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Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include γδ T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-γ. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, γδ T cells promote tumor cell growth. γδ T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated γδ T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-γ. Consistent with this finding, both T cell receptor (TCR)δ-deficient and IL-17–deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by γδ T cells in the tumor environment was essentially restricted to a highly proliferative CD27 ⁽⁻⁾ subset that expressed Vγ6 instead of the more common Vγ1 and Vγ4 TCR chains. The preferential expansion of IL-17–secreting CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17–dependent lymphoid/myeloid cross-talk involving γδ T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance.

The thymus produces γδ T cell subsets making either IFN-γ or IL-17. Silva-Santos and colleagues show that TCR signal strength within specific developmental windows is a major determinant of the generation of these γδ T cell subsets. The mouse thymus produces discrete γδ T cell subsets that make either interferon-γ (IFN-γ) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g +/− Cd3d +/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on γδ T cells. CD3DH mice had normal numbers and phenotypes of αβ thymocyte subsets, but impaired differentiation of fetal Vγ6 + (but not Vγ4 + ) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122 + NK1.1 + γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ + γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.

In recent years the role of diagnostic imaging by pelvic ultrasound in the diagnosis and staging of gynecological cancers has been growing exponentially. Evidence from recent prospective multicenter studies has demonstrated high accuracy for pre-operative locoregional ultrasound staging in gynecological cancers. Therefore, in many leading gynecologic oncology units, ultrasound is implemented next to pelvic MRI as the first-line imaging modality for gynecological cancer. The work herein is a consensus statement on the role of pre-operative imaging by ultrasound and other imaging modalities in gynecological cancer, following European Society guidelines.

Interleukin 17 (IL-17)-producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vγ6+ γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27- γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27- Vγ6+ γδ17 T-cell proliferation in vivo. Moreover, human Vδ1+ γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.

The aim of this article was to summarize the rationale for the pre-operative imaging work-up of histologically proven vulvar, vaginal, cervical, and endometrial cancers or clinically suspected tubo-ovarian carcinoma with a risk of malignancy >10%, as defined by the recent European Joint Guidelines developed under the umbrella of the European Society of Gynecological Oncology (ESGO) and listed in Table 2.1 The working groups preparing the ESGO guidelines have very carefully reviewed the available evidence to reduce unnecessary pre-operative investigations and speed up initiation of individualized treatment based on many factors, among them relevant imaging findings. According to patients, ultrasound was ranked the most preferred imaging method, while whole-body diffusion-weighted magnetic resonance imaging (MRI) was the least preferred.5 Although the indications for the different imaging methods at the pre-operative work-up are very carefully chosen, the risk of incidental findings cannot be fully avoided. [...]the joint current European Guidelines for the management of gynecological cancers have paid careful attention to guiding physicians to prompt and effective pre-operative work-ups without overburdening each patient with computed tomography (CT) or positron emission tomography (PET)-CT if only early disease is suspected.

Background As Parkinson’s disease (PD) progresses, patients experience difficulties with gait and balance, requiring assistive devices to ensure fall prevention and safety. Despite the advantages provided by these aids, many people with PD do not adhere to their use. Objective This study aims to explore the barriers to using assistive devices among people with PD and identify strategies to improve their adherence. Methods We used a qualitative, exploratory, and descriptive research design. Individual semi-structured interviews were conducted from October 2021 to July 2022, with participants selected through convenience sampling. Thematic analysis was performed to analyze data. Results Nineteen participants were interviewed, with the majority being male (63.2%) and a mean age of 72.3. This research identified several barriers to using assistive devices that were grouped under six broad themes and 14 subthemes. These themes included disease symptoms, physical limitations associated with holding the device, stigma, symbolism of the device, level of involvement of health professionals, and environmental factors. Concerning the strategies to improve adherence, they were grouped into themes that reflect different priority settings in the health sector. At the macro level, participants emphasized the significance of community education and intergenerational contact. At the meso level, participants highlighted the need for support groups, as well as prescription and training provided by health professionals. Finally, at the micro level, participants emphasized the importance of tailored care and shared decision-making. Conclusion This study’s findings offer insights on barriers and strategies reported by people with PD, improving assistive device utilization.

