Seven ways to get a grip on implementing Competency-Based Medical Education at the program level.

Competency-based medical education (CBME) curricula are becoming increasingly common in graduate medical education. Put simply, CBME is focused on educational outcomes, is independent of methods and time, and is composed of achievable competencies.1 In spite of widespread uptake, there remains much to learn about implementing CBME at the program level. Leveraging the collective experience of program leaders at Queen's University, where CBME simultaneously launched across 29 specialty programs in 2017, this paper leverages change management theory to provide a short summary of how program leaders can navigate the successful preparation, launch, and initial implementation of CBME within their residency programs.

Les programmes de formation médicale fondée sur les compétences (FMFC) sont de plus en plus répandus dans les études supérieures en médecine. En termes simples, la FMFC est centrée sur les résultats scolaires, elle est indépendante des méthodes et du temps, et est constituée de compétences réalisables.1 Malgré cette adoption généralisée, il reste encore beaucoup à apprendre sur la mise en œuvre de la FMFC au niveau des programmes. Tirant profit de l'expérience collective des responsables de programmes à l'Université Queen, où la FMFC a été lancée simultanément dans 29 programmes de spécialité en 2017,le présent article s'appuie sur la théorie de la gestion du changement pour produire un court résumé de la manière dont les responsables de programmes peuvent gérer avec succès la préparation, le lancement et la mise en œuvre initiale de la FMFC au sein de leurs programmes de résidence.

[Questioning the mechanism behind slow breathing and heart coherence training]. / Vraagtekens bij het werkingsmechanisme van slow-breathing en hartcoherentietraining.

BACKGROUND: Slow breathing and heart coherence training are being offered increasingly as treatments for anxiety, depression and stress-related mental and somatic complaints. Both of these interventions are aimed at influencing (i.e. increasing or optimising) heart rate variability and the mechanism involved is described in terms such as heart coherence, resonance breathing and heart-brain communication. AIM: To find out whether treatment effects are indeed based on the optimisation of heart rate variability. METHOD: Our literature search focused on 1) the assumption that poor mental health is definitely linked to deviant heart rate variability, and 2) the assumption that optimising heart rate variability leads specifically to a reduction of complaints and symptoms. RESULTS: There is insufficient evidence to support these two assumptions. CONCLUSION: Slow breathing and heart coherence training probably achieve their effects as a result of non-specific psychological mechanisms.

Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting.

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

Cocaine as a risk factor for neuroleptic-induced acute dystonia.

BACKGROUND: A prospective study was conducted to test the hypothesis that cocaine use is a risk factor for neuroleptic-induced acute dystonia (NIAD). METHOD: The study sample consisted of a high-risk group for NIAD, males aged 17-45 years who had received high-potency neuroleptics within 24 hours of admission and had not used neuroleptics in the month prior to admission. Patients were excluded if they suffered from a neurodegenerative disorder or were exposed to anticholinergics, benzodiazepines, promethazine, carbamazepine, phenytoin, or levodopa during the study. Twenty-nine patients--9 cocaine users and 20 nonusers--entered the study, which lasted 2 years. Patients were followed for 7 days. RESULTS: Cocaine-using psychiatric patients developed significantly more NIAD than did nonusers (relative risk = 4.4, 95% CI = 1.4 to 13.9). CONCLUSION: Cocaine use is a major risk factor for NIAD and should be added to the list of well-known risk factors. The authors strongly suggest that cocaine-using psychiatric patients who are started on a regimen of neuroleptics should also be administered an anticholinergic for at least 7 days to prevent NIAD.

Distribution of cytokeratin markers in Barrett's specialized columnar epithelium.

