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We provide an overview of housing privatization policies and outcomes in transition economies. Our primary aim is to collect and systematize key information concerning the institutional features of housing privatization in individual countries: we identify the initial conditions, the timeframe of housing privatization and its culmination, the extent of housing privatization, who decided about its terms and conditions, who was entitled to privatize the housing, and at what price. Furthermore, using micro-data covering all transition countries, we present new estimates of the extent of housing privatization, its dynamics during the second half of the 2000s, and the resulting housing tenure structure.

Abstract Background Prion diseases are neurodegenerative diseases that are characterized by the conversion of the cellular prion protein (PrPc) into a pathogenic isoform (PrPSc). It is known that neurodegeneration is often accompanied by the disturbance of cholesterol homeostasis. We have recently identified a set of genes that were upregulated after prion infection of N2a neuronal cells (Bach et al., 2009). Results We have now used ultra-deep sequencing technology to profile all microRNAs (miRNA) that could be associated with this effect in these N2a cells. Using stringent filters and normalization strategies we identified a small set of miRNAs that were up- or downregulated upon prion infection. Using bioinformatic tools we predicted whether the downregulated miRNAs could target mRNAs that have been previously identified to enhance cholesterol synthesis in these cells. Application of this joint profiling approach revealed that nine miRNAs potentially target cholesterol-related genes. Four of those miRNAs are localized in a miRNA-dense cluster on the mouse X-chromosome. Among these, twofold downregulation of mmu-miR-351 and mmu-miR-542-5p was confirmed by qRT-PCR. The same miRNAs were predicted as putative regulators of the sterol regulatory element-binding factor 2 (Srebf2), the low-density lipoprotein receptor (Ldlr) or the IPP isomerase. Conclusions The results demonstrate that joined profiling by ultra-deep sequencing is highly valuable to identify candidate miRNAs involved in prion-induced dysregulation of cholesterol homeostasis.

Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.

Abstract The aim of our study was to analyze the differential expression of miRNAs in the brains of BSE-infected cynomolgus macaques as a model for Creutzfeldt-Jakob disease (CJD). MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression by mRNA targeting. Among other functions they contribute to neuronal development and survival. Recently, the lack of miRNA processing has been shown to promote neurodegeneration and deregulation of several miRNAs has been reported to be associated with Scrapie in mice. Therefore, we hypothesized that miRNAs are also regulated in response to human prion disease. We have applied miRNA-microarrays to identify deregulated miRNA candidates in brains of BSE-infected macaques. Shock-frozen brain sections of six BSE-infected and five non-infected macaques were used to validate regulated miRNA candidates by two independent qRT-PCR-based methods. Our study revealed significant upregulation of hsa-miR-342-3p and hsa-miR-494 in the brains of BSE-infected macaques compared to non-infected animals. In a pilot study we could show that hsa-miR-342-3p was also upregulated in brain samples of human type 1 and type 2 sporadic CJD. With respect to the reported regulation of this miRNA in Scrapie-infected mice, we propose that upregulation of hsa-miR-342-3p may be a general phenomenon in late stage prion disease and might be used as a novel marker for animal and human TSEs.

