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Patient and public involvement in basic and clinical psychiatric research : a scoping review of reviews
Full text linkBackground: Patient and public involvement (PPI) in health research has become established as an essential
component of international health research. Particularly, patients and stakeholders’ commitment to psychiatric
research faces various challenges. This scoping review aimed to examine the existing literature to identify the aims,
methods, barriers, and facilitators of PPI in clinical and basic psychiatric research.
Methods: This scoping review’s methods were guided by the framework proposed by Arksey and O’Malley. The
literature search was conducted between October and November 2023 on six databases (MEDLINE, Web of Science,
EMBASE, PsycInfo, PubPsych, and the Cochrane Library). We included reviews that summarized the results of primary
studies describing methods for PPI in psychiatric scientific research, regardless of their subjects’ underlying psychiatric
conditions and the primary research context (clinical or preclinical). The inclusion criteria included a description of
the methods, components, and characteristics of participation in psychiatric research. We included reviews published
between 2008 and 2023 regardless of participants’ language, country, or age.
Findings: Twenty reviews comprising 429 studies were included. They revealed that PPI was used to pursue
various objectives (e.g., prioritizing research questions). Common methods included focus groups, advisory boards,
workshops and interviews. Only one review reported financial compensation for those involved. PPI ranged from
tokenism to involvement in data analysis and the dissemination of findings. Facilitators and barriers were identified
in relationship and communication factors, organizational and practical factors, and in (co-) researchers training. The
most frequently mentioned facilitators of successful PPI were trust and strong relationships. The most frequently
mentioned barrier was the power imbalance between the participants and researchers. We identified positive and
potential negative effects of PPI.
Conclusion: Golden rules for practice (clinical and basic research) derived from the results are as follows: (I) Foster a
culture of collaboration and mutual respect between researchers and PPI participants. (II) Provide adequate resources
and support for PPI activities, including funding and training programs. (III) Develop clear guidelines and standard
Utilization of mental health services in Germany during the first year of the COVID-19 pandemic : systematic review and meta-analysis
No full textHintergrund: In der COVID-19(„coronavirus disease 2019“)-Pandemie zeigten Studien Hinweise auf Veränderungen der Inanspruchnahme der stationären und ambulanten psychiatrisch-psychotherapeutischen Versorgung sowie der psychiatrischen Notfallversorgung. Beobachtungsebene und Repräsentativität dieser Studien waren jedoch heterogen. Ziele der Arbeit: Veränderungen der Inanspruchnahme psychiatrisch-psychotherapeutischer Versorgung im ersten Jahr der COVID-19-Pandemie wurden durch systematische Literatursuche, Bewertung der Qualitäts- und Beobachtungsebene sowie Metaanalyse der Effekte eingeordnet. Material und Methoden: Systematische Suche in PubMed, PsycInfo und Embase bis Juni 2023 sowie Nachsuche in PubMed bis einschließlich Oktober 2024. Daten wurden den Zeiträumen 1. Lockdownphase, Zwischenlockdownphase, 2. Lockdownphase, ganzes Pandemiejahr 2020 zugeordnet. Ergebnisse: Insgesamt konnten 17 Studien eingeschlossen werden. Es zeigten sich für die Anzahl stationärer Aufnahmen Reduktionen für die 1. Lockdownphase von RR 0,74; 95 %-KI [0,70; 0,79]; I2 95,5 %; t2 0,0053 und für die 2. Lockdownphase von RR 0,78; 95 %-KI [0,75; 0,81]; I2 97,1 %; t2 0,0058. Für psychiatrische Notfallversorgung wurden nur Studien niedriger Beobachtungsebene gefunden und für ambulante Inanspruchnahme nur zwei Studien mit unterschiedlichen Indikatoren. Bezüglich der Verordnung psychotroper Medikamente zeigten sich keine eindeutigen Veränderungen
Lipid-binding features and phosphoinositide-dependent function of the endocytic adaptor protein 2 (AP2)-complex from Arabidopsis thaliana
Full text linkRegulation of plasma membrane (PM) composition is crucial for plant cell function. Clathrin-mediated endocytosis (CME) is a key pathway for protein internalization from the PM. This study explores how anionic phospholipids, particularly phosphoinositides (PIs) regulate CME in Arabidopsis. Mutants with disrupted PI metabolism showed altered membrane order and impaired endocytosis. The AP2-complex, crucial for CME initiation, was found to directly bind PIs, especially PtdIns(4,5)P2, via polybasic regions. Mutated AP2-subunits with reduced lipid binding led to defective CME, as shown by reduced FM4-64 uptake and altered cargo internalization. AP2-subunits interacted with various lipid kinases important for PI biosynthesis, including PIP5K1, PIP5K2 and PIP5K6, which have been functionally implicated in CME. These findings suggest that PtdIns(4,5)P2 modulates CME through direct interaction with AP2, highlighting a molecular mechanism linking PI-metabolism to membrane trafficking in plants.Seiten gezählt als 1-95, XCVI-CXXXI
