A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Virtual and Augmented Reality in Post-stroke Rehabilitation: A Narrative Review.

Virtual reality (VR) and augmented reality (AR) are noble adjunctive technologies currently being studied for the neuro-rehabilitation of post-stroke patients, potentially enhancing conventional therapy. We explored the literature to find if VR/AR improves neuroplasticity in stroke rehabilitation for a better quality of life. This modality can lay the foundation for telerehabilitation services in remote areas. We analyzed four databases, namely Cochrane Library, PubMed, Google Scholar, and Science Direct, by searching the following keywords: ("Stroke Rehabilitation" [Majr]) AND ("Augmented Reality" [Majr]), Virtual Augmented Reality in Stroke Rehabilitation. All the available open articles were reviewed and outlined. The studies conclude that VR/AR can help in early rehabilitation and yield better results in post-stroke patients in adjunct to conventional therapy. However, due to the limited research on this subject, we cannot conclude that this information is absolute. Moreover, VR/AR was seldom customized according to the needs of stroke survivors, which would have given us the full extent of its application. Around the world, stroke survivors are being studied to verify the accessibility and practicality of these innovative technologies. Observations conclude that further exploration of the extent of the implementations and efficacy of VR and AR, combined with conventional rehabilitation, is fundamental.

An analysis of research biopsy core variability from over 5000 prospectively collected core samples.

Factors correlated with biopsy tissue adequacy and the prevalence of within-biopsy variability were evaluated. Totally, 1149 research biopsies were performed on 686 patients from which 5090 cores were assessed. Biopsy cores were reviewed for malignant percentage (estimated percentage of cells in the core that were malignant) and malignant area (estimated area occupied by malignant cells). Linear mixed models and generalized linear mixed models were used for the analysis. A total of 641 (55.8%) biopsies contained a core with <10% malignant percentage (inadequate core). The chance of an inadequate core was not influenced by core order, though the malignant area decreased with each consecutive core (p < 0.001). Younger age, bone biopsy location, appendiceal tumor pathology, and responding/stable disease prior to biopsy increased the odds of a biopsy containing zero adequate cores. Within-biopsy variability in core adequacy is prevalent and suggests the need for histological tumor quality assessment of each core in order to optimize translational analyses.

Stability of blood analytes after storage in BD SST tubes for 12 mo.

OBJECTIVES: We studied the stability of 33 analytes related to clinical chemistry, bone, and vitamin metabolism, after storage in serum separator tubes (SST). DESIGN AND METHODS: Blood was collected from 6 subjects using SST tubes. Some serum remained in the tube in contact with the barrier gel and was stored at -80 degrees C for 12 mo. RESULTS: Clinically significant changes occurred only in 1,25-dihydroxyvitamin D and retinol-binding protein. CONCLUSIONS: Freezing SST tubes before sample analysis is a viable option for some analytes.

Do blood-borne calcifying nanoparticles self-propagate?

The nanotechnology industry is currently in the process of producing new nanoparticles. The biological activity of nanoparticles including adverse as well as beneficial effects tends to increase as their size decreases. The smaller the particles are, the greater their bioactivity and toxicity. Thus, one can easily conjecture the impact ofa nanoparticle if it could also self-replicate. This in vitro study reveals the self-propagating ability of unique calcifying nanoparticles (CNP) that can be as small as 50 nm in size and found in blood, blood products, and calcified soft tissues. Although specific detection techniques, morphological characteristics and biomineralizing properties of CNP are well established, their genomic information and self-propagating capability have always been challenged. The objective of this study is to document the propagation of CNP under physiological conditions, using inverted light microscopy (LM) and the Biostation IM time-lapse imaging system. Their detailed morphological structure was examined using scanning (SEM) and transmission (TEM) electron microscopy. This present study, in conjunction with previous findings of metabolic activity, antibiotic sensitivity, antibody specificity, morphological aspects and infectivity, validates CNP as self-replicators. Therefore these sterile-filterable, blood-borne nanoparticles should be of concern to the nanomedicine industry.

