Association between patent ductus arteriosus flow and home oxygen therapy in extremely preterm infants.

BACKGROUND: Central blood flow measurements include the estimation of right and left ventricular output (RVO, LVO), superior vena cava (SVC) flow, and calculated patent ductus arteriosus (PDA) flow. We aimed to provide an overview of the maturation patterns of these values and the relationship between PDA flow and the need for home oxygen therapy. METHODS: This prospective single-center study was conducted in infants born at <26 weeks of gestation. We performed echocardiographic measurements five times during their life (from the 4th post-natal day to the 36th postmenstrual week). RESULTS: Sixty patients with a mean birth weight of 680 (590, 760) g were included. Postnatal development of LVO and PDA flow peaked at the end of the second postnatal week (427 and 66 mL/kg/min, respectively). The RVO increased between days 4 and 7-8. The SVCF was most stable. The development curves of PDA flow differed between the groups with (n = 28; 47%) and without home oxygen therapy. CONCLUSION: We present the central blood flow values and their postnatal development in infants <26 weeks of gestation. This study demonstrates the association between PDA flow and the future need for home oxygen therapy. IMPACT: This study enriches our knowledge of the long-term development of central blood flow parameters and derived patent ductus arteriosus (PDA) flow in extremely preterm infants (<26 weeks). While pulmonary resistance decreased, PDA flow continued to increase from day 4 to the end of the second week of life. Similarly, left ventricular output increased as a marker of preload. The superior vena cava flow remained stable. The observed association between PDA flow and an unfavorable respiratory outcome is important for future studies focusing on the prevention of chronic lung disease.

Retinoic acid associates with mortality of patients on long-term hemodialysis.

BACKGROUND: Retinol concentrations in serum are significantly higher in patients on hemodialysis (HD) compared to healthy controls. Its lower concentrations have been reported to be an independent predictor of mortality. ATRA - all-trans retinoic acid - is an important compound related to retinol. The objective was to determine ATRA concentrations in serum and to find their association with the prognosis of patients on long-term HD. METHODS: ATRA was determined by high-performance liquid chromatography in a group of 247 HD patients (follow-up five years) and 54 healthy controls. RESULTS: Although serum retinol concentrations were higher in the studied cohort of HD patients, ATRA was lower - median 1.13 (interquartile range 0.90-1.60) ng/mL in HD patients versus 1.42 (1.08-1.63) ng/mL in healthy controls, p = 0.02. Lower ATRA was significantly related to overall mortality of HD patients (HR (95%CI) 0.63 (0.47-0.85) per interquartile range, p = 0.003). The best prognosis was observed in patients with concentrations of both ATRA and retinol above the median (p = 0.003). CONCLUSIONS: We detected decreased retinoic acid levels in HD patients compared to healthy controls. Lower concentrations of ATRA represent a significant predictor of mortality and provide additional information to retinol.

Are haplotypes in a single methotrexate pathway more predictive for response in rheumatoid arthritis than in different pathways?

Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).

Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis.

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. METHODS: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. RESULTS: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6-10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients when tested alone. There was a significant interaction between PAPP-A and PAPP-A2 on the mortality due to infection of HD patients (p=0.008). If PAPP-A was below median, mortality due to infection was significantly higher for patients with PAPP-A2 values above median than for patients with low PAPP-A2 levels (p=0.011). CONCLUSION: PAPP-A2 is increased in HD patients and interacts with PAPP-A on patients´ prognosis.

Polymorphisms of the receptor for advanced glycation end products and glyoxalase I and long-term outcome in patients with breast cancer.

Receptor for advanced glycation end products and glyoxalase I metabolizing advanced glycation end product precursors may play important role in the pathogenesis and progression of cancer. Potential relation between soluble forms of receptor for advanced glycation end products (sRAGE), receptor for advanced glycation end products, glyoxalase I polymorphisms, and long-term outcome (median follow-up of 10.3 years) was studied in 116 patients with breast cancer. Gly82Ser and 2184 A/G RAGE polymorphisms were related to the mortality due to the breast cancer and -419 A/C glyoxalase I polymorphism was related to the overall mortality of the patients suggesting their role not only in the risk of breast cancer but also in the outcome of patients with breast cancer.

Comparison of DNA isolation using salting-out procedure and automated isolation (MagNA system).