Prospective clinical study to evaluate the success and survival of two-piece zirconia implants : a single-center study. 12-month results
Full text linkPurpose:
To evaluate the survival and success rates of a novel two-piece zirconia implant system restored with screw-retained glass–ceramic crowns over 12 months, including assessment of bone levels, soft tissue parameters, and patient-reported outcome measures.
Methods:
Twenty-four patients received single two-piece zirconia implants (CERALOG® Hexalobe) in healed sites. After a 6-month healing period, implants received provisional screw-retained crowns on PEKK temporary abutments, followed by definitive lithium disilicate crowns (IPS e.max Press) on PEKK abutments. Clinical and radiographic examinations were performed at implant placement, re-entry, definitive loading, and 12-month follow-up, along with patient-reported outcome measures.
Results:
The implant survival rate at 12 months was 60.9%. Nine implants were lost: two due to lack of osseointegration at re-entry, four due to mobility after loading, and three due to fractures in the coronal third after loading. Surviving implants showed stable soft tissue parameters with mean probing pocket depths of 2.7 ± 0.7 mm at 12 months. The mean distance from implant shoulder to first bone contact decreased from 1.9 ± 0.6 mm at loading to 1.4 ± 0.6 mm at 12 months. Patients with surviving implants reported high satisfaction scores (4.8 ± 0.4) for function and aesthetics.
Conclusions:
The two-piece zirconia implant system with screw-retained restorations showed unsatisfactory survival rates. The combination of ceramic implants with screw-retained prosthetic restorations may have contributed to the higher failure rates observed. As a pilot study with a relatively small sample size, these findings should be confirmed by larger multicenter studies to validate these preliminary results
Semisynthesis of novel alicyclic triterpene-triazole derivatives from Boswellia sacra gum resin : potential anti-breast cancer and immunomodulatory effects on T‑cell activation
Full text linkIn this current work, we report on the design, synthesis, cytotoxicity of new compounds, molecular docking studies, and in vitro and in silico evaluations of 24 new alicyclic triterpene amide-containing 1H-1,2,3-triazole derivatives (4, 5, 7a-7k and 8a–8k). All new compounds were characterized by 1H-, 13C-, 19F-NMR, and HR-ESI-MS spectroscopic techniques. X-ray crystallography unambiguously confirmed the exact structure of 4. The antibreast cancer activity of all compounds was evaluated against two prominent human breast and one normal cancer cell lines with IC50 values ranging from 352.31 to 61.47 μM (MDA-MB-231), 386.61 to 67.02 μM (MCF-7), and 445.37 to 103.41 μM (HDF), respectively. Eight derivatives (7b–7i) exhibited greater antiproliferative activities than the β-KBA (2) used as a reference compound. Compound 7f demonstrated noteworthy activity even at lower concentrations. In contrast, compounds 8a and 8k demonstrated relatively lower effects, being compared with parent compound 2. Furthermore, compound 7f significantly expanded CD4+ CD8- helper T cell population at both 5 and 10 μM concentrations, increasing the expression of PD-1 and TIGIT immune checkpoints at 5 μM. The binding modes of the most active hits (7b–7i) were deduced by in silico docking using cyclin-dependent kinase 4 (CDK4) as a prominent target. The molecular docking studies demonstrated appreciable binding interactions and docking scores of compounds at CDK-4 ligand binding site and a significant role for −OH in compound 2 and the amide linker and triazole moiety in the binding of these compounds
Laboratory heat transport experiments reveal grain-size- and flow-velocity-dependent local thermal non-equilibrium effects
Full text linkHeat transport in porous media is crucial for gaining Earth science process understanding and for engineering applications such as geothermal system design. While heat transport models are commonly simplified by assuming local thermal equilibrium (LTE; solid and fluid phases are averaged) or local thermal non-equilibrium (LTNE; solid and fluid phases are considered separately), heat transport has long been hypothesized, and reports have emerged. However, experiments with realistic grain sizes and flow conditions are still lacking in the literature. To detect LTNE effects, we conducted comprehensive laboratory heat transport experiments at Darcy velocities ranging from 3 to 23 m d−1 and measured the temperatures of fluid and solid phases separately for glass spheres with diameters of 5, 10, 15, 20, 25, and 30 mm. Four