Effects of selection stringency on the outcomes of directed evolution.

Directed evolution makes mutant lineages compete in climbing complicated sequence-function landscapes. Given this underlying complexity it is unclear how selection stringency, a ubiquitous parameter of directed evolution, impacts the outcome. Here we approach this question in terms of the fitnesses of the candidate variants at each round and the heterogeneity of their distributions of fitness effects. We show that even if the fittest mutant is most likely to yield the fittest mutants in the next round of selection, diversification can improve outcomes by sampling a larger variety of fitness effects. We find that heterogeneity in fitness effects between variants, larger population sizes, and evolution over a greater number of rounds all encourage diversification.

Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.

Comparison of TP53 Mutations in Myelodysplasia and Acute Leukemia Suggests Divergent Roles in Initiation and Progression.

TP53 mutation predicts adverse prognosis in many cancers, including myeloid neoplasms, but the mechanisms by which specific mutations impact disease biology, and whether they differ between disease categories, remain unknown. We analyzed TP53 mutations in four myeloid neoplasm subtypes (MDS, AML, AML with myelodysplasia-related changes (AML-MRC), and therapy-related acute myeloid leukemia (tAML)), and identified differences in mutation types, spectrum, and hotspots between disease categories and compared to solid tumors. Missense mutations in the DNA-binding domain were most common across all categories, whereas inactivating mutations and mutations outside the DNA binding domain were more common in AML-MRC compared to MDS. TP53 mutations in MDS were more likely to retain transcriptional activity, and co-mutation profiles were distinct between disease categories and mutation types. Our findings suggest that mutated TP53 contributes to initiation and progression of neoplasia via distinct mechanisms, and support the utility of specific identification of TP53 mutations in myeloid malignancies.

Evaluating molecular fingerprint-based models of drug side effects against a statistical control.

There are many machine learning models that use molecular fingerprints of drugs to predict side effects. Characterizing their skill is necessary for understanding their usefulness in pharmaceutical development. Here, we analyze a statistical control of side effect prediction skill, develop a pipeline for benchmarking models, and evaluate how well existing models predict side effects identified in pharmaceutical documentation. We demonstrate that molecular fingerprints are useful for ranking drugs by their likelihood to cause a given side effect. However, the predictions for one or more drugs overall benefit only marginally from molecular fingerprints when ranking the likelihoods of many possible side effects, and display at most modest overall skill at identifying the side effects that do and do not occur.

Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

Combinatorial and statistical prediction of gene expression from haplotype sequence.

MOTIVATION: Genome-wide association studies (GWAS) have discovered thousands of significant genetic effects on disease phenotypes. By considering gene expression as the intermediary between genotype and disease phenotype, expression quantitative trait loci studies have interpreted many of these variants by their regulatory effects on gene expression. However, there remains a considerable gap between genotype-to-gene expression association and genotype-to-gene expression prediction. Accurate prediction of gene expression enables gene-based association studies to be performed post hoc for existing GWAS, reduces multiple testing burden, and can prioritize genes for subsequent experimental investigation. RESULTS: In this work, we develop gene expression prediction methods that relax the independence and additivity assumptions between genetic markers. First, we consider gene expression prediction from a regression perspective and develop the HAPLEXR algorithm which combines haplotype clusterings with allelic dosages. Second, we introduce the new gene expression classification problem, which focuses on identifying expression groups rather than continuous measurements; we formalize the selection of an appropriate number of expression groups using the principle of maximum entropy. Third, we develop the HAPLEXD algorithm that models haplotype sharing with a modified suffix tree data structure and computes expression groups by spectral clustering. In both models, we penalize model complexity by prioritizing genetic clusters that indicate significant effects on expression. We compare HAPLEXR and HAPLEXD with three state-of-the-art expression prediction methods and two novel logistic regression approaches across five GTEx v8 tissues. HAPLEXD exhibits significantly higher classification accuracy overall; HAPLEXR shows higher prediction accuracy on approximately half of the genes tested and the largest number of best predicted genes (r2>0.1) among all methods. We show that variant and haplotype features selected by HAPLEXR are smaller in size than competing methods (and thus more interpretable) and are significantly enriched in functional annotations related to gene regulation. These results demonstrate the importance of explicitly modeling non-dosage dependent and intragenic epistatic effects when predicting expression. AVAILABILITY AND IMPLEMENTATION: Source code and binaries are freely available at https://github.com/rapturous/HAPLEX. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Suppression of myocardial glucose metabolism in FDG PET/CT: impact of dose variation in heparin bolus pre-administration.

