Imaging of plant calcium-sensor kinase conformation monitors real time calcium-dependent decoding in planta.

Changes in cytosolic calcium (Ca2+) concentration are among the earliest reactions to a multitude of stress cues. While a plethora of Ca2+-permeable channels may generate distinct Ca2+ signatures and contribute to response specificities, the mechanisms by which Ca2+ signatures are decoded are poorly understood. Here, we developed a genetically encoded Förster resonance energy transfer (FRET)-based reporter that visualizes the conformational changes in Ca2+-dependent protein kinases (CDPKs/CPKs). We focused on two CDPKs with distinct Ca2+-sensitivities, highly Ca2+-sensitive Arabidopsis (Arabidopsis thaliana) AtCPK21 and rather Ca2+-insensitive AtCPK23, to report conformational changes accompanying kinase activation. In tobacco (Nicotiana tabacum) pollen tubes, which naturally display coordinated spatial and temporal Ca2+ fluctuations, CPK21-FRET, but not CPK23-FRET, reported oscillatory emission ratio changes mirroring cytosolic Ca2+ changes, pointing to the isoform-specific Ca2+-sensitivity and reversibility of the conformational change. In Arabidopsis guard cells, CPK21-FRET-monitored conformational dynamics suggest that CPK21 serves as a decoder of signal-specific Ca2+ signatures in response to abscisic acid and the flagellin peptide flg22. Based on these data, CDPK-FRET is a powerful approach for tackling real-time live-cell Ca2+ decoding in a multitude of plant developmental and stress responses.

The effect of repeated concussions on clinical and neurocognitive symptom severity in different contact sports.

INTRODUCTION: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports-related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports-related concussions on clinical and neurocognitive health in different contact sports. MATERIALS AND METHODS: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports-related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments). RESULTS: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance. DISCUSSION: Repeated sports-related concussions appear to have a cumulative impact on clinical-but not cognitive-symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Liver stiffness and prediction of cardiac outcomes in patients with acute decompensated heart failure.

BACKGROUND: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however, it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. METHODS: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. RESULTS: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = .049). Moreover, the risk of composite outcome was highest in the 3rd tertile (> 39.8 kPa compared to 1st and 2nd combined, HR 2.83, 95% CI 1.20- 6.67, p = .02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = .01). CONCLUSIONS: LSM may serve as a novel noninvasive tool to determine LVAD, HT, or death in patients with ADHF.

Impaired Color Discrimination in Alzheimer Disease Dementia.

OBJECTIVE: Patients with Alzheimer disease dementia (ADD) often show impaired orientation and navigation. Signage offers an opportunity to compensate for these deficits, communicate information efficiently and facilitate wayfinding. Certain properties of signs such as colors and contrasts may beneficially affect the uptake and processing of information particularly in ADD patients. METHODS: Thirty-six healthy older adults and 30 ADD patients performed a computerized color perception task that required discriminating different color combinations. The effects of different contrast features on performance accuracy and speed in the 2 experimental groups were examined by nonparametric mixed analysis of variances. RESULTS: Analyses revealed a significant effect of contrast polarity on reaction times, significant effects of group on reaction times and errors as well as a marginally significant interaction of group×color on errors. All participants benefitted from positive contrast polarity (ie, dark target on lighter background) as indicated by increased performance speed. Furthermore, ADD patients reacted slower and less accurate than healthy controls, but showed higher accuracy at black-white and red-yellow than at blue-green color combinations. CONCLUSIONS: Our findings suggest the implementation of signs with positive contrast polarity to ensure faster reactions. In addition, certain color combinations may enhance accuracy, particularly in patients with ADD.

Children after uterus transplantation: 2-year outcomes from the Dallas UtErus Transplant Study (DUETS).

OBJECTIVE: To describe outcomes in the first 2 years of life for the children born in the Dallas UtErus Transplant Study. DESIGN: Cohort study comprising all live births from uterus transplantation at a single centre. SETTING: Baylor University Medical Center, Dallas, Texas. POPULATION: A total of 14 children from 12 uterus transplantation recipients. METHODS: Retrospective review of data through 2 years of life. MAIN OUTCOME MEASURES: Information on children's development was collected based on the Bright Futures Guideline and the Bright Futures Previsit Questionnaire. Primary outcomes were anthropometric measures (children's body length, weight, head circumference), neurological status, cognitive status and physical development at 6, 12, 18 and 24 months of age. RESULTS: The median gestational age at delivery was 36+6  weeks, with a median birthweight of 2940 g. Follow-up data were available for 13 offspring. Physical and neurological developmental milestones were met and were age appropriate in all children within the first 24 months. General health was good, and no abnormalities in immune development were found. Cognitive deviations were only mild and temporary and improved with interventions. CONCLUSIONS: The children's growth and physical, neurological and cognitive development were age appropriate within the first 2 years of life. To confirm these outcomes, further data should be collected in collaboration with other centres.

The 'marketplace of post-conflict assistance' in northern Uganda and beyond.

This paper puts forward the framework of the 'marketplace of post-conflict assistance' as a conceptual, analytical, and heuristic tool to comprehend better holistic dynamics in humanitarian and post-conflict contexts, where a variety of different actors offer various services and forms of assistance. It seeks to emphasise relations and interactions between service providers and intended beneficiaries in settings where there are often numerous different ways to conceptualise and manage problems stemming from armed conflict. This is demonstrated using one in-depth case study of a family in northern Uganda that has struggled for years with mental illness/spiritual problems. By framing the post-conflict space using the marketplace metaphor, it is possible to deepen understanding of how people try out different options to manage issues related to warfare and seek healing. Importantly, this framework also recognises the agency that people exercise in doing so, and how communities and service providers relate to each other.

Improving plant drought tolerance and growth under water limitation through combinatorial engineering of signalling networks.

Agriculture is by far the biggest water consumer on our planet, accounting for 70 per cent of all freshwater withdrawals. Climate change and a growing world population increase pressure on agriculture to use water more efficiently ('more crop per drop'). Water-use efficiency (WUE) and drought tolerance of crops are complex traits that are determined by many physiological processes whose interplay is not well understood. Here, we describe a combinatorial engineering approach to optimize signalling networks involved in the control of stress tolerance. Screening a large population of combinatorially transformed plant lines, we identified a combination of calcium-dependent protein kinase genes that confers enhanced drought stress tolerance and improved growth under water-limiting conditions. Targeted introduction of this gene combination into plants increased plant survival under drought and enhanced growth under water-limited conditions. Our work provides an efficient strategy for engineering complex signalling networks to improve plant performance under adverse environmental conditions, which does not depend on prior understanding of network function.

Preoperative synovial fluid culture poorly predicts the pathogen causing periprosthetic joint infection.

PURPOSE: We investigated the value of preoperative pathogen detection and evaluated its concordance with intraoperative cultures in patients with culture-positive periprosthetic joint infection (PJI). METHODS: Culture-positive PJI episodes with available preoperative (synovial fluid) and intraoperative cultures (periprosthetic tissue, synovial or sonication fluid) were analyzed. The pathogen detection rate in preoperative and intraoperative cultures was compared using Fisher's exact test and their concordance was calculated. RESULTS: Among 167 included PJI episodes, 150 were monomicrobial with coagulase-negative staphylococci (n = 55, 37%), S. aureus (n = 34, 23%), and streptococci (n = 21, 14%) being the most common pathogens. Seventeen episodes (10%) were polymicrobial infections. The pathogen(s) grew in preoperative culture in 110 and in intraoperative cultures in 153 episodes (66% vs. 92%, p < 0.001). The pathogen detection rate was lower in preoperative compared to intraoperative cultures for low-virulent pathogens (40% vs. 94%, p < 0.001), polymicrobial infections (59% vs. 100%, p = 0.007), and in delayed and late PJI (63% vs. 94%, and 66% vs. 91%, respectively, p < 0.001). Full concordance of preoperative and intraoperative cultures was found in 87 episodes (52%). The pathogen was detected solely preoperatively in 14 episodes (8%) and solely intraoperatively in 57 cases (34%); an additional pathogen was found in 3 episodes (2%) preoperatively and in 6 episodes (4%) intraoperatively. CONCLUSION: The concordance of preoperative and intraoperative cultures was poor (52%). The sole or an additional pathogen was found exclusively in intraoperative cultures in 38% of PJI episodes, hence preoperative synovial fluid cultures are considered unreliable for pathogen detection in PJI.

Symbol Comprehension in Patients With Alzheimer Disease Dementia, Mild Cognitive Impairment, and Major Depressive Disorder.

