Angiotensin II type 2 receptor stimulation increases the rate of NG108-15 cell migration via actin depolymerization

Angiotensin II (Ang II) has been reported to induce migration in neuronal cell types. Using time-lapse microscopy, we show here that Ang II induces acceleration in NG108-15 cell migration. This effect was antagonized by PD123319, a selective AT2 receptor antagonist, but not by DUP753, a selective AT1 receptor antagonist, and was mimicked by the specific AT2 receptor agonist CGP42112. This Ang II-induced acceleration was not sensitive to the inhibition of previously described signaling pathways of the AT2 receptor, guanylyl cyclase/cyclic GMP or p42/p44 mapk cascades, but was abolished by pertussis toxin treatment and involved PP2A activation. Immunofluorescence studies indicate that Ang II or CGP42112 decreased the amount of filamentous actin at the leading edge of the cells. This decrease was accompanied by a concomitant increase in globular actin levels. Regulation of actin turnover in actin-based motile systems is known to be mainly under the control of the actin depolymerizing factor and cofilin. Basal migration speed decreased by 77.2% in cofilin-1 small interfering RNA-transfected NG108-15 cells, along with suppression of the effect of Ang II. In addition, the Ang II-induced increase in cell velocity was abrogated in serum-free medium as well as by genistein or okadaic acid treatment in a serum-containing medium. Such results indicate that the AT2 receptor increases the migration speed of NG108-15 cells and involves a tyrosine kinase activity, followed by phosphatase activation, which may be of the PP2A type. Therefore, the present study identifies actin depolymerization and cofilin as new targets of AT2 receptor action, in the context of cellular migration.     

Trends in robot-assisted and virtual reality-assisted neuromuscular therapy: a systematic review of health-related multiplayer games

Background

Multiplayer games have emerged as a promising approach to increase the motivation of patients involved in rehabilitation therapy. In this systematic review, we evaluated recent publications in health-related multiplayer games that involved patients with cognitive and/or motor impairments. The aim was to investigate the effect of multiplayer gaming on game experience and game performance in healthy and non-healthy populations in comparison to individual game play. We further discuss the publications within the context of the theory of flow and the challenge point framework.

Methods

A systematic search was conducted through EMBASE, Medline, PubMed, Cochrane, CINAHL and PsycINFO. The search was complemented by recent publications in robot-assisted multiplayer neurorehabilitation. The search was restricted to robot-assisted or virtual reality-based training.

Results

Thirteen articles met the inclusion criteria. Multiplayer modes used in health-related multiplayer games were: competitive, collaborative and co-active multiplayer modes. Multiplayer modes positively affected game experience in nine studies and game performance in six studies. Two articles reported increased game performance in single-player mode when compared to multiplayer mode.

Conclusions

The multiplayer modes of training reviewed improved game experience and game performance compared to single-player modes. However, the methods reviewed were quite heterogeneous and not exhaustive. One important take-away is that adaptation of the game conditions can individualize the difficulty of a game to a player’s skill level in competitive multiplayer games. Robotic assistance and virtual reality can enhance individualization by, for example, adapting the haptic conditions, e.g. by increasing haptic support or by providing haptic resistance. The flow theory and the challenge point framework support these results and are used in this review to frame the idea of adapting players’ game conditions.

     

Effect of surgical and non-surgical periodontal treatment on periodontal status and subgingival microbiota

The purpose of this study was to evaluate, on a short-term basis, the clinical and microbiological effects of a single course of scaling and root planing as compared with those obtained by flap surgery in patients with moderate to advanced periodontitis. 11 patients participated in the study. Using a split-mouth design, one quadrant of the mouth was treated with reverse bevel flap surgery, whereas the contralateral one was subjected to a single course of scaling and root planing. 2 approximal sites on single-rooted teeth with a pocket depth greater than or equal to 5 mm were monitored clinically and microbiologically for 16 weeks after active treatment. Both techniques resulted in a gain of probable attachment levels, a reduction in bleeding on probing and a reduced mean pocket depth, although 31.2% of the sites in the scaling and root planing group still had 6-7 mm deep pockets at 8 and 16 weeks after treatment. Both techniques reduced median relative proportions and frequencies of detection of black-pigmented Bacteroides species. A highly statistically significant increase (p less than 0.01) in median proportions of oral streptococci was recorded only for surgery within the 1st month post-operatively. No correlation was found between residual pocket depth and any of the microbiological parameters considered in the study, suggesting that residual pocket depth does not exert a significant influence on bacterial subgingival recolonization after therapy. The results from this study suggest that surgery can be as effective as scaling and root planing in favoring the establishment of micro-organisms compatible with periodontal health, although this effect is limited to the 1st month after therapy.     

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.     

Is there an advantage in using homografts in patients with acute infective endocarditis of the aortic valve?

BACKGROUND AND AIM OF THE STUDY: Acute infective endocarditis is a surgical challenge, particularly when paravalvular abscesses and annular destruction are present. The choice of a homograft or mechanical valve prosthesis is an important issue in these patients. The study aim was to compare the outcome with homografts and mechanical valves in patients with acute infective endocarditis. METHODS: A total of 77 patients (mean age 49+/-9 years) operated on for acute endocarditis of the aortic valve was included in the study and analyzed retrospectively. The causative bacterium was isolated from blood cultures in 71 cases. Preoperatively, 21 patients required artificial ventilation and 24 had inotropic support due to hemodynamic instability. Aortic homografts were implanted in 43 patients, and mechanical valve prostheses in 34. The two patient groups were similar in terms of gender, age and preoperative inotropic support. In total, 31 patients (44%) had paravalvular abscesses, and a homograft was used significantly more often (77%, p <0.05) in these cases. Follow up examinations (clinical examination, ECG and transthoracic echocardiography) were performed six months postoperatively and continued on an annual basis. Endocarditis relapse was defined as persisting infection, whereas re-endocarditis indicated a new infection after an interval of at least six months. RESULTS: Perioperative mortality was 11.5% (5/43) in homograft patients. In the 38 survivors, follow up was complete and averaged 5.0+/-1.2 years. One patient had an endocarditis relapse three months after surgery. Re-endocarditis occurred in three patients after two or three years. One other patient had pseudoaneurysm formation without a need for intervention, and one had repeat aortic valve replacement due to dysfunction of the graft after four years. The other 33 patients had an uneventful follow up. Echocardiography revealed aortic insufficiency grade 1 in 12 cases (36%), with no progression during follow up. Perioperative mortality in mechanicat valve patients was 20.5% (n = 7) (p <0.05 versus homograft), and in those with paravalvular abscess, perioperative mortality was even higher than in homograft patients (4/7, 57.1% versus 3/24, 12.5%; p <0.05). When considering only patients without paravalvular abscess, there was no significant difference between groups (10.5% versus 12.5%). Three relapses occurred in mechanical valve patients (10.3%), but no endocarditis recurred during follow up. One late death (3.7%) occurred due to bleeding complicating long-term anticoagulation. CONCLUSION: The study results do not permit a general recommendation to be made for homograft use in patients with acute endocarditis. In cases with paravalvular abscesses, however, there was a trend towards improved outcome in the homograft group.     

Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.