Hypertrophic Cardiomyopathy (HCM) is often caused by heterozygous mutations in β-myosin heavy chain (MYH7, β-MyHC). In addition to hyper- or hypocontractile effects of HCM-mutations, heterogeneity in contractile function (contractile imbalance) among individual cardiomyocytes was observed in end-stage HCM-myocardium. Contractile imbalance might be induced by burst-like transcription, leading to unequal fractions of mutant versus wildtype mRNA and protein in individual cardiomyocytes (allelic imbalance). Until now it is not known if allelic and contractile imbalance are present early in HCM-development or rather occur in response to disease-associated remodeling. To address this question, we used patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with heterozygous MYH7-mutations R723G and G741R as models of early-stage HCM without secondary adaptions upon disease progression. R723G-hiPSC-CMs showed typical HCM-markers like hypertrophy and myofibrillar disarray. Using RNA-FISH and allele-specific single-cell-PCR, we show for both cell lines that MYH7 is transcribed in bursts. Highly variable mutant vs. wildtype MYH7-mRNA fractions in individual HCM-hiPSC-CMs indicated allelic imbalance. HCM-hiPSC-CM-lines showed functional alterations like slowed twitch contraction kinetics and reduced calcium sensitivity of myofibrillar force generation. A significantly larger variability in force generation or twitch parameters of individual HCM-hiPSC-CMs compared to WT-hiPSC-CMs indicated contractile imbalance. Our results with early-stage hiPSC-CMs strongly suggest that burst-like transcription and allelic imbalance are general features of CMs, which together with mutation-induced changes of sarcomere contraction could induce contractile imbalance in heterozygous CMs, presumably aggravating development of HCM. Genetic or epigenetic approaches targeting functional heterogeneity in HCM could lead to promising future therapies, in addition to myosin modulation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. Up to 40% of cases are associated with heterozygous mutations in myosin binding protein C (cMyBP-C, MYBPC3). Most of these mutations lead to premature termination codons (PTC) and patients show reduction of functional cMyBP-C. This so-called haploinsufficiency most likely contributes to disease development. We analyzed mechanisms underlying haploinsufficiency using cardiac tissue from HCM-patients with truncation mutations in MYBPC3 (MYBPC3 trunc ). We compared transcriptional activity, mRNA and protein expression to donor controls. To differentiate between HCM-specific and general hypertrophy-induced mechanisms we used patients with left ventricular hypertrophy due to aortic stenosis (AS) as an additional control. We show that cMyBP-C haploinsufficiency starts at the mRNA level, despite hypertrophy-induced increased transcriptional activity. Gene set enrichment analysis (GSEA) of RNA-sequencing data revealed an increased expression of NMD-components. Among them, Up-frameshift protein UPF3B, a regulator of NMD was upregulated in MYBPC3 trunc patients and not in AS-patients. Strikingly, we show that in sarcomeres UPF3B but not UPF1 and UPF2 are localized to the Z-discs, the presumed location of sarcomeric protein translation. Our data suggest that cMyBP-C haploinsufficiency in HCM-patients is established by UPF3B-dependent NMD during the initial translation round at the Z-disc., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To develop and assess the test-retest reliability of a survey exploring Australian high-performance female athlete's perspectives toward the periodic health evaluation and their perceived health needs., Methods: A structured three-phase method for survey development was used to develop the periodic health evaluation for female athletes (PHE FA) survey. Initially, a literature review and gap analysis was performed to identify themes and questions (Phase 1). Survey questions were developed covering demographic information (n = 9); sports-related medical screening (n = 19) and health needs and information (n = 7) (Phase 2). Test-retest reliability of the survey was then assessed (Phase 3). The survey was administered to a purposeful sample of seven high-performance level female athletes who completed the survey, on two separate occasions, 3 weeks apart via Checkbox© survey software (Checkbox Technology Inc., San Francisco, CA). Test-retest reliability was assessed using the intraclass correlation coefficient (ICC)., Results: The mean age of the athletes was 29 years (SD 4 years, range 24-34 years). All were able-bodied athletes and 71% participated in team sports. Eighty-six percent of athletes have competed in world championships and 71% were Olympians. The average ICC of all items was 0.998 (95% CI 0.997-0.998, p = 0.000) demonstrating excellent consistency of measures between the two time points.All the athletes preferred a Sport and Exercise Medicine Physician to conduct their PHE and 86% preferred a female doctor. The key topics of interest were pelvic floor health including incontinence (100%); fertility (86%); pregnancy (71%); and mental and emotional wellbeing (71%). Face-to-face education was the preferred option to receive health information., Conclusions: The PHE FA survey was co-created with an athlete and other key stakeholders. Excellent consistency of measures between the two time points was indicated by the high test-retest reliability of the PHE FA survey. Data collected using the PHE FA survey can contribute to informed evidence-based policies, and processes to support the health and wellbeing of female athletes.

Myosin heavy chain (MyHC) is the main determinant of contractile function. Human ventricular cardiomyocytes (CMs) predominantly express the β-isoform. We previously demonstrated that ∼80% of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) express exclusively β-MyHC after long-term culture on laminin-coated glass coverslips. Here, we investigated the impact of enzymatically detaching hESC-CMs after long-term culture and subsequently replating them for characterization of cellular function. We observed that force-related kinetic parameters, as measured in a micromechanical setup, resembled α- rather than β-MyHC-expressing myofibrils, as well as changes in calcium transients. Single-cell immunofluorescence analysis revealed that replating hESC-CMs led to rapid upregulation of α-MyHC, as indicated by increases in exclusively α-MyHC- and in mixed α/β-MyHC-expressing hESC-CMs. A comparable increase in heterogeneity of MyHC isoform expression was also found among individual human induced pluripotent stem cell (hiPSC)-derived CMs after replating. Changes in MyHC isoform expression and cardiomyocyte function induced by replating were reversible in the course of the second week after replating. Gene enrichment analysis based on RNA-sequencing data revealed changes in the expression profile of mechanosensation/-transduction-related genes and pathways, especially integrin-associated signaling. Accordingly, the integrin downstream mediator focal adhesion kinase (FAK) promoted β-MyHC expression on a stiff matrix, further validating gene enrichment analysis. To conclude, detachment and replating induced substantial changes in gene expression, MyHC isoform composition, and function of long-term cultivated human stem cell-derived CMs, thus inducing alterations in mechanosensation/-transduction, that need to be considered, particularly for downstream in vitro assays., (© 2023 Osten et al.)

Transcriptional bursting is a common expression mode for most genes where independent transcription of alleles leads to different ratios of allelic mRNA from cell to cell. Here we investigated burst-like transcription and its consequences in cardiac tissue from Hypertrophic Cardiomyopathy (HCM) patients with heterozygous mutations in the sarcomeric proteins cardiac myosin binding protein C (cMyBP-C, MYBPC3 ) and cardiac troponin I (cTnI, TNNI3 ). Using fluorescence in situ hybridization (RNA-FISH) we found that both, MYBPC3 and TNNI3 are transcribed burst-like. Along with that, we show unequal allelic ratios of TNNI3 -mRNA among single cardiomyocytes and unequally distributed wildtype cMyBP-C protein across tissue sections from heterozygous HCM-patients. The mutations led to opposing functional alterations, namely increasing (cMyBP-C c.927-2A>G ) or decreasing (cTnI R145W ) calcium sensitivity. Regardless, all patients revealed highly variable calcium-dependent force generation between individual cardiomyocytes, indicating contractile imbalance, which appears widespread in HCM-patients. Altogether, we provide strong evidence that burst-like transcription of sarcomeric genes can lead to an allelic mosaic among neighboring cardiomyocytes at mRNA and protein level. In HCM-patients, this presumably induces the observed contractile imbalance among individual cardiomyocytes and promotes HCM-development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burkart, Kowalski, Aldag-Niebling, Beck, Frick, Holler, Radocaj, Piep, Zeug, Hilfiker-Kleiner, dos Remedios, van der Velden, Montag and Kraft.)

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disease, is caused by several mostly heterozygous mutations in sarcomeric genes. Hallmarks of HCM are cardiomyocyte and myofibrillar disarray and hypertrophy and fibrosis of the septum and the left ventricle. To date, a pathomechanism common to all mutations remains elusive. We have proposed that contractile imbalance, an unequal force generation of neighboring cardiomyocytes, may contribute to development of HCM hallmarks. At the same calcium concentration, we found substantial differences in force generation between individual cardiomyocytes from HCM patients with mutations in β-MyHC (β-myosin heavy chain). Variability among cardiomyocytes was significantly larger in HCM patients as compared with donor controls. We assume that this heterogeneity in force generation among cardiomyocytes may lead to myocardial disarray and trigger hypertrophy and fibrosis. We provided evidence that burst-like transcription of the MYH7-gene, encoding for β-MyHC, is associated with unequal fractions of mutant per wild-type mRNA from cell to cell (cell-to-cell allelic imbalance). This will presumably lead to unequal fractions of mutant per wild-type protein from cell to cell which may underlie contractile imbalance. In this review, we discuss molecular mechanisms of burst-like transcription with regard to contractile imbalance and disease development in HCM.

Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomeric proteins. Thirty to forty percent of identified mutations are found in the ventricular myosin heavy chain (β-MyHC). A common mechanism explaining how numerous mutations in several different proteins induce a similar HCM-phenotype is unclear. It was proposed that HCM-mutations cause hypercontractility, which for some mutations is thought to result from mutation-induced unlocking of myosin heads from a so-called super-relaxed state (SRX). The SRX was suggested to be related to the "interacting head motif," i.e., pairs of myosin heads folded back onto their S2-region. Here, we address these structural states of myosin in context of earlier work on weak binding cross-bridges. However, not all HCM-mutations cause hypercontractility and/or are involved in the interacting head motif. But most likely, all mutations alter the force generating mechanism, yet in different ways, possibly including inhibition of SRX. Such functional-hyper- and hypocontractile-changes are the basis of our previously proposed concept stating that contractile imbalance due to unequal fractions of mutated and wildtype protein among individual cardiomyocytes over time will induce cardiomyocyte disarray and fibrosis, hallmarks of HCM. Studying β-MyHC-mutations, we found substantial contractile variability from cardiomyocyte to cardiomyocyte within a patient's myocardium, much higher than in controls. This was paralleled by a similarly variable fraction of mutant MYH7-mRNA (cell-to-cell allelic imbalance), due to random, burst-like transcription, independent for mutant and wildtype MYH7-alleles. Evidence suggests that HCM-mutations in other sarcomeric proteins follow the same disease mechanism.

