Vulnerable narcissism and body image centrality in cosplay practice: A sequential mediation model

In recent years, the cosplay practice has become a ubiquitous activity, representing a pivotal way to get in touch with the so-called geek culture and its media content (such as videogames, comics, manga). Cosplaying appeared related to narcissistic fragility which in turn is strictly linked to social appearance anxiety and self-objectification experiences. However, despite the body image centrality in cosplay practice, no studies evaluated cosplayers’ narcissistic vulnerability in association with these body imagerelated issues. A total of 926 young adults (73.2% female; 47.3% cosplayer; mean age=25.3 years) participated in the study. Results confirmed the direct and indirect effect of narcissistic vulnerability on social appearance anxiety (via body surveillance and body shame) among both cosplayers and noncosplayers. Overall, narcissistically vulnerable individuals, regardless of their involvement in cosplay practice, seem to experience higher body surveillance and body shame, which in turn might promote social appearance anxiety

Synthesis of “All-Cis” Trihydroxypiperidines from a Carbohydrate-Derived Ketone: Hints for the Design of New β-Gal and GCase Inhibitors

Pharmacological chaperones (PCs) are small compounds able to rescue the activity of mutated lysosomal enzymes when used at subinhibitory concentrations. Nitrogen-containing glycomimetics such as aza- or iminosugars are known to behave as PCs for lysosomal storage disorders (LSDs). As part of our research into lysosomal sphingolipidoses inhibitors and looking in particular for new β-galactosidase inhibitors, we report the synthesis of a series of alkylated azasugars with a relative “all-cis” configuration at the hydroxy/amine-substituted stereocenters. The novel compounds were synthesized from a common carbohydrate-derived piperidinone intermediate 8, through reductive amination or alkylation of the derived alcohol. In addition, the reaction of ketone 8 with several lithium acetylides allowed the stereoselective synthesis of new azasugars alkylated at C-3. The activity of the new compounds towards lysosomal β-galactosidase was negligible, showing that the presence of an alkyl chain in this position is detrimental to inhibitory activity. Interestingly, 9, 10, and 12 behave as good inhibitors of lysosomal β-glucosidase (GCase) (IC50 = 12, 6.4, and 60 µM, respectively). When tested on cell lines bearing the Gaucher mutation, they did not impart any enzyme rescue. However, altogether, the data included in this work give interesting hints for the design of novel inhibitors.España e Ministerio de Economía y Competitividad (CTQ2016-77270-R

A psychological intervention based on cognitive-behavioural therapy reduces psychopathological symptoms that indirectly influence the heart rate via cortisol in hypertensive patients: Preliminary results of a pilot study

ObjectiveThis study aimed at assessing the effectiveness of cognitive-behavioural therapy (CBT) integrated with psychoeducation in a group of hypertensive patients with clinically significant psychopathological symptoms.MethodsOne hundred hypertensive patients completed the Symptom Checklist-90-Revised. Of them, 17 scored above the clinical range (cut-off = 0.75) on the Global Severity Index and were included in the study. Psychological distress was assessed again after the intervention (T1) and 6 months after the end of treatment (T2). In addition, the cortisol dosage and the heart rate (HR) measurement were collected at both T0 and T2. Then, mediation analyses were carried out to calculate whether psychopathological distress might predict HR through elevated serum cortisol levels, at both T0 and T2.ResultsThe psychological intervention (CBT integrated with psychoeducation) reduced most of the psychopathological symptoms (anxiety, depression, somatisations, obsessions and compulsions, hostility, interpersonal sensitivity and paranoid ideation) but not cortisol dosage and HR measurement. However, psychological distress indirectly predicted HR via cortisol at T0 but not at T2.ConclusionThese results suggest and encourage the replicability of data in larger sample sizes and the comparison with a control group. Nevertheless, these results highlight a need for a multidimensional assessment of disorders affecting the mental and physical spheres of patients to support their overall well-being

Piperidine Azasugars Bearing Lipophilic Chains: Stereoselective Synthesis and Biological Activity as Inhibitors of Glucocerebrosidase (GCase)

