Packmem: a versatile tool to compute and visualize interfacial packing defects in lipid bilayers

The analysis of the structural organization of lipid bilayers is generally performed across the direction normal to the bilayer/water interface, whereas the surface properties of the bilayer at the interface with water are often neglected. Here, we present PackMem, a bioinformatic tool that performs a topographic analysis of the bilayer surface from various molecular dynamics simulations. PackMem unifies and rationalizes previous analyses based on a Cartesian grid. The grid allows identification of surface regions defined as lipid-packing defects where lipids are loosely packed, leading to cavities in which aliphatic carbons are exposed to the solvent, either deep inside or close to the membrane surface. Examples are provided to show that the abundance of lipid-packing defects varies according to the temperature and to the bilayer composition. Because lipid-packing defects control the adsorption of peripheral proteins with hydrophobic insertions, PackMem is instrumental for us to understand and quantify the adhesive properties of biological membranes as well as their response to mechanical perturbations such as membrane deformation

Implementing WHO-Quality Rights Project in Tunisia: Results of an Intervention at Razi Hospital

Background: The aims were: 1) to measure the attitudes of learners (and future trainers) before and after a course on WHO-Quality Rights (QR); 2) to evaluate a psychiatric ward, by previously trained staff on QR, comparing it with a previous evaluation and discussing an improvement plan. Methods: 1) Training sample: 19 subjects (8 males), 41.4±10.6 years, including jurists/lawyers, health professionals, and experts. The QR team developed the 26-item tool to assess the knowledge and attitudes of participants. 2) Evaluation of quality of care and respect for human rights in the ward was carried out on 20 staff representatives, 20 family members and 20 users with QRToolkit. Results: 1) Learning in QR has partially changed the knowledge and attitudes of trained people. 2) The evaluation shows significant delays in the implementation of the rights advocated by the United Nations Convention on the Human Rights of Persons with Disabilities (CRPD). In Themes 1, 3, 4 and 5, the evaluation shows no differences compared to 2014, but in Theme 2, the level was lower than four years before. Conclusion: The scarcity of resources due to the economic crisis that Tunisia is going through, cannot be considered the only cause of the delays highlighted. However, it is likely that in a context of uncertainty for the future, scarcity of resources and a decrease in staff (i.e., professionals dedicated to psychosocial intervention) may have demotivated the team towards recovery. The improvement in knowledge and attitudes of many staff members after the training may open future positive scenarios

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.</p> <p>Results</p> <p>We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.</p> <p>Conclusions</p> <p>Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.</p

Cross-national variations in reported discrimination among people treated for major depression worldwide: The ASPEN/INDIGO international study

Background: No study has so far explored differences in discrimination reported by people with major depressive disorder (MDD) across countries and cultures. Aims: To (a) compare reported discrimination across different countries, and (b) explore the relative weight of individual and contextual factors in explaining levels of reported discrimination in people with MDD. Method: Cross-sectional multisite international survey (34 countries worldwide) of 1082 people with MDD. Experienced and anticipated discrimination were assessed by the Discrimination and Stigma Scale (DISC). Countries were classified according to their rating on the Human Development Index (HDI). Multilevel negative binomial and Poisson models were used. Results: People living in 'very high HDI' countries reported higher discrimination than those in 'medium/low HDI' countries. Variation in reported discrimination across countries was only partially explained by individual-level variables. The contribution of country-level variables was significant for anticipated discrimination only. Conclusions: Contextual factors play an important role in anticipated discrimination. Country-specific interventions should be implemented to prevent discrimination towards people with MDD

Assessing health literacy in transplant patients to better tailor the content of their therapeutic education: an observational study

International audienceOBJECTIVES: Evaluate health literacy in transplant patients to better tailor the content of their continuing therapeutic education. METHODS: A 20-item questionnaire divided into five themes (sport/recreation, dietary measures, hygiene measures, recognition of the signs of graft rejection and medication management) was sent to transplant patient associations. Participants’ responses (a score out of 20 points), were analysed according to demographic characteristics, transplanted organ (kidney, liver or heart), type of donor (living or deceased), participation in a therapeutic patient education (TPE) programme, management of end-stage renal disease (with or without dialysis) and the date of transplant. RESULTS: 327 individuals completed the questionnaires (mean age 63.3±12.7 years, mean time post-transplant 13.1±12.1 years). From 2 years after transplantation, the patients’ score decreases significantly compared with the score obtained at hospital discharge. Patients who received TPE had significantly higher scores than patients who did not receive it, but only in the first 2 years post-transplant. The scores were different depending on the organs transplanted. Patients’ knowledge varied according to the theme; the percentage of errors being higher for questions related to hygienic and dietary rules. CONCLUSION: These findings highlight the importance of the role of the clinical pharmacist in maintaining the transplant recipient’s health literacy level over time to increase graft life. We show the topics on which pharmacists must acquire solid knowledge to best meet the needs of transplant patients

A pharmacist-led intervention to improve kidney transplant recipient outcomes and identify patients at risk of highly variable trough tacrolimus levels: a cohort study

International audienceObjectivesGiven the positive impact of appropriate medication management on graft outcome and therefore of patient survival and graft function, the pharmacist's role in the kidney transplantation team has evolved over recent decades. The primary objective of this study was to determine whether pharmacist-led intervention after kidney transplantation is associated with a lower graft rejection rate and intra-patient variation in tacrolimus trough concentrations (C-min). The study's secondary objective was to develop a questionnaire to identify patients at risk for highly variable C-min. MethodsWe retrospectively analysed kidney transplant recipients at Rennes University Hospital (France) between January 2013 and December 2020. Patients who received pharmacist-led education (intervention group, n=139) were compared with patients who did not (control group, n=131), according to graft survival at 1 year post-transplant, coefficient of variation (%CV) for the tacrolimus C-min, age, sex, length of hospital stay post-transplantation, body mass index, and Charlson Comorbidity Index. In the intervention group, a questionnaire assessing patient knowledge was introduced to compare scores with the %CV. ResultsIn the intervention group, 1 year post-transplant graft survival was higher (95.7% vs 88.5%, p=0.0289) and patients had fewer variabilities in C-min. The %CV was correlated with questionnaire scores (r=-0.9758, p&lt;0.0001). ConclusionsPharmacist-led interventions may have contributed to improved graft survival and patient management of immunosuppressants. Because %CV correlates with the patient questionnaire score, its introduction could be useful in identifying kidney transplant patients who would benefit most from a pharmacist-led patient education

Inverse Conformational Selection in Lipid-Protein Binding

Interest in lipid interactions with proteins and other biomolecules is emerging not only in fundamental biochemistry but also in the field of nanobiotechnology where lipids are commonly used, for example, in carriers of mRNA vaccines. The outward-facing components of cellular membranes and lipid nanoparticles, the lipid headgroups, regulate membrane interactions with approaching substances, such as proteins, drugs, RNA, or viruses. Because lipid headgroup conformational ensembles have not been experimentally determined in physiologically relevant conditions, an essential question about their interactions with other biomolecules remains unanswered: Do headgroups exchange between a few rigid structures, or fluctuate freely across a practically continuous spectrum of conformations? Here, we combine solid-state NMR experiments and molecular dynamics simulations from the NMRlipids Project to resolve the conformational ensembles of headgroups of four key lipid types in various biologically relevant conditions. We find that lipid headgroups sample a wide range of overlapping conformations in both neutral and charged cellular membranes, and that differences in the headgroup chemistry manifest only in probability distributions of conformations. Furthermore, the analysis of 894 protein-bound lipid structures from the Protein Data Bank suggests that lipids can bind to proteins in a wide range of conformations, which are not limited by the headgroup chemistry. We propose that lipids can select a suitable headgroup conformation from the wide range available to them to fit the various binding sites in proteins. The proposed inverse conformational selection model will extend also to lipid binding to targets other than proteins, such as drugs, RNA, and viruses.Peer reviewe