Search

Background: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling. The aim of this study is to assess the effectiveness and implementation of using the GPRI in improving patient outcomes after genetic counselling and testing for an inherited cancer predisposition. Methods: The PersOnalising gEneTIc Counselling (POETIC) trial is a hybrid type 2 effectiveness-implementation trial using a randomised control trial to assess the effectiveness of the GPRI in improving patient empowerment (primary outcome), while also assessing implementation from the perspective of clinicians and the healthcare service. Patients referred for a cancer risk assessment to the conjoint clinical genetics service of two metropolitan hospitals in Victoria, Australia, who meet the eligibility criteria and consent to POETIC will be randomised to the usual care or intervention group. Those in the intervention group will complete the GPRI prior to their appointment with the screening results available for the clinicians’ use during the appointment. Appointment audio recordings, clinician reported information about the appointment, patient-reported outcome measures, and clinical data will be used to examine the effectiveness of using the GPRI. Appointment audio recordings, health economic information, and structured interviews will be used to examine the implementation of the GPRI. Discussion: The POETIC trial takes a pragmatic approach by deploying the GPRI as an intervention in the routine clinical practice of a cancer-specific clinical genetics service that is staffed by a multidisciplinary team of genetics and oncology clinicians. Therefore, the effectiveness and implementation evidence generated from this real-world health service setting aims to optimise the relevance of the outcomes of this trial to the practice of genetic counselling while enhancing the operationalisation of the screening tool in routine practice. Trial registration: Australian New Zealand Clinical Trials Registry registration number 12621001582842p. Date of registration: 19th November 2021.

Glyceline, a deep eutectic solvent comprising glycerol and choline chloride, is a green nonaqueous solvent with potential industrial applications. Molecular mechanisms of surfactant self-assembly in deep eutectic solvents are expected to differ from those in their constituent polar components and are not well understood. Here we report the observation of self-assembled SDS fractal dendrites with dimensions up to ∼mm in glyceline at SDS concentrations as low as cSDS ∼ 0.1 wt%. The prevalence of these dendritic fractal aggregates led to the formation of a gel phase at SDS concentrations above ≥1.9 wt% (the critical gelation concentration cCGC). The gel microscopic structure was visualised using polarised light microscopy (PLM); rheology measurements confirmed the formation of a colloidal gel, where the first normal stress difference was negative and the elastic modulus was dominant. Detailed nano-structural characterisation by small-angle neutron scattering (SANS) further confirmed the presence of fractal aggregates. Such SDS aggregation or gelation has not been observed in water at such low surfactant concentrations, whereas SDS has been reported to form lamellar aggregates in glycerol (a component of glyceline). We attribute the formation of the SDS fractal dendrites to the condensation of counterions (i.e. the choline ions) around the SDS aggregates - a diffusion-controlled process, leading to the aggregate morphology observed. These unprecedented results shed light on the molecular mechanisms of surfactant self-assembly in deep eutectic solvents, important to their application in industrial formulation.

The use of fluorescent nanocrystals (NCs) as probes for bioimaging applications has emerged as an advantageous alternative to conventional organic fluorescent dyes. Therefore their toxicological evaluation and intracellular delivery are currently a primary field of research. In this work, hydrophobic and highly fluorescent CdSe@ZnS NCs were encapsulated into the lipid bilayer of liposomes by the micelle-to-vesicle transition (MVT) method. The obtained aqueous NC-liposome suspensions preserved the spectroscopic characteristics of the native NCs. A systematic study of the in vitro toxicological effect on HeLa cells of these red emitting NC-liposomes was then carried out and compared to that of empty liposomes. By using liposomes of different phospholipid composition, we evaluated the effect of the lipid carrier on the cytotoxicity towards HeLa cells. Surprisingly, a cell proliferation and death study along with the MTT test on HeLa cells treated with NC-liposomes have shown that the toxic effects of NCs, at concentrations up to 20 nM, are negligible compared to those of the lipid carrier, especially when this is constituted by the cationic phospholipid DOTAP. In particular, obtained data suggest that DOTAP has a dose- and time-dependent toxic effect on HeLa cells. In contrast, the addition of PEG to the liposomes does not alter significantly the viability of the cells. In addition, the ability of NC-liposomes to penetrate the HeLa cells was assessed by fluorescence and confocal microscopy investigation. Captured images show that NC-liposomes are internalized into cells through the endocytic pathway, enter early endosomes and reach lysosomes in 1 h. Interestingly, red emitting NCs co-localized with endosomes and were positioned at the limiting membrane of the organelles. The overall results suggest that the fluorescent system as a whole, NCs and their carrier, should be considered for the development of fully safe biological applications of CdSe@ZnS NCs, and provide essential indications to define the optimal experimental conditions to use the proposed system as an optical probe for future in vivo experiments.

