3D ultrasound strain imaging of puborectal muscle with and without unilateral avulsion.

Introduction And Hypothesis: The puborectal muscle (PRM), one of the female pelvic floor (PF) muscles, can get damaged during vaginal delivery, leading to disorders such as pelvic organ prolapse. Current diagnosis involves ultrasound (US) imaging of the female PF muscles, but functional information is limited. Previously, we developed a method for strain imaging of the PRM from US images in order to obtain functional information.

Unsupervised convolutional autoencoders for 4D transperineal ultrasound classification.

Purpose: 4D Transperineal ultrasound (TPUS) is used to examine female pelvic floor disorders. Muscle movement, like performing a muscle contraction or a Valsalva maneuver, can be captured on TPUS. Our work investigates the possibility for unsupervised analysis and classification of the TPUS data.

Tissue Characterization of Puborectalis Muscle From 3-D Ultrasound.

Pelvic floor (PF) muscles have the role of preventing pelvic organ descent. The puborectalis muscle (PRM), which is one of the female PF muscles, can be damaged during child delivery. This damage can potentially cause irreversible muscle trauma and even lead to an avulsion, which is disconnection of the muscle from its insertion point, the pubic bone.

Pessary fitting for pelvic organ prolapse: parameters associated with specific reasons for failure.

Introduction And Hypothesis: The objective was to assess if specific reasons for unsuccessful pessary fitting have different predictive parameters.

Methods: This is a prospective observational case-control study of women with symptomatic pelvic organ prolapse (POP) choosing pessary treatment. All women underwent an interview, clinical examination, and 3D/4D transperineal ultrasound (TPUS).

Parameters associated with unsuccessful pessary fitting for pelvic organ prolapse up to three months follow-up: a systematic review and meta-analysis.

Objectives: To clarify which parameters are associated with unsuccessful pessary fitting for pelvic organ prolapse (POP) at up to 3 months follow-up.

Methods: Embase, PubMed and Cochrane CENTRAL library were searched in May 2020. Inclusion criteria were: (1) pessary fitting attempted in women with symptomatic POP; (2) pessary fitting success among the study outcomes with a maximal follow-up of 3 months; (3) baseline parameters compared between successful and unsuccessful group.

Transperineal ultrasound to estimate the appropriate ring pessary size for women with pelvic organ prolapse.

Introduction And Hypothesis: The objective was to predict the successful ring pessary size based on the levator hiatal area (HA).

Methods: This is a prospective case-control study. Women with symptomatic pelvic organ prolapse (POP) choosing pessary treatment were included.

Appearance of the levator ani muscle subdivisions on 3D transperineal ultrasound.

Background: The levator ani muscle (LAM) consists of different subdivisions, which play a specific role in the pelvic floor mechanics. The aim of this study is to identify and describe the appearance of these subdivisions on 3-Dimensional (3D) transperineal ultrasound (TPUS). To do so, a study designed in three phases was performed in which twenty 3D TPUS scans of vaginally nulliparous women were assessed.

The effect of pessary treatment on puborectalis muscle function.

Introduction And Hypothesis: The objective was to assess if puborectalis muscle (PRM) function changes in women with pelvic organ prolapse (POP) undergoing pessary treatment.

Methods: This was a prospective cohort study of women with symptomatic POP choosing pessary treatment. An interview, clinical examination and 3D/4D transperineal ultrasound were performed at baseline and at 3-month follow-up.

3D Ultrasound Strain Imaging of Puborectalis Muscle.

The female pelvic floor (PF) muscles provide support to the pelvic organs. During delivery, some of these muscles have to stretch up to three times their original length to allow passage of the baby, leading frequently to damage and consequently later-life PF dysfunction (PFD). Three-dimensional (3D) ultrasound (US) imaging can be used to image these muscles and to diagnose the damage by assessing quantitative, geometric and functional information of the muscles through strain imaging.

Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.

Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemotactic responses of different NK cell subsets. Exposure of human peripheral blood NK cells to hypoxia for 16 or 96 h caused significant changes in the expression of 729 or 1,100 genes, respectively.

Cytokines can counteract the inhibitory effect of MEK-i on NK-cell function.

Oncogene-targeted therapies based on mutated BRAF- and/or MEK-specific inhibitors have been developed for melanoma treatment. Although these drugs induce tumor regression in a high percentage of patients, clinical responses are frequently limited in time and tumors often recur. Recent studies suggested that the combination of BRAF/MEK inhibition with immunotherapy could represent a promising strategy for the cure of melanoma.

Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC.

In certain infection sites or tumor tissues, the disruption of homeostasis can give rise to a hypoxic microenvironment, which, in turn, can alter the function of different immune cell types and favor the progression of the disease. Natural killer (NK) cells are directly involved in the elimination of virus-infected or transformed cells, however it is unknown whether their function is affected by hypoxia or not. In this study, we show that NK cells adapt to a hypoxic environment by upregulating the hypoxia-inducible factor 1α.

Melanoma cells become resistant to NK-cell-mediated killing when exposed to NK-cell numbers compatible with NK-cell infiltration in the tumor.

During the past few years, a number of studies reported that different melanoma cell lines could be extensively lysed in vitro by IL-2-activated NK cells at appropriate effector/target ratios. Here, we show, by histological evaluation of different melanoma lesions, that NK/target-cell ratios compatible with those allowing efficient melanoma cell killing in vitro are hardly reached at the tumor site. We then investigated the outcome of cocultures established at low NK/melanoma cell ratios.

Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity.

Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function.

The emerging role of HLA-E-restricted CD8+ T lymphocytes in the adaptive immune response to pathogens and tumors.

Human leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule of limited sequence variability that is expressed by most tissues albeit at low levels. HLA-E has been first described as the ligand of CD94/NKG2 receptors expressed mainly by natural killer (NK) cells, thus confining its role to the regulation of NK-cell function. However, recent evidences obtained by our and other groups indicate that HLA-E complexed with peptides can interact with alphabeta T-cell receptor (TCR) expressed on CD8(+) T cells.

Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity.

Although the role of the tumor microenvironment in the process of cancer progression has been extensively investigated, the contribution of different stromal components to tumor growth and/or evasion from immune surveillance is still only partially defined. In this study we analyzed fibroblasts derived from metastatic melanomas and provide evidence for their strong immunosuppressive activity. In coculture experiments, melanoma-derived fibroblasts sharply interfered with NK cell functions including cytotoxicity and cytokine production.

Natural killer cells kill human melanoma cells with characteristics of cancer stem cells.

Experimental and clinical data suggest that tumours harbour a cell population retaining stem cell characteristics that can drive tumorigenesis. CD133 is considered an important cancer stem cells (CSC)-associated marker. In a large variety of human malignancies, including melanoma, CD133(+) cells have been reported to comprise CSC.