BACKGROUND & AIMS: The cell of origin for Barrett's epithelium is unknown. A multilayered epithelium within Barrett's epithelium has been noted recently. To investigate the hypothesis that this multilayered epithelium may be a transitional stage between squamous and Barrett's epithelium, cytokeratin immunocytochemistry was used to examine normal squamous, Barrett's, and multilayered epithelium. METHODS: Seventeen endoscopic biopsy specimens taken from the squamo-Barrett's junction of 8 patients with Barrett's epithelium and 3 biopsy specimens from the gastroesophageal junction of 3 patients without Barrett's epithelium were investigated. Antibodies to cytokeratins 4 and 13 were used as markers for squamous differentiation, and antibodies to cytokeratins 8 and 19 were used as markers for glandular differentiation. Coded samples were evaluated by immunocytochemistry. RESULTS: In patients with Barrett's epithelium and control patients, staining with columnar markers was confined to either the Barrett's or the gastric columnar epithelium. Staining with squamous markers was confined to the adjacent squamous epithelium. In contrast, focal areas of multilayered epithelium amidst Barrett's epithelium stained with cytokeratin antibodies for both squamous and columnar epithelium. CONCLUSIONS: A focal multilayered epithelium within Barrett's epithelium that expresses concurrently both squamous and glandular cytokeratin markers is described. These findings suggest a multipotential cell as the cell of origin of Barrett's epithelium.

Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett's epithelium.

Barrett's esophagus is a metaplastic condition in which the normal stratified squamous epithelium of the distal esophagus is replaced by columnar epithelium. Our group has previously characterized a unique surface cell (the "distinctive cell") at the junction of squamous and Barrett's epithelium. This cell is notable for the simultaneous presence on its surface of both squamous and columnar cell features. The aims of our present study were, first, to evaluate prospectively the frequency with which Barrett's patients have the distinctive cell at the squamo-Barrett's junction; second, to further elucidate the characteristics of the distinctive cell; and third, to perform a combined morphological study of the squamo-Barrett's junction using scanning electron microscopy followed by transmission and light microscopy. We divided study patients into two groups: Group I consisted of Barrett's patients and group II of non-Barrett's control patients. Of eight group I Barrett's patients with junctional biopsies, three were noted to have the distinctive cell (37.5%). In contrast, this cell was not observed in any of the group II control patients. Biopsies in control patients as well as Barrett's patients without the distinctive cell revealed abrupt squamogastric or squamo-Barrett's junctions by scanning electron microscopy and light microscopy. In contrast, biopsies from the Barrett's patients with the distinctive cell revealed junctions that were not abrupt and had the distinctive cells overlying normal squamous epithelium. By scanning electron microscopy, the distinctive cells were flattened, polygonal cells with surface microvilli (a columnar cell feature) and were demarcated from one another by shallow depressions, or by intercellular ridges (a squamous cell feature). By transmission electron microscopy, the distinctive cells were cuboidal in shape with abundant apical microvilli and secretory vesicles. We have confirmed that distinctive cells are present in some Barrett's patients. This cell is a morphologic hybrid, sharing features of both squamous and columnar cells, and may be analogous to hybrid cells identified in other locations that undergo metaplasia (eg, the human cervix). Its origin may be the result of transformation of multipotential basal cells of squamous epithelial origin. We hypothesize that the distinctive cells may represent an intermediate stage in the development of Barrett's epithelium.

Exposure of the rat small intestine to raw kidney beans results in reorganization of absorptive cell microvilli.

BACKGROUND/AIMS: A single exposure to raw kidney beans (RKB) results in vesiculation, shortening, and then regrowth of microvilli in the rat small intestine. This study investigated changes that occur in the structure of microvilli 2-10 hours after RKB exposure. METHODS: Circumferences of microvilli from absorptive cells obtained sequentially after challenge with RKB or chow were assigned to one of three groups: small, intermediate, or large. The distribution and concentration of actin in intact mucosae or isolated epithelial sheets were determined by confocal laser scanning microscopy, immunocytochemistry, and immunoblot analysis with specific probes. RESULTS: Six hours after exposure to RKB, most microvilli were large, abnormal in shape, and contained significantly more actin filaments than large microvilli from control rats. In addition, the fluorescence intensity of F-actin increased within injured microvilli without changes in the total intracellular actin concentration. By 8-10 hours after challenge with RKB, some microvilli remained larger than those of control rats but had resumed their normal shape and contained fewer actin filaments than at 6 hours. CONCLUSIONS: Exposure of the rat small intestine to RKB results in enlargement of absorptive cell microvilli and reorganization of membrane and core actin filaments without changes in intracellular actin concentration. Enlarged microvilli are rapidly repaired.

