Long-range temporal correlations of broadband EEG oscillations for depressed subjects following different hemispheric cerebral infarction

Abnormal long-range temporal correlation (LRTC) in EEG oscillation has been observed in several brain pathologies and mental disorders. This study examined the relationship between the LRTC of broadband EEG oscillation and depression following cerebral infarction with different hemispheric lesions to provide a novel insight into such depressive disorders. Resting EEGs of 16 channels in 18 depressed (9 left and 9 right lesions) and 21 non-depressed (11 left and 10 right lesions) subjects following cerebral infarction and 19 healthy control subjects were analysed by means of detrended fluctuation analysis, a quantitative measurement of LRTC. The difference among groups and the correlation between the severity of depression and LRTC in EEG oscillation were investigated by statistical analysis. The results showed that LRTC of broadband EEG oscillations in depressive subjects was still preserved but attenuated in right hemispheric lesion subjects especially in left pre-frontal and right inferior frontal and posterior temporal regions. Moreover, an association between the severity of psychiatric symptoms and the attenuation of the LRTC was found in frontal, central and temporal regions for stroke subjects with right lesions. A high discriminating ability of the LRTC in the frontal and central regions to distinguish depressive from non-depressive subjects suggested potential feasibility for LRTC as an assessment indicator for depression following right hemispheric cerebral infarction. Different performance of temporal correlation in depressed subjects following the two hemispheric lesions implied complex association between depression and stroke lesion location.     

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.     

Stress inhibits psychomotor performance differently in simple and complex open field environments

Stress affects psychomotor profiles and exploratory behavior in response to environmental features. Here we investigated psychomotor and exploratory patterns induced by stress in a simple open-field arena and a complex, multi-featured environment. Groups of rats underwent seven days of restraint stress or no-stress conditions and were individually tested in three versions of the ziggurat task (ZT) that varied according to environmental complexity. The hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis due to stress procedure was evaluated by the pre- and post-stress levels of circulating corticosterone (CORT). Horizontal activity, exploration, and motivation were measured by the number of fields entered, the time spent in the central fields, path length and speed, and stop duration. In addition, vertical exploratory behavior was measured by the times rats climbed onto ziggurats. Stress-induced psychomotor changes were indicated by reduced path length and path speed and increased duration of stops only within the complex arena of the ZT. Rats in stress groups also showed a significant decline in the vertical movements as measured by the number of climbing onto ziggurats. No stress-induced changes were revealed by the simple open-field arena. The exploratory patterns of stressed animals suggest psychomotor inhibition and reduced novelty-seeking behaviors in an environment-dependent manner. Thus, multi-featured arenas that require complex behavioral strategies are ideally suited to reveal the inhibitory effects of stress on psychomotor capabilities in rodents.     

Variation of hamstrings lengths and velocities with walking speed

Crouch gait, one of the most prevalent movement abnormalities among children with cerebral palsy, is frequently treated with surgical lengthening of the hamstrings. To assist in surgical planning many clinical centers use musculoskeletal modeling to help determine if a patient’s hamstrings are shorter or lengthen more slowly than during unimpaired gait. However, some subjects with crouch gait walk slowly, and gait speed may affect peak hamstring lengths and lengthening velocities. The purpose of this study was to evaluate the effects of walking speed on hamstrings lengths and velocities in a group of unimpaired subjects over a large range of speeds and to determine if evaluating subjects with crouch gait using speed matched controls alters subjects’ characterization as having “short” or “slow” hamstrings. We examined 39 unimpaired subjects who walked at five different speeds. These subjects served as speed-matched controls for comparison to 74 subjects with cerebral palsy who walked in crouch gait. Our analysis revealed that peak hamstrings length and peak lengthening velocity in unimpaired subjects increased significantly with increasing walking speed. Fewer subjects with cerebral palsy were categorized as having hamstrings that were “short” (31/74) or “slow” (38/74) using a speed-matched control protocol compared to a non-speed-matched protocol (35/74 “short”, 47/74 “slow”). Evaluation of patients with cerebral palsy using speed-matched controls alters and may improve selection of patients for hamstrings lengthening procedures.     

Kidney Shear Wave Speed Values in Subjects with and without Renal Pathology and Inter-Operator Reproducibility of Acoustic Radiation Force Impulse Elastography (ARFI) - Preliminary Results

Aim

to assess the inter-operator reproducibility of kidney shear wave speed, evaluated by means of Acoustic Radiation Force Impulse (ARFI) elastography, and the factors which influence it.

