Impact of different placement depths on the crestal bone level of immediate versus delayed placed platform-switched implants

Purpose

The preservation of peri-implant bone is one requirement for long-term success of dental implants. The purpose of this study was to evaluate the impact of subcrestal placement on the crestal bone level of immediate versus delayed placed implants after loading.

Fear of pain and cortisol reactivity predict the strength of stress‐induced hypoalgesia

Background

Acute stress can have an effect on pain sensitivity, yet the direction of the effect – whether it is hypoalgesic or hyperalgesic – is mixed across studies. Moreover, which part of the stress response influences pain sensitivity is still unclear. In the current experimental study, we aim to examine the effect of acute stress on heat pain thresholds and pain tolerance levels in healthy participants, while taking into account individual differences in stress responses.

Methods

Forty‐two healthy participants were randomly assigned to either a well‐validated stress paradigm: the Maastricht Acute Stress Task (MAST; combining physical and psychological stressors) or to a nonstressful version of the task. Heat pain thresholds and tolerance levels were assessed at three times: prior to the MAST, immediately after the MAST during the presumed sympatho‐adrenal medullary (SAM) response, and 15 min after MAST to cover the presumed hypothalamus–pituitary–adrenal (HPA) axis response. Stress responses were assessed both subjectively and physiologically.

Results

We observed that the acute stress induction led to increased heat pain thresholds, an effect that was present only in participants showing a cortisol response following stress induction and only in the presumed HPA axis time window. The strength of this hypoalgesic effect was further predicted by the change in cortisol and by fear of pain levels.

Conclusions

Our findings indicate that the HPA axis – and not the autonomic – stress response specifically underlies this stress‐induced hypoalgesic effect, having important implications for clinical states with HPA axis dysfunctions.

Significance

This experimental study shows that an acute stress induction – that combines physical and psychological stressors – increases heat pain thresholds, but not tolerance in healthy participants. Furthermore, the magnitude of this stress‐induced hypoalgesic effect is predicted by cortisol reactivity and fear of pain, revealing specific involvement of the HPA axis stress system and interactions with pain‐related psychosocial aspects.     

Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro

Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Nitrogen-containing and non-nitrogen containing bisphosphonates have been compared. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5 × 10⁻⁵ M, 5 × 10⁻⁶ M, and 5 × 10⁻⁷ M over the experimental period of 14 days. Furthermore, the hOB cell lines were stimulated by clodronate at concentrations of 5 × 10⁻³ M, 5 × 10⁻⁵ M, and 5 × 10⁻⁶ M. At each point in time, the gene expression levels of RANKL and OPG were quantified by real-time RT-PCR. The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 × 10⁻⁵ M. Lower concentrations did not enhance the RANKL and OPG expression considerably. The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 × 10⁻³ M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Interestingly, clodronate might have little influence on osteoblast/osteoclast interaction with respect to OPG and RANKL gene expression.     

Adhesion molecule L1 is down-regulated in malignant peripheral nerve sheath tumors versus benign neurofibromatosis type 1-associated tumors

Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that is frequently associated with NF-1 is tumor progression from neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs). The aim of this study was to determine the expression of the neural L1 cell adhesion molecule in dermal-diffuse neurofibromas, plexiform neurofibromas, and MPNSTs of NF-1. We retrospectively analyzed surgically resected primary tumors, including 20 dermal neurofibromas, 23 plexiform neurofibromas, and 17 MPNSTs, by immunohistochemistry in paraffin sections of NF-1 tumors with the use of the L1-specific monoclonal antibody UJ127, which does not cross-react with other members of the L1 family. Immunostainings for CD34 and S100 were included to distinguish and allocate L1-expressing Schwann cells and perineural (specialized) fibroblasts. Our data showed that L1 is highly expressed in all benign NF-1 tumors and in some but not all MPNSTs. Furthermore, we demonstrated a correlation between L1 expression and differentiation grade of MPNSTs. There was a significant trend toward lower or nondetectable expression in the poorly differentiated MPNSTs, in contrast to all other tumor entities so far investigated, in which L1 expression correlated positive with malignancy, except for juvenile but not adult-derived neuroblastomas. Future studies are warranted to elucidate the molecular basis of the varying effects of the degree of L1 expression, receptor, and signal transduction mechanisms in different tumors.     

Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome

Objective

According to the Cognitive behavioral therapy (CBT) protocol for patients with Chronic Fatigue Syndrome (CFS), therapists are advised to categorize patients in relatively active and passive patients. However, evidence to support the differences in physical functioning between these subgroups is limited. Using the baseline data from a multicentre randomized controlled trial (FatiGo), the differences in actual and perceived physical functioning between active and passive patients with CFS were evaluated.

Methods

Sixty patients, who received CBT during the FatiGo trial were included. Based on the expert opinion and using the definitions of subgroups defined in the CBT protocols, the therapist categorized the patient. Data from an activity monitor was used to calculate actual physical functioning, physical activity, daily uptime, activity fluctuations and duration of rest during daily life. Perceived physical functioning was assessed by measuring physical activity, physical functioning and functional impairment with the Checklist Individual Strength, Short Form-36 and Sickness-Impact Profile 8.

Results

Relatively active patients have a significantly higher daily uptime and show significantly less fluctuations in activities between days. Passive patients experience a significantly lower level of physical functioning and feel more functionally impaired in their mobility. However, no significant differences were found in the other actual or perceived physical functioning indices.

Conclusions

A clear difference in actual and perceived physical functioning between relatively active and passive patients with CFS as judged by their therapists could not be found. Future research is needed to form a consensus on how to categorize subgroups of patients with CFS.     

Differences in curvature between constrained and unconstrained goal-directed movements to haptic targets

Trajectories of goal-directed movements are less curved for movements over a surface (constrained) than for movements in empty space (unconstrained). To study whether this difference arises from feeling the surface slip across the skin or having to control the movements in a third dimension, we manipulated the available tactile information and the compliance of the surface. Participants were instructed to make straight movements towards haptic targets in the mid-sagittal plane. We found that constrained movements were less curved than unconstrained movements. The reduction of curvature was also visible with strongly reduced tactile information and for very compliant surfaces, so feeling the surface slip across the skin and having to control the movements in the third dimension are not critical. The reduced curvature when moving over a surface might arise from the extra information that the surface gives about the third dimension or from the extra information about the direction of the movement provided by the additional force needed to overcome friction.     

Subtotal ablation of parietal epithelial cells induces crescent formation

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman's space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After >9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman's capsule and expressed the activation marker CD44 de novo. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents.