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.

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.

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.

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.

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.

Acute Alcohol-Associated Hepatitis in the COVID-19 Pandemic - a Structured Review.

Purpose of Review: The COVID-19 pandemic has been associated with a change in alcohol consumption, resulting in an increase in alcohol-related liver disease. In this study, we reviewed the literature on (acute) alcohol-associated hepatitis (AH) in the context of the COVID-19 pandemic. Methodology: PubMed, Ovid MEDLINE, Embase, Cochrane Library, and the pre-print servers medRxiv and bioRxiv were searched to retrieve 320 articles of which 15 abstracts, 7 full-text articles, 4 letters, 1 case report, and 1 poster were included for the final structured review. Recent Findings: The pandemic resulted in an increase in healthcare utilization related to alcohol consumption. Admissions related to AH increased by 50% (range: 11-100%) during this time, which was disproportionally high in women, younger adults, African Americans, Hispanics, and patients living in rural areas. During this period, the number of new waiting list registrations and candidates with AH receiving liver transplantation (LT) simultaneously increased, which highlights the need for an approach to providing improvised healthcare services at the regional and individual levels.

Stem rust on barberry species in Europe: Host specificities and genetic diversity.

The increased emergence of cereal stem rust in southern and western Europe, caused by the pathogen Puccinia graminis, and the prevalence of alternate (sexual) host, Berberis species, have regained attention as the sexual host may serve as source of novel pathogen variability that may pose a threat to cereal supply. The main objective of the present study was to investigate the functional role of Berberis species in the current epidemiological situation of cereal stem rust in Europe. Surveys in 11 European countries were carried out from 2018 to 2020, where aecial infections from five barberry species were collected. Phylogenetic analysis of 121 single aecial clusters of diverse origin using the elongation factor 1-α gene indicated the presence of different special forms (aka formae speciales) of P. graminis adapted to different cereal and grass species. Inoculation studies using aecial clusters from Spain, United Kingdom, and Switzerland resulted in 533 stem rust isolates sampled from wheat, barley, rye, and oat, which confirmed the presence of multiple special forms of P. graminis. Microsatellite marker analysis of a subset of 192 sexually-derived isolates recovered on wheat, barley and rye from the three populations confirmed the generation of novel genetic diversity revealed by the detection of 135 multilocus genotypes. Discriminant analysis of principal components resulted in four genetic clusters, which grouped at both local and country level. Here, we demonstrated that a variety of Berberis species may serve as functional alternate hosts for cereal stem rust fungi and highlights the increased risks that the sexual cycle may pose to cereal production in Europe, which calls for new initiatives within rust surveillance, epidemiological research and resistance breeding.

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.

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.

A Multi-OMICs Approach Sheds Light on the Higher Yield Phenotype and Enhanced Abiotic Stress Tolerance in Tobacco Lines Expressing the Carrot lycopene ß-cyclase1 Gene.

Recently, we published a set of tobacco lines expressing the Daucus carota (carrot) DcLCYB1 gene with accelerated development, increased carotenoid content, photosynthetic efficiency, and yield. Because of this development, DcLCYB1 expression might be of general interest in crop species as a strategy to accelerate development and increase biomass production under field conditions. However, to follow this path, a better understanding of the molecular basis of this phenotype is essential. Here, we combine OMICs (RNAseq, proteomics, and metabolomics) approaches to advance our understanding of the broader effect of LCYB expression on the tobacco transcriptome and metabolism. Upon DcLCYB1 expression, the tobacco transcriptome (~2,000 genes), proteome (~700 proteins), and metabolome (26 metabolites) showed a high number of changes in the genes involved in metabolic processes related to cell wall, lipids, glycolysis, and secondary metabolism. Gene and protein networks revealed clusters of interacting genes and proteins mainly involved in ribosome and RNA metabolism and translation. In addition, abiotic stress-related genes and proteins were mainly upregulated in the transgenic lines. This was well in line with an enhanced stress (high light, salt, and H2O2) tolerance response in all the transgenic lines compared with the wild type. Altogether, our results show an extended and coordinated response beyond the chloroplast (nucleus and cytosol) at the transcriptome, proteome, and metabolome levels, supporting enhanced plant growth under normal and stress conditions. This final evidence completes the set of benefits conferred by the expression of the DcLCYB1 gene, making it a very promising bioengineering tool to generate super crops.

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.

Predicting On-Road Driving Skills, Fitness to Drive, and Prospective Accident Risk in Older Drivers and Drivers with Mild Cognitive Impairment: The Importance of Non-Cognitive Risk Factors.

BACKGROUND: On-road driving behavior can be impaired in older drivers and particularly in drivers with mild cognitive impairment (MCI). OBJECTIVE: To determine whether cognitive and non-cognitive risk factors for driving safety may allow an accurate and economic prediction of on-road driving skills, fitness to drive, and prospective accident risk in healthy older drivers and drivers with MCI, we examined a representative combined sample of older drivers with and without MCI (N = 74) in an observational on-road study. In particular, we examined whether non-cognitive risk factors improve predictive accuracy provided by cognitive factors alone. METHODS: Multiple and logistic hierarchical regression analyses were utilized to predict different driving outcomes. In all regression models, we included cognitive predictors alone in a first step and added non-cognitive predictors in a second step. RESULTS: Results revealed that the combination of cognitive and non-cognitive risk factors significantly predicted driving skills (R2adjusted = 0.30) and fitness to drive (81.2% accuracy) as well as the number (R2adjusted = 0.21) and occurrence (88.3% accuracy) of prospective minor at-fault accidents within the next 12 months. In all analyses, the inclusion of non-cognitive risk factors led to a significant increase of explained variance in the different outcome variables. CONCLUSION: Our findings suggest that a combination of the most robust cognitive and non-cognitive risk factors may allow an economic and accurate prediction of on-road driving performance and prospective accident risk in healthy older drivers and drivers with MCI. Therefore, non-cognitive risk factors appear to play an important role.

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.

Assessing fitness to drive in older adults: Validation and extension of an economical screening tool.

OBJECTIVES: Due to demographic change, the number of older drivers with impaired driving skills will increase in the next decades. The current study aimed at the validation and extension of the screening tool Safety Advice For Elderly drivers (SAFE) that allows a cost-efficient assessment of driving-related risk factors in older drivers. METHOD: Seventy-four older drivers aged ≥65 years (M = 77 years) recruited from the general population were included in this prospective observational study. Receiver operating characteristic curve (ROC) and hierarchical logistic regression analyses were utilized to examine whether the SAFE and further evidence-based driving-related factors may allow the differentiation between fit and unfit older drivers assessed in standardized on-road driving assessments. RESULTS: ROC analyses revealed significant diagnostic accuracy of the number of SAFE risk factors in differentiating between fit and unfit older drivers (AUC = 0.71). A stepwise logistic regression model revealed that adding further evidence-based risk factors into the SAFE clearly improved diagnostic accuracy (AUC = 0.85). DISCUSSION: The current study shows that the risk assessed by the SAFE predicts on-road driving fitness in older adults. However, the results also suggest a need for a modification of the SAFE by the inclusion of additional evidence-based risk factors. With sensitivity and specificity scores of about 90 % and 75 %, this modified version may be more suitable for clinical use.

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.