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Background Virtual Reality (VR) is used as an effective tool for distraction and as an adjunct for pain management. This study was conducted to compare VR to standard iPad use after surgery and examine its effect on pain score and opioid consumption.Methods This was a randomized controlled study, with stratification by surgery type, age group (7-12yo, 13-18yo) and gender. Pain and anxiety were assessed with validated scales (STAI, FACES, VAS, FLACC) and outcomes were compared between each group.Results 50 of the 106 enrolled patients used the VR device. After adjusting for age, gender, and STAI, patients had a decreased FLACC score while using the VR device compared to the iPad group (odds ratio 2.95, P= .021). The younger patients were found to have lower FLACC scores while using the VR device (odds ratio 1.15, p=0.044); this finding was most significant when patients used the VR device for 20-30 minutes (odds ratio 1.67, P= .0003). Additionally, after adjusting for treatment group, gender, and STAI, the younger patients had higher odds of withdrawal or exclusion from the study (odds ratio 1.18, P= .021). No significant difference in opioid consumption between the groups was found.Discussion Virtual reality was well tolerated and more effective in decreasing pain during the immediate postoperative period than iPad use. Despite a slightly higher withdrawal rate, younger patients benefited more from the intervention.

ABSTRACTWhat was and what will remain of the Tokyo 2020/2021 Olympic and Paralympic Games? This special issue brings together assessments from different perspectives regarding diverse aspects of the impact and legacy of Tokyo’s second Summer Olympics. It is safe to say that Tokyo 2020/2021, as the COVID-19 games, did not fully achieve what the Japanese organizers had hoped it would. On the contrary, the Olympic dream of 2020 was postponed and met quite substantial opposition. This introduction discusses the main findings of the contributions and places them in the larger context. The focus is on four aspects of Tokyo 2020/2021: 1) the Olympics as a political project of the conservative establishment and former Prime Minister Abe Shinzō; 2) critical perspectives on the Olympics as a mega event; 3) social movements and protests against the Olympics; 4) impact of the Olympics on technological innovation and city infrastructure.

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.

Following progress in modern medicine, advances have been made in diagnosis and treatment tools. Multifunctional nanomaterials that combine therapeutic and diagnostic functions in a single nanostructured complex are known as ‘theranostics’. To obtain a theranostic, a single particle, usually a nanoparticle, is manufactured to contain a therapeutic element (such as a drug) coupled with an imaging element. There are many kinds of nanoparticles available today that can be used to obtain theranostics, such as liposomes, cyclodextrin, conjugates and complexes, dendrimers, vesicles, micelles, core-shell particles, microbubbles, and carbon nanotubes. Because these materials interact with and should have effects on biological systems, their use may overcome health challenges. Considering the novelty and importance of this subject, this review aims to present general information about theranostics and discuss the safety and presumable toxicity of these constructs. In addition, we describe the methodologies that can be used to assess the safety of theranostics. This review is based on a literature search on theranostics, using the Web of Science, PubMed and Science Direct as the main sources of information. The period of publication was not delimited due to the scarcity of information and publications on this topic. Although many promising theranostic systems have been investigated and may revolutionise therapy, when designing new tools, researchers need to find alternatives to minimise their toxicity. The study of the toxicology and biocompatibility of theranostics needs to be continued, including clinical studies, with the aim of benefitting many patients in the future.

The treatment of lymphatic anomaly, a rare devastating disease spectrum of mostly unknown etiologies, depends on the patient manifestations1. Identifying the causal genes will allow for developing affordable therapies in keeping with precision medicine implementation2. Here we identified a recurrent gain-of-function ARAFmutation (c.640T>C:p.S214P) in a 12-year-old boy with advanced anomalous lymphatic disease unresponsive to conventional sirolimus therapy and in another, unrelated, adult patient. The mutation led to loss of a conserved phosphorylation site. Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions, which were rescued using the MEK inhibitor trametinib. The functional relevance of the mutation was also validated by recreating a lymphatic phenotype in a zebrafish model, with rescue of the anomalous phenotype using a MEK inhibitor. Subsequent therapy of the lead proband with a MEK inhibitor led to dramatic clinical improvement, with remodeling of the patient’s lymphatic system with resolution of the lymphatic edema, marked improvement in his pulmonary function tests, cessation of supplemental oxygen requirements and near normalization of daily activities. Our results provide a representative demonstration of how knowledge of genetic classification and mechanistic understanding guides biologically based medical treatments, which in our instance was life-saving.

Combining zebrafish and mouse genetics, Cantù et al. identified a conserved β-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development.

In this work, we report the synthesis of a peptide analogue of the KTTKS, termed Ac- Wahx-KTTKS and evaluate its cytotoxicity and role in biosynthesis of collagen for future application in skin aging. The peptide was obtained with purity higher than 97.5%. In the cytotoxicity assay, we observed non-toxic effects for Ac-WAhx-KTTKS at concentrations below 600 µM for HaCaT and 500 µM for HepG2 cells, respectively. After 24 and 48 h it was possible to observe significant changes in collagen synthesis in the groups treated with various concentrations of the peptide. In conclusion, the Ac-Wahx- KTTKS peptide increased collagen synthesis in fibroblasts by 80% and it is a promising candidate for improving skin aging.

Nanocrystals of ZnO are currently attracting great interest as potential labels for biological applications, such as theranostic devices, due to their luminescent properties and low toxicity in vivo. It has been reported that doping with Mg2+ions could enhance the luminescence of ZnO quantum dots (QDs). In the present study Mg-doped ZnO QDs were synthesized by a hydrolysis and condensation reaction. Surface modification of the QDs was performed using oleic acid (OA) to hinder their aggregation and to provide them colloidal stability in non-polar environments. Mg2+ions could be incorporated into the ZnO wurtzite lattice owing to the very close values of the Mg2+and Zn2+ion radii. However, the dopant ions strongly influenced the growth and final size of ZnO nanocrystals, as evidenced by time-resolved synchrotron SAXS measurements. The presence of Mg prevented the aggregation of the primary nanoparticles. Doping with Mg2+ions widened the band gap of ZnO QDs and enhanced their visible luminescence. With increasing proportion of Mg2+ions, both the absorption and emission spectra experienced a blue shift. The luminescence went through a maximum for a 20 mol% nominal concentration of Mg2+ions in the reaction medium. The quantum yield (QY) of 20 mol% Mg-doped ZnO colloidal suspension (64%) was about 6 times higher than that of the ZnO suspension (10%). Mg-doped ZnO QDs capped by OA formed stable colloidal dispersions in chloroforme, with strong visible fluorescence (QY=38%), promising for biological imaging.