Aleš Kuběna

Nonadherence in inflammatory bowel disease: Results of factor analysis

Background: The purpose of the study was to assess overall nonadherence to treatment among patients with Crohns disease (CD) and ulcerative colitis (UC) in a single tertiary center. Methods: A total of 177 patients were enrolled in this study (84 males, 93 females; 117 CD, 60 UC). Patients were interviewed about their nonadherent behavior and their answers were analyzed using factor analysis. Urine samples were collected from a subcohort of 47 patients treated by mesalamine to verify the presence of 5‐ASA or its metabolites. Results: Overall intentional nonadherence was reported by 38.9% of patients; 18.6% of the patients discontinued the treatment at least once. Intentional dose reduction was reported by 18% of patients; 14.7% of patients occasionally did not refill their medications on time. There were no differences in adherence between males and females, disease type, previous bowel surgery, or marital, smoking, and nonsmoking status. More than 38% of patients reported unintentional nonadherence. Factor analysis proved that nonadherence increased with a higher education level of the patients and decreased with older age. Adverse drug effects strongly contributed to nonadherence. Nonadherent patients were more likely to be chronically active or in relapse (&tgr; = 0.212; P = 0.002). In the group of 47 patients whose urine was analyzed, 6 cases (12.7%) were negative for mesalamine or its metabolite. Conclusions: The overall intentional nonadherence with medical therapy is relatively high among IBD patients and should be taken into account when a patients response to treatment is unsatisfactory. Therefore, problems of nonadherence should be discussed with all IBD patients. (Inflamm Bowel Dis 2007)

The Distribution of Toxoplasma gondii Cysts in the Brain of a Mouse with Latent Toxoplasmosis: Implications for the Behavioral Manipulation Hypothesis

Background The highly prevalent parasite Toxoplasma gondii reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. Methodology/Principal Findings The distributions of T. gondii cysts and histopathological lesions in the brains of CD1 mice with latent toxoplasmosis were analyzed using standard histological techniques. Mice were infected per orally with 10 tissue cysts of the avirulent HIF strain of T. gondii at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. Conclusion/Significance The observed pattern of T. gondii distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism.

Influence of latent toxoplasmosis on the secondary sex ratio in mice

The sex ratio may be influenced by many factors, such as stress and immunosuppression, age of parents, parity and sex of preceding siblings. In animal systems, parasitism often changes the sex ratio of infected hosts, which can increase the probability of their transmission. The most common human protozoan parasite in developed countries, Toxoplasma gondii (prevalence 20%-80%), is known to change the behaviour of its intermediate hosts, thereby increasing the probability of transmission to its definitive host (the cat) by predation. The intermediate hosts, which under natural conditions are rodents, serve as the vector for Toxoplasma. Therefore, we speculate that Toxoplasma can alter the secondary sex ratio (i.e. male to female ratio in the offspring) of infected females to increase the proportion of (congenitally infected) male offspring, which are the more migratory sex in most rodent species. Here we studied the sex ratio of experimentally infected laboratory mice, expressed here as the proportion of males in the litter. In accordance with our hypothesis and results of previous retrospective cohort studies on human subjects, mice with toxoplasmosis produced a higher sex ratio than controls, in the early phase of latent infection. In the later phase of infection, mice with congenital toxoplasmosis had a lower sex ratio than controls, which is in accord with the Trivers-Willard hypothesis of sex ratio manipulation, suggesting that females in poor physical condition give birth to more female offspring.

Radix spp.: Identification of trematode intermediate hosts in the Czech Republic

Lymnaeid snails of the genus Radix serve as intermediate hosts of some schistosomes and fasciolids. In Europe, delineation of species within the genus Radix is unresolved and, therefore, spectrum of snail hosts susceptible to trematode infections is under discussion. We used and compared three criteria for species delineation using snails collected at 43 localities. (a) Sequence analysis of ITS-2 rDNA disclosed that the collected snails belong to four species — R. auricularia (Linnaeus, 1758), R. peregra (Müller, 1774), R. lagotis (Schrank, 1803) and R. labiata (Rossmaessler, 1835) (criteria and names are based on the work of Bargues et al. 2001). Occurrence of R. peregra in the Czech Republic was confirmed by molecular data for the first time. (b) Characterization of reproductive system disclosed differences in location, size and shape of bursa copulatrix and its ductus. Unfortunately, some R. labiata specimens shared morphological features of reproductive organs with R. lagotis. (c) Statistical analysis of shell morphology proved that significant differences exist among particular species. One prediction model showed that correct classification of species may be achieved in 82-84% of cases. However, identification of individual snails in the field (without knowledge of respective snail population and use of statistical tools) still remains a complicated issue due to overlaps of shell characteristics. Concerning the role in trematode transmission, R. lagotis, R. labiata and R. peregra are susceptible to Trichobilharzia regenti. Also, successful experimental infections of R. lagotis and R. labiata by Fascioloides magna were accomplished.

