Islet isolation assessment in man and large animals

Recent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity and in vitro and in vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 μ diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason, in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers. © 1990 Casa Editrice il Ponte

The neural substrate of positive bias in spontaneous emotional processing

Even in the presence of negative information, healthy human beings display an optimistic tendency when thinking of past success and future chances, giving a positive bias to everyday's cognition. The tendency to actively select positive thoughts suggests the existence of a mechanism to exclude negative content, raising the issue of its dependence on mechanisms like those of effortful control. Using perfusion imaging, we examined how brain activations differed according to whether participants were left to prefer positive thoughts spontaneously, or followed an explicit instruction to the same effect, finding a widespread dissociation of brain perfusion patterns. Under spontaneous processing of emotional material, recruitment of areas associated with effortful attention, such as the dorsolateral prefrontal cortex, was reduced relative to instructed avoidance of negative material (F(1,58) = 26.24, p = 0.047, corrected). Under spontaneous avoidance perfusion increments were observed in several areas that were deactivated by the task, including the perigenual medial prefrontal cortex. Furthermore, individual differences in executive capacity were not associated with positive bias. These findings suggest that spontaneous positive cognitive emotion regulation in health may result from processes that, while actively suppressing emotionally salient information, differ from those associated with effortful and directed control

Altered Perceptual Sensitivity to Kinematic Invariants in Parkinson's Disease

Ample evidence exists for coupling between action and perception in neurologically healthy individuals, yet the precise nature of the internal representations shared between these domains remains unclear. One experimentally derived view is that the invariant properties and constraints characterizing movement generation are also manifested during motion perception. One prominent motor invariant is the “two-third power law,” describing the strong relation between the kinematics of motion and the geometrical features of the path followed by the hand during planar drawing movements. The two-thirds power law not only characterizes various movement generation tasks but also seems to constrain visual perception of motion. The present study aimed to assess whether motor invariants, such as the two thirds power law also constrain motion perception in patients with Parkinson's disease (PD). Patients with PD and age-matched controls were asked to observe the movement of a light spot rotating on an elliptical path and to modify its velocity until it appeared to move most uniformly. As in previous reports controls tended to choose those movements close to obeying the two-thirds power law as most uniform. Patients with PD displayed a more variable behavior, choosing on average, movements closer but not equal to a constant velocity. Our results thus demonstrate impairments in how the two-thirds power law constrains motion perception in patients with PD, where this relationship between velocity and curvature appears to be preserved but scaled down. Recent hypotheses on the role of the basal ganglia in motor timing may explain these irregularities. Alternatively, these impairments in perception of movement may reflect similar deficits in motor production

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Advanced glycation endproducts and diabetes. Beyond vascular complications.

Advanced Glycation Endproducts (AGEs) are a group of heterogeneous compounds formed by the non enzymatic reactions between aldehydic group of reducing sugars with proteins, lipids or nucleic acids. Formation and accumulation of AGEs is related with the aging process and is accelerated in diabetes. Type 2 diabetes, the most common form of diabetes, is characterized by hyperglycaemia and insulin resistance associated to a progressive deterioration of beta cell function and mass. The pathogenic role of AGEs in vascular diabetic complications is widely recognised. Recently other aspects of the detrimental effects of AGEs in type 2 diabetes are emerged: AGEs interfere with the complex molecular pathway of insulin signaling, leading to insulin resistance; AGEs modify the insulin molecule, and, consequently, its function; AGEs decrease insulin secretion and insulin content. In this article we review the role of AGEs in type 2 diabetes, beyond their involvement in vascular complications