Measured Hyperelastic Properties of Cervical Tissue with Shear-Wave Elastography

The nonlinear mechanical behaviour of cervical tissue causes unpredictable changes in measured elastograms when pressure is applied. These uncontrolled variables prevent the reliable measurement of tissue elasticity in a clinical setting. Measuring the nonlinear properties of tissue is difficult due to the need for both shear modulus and strain to be taken simultaneously. A simulation-based method is proposed in this paper to resolve this. This study describes the nonlinear behaviour of cervical tissue using the hyperelastic material models of Demiray–Fung and Veronda–Westmann. Elastograms from 33 low-risk patients between 18 and 22 weeks gestation were obtained. The average measured properties of the hyperelastic material models are: Demiray–Fung—A1α = 2.07 (1.65–2.58) kPa, α = 6.74 (4.07–19.55); Veronda–Westmann—C1C2 = 4.12 (3.24–5.04) kPa, C2 = 4.86 (2.86–14.28). The Demiray–Fung and Veronda–Westmann models performed similarly in fitting to the elastograms with an average root mean square deviation of 0.41 and 0.47 ms−1, respectively. The use of hyperelastic material models to calibrate shear-wave speed measurements improved the consistency of measurements. This method could be applied in a large-scale clinical setting but requires updated models and higher data resolution.

Gonococcal invasion into epithelial cells depends on both cell polarity and ezrin

Neisseria gonorrhoeae (GC) establishes infection in women from the cervix, lined with heterogeneous epithelial cells from non-polarized stratified at the ectocervix to polarized columnar at the endocervix. We have previously shown that GC differentially colonize and transmigrate across the ecto and endocervical epithelia. However, whether and how GC invade into heterogeneous cervical epithelial cells is unknown. This study examined GC entry of epithelial cells with various properties, using human cervical tissue explant and non-polarized/polarized epithelial cell line models. While adhering to non-polarized and polarized epithelial cells at similar levels, GC invaded into non-polarized more efficiently than polarized epithelial cells. The enhanced GC invasion in non-polarized epithelial cells was associated with increased ezrin phosphorylation, F-actin and ezrin recruitment to GC adherent sites, and the elongation of GC-associated microvilli. Inhibition of ezrin phosphorylation inhibited F-actin and ezrin recruitment and microvilli elongation, leading to a reduction in GC invasion. The reduced GC invasion in polarized epithelial cells was associated with non-muscle myosin II-mediated F-actin disassembly and microvilli denudation at GC adherence sites. Surprisingly, intraepithelial GC were only detected inside epithelial cells shedding from the cervix by immunofluorescence microscopy, but not significantly in the ectocervical and the endocervical regions. We observed similar ezrin and F-actin recruitment in exfoliated cervical epithelial cells but not in those that remained in the ectocervical epithelium, as the luminal layer of ectocervical epithelial cells expressed ten-fold lower levels of ezrin than those beneath. However, GC inoculation induced F-actin reduction and myosin recruitment in the endocervix, similar to what was seen in polarized epithelial cells. Collectively, our results suggest that while GC invade non-polarized epithelial cells through ezrin-driven microvilli elongation, the apical polarization of ezrin and F-actin inhibits GC entry into polarized epithelial cells.

Effect of Zanthoxylum acanthopodium methanol extract on CDK4 expression to cervical cancer

Cervical cancer is a disease from the Human papillomavirus (HPV) through transmission, virus persistence, clone development until infecting the cells in the cervical. This study is to determine CDK4 expression in cervical cancer cells after being given Zanthoxylum acanthopodium methanol extract (ZAM) and the histological description of cervical cancer cells. This study consisted of 5 treatment groups. K-: control group, K+: rats model of cancer, P1: rats model of cancer with a dose of 100mg/BW of ZAM, P2: rats model of cancer with a dose of 200 mg/BW of ZAM, and P3: rats model of cancer with a dose of 400 mg/BW of ZAM. The cervical tissue was prepared on paraffin blocks and given Immunohistochemistry staining. Results showed that the expression of CDK4 are reduced in the ZAM treatment at doses of 200 and 400mg/KgBW (P<0.05) in cervical histology, but in doses of 100mg/kg BW, many brown marks are still visible on the cervical tissue. These proteins will bind, inhibit proteins, cell cycle development, modulate cell division, and signal transduction pathways of apoptotic signaling. The injection of benzopyrene and given ZAM in cervical tissue affect hematological values. ZAM affects and improves cervical histology after benzopyrene injection. The extract of andaliman can be developed into a cervical cancer drug candidate.

