Endoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic ...processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.
Donor peripheral blood mononuclear cells (PBMCs) and intraoperatively obtained periprosthetic fibroblast-like cells (PPFs) were (co-)cultured with ± macrophage-colony stimulating factor (MCSF) and Receptor Activator of NF-κB ligand (RANKL) in transwell and monolayer culture systems and examined for osteoclastogenic regulations MCSF, RANKL, osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) as well as the ability of bone resorption. Sequencing analysis compared dental and orthopaedic (co-)cultures.
Monolayer co-cultures of both origins expressed high levels of OPG, resulting in inhibition of osteolysis shown by resorption assay on dentin. The high OPG-expression, low RANKL/OPG ratios and a resulting inhibition of osteolysis were displayed by dental and orthopaedic PPFs in monolayer even in the presence of MCSF and RANKL, acting as osteoprotective and immunoregulatory cells. The osteoprotective function was only observed in monolayer cultures of dental and orthopaedic periprosthetic cells and downregulated in the transwell system. In transwell co-cultures of PBMCs/PPFs profound changes of gene expression, with a significant decrease of OPG (20-fold dental versus 100 fold orthopaedic), were identified. Within transwell cultures, which offer more
like conditions, RANKL/OPG ratios displayed similar high levels to the original periprosthetic tissue. For dental and orthopaedic implant loosening, overlapping findings in principal component and heatmap analysis were identified.
Thus, periprosthetic osteoclastogenesis may be a correlating immune process in orthopaedic and dental implant failure leading to comparable reactions with regard to osteoclast formation. The transwell cultures system may provide an
like model for the exploration of orthopaedic and dental implant loosening.
In this naturalistic study, 262 audiotaped psychotherapy sessions-randomly drawn from 81 individual therapies from eight different psychotherapy approaches-were rated completely on treatment ...adherence using a newly developed rating manual. In the therapy sessions, a relatively low percentage of treatment specific interventions (ranging from 4.2% to 27.8%) was found for all eight approaches, 50% to 73% of the interventions were nonspecific or common, and approximately 18% to 27% were intervention techniques from other approaches. Different types of psychotherapy differed highly significantly in levels of treatment adherence. There was no statistically significant association between the type of psychotherapy and its outcome, or between the degree of therapists' treatment fidelity and the treatment outcome. However, there were significant associations between therapists' degree of professional experience, clients' initial psychological burden, and treatment response. Clients' severity of psychological problems prior to treatment predicted quality of therapeutic alliance while therapists' treatment adherence was predicted by therapists' professional experience and by the quality of the therapeutic alliance. We discuss the seemingly indirect importance of treatment adherence for psychotherapy outcome that we found in this study in relation to findings from other studies and in the context of the role of schools within psychotherapy.
Co-culture studies investigating the role of periprosthetic fibroblasts (PPFs) in inflammatory osteoclastogenesis reveal contrary results, partly showing an osteoprotective function of fibroblasts ...and high OPG expression in monolayer. These data disagree with molecular analyses of original periosteolytic tissues. In order to find a more reliable model, PPFs were co-cultivated with peripheral blood mononuclear cells (PBMCs) in a transwell system and compared to conventional monolayer cultures. The gene expression of key regulators of osteoclastogenesis (macrophage colony-stimulating factor (MCSF), receptor activator of NF-κB ligand (RANK-L), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)) as well as the ability of bone resorption were analyzed. In monolayer co-cultures, PPFs executed an osteoprotective function with high OPG-expression, low RANK-L/OPG ratios, and a resulting inhibition of osteolysis even in the presence of MCSF and RANK-L. For transwell co-cultures, profound changes in gene expression, with a more than hundredfold decrease of OPG and a significant upregulation of TNFα were observed. In conclusion, we were able to show that a change of culture conditions towards a transwell system resulted in a considerably more osteoclastogenic gene expression profile, being closer to findings in original periosteolytic tissues. This study therefore presents an interesting approach for a more reliable in vitro model to examine the role of fibroblasts in periprosthetic osteoclastogenesis in the future.
Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. ...Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces.
Introduction
Identifying the critical isthmus region (CIR) of atrial re‐entry tachycardias (AT) is challenging. The Lumipoint® (LP) software, developed for the Rhythmia® mapping system, aims to ...facilitate the successful ablation of ATs by identifying the CIR.
Objective
The objective of this study was to evaluate the quality of LP regarding the percentage of arrhythmia‐relevant CIR in patients with atypical atrial flutter (AAF).