Methods

Our prospective pilot study included 107 subjects with or without kidney pathology in which kidney shear wave speed was evaluated by means of ARFI elastography. Intraclass correlation coefficient (ICC) was used to assess ARFI elastography reproducibility.

Results

A strong agreement was obtained between kidney shear wave speed measurements obtained by the two operators: ICC = 0.71 (right kidney) and 0.69 (left kidney). Smaller ICCs were obtained in “healthy subjects”, as compared to patients with kidney diseases (0.68 vs. 0.75), in women as compared with men (0.59 vs. 0.78), in subjects younger than 50 years as compared with those aged at least 50 years (0.63 vs. 0.71), in obese as compared with normal weight and overweight subjects (0.36 vs. 0.66 and 0.78) and in case of measurements depth <4 cm or >6 cm as compared with those performed at a depth of 4–6 cm from the skin (0.32 and 0.60 vs. 0.81).

Conclusion

ARFI elastography is a reproducible method for kidney shear wave speed assessment.     

A molecular dynamics approach to identify an oxysterol-based hedgehog pathway inhibitor

BackgroundMultiple oxysterols (OHCs) have demonstrated the ability to act as agonists or antagonists of the hedgehog (Hh) signaling pathway, a developmental signaling pathway that has been implicated as a potential therapeutic target in a variety of human diseases. These OHCs are known to modulate Hh signaling through direct binding interactions with the N-terminal cysteine rich domain (CRD) of Smoothened, a key regulator of Hh signal transduction.MethodsHomology modeling, molecular dynamics simulations, and MM/GBSA energy calculations were utilized to explore binding interactions between the OHC scaffold and the human Smoothened CRD. Follow-up cellular assays explored the in vitro activity of potential Hh pathway modulators.ResultsStructural features that govern key molecular interactions between the Smoothened CRD and the OHC scaffold were identified. Orientation of the iso-octyl side chain as well as the overall entropy of the OHC-CRD complex are important for determining activity against the Hh pathway. OHC 9, which was previously thought to be inactive because it was not an Hh agonist, was identified as an inhibitor of Hh signal transmission.ConclusionsCalculated MM/GBSA binding energies for OHCs in complex with the CRD of Smoothened correlate well with in vitro Hh modulatory activity. Compounds with high affinity stabilize Smoothened and are antagonists, whereas compounds with reduced affinity allow a conformational change in Smoothened that results in pathway activation.General significanceComputational modeling and molecular dynamics simulations can be used to predict whether a small molecule that binds the Smoothened CRD will be an agonist or antagonist of the pathway.     

The role of genetic factors in human radioresistance

The role of genetic factors in the development of chronic radiation disease (CRD), mostly caused by occupational external -exposure, was evaluated. The data of molecular genetic survey of a cohort of 985 workers at the nuclear power plant, the Mayak PA, were analyzed. Among the genetic markers tested, an association between the haptoglobin (Hp) genetic system and the development of CRD was established. It was demonstrated that the contribution of genetic factors to the CRD onset was realized not within the whole, but in a relatively narrow dose interval (70 to 400 cGy), i.e., was relative. Furthermore, at equal irradiation doses, relatively higher risk of CRD was observed among the Hp 2-2 phenotype carriers (1.96) compared to lower risk among the Hp 1-1 and Hp 2-1 phenotype carriers (0.64). It was shown that with the increase of the irradiation dose, genotypic differences in the CRD frequency decreased to the point of their complete disappearance. Comparison of the roles of the genetic factors in the onset of such deterministic irradiation effect as CRD, with their roles in the onset of lung cancer in tobacco smokers revealed similar patterns. A scheme of the relationships between the effector intensity and the differences in the genetically determined radioresistance is presented. The data obtained do not support the idea that the survivals of the atomic bombing of Hiroshima and Nagasaki were the most radioresistant individuals, who are not representative for evaluating the radiation risk.Translated from Genetika, Vol. 41, No. 1, 2005, pp. 85–92.Original Russian Text Copyright © 2005 by Telnov.     

Neurodevelopment in children with single-suture craniosynostosis and plagiocephaly without synostosis.