replicas of each size were embedded at discrete distances along the flow path in small glass beads to stabilize the flow field. Our sensors were meticulously calibrated, and measurements were post-processed to reveal LTNE, expressed as the difference between solid and fluid temperature during the passing of a thermal step input. To gain insight into the heat transport properties and processes, we simulated our experimental results in 1D using commonly accepted analytical solutions for LTE equations and a numerical solution for LTNE equations. Our results demonstrate significant LTNE effects with increasing grain size and water flow velocity. Surprisingly, the temperature differences between fluid and solid phases at the same depth were inconsistent, indicating non-uniform heat propagation likely caused by spatial variations in the flow field. The fluid temperature simulated by the LTE and LTNE models for small grain sizes (5–15 mm) showed similar fits to the experimental data, with the RMSE values differing by less than 0.01. However, for larger grain sizes (20–30 mm), the temperature difference between fluid and solid phases exceeded 5 % of the system's temperature gradient at flow velocities ≥17 m d−1, which falls outside the criteria for the LTE assumption. Additionally, for larger grain sizes (≥20 mm), the LTNE model failed to predict the magnitude of LTNE (i.e., temperature difference between fluid and solid phase in time series) for all tested flow velocities due to experimental conditions being inadequately represented by the 1D model with ideal step input. Future studies should employ more sophisticated numerical models to examine the heat transport processes and accurately analyze LTNE effects, considering non-uniform flow effects and multi-dimensional solutions. This is essential to determine the validity limits of LTE conditions for heat transport in natural systems such as gravel aquifers with grain sizes larger than 20 mm
Efficient crystallization of Apo Sirt2 for small-molecule soaking and structural analysis of ligand interactions
Full text linkThe selectivity pocket is a key binding site for inhibitors of the NAD+-dependent lysine deacylase Sirtuin 2 (Sirt2), a promising drug target in diseases like cancer. While small-molecule soaking can advance inhibitor development, the selectivity pocket is absent in available Sirt2 apo structures, and existing soaking systems like Sirt2–ADPribose (ADPR) suffer from unfavorable crystal packing that hinders ligand binding. We developed a method to rapidly generate high-quality Sirt2 apo crystals with an open selectivity pocket, suitable for high-throughput soaking. The induced-fit pocket forms upon seeding with a Sirtuin Rearranging ligand (SirReal) and is retained in the ligand-free apo structure. Screening the Maybridge Ro3-fragment library using a fluorescence polarization assay yielded three novel Sirt2-fragment-inhibitor structures. Additionally, our Sirt2 apo crystals can accommodate ligands at the acyl-lysine channel entrance and the cofactor binding site, as confirmed by binding of the peptide inhibitor KT9 and NAD+, facilitating SAR studies and inhibitor optimization
Uncovering hidden influences : impact of omitted covariates on the estimation of treatment effects using Cox regression in randomized and propensity score matched trials
Full text linkHazard ratios (HRs) are commonly used to describe treatment effects in trials focusing on time-to-event outcomes, but have faced growing criticism, particularly regarding non-collapsibility and causal interpretation. This work highlights another concern: unobserved or omitted covariates that induce bias in both randomized and propensity score matched trials. To address this, a new approach, “Dynamic Landmarking”, is introduced. It visually detects biased estimates by iteratively removing sorted observations and refitting Cox models. It also evaluates the balance of observed but omitted covariates using the sum of squared z-differences. Simulations confirm its effectiveness in identifying biased estimates and relevant omitted covariates that cause them. An application to 27 large RCTs found no empirical evidence of built-in selection bias, likely due to small treatment effects and strict inclusion criteria. Thus, HRs remain generally valid, at least regarding this type of bias
Patients' experiences of cognitive behavioural therapy integrated with activity pacing : a qualitative study
Full text linkBackground:
Our previous trial integrating cognitive behavioural therapy with activity pacing (CBT-AP) demonstrated the efficacy of CBT-AP in reducing cancer-related fatigue and depression, as well as improving the quality of life for patients with breast cancer. However, the range of subjective patient experiences on the effect of CBT-AP, including its content, context, and approach, has not been fully explored. This study aimed to explore patients’ experiences of CBT-AP among breast cancer patients.
