The Effect of Residential Aged Care Size,Ownership Model,and Multichain Affiliation on Resident Comfort and Symptom Management at the End of Life

Context

In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a residential aged care (RAC) facility.

Threshold concepts: A portal into new ways of thinking and practising in psychiatry

Abstract

Introduction: The theory of threshold concepts conjectures that there are areas in every educational curriculum that are challenging; however, mastering these areas transform the learner’s view of the subject. In psychiatry, research into threshold concepts can inform educators so that they can better support students with mastering these challenging areas.

Purpose: To identify threshold concepts, we conducted semi-structured interviews with six psychiatry educators and free-text surveys with medical students. To identify avenues for improving the curriculum, we discussed with educators, ways of improving understanding and looked at different approaches to learning.

Materials and methods: From our analysis of all responses, we derived three threshold concepts: Therapeutic Risk-Taking, the Biopsychosocial Model, and the Concept of Diagnosis in psychiatry. The majority of students experienced difficulties grasping these concepts and applying them in their patient interactions.

Results and conclusions: Hence, we propose focused teaching activities that can help students cross these thresholds: student Balint groups exploring therapeutic risk, student Balint groups exploring the role of a psychiatrist, exposure to psychological therapies/psychotherapy skills and explicit diagnostic reasoning. These activities can be integrated into the undergraduate curriculum to help medical students develop a better understanding and appreciation of psychiatry.     

Case report--Scanora imaging of an unusual unerupted tooth located entirely below the inferior dental canal

We present an unusual case of an unerupted tooth located beneath the inferior dental canal (IDC) seen as an incidental finding on a dental panoramic radiograph (DPR). An unerupted premolar was identified on the DPR lying horizontally and located entirely below the inferior dental canal in the first and second molar region. The crown was distally orientated and was somewhat demineralised. As this unerupted tooth appeared to have an intimate relationship with the inferior dental canal, which in turn had a close relationship with the distal roots of the lower left first molar, this relationship was investigated further. Spiral tomography using Soredex's Scanora unit was used to obtain three contiguous 2 mm thick cross-sectional images of the area, which showed the separation of the inferior dental canal from both the first molar tooth above and the unerupted premolar. This case highlights the role of Scanora cross-sectional imaging in establishing accurately the relationship between teeth and the inferior dental canal and to document the unusual position of this unerupted tooth.     

Short-Term Skin Reactions Associated to Sleeve Gastrectomy in Eight Patients

Background

Bariatric procedures have beneficial effects on metabolic disturbances, including dermatological conditions. Short-term skin reactions associated with sleeve gastrectomy are not described in the literature.

Methods

We reviewed our database for patients who underwent bariatric surgery between May and October 2013 who reported a cutaneous rash during the short-term post-surgical period.

Results

Of a total of 195 patients, 8 (0.02 %) developed acute skin reactions during the first 3 months. Case 1 was compatible with reticulated papillomatosis. Case 2 was diagnosed as recurrent angioedema. Cases 3, 4, and 7 presented a cutaneous drug reaction to vitamin supplementation. Cases 5, 6, and 8 seemed to be secondary to xerosis and responded to lubrication.

Conclusion

Acute cutaneous skin reactions after bariatric surgery are unusual. When they do occur, they appear to be benign conditions.     

From the Cover: A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs

The recent success of antibody–drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer.Microtubule-targeting agents such as the taxanes and the vinca alkaloids represent a successful class of anticancer drugs (1). Vinblastine, for example, is a microtubule-destabilizing agent (MDA) that is widely used in combination therapy for the treatment of childhood and adult malignancies (2). The broad clinical application of MDAs, however, is hampered by their severe adverse effects (3). This problem has been very recently addressed by the use of antibody–drug conjugate (ADC) approaches, which have revived interest in the development of highly potent MDAs for therapeutic use (4–6).For several important MDAs, the molecular mechanism of action on tubulin and microtubules has so far remained elusive. Rhizoxin, for example, is a potent MDA that has been investigated in phase 2 clinical trials, but for reasons poorly understood, it has demonstrated only very limited clinical efficacy (7). At the molecular level, it is well established that rhizoxin interferes with the binding of vinblastine to tubulin; however, the exact location of its binding site has been a matter of debate (8–10). Interestingly, biochemical and mutagenesis data suggest that the structurally unrelated MDA maytansine (9, 11), which is part of an ADC that was recently approved by the FDA for the treatment of advanced breast cancer (11, 12), and the phase 1 drug PM060184 (13, 14) (Fig. 1A) share a common tubulin-binding site with rhizoxin (9, 13, 14). These two latter drugs have also been reported to interfere with the binding of vinblastine; however, as for rhizoxin, the exact binding sites and modes of action of maytansine and PM060184 have not been elucidated (9, 14–16).Open in a separate windowFig. 1.Structure of the tubulin–rhizoxin F complex. (A) Chemical structures of rhizoxin F, maytansine, and PM060184. (B) Overall view of the T₂R-TTL–rhizoxin F complex. Tubulin (gray), RB3 (light green), and TTL (violet) are shown in ribbon representation; the MDA rhizoxin F (orange) and GDP (cyan) are depicted in spheres representation. As a reference, the vinblastine structure (yellow, PDB ID no. 1Z2B) is superimposed onto the T₂R complex. (C) Overall view of the tubulin–rhizoxin F interaction in two different orientations. The tubulin dimer with bound ligand (α-tubulin-2 and β-tubulin-2 of the T₂R-TTL–rhizoxin F complex) is shown in surface representation. The vinblastine structure is superimposed onto the β-tubulin chain to highlight the distinct binding site of rhizoxin F. All ligands are in sphere representation and are colored in orange (rhizoxin F), cyan (GDP), and yellow (vinblastine). (D) Close-up view of the interaction observed between rhizoxin F (orange sticks) and β-tubulin (gray ribbon). Interacting residues of β-tubulin are shown in stick representation and are labeled.To establish the exact tubulin-binding site of rhizoxin, maytansine, and PM060184 and to clarify their specific interactions with the protein, we have investigated the structures of the corresponding ligand–tubulin complexes by X-ray crystallography. Our data reveal a new tubulin-binding site and pharmacophore for small molecules, and binding to this site is associated with a distinct molecular mechanism for the inhibition of microtubule formation.