Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis.

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.

[Study on the incidence and characteristics of carotid canal dehiscence with high resolution CT].

Objective:To discuss the total incidence and characteristics of carotid canal dehiscence in Chinese adults with high resolution CT. At the same time, it provide basic data for otology clinical medical personnel to further understand the anatomical structure of ear and carry out auditory surgery.Method:Temporal bone HRCT images of 643 consecutive subjects who underwent CT scanner were analyzed retrospectively. The coronal, sagittal, and oblique sagittal plane were reconstructioned for some suspected subjects. Contrast the incidence of carotid canal dehiscence in different sex, bilateral and age groups.Result:In 643 patients, 43 cases found the carotid canal dehiscence, and the total incidence of carotid canal dehiscence was 6.7%.The incidence of carotid canal dehiscence for male and female were 5.9%(16/269)and 7.2%(27/374)(P > 0.05),and there was no statistically significant difference in the incidence of carotid canal dehiscence between sexes. The incidence of carotid canal dehiscence for age 40-59 was much higher than those of other age groups (P< 0.05),however, there was no significant difference between groups of age 20-39 and ≥60(P> 0.05).The location of the carotid canal dehiscence in 43 cases was located in the mesotympanum near the Eustachian tube orifice. Carotid artery tube ruptures are mostly small defects, but 11 cases with major defect.Conclusion:The toatal incidence of carotid canal dehiscence is 6.7% in Chinese adults (males: 5.9%,females: 7.2%), especially high incidence at group of age 40-59 (10.7%). Carotid canal dehiscence can be diagnosed accurately by HRCT and multiplanar reconstruction.

[Neurosyphilis and HIV co-infection with the initial symptom of sudden deafness and optic atrophy: a case report].

A 46-year-old male presented with left ear hearing loss,vertigo,tinnitus and left eye blurred vision. Pure tone audiometry showed left ear had been total deafness. Treponema pallidum particle agglutination (TPPA) assay was reactive. The serum rapid plasma regain (RPR) was 1∶16. Human immunodeficiency virus(HIV) 1/2 antibody immunoassay was positive，and the CD4 cell count was low at 100 cells/µl. Cerebrospinal fluid (CSF) TPPA was positive,with a white blood cell count of 53×10 6 /L and protein level of 1.08 g/L.The diagnosis was:①left ear sudden deafness(total deafness type);②neurosyphilis;③acquired immune deficiency syndrome(AIDS).

[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

Objective:To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method:Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result:Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion:Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex.

Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor.

A possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21(CIP1/WAF1) expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth.

Echocardiographic assessment of obstructive lesions in atrioventricular septal defects.

OBJECTIVES: We sought to determine the accuracy of transthoracic echocardiography (TTE) in identifying risk factors in patients with an atrioventricular septal defect (AVSD). BACKGROUND: Atrioventricular septal defect is a common lesion, and many decisions about it are based on echocardiography alone. The identification of associated left-sided inflow and outflow obstructive lesions is important, as they are responsible for mortality and morbidity. METHODS: Between 1983 to 1998, 549 patients with AVSD underwent repair. The TTE findings were correlated with surgery, angiocardiography, autopsy or postoperative TTE. Papillary muscle measurements were made in those with either a left ventricular outflow tract (LVOT) or left ventricular inflow abnormality and compared with those measurements from control subjects. Measurements of the LVOT were made in patients with an identified LVOT abnormality. RESULTS: There were 63 missed lesions, decreasing over time. Double-orifice left atrioventricular valve (DOLAVV) and nonobstructive chordae in the LVOT were more often missed. Reoperation was performed to address a missed lesion in 2 of 68 patients. Two of 55 patients died of reasons related to a missed lesion. In 67% of patients, DOLAVV was missed. Abnormal papillary muscle angles were seen with either a LVOT abnormality or DOLAVV. High insertion of the anterolateral papillary muscle was a risk factor for death or residual LVOT obstruction. Abnormal LVOT measurements were found in patients with tunnel obstruction and those with an acquired subaortic ridge. CONCLUSIONS: Transthoracic echocardiography provides accurate preoperative information on AVSD.