INTRODUCTION: Previous research suggests that specific symbol features attenuate symbol comprehension deficits in seniors suffering from Alzheimer disease dementia (ADD). However, it remains unclear whether these findings also apply to other disorders associated with cognitive dysfunctions. METHODS: Ninety healthy controls, 30 patients with major depressive disorder (MDD), 35 patients with mild cognitive impairment (MCI), and 55 patients with ADD performed a Symbol Processing Task with 4 different symbol categories. Nonparametric between×within subjects analyses were conducted to examine the impact of different symbol categories on performance accuracy in all experimental groups. RESULTS: Analyses revealed a higher symbol comprehension accuracy in healthy seniors than in MDD, MCI, and ADD patients, with the lowest accuracy rates shown by ADD patients. Although the type of symbol hardly affected performance accuracy in healthy seniors and MDD patients, different symbol categories influenced the performance of MCI and ADD patients significantly. CONCLUSIONS: Our findings indicate that symbols with distracting features impede symbol comprehension in ADD and MCI. Symbols with visual cues, by contrast, facilitate symbol comprehension in ADD and may even be advantageous over standardized symbols used in public life.

Ca2+ coordination controls sonic hedgehog structure and its Scube2-regulated release.

Proteolytic processing of cell-surface-bound ligands, called shedding, is a fundamental system to control cell-cell signaling. Yet, our understanding of how shedding is regulated is still incomplete. One way to increase the processing of dual-lipidated membrane-associated Sonic hedgehog (Shh) is to increase the density of substrate and sheddase. This releases and also activates Shh by the removal of lipidated inhibitory N-terminal peptides from Shh receptor binding sites. Shh release and activation is enhanced by Scube2 [signal sequence, cubulin (CUB) domain, epidermal growth factor (EGF)-like protein 2], raising the question of how this is achieved. Here, we show that Scube2 EGF domains are responsible for specific proteolysis of the inhibitory Shh N-terminus, and that CUB domains complete the process by reversing steric masking of this peptide. Steric masking, in turn, depends on Ca2+ occupancy of Shh ectodomains, unveiling a new mode of shedding regulation at the substrate level. Importantly, Scube2 uncouples processing of Shh peptides from their lipid-mediated juxtamembrane positioning, and thereby explains the long-standing conundrum that N-terminally unlipidated Shh shows patterning activity in Scube2-expressing vertebrates, but not in invertebrates that lack Scube orthologs.

Effectiveness of inpatient versus outpatient complex treatment programs in depressive disorders: a quasi-experimental study under naturalistic conditions.

BACKGROUND: Due to long waiting periods for outpatient psychotherapy and the high resource requirements of inpatient treatment, there is a need for alternative treatment programs for patients with depressive disorders. Thus, we investigated the effectiveness of the "Bielefeld Outpatient Intensive Treatment Program of Depression" (BID) in comparison with a typical inpatient treatment program by using a prospective quasi-experimental observational study. We assumed (i) that both complex programs are effective in pre-post analyses after 6 weeks and (ii) that inpatient treatment is more effective compared with the outpatient program. METHODS: Four hundred patients with depressive psychopathology - a majority with depressive episodes (ICD-10 F3X) - took part in the BID and 193 in the inpatient program. Different self- (i.e., BDI) and expert measures (i.e., MADRS) of psychopathology at baseline (t1) and 6 weeks later (t2) were applied to examine treatment effects. RESULTS: Treatment effects were high in separate analyses of both groups with Cohen's d ranging from 1.10 to 1.76., while ANOVA comparative analyses did not reveal any significant differences between both treatment settings nor did a set of independent covariates analyzed here. Response rates of BDI (p = .002) and MADRS (p = .001) were higher in the outpatient group. Results indicate BID not to be inferior compared to an inpatient program, although diverging pathways to treatment, higher rates of clinical recurrent depressive disorders and severe episodes as well as lower rates of employment and partnership in the inpatient treatment group have to be considered. CONCLUSION: Outpatient intensive treatment programs may represent a solution for patients needing more than a treatment session once per week but less than a complex inpatient or day clinic program.

Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells.

