RESUMEN

Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits, and maintain user safety. This paper describes the development of a self-directed, digital intervention for psychedelic preparation. Drawing on elements from the UK Medical Research Council (MRC) framework for developing complex interventions, the design was informed by a four-factor model of psychedelic preparedness, using a person-centred approach. Our mixed-methods investigation consisted of two studies. The first involved interviews with 19 participants who had previously attended a 'high-dose' psilocybin retreat, systematically exploring their preparation behaviours and perspectives on the proposed intervention. The second study engaged 28 attendees of an ongoing psilocybin retreat in co-design workshops, refining the intervention protocol using insights from the initial interviews. The outcome is a co-produced 21-day digital course (Digital Intervention for Psychedelic Preparation (DIPP)), that is organised into four modules: Knowledge-Expectation, Psychophysical-Readiness, Safety-Planning, and Intention-Preparation. Fundamental components of the course include daily meditation practice, supplementary exercises tied to the weekly modules, and mood tracking. DIPP provides a comprehensive and scalable solution to enhance psychedelic preparedness, aligning with the broader shift towards digital mental health interventions.

Asunto(s)

RESUMEN

BACKGROUND: To develop and examine user acceptance and content validity of a structured program to facilitate safe but challenging oral intake during radiotherapy (RT) delivered by a speech language pathologist (SLP)-the Eat-All Through Radiation Therapy (EAT-RT) program. METHODS: EAT-RT was developed through expert consensus of SLPs at the Princess Margaret Cancer Centre (Canada) and M D Anderson Cancer Center using a conceptual framework of a diet hierarchy and a mealtime routine. EAT-RT was refined by practicing SLPs, and then disseminated for a 4-week clinical pilot at seven sites who were subsequently invited to participate in an online survey. RESULTS: Twelve SLPs from six sites piloted EAT-RT therapy with a median of eight patients (IQR: 2-15) before and/or during RT. All SLPs reported EAT-RT added value to their practice, harmonized well with exercises, and its content was helpful; 11 (92%) reported EAT-RT facilitated patient understanding and indicated the desire to continue using EAT-RT. CONCLUSION: The EAT-RT program was accepted by North American SLPs. The findings support the content and value of EAT-RT to facilitate oral intake in patients with head and neck cancer throughout RT.

Asunto(s)

RESUMEN

The intracellular Gram-negative bacterium, Coxiella burnetii, is a worldwide zoonotic pathogen and the causative agent of Q fever. The standard of care for C. burnetii infections involves extended periods of antibiotic treatment and the development of doxycycline-resistant strains stress the need for new treatment strategies. A previously developed axenic medium has facilitated in vitro growth of the organism. In this study, we have developed a simple culture method that is inexpensive, reliable and utilizes a modular hypoxic chamber system for either small or large scale production of bacteria without the need of a tri-gas incubator. This method provides consistent growth and yields sufficient viable bacteria within four days of culture and can be used for high-throughput screening. The viable bacteria were quantified by counting colony forming units and total bacteria were enumerated using a genomic equivalent method. The characterized bacterial inoculum was then used to optimize cell-based high-throughput immunofluorescence assays with a goal to quantify intracellular bacteria and then screen and identify compounds that inhibit early stages of C. burnetii infection in macrophages.

Asunto(s)

RESUMEN

Background: Current surgical risk assessment tools fall short of appreciating geriatric risk factors including cognitive deficits, depressive, and frailty symptoms that may worsen outcomes post-transcatheter aortic valve implantation (TAVI). This study hypothesized that a screening tool, SMARTIE, would improve detection of these risks pre-TAVI, and thus be predictive of postoperative delirium (POD) and 30-day mortality post-TAVI. Design: Prospective observational cohort study, using a historical cohort for comparison. Participants: A total of 234 patients (age: 82.2±6.7 years, 59.4% male) were included. Half were screened using SMARTIE. Methods: The SMARTIE cohort was assessed for cognitive deficits and depressive symptoms using the Mini-Cog test and PHQ-2, respectively. Measures of frailty included activities of daily living inventory, the Timed Up and Go test and grip strength. For the pre-SMARTIE cohort, we extracted cognitive deficits, depression and frailty symptoms from clinic charts. The incidence of POD and 30-day mortality were recorded. Bivariate chi-square analysis or t-tests were used to report associations between SMARTIE and pre-SMARTIE groups. Multivariable logistic regression models were employed to identify independent predictors of POD and 30-day mortality. Results: More patients were identified with cognitive deficits (χ2=11.73, p=0.001), depressive symptoms (χ2=8.15, p=0.004), and physical frailty (χ2=5.73, p=0.017) using SMARTIE. Cognitive deficits were an independent predictor of POD (OR: 8.4, p<0.01) and 30-day mortality (OR: 4.04, p=0.03). Conclusion: This study emphasized the value of screening for geriatric risk factors prior to TAVI by demonstrating that screening increased identification of at-risk patients. It also confirmed findings that cognitive deficits are predictive of POD and mortality following TAVI.

