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Objective Evidence of geographical variation in total hip replacement (THR) and deviations from treatment guidelines persists. In this exploratory study, we aim to gain an in-depth understanding of patients’ healthcare trajectories by identifying and visualising medication use patterns in coxarthrosis patients before surgery. We examine their association with patient characteristics and THR, and compare them with recommendations on mild analgesics, opioid prescription and exhaustion of conservative therapy.Methods In this exploratory study, we apply State Sequence Analysis (SSA) on German health insurance data (2012–2015). We analyse a cohort of coxarthrosis patients, half of whom underwent THR after a 1 year observation period and half of whom did not undergo surgery until at least 1 year after the observation period. Hierarchical states are defined based on prescriptions. We construct sequences, calculate sequence similarity using optimal matching and identify medication use patterns via clustering. Patterns are visualised, descriptive statistics are presented and logistic regression is employed to investigate the association of medication patterns with subsequent THR.Results Seven distinct medication use patterns are identified, correlating strongly with patient characteristics and subsequent THR. Two patterns leading to THR demonstrate exhaustion of pharmacological therapy. Opioid use is concentrated in two small patterns with low odds for THR. The most frequent pattern lacks significant pharmacological therapy.Conclusions This SSA uncovers heterogeneity in medication use patterns before surgery in coxarthrosis patients. Cautious opioid handling and adherence to a stepped prescription approach are observed, but many patients display low medication therapy usage and lack evidence of exhausting conservative options before surgery.

Abstract Background Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. Methods The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. Discussion The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. Trial registration The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

Abstract Background Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. Methods The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age

Abstract Background Coronary angiographies (CAs) are among the most common diagnostic procedures carried out in German hospitals, and substantial regional differences in their frequency of use have been documented. Given the heterogeneity with regard to the expected benefits and the varying scope for discretion depending on the indication for the procedure, we hypothesized that the observed variation and the association of need and supply factors differs by indication for CA. Methods We investigated the correlation between supply factors and the regional rates of CAs in Germany while controlling for need using spatial‐autoregressive error models (SARE) and spatial cross-regressive models with autoregressive errors (SCRARE). The overall rates of CAs and the rates in specific patient subgroups, namely, patients with and without myocardial infarction (MI), were calculated based on a comprehensive set of nationwide routine data from three statutory health insurances at the district level. Results Although little variation was found in cases with MI, considerable variation was seen in the overall cases and cases without MI. The SARE models revealed a positive association between the number of hospitals with a cardiac catheterization laboratory per 10,000 population and the rates of overall cases and cases without MI, whereas no such relationship existed in cases with MI. Additionally, an association between regional deprivation and the rates of CAs was found in cases with MI, but no such association was seen in cases without MI. Conclusions The results supported the hypothesis that the relative association of need and supply factors differed by the indication for CA. Although the regional differences in the frequency of use of CAs can only be explained in part by the factors examined in our study, it offers insight into patient access to and the provision of CA services and can provide a platform for further local research.

Abstract Background Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). Methods This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention “ImPuls”, among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios. Discussion Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings. Trial registration The study was registered in the German Clinical Trials Register (ID: DRKS00024152 , 05/02/2021).

Abstract Background Patients in Germany are free to seek care from any office-based physician and can always ask for multiple opinions on a diagnosis or treatment. The high density of physicians and the freedom to choose among them without referrals have led to a need for better coordination between the multiple health professionals treating any given patient. The objectives of this study are to (1) identify informal networks of physicians who treat the same patient population, (2) provide these physicians with feedback on their network and patients, using routine data and (3) give the physicians the opportunity to meet one another in facilitated network meetings. Methods The Accountable Care Deutschland (ACD) study is a prospective, non-blinded, cluster-randomised trial comprising a process and economic evaluation of informal networks among 12,525 GPs and office-based specialists and their 1.9 million patients. The units of allocation are the informal networks, which will be randomised either to the intervention (feedback and facilitated meetings) or control group (usual care). The informal networks will be generated by identifying connections between office-based physicians using complete datasets from the Regional Associations of Statutory Health Insurance (SHI) Physicians in Hamburg, Schleswig Holstein, North Rhine and Westphalia Lip, as well as data from three large statutory health insurers in Germany. The physicians will (a) receive feedback on selected indicators of their own treatment activity and that of the colleagues in their network and (b) will be invited to voluntary, facilitated network meetings by their Regional Association of SHI physicians. The primary outcome will be ambulatory-care-sensitive hospitalisations at baseline, at the end of the 2-year intervention period, and at six months and at 12 months after the end of the intervention period. Data will be analysed using the intention-to-treat principle. A pilot study preceded the ACD study. Discussion Cochrane reviews show that feedback can improve everyday medical practice by shedding light on previously unknown relationships. Providing physicians with information on how they are connected with their colleagues and what the outcomes are of care delivered within their informal networks can help them make these improvements, as well as strengthen their awareness of possible discontinuities in the care they provide. Trial registration German Clinical Trials Register DRKS00020884 . Registered on 25 March 2020—retrospectively registered.

We present a quasinormal-mode (QNM) theory for coupled loss and gain resonators working in the vicinity of an exceptional point. Assuming linear media, which can be fully quantified using the complex pole properties of the QNMs, we show how the QNMs yield a quantitatively accurate model to a full classical dipole spontaneous-emission response in Maxwell’s equations at a variety of spatial positions and frequencies (under linear response). We also develop an intuitive QNM coupled-mode theory, which can be used to accurately model such systems using only the QNMs of the bare resonators, where the hybrid QNMs of the complete system are automatically obtained. Near a lossy exceptional point, whose general properties are broadened and corrected through use of QNM theory, we analytically show how the QNMs yield a Lorentzian-like and a Lorentzian-squared-like response for the spontaneous-emission line shape consistent with other works. However, using rigorous analytical and numerical solutions for microdisk resonators, we demonstrate that the general line shapes are far richer than what has been previously predicted. Indeed, the classical picture of spontaneous emission can take on a wide range of positive and negative Purcell factors from the hybrid modes of the coupled loss-gain system. The negative Purcell factors are unphysical and signal a clear breakdown of the classical dipole picture of spontaneous emission in such media, though the concept of a negative local density of states is correct. This finding has enabled a quantum fix to the decay of a two-level-system dipole emitter in amplifying and lossy media [Franke et al., Phys. Rev. Lett. 127, 013602 (2021)PRLTAO0031-900710.1103/PhysRevLett.127.013602], and we further show and discuss the impact of this fix using the QNMs of the microdisk resonators. We also show the rich spectral features of the Green’s function propagators, which can be used to model various physical observables, such as photon detection.

Objectives To examine the role of hospitals and office-based physicians in empirical networks that deliver care to the same population with regard to the timely provision of appropriate care after hospital discharge.Design Secondary data analysis of a nationwide cohort using cross-classified multilevel models.Setting Transition from hospital to ambulatory care.Participants All patients discharged for acute myocardial infarction (AMI) from Germany’s largest statutory health insurance fund group in 2011.Main outcome measure Patients’ odds of receiving a statin prescription within 30 days after hospital discharge.Results We found significant variation in 30-day statin prescribing between hospitals (median OR (MOR) 1.40; 95% credible interval (CrI) 1.36 to 1.45), hospital-physician pairs caring for the same patients (MOR 1.32; 95% CrI 1.26 to 1.38) and to a lesser extent between physicians (MOR 1.14; 95% CrI 1.11 to 1.19). About 67% of the variance between hospital-physician pairs and about 45% of the variance between hospitals was explained by hospital characteristics including a rural location, teaching status and the number of beds, the number of patients shared between a hospital and an office-based physician as well as 16 patient characteristics, including multimorbidity and dementia. We found no impact of physician characteristics.Conclusions Timely prescription of appropriate secondary prevention pharmacotherapy after AMI is subject to considerable practice variation which is not consistent with clinical guidelines. Hospitals contribute more to the observed variation than physicians, and most of the variation lies at the patient level. To ensure care continuity for patients, it is important to strengthen hospital capacity for discharge management and coordination between hospitals and office-based physicians.

We employ a recently developed quantization scheme for quasinormal modes (QNMs) to study a nonperturbative open cavity–QED system consisting of a hybrid metal-dielectric resonator coupled to a quantum emitter. This hybrid cavity system allows one to explore the complex coupling between a low-Q (quality factor) resonance and a high-Q resonance, manifesting in a striking Fano resonance, an effect that is not captured by traditional quantization schemes using normal modes or a Jaynes-Cummings (JC)–type model. The QNM quantization approach rigorously includes dissipative coupling between the QNMs and is supplemented with generalized input-output relations for the output electric field operator for multiple modes in the system and correlation functions outside the system. The role of the dissipation-induced mode coupling is explored in the strong coupling regime between the photons and emitter beyond the first rung of the JC dressed-state ladder. Important differences in the quantum master equation and input-output relations between the QNM quantum model and phenomenological dissipative JC models are found. For the hybridized high-Q cavity mode, we show how the dissipation-induced coupling causes a significant reduction in the cavity-emitter coupling rate, and the cavity decay rate, compared to a simpler JC model. In a second step, numerical results for the Fock distributions and system as well as output correlation functions obtained from the quantized QNM model for the hybrid structure are compared with results from a phenomenological approach. We demonstrate explicitly how the quantized QNM model manifests in multiphoton quantum correlations beyond what is predicted by the usual JC models.

We provide theory and formal insight on the Green function quantization method for absorptive and dispersive spatial-inhomogeneous media in the context of dielectric media. We show that a fundamental Green function identity, which appears, e.g., in the fundamental commutation relation of the electromagnetic fields, is also valid in the limit of nonabsorbing media. We also demonstrate how the zero-point field fluctuations yields a nonvanishing surface term in configurations without absorption, when using a more formal procedure of the Green function quantization method. We then apply the presented method to a recently developed theory of photon quantization using quasinormal modes [Franke et al., Phys. Rev. Lett. 122, 213901 (2019)PRLTAO0031-900710.1103/PhysRevLett.122.213901] for finite nanostructures embedded in a lossless background medium. We discuss the strict dielectric limit of the commutation relations of the quasinormal mode operators and present different methods to obtain them, connected to the radiative loss for nonabsorptive but open resonators. We show exemplary calculations of a fully three-dimensional photonic crystal beam cavity, including the lossless limit, which supports a single quasinormal mode and discuss the limits of the commutation relation for vanishing damping.

Dicaffeoylquinic acids (DCQAs) are polyphenolic compounds found in various medicinal plants such as Echinacea species and Hedera helix, whose multi-constituent extracts are used worldwide to treat respiratory diseases. Besides triterpenes, saponins, alkamides, and other constituents, DCQAs are an important group of substances for the pharmacological activity of plant-derived extracts. Therefore, the pharmacological properties of DCQAs have been studied over the last decades, suggesting antioxidative, anti-inflammatory, antimicrobial, hypoglycaemic, cardiovascular protective, neuroprotective, and hepatoprotective effects. However, the beneficial pharmacological profile of DCQAs has not yet been linked to their use in treating respiratory diseases such as acute or even chronic bronchitis. The aim of this review was to assess the potential of DCQAs for respiratory indications based on published in vitro and in vivo pharmacological and pre-clinical data, with particular focus on antioxidative, anti-inflammatory, and respiratory-related effects such as antitussive or antispasmodic properties. A respective literature search revealed a large number of publications on the six DCQA isoforms. Based on this search, a focus was placed on 1,3-, 3,4-, 3,5-, and 4,5-DCQA, as the publications focused mainly on these isomers. Based on the available pre-clinical data, DCQAs trigger cellular mechanisms that are important in the treatment of respiratory diseases such as decreasing NF-κB activation, reducing oxidative stress, or activating the Nrf2 pathway. Taken together, these data suggest an essential role for DCQAs within herbal medicines used for the treatment of respiratory diseases and highlights the need for the identifications of DCQAs as lead substances within such extracts.

Abstract Chronic stress is associated with major depressive disorder (MDD). Increased glucocorticoid levels caused by uncontrolled release through the hypothalamic‒pituitary‒adrenal (HPA) axis can cause changes in the lipid content of the cellular plasma membrane. These changes are suspected to be involved in the development of depressive disorders. St. John's wort extract (SJW) Ze 117 has long been used as an alternative to synthetic antidepressants. Part of its effect may be due to an effect on the cellular lipid composition and thus on the properties of plasma membranes and receptor systems embedded therein. In this study, we investigated the effect of Ze 117 on that of dexamethasone and simvastatin. Dexamethasone increases the fluidity of C6 cell plasma membranes. This effect is counteracted by administration of Ze 117. Here we demonstrate that this is not due to a change in C16:1/16:0 and C18:1/18:0 ratios in C6 cell fatty acids. On the other hand, Ze 117 increased the cellular cholesterol content by 42.5%, whereas dexamethasone reduced cholesterol levels similarly to simvastatin. Lowering cholesterol levels by dexamethasone or simvastatin resulted in decreased β-arrestin 2 recruitment to the 5-HT1a receptor. This effect was counterbalanced by Ze 117, whereas the SJW extract had little effect on β-arrestin 2 recruitment in non-stressed cells. Taken together, in C6 cells, Ze 117 induces changes in membrane fluidity through its effect on cellular cholesterol metabolism rather than by affecting fatty acid saturation. This effect is reflected in an altered signal transduction of the 5-HT1a receptor under Ze 117 administration. The current in vitro results support the hypothesis that Ze 117 addresses relevant parts of the cellular lipid metabolism, possibly explaining some of the antidepressant actions of Ze 117.

Abstract Background Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors. Methods Since changes in cellular membrane properties are considered to play an important role in the development of depression, the effect of St. John’s wort extract Ze 117 on plasma membrane fluidity in peripheral blood mononuclear cells (PBMC) was investigated using fluorescence anisotropy measurements. Changes in fatty acid residues in phospholipids after treatment of cortisol-stressed [1 μM] PBMCs with Ze 117 [10–50 µg/ml] were analyzed by mass spectrometry. Results Cortisol increased membrane fluidity significantly by 3%, co-treatment with Ze 117 [50 µg/ml] counteracted this by 4.6%. The increased membrane rigidity by Ze 117 in cortisol-stressed [1 μM] PBMC can be explained by a reduced average number of double bonds and shortened chain length of fatty acid residues in phospholipids, as shown by lipidomics experiments. Conclusion The increase in membrane rigidity after Ze 117 treatment and therefore the ability to normalize membrane structure points to a new mechanism of antidepressant action of the extract.

Background: Adenosine A1 receptor (A1AR) plays a prominent role in neurological and cardiac diseases and inflammatory processes. Its endogenous ligand adenosine is known to be one of the key players in the sleep–wake cycle. Like other G protein-coupled receptors (GPCRs), stimulation of A1AR leads to the recruitment of arrestins in addition to the activation of G proteins. So far, little is known about the role of these proteins in signal transduction and regulation of A1AR compared to the activation of G proteins. In this work, we characterized a live cell assay for A1AR-mediated β-arrestin 2 recruitment. We have applied this assay to a set of different compounds that interact with this receptor.Methods: Based on NanoBit® technology, a protein complementation assay was developed in which the A1AR is coupled to the large part of the nanoluciferase (LgBiT), whereas its small part (SmBiT) is fused to the N-terminus of β-arrestin 2. Stimulation of A1AR results in the recruitment of β-arrestin 2 and subsequent complementation of a functional nanoluciferase. For comparison, corresponding data on the effect of receptor stimulation on intracellular cAMP levels were collected for some data sets using the GloSensor™ assay.Results: The assay gives highly reproducible results with a very good signal-to-noise ratio. Capadenoson, in contrast to adenosine, CPA, or NECA, shows only partial agonism in this assay with respect to the recruitment of β-arrestin 2, whereas it shows full agonism in the case of the inhibitory effect of A1AR on cAMP production. By using a GRK2 inhibitor, it becomes clear that the recruitment is at least partially dependent on the phosphorylation of the receptor by this kinase. Interestingly, this was also the first time that we demonstrate the A1AR-mediated recruitment of β-arrestin 2 by stimulation with a valerian extract.Conclusion: The presented assay is a useful tool for the quantitative study of A1AR-mediated β-arrestin 2 recruitment. It allows data collection for stimulatory, inhibitory, and modulatory substances and is also suitable for more complex substance mixtures such as valerian extract.

Background: 5-HT2A receptors play an important role in the development and therapy of depression. St. John's wort (SJW) extracts are used in the treatment of depression. The effects of pre-treatment with SJW extract on the behaviour of 5-HT2A receptors in the plasma membrane have not been well described at the molecular level. Methods: In this work, the influence of the SJW extract STW3-VI on 5-HT2A receptor internalization and calcium response under stimulating conditions are determined using different reporter cell lines. Influences on 5-HT2A receptor binding as well as on the lateral diffusion behaviour of receptor-ligand complexes (RLC) in the plasma membrane are investigated by fluorescence correlation spectroscopy (FCS) and single particle tracking (SPT) in real time on living cells. Therefore, a selective fluorescently labeled ligand was first developed. Results: STW3-VI pre-treatment inhibited both the 5-HT2A receptor internalization and the calcium response after agonistic stimulation with (±)-TCB-2, which suggests an inhibitory effect. Receptor binding studies using FCS surprisingly showed a dose-dependent increase in 5-HT2A receptor binding under STW3-VI. However, it is noticeable that there was a clear redistribution towards faster diffusing RLC, who possibly contribute less to signal transduction. The diffusive states of 5-HT2A receptors identified by SPT changed also under STW3-VI. Remarkably, there was a redistribution from faster diffusing to immobile RLC, while at the same time the transition probabilities for a receptor to change the diffusive state decreased clearly compared to control cells. This particular lateral diffusion behaviour likely characterizes 5-HT2A receptors with impaired signal transduction. Conclusion: The present data indicate a correlation between receptor status and lateral mobility, with STW3-VI apparently having an inhibitory effect on 5-HT2A receptor-mediated signaling in the cell models used here. Single-molecule techniques such as FCS and SPT provide important data that contribute to a better understanding of therapeutically relevant drug-target interactions and downstream regulatory processes.

The β2-adrenergic receptor (β2AR) is relevant for surfactant formation in alveolar type 2 cells and reduction of intracellular calcium concentration in bronchial muscle cells and thus for secretolytic and bronchospasmolytic effects. Herbal medicinal products that affect the β2AR system are used to treat common cold and bronchitis accompanied with mucus covered and narrowed airways. The present work compares the influence of an ivy preparation and an ivy/thyme combination on the β2-adrenergic signal transduction. For receptor binding studies and characterization of the lateral mobility of β2AR we have used single molecule detection by fluorescence correlation spectroscopy and single particle tracking. For the determination of both the second messenger cAMP and the internalization of β2AR we have generated luciferase based reporter cell lines, which produce a cAMP-dependent luciferase in the cytosol and express β2AR with extracellular luciferase moiety in the plasma membrane. While both preparations increased the β2AR binding, a significant increase of the cAMP level was observed only for the ivy preparation, which can be explained by the inhibited internalization of HiBiT-tagged β2AR under stimulating conditions. In contrast, isoprenaline-mediated internalization of HiBiT-tagged β2AR of ivy/thyme combination pre-treated cells was not inhibited. Cells comparatively pre-treated with a thyme preparation did not show inhibition of ß2AR internalization either. Furthermore, SNAP-tagged β2AR of ivy preparation pre-treated cells, which were not internalized after isoprenaline stimulation, showed a redistribution from fast-to-slowly diffusing β2AR. A corresponding redistribution of these receptors was not observed after pre-treatment with both the ivy/thyme combination and the thyme preparation. Comparable to the ivy/thyme combination, no decrease in the intratrack transitioning probability ratio (p23/p32) for fast and slow diffusing β2AR was found for the thyme preparation, which, however, significantly decreased for control cells and for pre-treatment with the ivy preparation under stimulating conditions. It can therefore be concluded that the thyme fluid extract fraction in the ivy/thyme combination may have in part a negative effect on the β2-adrenergic signal transduction.

Perlucin is one of the proteins of the organic matrix of nacre (mother of pearl) playing an important role in biomineralisation. This nacreous layer can be predominately found in the mollusc lineages and is most intensively studied as a compound of the shell of the marine Australian abalone Haliotis laevigata. A more detailed analysis of Perlucin will elucidate some of the still unknown processes in the complex interplay of the organic/inorganic compounds involved in the formation of nacre as a very interesting composite material not only from a life science-based point of view. Within this study we discovered three unknown Perlucin splice variants of the Australian abalone H. laevigata. The amplified cDNAs vary from 562 to 815 base pairs and the resulting translation products differ predominantly in the absence or presence of a varying number of a 10 mer peptide C-terminal repeat. The splice variants could further be confirmed by matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-ToF MS) analysis as endogenous Perlucin, purified from decalcified abalone shell. Interestingly, we observed that the different variants expressed as maltose-binding protein (MBP) fusion proteins in E. coli showed strong differences in their influence on precipitating CaCO3 and that these differences might be due to a splice variant-specific formation of large protein aggregates influenced by the number of the 10 mer peptide repeats. Our results are evidence for a more complex situation with respect to Perlucin functional regulation by demonstrating that Perlucin splice variants modulate the crystallisation of calcium carbonate. The identification of differentially behaving Perlucin variants may open a completely new perspective for the field of nacre biomineralisation.