Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development.

Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. We found that rodent and human T lymphocytes release exosomes containing the microRNAs (miRNAs) miR-142-3p, miR-142-5p, and miR-155, which can be transferred in active form to β cells favoring apoptosis. Inactivation of these miRNAs in recipient β cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development. Islets from protected NOD mice display higher insulin levels, lower insulitis scores, and reduced inflammation. Looking at the mechanisms underlying exosome action, we found that T lymphocyte exosomes trigger apoptosis and the expression of genes involved in chemokine signaling, including Ccl2, Ccl7, and Cxcl10, exclusively in β cells. The induction of these genes may promote the recruitment of immune cells and exacerbate β cell death during the autoimmune attack. Our data point to exosomal-miRNA transfer as a communication mode between immune and insulin-secreting cells

Employment rates in flexible assertive community treatment teams in The Netherlands:An observational study

We determined the proportions of clients treated in Flexible Assertive Community Treatment teams who were unemployed and gained employment and who were employed and lost employment. Secondly, we explored the demographical and clinical factors associated with employment. Data were collected during routine outcome monitoring. We calculated differences in employment rates over a year and explored differences in demographic characteristics at baseline between patient groups. Logistic regression analysis was used to estimate the role of clinical predictor variables on employment status. Over time, 10% remained employed, 5% lost their employment, 3% gained employment and 82% remained unemployed. Clients who found employment were younger, more often male, and had significantly fewer psychosocial problems and a higher subjective quality of life during follow-up than those who remained unemployed. Problems with motivation for treatment at baseline were related to losing employment or remaining unemployed. Better implementation of vocational services is very important for increasing the number of clients gaining employment

Reproducibility of 3 different tracing methods based on cone beam computed tomography in determining the anatomical position of the mandibular canal.

Contains fulltext : 89402.pdf (publisher's version ) (Closed access)PURPOSE: To investigate the reproducibility of 3 different tracing methods to determine a reliable method to define the proper anatomical position of the mandibular canal based on cone beam computed tomography (CBCT) data. MATERIALS AND METHODS: Five dentate and 5 edentate patients were selected at random from the CBCT database. Two independent observers traced both the left and the right mandibular canal using 3-dimensional image-based planning software (Procera System NobelGuide; Nobel Biocare, Goteborg, Sweden). All mandibular canals were traced using 3 different methods. Method I was based on coronal views, also known as cross-sections. Panorama-like reconstructions were the starting point for method II. The third method combined methods I and II. RESULTS: With respect to interobserver reliability, no significant difference (P = .34) for the various methods was observed. The reproducibility was better in edentate than in dentate jaws (P = .0015). The difference between 2 tracings was the lowest for the combined method: within a range of 1.3 mm in 95% of the course of the canal. The most obvious deviations were mainly seen in the anterior part of the canal. CONCLUSIONS: The best reproducible method for mandibular canal tracing is the combined method III. Between observers, still a mean 95th percentile deviation threshold of 1.3 mm (SD 0.384) is noted, indicating that a safety zone of 1.7 mm should be respected. When planning surgery on CBCT-based data, surgeons should be aware of the obvious deviations located in the region of the anterior loop of the canal.1 april 201

Different perspectives of clinicians and patients with severe mental illness on motivation for treatment

The present study assessed motivation for engaging in treatment as rated by clinicians (n = 57) and patients with severe mental illness (SMI, n = 294) using measures based on three different motivation theories. Questionnaires were derived from self-determination theory, the transtheoretical model and the integral model of treatment motivation. It was investigated to which extent clinicians of patients with SMI were able to estimate their patient's perspective on motivation for engaging in treatment, to which extent they agreed on the patient's motivation and which factors were associated with estimation and agreement on treatment motivation. It was found that clinicians were poorly to moderately capable of estimating their patient's type of motivation and readiness for change. Further, agreement on the level of motivation between patients and clinicians was moderate. These findings were consistent across diagnostic groups (psychotic and personality disorders). A higher quality therapeutic relationship was generally associated with higher clinician-rated motivation. The patient's ethnicity and socially desirable responding were factors that differentiated between scales of different motivation theories. It is concluded that patients with SMI and their clinicians have different perceptions on the patient's motivation for engaging in psychiatric treatment, regardless of the theoretical framework that is used to measure motivation. The findings imply that a negotiated approach is needed where both perceptions of clinicians and patients on motivation for treatment are considered to ensure effective mental health interventions. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message Clinicians show poor to moderate capability in estimating how patients perceive their motivation for engaging in treatment, especially so when the patient's motives revolve around feelings of shame and guilt. Clinicians generally give higher motivation ratings for patients where they experience a higher quality therapeutic relationships with, whereas—depending on the scale that is used to measure motivation—they give lower ratings to patients who respond in socially desirable ways and to ethnic minority patients. As patients with SMI and their clinicians have different perceptions on the patient's motivation for engaging in psychiatric treatment (regardless of the theoretical framework that is used to assess motivation), this implies that a negotiated approach is needed where both perceptions of clinicians and patients on motivation for treatment are considered to ensure effective mental health interventions

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study

Objective: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. Background: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. Methods: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. Results: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were 725,400 per 10,000 patients. Conclusions: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit