How many forms of perseveration? Evidence from cancellation tasks in right hemisphere patients

Neglect patients' performance during cancellation tasks is characterized by left sided omissions and, in many cases, by the production of inappropriate material of various kinds in the ipsilesional space, e.g. additional marks over already cancelled targets, marks drawn away from targets, scribbles, irrelevant drawings. It is unclear whether these behaviours, which have collectively been called perseverative, are functionally and anatomically connected and whether they correlate with the severity of neglect. Here we report a retrospective study on 33 right brain damaged patients with neglect after right hemisphere lesions in whom we measured the intensity of perseveration of the three following kinds: (1) ‘additional marks' (AM) perseveration where patients cancelled a target with two or more well separated marks; (2) ‘scribble’ perseveration, where patients, instead of cancelling the target with a single pen stroke as required by the task, performed multiple pen strokes without breaking the pen-to-paper contact, with the final product being a scribble; (3) ‘flying marks’ (FM) perseveration where patients produced cancellation marks well away from the targets. We found that AM and FM perseveration correlated with neglect severity, while ‘scribble’ perseveration did not. The lesion-symptom mapping showed three separate anatomical areas in the right hemisphere: ‘scribble’ perseveration was associated with lesions of the orbitofrontal cortex and caudate nucleus; AM perseveration was associated with damage to the rolandic operculum, superior temporal gyrus and inferior frontal gyrus; FM perseveration was associated with damage to the dorsal premotor cortex and the temporal pole. Neglect severity followed damage to a region which grossly corresponds to the sum of the regions associated with AM and FM perseveration respectively. This complex behavioural and anatomical pattern is interpreted in terms of a three-factor model, in which AM perseveration is caused by a deficit of disengagement of attention from the right side (also causing omissions), FM perseveration is caused by directional hypokinesia (also causing left-side omissions), and ‘scribble’ perseveration is the consequence of a failure to inhibit an initiated motor act, which is completely separate (both anatomically and functionally) from the disorder inducing omissions.     

Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure

Background  

Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.     

Treating Eating Disorders at Higher Levels of Care: Overview and Challenges

Higher levels of care (HLC)—including inpatient hospitalization, residential treatment, partial hospitalization, and intensive outpatient treatment—are frequently utilized within routine care for eating disorders. Despite widespread use, there is limited research evaluating the efficacy of HLC, as well as clinical issues related to care in these settings. This review describes the different levels of care for eating disorders and briefly reviews the most up-to-date guidelines and research regarding how to choose a level of care. In addition, as HLC approaches for ED continue to be developed and refined, pragmatic and conceptual challenges have emerged that provide barriers to clinical efficacy and the execution of high-quality treatment research. This review includes a discussion of various issues specific to HLC, as well as a summary of recent literature addressing them.     

Three-dimensional finite-element analysis of a central lower incisor under labial and lingual loads

IntroductionThe aim was to evaluate the differences between labial and lingual application of an orthodontic force. This was achieved using a three-dimensional CAD design software model of a real lower incisor surrounded by a prismatic representation of the mandibular bone. This model was subjected to various loading conditions, with finite-element analysis.Materials and methodsCone-beam computed tomography scanning was used to create a three-dimensional geometric model of a lower incisor, together with its simulated periodontal ligament. This model was then meshed and analysed with commercial finite-element code. Various single and combined forces and moments were applied to each side of the simulated lower incisor at the centre of the clinical crown. To evaluate the effects of the various forces considered, the instantaneous displacement and stress generated in the bone and the periodontal ligament were measured, as a comparison of the labial and lingual loading sites.ResultsDental movement was only influenced by the side of the force application when an intrusive component was present. The simulations showed larger displacement when a vertical force was present at the lingual surface. In general, this movement was of the tipping type when the combined forces were applied, while there was greater intrusion upon application of combined forces and an anticlockwise moment to the labial surface.ConclusionsApplication of an intrusive lingual force to a lower incisor appears to generate bodily movement, while the same intrusive labial force appears to lead to labial tipping. Subject to further study, this should be taken into consideration when devising treatment plans for fixed appliances.     

Identification of a novel selective serotonin reuptake inhibitor by coupling monoamine transporter-based virtual screening and rational molecular hybridization

Ligand virtual screening (VS) using the vestibular binding pocket of a 3-D monoamine transporter (MAT) computational model followed by in vitro pharmacology led to the identification of a human serotonin transporter (hSERT) inhibitor with modest affinity (hSERT K(i) = 284 nM). Structural comparison of this VS-elucidated compound, denoted MI-17, to known SERT ligands led to the rational design and synthesis of DJLDU-3-79, a molecular hybrid of MI-17 and dual SERT/5-HT(1A) receptor antagonist SSA-426. Relative to MI-17, DJLDU-3-79 displayed 7-fold improvement in hSERT binding affinity and a 3-fold increase in [(3)H]-serotonin uptake inhibition potency at hSERT/HEK cells. This hybrid compound displayed a hSERT:hDAT selectivity ratio of 50:1, and a hSERT:hNET (human norepinephrine transporter) ratio of >200:1. In mice, DJLDU-3-79 decreased immobility in the tail suspension test comparable to the SSRI fluvoxamine, suggesting that DJLDU-3-79 may possess antidepressant properties. This proof of concept study highlights MAT virtual screening as a powerful tool for identifying novel inhibitor chemotypes and chemical fragments for rational inhibitor design.     

Evaluation of smear layer removal by bicarbonate soda,ethylenediamine tetraacetic acid with cetrimide and sodium hypochlorite with a new model

Various methods are used to evaluate irrigants. The primary aim was to develop a model for preliminary testing of potential irrigants. The second aim was to investigate the effect of bicarbonate soda on smear layer by comparing it with ethylenediamine tetraacetic acid with cetrimide (EDTAC) and sodium hypochlorite (NaOCl). Extracted human single‐canal teeth were halved, and a uniform filing method was used to create smear layer. The following solutions were then applied – distilled water (control), 1% NaOCl, 17% EDTAC and bicarbonate soda at concentrations of 1%, 5%, 10% and 15%. Some samples had multiple solutions in different sequences. Samples were examined by scanning electron microscopy. Representative images were scored based on the degree of smear layer remaining. Results were analysed with the SAS system, using the GENMOD procedure. Complete smear layer was found in samples treated with all solutions except EDTAC used alone. There were no significant differences between the sequences, EDTAC/NaOCl/EDTAC and NaOCl/EDTAC/NaOCl. There were no significant differences between groups with and without bicarbonate soda. In conclusion, the model was effective for testing chemical effects on solutions on smear layer. Bicarbonate soda did not remove smear layer and provided no additional cleaning effects after EDTAC and NaOCl.