The cardiovascular phenotype of adult patients with phenylketonuria

BACKGROUND: Patients with Phenylketonuria (PKU) are exposed to multiple cardiovascular risk factors, but the clinical significance of these abnormalities is yet unknown. The purpose of this study was to characterize the cardiovascular phenotype in adult patients with PKU by clinical and dietary data, measurements of biochemical markers, and non-invasive examination of vascular functions. RESULTS: Twenty-three adult patients with PKU (age: 18-47 y; 30.8 ± 8.4 y) and 28 healthy controls (age: 18-47 y; 30.1 ± 9.1 y) were included in this study. PKU patients had significantly higher systolic and diastolic blood pressure, increased resting heart rate and a higher body mass index. Total cholesterol and non-HDL cholesterol levels were significantly increased in PKU patients, whereas plasma levels of HDL cholesterol and its subfraction HDL2 (but not HDL3) were significantly decreased. The inflammatory markers C-reactive protein and serum amyloid A protein and the serum oxidative stress marker malondialdehyde were significantly higher in patients with PKU. Venous occlusion plethysmography showed marked reduction in post-ischemic blood flow and the carotid to femoral pulse wave velocity was significantly increased demonstrating endothelial dysfunction and increased vascular stiffness. CONCLUSIONS: This study shows that the cardiovascular phenotype of adult PKU patients is characterized by an accumulation of traditional cardiovascular risk factors, high levels of inflammatory and oxidative stress markers, endothelial dysfunction and vascular stiffness. These data indicate the need for early cardiovascular risk reduction in patients with PKU

Influence of spatial interpolation methods for climate variables on the simulation of discharge and nitrate fate with SWAT

For ecohydrological modeling climate variables are needed on subbasin basis. Since they usually originate from point measurements spatial interpolation is required during preprocessing. Different interpolation methods yield data of varying quality, which can strongly influence modeling results. Four interpolation methods to be compared were selected: nearest neighbour, inverse distance, ordinary kriging, and kriging with external drift (Goovaerts, 1997). This study presents three strategies to evaluate the influence of the interpolation method on the modeling results of discharge and nitrate load in the river in a mesoscale river catchment (∼1000 km2) using the Soil and Water Assessment Tool (SWAT, Neitsch et al., 2005) model: I. Automated calibration of the model with a mixed climate data set and consecutive application of the four interpolated data sets. II. Consecutive automated calibration of the model with each of the four climate data sets. III. Random generation of 1000 model parameter sets and consecutive application of the four interpolated climate data sets on each of the 1000 realisations, evaluating the number of realisations above a certain quality criterion threshold. Results show that strategies I and II are not suitable for evaluation of the quality of the interpolated data. Strategy III however proves a significant influence of the interpolation method on nitrate modeling. A rank order from the simplest to the most sophisticated method is visible, with kriging with external drift (KED) outperforming all others. Responsible for this behaviour is the variable temperature, which benefits most from more sophisticated methods and at the same time is the main driving force for the nitrate cycle. The missing influence of the interpolation methods on discharge modeling is explained by a much higher measuring network density for precipitation than for all other climate variables

Comment of the use of dichloromethyl methyl ether as formylating agent

In contrast to normal alkenes, dialkylacetylenes can be formylated with dichloromethyl methyl ether (1) in the presence of 1.2 equivalents of boron trichloride. A rationalisation for the different behaviour of alkenes and alkynes arises from the NMR specktroscopic investigation of the reaction intermediates

Taylor-Couette turbulence at radius ratio η=0.5\eta=0.5: scaling, flow structures and plumes

Using high-resolution particle image velocimetry we measure velocity profiles, the wind Reynolds number and characteristics of turbulent plumes in Taylor-Couette flow for a radius ratio of 0.5 and Taylor number of up to $6.2\cdot10^9$. The extracted angular velocity profiles follow a log-law more closely than the azimuthal velocity profiles due to the strong curvature of this $\eta=0.5$ setup. The scaling of the wind Reynolds number with the Taylor number agrees with the theoretically predicted 3/7-scaling for the classical turbulent regime, which is much more pronounced than for the well-explored $\eta=0.71$ case, for which the ultimate regime sets in at much lower Ta. By measuring at varying axial positions, roll structures are found for counter-rotation while no clear coherent structures are seen for pure inner cylinder rotation. In addition, turbulent plumes coming from the inner and outer cylinder are investigated. For pure inner cylinder rotation, the plumes in the radial velocity move away from the inner cylinder, while the plumes in the azimuthal velocity mainly move away from the outer cylinder. For counter-rotation, the mean radial flow in the roll structures strongly affects the direction and intensity of the turbulent plumes. Furthermore, it is experimentally confirmed that in regions where plumes are emitted, boundary layer profiles with a logarithmic signature are created

