Understanding Pancreas Development for β-Cell Repair and Replacement Therapies

The lack or dysfunction of insulin-producing β-cells is the cause of all forms of diabetes. In vitro generation of β-cells from pluripotent stem cells for cell-replacement therapy or triggering endogenous mechanisms of β-cell repair have great potential in the field of regenerative medicine. Both approaches rely on a thorough understanding of β-cell development and homeostasis. Here, we briefly summarize the current knowledge of β-cell differentiation during pancreas development in the mouse. Furthermore, we describe how this knowledge is translated to instruct differentiation of both mouse and human pluripotent stem cells towards the β-cell lineage. Finally, we shortly summarize the current efforts to identify stem or progenitor cells in the adult pancreatic organ and to harness the endogenous regenerative potential. Understanding development and regeneration of β-cells already led to identification of molecular targets for therapy and informed on pathomechanisms of diabetes. In the future might lead to β-cell repair and replacement therapies.     

Comparison of revision strategies for failed C2-posterior cervical pedicle screws: a biomechanical study

Study purpose

With increasing usage within challenging biomechanical constructs, failures of C2 posterior cervical pedicle screws (C2-pCPSs) will occur. The purpose of the study was therefore to investigate the biomechanical characteristics of two revision techniques after the failure of C2-pCPSs.

Materials and methods

Twelve human C2 vertebrae were tested in vitro in a biomechanical study to compare two strategies for revision screws after failure of C2-pCPSs. C2 pedicles were instrumented using unicortical 3.5-mm CPS bilaterally (Synapse/Synthes, Switzerland). Insertion accuracy was verified by fluoroscopy. C2 vertebrae were potted and fixed in an electromechanical testing machine with the screw axis coaxial to the pullout direction. Pullout testing was conducted with load and displacement data taken continuously. The peak load to failure was measured in newtons (N) and is reported as the pullout resistance (POR). After pullout, two revision strategies were tested in each vertebra. In Group-1, revision was performed with 4.0-mm C2-pCPSs. In Group-2, revision was performed with C2-pedicle bone-plastic combined with the use of a 4-mm C2-pCPSs. For the statistical analysis, the POR between screws was compared using absolute values (N) and the POR of the revision techniques normalized to that of the primary procedures (%).

Results

The POR of primary 3.5-mm CPSs was 1,140.5 ± 539.6 N for Group-1 and 1,007.7 ± 362.5 N for Group-2; the difference was not significant. In the revision setting, the POR in Group-1 was 705.8 ± 449.1 N, representing a reduction of 38.1 ± 32.9 % compared with that of primary screw fixation. For Group-2, the POR was 875.3 ± 367.9 N, representing a reduction of 13.1 ± 23.4 %. A statistical analysis showed a significantly higher POR for Group-2 compared with Group-1 (p = 0.02). Although the statistics showed a significantly reduced POR for both revision strategies compared with primary fixation (p < 0.001/p = 0.001), the loss of POR (in %) in Group-1 was significantly higher compared with the loss in Group-2 (p = 0.04).

Conclusions

Using a larger-diameter screw combined with the application of a pedicle bone-plastic, the POR can be significantly increased compared with the use of only an increased screw diameter.     

In vivo analysis of cervical kinematics after implantation of a minimally constrained cervical artificial disc replacement

Introduction

To better understand cervical kinematics following cervical disc replacement (CDR), the in vivo behavior of a minimally constrained CDR was assessed.

Methods

Radiographic analysis of 19 patients undergoing a 1-level CDR from C4–5 to C6–7 (DISCOVER, Depuy-Spine, USA) was performed. Neutral–lateral and flexion–extension radiographs obtained at preop, postop and late follow-up were analyzed for segmental angle and global angle (GA C2–7). Flexion–extension range of motion was analyzed using validated quantitative motion analysis software (QMA®, Medical Metrics, USA). The FSU motion parameters measured at the index and adjacent levels were angular range of motion (ROM), translation and center of rotation (COR). Translation and COR were normalized to the AP dimension of the inferior endplate of the caudal vertebra. All motion parameters, including COR, were compared with normative reference data.