The objective of this study was to determine whether children with nonsyndromic craniosynostosis and plagiocephaly without synostosis demonstrated cognitive and psychomotor delays when compared with a standardized population sample. This was the initial assessment of a larger prospective study, which involved 21 subjects with nonsyndromic craniosynostosis (mean age, 10.9 months) and 42 subjects with plagiocephaly without synostosis (mean age, 8.4 months). Each child was assessed using the Bayley Scales of Infant Development-II (BSID-II) for cognitive and psychomotor development before therapeutic intervention (surgery for craniosynostosis and molding-helmet therapy for plagiocephaly without synostosis). The distribution of the scores was divided into four groups: accelerated, normal, mild delay, and significant delay. The distributions of the mental developmental index (MDI) and the psychomotor developmental index (PDI) were then compared with a standardized Bayley's age-matched population, using Fisher's exact chi-square test. Within the craniosynostosis group, the PDI scores were significantly different from the standardized distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the craniosynostosis group were accelerated, 43 percent were normal, 48 percent had mild delay, and 9 percent had significant delay. In contrast, the MDI scores were not statistically different (p = 0.08). Within the group with plagiocephaly without synostosis, both the PDI and MDI scores were significantly different from the normal curve distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the group with plagiocephaly without synostosis were accelerated, 67 percent were normal, 20 percent had mild delay, and 13 percent had significant delay. With regard to the MDI scores, 0 percent of the subjects in this group were accelerated, 83 percent were normal, 8 percent had mild delay and 9 percent had significant delay. This study indicates that before any intervention, subjects with single-suture syndromic craniosynostosis and plagiocephaly without synostosis demonstrate delays in cognitive and psychomotor development. Continued postintervention assessments are needed to determine whether these developmental delays can be ameliorated with treatment.     

Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1

The cation-permeable channel PKD2L1 forms a homomeric assembly as well as heteromeric associations with both PKD1 and PKD1L3, with the cytoplasmic regulatory domain (CRD) of PKD2L1 often playing a role in assembly and/or function. Our previous work indicated that the isolated PKD2L1 CRD assembles as a trimer in a manner dependent on the presence of a proposed oligomerization domain. Herein we describe the 2.7? crystal structure of a segment containing the PKD2L1 oligomerization domain which indicates that trimerization is driven by the β-branched residues at the first and fourth positions of a heptad repeat (commonly referred to as "a" and "d") and by a conserved R-h-x-x-h-E salt bridge motif that is largely unique to parallel trimeric coiled coils. Further analysis of the PKD2L1 CRD indicates that trimeric association is sufficiently strong that no other species are present in solution in an analytical ultracentrifugation experiment at the lowest measurable concentration of 750nM. Conversely, mutation of the "a" and "d" residues leads to formation of an exclusively monomeric species, independent of concentration. Although both monomeric and WT CRDs are stable in solution and bind calcium with 0.9μM affinity, circular dichroism studies reveal that the monomer loses 25% more α-helical content than WT when stripped of this ligand, suggesting that the CRD structure is stabilized by trimerization in the ligand-free state. This stability could play a role in the function of the full-length complex, indicating that trimerization may be important for both homo- and possibly heteromeric assemblies of PKD2L1.     

Postural control adaptability to floor oscillation in the elderly

We established a method to evaluate postural control adaptability, applying it to 341 subjects, aged 18-29 years (young subjects) and 50-79 years, in order to investigate the influences of age and gender on adaptability. Subjects stood with eyes closed on a force plate fixed to a floor oscillator, which was sinusoidally oscillated in the anteroposterior direction with 0.5 Hz frequency and 2.5 cm amplitude. Five trials of 1-minute oscillation were conducted, with a short rest between trials. The mean speed of fluctuation of the center of foot pressure (CFP), as detected by the force plate, was calculated as an index of postural steadiness. Mean CFP speed decreased significantly in all age groups with trial repetition. The adaptability capability of elderly subjects was categorized as "good," "moderate," or "poor," as evaluated against a standard value, based on the variation of the regression of mean CFP speed between the 1st and 5th trials in young subjects. Results showed that the magnitude of reduction in the mean speed, with practice, was linearly related to the initial mean speed. We found a general decline in adaptability, and increase in initial mean speed, in subjects aged 60 years and older, with no gender difference detected in any age group. The proportion of subjects exhibiting moderate and poor adaptability increased gradually with age. In conclusion, age, but not gender, appears to affect adaptation of postural sway with short-term practice, although some elderly subjects maintain postural sway velocity and adaptability capabilities similar to those of young subjects.     

