Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease.

BACKGROUND: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. AIMS: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. METHODS: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima­media thickness and atherosclerotic plaques were assessed by ultrasonography. RESULTS: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima­media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C­reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). CONCLUSIONS: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.

Cardiovascular risk in chronic kidney disease patients: intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries.

BACKGROUND: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD). METHODS: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red. RESULTS: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]. CONCLUSIONS: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

[Patient receiving peritoneal dialysis after treatment of ovarian cancer]. / Pacjentka dializowana otrzewnowo, po leczeniu nowotworu zlosliwego jajnika.

Peritoneal dialysis is one of the three available options for renal replacement therapy. This method of treatment of end-stage renal disease gives patients relatively high sense of independence and control over their disease, especially in comparison with hemodialysis, and therefore is often preferable method for young individuals wishing to lead an active lifestyle. We present a case of 22 year old female patient with stage 5 of chronic kidney disease, which is a consequence of multi-agent chemotherapy for endo-dermal sinus tumor of the right ovary (diagnosed at the age of 13). Particularly important in the context of treating our patient with peritoneal dialysis is the fact of confirmed metastases into the peritoneum, which was the reason for the use of chemotherapy reserved for high-risk patients (ifosfamide + etoposide + cisplatin). The selected program of chemotherapy provided effective eradication of cancer, but a side effect of treatment was renal tubular damage. In the period from 03.2006 to 05.2007 our patient required hemodialysis (with gradually reduce dose of dialysis), at a later time to 12.2011 patient did not require renal replacement therapy (stable renal function were observed at the stage 4 of chronic kidney disease), but in 12.2011 resumption of dialysis was necessary and the patient, in accordance with her selection, is receiving peritoneal dialysis. Qualification of our patient for treatment with peritoneal dialysis was associated with reasonable concern about the ability to provide acceptable adequacy of dialysis. Apprehensions proved to be unfounded, the clinical observation of the patient presents proper ratios of dialysis adequacy. Our patient was also qualified for renal transplantation.

Insula and inferior frontal triangularis activations distinguish between conditioned brain responses using emotional sounds for basic BCI communication.

In order to enable communication through a brain-computer interface (BCI), it is necessary to discriminate between distinct brain responses. As a first step, we probed the possibility to discriminate between affirmative ("yes") and negative ("no") responses using a semantic classical conditioning paradigm, within an fMRI setting. Subjects were presented with congruent and incongruent word-pairs as conditioned stimuli (CS), respectively eliciting affirmative and negative responses. Incongruent word-pairs were associated to an unpleasant unconditioned stimulus (scream, US1) and congruent word-pairs were associated to a pleasant unconditioned stimulus (baby-laughter, US2), in order to elicit emotional conditioned responses (CR). The aim was to discriminate between affirmative and negative responses, enabled by their association with the positive and negative affective stimuli. In the late acquisition phase, when the US were not present anymore, there was a strong significant differential activation for incongruent and congruent word-pairs in a cluster comprising the left insula and the inferior frontal triangularis. This association was not found in the habituation phase. These results suggest that the difference in affirmative and negative brain responses was established as an effect of conditioning, allowing to further investigate the possibility of using this paradigm for a binary choice BCI.

Impaired fasting glucose and diabetes as predictors for radial artery calcification in end stage renal disease patients.

Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20-24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death.

Redundant sensory information does not enhance sequence learning in the serial reaction time task.

In daily life we encounter multiple sources of sensory information at any given moment. Unknown is whether such sensory redundancy in some way affects implicit learning of a sequence of events. In the current paper we explored this issue in a serial reaction time task. Our results indicate that redundant sensory information does not enhance sequence learning when all sensory information is presented at the same location (responding to the position and/or color of the stimuli; Experiment 1), even when the distinct sensory sources provide more or less similar baseline response latencies (responding to the shape and/or color of the stimuli; Experiment 2). These findings support the claim that sequence learning does not (necessarily) benefit from sensory redundancy. Moreover, transfer was observed between various sets of stimuli, indicating that learning was predominantly response-based.