All morphogens of the Hedgehog (Hh) family are synthesized as dual-lipidated proteins, which results in their firm attachment to the surface of the cell in which they were produced. Thus, Hh release into the extracellular space requires accessory protein activities. We suggested previously that the proteolytic removal of N- and C-terminal lipidated peptides (shedding) could be one such activity. More recently, the secreted glycoprotein Scube2 (signal peptide, cubulin domain, epidermal-growth-factor-like protein 2) was also implicated in the release of Shh from the cell membrane. This activity strictly depended on the CUB domains of Scube2, which derive their name from the complement serine proteases and from bone morphogenetic protein-1/tolloid metalloproteinases (C1r/C1s, Uegf and Bmp1). CUB domains function as regulators of proteolytic activity in these proteins. This suggested that sheddases and Scube2 might cooperate in Shh release. Here, we confirm that sheddases and Scube2 act cooperatively to increase the pool of soluble bioactive Shh, and that Scube2-dependent morphogen release is unequivocally linked to the proteolytic processing of lipidated Shh termini, resulting in truncated soluble Shh. Thus, Scube2 proteins act as protease enhancers in this setting, revealing newly identified Scube2 functions in Hh signaling regulation.

"A bend in time": Shaping the sheath facilitates left atrial appendage closure.

OBJECTIVES: The purpose of this study is to determine feasibility, safety, and effectiveness of the "shape-the-sheath" method in left atrial appendage closure. BACKGROUND: LAA occlusion is often a difficult procedure, due to not just the learning curve but also the three-dimensional variable nature of the left atrial appendage. Multiple sheaths have been created for various takeoffs. The purpose of this article is to show the feasibility of the "shape-the-sheath" method in left atrial appendage closure. METHODS: Ten consecutive patients undergoing LAA occlusion without the "shape-the-sheath" method were compared to 10 consecutive patients undergoing LAA occlusion with the "shape-the-sheath" method using the Amplatzer Cardiac Plug (ACP) system and the Amplatzer TorqVue 45×45 sheath. RESULTS: The "shape-the-sheath" method resulted in significant decreases in fluoroscopy time (7.2±3.0 min vs. 13.7±6.7 min, P<0.05), number of partial recaptures (0% vs. 50%, P<0.05), with a trend toward decrease in the number of complete recaptures (0 vs. 40%, P=0.09) compared to conventional sheath use. CONCLUSIONS: Shaping-the-sheath is a simple, elegant way to help conform delivery systems to better access the LAA and ensure stable position. Further experience with this procedure optimization step is warranted.

Use of EchoNavigator, a novel echocardiography-fluoroscopy overlay system, for transseptal puncture and left atrial appendage occlusion.

Structural heart disease requires a coordinated effort to join echocardiographic and fluoroscopic data. Various methods have been used, including echocardiography, CT, and MRI. We report on the use of EchoNavigator (Philips Inc., Amsterdam, Netherlands), a novel echocardiographic-fluoroscopic fusion system. This new system allows real-time integration and marking of important structures that track on fluoroscopy even with movement of the C-arm. In this article, we describe potential uses for this system in respect to transseptal puncture and left atrial appendage closure.

A Comparison of Two Transport Monitor Systems With Regard to Efficiency and Staff Satisfaction in the Perioperative Setting.

BACKGROUND: Medical research aims to improve patient safety and efficiency in the perioperative setting. One critical aspect of patient safety is the intrahospital transfer of patients. Also, reliable monitoring of vital signs is crucial to support the medical staff. This study was conducted to assess two monitoring systems in terms of the handover time and staff satisfaction. METHODS: To assess several aspects, two monitoring systems were compared: an organizational unit-related monitoring system that needs to be changed and brought back to the initial organizational unit after the patient transfer and a patient-specific monitoring system that accompanies the patient during the whole perioperative process. RESULTS: In total, 243 patients were included, and 375 transfers were examined to analyze economic factors, including differences in handover times and user-friendliness. To this end, 30 employees of the Heidelberg University Hospital were asked about their satisfaction with the two monitoring systems based on a systematic questionnaire. It could be shown that, especially during transfers from the operating theater to the intensive care unit or the recovery room, the time from arrival to fully centralized monitoring and the total handover time were significantly shorter with the patient-specific monitoring system (p < 0.001). Furthermore, the staff was more satisfied with the patient-specific monitor system in terms of flexibility, cleanability and usability. CONCLUSION: The increased employee satisfaction and significant time benefits during intrahospital transports may increase patient safety and efficiency of patient care, reduce employee workload, and reduce costs in the overall context of patient care.