Isolation of genomic DNA is a key step in genetic analysis. The aim of the study was to evaluate the suitability of isolation of DNA from peripheral blood with manual salting-out procedure and automated MagNA system under specific conditions. The impact of storage conditions, type of material (whole blood or blood cells), and method used for DNA extraction were evaluated in terms of DNA yield, its purity, and integrity. Fresh material, and material stored at 2-8°C for 1-4 weeks and frozen at -80°C were tested. For fresh samples, salting-out method gives higher yield than MagNA, irrespectively, on material used. Neither the yield of salting-out method nor its purity decreases during the storage of the samples in the fridge (2-8°C) during 4 weeks. Concerning MagNA, storage of blood cells in the fridge decreases the yield of DNA as well as its purity. For frozen samples, for whole blood, MagNA gives better results while for blood cells, salting-out method seems to be better. For fresh samples, salting-out method is the preferred one, and both whole blood and blood cells can be used. For frozen samples, the preferred method depends on the material.

Free Associations Mirroring Self- and World-Related Concepts: Implications for Personal Construct Theory, Psycholinguistics and Philosophical Psychology.

People construe reality by using words as basic units of meaningful categorization. The present theory-driven study applied the method of a free association task to explore how people express the concepts of the world and the self in words. The respondents were asked to recall any five words relating with the word world. Afterward they were asked to recall any five words relating with the word self. The method of free association provided the respondents with absolute freedom to choose any words they wanted. Such free recall task is suggested as being a relatively direct approach to the respondents' self- and world-related conceptual categories, without enormous rational processing. The results provide us, first, with associative ranges for constructs of the world and the self, where some associative dimensions are defined by semantic polarities in the meanings of peripheral categories (e.g., Nature vs. Culture). Second, our analysis showed that some groups of verbal categories that were associated with the words world and self are central, while others are peripheral with respect to the central position. Third, the analysis of category networks revealed that some categories play the role of a transmitter, mediating the pathway between other categories in the network.

Cys327Cys polymorphism of the PAPP-A gene (pregnancy associated plasma protein A) is related to mortality of long term hemodialysis patients.

OBJECTIVES: PAPP-A is an independent mortality predictor of long term hemodialysis patients and a prognostic marker of acute coronary syndrome in general population. Cys327Cys PAPP-A polymorphism (SNP) (rs12375498) was found to be of significance in preeclampsia and the C allele of the PAPP-A C/G SNP (rs13290387) was defined as an independent risk factor for acute myocardial infarction. The aim of the study was to test the role of these PAPP-A SNPs in long term hemodialysis patients. DESIGN AND METHODS: The studied group consisted of 464 subjects - 319 long term hemodialysis patients (183 men, 136 women, 62±14years) and 145 controls (65 men, 80 women, 49±14years). A subgroup of 211 hemodialysis patients (118 men, 93 women, 63±13years) was prospectively followed up for 4.5years. During the follow up, 111 patients died, 51 of them due to cardiovascular events. PAPP-A SNPs were analyzed by DNA sequencing and serum PAPP-A was measured by TRACE. RESULTS: Both SNPs were in Hardy-Weinberg equilibrium. Allelic and genotype frequencies did not differ between patients and controls and were not related to serum PAPP-A concentrations. Cys327Cys SNP was significant for patients' survival (HR (95% CI): 1.616 (1.110-2.353), nominal p=0.012, corrected p=0.036) while C/G SNP was not. CONCLUSIONS: Our study shows for the first time the significance of Cys327Cys PAPP-A SNP (rs12375498) for overall mortality of long term hemodialysis patients. Although it does not influence the concentration of PAPP-A it still could affect the correct function of this enzyme which has to be clarified in further studies.

The fate of atmospherically derived Pb in Central European catchments: insights from spatial and temporal pollution gradients and Pb isotope ratios.

Soils in polluted regions are generally regarded as a delayed, long-lasting source for Pb contamination of aquatic systems. Lead deposited on topsoil is slowly transported downward with particulate and colloidal organic matter, driven by infiltrating precipitation. Then, Pb is tightly retained in mineral soil. Lead export from catchments is extremely low and decoupled from the atmospheric input. We tested this hypothesis in 11 small catchments, differing in pollution levels. Input/ouput Pb fluxes were monitored for 14-15 years in an era of decreasing industrial Pb emission rates. Between 1996/1997 and 2010, Pb deposition fluxes decreased significantly, on average by 80%. At the beginning of the monitoring, Pb export constituted 2 to 58% of Pb input. At the end of the monitoring, Pb export constituted 2 to 95% of Pb input. Highly polluted sites in the northeast exported significantly more Pb than less polluted sites further south. The (206)Pb/(207)Pb isotope ratios of runoff (1.16) were identical to those of topsoil and present-day deposition, and different from mineral soil and bedrock. Lead isotope systematics and between-site flux comparisons indicated that a portion of the incoming Pb had a relatively short residence time in the catchments, on the order of decades.

Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study.

Prognosis of patients with pancreas cancer is very poor. The aim of the study was to test the significance of laboratory parameters in the prognosis of patients with pancreas cancer. The studied group included 57 patients (31 men, 26 women, mean age 65 ± 9 years). Blood was collected at the time of diagnosis of pancreas cancer and basic laboratory parameters, including nutritional and inflammatory markers and tumour markers were measured. Patients were followed up until death (median survival 147 days). Ferritin, iron, albumin, prealbumin, cholinesterase, haemoglobin, C-reactive protein, alkaline phosphatase and carcinoembryonic antigen were significant for patients' prognosis in univariate analysis while CA 19-9, bilirubin, liver, pancreas and kidney tests and lipids were not. Multivariate Cox regression demonstrated ferritin, iron and albumin as independent mortality predictors (RR (95%CI), per standard deviation: ferritin 1.497(1.215-2.241), p = 0.002; albumin, 0.716(0.521-0.977), p = 0.035; iron, 0.678(0.504-0.915), p = 0.010). Iron correlated significantly with albumin (r = 0.397, p = 0.002) but neither iron nor albumin correlated with ferritin. Patients who survived 100 days had significantly lower ferritin (median 239 µg/l vs. non-survivors 435 µg/l, p = 0.014), significantly higher albumin but the difference in serum iron was not quite significant. ROC analysis for ferritin revealed AUC for 100 days survival of 0.710, p = 0.007 (and 0.725, p = 0.004 for 200 days survival). AUC for albumin for 100 days survival was not significant (p = 0.073). This study points out ferritin as an independent mortality predictor in patients with pancreas cancer. High serum levels of ferritin at the time of diagnosis of pancreas cancer indicate bad prognosis of the patient.

EN-RAGE (extracellular newly identified receptor for advanced glycation end-products binding protein) and mortality of long-term hemodialysis patients: A prospective observational cohort study.

OBJECTIVES: EN-RAGE is extracellular newly identified receptor for advanced glycation end-products binding protein playing a role in inflammation. The aim was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis patients (HD). DESIGN AND METHODS: This is a prospective observational cohort study in 261 HD patients followed up for five years. Laboratory parameters were measured at the beginning of the study. RESULTS: EN-RAGE was slightly but unsignificantly increased in HD patients compared with healthy controls and correlated significantly with inflammatory markers. Univariate Cox analysis demonstrated EN-RAGE as a significant predictor for mortality due to infection (HR (95%CI): 1.305 (1.063-1.602), per standard deviation, p=0.01), but this significance disappeared in multivariate Cox analysis when CRP was included into the model. CONCLUSIONS: Our study demonstrates EN-RAGE as an inflammatory biomarker. It is related to mortality of HD patients due to infection, but in our study, it did not provide additional information to CRP.

Olfactory perception is positively linked to anxiety in young adults.

Olfactory abilities show a high degree of inter-individual variability and this could be partly related to personality differences. Here, in two studies, we tested a potential link between personality dimensions and olfactory perception. Sixty-eight (study 1) and a hundred and fifty-six (study 2) young adults completed the Big Five questionnaire and performed the Sniffin' Sticks test for assessing odour threshold, identification, and (in study 2) discrimination. In neither study did we find a significant link between personality dimensions and olfactory identification scores. However, in study 1, we found a significant positive correlation between the neuroticism dimension and olfactory sensitivity. This was mainly due to the anxiety and self-consciousness subscales, which load onto the neuroticism dimension. In a follow-up study, we again found a significant association between anxiety and odour perception, specifically in odour discrimination. Our results indicate that variability in anxiety could partly explain the high inter-individual variation in olfactory perception.

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.

The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis.