Diagnosis and treatment of celiac sprue.

Celiac sprue, also termed celiac disease or gluten-sensitive enteropathy, is a chronic disease in which malabsorption of nutrients is caused by a characteristic, but nonspecific, lesion of the small-intestinal mucosa. The lesion is produced, through unclear mechanisms, by protein constituents of some cereal grains. Exclusion of wheat gluten and rye, barley, and oat prolamins from the diet results in a prompt improvement in absorption, along with reversion, toward normal, of the associated small-intestinal lesion. The spectrum of manifestations of celiac sprue is remarkably broad, but the severity of disease generally correlates with the length of small intestine that is damaged. When most or all of the small-intestinal mucosa is involved, symptoms are severe and malabsorption is generalized. In such patients, a diagnosis of celiac sprue is usually considered. When, on the other hand, the mucosal lesion is limited to the duodenum and proximal jejunum, overt gastrointestinal symptoms and steatorrhea may be absent. In those patients, clinical manifestations, if present at all, may reflect malabsorption of only one or two substances, notably iron and folate, that normally are absorbed somewhat selectively by the proximal intestine. Arriving at the correct diagnosis in such cases may be quite challenging.

Rat intestinal M cells contain acidic endosomal-lysosomal compartments and express class II major histocompatibility complex determinants.

BACKGROUND: It is generally believed that M cells do not modify the antigens they transport from the intestinal lumen to underlying immunocompetent cells because it has been reported that M cells contain few elements of the lysosomal system. METHODS: We used specific cytochemical and immunocytochemical probes to examine whether M cells in jejunal Peyer's patches of adult rats contain the requisite intracellular components to process and potentially present endocytosed antigens. RESULTS: M cells contained acid phosphatase-enriched prelysosomelike and lysosomelike structures. A basic congener of dinitrophenol, which concentrates in acidic cell compartments, is localized following its instillation into Peyer's patch-containing ligated jejunal loops to the endosomal-lysosomal system of M cells. Prelysosomelike and lysosomelike structures in ultrathin cryosections of M cells reacted with polyclonal antibody to a membrane glycoprotein (lgp120) enriched in prelysosomes and lysosomes. Using monoclonal antibody OX6 as a probe, M cells expressed the major histocompatibility complex (MHC) class II determinant, Ia, on the basolateral plasma membrane and in organelles with structural features of endosomes, prelysosomes, and lysosomes. Expression was enhanced by pretreatment with interferon gamma. CONCLUSIONS: M cells possess acidic endosomal and acid phosphatase-containing prelysosomal and lysosomal compartments and express MHC class II determinants. Hence, M cells may have the capacity to process and present endocytosed antigens to adjacent intraepithelial T lymphocytes.

Expression of a nonpolymorphic MHC class I-like molecule, CD1D, by human intestinal epithelial cells.

The human CD1 locus encodes three nonpolymorphic MHC class I-like cell surface glycoproteins, CD1a-c, which are expressed primarily by immature thymocytes. A mAb and antipeptide antiserum were utilized to determine the tissue distribution of a fourth CD1 molecule, CD1d. Within the lymphoid lineage, CD1d was expressed on B cells but not on thymocytes. Immunoperoxidase staining of fresh frozen intestinal tissues demonstrated that the majority of intestinal epithelial cells, with the exception of cells at the base of some crypts, expressed CD1d. The CD1d staining was observed in the cytoplasm and along the basolateral membranes of the epithelial cells. The intestinal epithelial cell expression of CD1d was confirmed by immunoblotting with a CD1d antipeptide antiserum. Further immunoperoxidase studies indicated that CD1d, unlike murine CD1, was also expressed by nonlymphoid tissues outside of the gastrointestinal tract. The expression of CD1d outside the lymphoid and myeloid lineages clearly distinguishes this molecule from CD1a-c and suggests that it may serve a distinct function. The prominent expression of CD1d by intestinal epithelial cells suggests that this molecule may be an important ligand for T lymphocytes within the gut-associated lymphoid tissue.

