Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity

BACKGROUND: Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF. METHODS: Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann–Whitney U-test and the chi-square test. RESULTS: Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively). CONCLUSIONS: A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity

3D imaging of proximal caries in posterior teeth using optical coherence tomography

Optical coherence tomography (OCT) can create cross-sectional images of tooth without X-ray exposure. This study aimed to investigate the diagnostic accuracy of 3D imaging of OCT for proximal caries in posterior teeth. Thirty-six human molar teeth with 51 proximal surfaces visibly 6 intact, 16 slightly demineralized, and 29 distinct carious changes were mounted to take digital radiographs and 3D OCT images. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the diagnosis of enamel caries and dentin caries were calculated to quantify the diagnostic ability of 3D OCT in comparison with digital radiography. Diagnostic accuracy was evaluated by the agreement with histology using weighted Kappa. OCT showed significantly higher sensitivity, AUC and Kappa values than radiography. OCT can be a safer option for the diagnosis of proximal caries in posterior teeth that can be applied to the patients without X-ray exposure

Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell coun

Clinical Significance of Reverse Redistribution Phenomenon for 201Tl Scintigraphy in Nonischemic Disease

The reverse redistribution phenomenon (RR) on 201Tl SPECT has been focused mainly on ischemic improvement regions after reperfusion therapy or vasospastic angina pectoris. However, RR analysis has not been used in the context of non-ischemic disease. The aim of this study was to evaluate the clinical role of RR on 201Tl SPECT in patients without a history of myocardial ischemia. We retrospectively enrolled 86 patients showing RR by myocardial perfusion SPECT and studied 75 other patients as a control group. For quantitative analysis, each 201Tl SPECT polar map was divided into 13 segments. Differences between the RR and control group were assessed with respect to patient characteristics and cardiac event-free survival using the Kaplan-Meier method. RR was detected frequently in the inferoposterior wall, septal portion of the anterior wall, and septum. The two groups showed signi_cant differences in rates of heart failure (P ＜ 0.01), hypertrophic cardiomyopathy (P ＜ 0.05), and wall motion abnormality (P ＜ 0.05), but not in the rate of event occurrence. The study demonstrated that RR on 201Tl SPECT could indicate the existence of myocardial damage ; however, it would not be a factor that determines the prognosis

Akt1 in Osteoblasts and Osteoclasts Controls Bone Remodeling

Bone mass and turnover are maintained by the coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts, under regulation of many systemic and local factors. Phosphoinositide-dependent serine-threonine protein kinase Akt is one of the key players in the signaling of potent bone anabolic factors. This study initially showed that the disruption of Akt1, a major Akt in osteoblasts and osteoclasts, in mice led to low-turnover osteopenia through dysfunctions of both cells. Ex vivo cell culture analyses revealed that the osteoblast dysfunction was traced to the increased susceptibility to the mitochondria-dependent apoptosis and the decreased transcriptional activity of runt-related transcription factor 2 (Runx2), a master regulator of osteoblast differentiation. Notably, our findings revealed a novel role of Akt1/forkhead box class O (FoxO) 3a/Bim axis in the apoptosis of osteoblasts: Akt1 phosphorylates the transcription factor FoxO3a to prevent its nuclear localization, leading to impaired transactivation of its target gene Bim which was also shown to be a potent proapoptotic molecule in osteoblasts. The osteoclast dysfunction was attributed to the cell autonomous defects of differentiation and survival in osteoclasts and the decreased expression of receptor activator of nuclear factor-κB ligand (RANKL), a major determinant of osteoclastogenesis, in osteoblasts. Akt1 was established as a crucial regulator of osteoblasts and osteoclasts by promoting their differentiation and survival to maintain bone mass and turnover. The molecular network found in this study will provide a basis for rational therapeutic targets for bone disorders