Cervical avulsion during induced labour: diagnosis, intraoperative management and postoperative course

We report the presentation, operative management and follow-up of a 31-year-old nulliparous woman who experienced a cervical avulsion injury (CAI) during labour. The woman was induced with dinoprostone gel, followed by oxytocin infusion and had a prolonged active phase. During the second stage, fetal decelerations were noted and the consultant asked to make a plan for delivery. When assessing to perform a midpelvic instrumental delivery, a cord of tissue was felt below the fetal head. A caesarean delivery was recommended based on this finding. After delivery, injuries to the broad ligament, posterior lower uterine segment vagina and cervix were repaired. The cervix was retained with the intent that some tissue be salvaged. At 6-week follow-up, transvaginal ultrasound confirmed blood flow in the cervical tissue, though cervical insufficiency was suspected on clinical examination. Our findings reinforce the seriousness of CAI and support conservative surgical management as opposed to trachelectomy or hysterectomy.

Low proteolytic processing of histone H3 in cervical tissue positive to hrHPV

During the different stages of cervical carcinogenesis there is an accumulation of epigenetic alterations leading to changes in gene expression. High-risk human papillomavirus (hrHPV) is a primary risk factor for cervical cancer (CC). Impaired proteolytic processing of histone H3 constitutes a potential epigenetic mechanism in CC. However, whether this event occurs in early stages of the HPV infection is unknown. Using human cervical samples with normal pathology but positive and negative to hrHPV, we identified that the H3 cleavage was low in the hrHPV positive cervix compared to the hrHPV negative cervix. These results suggest that low H3 processing previously observed in CC may be a primary effect of hrHPV infection.

p16 is superior to Stathmin-1 and HSP27 in identifying cervical dysplasia

Background The aim of this study was to determine how Stathmin-1 and Heat Shock Protein 27 (HSP27) can be used as adjunctive biomarkers to differentiate high-grade dysplasia from benign/reactive lesions in cervical tissues. In addition, we aimed to see if any of these markers can differentiate endometrial from endocervical adenocarcinomas. Methods Fifty cases including benign cervical tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ of the endocervix, invasive endocervical adenocarcinoma, and endometrial adenocarcinoma were selected. Stathmin-1 and HSP27 immunohistochemistry (IHC) were performed for each case and the results were compared to the previously available p16 IHC stains. Results p16 stained positively in 100% of HSIL, endocervical adenocarcinoma in situ, and invasive endocervical cases. Stathmin-1 stained positively in 43% of HSIL and 90% of endocervical adenocarcinoma in situ and all invasive endocervical cases. Stathmin-1 and p16 were negative in all benign cervical samples. Stathmin-1, HSP27, and p16 stained 100% of LSIL cases. HSP27 stained indiscriminately, including 100% of benign cervical tissue. 87% of the endometrial adenocarcinomas stained positively for p16, Stathmin-1, and HSP27. Conclusion p16 remains superior to both Stathmin-1 and HSP27 in differentiating dysplasia from benign, reactive changes of the cervix.

Mueller matrix imaging for collagen scoring in mice model of pregnancy

Preterm birth risk is associated with early softening of the uterine cervix in pregnancy due to the accelerated remodeling of collagen extracellular matrix. Studies of mice model of pregnancy were performed with an imaging Mueller polarimeter at different time points of pregnancy to find polarimetric parameters for collagen scoring. Mueller matrix images of the unstained sections of mice uterine cervices were taken at day 6 and day 18 of 19-days gestation period and at different spatial locations through the cervices. The logarithmic decomposition of the recorded Mueller matrices mapped the depolarization, linear retardance, and azimuth of the optical axis of cervical tissue. These images highlighted both the inner structure of cervix and the arrangement of cervical collagen fibers confirmed by the second harmonic generation microscopy. The statistical analysis and two-Gaussians fit of the distributions of linear retardance and linear depolarization in the entire images of cervical tissue (without manual selection of the specific regions of interest) quantified the randomization of collagen fibers alignment with gestation time. At day 18 the remodeling of cervical extracellular matrix of collagen was measurable at the external cervical os that is available for the direct optical observations in vivo. It supports the assumption that imaging Mueller polarimetry holds promise for the fast and accurate collagen scoring in pregnancy and the assessment of the preterm birth risk.