The Premetastatic Lymph Node Niche in Gynecologic Cancer.

It has been suggested that a primary tumor can "prepare" the draining of lymph nodes to "better accommodate" future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.

Sustainable Earthquake Resilience with the Versatile Shape Memory Alloy (SMA)-Based Superelasticity-Assisted Slider.

Earthquakes threaten humanity globally in complex ways that mainly include various socioeconomic consequences of life and property losses. Resilience against seismic risks is of high importance in the modern world and needs to be sustainable. Sustainable earthquake resilience (SER) from the perspective of structural engineering means equipping the built environment with appropriate aseismic systems. Shape memory alloys (SMAs) are a class of advanced materials well suited for fulfilling the SER demand of the built environment. This article explores how this capability can be realized by the innovative SMA-based superelasticity-assisted slider (SSS), recently proposed for next-generation seismic protection of structures. The versatility of SSS is first discussed as a critical advantage for an effective SER. Alternative configurations and implementation styles of the system are presented, and other advantageous features of this high-tech isolation system (IS) are studied. Results of shaking table experiments, focused on investigating the expected usefulness of SSS for seismic protection in hospitals and conducted at the structural earthquake engineering laboratory of the University of Bonab, are then reported. SSS is compared with currently used ISs, and it is shown that SSS provides the required SER for the built environments and outperforms other ISs by benefitting from the pioneered utilization of SMAs in a novel approach.

Low-intensity pulsed ultrasound increases neurotrophic factors secretion and suppresses inflammation inin vitromodels of peripheral neuropathies.

Objective. In this study, we aimed to verify the beneficial effects of low-intensity pulsed ultrasound (LIPUS) stimulation on two cell types: H2O2-treated RSC96 Schwann cells and THP-1 macrophages, used to model neuropathic inflammation.Approach. Using a set-up guaranteeing a fine control of the ultrasound dose at the target, different frequencies (38 kHz, 1 MHz, 5 MHz) and different intensities (20, 100, 500 mW cm-2) were screened to find the most effective experimental conditions for triggering beneficial effects on metabolic activity and release of neurotrophic cytokines (ß-nerve growth factor, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor) of RSC96 cells. The combination of parameters resulting the optimal one was applied to evaluate anti-inflammatory effects in terms of reactive oxygen species (ROS) and tumor necrosis factor-α(TNF-α) production, also investigating a possible anti-oxidant activity and mechanotransduction pathway for the anti-inflammatory process. The same optimal combination of parameters was then applied to THP-1 cells, differentiated into M1 and M2 phenotypes, to assess the effect on the expression and release of pro-inflammatory markers (TNF-α, interleukin (IL)-1ß, IL-6, IL-8) and anti-inflammatory ones (IL-10 and CD206).Main results.5 MHz and 500 mW cm-2were found as the optimal stimulation parameters on RSC96 cells. Such parameters were also found to suppress ROS and TNF-αin the same cell line, thus highlighting a possible anti-inflammatory effect, involving the NF-kB pathway. An anti-oxidant effect induced by LIPUS was also observed. Finally, the same LIPUS parameters did not induce any differentiation towards the M1 phenotype of THP-1 cells, whereas they decreased TNF-αand IL-8 gene expression, reduced IL-8 cytokine release and increased IL-10 cytokine release in M1-polarized THP-1 cells.Significance.This study represents the first step towards the use of precisely controlled LIPUS for the treatment of peripheral neuropathies.

Adverse clinical events during the first 24 h of bedrest following cardiac electronic device implantation: a prospective observational study.

AIMS: To describe the incidence and impact of adverse clinical events (ACEs) during first 24 h of bedrest of patients after cardiac implantable electronic device (CIED) implantation. METHODS AND RESULTS: We conducted a prospective observational study of patients aged over 18 years undergoing elective placement of permanent bicameral pacemaker (PM), cardiac resynchronization therapy (CRT) PM, CRT defibrillator, or implantable cardioverter-defibrillator. Patients were maintained on bedrest post-operatively for 24 h and delirium, post-operative urinary retention, severe post-operative pain, pressure ulcer, and sleep disturbance were recorded using standardized assessments. Of 90 patients, 66 (73.3%) were male and average age was 76 ± 10 years. The median time to first mobilization was 23 (21-24) h. The adverse clinical events occurred in 48/90, with severe pain (38/90), sleep disturbance (12/90), delirium (9/90), and urinary retention requiring urinary catheterization (8/90) most frequent. Patients receiving implantable cardioverter-defibrillator or CRT defibrillator experienced ACEs significantly more frequently than those receiving PM. Adverse clinical event was associated with prolonged hospital stay [odds ratio (OR) 2.5; 95% confidence interval (CI) 1.16-6.17]. Patients with delirium were more dependent for daily living activities on admission (OR 8.0; 95% CI 1.55-41.3). CONCLUSION: Adverse clinical events frequently occur post-insertion of a CIED and impact patient clinical course and experience. The progressive increase in ageing and frailty of CIED implant candidates requires special nursing attention to improve patients' satisfaction and to prevent increased healthcare resource use.

Needle-free connectors to prevent central venous catheter occlusion at a tertiary cardiac center: A prospective before and after intervention study.

OBJECTIVES: To evaluate the effectiveness of needle-free connectors to maintain Central Venous Catheter-CVC patency. BACKGROUND: Loss of patency is a common complication associated with CVC. For patients, this can be stressful and painful, and can result in a delay in infusion therapy. Pressure-activated anti-reflux needle-free connectors are one of the most modern devices; however, no studies have compared this connector with the open-system three-way stopcock in terms of the incidence of CVC occlusion. METHODS: This study is a prospective before and after intervention study. From March to August 2018, an observation phase was conducted with the three-way stopcock as the standard central venous catheter hub and closure system (phase 1). After implementation of needle-free connectors (phase 2), post-intervention observations were made from September 2019 to January 2020 (phase 3). RESULTS: Of 199 CVCs analyzed, 41.2% (40/97) occluded in at least one lumen in the first phase, and 13.7% (14/102) occluded after introducing the technological device, absolute risk reduction 27.5% (95% confidence interval 15.6%-39.4%). The lumens supported by needle-free connectors showed a higher probability of maintaining patency compared with three-way stopcocks. No differences were observed in the rate of infection. CONCLUSIONS: Pressure-activated anti-reflux needle-free connectors are effective and safe devices suitable for the management of vascular access in cardiac patient care. Staff training, even on apparently simple devices, is essential to avoid the risk of infection.