Combined expectancies: electrophysiological evidence for the adjustment of expectancy effects

BACKGROUND: When subjects use cues to prepare for a likely stimulus or a likely response, reaction times are facilitated by valid cues but prolonged by invalid cues. In studies on combined expectancy effects, two cues can independently give information regarding two dimensions of the forthcoming task. In certain situations, cueing effects on one dimension are reduced when the cue on the other dimension is invalid. According to the Adjusted Expectancy Model, cues affect different processing levels and a mechanism is presumed which is sensitive to the validity of early level cues and leads to online adjustment of expectancy effects at later levels. To examine the predictions of this model cueing of stimulus modality was combined with response cueing. RESULTS: Behavioral measures showed the interaction of cueing effects. Electrophysiological measures of the lateralized readiness potential (LRP) and the N200 amplitude confirmed the predictions of the model. The LRP showed larger effects of response cues on response activation when modality cues were valid rather than invalid. N200 amplitude was largest with valid modality cues and invalid response cues, medium with invalid modality cues, and smallest with two valid cues. CONCLUSION: Findings support the view that the validity of early level expectancies modulates the effects of late level expectancies, which included response activation and response conflict in the present study

Dynamical Disease: Identification, Temporal Aspects and Treatment Strategies for Human Illness

Dynamical diseases are characterized by sudden changes in the qualitative dynamics of physiological processes, leading to abnormal dynamics and disease. Thus, there is a natural matching between the mathematical field of nonlinear dynamics and medicine. This paper summarizes advances in the study of dynamical disease with emphasis on a NATO Advanced Research Workshop held in Mont Tremblant, Quebec, Canada in February 1994. We describe the international effort currently underway to identify dynamical diseases and to study these diseases from a perspective of nonlinear dynamics. Linear and nonlinear time series analysis combined with analysis of bifurcations in dynamics are being used to help understand mechanisms of pathological rhythms and offer the promise for better diagnostic and therapeutic techniques

Developmental Expression of the 84-kDa ODF Sperm Protein: Localization to both the Cortex and Medulla of Outer Dense Fibers and to the Connecting Piece

AbstractOuter dense fibers (ODF) are specialized cytoskeletal elements of the mammalian sperm tail which are composed of several prominent proteins. We previously reported the isolation of a cDNA (111-450) encoding a putative 84-kDa ODF protein. Here we demonstrate by independent cDNA isolations and by translational/immunoprecipitation of testicular mRNAs using anti-ODF 84 antibodies that 111-450 cDNA encodes the 84-kDa protein. We then analyzed the testicular expression of the ODF 84 mRNA and protein. Riboprobes generated from the clones recognized four testicular-specific transcripts of 1.6, 2.2, 2.4, and 2.8 kb in both rat and bull of which the immunoprecipitable product of the 2.4-kb mRNA comigrates with ODF 84 protein. Developmental Northerns indicated that the 2.2- and 2.4-kb mRNAs are first transcribed during meiotic prophase while the other two species are first expressed in round spermatids. The levels of all the transcripts steadily increased up to elongated spermatids. Immunocytochemistry revealed that the anti-84 reactive ODF proteins were synthesized and assembled in the cytoplasm of elongated spermatids (steps 9–18) with peak activity occurring in step 16 of spermiogenesis. Immunogold labeling was selective to the assembling ODF and connecting piece of the tail and to granulated bodies of the cytoplasmic lobe. Both the striated collar and capitulum of the connecting piece were immunolabeled as well as the basal plate of the implantation fossa. A combination of pre- and postembedding immunogold labeling provided evidence that the 84-kDa ODF protein is localized to both the cortex and medulla of the ODF in contrast to the sole medullary localization of the major 27-kDa ODF protein. Thus the 84-kDa ODF protein, encoded by the 2.4 transcript, is translationally regulated, packaged after synthesis into granulated bodies, assembled in a proximal to distal direction along the axoneme and may interact by means of leucine zippers specifically with the 27-kDa ODF protein during assembly. Its localization to both the cortex and medulla of the ODF, as opposed to exclusive medullary localization of the 27-kDa ODF protein, and the presence of two leucine zippers, only one of which interacts with the 27-kDa ODF, suggests that it could act as a link between proteins of the two regions of the ODF