Ischemia and reperfusion injury in kidney transplantation : relevant mechanisms in injury and repair

Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atrophy. Recently, more insight has been gained in the underlying molecular pathways and signalling cascades involved, which opens the door to new therapeutic opportunities aiming to reduce IRI and improve graft survival. This review systemically discusses the specific molecular pathways involved in the pathophysiology of IRI and highlights new therapeutic strategies targeting these pathways

Anti-HEV seroprevalence and rate of viremia in a German cohort of dogs, cats, and horses

Hepatitis E virus (HEV) genotype 3 infections in Germany are mainly transmitted zoonotically through the consumption of swine meat. Furthermore, there is evidence that pets might come into contact with HEV, but the relevance of companion animals as possible sources of HEV transmission in Germany still needs to be defined. A monitoring study was therefore carried out on dogs, cats, and horses from Germany. In total 365 serum samples from pets (124 dogs, 119 cats, and 122 horses) were tested for HEV by PCR and for anti-HEV antibodies by a commercial ELISA. The HEV seroprevalence determined by the sero-assay varied significantly between dogs (10%), cats (6%), and horses (2%). Liver injury-related enzymes, alanine transaminase (ALT), and aspartate transaminase (AST) showed no differences between HEV-positive or negative animals. None of the pet serum samples tested positive for PCR. This serological study suggests that dogs and cats are significantly exposed to HEV in Germany, while horses are of minor relevance

Double blockade of CD14 and complement C5 abolishes the cytokine storm and improves morbidity and survival in polymicrobial sepsis in mice

Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)–induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54–95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24–48 h). Combined treatment increased median survival to 96 h (range 24–240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24–48 h] and 48 h [24–96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis

Strong-field control of the dissociative ionization of N2O with near-single-cycle pulses

The dissociative ionization of N2O by near-single-cycle laser pulses is studied using phase-tagged ion-ion coincidence momentum imaging. Carrier-envelope phase (CEP) dependences are observed in the absolute ion yields and the emission direction of nearly all ionization and dissociation pathways of the triatomic molecule. We find that laser-field-driven electron recollision has a significant impact on the dissociative ionization dynamics and results in pronounced CEP modulations in the dication yields, which are observed in the product ion yields after dissociation. The results indicate that the directional emission of coincident N+ and NO+ ions in the denitrogenation of the dication can be explained by selective ionization of oriented molecules. The deoxygenation of the dication with the formation of coincident N-2(+) + O+ ions exhibits an additional shift in its CEP dependence, suggesting that this channel is further influenced by laser interaction with the dissociating dication. The experimental results demonstrate how few-femtosecond dynamics can drive and steer molecular reactions taking place on (much) longer time scales

Analyzing Zero Returns to Education in Germany: Heterogeneous Effects and Skill Formation

We analyze the effect of education on wages using German Socio-Economic Panel data and regional variation in mandatory years of schooling and the supply of schools. This allows us to estimate more than one local average treatment effect and heterogeneous effects for different groups of compliers. Our results are in line with previous studies that do not find an effect of compulsory schooling on wages in Germany. We go beyond these studies and test a potential reason for it, namely that basic skills are learned earlier in Germany and additional years of schooling are not effective anymore. This is done by also estimating the effect of education on cognitive skills. The results suggest that education after the eighth year does not seem to have a causal effect on cognitive skills in Germany. This is consistent with the explanation for zero effects of schooling on earnings

International ResearchKit app for women with menstrual pain : development, access, and engagement

Background: Primary dysmenorrhea is a common condition in women of reproductive age. A previous app-based study undertaken by our group demonstrated that a smartphone app supporting self-acupressure introduced by a health care professional can reduce menstrual pain. Objective: This study aims to evaluate whether a specific smartphone app is effective in reducing menstrual pain in 18- to 34-year-old women with primary dysmenorrhea in a self-care setting. One group of women has access to the full-featured study app and will be compared with 2 control groups who have access to fewer app features. Here, we report the trial design, app development, user access, and engagement. Methods: On the basis of the practical implications of the previous app-based study, we revised and reengineered the study app and included the ResearchKit (Apple Inc) framework. Behavior change techniques (BCTs) were implemented in the app and validated by expert ratings. User access was estimated by assessing recruitment progress over time. User evolution and baseline survey respondent rate were assessed to evaluate user engagement. Results: The development of the study app for a 3-armed randomized controlled trial required a multidisciplinary team. The app is accessible for the target population free of charge via the Apple App Store. In Germany, within 9 months, the app was downloaded 1458 times and 328 study participants were recruited using it without external advertising. A total of 98.27% (5157/5248) of the app-based baseline questions were answered. The correct classification of BCTs used in the app required psychological expertise. Conclusions: Conducting an innovative app study requires multidisciplinary effort. Easy access and engagement with such an app can be achieved by recruitment via the App Store. Future research is needed to investigate the determinants of user engagement, optimal BCT application, and potential clinical and self-care scenarios for app use

Social Contacts and the Economic Performance of Immigrants: A Panel Study of Immigrants in Germany

Using data from the German Socio-Economic Panel, we examined the impact of social contacts on immigrant occupational status and income. In addition to general social contacts, we also analyzed the effects of bonding (i.e., co-ethnic) and bridging (i.e., interethnic) ties on economic outcomes. Results show that general social contacts have a positive effect on the occupational status and, in particular, annual income of immigrants. We also find that bridging ties with Germans lead to higher occupational status, but not to increased income. These effects remain visible even when social contacts are measured (at least) one year prior to the economic outcomes, as well as when earlier investments in German human capital are considered. Finally, we show that co-ethnic concentration in the region of residence weakly affects economic returns to German language proficiency and schooling

The Competition between Relationship-Based Microfinance and Transaction Lending

We empirically analyze the competition between a relationship lender and a transaction lender in the credit business with micro and small entrepreneurs. Drawing on a data set about the customers of the relationship lender ProCredit Ecuador combined with data about all other loans of these customers in the Ecuadorian banking system, we are able to analyze the competition between different banking types. We find that the quality of ProCredit borrowers who have a trans- action loan as well is below average. They also have higher default probabilities. Furthermore, we find evidence that ProCredit customers with payment problems prefer to serve their relationship loan while defaulting on their transaction loan. These findings suggest that customers of a relationship bank value their banking relationship and try to protect it as long as possible. This result stands in contrast to the common presumption that the market entrance of transaction lenders will destroy the market for lenders applying relationship lending techniques

The effects of immigration on wages: An application of the structural skill-cell approach

This paper investigates how recent immigration inflows from 2002 to 2008 have affected wages in Switzerland. This period is of particular interest as it marks the time during which the bilateral agreement with the EU on the free cross-border movement of workers has been effective. Since different types of workers are likely to be unevenly affected by recent immigration inflows, we follow the ”structural skill-cell approach” as for example employed by Borjas (2003) and Ottaviano and Peri (2008). This paper provides two main contributions. First, we estimate empirically the elasticities of substitution between different types of workers in Switzerland. Our results suggest that natives and immigrants are imperfect substitutes. Regarding different skill levels, the estimates indicate that workers are imperfect substitutes across broad education groups and across different experience groups. Second, the estimated elasticities of substitution are used to simulate the impact on domestic wages using the actual immigration inflows from 2002 to 2008. For the long run, the simulations produce some notable distributional consequences across different types of workers: While previous immigrants incur wage losses (−1.6%), native workers are not negatively affected on average (+0.4%). In the short run, immigration has a negative macroeconomic effect on the average wage, which, however, gradually dies out in the process of capital adjustment