INTRODUCTION: Adequate suppression of physiologic myocardial glucose uptake is important to ensure the interpretability and diagnostic reliability of [18F]fluorodeoxyglucose (FDG) PET/CT studies performed in the context of cardiac inflammation and infection. This study describes our experience with 4 preparatory protocols used in our institution. METHODS: FDG PET/CT scans were performed according to 4 preparatory protocols (716 scans total), i.e. 6-h fast (group 1), low-carbohydrate diet plus 12-h fast (group 2), low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (15 IU/kg) (group 3), and low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (50 IU/kg) (group 4). Consecutive scans were retrospectively included from time frames during which the particular protocol was used. FDG uptake in normal myocardium was scored on a scale ranging from 0 (uptake less than that in the left ventricular blood pool) to 4 (diffuse uptake greater than that in the liver). Complete suppression was defined as uptake less than or equal to the blood pool (scores 0-1). RESULTS: Complete suppression was accomplished in 27% in group 1, 68% in group 2, 69% in group 3 and 81% in group 4. Complete suppression was significantly lower in group 1 compared with all other groups (P < 0.0001 for all comparisons) and significantly higher in group 4 compared with group 2 (P = 0.005) and group 3 (P = 0.007). Groups 2 and 3 did not differ significantly (P = 0.92). CONCLUSION: A total of 50 IU/kg single-dose heparin administration before FDG PET/CT in addition to a low-carbohydrate diet and prolonged fast significantly outperformed protocols with no or lower dose (15 IU/kg) heparin in completely suppressing myocardial glucose metabolism.

Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study.

BACKGROUND: Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson's disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment. METHODS: A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson's Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment. DISCUSSION: The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI. TRIAL REGISTRATION: Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014-001501-32, Clinicaltrials.gov: NCT02480803.

Detoxifying deoxynivalenol (DON)-contaminated feedstuff: consequences of sodium sulphite (SoS) treatment on performance and blood parameters in fattening pigs.

A 10-week feeding experiment was carried out examining the effects of deoxynivalenol (DON)-contaminated maize treated with different sodium sulphite (SoS) concentrations on performance, health and DON-plasma concentrations in fattening pigs. Two maize batches were used: background-contaminated (CON, 0.73 mg/kg maize) and Fusarium-toxin contaminated (DON, 44.45 mg/kg maize) maize. Both were wet preserved at 20% moisture content, with one of three (0.0, 2.5, 5.0 g/kg maize) sodium sulphite concentrations and propionic acid (15%). Each maize batch was then mixed into a barley-wheat-based diet at a proportion of 10%, resulting in the following 6 feeding groups: CON- (CON + 0.0 g SoS/kg maize), CON2.5 (CON + 2.5 g SoS/kg maize), CON5.0 (CON + 5.0 g SoS/kg maize), DON- (DON + 0.0 g SoS/kg maize), DON2.5 (DON + 2.5 g SoS/kg maize) and DON5.0 (DON + 5.0 g SoS/kg maize). Dietary DON concentration was reduced by ~ 36% in group DON2.5 and ~ 63% in group DON5.0. There was no impact on ZEN concentration in the diets due to SoS treatment. Pigs receiving diet DON- showed markedly lower feed intake (FI) compared to those fed the control diets. With SoS-treatment of maize, FI of pigs fed the DON diet (DON5.0: 3.35 kg/d) were comparable to that control (CON-: 3.30 kg/day), and these effects were also reflected in live weight gain. There were some effects of SoS, DON or their interaction on serum urea, cholesterol and albumin, but always within the physiological range and thus likely negligible. SoS wet preservation of Fusarium-toxin contaminated maize successfully detoxified DON to its innocuous sulfonates, thus restoring impaired performance in fatteners.

Evaluation of maternal attachment, self-efficacy, levels of depression, and anxiety in mothers who have babies diagnosed with retinopathy of prematurity.

PURPOSE: The aim of this study is to evaluate the emotional stress and its effects on parental self-efficacy and mother-infant attachment in mothers whose babies were diagnosed with retinopathy of prematurity (ROP). METHODS: Study sample was consisted of voluntarily participating 82 mothers whose babies were first diagnosed with ROP, 83 mothers of preterm babies without ROP, and 85 mothers of term babies admitting for their routine visits. Sociodemographic data form maternal attachment scale, state-trait anxiety inventory, Edinburgh postnatal depression scale, and parental self-efficacy scale were applied to study participants, and the overall results of three groups were statistically compared. RESULTS: The sociodemographic features of three study groups were similar. Statistical significant differences were found in depression and state anxiety levels among study groups, while maternal attachment scale and trait anxiety level scores and parental self-efficacy scale total score were similar in study groups. Maternal depression and state-anxiety levels were tend to be higher in mother of children diagnosed with ROP and prematurity; however, there were no statistically significant differences between levels of mothers' of premature children with or without ROP. CONCLUSION: This is the first study in literature assessing the additional effect of ROP on the anxiety and depression levels of recent mothers, as well as mother-infant attachment and parental self-efficacy. Supporting of mothers having an infant with diagnosed ROP is crucial because of feeling themselves inefficient and responsible for all interventions applied to their babies.

Comparison of calculated and experimentally determined SID of CP and AA in complex diets differing in AA contents for grower finisher pigs.

In practice, the content of standardized ileal digestible AA in complex feeds for pigs is calculated on the basis of tabulated values for individual feedstuffs. It comes into question, however, whether this truly reflects an accurate content based upon the estimate made for the individual feedstuffs. The objective of this study was to compare standardized ileal digestibility (SID) of crude protein (CP) and selected AA in complex feeds for grower and finisher pigs either calculated or experimentally determined. Six diets with increasing AA levels were prepared for grower (BW from 30 to 70 kg) and finisher (BW from 70 to 120 kg) feed. Crystalline L-lys, DL-met and L-thr were added to both diets, L-trp and L-val only to the grower feed. SID of both CP and AA was calculated from feed tables and experimentally determined in six adult minipigs (MINILEWE) with ileorectal anastomosis. With increasing AA levels, experimentally determined SID of supplemented AA increased (p < 0.05), but SID of CP (p ≥ 0.05) was not affected. In both grower and finisher feed, calculated and experimentally determined SID of CP, Met, Cys, Trp, Ile and Tyr differed by more than 2% units, but those of Lys and His only in the finisher feed. Yet this effect was not directly consistent. The margin of error following estimation of SID of AA via tabulated values for individual feedstuffs, however, seems to be acceptable for practical use.

Effects of two commercial diets and technical feed treatment on stomach lesions and immune system of fattening pigs.

The impact of technical feed treatment and diet on stomach lesions and traits of the local and systemic immune system were investigated in fattening pigs. Feeding groups differed in technical feed treatment (standard ground meal vs. finely ground and pelleted feed) and diet (soya bean meal vs. rapeseed meal/DDGS/soya beans). Pigs were fattened approximately 10 weeks by ad libitum feeding and slaughtered subsequently. Gastric alterations were assessed by a macroscopic scoring system [macroscopic stomach score (MSC) 0 =  normal to 4 =  severe lesions]. For immunological investigations, lymphocytes from blood and jejunal tissues were isolated. T-cell phenotyping was carried out by staining intestinal lymphocytes with monoclonal antibodies for CD4 and CD8 and flow cytometric measurements. MSC was higher in animals fed finely ground and pelleted feed compared with their counterparts. Significant interactions between diet and feed treatment considering the MSC were observed (p = 0.027). There was no effect of diet or technical feed treatment on T cells of blood, Lymphonodi gastrici or lamina propria (LP) and intraepithelial cells. However, technical feed treatment significantly affected subsets of CD4+ , CD8+ , CD8low , CD4/CD8 double-positive T cells, the mean fluorescence intensity of CD4+ T cells and the ratio of CD8low /CD8high T cells in Peyer's patches (PP). All named parameters were reduced in PP of animals fed finely ground and pelleted feed compared with animals fed standard ground meal. Furthermore, significant differences between T cells of lymph nodes and LP were observed between animals with middle MSC (MSC = 1-2.5) and animals with high MSC (MSC = 3-4). Significant alterations in T cells of PP were observed between animals of low (MSC = 0-0.5) and high MSC. The observed effects provide the evidence that the impact of technical feed treatment is not limited on the stomach lesions. Possible stimuli and consequences of the immune system should be studied in more detail.

Changing trends over the last decade in the aetiology of childhood blindness: a study from a tertiary referral centre.

