Histopathological and immunological characteristics of placentas infected with chikungunya virus.

Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1-4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-ß and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.

A prognostic value of CD45RA+, CD45RO+, CCL20+ and CCR6+ expressing cells as 'immunoscore' to predict cervical cancer induced by HPV.

The interplay between cervical cancer (CC) and immune cells, mainly intratumoral lymphocytes, has a pivotal role in carcinogenesis. In this context, we evaluated the distribution of CD45RA+ and CD45RO+ cells as well as CCR6+ and CCL20+ cells in intraepithelial (IE) and marginal stroma (MS) areas from cervical intraepithelial neoplasia (CIN) I-III, and CC as 'immunoscore' for HPV-induced CC outcome. We observed increased CD45RA+ and CD45RO+ cells distribution in IE and MS areas in the CC group compared to CIN groups and healthy volunteers. Interestingly, there is a remarkable reduction of CCL20+ expressing cells distribution according to lesion severity. The CC group had a significant decrease in CCL20+ and CCR6+-expressing cells distribution in both IE and MS areas compared to all groups. Using the 'immunoscore' model, we observed an increased number of women presenting high CD45RA+/CD45RO+ and low CCL20+/CCR6+ 'immunoscore' in the CC group. Our results suggested a pattern in cervical inflammatory process with increasing CD45RA+/CD45RO+, and decreasing CCL20+/CCR6+ expression in accordance with CIN severity. Taken together, these markers could be evaluated as 'immunoscore' predictors to CC response. A more comprehensive analysis of longitudinal studies should be conducted to associate CD45RA+/CD45RO+ and CCL20+/CCR6+ 'immunoscore' to CC progression and validate its value as a prognosis method.

Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses.

The most frequent fetal birth defect associated with prenatal Zika virus (ZIKV) infection is brain calcification, which in turn may potentially affect neurological development in infants. Understanding the mechanism could inform the development of potential therapies against prenatal ZIKV brain calcification. In perivascular cells, bone morphogenetic protein (BMP) is an osteogenic factor that undergoes maturation to activate osteogenesis and calcification. Here, we show that ZIKV infection of cultivated primary human brain pericytes triggers BMP2 maturation, leading to osteogenic gene expression and calcification. We observed extensive calcification near ZIKV+ pericytes of fetal human brain specimens and in vertically transmitted ZIKV+ human signal transducer and activator of transcription 2-knockin mouse pup brains. ZIKV infection of primary pericytes stimulated BMP2 maturation, inducing osteogenic gene expression and calcification that were completely blocked by anti-BMP2/4 neutralizing antibody. Not only did ZIKV NS3 expression alone induce BMP2 maturation, osteogenic gene expression and calcification, but purified NS3 protease also effectively cleaved pro-BMP2 in vitro to generate biologically active mature BMP2. These findings highlight ZIKV-induced calcification where the NS3 protease subverts the BMP2-mediated osteogenic signalling pathway to trigger brain calcification.

TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression.

TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 and rs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p < 0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression.

Antenatal Diagnosis of a Large Immature Abdominal Wall Teratoma by 2D-3D Ultrasound Using HDlive and Magnetic Resonance Imaging.

We describe the first case of prenatally detected teratoma of the fetal abdomen wall using ultrasound and fetal magnetic resonance imaging (MRI). A heterogeneous mass, partly solid and cystic, originating from the anterior abdominal wall of the fetus close to an omphalocele sac was detected by means of 2D/3D ultrasound and MRI. Amniodrainage was performed and due to sign of impending fetal risk, an emergency Cesarean section was performed. A bulky, crumbly and bleeding tumoral mass was confirmed at delivery. Ligation of the supplying artery to the tumor was complicated by uncontrollable hemorrhage and early neonatal death. Pathology identified the tumor as an immature teratoma of the anterior fetal abdominal wall. 2D/3D ultrasound, especially using HDlive application and MRI demonstrated accurate detection and characterization of this congenital tumor.

Simple hyperplasia versus proliferative endometrium: stereological study

The diagnosis of some forms of hyperplastic endometrium continues to present difficulties for the practicing pathologist. One of the major problems is the lack of a standard terminology for endometrial classification. Therefore, morphometrical techniques could help the accurate diagnosis. Thirteen samples of endometrium with simple hyperplasia and thirteen samples of proliferative endometrium were analyzed by light microscopy and stereology. We determined the volume density, the surface density and the length density (Vv, Sv, Lv) of the glands (epithelium and lumen) and the stroma. Volume densities of the epithelium and lumen as well as the surface density of the inner perimeter of the glands were greater in simple hyperplasia than in proliferative endometrium (p < 0.05). But the volume density of the stroma was greater in proliferative endometrium than in simple hyperplasia (p < 0.05). The length density of the glands and the surface density of the outer perimeter were not different comparing these two groups. Present results agree with previous studies that have pointed out the importance of quantitative parameters in the diagnosis of the endometrial pathologies offering new stereological parameters to this analysis