BACKGROUND: We hypothesized that with the administration of teriparatide (TPTD) treatment at different times, we would be able to modify the physiological circadian rhythm of bone turnover. METHODS: The concentration of serum C-terminal telopeptide of collagen type I (ßCTX), serum N-terminal propeptide of procollagen type I (P1NP), serum ionized calcium (iCa), and plasma PTH were measured every 3 h over a 24 h period in 14 postmenopausal osteoporotic women (aged 72.4±9.3 years) treated with 20 µg TPTD for long term, given at different times of the day. General linear model-repeated measurements (GLM RM) were performed to analyze the circadian rhythms as well as intergroup comparisons. RESULTS: GLM-RM for both related groups showed a significant influence of time of day on all measured variables except P1NP. The analysis for each group separately provided a powerful model for ßCTX (P<0.001, η(2)=0.496), serum iCa (P<0.001, η(2)=0.423), plasma PTH (P<0.001, η(2)=0.283), and serum PINP (P<0.001, η(2)=0.248). While the evening TPTD treatment showed a marked circadian rhythm for serum ßCTX, the morning TPTD treatment rather suggested circasemidian rhythm. The P1NP rhythm followed a much smaller amplitude of the rhythm than ßCTX. Changes in serum iCa were positively related to changes in serum ßCTX (P<0.001) and negatively related to changes in PTH (P<0.001). CONCLUSION: Timing of TPTD administration may significantly change the 24 h variation in bone turnover markers as well as calcium-parathyroid axis in postmenopausal osteoporotic women.

Pattern of money allocation in experimental games supports the stress hypothesis of gender differences in Toxoplasma gondii-induced behavioural changes.

Latent toxoplasmosis has been previously found to cause behavioural and personality changes in humans, which are specific for each gender. Here we tested the stress hypothesis of these gender differences based on the assumption that latent toxoplasmosis causes long-term subliminal stress. In line with this hypothesis, the gender difference will appear specifically in situations with interpersonal context because in contrast to the typical individualistic coping style of men, women have a tendency to express elevated prosocial behaviour under stress. Altogether 295 biology students (29/191 females and 27/104 males infected by T. gondii) played a modified version of the Dictator Game and the Trust Game. As predicted, a gender difference in the effect of latent toxoplasmosis was found for the measure of reciprocal altruism in the Trust Game (p = 0.016), but both genders appeared less generous when infected in the Dictator Game modified to minimize social connotation (p = 0.048).

Osteoporosis risk assessment and management in primary care: focus on quantity and quality.

INTRODUCTION AND HYPOTHESIS: Early identification of high-risk patients by general practitioners (GPs) plays the key role in the management of osteoporosis (OP). METHODS: We conducted a postal questionnaire survey among 1500 Czech GPs to examine their behaviour related to OP. RESULTS: The overall questionnaire return rate was 38%. The respondents (mean age 52 years; 61.5% women) did not differ from non-respondents. OP knowledge correlated negatively with age (P<0.001). The most common reason for both suspicion of OP and referral for suspected OP is the patient's complaints. When the initial skeletal examination for suspected OP is conducted on the GP's initiative, it is most often X-ray (76%) followed by osteodensitometry (61%). The respondents address five patients (median) per month about this issue. The number of referrals to a specialist for suspected OP during the last quarter was 5 (median). The most commonly reported barriers to OP management were financial limits set by the health insurance agency (71%) and lack of authorization to prescribe selected drugs (71%). CONCLUSIONS: The GPs should pay greater attention to risk factors and be more active in the detection of at-risk patients. It is necessary to motivate the GPs and to overcome the barriers to effective clinical practice.

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 retinol's role in immune response and differentiation.

Specialized use of two fingers in free-ranging aye-ayes (Daubentonia madagascariensis).

The aye-aye (Daubentonia madagascariensis) possesses a highly specialized hand with two fingers, the third and the fourth, being used in a way unparalleled by any other primate. We observed the use of the third and the fourth fingers in various activities in four free-ranging aye-ayes. We found that the thin third finger was used exclusively or preferably for tapping, inserting into the mouth (probably for cleaning the teeth) and probing for nectar, kernels and insects in bamboo, twigs and live wood. In contrast, the robust fourth finger was used preferably when eating jackfruit (Artocarpus heterophyllus). When probing for invertebrates in soft plant tissues and in dead wood, both fingers were used in high proportions. To extract the contents from coconuts, the two fingers were apparently used for different tasks. From this small (686 observations), but unique, study of free-ranging aye-ayes, we conclude that the third finger appears to be specialized for use in tasks requiring high mobility, sensitivity and precision, whereas the fourth finger appears to be specialized for tasks requiring strength, scooping action and deep access.