Structure and function of intestinal M cells.

M cells are structurally distinctive, uniquely permeable epithelial cells found only overlying the domes of mucosal lymphoid follicles. Antigenic macromolecules and some viruses, bacteria, and protozoa enter their apical surface by endocytosis or phagocytosis. These substances traverse the M-cell cytoplasm by transcytosis, breaching the epithelial barrier, and then interact with the subepithelial immunocompetent cells to initiate mucosal and systemic immune responses. The M cell serves as a portal of entry for selected pathogens that cause disease locally in the wall of the intestine or, following dissemination, at distant sites. The mechanisms that regulate adherence to and penetration of M cells by macromolecules and microorganisms are not known, but selective binding of secretory IgA to the luminal surface may be important. Whether M cells simply serve a sieving function and always transport substances unchanged across the epithelial barrier or whether they also sort and process antigens they endocytose and present them to adjacent lymphoid cells requires further study.

Structure and permeability differ in subepithelial villus and Peyer's patch follicle capillaries.

Intravenously injected sheep antilaminin immunoglobulin G conjugated with horseradish peroxidase uniformly labeled the basement membrane of mouse villus epithelium but not that of Peyer's patch follicle domes, although laminin is abundant in both. This suggested differences in the permeability of capillaries underlying these epithelia. Therefore, the fine structure of mouse subepithelial villus and follicle capillaries and their permeability to selected macromolecules was compared. Fenestrae, abundant in villus capillaries, were extremely rare in dome capillaries as assessed by electron microscopy of tissue sections and freeze-fracture replicas. Two minutes after IV-injected horseradish peroxidase and 9 minutes after IV-injected hemoglobin, reaction product decorated the pericapillary space of 97% and 95%, respectively, of capillary profiles in the upper half of villi but only 28% and 2%, respectively, of capillary profiles in the upper half of patch domes. Reaction product was intense surrounding most villus capillaries but, when present, was faint in dome capillary adventitia. These results indicate that most subepithelial capillaries in mouse Peyer's patch domes, unlike those in villi, generally lack endothelial fenestrae, and the dome capillary network is less permeable to some macromolecules than that of the villus.

Epithelial basement membrane of mouse jejunum. Evidence for laminin turnover along the entire crypt-villus axis.

Little is known regarding turnover of the epithelial basement membrane in adult small intestine. Are components degraded and inserted along the length of the crypt-villus axis or selectively in the crypt region with subsequent migration of basement membrane from crypt to villus tip in concert with epithelium? We injected affinity-purified sheep anti-laminin IgG or sheep anti-laminin IgG complexed to horseradish peroxidase (HRP) into mice to label basement membrane laminin in vivo. Fluorescence microscopy revealed linear fluorescence along the length of the jejunal epithelial basement membrane 1 d after anti-laminin IgG injection. By 1 wk, small nonfluorescent domains were interposed between larger fluorescent domains. Over the next 5 wk the lengths of nonfluorescent domains increased progressively whereas those of fluorescent domains decreased. Additionally, electron microscopy revealed HRP reaction product along the length of the epithelial basement membrane after 1 d whereas unlabeled or lightly labeled domains that increased in length with time were observed interposed between heavily labeled domains by 2 and 4 wk along the entire crypt-villus axis. We conclude that laminin turnover occurs focally in the epithelial basement membrane of mouse jejunum along the crypt-villus axis over a period of weeks and that this basement membrane does not comigrate in concert with its overlying epithelium.

Intraluminal proteolytic activation plays an important role in replication of type 1 reovirus in the intestines of neonatal mice.

