD using a 1:2 ratio and were followed for 3 years. The study outcomes included in-hospital outcomes and the 3-year mortality rate. A subgroup analysis was conducted by comparing the dialytic patients with the non-dialytic CKD patients. RESULTS: The study comprised 1008 CKD patients and 2016 non-CKD patients after propensity score matching. The CKD patients had higher in-hospital mortality rates [69.5% vs 62.2%; adjusted odds ratio 1.41; 95% confidence interval (CI) 1.15-1.72] than the non-CKD patients. The 3-year mortality rate was 80.4% in the CKD group and 68% in the non-CKD group (adjusted hazard ratio 1.17; 95% CI 1.06-1.28). The subgroup analysis showed that the 3-year mortality rates were 84.5% and 78.4% in the dialytic and non-dialytic patients, respectively. No difference in the 3-year mortality rate was noted between the 2 CKD subgroups (P = 0.111). CONCLUSIONS: CKD was associated with increased risks of in-hospital and mid-term mortalities in patients who received ECMO treatment. Furthermore, no difference in survival was observed between the patients with end-stage renal disease and non-dialytic CKD patients.

Late migration of a Sideris septal occluder device for closure of atrial septal defect into the left atrium with mitral valve obstruction.

The transcatheter closure of atrial septal defects provides an alternative to surgery, and various devices, such as the Sideris buttoned device, have been prescribed. Late complications have been rare and have not yet been reported within 2 years of implantation. This report presents a case of delayed migration of a Sideris buttoned device occurring 6 years after successful implantation. In conclusion, this report provides a reminder of the need for careful long-term follow-up of patients receiving transcatheter closure of atrial septal defects, particularly in cases involving the implantation of early-generated devices.

Four and half lim protein 2 (FHL2) stimulates osteoblast differentiation.

UNLABELLED: FHL2, a molecule that interacts with many integrins and transcription factors, was found to play an important role in osteoblast differentiation. Overexpression of FHL2 increases the accumulation of osteoblast differentiation markers and matrix mineralization, whereas FHL2 deficiency results in inhibition of osteoblast differentiation and decreased bone formation. INTRODUCTION: Integrin-matrix interaction plays a critical role in osteoblast function. It has been shown that the cytoplasmic domains of integrin beta subunits mediate signal transduction induced by integrin-matrix interaction. We reasoned that the identification of proteins interacting with beta-cytoplasmic tails followed by analysis of the function of these proteins would enhance our understanding on integrin signaling and the roles of these proteins in osteoblast activities. MATERIALS AND METHODS: Yeast two hybrid assay was used to identify proteins interacting with the cytoplasmic domain of integrin beta5 subunit. The association of these proteins with integrin alphavbeta5 was confirmed by confocal analysis and co-immunoprecipitation. A stable MC3T3-E1 cells line overexpressing Four and Half Lim Protein 2 (FHL2) and mouse osteoblasts deficient in FHL2 were used to study the roles of FHL2 in osteoblast differentiation and bone formation. Matrix protein expression was determined by mRNA analysis and Western blotting. Matrix mineralization was detected by Alizarin red staining. Alkaline phosphatase activity was also measured. muCT was used to determine bone histomorphometry. RESULTS AND CONCLUSIONS: FHL2 and actin-binding proteins, palladin and filamin A, were identified as proteins interacting with beta5 cytoplasmic domain. FHL2 co-localized with alphavbeta5 at the focal adhesion sites in association with palladin and filamin A. FHL2 was also present in nuclei. Osteoblasts overexpressing FHL2 exhibited increased adhesion to and migration on matrix proteins. Conversely, FHL2 stimulation of CREB activity was dependent on integrin function because it was inhibited by Gly-Arg-Gly-Asp-Ser (GRGDS) peptide. The expression of osteoblast differentiation markers and Msx2 was upregulated, and bone matrix mineralization was increased in FHL2 overexpressing cells. In contrast, FHL2-deficient bone marrow cells and osteoblasts displayed decreased osteoblast colony formation and differentiation, respectively, compared with wildtype cells. Moreover, FHL2-deficient female mice exhibited greater bone loss than the wildtype littermates after ovariectomy. Thus, FHL2 plays an important role in osteoblast differentiation and bone formation.