Auditory and visual event-related potentials in a controlled investigation of HIV infection

Auditory and visual event-related brain potentials (ERPs) were used to complement neuropsychological and medical assessment in neurologically healthy subjects with asymptomatic and symptomatic human immunodeficiency virus type 1 (HIV-1) infection. Auditory and visual ERPs, recorded using standard oddball paradigms, disclosed delays in late waves (N2 and P3) in symptomatic subjects (CDC stage IV) when compared with matched controls. Abnormally delayed P3 waves in at least one modality were recorded in 41% of symptomatics and this was associated with deficits in neuropsychological performance, particularly psychomotor slowing. However, no differences in late wave latencies between asymptomatic and control subjects were found, though asymptomatics showed delays in auditory N1 and P2 latencies. The number of morphological abnormalities, such as indiscernible late waves as well as topographical variability of the P3 wave, was increased in both HIV seropositive groups and possibly indicates a distinct mechanism of impairment, different from latency delay. Whilst P3 delay in symptomatics was not associated with changes in immune function (T4 cells) there was, however, a link with anaemia and subclinical hepatic dysfunction.     

Exploring CRD mobility during RAS/RAF engagement at the membrane

During the activation of mitogen-activated protein kinase (MAPK) signaling, the RAS-binding domain (RBD) and cysteine-rich domain (CRD) of RAF bind to active RAS at the plasma membrane. The orientation of RAS at the membrane may be critical for formation of the RAS-RBDCRD complex and subsequent signaling. To explore how RAS membrane orientation relates to the protein dynamics within the RAS-RBDCRD complex, we perform multiscale coarse-grained and all-atom molecular dynamics (MD) simulations of KRAS4b bound to the RBD and CRD domains of RAF-1, both in solution and anchored to a model plasma membrane. Solution MD simulations describe dynamic KRAS4b-CRD conformations, suggesting that the CRD has sufficient flexibility in this environment to substantially change its binding interface with KRAS4b. In contrast, when the ternary complex is anchored to the membrane, the mobility of the CRD relative to KRAS4b is restricted, resulting in fewer distinct KRAS4b-CRD conformations. These simulations implicate membrane orientations of the ternary complex that are consistent with NMR measurements. While a crystal structure-like conformation is observed in both solution and membrane simulations, a particular intermolecular rearrangement of the ternary complex is observed only when it is anchored to the membrane. This configuration emerges when the CRD hydrophobic loops are inserted into the membrane and helices α3–5 of KRAS4b are solvent exposed. This membrane-specific configuration is stabilized by KRAS4b-CRD contacts that are not observed in the crystal structure. These results suggest modulatory interplay between the CRD and plasma membrane that correlate with RAS/RAF complex structure and dynamics, and potentially influence subsequent steps in the activation of MAPK signaling.     

Relationships between Cerebral Blood Flow Dynamics and Bioelectric Activity of the Human Brain in Experimental Acute Hypoxia

The relationships between the parameters of oxygen content in the body (hemoglobin saturation with oxygen and trancutaneous oxygen tension), central hemodynamics (cardiac output), and cerebral hemodynamics (cerebral blood flow rate) were studied during a hypoxic test (inhalation of an oxygen–nitrogen mixture containing 8% oxygen for 15 min). Special attention was paid to the relationships between the dynamics of cerebral blood flow and cerebral bioelectric activity measured by EEG parameters. It was demonstrated that the trancutaneous oxygen tension decreased to a greater extent than the hemoglobin saturation with oxygen and the cerebral blood flow increased to a greater extent than the cardiac output. The increase in cerebral blood flow and the increase in the indices and power of and EEG waves in the course of hypoxia were strongly positively correlated with each other in most subjects. However, if these parameters were considered in the series of subjects, the degree of the increase in the indices and power of and waves in different subjects was negatively correlated with the increase in the cerebral blood flow. The results are explained in terms of redistribution of blood flow in the body to provide a better oxygen supply to the brain and optimization of the ratios between the cerebral oxygen consumption and the functional load on the system of oxygen supply.     

Assessment of dynamic changes in cerebral autoregulation.

Cerebral autoregulation (CA) is a control mechanism that adjusts cerebral vasomotor tone in response to changes in arterial blood pressure (ABP) to ensure a nearly constant cerebral blood flow. Patient treatment could be optimized if CA monitoring were possible. Whereas the concept of static CA assessment is simply based on comparison of mean values obtained from two stationary states (e.g., before and after a pressure change), the evaluation of dynamic CA is more complex. Among other methods, moving cross-correlation analysis of slow waves in ABP and cerebral blood flow velocity (CBFV) seems to be appropriate to monitor CA quasi-continuously. The calculation of an "instantaneous transfer function" between ABP and CBFV oscillations in the low-frequency band using the Wigner-Ville distribution may represent an acceptable compromise in time-frequency resolution for continuous CA monitoring.     

