Debate: Why should gender-affirming health care be included in health science curricula?

Background Every person who seeks health care should be affirmed, respected, understood, and not judged. However, trans and gender diverse people have experienced significant marginalization and discrimination in health care settings. Health professionals are generally not adequately prepared by current curricula to provide appropriate healthcare to trans and gender diverse people. This strongly implies that health care students would benefit from curricula which facilitate learning about gender-affirming health care. Main body Trans and gender diverse people have been pathologized by the medical profession, through classifications of mental illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Disease (ICD). Although this is changing in the new ICD-11, tension remains between depathologization discourses and access to gender-affirming health care. Trans and gender diverse people experience significant health disparities and an increased burden of disease, specifically in the areas of mental health, Human Immunodeficiency Virus, violence and victimisation. Many of these health disparities originate from discrimination and systemic biases that decrease access to care, as well as from health professional ignorance. This paper will outline gaps in health science curricula that have been described in different contexts, and specific educational interventions that have attempted to improve awareness, knowledge and skills related to gender-affirming health care. The education of primary care providers is critical, as in much of the world, specialist services for gender-affirming health care are not widely available. The ethics of the gatekeeping model, where service providers decide who can access care, will be discussed and contrasted with the informed-consent model that upholds autonomy by empowering patients to make their own health care decisions. Conclusion There is an ethical imperative for health professionals to reduce health care disparities of trans and gender diverse people and practice within the health care values of social justice and cultural humility. As health science educators, we have an ethical duty to include gender-affirming health in health science curricula in order to prevent harm to the trans and gender diverse patients that our students will provide care for in the future

Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction

The depletion of cholesterol from membranes, mediated by β-cyclodextrin (β-CD) is well known and documented, but the molecular details of this process are largely unknown. Using molecular dynamics simulations, we have been able to study the CD mediated extraction of cholesterol from model membranes, in particular from a pure cholesterol monolayer, at atomic resolution. Our results show that efficient cholesterol extraction depends on the structural distribution of the CDs on the surface of the monolayer. With a suitably oriented dimer, cholesterol is extracted spontaneously on a nanosecond time scale. Additional free energy calculations reveal that the CDs have a strong affinity to bind to the membrane surface, and, by doing so, destabilize the local packing of cholesterol molecules making their extraction favorable. Our results have implications for the interpretation of experimental measurements, and may help in the rational design of efficient CD based nano-carriers

Binding of quinazolinones to c-KIT G-quadruplex; an interplay between hydrogen bonding and π-π stacking

Stabilization of G-quadruplex structures in the c-KIT promoter with the aid of ligands has become an area of great interest in potential cancer therapeutics. Understanding the binding process between ligands and G-quadruplex is essential for a discovery of selective ligands with high binding affinity to G-quadruplex. In the present work, binding mechanisms of 4-quinazolinones to c-KIT G-quadruplex were investigated theoretically by means of molecular dynamics (MD) simulations. To explore the binding affinity of ligands, binding free energy calculations were performed using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. We demonstrate that the key interactions in G-quadruplex-ligand complexes are π-π stacking and hydrogen bond interactions. However, neither of these two interactions alone determines the stability of the G-quadruplex-ligand complexes; rather, it is the result of an intricate interplay between the two. To further examine the nature of the binding, a free energy decomposition analysis at residue level was carried out. The results clearly demonstrate the crucial roles of two hot spot residues (DG4 and DG8) for the binding of ligands to c-KIT G-quadruplex, and highlight the importance of the planar aromatic moiety of ligands in G-quadruplex stabilization via π-π stacking interactions. Our study can assist in the design of new derivatives of 4-quinazolinone with high binding affinity for c-KIT G-quadruplex

Comparing Dimerization Free Energies and Binding Modes of Small Aromatic Molecules with Different Force Fields

Dimerization free energies are fundamental quantities that describe the strength of interaction of different molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely difficult, due to the size of the systems and the small energy differences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings, and compared three models from popular online servers for atomistic force fields, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force field, the profiles for the dimerization free energy of these compounds are very similar. However, significant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecules, resulting in force field dependent preferred stacking modes; for example, in the cases of pyrene and tetracene. Our results provide a useful background study for using topology builders to model systems which rely on stacking of aromatic moieties, and are relevant in areas ranging from drug design to supramolecular assembly

Capturing Membrane Phase Separation by Dual Resolution Molecular Dynamics Simulations

[Image: see text] Understanding the lateral organization in plasma membranes remains an open problem and is of great interest to many researchers. Model membranes consisting of coexisting domains are commonly used as simplified models of plasma membranes. The coarse-grained (CG) Martini force field has successfully captured spontaneous separation of ternary membranes into a liquid-disordered and a liquid-ordered domain. With all-atom (AA) models, however, phase separation is much harder to achieve due to the slow underlying dynamics. To remedy this problem, here, we apply the virtual site (VS) hybrid method on a ternary membrane composed of saturated lipids, unsaturated lipids, and cholesterol to investigate the phase separation. The VS scheme couples the two membrane leaflets at CG and AA resolution. We found that the rapid phase separation reached by the CG leaflet can accelerate and guide this process in the AA leaflet

Direct and Regioselective Di-alpha-fucosylation on the Secondary Rim of beta-Cyclodextrin

A straightforward glycosylation method is described to regio- and stereoselectively introduce two alpha-L-fucose moieties directly to the secondary rim of beta-cyclodextrin. Using NMR and MS fragmentation studies, the nonasaccharide structure was determined, which was also visualized using molecular dynamics simulations. The reported glycosylation method proved to be robust on gram-scale, and may be generally applied to directly glycosylate beta-cyclodextrins to make well-defined multivalent glycoclusters.</p