Effects of Tin on Enzyme Activity in Holothuria grisea (Echinodermata: Holothuroidea).

This study evaluated the effect of tin exposure on enzyme activity in the sea cucumber (Holothuria grisea Selenka, 1867). After exposure to 0 (control), 0.04, 0.08, or 0.12 mg L-1 tin, we tested the activities of total cholinesterase in longitudinal muscles, acid phosphatase in gonads and the respiratory tree, as well as alkaline phosphatase in the intestines during a 96-h bioassay. Regression analyses showed that all enzyme activities declined with increasing tin concentrations, except for acid phosphatase in the respiratory tree, which were similarly, inhibited at all tin concentrations. These results indicate that H. grisea is a potential bioindicator for seascape habitat monitoring programs, as its biochemical markers show sensitivity to trace elements that can indicate a rise in pollution levels.

The Internalized Stigma of Mental Illness: Cross-Cultural Adaptation and Psychometric Properties of the Portuguese Version of the ISMI Scale.

This study examined the psychometric properties of the Portuguese version of the ISMI scale in a sample of 253 adult psychiatric outpatients. The exploratory factor analysis replicated the five factor structure of the scale. The results revealed good internal consistency. Criterion-related validity supported the variability in response to stigma across clinical diagnoses. Thus, the Portuguese version of the ISMI scale can be considered appropriate to measure and differentiate between stigmatization experiences. Also, in order to design more focused approaches aimed to reduce the negative effects of internalized stigma, its use in institutional and in community-based mental health services is recommended.

Virtual reality exposure on nicotine craving.

Several forms of treatment for nicotine dependence that combine the classical smoking cessation strategies with new Virtual Reality (VR) exposure techniques to smoking-related cues are in development. In this line, the main goal of our study was to develop a virtual platform in order to induce cravings in smokers. Sixty undergraduate students were randomly assigned to two different virtual environments (high-arousal cues and low-arousal cues). Both environments were based on a three-room apartment with commercial music playing and virtual characters interacting in a social event. The assessment was carried out before and after exposure through psychophysiological activation and self-report data for craving and nicotine dependence levels. No statistical differences were observed between smokers and non-smokers in psychophysiological activation. As far as self-report data is concerned, smokers revealed a significant increase in craving after the VR exposure to high arousal environments. Overall results were in line with previous studies suggesting the use of virtual environments as a tool for the existing smoking cessation programs.

Fluorescent light-up acridine orange derivatives bind and stabilize KRAS-22RT G-quadruplex.

KRAS is often found mutated in lethal cancers and should be an important target for anticancer drug development. However, no effective inhibitor has been reported so far, prompting the scientific community to describe the RAS proteins as nearly "undruggable". Recent approaches developed to modulate KRAS protein expression comprises the targeting of G-quadruplex (G4) structures formed within the nuclease hypersensitive element of KRAS promoter region, by designing small and specific ligands to stabilize the tertiary fold and reduce gene expression. In this work, we report in vitro and in silico studies of novel acridine orange (AO) derivatives (C3-C8), developed as G4 stabilizing agents. The results show that the ligands bind with high affinity and stabilize KRAS22-RT G4 with modest specificity over duplex DNA. The most promising ligand C8 stabilizes the structure by ≈ 40 °C. Molecular docking using NMR-derived distance restraints reveal atomic details about the ligand structural features in the interaction with KRAS22-RT G4. In vitro studies with HeLa cells show that the ligands are cytotoxic with IC50 values between 0.9 µM and 5.7 µM. Moreover, the ligands tend to localize in the nucleus as shown by confocal fluorescence microscopy. Overall, these results show that the reported AO ligands display favourable properties as G4 ligands and this study provides structural detail for the development of lead KRAS G4 ligands.

Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA.

A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners.

Coalizäo carpal escafóide-trapézio sintomática: relato de caso / Symptomatic scaphotrapezius carpal coalition

Os autores descrevem caso de coalizäo carpal escafóide-trapézio sintomática. Este tipo de coalizÒo é raro e o tratamento cirúrgico com realizaçäo de artrodese triescafóide proporcionou diminuiçäo da amplitude articular com desaparecimento da dor.