A comparison of cerebral activity in the prefrontal region between young adults and the elderly while driving

The purpose of this study is to investigate the difference of cerebral activity in the prefrontal region between young adults and elderly subjects during driving. The procedure of the experiment was explained to the subjects and informed consent was obtained. Fourteen young male adults (21.6+/-0.76 yrs), seven elderly males (69.9+/-4.91 yrs), and seven elderly females (66.6+/-6.02 yrs) volunteered as subjects for the experiments. Non-invasive measurement of regional cerebral activity was estimated by measuring the deoxygenated hemoglobin, oxygenated hemoglobin, and total hemoglobin of both sides of the prefrontal region using near-infrared spectroscopy (NIRS) and time-resolved spectroscopy (TRS). The distance to the vehicle in front, speed, and braking were recorded and the behavior of the drivers was obtained using a CCD camera and video recorder. Temperature and relative humidity in the experimental car were 23-25 degrees Centigrade and 30-40%RH respectively. Background noise in the car was 50-65 dB (A). The less experienced young adults display a greater increase in prefrontal cerebral activity than do the experienced young adults during driving. Prefrontal cerebral activity in elderly subjects is lower than that in young adults at rest and shows little variation compared with young adults during driving. Less experienced young adults and elderly males display similar behavior patterns in driving, such as not observing the door mirror carefully when changing lane. The less experienced young adults are considered to be less adapted to driving. It is possible to evaluate adaptability for driving by means of measuring cerebral hemodynamic changes while driving.     

Epidemiological Trends of Dengue Disease in Brazil (2000–2010): A Systematic Literature Search and Analysis

A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Brazil reported between 2000 and 2010. The protocol was registered on PROSPERO (CRD42011001826: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42011001826). Between 31 July and 4 August 2011, the published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database. A total of 714 relevant citations were identified, 51 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Brazil, in this period, was characterized by increases in the geographical spread and incidence of reported cases. The overall increase in dengue disease was accompanied by a rise in the proportion of severe cases. The epidemiological pattern of dengue disease in Brazil is complex and the changes observed during this review period are likely to have been influenced by multiple factors. Several gaps in epidemiological knowledge regarding dengue disease in Brazil were identified that provide avenues for future research, in particular, studies of regional differences, genotype evolution, and age-stratified seroprevalence.

Systematic Review Registration

PROSPERO registration number: CRD42011001826.     

Impaired Cerebral Autoregulation Is Associated with Brain Atrophy and Worse Functional Status in Chronic Ischemic Stroke

Dynamic cerebral autoregulation (dCA) is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL), modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ( = 0.029), faster gait speed ( = 0.018) and lower IADL score (0.002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.     

Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome

Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of c-fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2-21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semiquantitative analysis of c-fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c-fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.     

Neural correlates of the difference between working memory speed and simple sensorimotor speed: an fMRI study

The difference between the speed of simple cognitive processes and the speed of complex cognitive processes has various psychological correlates. However, the neural correlates of this difference have not yet been investigated. In this study, we focused on working memory (WM) for typical complex cognitive processes. Functional magnetic resonance imaging data were acquired during the performance of an N-back task, which is a measure of WM for typical complex cognitive processes. In our N-back task, task speed and memory load were varied to identify the neural correlates responsible for the difference between the speed of simple cognitive processes (estimated from the 0-back task) and the speed of WM. Our findings showed that this difference was characterized by the increased activation in the right dorsolateral prefrontal cortex (DLPFC) and the increased functional interaction between the right DLPFC and right superior parietal lobe. Furthermore, the local gray matter volume of the right DLPFC was correlated with participants' accuracy during fast WM tasks, which in turn correlated with a psychometric measure of participants' intelligence. Our findings indicate that the right DLPFC and its related network are responsible for the execution of the fast cognitive processes involved in WM. Identified neural bases may underlie the psychometric differences between the speed with which subjects perform simple cognitive tasks and the speed with which subjects perform more complex cognitive tasks, and explain the previous traditional psychological findings.     

Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice with Late Stage Renal Disease

Objectives

Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD.

Methods and Results

CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD.

Conclusion

Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice.