L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

AIM To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. METHODOLOGY Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. RESULTS Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with L-mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 levels (P < 0.05). CONCLUSIONS The prolyl hydroxylase inhibitor L-mimosine increased VEGF production via HIF-1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.

Successful transnasal delivery of stem cells in a rat model of perinatal hypoxic-ischemic brain injury

OBJECTIVE: New routes for cell transplantation into the brain need to be explored as intracerebral or intrathecal applications have a high risk to cause damage to the central nervous system. It has been hypothesized that transnasally administrated cells bypass the blood-brain barrier and migrate along the olfactory neural route into the brain and cerebrospinal fluid. Our goal is to confirm this hypothesis by transnasally administrating Wharton’s Jelly mesenchymal stem cells (WJ-MSC) and neural progenitor cells (NPC) to perinatal rats in a model of hypoxic-ischemic brain injury. STUDY DESIGN: Four-day-old Wistar rat pups, previously brain-damaged by combined hypoxic-ischemic and inflammatory insult, either received WJ-MSC or green fluorescent protein-expressing NPC: The heads of the rat pups were immobilized and 3 ml drops containing the cells (50’000 cells/ml) were placed on one nostril allowing it to be snorted. This procedure was repeated twice, alternating right to left nostril with an interval of one minute between administrations. The rat pups received a total of 600’000 cells. Animals were sacrificed 24h, 48h or 7 days after the application of the cells. Fixed brains were collected, embedded in paraffin and sectioned. RESULTS: Transplanted cells were found in the layers of the olfactory bulb (OB), the cerebral cortex, thalamus and the hippocampus. The amount of cells was highest in the OB. Animals treated with transnasally delivered stem cells showed significantly decreased gliosis compared to untreated animals. CONCLUSION: Our data show that transnasal delivery of WJ-MSC and NPC to the newborn brain after perinatal brain damage is successful. The cells not only migrate the brain, but also decrease scar formation and improve neurogenesis. Therefore, the non-invasive intranasal delivery of stem cells to the brain may be the preferred method for stem cell treatment of perinatal brain damage and should be preferred in future clinical trials.

Standard model cross-over on the lattice

With the physical Higgs mass the standard model symmetry restoration phase transition is a smooth cross-over. We study the thermodynamics of the cross-over using numerical lattice Monte Carlo simulations of an effective SU(2)×U(1) gauge+Higgs theory, significantly improving on previously published results. We measure the Higgs field expectation value, thermodynamic quantities like pressure, energy density, speed of sound and heat capacity, and screening masses associated with the Higgs and Z fields. While the cross-over is smooth, it is very well defined with a width of only ∼5  GeV. We measure the cross-over temperature from the maximum of the susceptibility of the Higgs condensate, with the result Tc=159.5±1.5  GeV. Outside of the narrow cross-over region the perturbative results agree well with nonperturbative ones.

Comparison of two protocols of periosteal distraction osteogenesis in a rabbit calvaria model

The regenerative pathways during periosteal distraction osteogenesis may be influenced by the local environment composed by cells, growth factors, nutrition and mechanical load. The aim of the present study was to evaluate the influence of two protocols of periosteal distraction on bone formation. Custom made distraction devices were surgically fixed onto the calvariae of 60 rabbits. After an initial healing period of 7 days, two groups of animals were submitted to distraction rates of 0.25 and 0.5 mm/24 h for 10 days, respectively. Six animals per group were sacrificed 10 (mid-distraction), 17 (end-distraction), 24 (1-week consolidation), 31 (2-week consolidation) and 77 days (2-month consolidation) after surgery. Newly formed bone was assessed by means of micro-CT and histologically. Expression of transcripts encoding tissue-specific genes (BMP-2, RUNX2, ACP5, SPARC, collagen I α1, collagen II α1 and SOX9) was analyzed by quantitative PCR. Two patterns of bone formation were observed, originating from the old bone surface in Group I and from the periosteum in Group II. Bone volume (BV) and bone mineral density (BMD) significantly increased up to the 2-month consolidation period within the groups (p < 0.05). Significantly more bone was observed in Group II compared to Group I at the 2-month consolidation period (p < 0.001). Expression of transcripts encoding osteogenic genes in bone depended on the time-point of observation (p < 0.05). Low level of transcripts reveals an indirect role of periosteum in the osteogenic process. Two protocols of periosteal distraction in the present model resulted in moderate differences in terms of bone formation.

Cryoinjury as a myocardial infarction model for the study of cardiac regeneration in the zebrafish.

The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than on tissue damage. We recently characterized the cellular response and regenerative capacity of the zebrafish heart after cryoinjury (CI), an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). After anesthesia, localized CI with a liquid nitrogen-cooled copper probe induced damage in 25% of the ventricle, in a procedure requiring <5 min. Here we present a detailed description of the technique, which provides a valuable system for the study of the mechanisms of heart regeneration and scar removal after MI in a versatile vertebrate model.