Results

The average patient age was 43.5 ± 7.3 years. The mean follow-up was 15.3 ± 7.2 months. C2–7 ROM was 35.9° ± 15.7° at preop and 45.4° ± 13.6° at follow-up (?p < .01). Based on the QMA at follow-up, angular ROM at the CDR level measured 9.8° ± 5.9° and translation was 10.1 ± 7.8 %. Individuals with higher ROM at the CDR level had increased translation at that level (p < .001, r = 0.97), increased translation and ROM at the supra-adjacent level (p < .001, r = .8; p = .005, r = .6). There was a strong interrelation between angular ROM and translation at the supra-adjacent level (p < .001, r = .9) and caudal-adjacent level (p < .001, r = .9). The location of the COR at the CDR- and supra-adjacent levels was significantly different for the COR-X (p < .001). Notably, the COR-Y at the CDR level was significantly correlated with the extent of CDR-level translation (p = .02, r = .6). Shell angle, which may be influenced by implant size and positioning had no impact on angular ROM but was correlated with COR-X (p = .05, r = ?.6) and COR-Y (p = .04, r = ?.5).

Conclusion

The COR is an important parameter for assessing the ability of non-constrained CDRs to replicate the normal kinematics of a FSU. CDR size and location, both of which can impact shell angle, may influence the amount of translation by affecting the location of the COR. Future research is needed to show how much translation is beneficial concerning clinical outcomes and facet loading.     

Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Social media in dental education: a call for research and action

Social media are part of the fabric of today's world, from which health care is not excluded. Based on its distribution capacity, a single individual can cause an amount of damage to an institution that only a few decades ago required access to a mainstream news media outlet. Despite the obvious parallels in professional standards in the medical and dental communities, the scholarly activity and resulting collegial discourse observed among medical professionals remain unmatched in the dental education literature. As a result, a rigorous research agenda on the topic is indicated. Once these results are evaluated and thoroughly vetted, actions should be tailored to address the needs, minimize the threats, and maximize the opportunities that have been already noted by the medical profession. Regardless of input, albeit internal or external, a cadre of individuals who are willing to develop philosophy, policy, and procedure related to the use of social media policies in dental education can then be identified to evaluate the issues unique to the institution and perhaps the profession.     

Pelvic tilt compensates for increased acetabular anteversion

Purpose

Pelvic tilt determines functional orientation of the acetabulum. In this study, we investigated the interaction of pelvic tilt and functional acetabular anteversion (AA) in supine position.

Methods

Pelvic tilt and AA of 138 individuals were measured by computed tomography (CT). AA was calculated in relation to the anterior pelvic plane (APP) and relative to the table plane. We analysed these parameters for gender-specific and age-related differences.

Results

The mean pelvic tilt was -0.1?±?5.5°. Pelvic sagittal rotation displayed no gender nor age related differences. Females showed higher angles of AA compared with males (20.0° vs 17.2°, p?<?0.001; AA relative to the APP). Anterior tilting of the pelvis positively correlated with AA and individuals with high AA had a higher anterior pelvic tilt compared with those with low AA (p?<?0.0001; AA relative to the APP).

Conclusions

AA has to be calculated regarding pelvic sagittal rotation for correct acetabular orientation. Pelvic tilt is dependent on acetabular orientation and compensates for increased AA.