The aim of the present investigation was to evaluate the influence of liposome formulation on the ability of vesicles to penetrate a pathological mucus model obtained from COPD affected patients in order to assess the potential of such vesicles for the treatment of chronic respiratory diseases by inhalation. Therefore, Small Unilamellar Liposomes (PLAIN-LIPOSOMEs), Pluronic (R) F127-surface modified liposomes (PF-LIPOSOMEs) and PEG 2000PE-surface modified liposomes (PEG-LIPOSOMEs) were prepared using the micelle-to-vesicle transition (MVT) method and beclomethasone dipropionate (BDP) as model drug. The obtained liposomes showed diameters in the range of 40-65 nm, PDI values between 0.25 and 0.30 and surface electric charge essentially close to zero. The encapsulation efficiency was found to be dependent on the BDP/lipid ratio used and, furthermore, BDP-loaded liposomes were stable in size both at 37 degrees C and at 4 degrees C. All liposomes were not cytotoxic on H441 cell line as assessed by the MTT assay. The liposome uptake was evaluated through a cytofluorimetric assay that showed a non-significant reduction in the internalization of PEG-LIPOSOMEs as compared with PLAIN-LIPOSOMEs. The penetration studies of mucus from COPD patients showed that the PEG-LIPOSOMEs were the most mucus-penetrating vesicles after 27 h. In addition, PEG-and PF-LIPOSOMEs did not cause any effect on bronchoalveolar lavage fluid proteins after aerosol administration in the mouse. The results highlight that PEG-LIPOSOMEs show the most interesting features in terms of penetration through the pathologic sputum, uptake by airway epithelial cells and safety profile.

Background: It is not clear whether naltrexone is effective in reducing alcohol consumption among patients with clinically significant mood symptoms and whether naltrexone favorably interacts with antidepressant medications when they are co-prescribed. Methods: This study reflects a secondary analysis of the first 13 weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d in 627 alcohol dependent military veterans receiving Twelve Step Facilitation therapy at 20 VA Medical Centers. This study included patients with comorbid mood and anxiety disorders, providing they did not need treatment for these comorbid conditions at the time of study entry. Sixty patients developed sufficiently severe mood symptoms while on study medication that they required antidepressant treatment. This analysis evaluated whether the efficacy of naltrexone and placebo was influenced by the prescription of antidepressant medications to some study patients for their mood and anxiety symptoms. Results: In patients randomized to placebo (n = 209), prescription of antidepressants was associated with a significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs. lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving naltrexone (n = 418) was larger than the group assigned to placebo, there were no significant differences in drinking-related outcomes in the groups who did or did not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se = 1.69, p = 0.47). Among the group of patients receiving antidepressants, naltrexone prescription was associated with a reduction in the percent drinking days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85, F(1,556) = 5.84, p = 0.02]. Conclusions: Further investigation will be needed to determine whether naltrexone is efficacious among depressed alcohol dependent patients and whether naltrexone and antidepressant medications show interactive efficacy for treating alcohol dependence.