Situational adaptiveness of control orientation mediates relation between fixed-world view and youth well-being in three cultures

When proposing primary control (changing the world to fit self)/secondary control (changing self to fit the world) theory, Weisz et al. (1984) argued for the importance of the “serenity to accept the things I cannot change, the courage to change the things I can” (p. 967), and the wisdom to choose the right control strategy that fits the context. Although the dual processes of control theory generated hundreds of empirical studies, most of them focused on the dichotomy of PC and SC, with none of these tapped into the critical concept: individuals’ ability to know when to use what. This project addressed this issue by using scenario questions to study the impact of situationally adaptive control strategies on youth well-being. To understand the antecedents of youths’ preference for PC or SC, we also connected PCSC theory with Dweck’s implicit theory about the changeability of the world. We hypothesized that youths’ belief about the world’s changeability impacts how difficult it was for them to choose situationally adaptive control orientation, which then impacts their well-being. This study included adolescents and emerging adults between the ages of 18 and 28 years (Mean = 20.87 years) from the US (n = 98), China (n = 100), and Switzerland (n = 103). Participants answered a questionnaire including a measure of implicit theories about the fixedness of the external world, a scenario-based measure of control orientation, and several measures of well-being. Preliminary analyses of the scenario-based control orientation measures showed striking cross-cultural similarity of preferred control responses: while for three of the six scenarios primary control was the predominately chosen control response in all cultures, for the other three scenarios secondary control was the predominately chosen response. This suggested that youths across cultures are aware that some situations call for primary control, while others demand secondary control. We considered the control strategy winning the majority of the votes to be the strategy that is situationally adaptive. The results of a multi-group structural equation mediation model with the extent of belief in a fixed world as independent variable, the difficulties of carrying out the respective adaptive versus non-adaptive control responses as two mediating variables and the latent well-being variable as dependent variable showed a cross-culturally similar pattern of effects: a belief in a fixed world was significantly related to higher difficulties in carrying out the normative as well as the non-normative control response, but only the difficulty of carrying out the normative control response (be it primary control in situations where primary control is normative or secondary control in situations where secondary control is normative) was significantly related to a lower reported well-being (while the difficulty of carrying out the non-normative response was unrelated to well-being). While previous research focused on cross-cultural differences on the choice of PC or SC, this study shed light on the universal necessity of applying the right kind of control to fit the situation.

Shape model, reference system definition, and cartographic mapping standards for comet 67P/Churyumov-Gerasimenko Stereo-photogrammetric analysis of Rosetta/OSIRIS image data

We analyzed more than 200 OSIRIS NAC images with a pixel scale of 0.9-2.4 m/pixel of comet 67P/Churyumov-Gerasimenko (67P) that have been acquired from onboard the Rosetta spacecraft in August and September 2014 using stereo-photogrammetric methods (SPG). We derived improved spacecraft position and pointing data for the OSIRIS images and a high-resolution shape model that consists of about 16 million facets (2 m horizontal sampling) and a typical vertical accuracy at the decimeter scale. From this model, we derive a volume for the northern hemisphere of 9.35 km(3) +/- 0.1 km(3). With the assumption of a homogeneous density distribution and taking into account the current uncertainty of the position of the comet's center-of-mass, we extrapolated this value to an overall volume of 18.7 km(3) +/- 1.2 km(3), and, with a current best estimate of 1.0 X 10(13) kg for the mass, we derive a bulk density of 535 kg/m(3) +/- 35 kg/m(3). Furthermore, we used SPG methods to analyze the rotational elements of 67P. The rotational period for August and September 2014 was determined to be 12.4041 +/- 0.0004 h. For the orientation of the rotational axis (z-axis of the body-fixed reference frame) we derived a precession model with a half-cone angle of 0.14 degrees, a cone center position at 69.54 degrees/64.11 degrees (RA/Dec J2000 equatorial coordinates), and a precession period of 10.7 days. For the definition of zero longitude (x-axis orientation), we finally selected the boulder-like Cheops feature on the big lobe of 67P and fixed its spherical coordinates to 142.35 degrees right-hand-rule eastern longitude and -0.28 degrees latitude. This completes the definition of the new Cheops reference frame for 67P. Finally, we defined cartographic mapping standards for common use and combined analyses of scientific results that have been obtained not only within the OSIRIS team, but also within other groups of the Rosetta mission.

Type A aortic dissection model to improve endovascular research and technologies.

OBJECTIVE Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. METHODS Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. RESULTS Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. CONCLUSION This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.

The strengh model of self-control in sport and exercise psychology

The strength model of self-control assumes that all acts of self-control (e.g., emotion regulation, persistence) are empowered by a single global metaphorical strength that has limited capacity. This strength can become temporarily depleted after a primary self-control act, which, in turn, can impair performance in subsequent acts of self-control. Recently, the assumptions of the strength model of self-control also have been adopted and tested in the field of sport and exercise psychology. The present review paper aims to give an overview of recent developments in self-control research based on the strength model of self-control. Furthermore, recent research on interventions on how to improve and revitalize self-control strength will be presented. Finally, the strength model of self-control has been criticized lately, as well as expanded in scope, so the present paper will also discuss alternative explanations of why previous acts of self-control can lead to impaired performance in sport and exercise.