Lower Retinol Levels as an Independent Predictor of Mortality in Long-term Hemodialysis Patients: A Prospective Observational Cohort Study

BACKGROUND Malnutrition, inflammation, and oxidative stress are inter-related mechanisms linked to the progression of cardiovascular disease and prognosis of long-term hemodialysis (HD) patients. In this study, we focus on antioxidant vitamins and trace elements and the relationship of their serum levels to the prognosis of long-term HD patients. STUDY DESIGN Prospective observational cohort study. SETTING & PARTICIPANTS 261 long-term HD patients prospectively followed up for 5 years (2003-2008). The control group consisted of 66 healthy participants. PREDICTORS Retinol, alpha-tocopherol, retinol-binding protein 4 (RBP-4), and the trace elements zinc and selenium. OUTCOMES Mortality and cardiovascular mortality. During follow-up, 146 patients (56%) died, and for 71 of these, death was due to cardiovascular causes. MEASUREMENTS Retinol, alpha-tocopherol, RBP-4, zinc, selenium, and basic nutritional and inflammatory parameters measured at the beginning of the study. RESULTS Retinol and RBP-4 levels were significantly increased, whereas retinol:RBP-4 ratio and alpha-tocopherol, selenium, and zinc levels were decreased in HD patients compared with controls (retinol, 168.1 +/ 64.4 microg/dL in HD patients vs 99.1 +/-23.3 [corrected] microg/dL in controls; P<0.001). Lower retinol level was found to be a significant independent predictor of overall and cardiovascular mortality in multivariate Cox analysis (HR, 0.733 [95% CI, 0.599-0.896], P=0.002, and 0.694 [95% CI, 0.511-0.942], P=0.02, per 1 SD, respectively). The worst prognoses for patients with lower retinol levels were observed when these were combined with low albumin levels. LIMITATIONS Sample size, investigation of prevalent, not incident, dialysis patients. CONCLUSIONS This is the first study showing a lower retinol level as an independent predictor of overall and cardiovascular mortality in HD patients. It has to be elucidated whether the beneficial effects of higher serum retinol levels should be attributed to only better nutritional support or also to retinols role in immune response and differentiation.

Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life

Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p=0.039), to roll from supine to prone position (p=0.022) and were slightly later to begin crawling (p=0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed.

Digit ratio (2D:4D) and Cattell's personality traits

The ratio between second and fourth finger (2D:4D) is sexually dimorphic; it is lower in men than in women. Studies using broad personality domains yielded correlations of 2D:4D with neuroticism, extraversion or agreeableness, but the obtained results have been inconsistent. We correlated 2D:4D of 184 women and 101 men with their scores in Cattells 16 Personality Factor (16PF) Questionnaire. We found women with a higher (more ‘feminine’) right hand 2D:4D to score lower in emotional stability and social boldness and higher in privateness. Mediator analysis showed emotional stability to be probably primarily correlated with 2D:4D and to act as a mediator between 2D:4D and social boldness. Privateness appears to be mediated by an even more complex path. We discuss the usefulness of primary‐level personality questionnaires and mediator analyses in the investigation of psycho‐morphological associations. Copyright

On intersection representations of co-planar graphs

Abstract We show that complements of planar graphs have intersection representations by convex sets in the plane, i.e., for every planar graph, one can assign convex sets in the plane to its vertices in such a way that two of the sets are disjoint if and only if the correspondning vertices are adjacent. This fact has a complexity consequence — it follows that the problem of determining the clique number of an intersection graph of convex sets in the plane is NP-hard. We note that the complexity of this problem for intersection graphs of straight line segments in the plane is unknown.

Pregnancy-Associated Plasma Protein A as an Independent Mortality Predictor in Long-Term Hemodialysis Patients

Background/Aims: Pregnancy-associated plasma protein A (PAPP-A) is a biomarker related to vascular damage. The aim of the study was to focus on PAPP-A and related parameters and their relationship to the prognosis of long-term hemodialysis (HD) patients. Methods: This is a prospective observational cohort study which included 261 long-term HD patients followed up for 5 years and 66 healthy subjects. PAPP-A, placental growth factor (PlGF), matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-4 (IGFBP-4), and cardiac, nutritional and inflammatory parameters were measured at the beginning of the study and tested as predictors of mortality. Results: PAPP-A, PlGF, IGF-1, IGFBP-4 and MMP-2 were significantly increased in HD patients compared to controls (PAPP-A 27.6 ± 15.5 mIU/l in HD vs. 9.4 ± 2.5 mIU/l in controls, p < 0.001). Increased PAPP-A was a significant independent predictor of overall mortality and mortality due to infection in the multivariate Cox analysis [HR (95% CI): 1.237 (1.060–1.444), p = 0.007, and 1.416 (1.115–1.798), p = 0.004, per standard deviation, respectively]. PAPP-A was not related to cardiovascular mortality. Conclusion: Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study.

Genetic predisposition to advanced glycation end products toxicity is related to prognosis of chronic hemodialysis patients.

Background: Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states. Aim: To study the relationship of A419C GLO I and four RAGE polymorphisms (–429T/C, –374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. Methods: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. Results: The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE –429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE –429CC 2.28 (95% CI 1.04–4.99), RAGE 2184GG 3.16 (95% CI 1.44–6.93), and GLO I 419CC 1.75 (95% CI 1.08–2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE –429CC 3.54 (95% CI 1.37–9.14) and RAGE 2184GG 5.04 (95% CI 1.93–13.11). Conclusion: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.