Methods:
Patients with breast cancer who attended CBT-AP sessions were interviewed. The interviews continued until data saturation was achieved, with no new findings emerging. A total of 20 women, aged 24 to 62, at various stages of cancer and undergoing chemotherapy were involved in the study. The collected data was transcribed, translated and coded following themes developed in line with the objective of the study, ensuring sensitivity to context, rigour, transparency, and impact throughout the research process.
Results:
The data identified six major themes: the content of the therapy, the context of the therapy, experiences with the implementation of the therapy, benefits of the therapy, the therapeutic approach, and recommendations. Findings revealed that participants described all components of CBT-AP as important, with the content addressing common symptoms related to the disease and its treatment. Participants reported positive effects on their physical, psychological, and social health following the therapy. While the majority preferred face-to-face sessions, a significant number favoured a combination of face-to-face and telephone sessions. The participant’s manual was found to be easily understandable and clear.
Conclusion:
The findings suggest that participants had positive experiences with the therapy. Based on these experiences, it is recommended that specific components and delivery methods of CBT-AP, such as patient-centered content and flexible delivery options, be considered key factors to enhance its acceptability and feasibility. While this study highlights CBT-AP’s potential to improve quality of life of breast cancer patients, further research is needed to evaluate its broader application and long-term impact in various healthcare settings, particularly for diverse patient populations
Genome-scale metabolic model of Staphylococcus epidermidis ATCC 12228 matches in vitro conditions
Full text linkStaphylococcus epidermidis, a commensal bacterium inhabiting collagen-rich areas like human skin, has gained significance due to its probiotic potential in the nasal microbiome and as a leading cause of nosocomial infections. While infrequently leading to severe illnesses, S. epidermidis exerts a significant influence, particularly in its close association with implant-related infections and its role as a classic opportunistic biofilm former. Understanding its opportunistic nature is crucial for developing novel therapeutic strategies, addressing both its beneficial and pathogenic aspects, and alleviating the burdens it imposes on patients and healthcare systems. Here, we employ genome-scale metabolic modeling as a powerful tool to elucidate the metabolic capabilities of S. epidermidis. We created a comprehensive computational resource for understanding the organism’s growth conditions within diverse habitats by reconstructing and analyzing a manually curated and experimentally validated metabolic model. The final network, iSep23, incorporates 1,415 reactions, 1,051 metabolites, and 705 genes, adhering to established community standards and modeling guidelines. Benchmarking with the Metabolic Model Testing suite yields a high score, indicating the model’s remarkable semantic quality. Following the findable, accessible, interoperable, and reusable (FAIR) data principles, iSep23 becomes a valuable and publicly accessible asset for subsequent studies. Growth simulations and carbon source utilization predictions align with experimental results, showcasing the model’s predictive power. Ultimately, this work provides a robust foundation for future research aimed at both exploiting the probiotic potential and mitigating the pathogenic risks posed by S. epidermidis