Prevalence and pathophysiology of early dumping in patients after primary Roux-en-Y gastric bypass during a mixed-meal tolerance test

Background

Early dumping is a poorly defined and incompletely understood complication after Roux-en-Y gastric (RYGB).

Pharmacy in transition: A work sampling study of community pharmacists using smartphone technology

Introduction

The nature of community pharmacy is changing, shifting from the preparation and distribution of medicines to the provision of cognitive pharmaceutical services (CPS); however, often the provision of traditional services leaves little time for innovative services. This study investigated the time community pharmacists spend on the tasks and activities of daily practice and to what extent they are able to implement CPS-related services in daily practice.

An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset within a few days to months after birth, resulting in persistent watery diarrhea. Mutations in the myosin Vb gene (MYO5B) have been identified in the majority of MVID patients. However, the exact pathophysiology of MVID still remains unclear. To address the specific role of MYO5B in the intestine, we generated an intestine-specific conditional Myo5b-deficient (Myo5b^fl/fl;Vil-CreERT2) mouse model. We analyzed intestinal tissues and cultured organoids of Myo5b^fl/fl;Vil-CreERT2 mice by electron microscopy, immunofluorescence, and immunohistochemistry. Our data showed that Myo5b^fl/fl;Vil-CreERT2 mice developed severe diarrhea within 4 d after tamoxifen induction. Periodic Acid Schiff and alkaline phosphatase staining revealed subapical accumulation of intracellular vesicles in villus enterocytes. Analysis by electron microscopy confirmed an almost complete absence of apical microvilli, the appearance of microvillus inclusions, and enlarged intercellular spaces in induced Myo5b^fl/fl;Vil-CreERT2 intestines. In addition, we determined that MYO5B is involved not only in apical but also basolateral trafficking of proteins. The analysis of the intestine during the early onset of the disease revealed that subapical accumulation of secretory granules precedes occurrence of microvillus inclusions, indicating involvement of MYO5B in early differentiation of epithelial cells. By comparing our data with a novel MVID patient, we conclude that our mouse model completely recapitulates the intestinal phenotype of human MVID. This includes severe diarrhea, loss of microvilli, occurrence of microvillus inclusions, and subapical secretory granules. Thus, loss of MYO5B disturbs both apical and basolateral trafficking of proteins and causes MVID in mice.Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with autosomal recessive inheritance, which was first described in 1978 (1). MVID patients cannot take up any nutrients and are often completely dependent on parenteral nutrition. The disease is characterized by villus atrophy, (partial) loss of microvilli on the apical plasma membrane of intestinal epithelial cells, and accumulation of intracellular vesicles/vacuoles, containing apical proteins and microvilli (2, 3). In addition, some studies also show mislocalization of apical and basolateral proteins, occasional crypt hyperplasia, and villus fusion (4–6).In the great majority of patients, MVID is caused by mutations in MYO5B, encoding the motorprotein, myosin Vb (5). In two patients, mutations in syntaxin 3 (STX3) caused a variant form of MVID (7). More than 41 unique mutations along the different regions in MYO5B have been identified in MVID patients, including deletions and nonsense, missense, and splice-site mutations (8–10). MYO5B is coding for the actin-based myosin 5b motor protein, which regulates apical membrane trafficking (5, 11). MYO5B functions as a homodimer and has three functional domains: an N-terminal motor domain, a calmodulin-binding domain, and a C-terminal tail, which binds cargo through association with the small GTPases RAB8A and/or RAB11A (12, 13). Altered expression of myosin Vb affects the apical membrane trafficking mechanism in epithelial cells, causing mislocalization of apical brush border proteins, such as villin (vil), CD10, or alkaline phosphatase (ALP) in the cytoplasm of duodenal enterocytes (2, 3, 5), and an increased apical localization of transferrin receptor (5, 14).Although mouse models mimicking certain features of MVID have previously been described, such as Rab8 (15), Cdc42 (16, 17), and Rab11a knockout (KO) mice (18, 19), no mutations in the coding regions of those genes have been reported in human MVID patients. Current in vitro models to study apical trafficking and polarization-associated diseases such as MVID are the parental Caco2 cell line, Caco-BBE, and LS174 W4 cells, in which polarization can be induced in vitro (4, 8, 12, 20). Although valuable knowledge about the function of MYO5B in polarization was gained in these models, the direct relevance of the colon cancer cell lines for the disease is questionable, and diverging results have been obtained with knockdown of MYO5B in the parental Caco2 cells compared with the more polarized Caco-BBE cells (8, 12, 20). As such, we here present an inducible MVID mouse model that recapitulates the genetic defects in man, which allows analysis of the role of MYO5B in a physiological setting and the sequence of events in MVID pathophysiology.     