Objectives: The aim of this study was to detect the seroprevalence of Crimean-Congo haemorrhagic fever virus (CCHFV) in patients with fever of unknown origin (FUO) in endemic (Kyzylorda) and non-endemic (Almaty) oblasts of Kazakhstan., Methods: Paired serum samples from 802 patients with FUO were collected. Serum samples were investigated by ELISA to detect IgG and IgM antibodies against CCHFV. Sera with suspected acute infection were further investigated by RT-PCR to detect the viral RNA., Results: IgG antibodies were detected in 12.7% of the sera from both oblasts. Acute infection was shown by IgM ELISA in four patients from Kyzylorda, with only one developing severe CCHF. Viral RNA was found by RT-PCR in the other three patients' sera. Phylogenetic analysis of partial L and S segments revealed CCHFV genotype Asia 2 and a possible reassortment between the genotypes Asia 1/Asia 2. Animal husbandry, such as working with cattle and horses, was significantly associated with CCHFV seropositivity., Conclusions: The antibodies and viral RNA detected in sera indicate that mild or even asymptomatic CCHFV infections are presented in Kazakhstan. This study describes the circulation of CCHFV in the so far non-endemic Almaty oblast for the first time. In conclusion, physicians treating patients with FUO in Kazakhstan should be aware of mild CCHF., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

During CRISPR/Cas9 mediated genome editing, site-specific double strand breaks are introduced and repaired either unspecific by non-homologous end joining (NHEJ) or sequence dependent by homology directed repair (HDR). Whereas NHEJ-based generation of gene knock-out is widely performed, the HDR-based knock-in of specific mutations remains a bottleneck. Especially in primary cell lines that are essential for the generation of cell culture and animal models of inherited human diseases, knock-in efficacy is insufficient and needs significant improvement. Here, we tested two different approaches to increase the knock-in frequency of a specific point mutation into the MYH7 -gene in porcine fetal fibroblasts. We added a small molecule inhibitor of NHEJ, SCR7 (5,6-bis((E)-benzylideneamino)-2-mercaptopyrimidin-4-ol), during genome editing and screened cell cultures for the point mutation. However, this approach did not yield increased knock-in rates. In an alternative approach, we fused humanized Cas9 (hCas9) to the N-terminal peptide of the Geminin gene ( GMNN ). The fusion protein is degraded in NHEJ-dominated cell cycle phases, which should increase HDR-rates. Using hCas9- GMNN and point mutation-specific real time PCR screening, we found a two-fold increase in genome edited cell cultures. This increase of HDR by hCas9- GMNN provides a promising way to enrich specific knock-in in porcine fibroblast cultures for somatic cloning approaches.

Hypertrophic Cardiomyopathy (HCM) has been related to many different mutations in more than 20 different, mostly sarcomeric proteins. While development of the HCM-phenotype is thought to be triggered by the different mutations, a common mechanism remains elusive. Studying missense-mutations in the ventricular beta-myosin heavy chain (β-MyHC, MYH7 ) we hypothesized that significant contractile heterogeneity exists among individual cardiomyocytes of HCM-patients that results from cell-to-cell variation in relative expression of mutated vs. wildtype β-MyHC. To test this hypothesis, we measured force-calcium-relationships of cardiomyocytes isolated from myocardium of heterozygous HCM-patients with either β-MyHC-mutation Arg723Gly or Arg200Val, and from healthy controls. From the myocardial samples of the HCM-patients we also obtained cryo-sections, and laser-microdissected single cardiomyocytes for quantification of mutated vs. wildtype MYH7 -mRNA using a single cell RT-qPCR and restriction digest approach. We characterized gene transcription by visualizing active transcription sites by fluorescence in situ hybridization of intronic and exonic sequences of MYH7 -pre-mRNA. For both mutations, cardiomyocytes showed large cell-to-cell variation in Ca ++ -sensitivity. Interestingly, some cardiomyocytes were essentially indistinguishable from controls what might indicate that they had no mutant β-MyHC while others had highly reduced Ca ++ -sensitivity suggesting substantial fractions of mutant β-MyHC. Single-cell MYH7 -mRNA-quantification in cardiomyocytes of the same patients revealed high cell-to-cell variability of mutated vs. wildtype mRNA, ranging from essentially pure mutant to essentially pure wildtype MYH7 -mRNA. We found 27% of nuclei without active transcription sites which is inconsistent with continuous gene transcription but suggests burst-like transcription of MYH7 . Model simulations indicated that burst-like, stochastic on/off-switching of MYH7 transcription, which is independent for mutant and wildtype alleles, could generate the observed cell-to-cell variation in the fraction of mutant vs. wildtype MYH7 -mRNA, a similar variation in β-MyHC-protein, and highly heterogeneous Ca ++ -sensitivity of individual cardiomyocytes. In the long run, such contractile imbalance in the myocardium may well induce progressive structural distortions like cellular and myofibrillar disarray and interstitial fibrosis, as they are typically observed in HCM.

