Peritoneal and renal DKK3 clearance in peritoneal dialysis.

BACKGROUND: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis. METHODS: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics. RESULTS: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3. CONCLUSION: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.

Pre-transplant serum Beta Trace Protein indicates risk for post-transplant major cardiac adverse events.

BACKGROUND: Beta Trace Protein (BTP) is a biomarker for residual kidney function which has been linked to cardiovascular and all-cause mortality in haemodialysis patients. Following renal transplantation, recipients remain at increased risk for cardiovascular events compared with the general population. We aimed to determine the relationship of pre-transplant BTP to major adverse cardiac events (MACE) in patients following kidney transplantation. METHODS: We included 384 patients with end-stage renal disease who received a kidney transplant. MACE was defined as myocardial infarction (ST-segment elevation or non-ST-segment elevation, stroke or transient ischemic attack), coronary artery disease requiring intervention or bypass or death for cardiovascular reason. The association between pre-transplant serum BTP concentration and post-transplant MACE was evaluated by Kaplan-Meier and Cox regression analyses. RESULTS: Post-transplant MACE occurred in 70/384 patients. Pre-transplant BTP was significantly higher in patients with post-transplant MACE (14.36 ± 5.73 mg/l vs. 11.26 ± 5.11 mg/l; p < .01). Next to smoking (HR 1.81), age > 56.38 years (HR 1.97) and pre-existing coronary heart disease (HR 8.23), BTP above the cut off value of 12.7 mg/l was confirmed as independent risk factor for MACE (HR 2.02, all p < .05). MACE-free survival inversely correlated with pre-transplant BTP levels. CONCLUSIONS: Pre-transplant serum BTP concentration may identify renal transplant recipients with higher risk of post-transplant MACE.

NT-proBNP as predictor of major cardiac events after renal transplantation in patients with preserved left ventricular ejection fraction.

BACKGROUND: For the improvement of outcome after renal transplantation it is important to predict future risk of major adverse cardiac events as well as all-cause mortality. We aimed to determine the relationship of pre-transplant NT-proBNP with major adverse cardiac events and all-cause mortality after transplant in patients on the waiting-list with preserved left ventricular ejection fraction. PATIENTS AND METHODS: We included 176 patients with end-stage renal disease and preserved left ventricular ejection fraction who received a kidney transplant. MACE was defined as myocardial infarction (ST-segment elevation [STEMI] or non-ST-segment elevation [NSTEMI]), stroke or transient ischemic attack), coronary artery disease requiring intervention or bypass or death from cardiovascular causes. RESULTS: MACE occurred in 28/176 patients. Patients with NT-proBNP levels above 4350 pg/ml had 1- and 5-year survival rates of 90.67% and 68.20%, whereas patients with NT-proBNP levels below 4350 pg/ml had 1- and 5-year survival rates of 100% and 90.48% (p < 0.01). 1- and 5-year MACE-free survival rates were calculated as 78.82% and 74.68% for patients with NT-proBNP > 4350 pg/ml and 93.33% and 91.21% for patients with NT-proBNP < 4350 pg/ml (p < 0.01). CONCLUSIONS: Pre-transplant NT-proBNP might identify renal transplant candidates at risk for MACE after transplant.

Defending in 4-4-2 or 5-3-2 formation? small differences in footballers' collective tactical behaviours.

This study explored footballers' tactical behaviours, based on their position data, as an effect of two defending formations, 4-4-2 and 5-3-2, using an experimental approach. Sixty-nine youth footballers participated in this 11-versus-11 study, performing 72 trials of attack-versus-defence. Players' position data were tracked using a local positioning system, and processed to calculate measures of collective movement. This was supplemented by the analysis of passing networks. The results showed small differences between the two conditions. Compared to a 4-4-2 formation, defending in 5-3-2 reduced dispersion (-0.69 m,p=0.012), midfield-forward distance (-0.81 m, p=0.047), and defence-forward distance (-1.29 m, p=0.038); the consequent effects on attacking teams included reduced team widths (-1.78 m, p=0.034), reduced necessity for back-passes to the goalkeeper, and less connectivity in the passing network. The effects of the two defending formations seem to have the greatest impact on fullbacks of the attacking teams, since they were main contributors of the reduced team widths, received more passes, and had higher betweenness centrality in the right-back position during 5-3-2 defending. In summary, the present study potentially demonstrates how the underlying mechanisms in players' collective movements and passing behaviours show that the 5-3-2 is more conservatively defensive than the 4-4-2.