Asunto(s)

RESUMEN

Critical bacterial pathogens of public health and biodefense concerns were engineered to constitutively express Escherichia coli enzyme thymidine kinase (TK) that allows for noninvasive nuclear imaging via phosphorylation and entrapment of radiolabeled nucleoside analog 1-(2'deoxy-2'-fluoro-ß-D-arabinofuranosyl)-5-iodouracil (FIAU). Expression of functional TK was established using a nucleoside analog Zidovudine that impeded the growth of tk-engineered bacteria. Significantly, no observable growth differences were detected for FIAU. High resolution mass spectrometry with Pseudomonas aeruginosa PAO1 and its tk variant (PAO1TK) confirmed FIAU phosphorylation and retention only in PAO1TK. In vitro gamma counting with wild-type PAO1, Acinetobacter baumannii and Burkholderia pseudomallei Bp82 and their tk derivatives with [18F]FIAU further confirmed that tk variants selectively incorporated the radiotracer, albeit with varying efficiencies. In vitro [18F]FIAU labeling coupled with in vivo Positron Emission Tomography/Computed Tomography (PET/CT) imaging of PAO1 and PAO1TK confirmed that only PAO1TK can be imaged in mice at sensitivities ≥107 bacteria per infection site. This was further verified by administering [18F]FIAU to animals infected with PAO1 and PAO1TK. Utility of tk-engineered P. aeruginosa in noninvasive PET/CT imaging for bacterial therapeutic evaluation in animals was demonstrated employing antibiotic ciprofloxacin, underscoring the immediate use of PAO1TK and potentially other engineered pathogens for evaluating experimental therapeutics.

Asunto(s)

RESUMEN

OBJECTIVES: To quantitatively summarize changes in cognitive performance in individuals with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). DESIGN: Metaanalysis. PARTICIPANTS: Individuals undergoing TAVI (N = 1,065 (48.5% male) from 18 studies, average age ≥80). MEASUREMENTS: The MEDLINE, EMBASE, and Cochrane Central databases were searched for original peer-reviewed reports assessing cognitive performance using standardized cognitive tests before and after TAVI. Data were extracted for cognitive scores before TAVI; perioperatively (within 7 days after TAVI); 1, 3, and 6 months after TAVI, and 12 to 34 months after TAVI (over the long term). Standardized mean differences (SMDs) were generated using random-effects models for changes in cognition at each time point. Metaregression analyses were conducted to assess the association between population and procedural characteristics and cognitive outcomes. Risk of bias was assessed. RESULTS: There were no significant changes from baseline in perioperative cognitive performance (SMD = 0.05, 95% confidence interval (CI) = -0.08-0.18; z = 0.75, P = .46), although overall cognitive performance had improved significantly 1 month after TAVI (SMD = -0.33, 95% CI = -0.50 to -0.16; z = 3.83, P < .001). There were no differences in cognitive performance 3 and 6 months after TAVI or over the long term. Cognitive outcomes were not associated with any covariates in regression analyses. CONCLUSION: Cognitive performance is preserved after TAVI, suggesting TAVI is not detrimental to cognition.

Asunto(s)

RESUMEN

OBJECTIVE: The goal of this meta-analysis was to quantitatively summarize the evidence available on the differences in grey matter volume between lithium-treated and lithium-free bipolar patients. METHODS: A systematic search was conducted in Cochrane Central, Embase, MEDLINE, and PsycINFO databases for original peer-reviewed journal articles that reported on global grey matter volume in lithium-medicated and lithium-free bipolar patients. Standard mean difference and Hedges' g were used to calculate effect size in a random-effects model. Risk of publication bias was assessed using Egger's test and quality of evidence was assessed using standard criteria. RESULTS: There were 15 studies with a total of 854 patients (368 lithium-medicated, 486 lithium-free) included in the meta-analysis. Global grey matter volume was significantly larger in lithium-treated bipolar patients compared to lithium-free patients (SMD: 0.17, 95% CI: 0.01-0.33; z = 2.11, p = 0.035). Additionally, there was a difference in global grey matter volume between groups in studies that employed semi-automated segmentation methods (SMD: 0.66, 95% CI: 0.01-1.31; z = 1.99, p = 0.047), but no significant difference in studies that used fully-automated segmentation. No publication bias was detected (bias coefficient = - 0.65, p = 0.46). LIMITATIONS: Variability in imaging methods and lack of high-quality evidence limits the interpretation of the findings. CONCLUSIONS: Results suggest that lithium-treated patients have a greater global grey matter volume than those who were lithium-free. Further study of the relationship between lithium and grey matter volume may elucidate the therapeutic potential of lithium in conditions characterized by abnormal changes in brain structure.

Asunto(s)

RESUMEN

The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.

Asunto(s)

RESUMEN

BACKGROUND: Major depressive disorder (MDD) may be associated with oxidative damage to lipids, which can potentially affect mood-regulating pathways. This meta-analysis summarizes current knowledge regarding lipid peroxidation markers in clinical samples of MDD and the effects of antidepressant pharmacotherapy on those markers. METHODS: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Collaboration were searched for original, peer-reviewed articles measuring markers of lipid peroxidation in patients with MDD and nondepressed healthy controls up to April 2015. Standardized mean differences (SMDs) were generated from random effects models summarizing mean (± standard deviations) concentrations of selected markers. RESULTS: Lipid peroxidation was greater in MDD than in controls (studies =17, N=857 MDD/782 control, SMD =0.83 [0.56-1.09], z=6.11, P<0.01, I (2)=84.0%) and was correlated with greater depressive symptom severity (B=0.05, df=8, P<0.01). Antidepressant treatment was associated with a reduction in lipid peroxidation in MDD patients (studies=5, N=222, SMD=0.71 [0.40-0.97], P<0.01; I (2)=42.5%). LIMITATIONS: Lipid peroxidation markers were sampled from peripheral blood, included studies comparing MDD to controls were all cross-sectional, and only five antidepressant treatment studies were eligible for inclusion. CONCLUSION: Increased lipid peroxidation was associated with MDD and may be normalized by antidepressants. Continued investigation of lipid peroxidation in MDD is warranted.