Newly diagnosed hepatitis C infection after pancreas transplantation with multiple treatment failures.

This case represents the first report of a detected hepatitis C virus (HCV) infection following a pancreas transplantation that failed two different sofosbuvir (SOF)-based treatments. We present the case of a woman in her 30s with a history of kidney transplantation, who developed viremic symptoms 3 months after pancreas transplantation and with two subsequent negative HCV antibody tests. Further work-up revealed a positive HCV RNA test (genotype 1A, treatment naive). Two different direct-acting antiviral agents regimes with SOF failed in our case, and the patient achieved a sustained virological response with a 16-week course of glecaprevir/pibrentasvir.

Give Me a Sign: Concrete Symbols Facilitate Orientation in Alzheimer's Disease Dementia.

OBJECTIVES: Persons with Alzheimer's disease dementia (ADD) often show impaired orientation, particularly in unknown environments. Signs may offer an opportunity to compensate for these deficits and thus improve participation. METHODS: We assessed 30 persons with ADD and 36 healthy controls by using a sign comprehension paradigm (SCP) in a real-life environment. Nonparametric mixed model analyses of variance were used to analyze the effect of different symbols and additional scripture (coding condition) on SCP performance speed and accuracy. RESULTS: Analyses revealed a significant main effect of symbol design on SCP speed as well as an interaction effect of group × symbol, indicating a benefit of concrete, optimized signs for persons with ADD. Furthermore, analyses of SCP error rates revealed the main effects of group and coding condition as well as an interaction effect of group × coding. Persons with ADD made more errors than healthy controls, but SCP error rates decreased significantly in ADD in the double-coding condition. DISCUSSION: Our findings revealed an advantage of concrete double-coded symbols over conventional symbols and therefore strongly suggest the implementation of concrete double-coded signs to support older people living with ADD.

Immunosuppression in Uterus Transplantation: Experience From the Dallas Uterus Transplant Study.

BACKGROUND: Uterus transplantation is a temporary transplant allowing women with absolute uterine factor infertility to experience pregnancy and childbirth. The degree of immunosuppression (IS) required to prevent rejection while minimizing toxicity to the recipient and fetus remains an area of investigation. METHODS: In this article, we describe immunosuppressive therapy, rejection episodes, infections, and adverse events in 14 uterus transplant recipients. Induction consisted of antithymocyte globulin and methylprednisolone. Ten recipients (71%) received no steroids postoperatively, and 4 (29%) had steroids tapered off at 42 d. All received oral tacrolimus, either immediate release (n = 2, 14%) or extended release (n = 12, 86%). Mycophenolate was used in 4 cases (29%), de novo azathioprine in 9 (64%), and de novo everolimus in 1 (7%). RESULTS: Sixteen clinically silent, treatment-responsive rejection episodes occurred in 10 recipients. Five recipients (36%) experienced acute kidney injury. In 3 recipients, IS was discontinued due to renal dysfunction. Eleven infection episodes were noted in 7 recipients. No babies had congenital abnormalities. CONCLUSIONS: Our experience demonstrates that safe IS regimens can be used for uterus transplant recipients before and during pregnancy.

Overestimation of on-road driving performance is associated with reduced driving safety in older drivers.

OBJECTIVES: Older drivers often show less precise self-ratings with a tendency to overestimate themselves. It is unclear, however, how overestimators differ from underestimators or drivers with adequate self-ratings. METHODS: 59 healthy older drivers participated in this on-road study. Besides standardized on-road driving assessment, the study protocol included the collection of neuropsychological and driving-related data as well as different self-ratings. Statistical analyses involved correlations between different subjective and objective ratings as well as statistical comparisons between drivers who overestimated and drivers who adequately rated their on-road driving performance (no drivers underestimated their performance). RESULTS: Despite positive correlations between different self- and expert ratings, our results revealed that 25 % of the participants overestimated their on-road driving skills. Among other things, overestimators showed poorer on-road driving performances, more prospective near and minor at-fault accidents, poorer cognitive performances in specific driving-related domains and reduced annual mileage. DISCUSSION: Our results suggest that older drivers who overestimate their driving skills show poorer performances within a broad range of skills that directly reflect or are closely related to driving safety. Against the background that an adequate self-assessment is required by German traffic regulations, our findings suggest that overestimators represent a risk group among the population of older drivers.