We report a straightforward synthetic strategy for the preparation of trihydroxypiperidine azasugars decorated with lipophilic chains at both the nitrogen and the adjacent carbon as potential inhibitors of the lysosomal enzyme glucocerebrosidase (GCase), which is involved in Gaucher disease. The procedure relies on the preparation of C-erythrosyl N-alkylated nitrones 10 through reaction of aldehyde 8 and primary amines 13 followed by oxidation of the imines formed in situ with the methyltrioxorhenium catalyst and urea hydrogen peroxide. The addition of octylMgBr to nitrone 10e provided access to both epimeric hydroxylamines 21 and 22 with opposite configuration at the newly created stereocenter in a stereodivergent and completely stereoselective way, depending on the absence or presence of BF3·Et2O. Final reductive amination and acetonide deprotection provided compounds 14 and 15 from low-cost d-mannose in remarkable 43 and 32% overall yields, respectively, over eight steps. The C-2 R-configured bis-alkylated trihydroxypiperidine 15 was the best ligand for GCase (IC50 = 15 μM), in agreement with MD simulations that allowed us to identify the chair conformation corresponding to the best binding affinity.MINECO (CTQ2016- 77270-R) and (PID2019-104090RB-100

Light-triggered control of Glucocerebrosidase inhibitors: towards photoswitchable pharmacological Chaperones

Piperidine-based photoswitchable derivatives have been developed as putative pharmacological chaperones for glucocerebrosidase (GCase), the defective enzyme in Gaucher disease (GD). The structure-activity study revealed that both the iminosugar and the light-sensitive azobenzene are essential features to exert inhibitory activity towards human GCase and a system with the correct inhibition trend (IC50 of the light-activated form lower than IC50 of the dark form) was identified. Kinetic analyses showed that all compounds are non-competitive inhibitors (mixed or pure) of GCase and the enzyme allosteric site involved in the interaction was identified by means of MD simulations. A moderate activity enhancement of mutant GCase assessed in GD patients' fibroblasts (ex vivo experiments) carrying the most common mutation was recorded. This promising observation paves the way for further studies to improve the benefit of the light-to-dark thermal conversion for chaperoning activity

Tumor targeting by monoclonal antibody functionalized magnetic nanoparticles

Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer therapy. Several magnetic nanoparticles (MNPs) were analyzed as potential tumor-targeted drug-loaded nanocarriers after functionalization with anti-Met oncogene (anti-Met/HGFR) monoclonal antibody (mAb) and doxorubicin (DOXO). Their cytocompatibility, stability, immunocompetence (immunoprecipitation), and their interactions with cancer cells in vitro (Perl's staining, confocal microscopy, cytotoxic assays: MTT, real time toxicity) and with tumors in vivo (Perl's staining) were evaluated. The simplest silica- and calcium-free mAb-loaded MNPs were the most cytocompatible, the most stable, and showed the best immunocompetence and specificity. These mAb-functionalized MNPs specifically interacted with the surface of Met/HGFR-positive cells, and not with Met/HGFR-negative cells; they were not internalized, but they discharged in the targeted cells DOXO, which reached the nucleus, exerting cytotoxicity. The presence of mAbs on DOXO-MNPs significantly increased their cytotoxicity on Met/HGFR-positive cells, while no such effect was detectable on Met/HGFR-negative cells. Bare MNPs were biocompatible in vivo; mAb presence on MNPs induced a better dispersion within the tumor mass when injected in situ in Met/HGFR-positive xenotumors in NOD/SCID-γnull mice. These MNPs may represent a new and promising carrier for in vivo targeted drug delivery, in which applied gradient and alternating magnetic fields can enhance targeting and induce hyperthermia respectively

Patient-specific Monte Carlo-based organ dose estimates in spiral CT via optical 3D body scanning and adaptation of a voxelized phantom dataset: proof-of-principle

: Objective. We present a method for personalized organ dose estimates obtained before the CT exam, via 3D optical body scanning and Monte Carlo (MC) simulations.Approach. A voxelized phantom is derived by adapting a reference phantom to the body size and shape measured with a portable 3D optical scanner, which returns the 3D silhouette of the patient. This was used as an external rigid envelope for incorporating a tailored version of the internal body anatomy derived from a phantom dataset (National Cancer Institute, NIH, USA) matched for gender, age, weight, and height. The proof-of-principle was conducted on adult head phantoms. The Geant4 MC code provided estimates of the organ doses from 3D absorbed dose maps in voxelized body phantom.Main results. We applied this approach for head CT scanning using an anthropomorphic voxelized head phantom derived from 3D optical scans of mannequins. We compared the estimates of head organ doses with those provided by the NCICT3.0 software (NCI, NIH, USA). Head organ doses differed up to 38% using the proposed personalized estimate and MC code, with respect to corresponding estimates calculated for the standard (non-personalized) reference head phantom. Preliminary application of the MC code to chest CT scans is shown. Real-time pre-exam personalized CT dosimetry is envisaged with adoption of a GPU-based fast MC code.Significance. The developed procedure for personalized organ dose estimates before the CT exam, introduces a new approach for realistic description of size and shape of patients via voxelized phantoms specific for each patient