     

Short Bouts of Intensive Exercise During the Workday Have a Positive Effect on Neuro‐cognitive Performance

Beside its positive impact on physical health, exercise is indicated to positively affect cognitive performance based on a relocation of cortical activity. This study examined the influence of different types of breaks on cognitive performance and related cortical activity in office‐based employees. Breaks were filled with exercise, resting or a usual break and a control condition where employees continued working without any break. Cognitive performance was assessed using the d2‐R test and two commercially available cognitive tasks. Brain cortical activity was recorded using electroencephalography before and after breaks. Individual's mood was analysed using a profile of mood state. Results indicate a positive effect of a 3‐min boxing intervention on cognitive performance, mirrored by a decrease in prefrontal cortex activity. Although perceived psychological state was increased after the usual break, this is reflected in neither cortical activity nor cognitive performance. With respect to the fact that also bike activity resulted an increase in prefrontal alpha‐2 activity, a positive effect of exercise on neuro‐cognitive performance can be stated. Health and economic benefits may result from brief physical activity breaks and help to maintain workplace performance and job satisfaction. Copyright © 2015 John Wiley & Sons, Ltd.     

Effects of Cycling Versus Running Training on Sprint and Endurance Capacity in Inline Speed Skating

The purpose of this study was to compare the effects of running versus cycling training on sprint and endurance capacity in inline speed skating. Sixteen elite athletes (8 male, 8 female, 24 ± 8 yrs) were randomly assigned into 2 training groups performing either 2 session per week of treadmill running or ergometer cycling in addition to 3 skating specific sessions (technique, plyometrics, parkour) for 8 weeks. Training intensity was determined within non-specific (cycling or running) and effects on specific endurance capacity within a specific incremental exercise test. Before and after the intervention all athletes performed a specific (300m) and one non-specific (30s cycling or 200m running) all-out sprint test according to the group affiliation. To determine the accumulation of blood lactate (BLa) and glucose (BGL) 20 μl arterialized blood was drawn at rest, as well as in 1 min intervals for 10 min after the sprint test. The sport-specific peak oxygen uptake (VO₂ peak) was significantly increased (+17%; p = 0.01) in both groups and highly correlated with the sprint performance (r = -0.71). BLa values decreased significantly (-18%, p = 0.02) after the specific sprint test from pre to post-testing without any group effect. However, BGL values only showed a significant decrease (-2%, p = 0.04) in the running group. The close relationship between aerobic capacity and sprint performance in inline speed skating highlights the positive effects of endurance training. Although both training programs were equally effective in improving endurance and sprint capacities, the metabolic results indicate a faster recovery after high intensity efforts for all athletes, as well as a higher reliance on the fat metabolism for athletes who trained in the running group.

Key points

• In addition to a highly developed aerobic performance inline speed skaters also require a highly trained anaerobic capacity to be effective in the sprint sections such as the mass start, tactical attacks and finish line sprint.
• An 8-week low-intensity endurance training program of either cycling or running training combined with additional routine training improves classical aerobic characteristics (17% increase of VO₂ peak), as well as values for acceleration and speed.
• Athletes who trained in the running group demonstrated a higher reliance on the fat metabolism in the sport-specific post-testing.
• The significant reduction in anaerobic ATP turnover during repeated sprints appears to be partially compensated by an increase in VO₂ in subsequent sprint. The results revealed a close relationship between the aerobic capacity and sprint performance in inline speed skating.

Key words: Aerobic metabolism, blood glucose concentration, all-out sprint test     

Discontinuous presentation of ambiguous figures: how interstimulus-interval durations affect reversal dynamics and ERPs

If we observe an ambiguous figure, our percept is unstable and alternates between the possible interpretations. Periodically interrupting the presentation sizably modulates the spontaneous reversal rate. We here studied event-related potential (ERP) correlates of the neural processes underlying these strong modulations. An ambiguous Necker stimulus was presented discontinuously with four randomly varying interstimulus intervals (ISI; 14, 43, 130, 390 ms) while participants indicated perceptual reversals. EEG was selectively averaged with respect to the participants' percept and ISI. ERP traces varied markedly between ISIs. A simple model explained a major part of this variation and showed that the ISI-dependent ERP modulation occurs after disambiguation has already taken place. We suggest that perceptual stability (or reversal) depends on a system state, slowly changing from one reversal to the next. ISI can shift this state on a scale between stability and instability.