Anterior disk displacement of the temporomandibular joint

Summary In order to examine the diagnostic significance of typical clinical symptoms in temporomandibular joint (TMJ) disorders for diagnosis of anterior disk displacement, clinical findings were compared with the degree of disk displacement in 84 TMJs of 59 patients with TMJ disorders, who were examined clinically and by means of magnetic resonance imaging (MRI). The control group consisted of 31 subjects with no TMJ symptoms. No significant correlation between the degree of anterior disk displacement and palpation pain of the masticatory muscles or clicking/crepitus of the TMJ could be found. Joint clicking was observed in 65% of patients with TMJ symptoms in normal disk position (NDP). The percentage of joint clicking was almost the same in patients with anterior disk displacement with reposition (ADWR) (68%). There were significant correlations between active mouth opening and disk position as well as between a history of pain and disk position. Patients with NDP and ADWR had almost identical mouth opening values: 48 (±5) mm and 46 (±5) mm respectively. In contrast to these groups the mean values decreased significantly to 42 (±6) mm in patients with anterior disk displacement without reposition (ADWOR). There were no significant correlations between occlusal findings (centric relation and habitual relation, early occlusal contacts, abrasion facets) and disk position when viewed either collectively or individually.

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Anteriore Verlagerung des Discus articularis des Kiefergelenkes

Zusammenfassung Zur Überprüfung der Wertigkeit typisch klinischer Symptome für Funktionsstörungen zur Diagnose von Diskusverlagerungen wurden 84 Kiefergelenke von 59 Patienten mit Funktionsstörungen und 31 Kiefergelenke von klinisch asymptomatischen Probanden mittels Magnetresonanztomographie (MRT) untersucht und die einzelnen klinischen Befunde der Art der Diskusvergerung gegenübergestellt. Zwischen dem Grad der anterioren Diskusverlagerung und einem positiven Palpationsbefund der Kaumuskulatur, einem Palpationsschmerz der Kiefergelenke und dem Auftreten von Gelenkgeräuschen ergaben sich keine signifikanten Beziehungen. Bei funktionsgestörten Patienten zeigte sich mit 65% bei normaler Diskusposition (NDP) fast ebenso oft ein Gelenkknacken wie bei Patienten mit anteriorer Diskusverlagerung mit Reposition (VMR, 68%). Signifikante Beziehungen bestanden zwischen aktiver Mundöffnung und Diskusposition sowie anamnestisch angegebenen Schmerzen und Diskusposition. Während bei NDP- und VMR-Patienten mit 48 (±5) mm und 46 (±5) mm ähnlich hohe Mundöffnungswerte vorlagen, nahmen diese bei Patienten mit anteriorer Diskusverlagerung ohne Reposition (VOR) auf 42 (±6) mm signifikant ab. Okklusale Befunde (Differenz zwischen zentrischer und habitueller Okklusion >2 mm, vorzeitige okklusale Kontakte, Auftreten von Schliffacetten) zeigten in ihrer Gesamtheit wie auch in der Einzelbetrachtung keine signifikanten Beziehungen zur Diskusposition. Die Ergebnisse zeigen, daß für die Diagnostik von Funktionsstörungen allgemein als bedeutend anerkannte klinische Symptome in bezug auf die Art und das Vorliegen einer anterioren Diskusverlagerung allein keine sichere Aussage zulassen. Dies betrifft besonders die anteriore Diskusverlagerung ohne Reposition. Gleichzeitig wird die Zuverlässigkeit der MRT für die klinisch oft schwierige Diagnostik der Bestimmung der Diskusverlagerung bei Patienten mit Funktionsstörungen des Kausystems bestätigt.

     

Social Relationship Factors,Preoperative Depression,and Hospital Length of Stay in Surgical Patients

Purpose

The interrelated associations of social relationship factors, depression, and outcomes of surgical patients are yet unexplored. The purpose of this study was to investigate whether depression mediates effects of general social support, loneliness, and living alone on hospital length of stay (LOS) of 2487 patients from diverse surgical fields.

Method

Social relationship factors and depression were assessed prior to surgery. The PROCESS macro for SPSS was used to conduct three simple mediation models that tested the indirect effects of social relationship factors on LOS mediated through depression. The models were adjusted for age, gender, preoperative physical health, surgical field, severity of medical comorbidity, and extent of surgical procedure.

Results

Social support and loneliness had significant indirect effects on LOS that were statistically mediated by preoperative depression. Lower social support and the feeling of loneliness were considerably related to higher depression which predicted longer LOS. While social support and loneliness had no direct effects on LOS, there was a small significant direct association of living alone with shorter LOS.

Conclusion

Data suggest that social support and loneliness are indirectly related with surgical outcomes by an association with depression which in turn is related to worse outcomes.

Trial Registration

NCT01357694