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

Objective: The aim of this study was to investigate if there is an independent association between substance use and satisfaction in vocational education. Methods: A cross-sectional study of 5 688 first-year apprentices from 49 vocational schools, mean age 19.4 years (SD=3.9 years) was undertaken. Data were analysed using multilevel linear regression analysis. Predictors were use of tobacco, alcohol, cannabis and pharmaceuticals as well as personal characteristics (sex, age, migration background, educational level, financial status, chronic diseases, psychological distress, physical activity, media use, personality) and vocational/firm characteristics (firm size, number of apprentices, perceived quality of mentoring, amount of pay, vocational field, working conditions, over- and underload, housing situation, number of previous apprenticeships, first choice). Vocational satisfaction was used as primary outcome. Results: Satisfaction was most strongly associated with perceived quality of mentoring, judgement that the chosen education was first choice and working climate in the training company. In addition, only problematic alcohol use remained significant in the multivariate analysis. There was no association in the adjusted model between vocational satisfaction and daily tobacco use or problematic use of cannabis and pharmaceuticals. Conclusions: Results suggest that problematic alcohol use could be an independent risk factor for problems in vocational education., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: We investigated the effect of stimulation intensity (in percent of maximal tolerated stimulation current, mTSC), frequency, and impulse width on muscle fatigue., Methods: Using a randomized crossover design, 6 parameter combinations (80% mTSC, 80 Hz, 400 μs; 60% mTSC, 80 Hz, 400 μs; 80% mTSC, 20 Hz, 400 μs; 60% mTSC, 20 Hz, 400 μs; 80% mTSC, 80 Hz, 150 μs; 60% mTSC, 80 Hz, 150 μs) were tested in both legs of 13 athletic men (age 26 ± 2.3). The slope of the linear regression line over all tetani (FIS) and the number of tetani whose force was above 50% of the initial tetanus (FIN) were used to quantify fatigue., Results: FIS and FIN were significantly lower in high-frequency protocols. No effects on FIS and FIN were found for intensity and impulse width., Conclusions: Stimulation frequency, but not impulse width or intensity, affected fatigue kinetics., (© 2015 Wiley Periodicals, Inc.)

Aim: If unaccustomed lengthening contractions are repeated within a certain period of time, muscle damage symptoms are blunted. This observation, often referred to as the repeated bout effect (RBE), also holds true for the response of muscle damage markers like creatine kinase (CK). However, measuring plasma enzyme activity rather than the concentration of enzyme protein might conceal the actual amount of damaged tissue. Therefore, the primary aim of the study was to investigate if the RBE of CK can partially be explained by enzyme inactivation., Methods: Ten healthy male subjects performed two bouts of 100 drop-to-vertical jumps (DVJs) from a 70-cm high platform at an interval of three weeks. CK activity, CK concentration, and neutrophils were measured prior to, and on four consecutive days after the interventions., Results: Besides significant main effects, there was a significant group by time interaction for the specific CK activity (CK activity in blood [U/L] divided by the enzyme concentration [ng/mL]). Higher values following the first bout (133.1±99.4 U/µg) than the second bout (94.7±63.0 U/µg) indicate that the ratio of inactive to active CK molecules increased. Neutrophil levels were similar following both bouts and differed only at 8 hours (7.0±2.5 bout 1, 5.1±1.6 bout 2)., Conclusion: The findings of the present study support the hypothesis that the blunted response of CK activity after a repeated bout of eccentric exercise is not solely the result of tissue protection, but can be at least partially attributed to enzyme inactivation.