Beta-trace protein as a potential biomarker of residual renal function in patients undergoing peritoneal dialysis.

BACKGROUND: Residual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients. METHODS: In this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes. RESULTS: In peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (rs = - 0.58, p < 0.001), residual creatinine clearance (ClCr) (rs = - 0.69, p < 0.001) and total urea clearance (Clurea) (rs = - 0.56, p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m2 (SD ± 1.38) and mean renal removal 15.14 L/week/1.73m2 (SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = - 0.41, p = 0.035) and renal creatinine clearance over time (r = - 0.79, p = p < 0.001). CONCLUSION: BTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.

The porous high-press? An experimental approach investigating tactical behaviours from two pressing strategies in football.

The aim of this study was to analyse footballers' tactical behaviours from their position data, as an effect of two contrasting pressing strategies, high-press defending and deep-defending, using a trial-based experimental approach. Sixty-nine youth footballers participated in this 11 versus 11 study, performing 72 trials of attack versus defence, in a counterbalanced crossover study design. Players' position data were captured using a local positioning system, and processed to calculate measures of inter-team distance, trial duration, distance to nearest opponent, dispersion, team length, team width, team shape, space control gain, inter-line distance, and individual area. This was augmented by the notational analyses of passes. The findings showed that using a high-press defending strategy leads to: closer inter-team distance; larger dispersion, due to a longer team length; and larger inter-line distances between defenders, midfielders, and forwards. The resulting effects on the attacking team include reduced ball possession time; larger individual areas for attacking midfielders and forwards; longer team length; and more penetrative passes performed. Some differences in marking behaviour were also observed. Consequently, the study recommends that high-press defending be used sparingly due to these trade-offs.

When polyuria does not stop: a case report on an unusual complication of hantavirus infection.

BACKGROUND: The clinical features, course and outcome of hantavirus infection is highly variable. Symptoms of the central nervous system may occur, but often present atypically and diagnostically challenging. Even though the incidence of hantavirus infection is increasing worldwide, this case is the first to describe diabetes insipidus centralis as a complication of hantavirus infection in the Western world. CASE PRESENTATION: A 49-year old male presenting with severe headache, nausea and photophobia to our neurology department was diagnosed with acute haemorrhage in the pituitary gland by magnetic resonance imaging. In the following days, the patient developed severe oliguric acute kidney failure. Diagnostic workup revealed a hantavirus infection, so that the pituitary haemorrhage resulting in hypopituitarism was seen as a consequence of hantavirus-induced hypophysitis. Under hormone replacement and symptomatic therapy, the patient's condition and kidney function improved considerably, but significant polyuria persisted, which was initially attributed to recovery from kidney injury. However, water deprivation test revealed central diabetes insipidus, indicating involvement of the posterior pituitary gland. The amount of urine production normalized with desmopressin substitution. CONCLUSION: Our case report highlights that neurological complications of hantavirus infection should be considered in patients with atypical clinical presentation.

Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy.

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy. Since antigen-presentation is the central similarity in the pathologies, this study focuses on antigen-presentation in CALT Morphology and the expression of CALT, which was investigated in mice after induction of dry-eye, ocular allergy, topical antigen-stimulation, and after local depletion of phagocytic cells. Antigen uptake was investigated after the application of fluorescent ovalbumin (OVA). OSD influences the appearance and morphology of CALT in a disease-dependent manner. Ocular allergy leads to an increase and dry-eye disease to a decrease in number and size of CALT. The development of CALT is dependent on the presence of APCs. Professional APCs are present in CALT, and soluble antigen is transported into the follicle. CALT appearance is disease-specific and indicative of differing functions. Although the specific involvement of CALT in OSD needs further study, the existence of functional APCS and antigen-uptake supports the hypothesis that CALT is an immunological key player at the ocular surface.

Urinary tract infection: recent insight into the evolutionary arms race between uropathogenic Escherichia coli and our immune system.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Humans evolved various immune-dependent and independent defense mechanisms, while pathogens evolved multiple virulence factors to fight back. This article summarizes recent findings regarding the arms race between hosts and pathogens in UTIs. It was recently reported that macrophage subsets regulate neutrophil-mediated defense in primary UTIs but seem to subvert adaptive immunity upon re-infection. Moreover, some bacterial strains can survive inside macrophages, leading to recurrent infections. Inflammasome activation results in infected host cell death and pathogen release, facilitating the removal of intracellular bacteria. As a counteraction, some bacteria evolved mechanisms to disrupt inflammasome activation. Mucosal-associated invariant T cells are further effectors that can lyse infected epithelial cells and release intracellular bacteria. Once released, the bacteria are phagocytosed by neutrophils. However, some bacteria can inhibit neutrophil migration and deprive neutrophils of nutrients. Furthermore, the complement system, considered generally bactericidal, is exploited by the bacteria for cellular invasion. Another weapon against UTI is antimicrobial peptides, e.g. ribonuclease 7, but its production is inhibited by certain bacterial strains. Thus the arms race in UTI is ongoing, and knowing the enemy's methods can help in developing new drugs to win the race.

The influence of motivation on stress: is it stressful not to fit?

The present research elaborates on the regulatory fit hypothesis by investigating a biological stress marker in a motivational fit- and non-fit-situation. Recent stress theories lead to the assumption that the participants' stress level in fit-situations remains constant or rather decreases, whereas under non-fit-conditions an increase of the stress activity is observed. We tested this hypothesis by assessment of salivary α-amylase (sAA), a saliva-based stress marker presumed to reflect noradrenergic activity. The results indicated that participants in a fit-situation show a decrease in sAA, whereas participants in a non-fit-situation demonstrate a contrary effect with an increase in sAA. These findings extend the concept of regulatory fit by illustrating that there are differences in sAA activity depending on whether participants are in a fit-situation. The experience of regulatory fit appears to be associated with a reduction of stress.

Recent Insights in Noninvasive Diagnostic for the Assessment of Kidney and Cardiovascular Outcome in Kidney Transplant Recipients.

Kidney transplantation improves quality of life and prolongs survival of patients with end-stage kidney disease. However, kidney transplant recipients present a higher risk for cardiovascular events compared to the general population. Risk assessment for graft failure as well as cardiovascular events is still based on invasive procedures. Biomarkers in blood and urine, but also new diagnostic approaches like genetic or molecular testing, can be useful tools to monitor graft function and to identify patients of high cardiovascular risk. Many biomarkers have been introduced, whereas most of these biomarkers have not been implemented in clinical routine. Here, we discuss recent developments in biomarkers and diagnostic models in kidney transplant recipients. Because many factors impact graft function and cardiovascular risk, it is most likely that no biomarker will meet the highest demands and standards. We advocate to shift focus to the identification of patients benefitting from molecular and genetic testing as well as from analysis of more specific biomarkers instead of finding one biomarker fitting to all patients.

The impact of a sports vision training program in youth field hockey players.

The aim of this study was to investigate whether a sports vision training program improves the visual performance of youth male field hockey players, ages 12 to 16 years, after an intervention of six weeks compared to a control group with no specific sports vision training. The choice reaction time task at the D2 board (Learning Task I), the functional field of view task (Learning Task II) and the multiple object tracking (MOT) task (Transfer Task) were assessed before and after the intervention and again six weeks after the second test. Analyzes showed significant differences between the two groups for the choice reaction time task at the D2 board and the functional field of view task, with significant improvements for the intervention group and none for the control group. For the transfer task, we could not find statistically significant improvements for either group. The results of this study are discussed in terms of theoretical and practical implications. Key pointsPerceptual training with youth field hockey playersCan a sports vision training program improve the visual performance of youth male field hockey players, ages 12 to 16 years, after an intervention of six weeks compared to a control group with no specific sports vision training?The intervention was performed in the "VisuLab" as DynamicEye(®) SportsVision Training at the German Sport University Cologne.We ran a series of 3 two-factor univariate analysis of variance (ANOVA) with repeated measures on both within subject independent variables (group; measuring point) to examine the effects on central perception, peripheral perception and choice reaction time.The present study shows an improvement of certain visual abilities with the help of the sports vision training program.

Investigating Care Dependency and Its Relation to Outcome (ICARE): Results From a Naturalistic Study of an Intensive Day Treatment Program for Depression.

Background: This study explores the association of experienced dependency in psychotherapy as measured with the CDQ (Care Dependency Questionnaire) and treatment outcome in depression. Furthermore, the course of care dependency and differences in the CDQ scores depending on the received type of treatment, MCT (metacognitive therapy), or CBASP (cognitive behavioral analysis system of psychotherapy), were investigated. Methods: The study follows a prospective, parallel group observational design. Patients suffering from depression received an 8-week intensive day clinic program, which was either CBASP or MCT. The treatment decision was made by clinicians based on the presented symptomatology and with regard to the patients' preferences. The patients reported depressive symptoms with the QIDS-SR16 (Quick Inventory of Depressive Symptomatology) and levels of experienced care dependency with the German version of the CDQ on a weekly basis. Mixed-model analyses were run to account for the repeated-measures design. Results: One hundred patients were included in the analyses. Results indicate that higher levels of care dependency might predict a less favorable outcome of depressive symptomatology. Levels of care dependency as well as depressive symptoms decreased significantly over the course of treatment. There was no significant between-group difference in care dependency between the two treatment groups. Conclusion: The results suggest that care dependency might be associated with a worse treatment outcome in depressed patients. In general, care dependency seems to be a dynamic construct, as it is changing over time, while the levels of care dependency seem to be independent from the received type of treatment. Future research should continue investigating the mechanisms of care dependency in a randomized controlled design. Clinical Trial Registration: https://www.drks.de/drks_web/, identifier: DRKS00023779.

A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation.

The Western diet is rich in salt, which poses various health risks. A high-salt diet (HSD) can stimulate immunity through the nuclear factor of activated T cells 5 (Nfat5)-signaling pathway, especially in the skin, where sodium is stored. The kidney medulla also accumulates sodium to build an osmotic gradient for water conservation. Here, we studied the effect of an HSD on the immune defense against uropathogenic E. coli-induced pyelonephritis, the most common kidney infection. Unexpectedly, pyelonephritis was aggravated in mice on an HSD by two mechanisms. First, on an HSD, sodium must be excreted; therefore, the kidney used urea instead to build the osmotic gradient. However, in contrast to sodium, urea suppressed the antibacterial functionality of neutrophils, the principal immune effectors against pyelonephritis. Second, the body excretes sodium by lowering mineralocorticoid production via suppressing aldosterone synthase. This caused an accumulation of aldosterone precursors with glucocorticoid functionality, which abolished the diurnal adrenocorticotropic hormone-driven glucocorticoid rhythm and compromised neutrophil development and antibacterial functionality systemically. Consistently, under an HSD, systemic Listeria monocytogenes infection was also aggravated in a glucocorticoid-dependent manner. Glucocorticoids directly induced Nfat5 expression, but pharmacological normalization of renal Nfat5 expression failed to restore the antibacterial defense. Last, healthy humans consuming an HSD for 1 week showed hyperglucocorticoidism and impaired antibacterial neutrophil function. In summary, an HSD suppresses intrarenal neutrophils Nfat5-independently by altering the local microenvironment and systemically by glucocorticoid-mediated immunosuppression. These findings argue against high-salt consumption during bacterial infections.