Methods
In this retrospective study, we analyzed 57 AAF forms. Electrical activity (EA) was mapped over tachycardia cycle length resulting in a two‐dimensional EA pattern. The hypothesis was that EA minima suggest potential CIRs with slow‐conduction‐zone.
Results
A total of n = 33 patients were included, with the majority of patients being already preablated (69.7%). LP algorithm identified a mean of 2.4 EA minima and 4.4 suggested CIRs per AAF form. Overall, we observed a low probability of identifying only the relevant CIR (POR) at 12.3% but a high probability that at least one CIR is detected (PALO) at 98.2%. Detailed analysis revealed EA minima depth (≤20%) and width (>50 ms) as the best predictors of relevant CIRs. Wide minima occurred rarely (17.5%), while low minima were more frequently present (75.4%). Minima depth of EA ≤ 20% showed the best PALO/POR overall (95% and 60%, respectively). Analysis in recurrent AAF ablations (five patients) revealed that CIR in de novo AAF was already detected by LP during the index procedure.
Conclusion
The LP algorithm provides an excellent PALO (98.2%), but poor POR (12.3%) to detect the CIR in AAF. POR improved by preselection of the lowest and widest EA minima. In addition, there might be the role of initial bystander CIRs becoming relevant for future AAFs.
In an unselected cohort of 33 patients presenting with n = 57 atypical atrial flutter forms application of the Lumipoint (LP) algorithm with preselection by electrical minima of ≤20% resulted in a probability of >90% of identifying a critical isthmus region (CIR) and probability of 60% of specific CIR only identification.
Introduction
Left atrial flutter predominantly occurs after surgical or ablation procedures but this entity has also been recently reported in individuals without previous interventions. The use of ...high‐density electroanatomical mapping‐systems (HDM) has improved the understanding of underlying mechanisms beyond entrainment maneuvers and substrate analyses. We aimed to evaluate the mechanism of left atrial (LA) flutters in preablated vs ablation‐naïve individuals and sought to assess the efficacy of empiric ablations sets in these groups.
Methods and results
We included 55 patients admitted for ablation of LA flutter between July 2017 and August 2019. On the basis of HDM analyses the arrhythmia mechanism was determined with consecutive ablation targeting the suspected critical isthmus.
Mean age was 69.8 ± 10.7 years, with 26 of 55 (47.3%) male patients. Thirty‐nine (71%) patients had previously undergone LA ablation. Arrhythmia mechanisms differed between preablated and ablation‐naïve patients as anatomical structure‐related LA flutters (perimitral, roof‐dependent, within‐pulmonary veins) were more frequent in the preablated cohort compared to ablation‐naïve individuals (74.4% vs 43.8%; P = .03). In ablation‐naïve patients, most flutters (9 of 16, 56.3%) were related to low‐voltage areas at the anterior/posterior wall. Acute termination rates were high (>90%) in both groups. Empirical mitral isthmus or roof lines showed a potential higher success rate in preablated patients.
Conclusion
We identified different mechanisms of LA flutters in preablated vs ablation‐naïve patients. In ablation‐naïve patients, most tachycardias involved low‐voltage areas rather than anatomical structures. Using HDM, acute success rates were high. Hypothetical linear ablations were less successful in ablation‐naïve individuals, further highlighting the need to identify the specific individual tachycardia mechanism in these patients.
Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation ...COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.
Abstract
Introduction
Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture ...systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures.
Methods
PPFs from periprosthetic tissues (
n
= 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (
n
= 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 10
3
/cm
2
) or multilayer cultures (density 8.5 × 10
5
/cm
2
) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR.
Results
Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased.
Conclusion
The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.
Objective: This paper addresses the results of two samples of a large naturalistic (effectiveness study) outpatient process-outcome study in Switzerland (Practice-Oriented Outpatient Psychotherapy ...Study). Ten different types of psychotherapy were investigated by looking at the role of the sex or gender of therapists and patients with regard to treatment outcome by including several nonspecific therapeutic factors. Method: Ten different types of psychotherapy, 237 patients, and 68 therapists were included in the study. A subsample of 116 cases was analyzed with regard to therapists' technical interventions. Results: Sex and gender issues of both therapists and patients did not play a crucial role in any type of psychotherapy investigated. Gender issues appeared to play an indirect role. Female therapists intervene more empathically, whereas male therapists tend to use more confrontational techniques. Conclusions: Since the results show that therapists differ substantially with regard to their intervention techniques due to their sex, they should become more conscious of their interventions by considering patients' severity of psychological problems and patients' level of psychological functioning so as to not over or underchallenge them.
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