Hemispheric asymmetry in the efficiency of attentional networks.

Despite the fact that hemispheric asymmetry of attention has been widely studied, a clear picture of this complex phenomenon is still lacking. The aim of the present study was to provide an efficient and reliable measurement of potential hemispheric asymmetries of three attentional networks, i.e. alerting, orienting and executive attention. Participants (N=125) were tested with the Lateralized Attention Network Test (LANT) that allowed us to investigate the efficiency of the networks in both visual fields (VF). We found a LVF advantage when a target occurred in an unattended location, which seems to reflect right hemisphere superiority in control of the reorienting of attention. Furthermore, a LVF advantage in conflict resolution was observed, which may indicate hemispheric asymmetry of the executive network. No VF effect for alerting was found. The results, consistent with the common notion of general right hemisphere dominance for attention, provide a more detailed account of hemispheric asymmetries of the attentional networks than previous studies using the LANT task.

Time-course of hemispheric preference for processing contralateral relevant shapes: P1pc, N1pc, N2pc, N3pc.

A most sensitive and specific electrophysiological indicator of selective processing of visual stimuli is the N2pc component. N2pc is a negative EEG potential peaking 250 ms after stimulus onset, recorded from posterior sites contralateral to relevant stimuli. Additional deflections preceding or following N2pc have been obtained in previous studies, possibly produced by specific stimulus features or specific prime-target sequences. To clarify the entire time-course of the contralateral- ipsilateral (C-I) difference recorded from the scalp above visual cortex in response to left-right pairs of targets and distracters, C-I differences were here compared between two types of stimuli and between stimuli that were or were not preceded by masked neutral primes. The C-I difference waveform consisted of several peaks, termed here P1pc (60-100 ms after target onset), N1pc (120-160 ms), N2pc (220-280 ms), and N3pc (360-400 ms). Being markedly enhanced when stimuli were preceded by the neutral primes, P1pc may indicate a response to stimulus change. Also, when stimuli were primed, N2pc reached its peak earlier, thereby tending to merge with N1pc. N3pc seemed to increase when target discrimination was difficult. N1pc, N2pc, and N3pc appear as three periods of one process. N3pc probably corresponds to L400 or SPCN as described in other studies. These observations suggest that the neurophysiological basis of stimulus-driven focusing of attention on target stimuli is a process that lasts for hundreds of milliseconds, with the relevant hemisphere being activated in an oscillating manner as long as required by the task.

Are low and high number magnitudes processed differently while resolving the conflict evoked by the SNARC effect?

In the brain, numbers are thought to be represented in a spatially organised fashion on what is known as the Mental Number Line (MNL). The SNARC (Spatial-Numerical Association of Response Codes) effect refers to the faster responses to digits when the reaction side is congruent with the digit position on the MNL (e.g. a left-handed response to a small magnitude) and the slowing down of responses (inhibition) in the case of incongruity. We examined the electrophysiological correlates of conflict, which are linked to that of inhibition, to shed light on the relationship between the SNARC effect and executive attention. Event-related potentials (ERPs) were recorded from twenty-nine participants during a parity-judgment task. The participants responded more quickly on congruent than on incongruent trials. The congruency effect was reflected in early sensory (N1, N2) components above parieto-occipital and frontal regions, as well as in the later P3 component above centro-parietal areas. Moreover, both the N1 amplitude and N2 latency were greater with high than low magnitude digit targets. P3 amplitude modulation implies that the SNARC effect is the result of first evoking the parallel processing of digit magnitude categorisation (in the occipital and central areas) and numeric conflict detection (in the parieto-occipital and frontal areas) and secondly conflict monitoring and resolution localised in the centro-parietal and frontal sites. These results also suggest that the left hemisphere specialises in conflict processing of high magnitude digit targets, while the right hemisphere of low digit magnitudes.

Increasing stimulus intensity does not affect sensorimotor synchronization.