A tactical comparison of the 4-2-3-1 and 3-5-2 formation in soccer: A theory-oriented, experimental approach based on positional data in an 11 vs. 11 game set-up.

The presented field experiment in an 11 vs. 11 soccer game set-up is the first to examine the impact of different formations (e.g. 4-2-3-1 vs. 3-5-2) on tactical key performance indicators (KPIs) using positional data in a controlled experiment. The data were gathered using player tracking systems (1 Hz) in a standardized 11 vs. 11 soccer game. The KPIs were measured using dynamical positioning variables like Effective Playing Space, Player Length per Width ratio, Team Separateness, Space Control Gain, and Pressure Passing Efficiency. Within the experimental positional data analysis paradigm, neither of the team formations showed differences in Effective Playing Space, Team Separateness, or Space Control Gain. However, as a theory-based approach predicted, a 3-5-2 formation for the Player Length per Width ratio and Pressure Passing Efficiency exceeded the 4-2-3-1 formation. Practice task designs which manipulate team formations therefore significantly influence the emergent behavioral dynamics and need to be considered when planning and monitoring performance. Accordingly, an experimental positional data analysis paradigm is a useful approach to enable the development and validation of theory-oriented models in the area of performance analysis in sports games.

Influence of genetic variations in the SOD1 gene on the development of ascites and spontaneous bacterial peritonitis in decompensated liver cirrhosis.

BACKGROUND: The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated. PATIENTS AND METHODS: Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver transplantation. In addition, 344 cirrhotic patients with ascites were analyzed in a cohort of 521 individuals in terms of the relationship of these polymorphisms with spontaneous bacterial peritonitis (SBP). RESULTS: Although rs3844942 showed no associations with complications of cirrhosis, we observed a significant association between rs1041740 and the presence of ascites and SBP in the discovery cohort of patients with cirrhosis. Importantly, the association with SBP was not confirmed in the validation cohort of patients with ascites. By contrast, a trend toward lower SBP rates was observed in carriers of rs1041740. In this cohort, rs1041740 was not associated with survival. CONCLUSION: These data suggest a complex role of SOD1 in different processes leading to complications of liver cirrhosis. rs1041740 might be associated with the development of ascites and possibly plays a role in SBP once ascites has developed.

Top 10 Research Questions Related to Teaching Games for Understanding.

In this article, we elaborate on 10 current research questions related to the "teaching games for understanding" (TGfU) approach with the objective of both developing the model itself and fostering game understanding, tactical decision making, and game-playing ability in invasion and net/wall games: (1) How can existing scientific approaches from different disciplines be used to enhance game play for beginners and proficient players? (2) How can state-of-the-art technology be integrated to game-play evaluations of beginners and proficient players by employing corresponding assessments? (4) How can complexity thinking be utilized to shape day-to-day physical education (PE) and coaching practices? (5) How can game making/designing be helpfully utilized for emergent learning? (6) How could purposeful game design create constraints that enable tactical understanding and skill development through adaptive learning and distributed cognition? (7) How can teacher/coach development programs benefit from game-centered approaches? (8) How can TGfU-related approaches be implemented in teacher or coach education with the goal of facilitating preservice and in-service teachers/coaches' learning to teach and thereby foster their professional development from novices to experienced practitioners? (9) Can the TGfU approach be considered a helpful model across different cultures? (10) Can physical/psychomotor, cognitive, affective/social, and cultural development be fostered via TGfU approaches? The answers to these questions are critical not only for the advancement of teaching and coaching in PE and sport-based clubs, but also for an in-depth discussion on new scientific avenues and technological tools.