Association between Randall's plaque and calcifying nanoparticles.

OBJECTIVES: Randall initially described calcified subepithelial papillary plaques, which he hypothesized as nidi for urinary calculi. The discovery of calcifying nanoparticles (CNP), also referred to as nanobacteria, in calcified soft tissues has raised another hypothesis about their possible involvement in urinary stone formation. This research is the first attempt to investigate the potential association of these two hypotheses. METHODS: We collected renal papilla and blood samples from 17 human patients who had undergone laparoscopic nephrectomy. Immunohistochemical staining (IHS) was applied using monoclonal antibody (mAb) against CNP. Homogenized papillary tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were performed on papillary samples. Serum samples were tested for CNP antigen and antibody with enzyme-linked immunosorbent assay (ELISA). RESULTS: Randall's plaques (RP) were visible on gross inspection in 11 out of 17 samples. IHS was positive for CNP antigen in 8 of the visually positive samples, but in only 1 of the remaining samples. SEM revealed spherical apatite-formations in 14 samples confirmed by EDS analysis. In cultures, all serum samples and 13 tissue homogenates grew CNP. In ELISA, 14 samples were positive for CNP-antigen and 11 samples were positive for CNP-antibody. CONCLUSION: There was evidence of a link between detection of CNP and presence of RP. Although causality was not demonstrated, these results suggest that further studies with negative control samples should be made to explore the etiology of RP formation, thus leading to a better understanding of the pathogenesis of stone formation.

Optical sensor based on fluorescent quenching and pulsed blue LED excitation for long-term monitoring of dissolved oxygen in NASA space bioreactors.

There is a need to monitor the concentration of dissolved oxygen (DO) present in the culture medium for NASA's space cell biology experiments, as well as in earth-based cell cultures. Continuous measurement of DO concentration in the cell culture medium in perfused bioreactors requires that the oxygen sensor provide adequate sensitivity and low toxicity to the cells, as well as maintain calibration over several weeks. Although there are a number of sensors for dissolved oxygen on the market and under development elsewhere, very few meet these stringent conditions. An in-house optical oxygen sensor (HOXY) based on dynamic fluorescent quenching of Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) chloride and a pulsed blue LED light source was developed in our laboratory to address these requirements. The sensing element consisted of the fluorescent dye embedded in a silicone matrix and coated onto a glass capillary. Photobleaching was minimized by a pulsed LED light source. The total noise in the sensor output is 2% and the sensor dynamic range is 0 to 200 mm Hg. The resolution of the sensor is 0.1 mm Hg at 50 mm Hg, and 0.25 mm Hg at 130 mm Hg, while the accuracy is 5%. The LED-based oxygen sensor exhibited stable performance and low drift, making it compatible for space-flight bioreactor systems.

Continuous glucose monitoring and control in a rotating wall perfused bioreactor.

A glucose control system consisting of a single in-line glucose sensor, concentrated glucose solution, and computer hardware and software were developed. The system was applied to continuously control glucose concentrations of a perfusion medium in a rotating wall perfused vessel (RWPV) bioreactor culturing BHK-21 cells. The custom-made glucose sensor was based on a hydrogen peroxide electrode. The sensor continuously and accurately measured the glucose concentration of GTSF-2 medium in the RWPV bioreactor during cell culture. Three sets of two-point calibrations were applied to the glucose sensor during the 55-day cell culture. The system first controlled the glucose concentration in perfusing medium between 4.2 and 5.6 mM for 36 days and then at different glucose levels for 19 days. A stock solution with a high glucose concentration (266 mM) was used as the glucose injection solution. The standard error of prediction (SEP) for glucose measurement by the sensor, compared to measurement by the Beckman glucose analyzer, was +/-0.4 mM for 55 days.