When people synchronize taps with isochronously presented stimuli, taps usually precede the pacing stimuli [negative mean asynchrony (NMA)]. One explanation of NMA [sensory accumulation model (SAM), Aschersleben in Brain Cogn 48:66-79, 2002] is that more time is needed to generate a central code for kinesthetic-tactile information than for auditory or visual stimuli. The SAM predicts that raising the intensity of the pacing stimuli shortens the time for their sensory accumulation, thereby increasing NMA. This prediction was tested by asking participants to synchronize finger force pulses with target isochronous stimuli with various intensities. In addition, participants performed a simple reaction-time task, for comparison. Higher intensity led to shorter reaction times. However, intensity manipulation did not affect NMA in the synchronization task. This finding is not consistent with the predictions based on the SAM. Discrepancies in sensitivity to stimulus intensity between sensorimotor synchronization and reaction-time tasks point to the involvement of different timing mechanisms in these two tasks.

Negative compatibility effect: the object-updating hypothesis revisited.

A prime even if backward masked can affect the reaction to a subsequently presented target. According to the object-updating hypothesis, negative CE (i.e. longer reactions in the compatible than incompatible trials) occurs due to the interaction between prime and a subsequent stimulus (usually a mask or flanker). Its crucial assumption is that only new elements of the mask can affect the response. As the masks are usually composed of figures that call for both possible responses, the masks' new element calls for a response opposite to that initialized by the prime. Here an experiment is described in which the prime and target were two arrowheads pointing to left or right. Two different flankers were composed from the two heads pointing to the opposite directions. In contrast to the OU hypothesis, NCEs were different for the two flankers. This finding contradicts the OU hypothesis.

On why left events are the right ones: neural mechanisms underlying the left-hemifield advantage in rapid serial visual presentation.

When simultaneous series of stimuli are rapidly presented left and right, containing two target stimuli T1 and T2, T2 is much better identified when presented in the left than in the right hemifield. Here, this effect was replicated, even when shifts of gaze were controlled, and was only partially compensated when T1 side provided the cue where to expect T2. Electrophysiological measurement revealed earlier latencies of T1- and T2-evoked N2(pc) peaks at the right than at the left visual cortex, and larger right-hemisphere T2-evoked N2(pc) amplitudes when T2 closely followed T1. These findings suggest that the right hemisphere was better able to single out the targets in time. Further, sustained contralateral slow shifts remained active after T1 for longer time at the right than at the left visual cortex, and developed more consistently at the right visual cortex when expecting T2 on the contralateral side. These findings might reflect better capacity of right-hemisphere visual working memory. These findings about the neurophysiological underpinnings of the large right-hemisphere advantage in this complex visual task might help elucidating the mechanisms responsible for the severe disturbance of hemineglect following damage to the right hemisphere.

Changes in processing of masked stimuli across early- and late-night sleep: a study on behavior and brain potentials.

Sleep has proven to support the memory consolidation in many tasks including learning of perceptual skills. Explicit, conscious types of memory have been demonstrated to benefit particularly from slow-wave sleep (SWS), implicit, non-conscious types particularly from rapid eye movement (REM) sleep. By comparing the effects of early-night sleep, rich in SWS, and late-night sleep, rich in REM sleep, we aimed to separate the contribution of these two sleep stages in a metacontrast masking paradigm in which explicit and implicit aspects in perceptual learning could be assessed separately by stimulus identification and priming, respectively. We assumed that early sleep intervening between two sessions of task performance would specifically support stimulus identification, while late sleep would specifically support priming. Apart from overt behavior, event-related EEG potentials (ERPs) were measured to record the cortical mechanisms associated with behavioral changes across sleep. In contrast to our hypothesis, late-night sleep appeared to be more important for changes of behavior, both for stimulus identification, which tended to improve across late-night sleep, and for priming, with the increase of errors induced by masked stimuli correlating with the duration of REM sleep. ERP components proved sensitive to presence of target shapes in the masked stimuli and to their priming effects. Of these components, the N2 component, indicating processing of conflict, became larger across early-night sleep and was related to the duration of S4 sleep, the deepest substage of SWS containing particularly high portions of EEG slow waves. These findings suggest that sleep promotes perceptual learning primarily by its REM sleep portion, but indirectly also by way of improved action monitoring supported by deep slow-wave sleep.