AIMS: To discern treatable and preventable causes of childhood blindness by evaluating the aetiologic factors, and to compare the distribution of the most commonly affected anatomic sites of severe visual impairment (SVI) with our previous published data. METHODS: The charts of 11 871 patients followed between June 2002 and May 2014 were reviewed retrospectively, and 695 patients (5.9%) who had SVI or blindness in accordance with WHO criteria were enrolled. The results of ophthalmologic examinations and coexistence of any systemic disease were documented and checked against our published clinic data concerning the aetiology of childhood blindness before 2002. χ(2) test was used for statistics. RESULTS: Mean age was 47.0±51.9 months (median: 24 months). Cortical visual impairment (CVI) was present in 212 cases (30.5%) and 20.3% of those had a history of premature birth. The most common anatomic sites of SVI were retina (24.6%) and crystalline lens (17.1%). When compared with our previous data, we found a significant increase in the prevalence of CVI (p=0.046) and decrease in the frequency of SVI due to uveal disorders (p<0.001). Prevalence of blindness secondary to retinopathy of prematurity reduced by a third (p=0.280), and a significant decrease in aphakia-related SVI (p=0.028) was achieved within the last decade. CONCLUSIONS: The prevalence of CVI was found to be relatively increased due to the significant reduction in the frequency of preventable causes of SVI. Furthermore our clinical practice for visual rehabilitation in aphakia has resulted in a considerable decrease in SVI in the last decade.

Ocular disorders in children with spastic subtype of cerebral palsy.

AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors. METHODS: Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student's t tests were used in the statistical analysis. RESULTS: The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4%) and tetraplegia (36.1%) were found to be higher than the frequency of hemiplegia (16.5%) in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P=0.000). Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6%) had nystagmus and 107 children (55.2%) had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P=0.024, respectively). Abnormal morphology of the optic disc was present in 152 eyes (39.2%). Severe periventricular leukomalacia (PVL) was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P=0.000). CONCLUSION: Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.

Dominant-negative mechanism of leukemogenic PAX5 fusions.

PAX5 encodes a master regulator of B-cell development. It fuses to other genes associated with acute lymphoblastoid leukemia (ALL). These fusion products are potent dominant-negative (DN) inhibitors of wild-type PAX5, resulting in a blockade of B-cell differentiation. Here, we show that multimerization of PAX5 DNA-binding domain (DBD) is necessary and sufficient to cause extremely stable chromatin binding and DN activity. ALL-associated PAX5-C20S results from fusion of the N-terminal region of PAX5, including its paired DBD, to the C-terminus of C20orf112, a protein of unknown function. We report that PAX5-C20S is a tetramer, which interacts extraordinarily stably with chromatin as determined by Fluorescence Recovery After Photobleaching in living cells. Tetramerization, stable chromatin binding and DN activity all require a putative five-turn amphipathic α-helix at the C-terminus of C20orf112, and does not require potential corepressor binding peptides elsewhere in the sequence. In vitro, the monomeric PAX5 DBD and PAX5-C20S binds a PAX5-binding site with equal affinity when it is at the center of an oligonucleotide too short to bind to more than one PAX5 DBD. But, PAX5-C20S binds the same sequence with 10-fold higher affinity than the monomeric PAX5 DBD when it is in a long DNA molecule. We suggest that the increased affinity results from interactions of one or more of the additional DBDs with neighboring non-specific sites in a long DNA molecule, and that this can account for the increased stability of PAX5-C20S chromatin binding compared with wild-type PAX5, resulting in DN activity by competition for binding to PAX5-target sites. Consistent with this model, the ALL-associated PAX5 fused to ETV6 or the multimerization domain of ETV6 SAM results in stable chromatin binding and DN activity. In addition, PAX5 DBD fused to artificial dimerization, trimerization and tetramerization domains results in parallel increases in the stability of chromatin binding and DN activity. Our studies suggest that oncogenic fusion proteins that retain the DBD of the transcription factor (TF) and the multimerization sequence of the partner protein can act in a DN manner by multimerizing and binding avidly to gene targets, preventing the normal TF from binding and inducing expression of its target genes. Inhibition of this multimeriztion may provide a novel therapeutic approach for cancers with this or similar fusion proteins.

Delivery of an EBV episome by a self-circularizing helper-dependent adenovirus: long-term transgene expression in immunocompetent mice.

Epstein-Barr virus (EBV) evolved an episomal system for maintaining life-long, latent infection of human B lymphocytes. Circular episomes engineered from EBV components required for this latent form of infection have the capacity to persist in most types of replicating mammalian cells without DNA integration and the pitfalls of insertional mutagenesis. EBV episomes are typically transduced using low-efficiency methods. Here we present a method for efficient delivery of EBV episomes to nuclei of hepatocytes in living mice using a helper-dependent adenoviral vector and Cre-mediated recombination in vivo to generate circular EBV episomes following infection. Cre is transiently expressed from a hepatocyte-specific promoter so that vector generation and transgene expression are tissue specific. We show long-term persistence of the circularized vector DNA and expression of a reporter gene in hepatocytes of immunocompetent mice.

Attitudes, knowledge and experience of nurses working in psychiatric hospitals in Greece, regarding borderline personality disorder: a comparative study.

The objectives of this study is to determine the knowledge, attitudes and experience of psychiatric nurses regarding clients with Borderline Personality Disorder (BPD) and to compare nurses working in Psychiatric Hospitals with those in Psychiatric Clinics of General Hospitals. The study was performed in two public Psychiatric Hospitals and the Psychiatric Clinics of two public General Hospitals in the area of Greater Athens. The 23-item questionnaire of Cleary et al. was used in this study. It was sent to all nurses (n = 127) in 15 psychiatric wards. The staff have good enough knowledge regarding the diagnosis and treatment of the BPD patients. In Psychiatric Hospitals (A) the staff comes in contact with BPD patients less frequently than in the Psychiatric Clinics in General Hospitals (B). In the diagnostic question of 'the unstable mood with rapid shifts' most of the nurses who responded correctly belong to group A than to group B. In group A, nurses believe that not informing the patients of their disorder is the reason for their inadequate treatment, while in group B it is not reported as a reason. In group A, the staff consider that it is within their role to assess BPD patients, far more than in group B. Our hypothesis that nurses in psychiatric hospitals had less knowledge and experience as well as negative attitudes towards BPD patients was not confirmed, although the contact frequency with BPD patients was found statistically low.

Efficacy of occlusion treatment in amblyopia and clinical risk factors affecting the results of treatment.

PURPOSE: To evaluate the factors influencing visual outcome in strabismic, strabismic-anisometropic and anisometropic amblyopia following occlusion treatment. METHODS: Records of 128 pediatric patients who had been treated for amblyopia by occlusion of the fellow eye between March 1992 and March 2003 were reviewed retrospectively. Age and level of visual acuity at initiation of treatment, occlusion time (full-time, part-time or minimal) and type of amblyopia were analyzed for the effect on visual outcome. RESULTS: The mean age of the patients was 5.69 +/- 2.01 years (3 to 12 years). Mean follow-up time was 3 years 2 months (6 months to 10 years). Mean visual acuity improvements were similar for the subtypes of amblyopia (strabismic amblyopia 0.38 +/- 0.29 logMAR units, strabismic-anisometropic amblyopia 0.46 +/- 0.40 logMAR units, anisometropic amblyopia 0.35 +/- 0.24 logMAR units). Level of initial visual acuity, age at initiation of treatment and type of occlusion correlated with the final visual acuity (p = 0.000, p = 0.035, p = 0.012, respectively). When the analysis was performed according to the subtypes of amblyopia, initial visual acuity was the only factor associated with the final visual acuity in all types of amblyopia (p < 0.05). CONCLUSION: The level of initial visual acuity is the most significant factor determining the success of treatment in amblyopia.

Psychosocial aspects of mothers of children with strabismus.

PURPOSE: The aim of the study was to investigate the psychological profile of mothers of children with strabismus, their attitudes to their children, and their family functioning. METHODS: This study was conducted at Dokuz Eylül University School of Medicine, from 2000 to 2002 and involved a series of 30 children with strabismus and 31 healthy controls. All mothers were asked to complete Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Parental Attitude Research Instrument (PARI), and Family Assessment Device (FAD). RESULTS: Mothers of the children with strabismus had significantly higher depression scores ( P = 0.042) compared with mothers of the control group. They demonstrated significantly lower scores in democratic attitude, meaning that they failed to constitute a supportive and friendship relation with their children, ( P = 0.0001). These mothers had significantly higher scores in rejection of maternal role ( P = 0.017) as compared with mothers of the control group. They were nervous, distressed, and angry in the relationship with their children, with unhappiness and more dissatisfaction with respect to maternal role. Mothers of the children with strabismus had poor role functioning in the family, which is related to satisfying the food, clothing, and support needs ( P = 0.034). They also had poor affective responsiveness, which means the ability of family members to respond with appropriate emotion ( P = 0.003), and poor general functioning ( P = 0.040) as compared with mothers of the control group. CONCLUSIONS: This study demonstrated that, for mothers who have children with strabismus, strabismus had an adverse effect on their lives, and their family relationships.