Oral inoculation of suckling mice with reovirus serotype 1 (strain Lang) results in the conversion of intact virions to intermediate subviral particles (ISVPs) in the intestinal lumen. Digestion of virus in vitro with chymotrypsin or trypsin reveals two distinct forms of ISVPs, while the predominant species of ISVPs found in the small intestinal lumen appears to be identical to the chymotrypsin product. The in vivo conversion of virions to ISVPs was blocked by pretreatment of mice with protease inhibitors, resulting in inefficient replication of reovirus in intestinal tissue. The early inhibition of viral replication in suckling mice pretreated with protease inhibitors was not observed when suckling mice were inoculated with ISVPs generated by in vitro digestion with either chymotrypsin or trypsin. However, replication was decreased during secondary rounds of replication in mice receiving repeated doses of protease inhibitors, suggesting that luminal proteolytic digestion is important in rendering progeny virions infectious in the gut.

Repair of microvilli in the rat small intestine after damage with lectins contained in the red kidney bean.

That microvilli of intestinal absorptive cells in the duodenum and jejunum are disrupted by acute challenge with lectins contained in raw kidney beans (RKB) was shown nearly 10 yr ago by light microscopy. However, the precise morphologic damage produced by RKB has not been characterized, and it is not known whether microvilli, once damaged, undergo repair. We have examined these issues by challenging rats with suspensions of 300 mg of RKB, boiled beans, or standard laboratory chow by orogastric lavage. Microvillus length was measured in electron micrographs from 6 to 20 h after challenge. Epithelial cell migration was determined by autoradiography after injection of [3H]thymidine. After challenge with RKB, microvilli (a) showed extensive vesiculation along the length of villi 2-4 h after challenge; (b) were reduced significantly in length along the entire villus 6 h after challenge; and (c) were near normal in length by 20 h after challenge. Microvillus length was also reduced significantly 6 h after challenge with boiled beans. The rate of cell migration was not accelerated by treatment with RKB. These data suggest that damage to microvilli caused by 300 mg of RKB is self-limited and reversible; microvilli once damaged by RKB are repaired. Repair of microvilli is due to intrinsic reparative processes rather than accelerated replacement of damaged cells. We speculate that microvilli may be repeatedly damaged and repaired after ingestion of dietary lectins.

[The use of the residual range as the exclusive energy parameter in electron dosimetry]. / Zur Verwendung der Restreichweite als alleinigen Energieparameter in der Elektronendosimetrie.

A commonly used procedure to determine the absorbed dose to water in a high energy electron beam is based on the assumption that the response of an air-filled plane parallel chamber for this quantity is only a function of the difference between practical range and measuring depth (the residual range). This procedure is said to be applicable to almost all electron energies and spectra in practical use. The response of a plane parallel chamber in a water phantom was determined by means of ferrous sulphate dosimeters in radiation fields of a linear accelerator. The results show that the residual range is insufficient as the only energy parameter.

Immunocytochemical localization of actin in epithelial cells of rat small intestine by light and electron microscopy.

We used post-embedding immunocytochemical techniques and affinity-purified anti-actin antibody to evaluate localization of actin in epithelial cells of small intestine by fluorescence and electron microscopy. Small intestine was fixed with 2% formaldehyde-0.1% glutaraldehyde and embedded in Lowicryl K4M. One-micron or thin sections were stained with antibody followed by rhodamine- or colloidal gold-labeled goat anti-rabbit IgG, respectively. Label was present overlying microvilli, the apical terminal web, and the cytoplasm directly adjacent to occluding and intermediate junctions. Label was associated with outer mitochondrial membranes of all cells and the supranuclear Golgi region of goblet cells. Lateral cytoplasmic interdigitations between mature cells and subplasmalemmal filaments next to intrusive cells were densely labeled. The cytoplasm adjacent to unplicated domains of lateral membrane was focally labeled. Label was prominent over organized filament bundles within the subplasmalemmal web at the base of mature cells, whereas there was focal labeling of the cytoplasm adjacent to the basal membrane of undifferentiated cells. Basolateral epithelial cell processes were labeled. Label was focally present overlying the cellular ground substance. Our results demonstrate that actin is distributed in a distinctive fashion within intestinal epithelial cells. This distribution suggests that in addition to its function as a structural protein, actin may participate in regulation of epithelial tight junction permeability, in motile processes including migration of cells from the crypt to the villus tip, in accommodation of intrusive intraepithelial cells and in adhesion of cells to one another and to their substratum.