Facing facts: neuronal mechanisms of face perception.

The face is one of the most important stimuli carrying social meaning. Thanks to the fast analysis of faces, we are able to judge physical attractiveness and features of their owners' personality, intentions, and mood. From one's facial expression we can gain information about danger present in the environment. It is obvious that the ability to process efficiently one's face is crucial for survival. Therefore, it seems natural that in the human brain there exist structures specialized for face processing. In this article, we present recent findings from studies on the neuronal mechanisms of face perception and recognition in the light of current theoretical models. Results from brain imaging (fMRI, PET) and electrophysiology (ERP, MEG) show that in face perception particular regions (i.e. FFA, STS, IOA, AMTG, prefrontal and orbitofrontal cortex) are involved. These results are confirmed by behavioral data and clinical observations as well as by animal studies. The developmental findings reviewed in this article lead us to suppose that the ability to analyze face-like stimuli is hard-wired and improves during development. Still, experience with faces is not sufficient for an individual to become an expert in face perception. This thesis is supported by the investigation of individuals with developmental disabilities, especially with autistic spectrum disorders (ASD).

Selection of features within and without objects: effects of gestalt appearance and object-based instruction on behavior and event-related brain potentials.

We studied how physical and instructed embedding of features in gestalts affects perceptual selection. Four ovals on the horizontal midline were either unconnected or pairwise connected by circles, forming ears of left and right heads (gestalts). Relevant to responding was the position of one colored oval, either within its pair or relative to fixation ("object-based" or "fixation-based" instruction). Responses were faster under fixation- than object-based instruction, less so with gestalts. Previously reported increases of N1 when evoked by features within objects were replicated for fixation-based instruction only. There was no effect of instruction on N2pc. However P1 increased under the adequate instruction, object-based for gestalts, fixation-based for unconnected items, which presumably indicated how foci of attention were set by expecting specific stimuli under instructions that specified how to bind these stimuli to objects.

The negative compatibility effect with nonmasking flankers: a case for mask-triggered inhibition hypothesis.

Visual targets which follow a prime stimulus and a mask can be identified faster when they are incompatible rather than compatible with the prime (negative compatibility effect--NCE). According to the self-inhibition hypothesis, the initial activation of the motor response is elicited by the prime based on its identity. This activation leads to benefits for compatible trials and costs for incompatible trials. This motor activation is followed by an inhibition phase, leading to an NCE if perceptual evidence of the prime is immediately removed by the mask. The object-updating and mask-triggered inhibition hypotheses emphasize the role of the mask content (i.e. whether the mask possesses target-like features). We show that the NCE may appear even if nonmasking neutral flankers are presented instead of a mask. Moreover, although with target-like flankers the NCE is larger, it occurred if flankers and targets are built from dissimilar elements. Therefore, masks/flankers can evoke an inhibition phase independently of whether or not they remove evidence for the prime and whether they are similar to the targets.

What determines the direction of subliminal priming.

Masked stimuli (primes) can affect the preparation of a motor response to subsequently presented target stimuli. Reactions to the target can be facilitated (straight priming) or inhibited (inverse priming) when preceded by a compatible prime (calling for the same response) and also when preceded by an incompatible prime. Several hypotheses are currently under debate. These are the self-inhibition (SI) hypothesis, the object-updating (OU) hypothesis, and mask-triggered inhibition (MTI) hypothesis. All assume that the initial activation of the motor response is elicited by the prime according to its identity. This activation inevitably leads to straight priming in some cases and the mechanisms involved are undisputed. The hypotheses differ, however, as to why inverse priming occurs. The self-inhibition (SI) hypothesis assumes that the motor activation elicited by a prime is automatically followed by an inhibition phase, leading to inverse priming if three conditions are fulfilled: perceptual evidence for the prime has to be sufficiently strong, it has to be immediately removed by the mask, and the delay between the prime and target has to be long enough for inhibition to become effective. The object-updating (OU) hypothesis assumes that inverse priming is triggered by the mask, provided that it contains features calling for the alternative response (i.e. the one contrasting with the response induced by the prime). The MTI hypothesis assumes that the inhibitory phase is triggered by each successive stimulus which does not support the perceptual hypothesis provided by the prime. Based mostly on our own experiments, we argue that (1) attempts to manipulate the three factors required by the SI hypothesis imply changes of other variables and that (2) indeed, other variables seem to affect priming: prime-mask perceptual interaction and temporal position of the mask. These observations are in favor of the MTI hypothesis. A limiting factor for all three hypotheses is that inverse priming is larger for arrows than for other shapes, making it doubtful as to what extent the majority of studies on inverse priming, due to their use of arrows, can be generalized to other stimuli.

Disentangling neural processing of masked and masking stimulus by means of event-related contralateral - ipsilateral differences of EEG potentials.

In spite of the excellent temporal resolution of event-related EEG potentials (ERPs), the overlapping potentials evoked by masked and masking stimuli are hard to disentangle. However, when both masked and masking stimuli consist of pairs of relevant and irrelevant stimuli, one left and one right from fixation, with the side of the relevant element varying between pairs, effects of masked and masking stimuli can be distinguished by means of the contralateral preponderance of the potentials evoked by the relevant elements, because the relevant elements may independently change sides in masked and masking stimuli. Based on a reanalysis of data from which only selected contralateral-ipsilateral effects had been previously published, the present contribution will provide a more complete picture of the ERP effects in a masked-priming task. Indeed, effects evoked by masked primes and masking targets heavily overlapped in conventional ERPs and could be disentangled to a certain degree by contralateral-ipsilateral differences. Their major component, the N2pc, is interpreted as indicating preferential processing of stimuli matching the target template, which process can neither be identified with conscious perception nor with shifts of spatial attention. The measurements showed that the triggering of response preparation by the masked stimuli did not depend on their discriminability, and their priming effects on the processing of the following target stimuli were qualitatively different for stimulus identification and for response preparation. These results provide another piece of evidence for the independence of motor-related and perception-related effects of masked stimuli.

Conscious contributions to subliminal priming.

Choice reaction times to visual stimuli (targets) may be influenced by preceding subliminal stimuli (primes). Some authors reported a straight priming effect i.e., responses were faster when primes and targets called for the same response than when they called for different responses. Others found the reversed pattern of results. Eimer and Schlaghecken [Eimer, M. & Schlaghecken, F. (2002). Links between conscious awareness and response inhibition: evidence from masked priming. Psychonomic Bulletin &Review, 9, 514-520.] showed recently that straight priming occurs whenever a prime is not efficiently masked thereby the information provided by the prime is accessible for consciousness. In the present study, a hypothesis is tested that straight priming is due to mediation of consciousness. To test this hypothesis, prime validity was manipulated. We showed that even when no mask was used so that participants could fully and consciously perceive the prime and participants were informed that primes were mostly invalid, for the short prime-target ISI interval (100 ms) straight priming occurred. The priming was inverse when the ISI was 800 ms. This indicates that participants were able to use the information provided by the prime to prepare the response opposite to that cued by the prime but only if the time between the prime and the target was long enough.

Mask- and distractor-triggered inhibitory processes in the priming of motor responses: an EEG study.

Masked stimuli presented near the threshold of conscious awareness may act as primes, affecting responses to subsequent targets. With arrows as primes and targets, the prime-mask-target sequence has been shown to evoke triphasic lateralized readiness potentials (LRP) with two phases of imbalance between hemispheres preceding the target-related contralateral preponderance of negativity: first a negative, then a positive preponderance contralateral to prime direction. The present article provides evidence that the second wave is related to mask presentation and reflects inhibitory processing independent of reductions in prime visibility, even being evoked by nonmasking distractors that leave the prime fully accessible for consciousness. Of all hypotheses put forward to account for inverse effects in masked priming, this finding is most compatible with the mask-triggered inhibition hypothesis suggested by P. Jaskowski (2007).