Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.     

3D Bioprinting of Human Adipose-Derived Stem Cells and Their Tenogenic Differentiation in Clinical-Grade Medium

Defining the best combination of cells and biomaterials is a key challenge for the development of tendon tissue engineering (TE) strategies. Adipose-derived stem cells (ASCs) are ideal candidates for this purpose. In addition, controlled cell-based products adherent to good manufacturing practice (GMP) are required for their clinical scale-up. With this aim, in this study, ASC 3D bioprinting and GMP-compliant tenogenic differentiation were investigated. In detail, primary human ASCs were embedded within a nanofibrillar-cellulose/alginate bioink and 3D-bioprinted into multi-layered square-grid matrices. Bioink viscoelastic properties and scaffold ultrastructural morphology were analyzed by rheology and scanning electron microscopy (SEM). The optimal cell concentration for printing among 3, 6 and 9 × 10⁶ ASC/mL was evaluated in terms of cell viability. ASC morphology was characterized by SEM and F-actin immunostaining. Tenogenic differentiation ability was then evaluated in terms of cell viability, morphology and expression of scleraxis and collagen type III by biochemical induction using BMP-12, TGF-β3, CTGF and ascorbic acid supplementation (TENO). Pro-inflammatory cytokine release was also assessed. Bioprinted ASCs showed high viability and survival and exhibited a tenocyte-like phenotype after biochemical induction, with no inflammatory response to the bioink. In conclusion, we report a first proof of concept for the clinical scale-up of ASC 3D bioprinting for tendon TE.     

The Perceptual Quality of the Oculus Rift for Immersive Virtual Reality

The recent release of the Oculus Rift, originally developed for entertainment applications, has reignited the interest of researchers and clinicians toward the use of head-mounted-displays in basic behavioral research and physical and psychological rehabilitation. However, careful evaluation of the Oculus Rift is necessary to determine whether it can be effectively used in these novel applications. In this article we address two issues concerning the perceptual quality of the Oculus Rift. (a) Is the Oculus able to generate an acceptable degree of immersivity? In particular, is it possible to elicit the sensation of presence via the virtual stimuli rendered by the device? (b) Does the Virtual Reality experienced through the Oculus Rift induce physical discomfort? To answer these questions, we employed four virtual scenarios in three separate experiments and evaluated performance with objective and subjective outcomes. In Experiment 1 we monitored observers’ heart rate and asked them to rate their Virtual Reality experience via a custom questionnaire. In Experiment 2 we monitored observers’ head movements in reaction to virtual obstacles and asked them to fill out the Simulator Sickness Questionnaire (Kennedy et al., 1993) both before and after experiencing Virtual Reality. In Experiment 3 we compared the Oculus Rift against two other low-cost devices used in immersive Virtual Reality: the Google cardboard and a standard 3DTV monitor. Observers’ heart rate increased during exposure to Virtual Reality, and they subjectively reported the experience to be immersive and realistic. We found a strong relationship between observers’ fear of heights and vertigo experienced during one of the virtual scenarios involving heights, suggesting that observers felt a strong sensation of presence within the virtual worlds. Subjects reacted to virtual obstacles by moving to avoid them, suggesting that the obstacles were perceived as real threats. Observers did not experience simulator sickness when the exposure to Virtual Reality was short and did not induce excessive amounts of vection. Compared to the other devices the Oculus Rift elicited a greater degree of immersivity. Thus our investigation suggests that the Oculus Rift head-mounted-display is a potentially powerful tool for a wide array of basic research and clinical applications.     

Tetrazine‐Responsive Self‐immolative Linkers

Molecules that undergo activation or modulation following the addition of benign external small‐molecule chemical stimuli have numerous applications. Here, we report the highly efficient “decaging” of a variety of moieties by activation of a “self‐immolative” linker, by application of water‐soluble and stable tetrazine, including the controlled delivery of doxorubicin in a cellular context.     

Treating Prostate Cancer by Antibody–Drug Conjugates

Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP–ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called “antibody–drug conjugates” (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells’ surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.     

In-plane behavior of perforated brick masonry walls

This paper reports the results of experimental and theoretical research conducted on perforated brick masonry walls under in-plane loading. The walls?? structural behavior depends strongly on their specific features, e.g. geometry, mechanical properties of the masonry material, brick arrangement and loading conditions. The experimental program was designed to study the incidence of brick arrangement in the spandrels and piers, and of the acting vertical load on the failure mode and load-bearing capacity of the walls. Six specimens of brick masonry wall with a central opening were submitted to a constant vertical load and a monotonic horizontal force that was gradually increased until the kinematic mechanism condition was reached. The object of the theoretical research was to develop a simplified analytical model for describing the kinematic mechanism of the walls. The results of the experiments indicate that brick arrangement strongly influences the failure mode and load-bearing capacity of the walls. Proper a priori assessment of the failure mode of walls becomes fundamental to an accurate evaluation of their load-bearing capacity using the proposed model.