Regardless of the benefits of fall prevention programs, people with Parkinson’s disease (PD) will still fall. Therefore, it is crucial to explore novel therapeutic approaches that are well-accepted and effective for addressing fall risk and the fear of falls among this population. The present study aims to assess the feasibility of the Landing Wise program as a therapeutic intervention for reducing the fear of falling in people with PD. A mixed-methods study will be conducted using convenience sampling to recruit 20 people with PD with a moderate concern of falling from a Parkinson’s Patients Association. In addition to usual care, participants will attend 2 days per week, 90 min group sessions for 8 weeks. The intervention combines group cognitive behavioral intervention with the training of safe landing strategies. Feasibility will be assessed by six key domains (recruitment strategy and rates, enrollment, retention, acceptability, reasons for decline/withdrawal, and adverse events). Quantitative data will be analyzed using descriptive statistics to characterize the sample, followed by inferential statistics to evaluate differences in the Short Falls Efficacy Scale-International Scale, Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Timed Up Go, 6-Minutes Walking Distance, and fall frequency and severity scores between baseline and final assessment. Qualitative data will be analyzed using an inductive thematic analysis process. There is a growing interest in developing new effective therapeutic approaches for people with PD. If proven program feasibility, this study precedes a randomized controlled trial to establish the effectiveness of the Landing Wise program.

Interleukin 17 (IL-17)-producing gamma delta T cells (gamma delta 17T cells) have been recently found to promote tumor growth and metastasis formation. How such gamma delta 17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing gamma delta 17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27(-) V gamma 6(+) gamma delta 17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27(-) gamma delta 17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27(-)- gamma y6(+)gamma delta 117 T-cell proliferation in vivo. Moreover, human delta 5 (+)gamma delta 5 T cells, which contain most gamma delta 51 7T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS gamma delta 177 T-cell axis in the tumor microenvironment.

Pelvic floor dysfunction (PFD) is common to be associated with pregnancy and birth. To date, no research has been done to understand whether the perineal massage and warm compresses technique has an impact on pelvic floor dysfunction. To assess the impact of perineal massage and warm compresses technique during the second stage of labor in pelvic floor dysfunction at 3 and 6 months postpartum. Of the 800 women recruited to randomised controlled trial to prevent perineal trauma, 496 were included in the study, with 242 (48.8%) assigned to the Perineal Massage and Warm Compresses (PeMWaC) group and 254 (51.2%) to the control group (hands-on). Used the Pelvic Floor Distress Inventory-20 (PFDI-20). The questionnaire is divided into three subscales: Urinary (UDI), Colorectal-Anal (CRADI), and Pelvic Organ Prolapse Distress Inventory (POPDI). The PeMWaC group had a significantly higher frequency of intact perineum ( p  < 0.001) and low-severity vaginal tears (tears without any other degree of perineal trauma) ( p  = 0.031) compared to the control group, while the control group had significantly more patients who suffered high-severity vaginal/perineal trauma (second degree perineal tears) ( p  = 0.031) and patients without spontaneous perineal trauma or vaginal tears who underwent episiotomy ( p  < 0.001). In addition, at 3 months postpartum, women in the control group had a higher Urinary Distress Inventory (UDI) score and global score, compared to the PeMWaC group, and after controlling for confounding variables, the perineal massage and warm compresses technique was associated with lower UDI scores at 3 months postpartum compared to control group. At 6 months postpartum, there were no differences in the UDI or global scores, indicating general recovery from perineal trauma. In addition to reducing perineal trauma during birth, the perineal massage and warm compresses technique was associated with a lower prevalence of early PFD symptoms, mainly urinary distress, at 3 months. Trial registration http://www.ClinicalTrials.gov NCT05854888, retrospectively registered.