Regionally specific cortical thinning in children with sickle cell disease

Sickle cell disease (SCD) is a chronic disease with a significant rate of neurological complications in the first decade of life. In this retrospective study, cortical thickness was examined in children with SCD who had no detectable abnormalities on conventional magnetic resonance imaging/magnetic resonance angiography. Regional differences in cortical thickness from SCD were explored using age-matched healthy controls as comparison. A comparison analysis was done for SCD (n = 28) and controls (n = 29) based on age (5-11; 12-21 years), due to the age-dependent variation in cortex maturation. Distinct regions of thinning were found in SCD patients in both age groups. The number, spatial extent, and significance (P < 0.001) of these areas of thinning were increased in the older SCD group. Regions of interest (ROIs) were defined on the areas of highly significant thinning in the older group and then mapped onto the younger cohort; a multiparametric linear regression analysis of the ROI data demonstrated significant (P < 0.001) cortical thinning in SCD subjects, with the largest regions of thinning in the precuneus and the posterior cingulate. The regionally specific differences suggest that cortical thickness may serve as a marker for silent insults in SCD and hence may be a useful tool for identifying SCD patients at risk for neurological sequelae.     

Functional neuroanatomical investigation of vision-related acupuncture point specificity--a multisession fMRI study

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple-session experiment to test whether electroacupuncture stimulation at two TCM vision-related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non-acupoint (NAP). Six normal, acupuncture naive subjects completed the study. Each subject participated in six identical scanning sessions. Voxelwise group analysis showed that electroacupuncture stimulation at both vision-related acupoints and the NAP produced modest, comparable fMRI signal decreases in the occipital cortex, including the bilateral cuneus, calcarine fissure and surrounding areas, lingual gyrus, and lateral occipital gyrus. Further analysis of fMRI signal changes in occipital cortex showed no significant difference among the three points, UB 60, GB 37, and NAP. Our results thus do not support the view that acupuncture stimulation at vision-related acupoints induces specific fMRI blood oxygen level dependent (BOLD) signal changes in the occipital cortex. We speculate that cross modal inhibition, produced by needling-evoked somatosensory stimulation, may account for our finding of BOLD signal decreases in the occipital cortex. Given the complexity of acupuncture systems and brain activity, additional work is required to determine whether functional neuroanatomical correlates of acupoint specificity can be validated by means of brain imaging tools.     

Length-dependence of lymphatic phasic contractile activity under isometric and isobaric conditions

OBJECTIVE: Experiments were designed to determine if the effect of preload on the spontaneous contractile activity of rat mesenteric lymphatics would be different under isometric and isobaric conditions. METHODS: Isobaric protocols on cannulated, pressurized rat mesenteric lymphatics ( approximately 120 microm, ID) measured the effects of lumenal pressure on contraction amplitude, frequency, and rate of diameter change (dD/dt). Analogous protocols were conducted using a wire myograph to determine the effects of passive force (preload) on the characteristics of spontaneous, isometric force transients. Servo-control systems allowed responses to ramp or step increases in preload/pressure to be tested. RESULTS: Under isobaric conditions, contraction amplitude was maximal at the lowest pressure tested (1 cm H(2)O), and progressively declined with pressure elevation to 10 cm H(2)O. Changes in dD/dt followed a similar pattern. In contrast, contraction frequency progressively increased with pressure. Under isometric conditions, the amplitude of spontaneous force transients was maximal at preloads of 0.3-0.4 mN, with dF/dt following a similar pattern; the average peak amplitude was approximately 15% of the maximal active contractile force developed during agonist stimulation. The frequency of the transients increased with preload from 0.05 to 0.3 mN, and remained constant at higher preloads. The amplitude-frequency product, an estimate of lymphatic pumping ability, reached a maximum value at 0.4 mN in isometric vessels and at 6 cm H(2)O in isobaric vessels. CONCLUSIONS: Isometric and isobaric methods yielded qualitatively similar indices of spontaneous contractile activity. However, the ranges of amplitude and frequency changes were much greater under isobaric conditions (3- to 5-fold) than under isometric conditions (50-80%).     

Infantile onset of hereditary spastic paraplegia poorly predicts the genotype

Age of symptom onset of hereditary spastic paraplegia varies from infancy to the eighth decade. Infantile onset of hereditary spastic paraplegia without a positive family history may cause difficulties in reaching the correct diagnosis and misdiagnosis as a diplegic form of cerebral palsy is particularly common. Infantile onset of hereditary spastic paraplegia caused by mutations in the spastin gene (SPAST) is very rare and previously was mostly associated with codominant mutations in this gene. We present a kindred with infantile onset of spastic paraplegia in three successive generations caused by confirmed de novo novel mutation 1537G>A (G471D) in SPAST. Several family members were previously diagnosed as having cerebral palsy. Infantile onset of hereditary spastic paraplegia may be caused by mutations in multiple genes, and this phenotype does not reliably predict the genotype. Pediatric neurologists need to be aware of relatively frequent de novo mutations in hereditary spastic paraplegia genes and a possibility that this condition presents in infancy without a positive family history.     

Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by 19F NMR of VCAM-1 targeted nanobeacons

We have designed multifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1), which is up-regulated in numerous inflammatory processes. These perfluorocarbon-cored nanoparticles emit a unique ¹⁹F magnetic resonance (MR) signature, providing the potential to localize and quantify VCAM-1 expression in early atherosclerosis. Nanoparticle-VCAM-1 targeting specificity was confirmed by in vitro binding and competition studies. ApoE-null and control C57-BL6 mice (n = 6/group), fed a Western diet for 35 weeks, were injected i.v. with targeted or non-targeted nanoparticles. After two hours, kidneys were excised and prepared for analysis. ApoE-null kidneys exhibited increased VCAM-1-targeted nanoparticle content over healthy controls by ¹⁹F MR spectroscopy (36.5+8.8 vs. 9.3+2.2 × 10⁸/g, P < .05), which correlated with increased VCAM-1 staining (2.5 ± 1.3% vs. 0.9 ± 0.3%, P < .05); their relative biodistributions were confirmed by fluorescence microscopy and MR imaging. These molecular imaging agents offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising ¹⁹F MR spectroscopy and imaging.From the Clinical EditorMultifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1) are reported in this paper. These perfluorocarbon-cored nanoparticles offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising 19F MR spectroscopy and imaging.     

Cultural mosaics and mental models of nature

For much of their history, the relationship between anthropology and psychology has been well captured by Robert Frost's poem, "Mending Wall," which ends with the ironic line, "good fences make good neighbors." The congenial fence was that anthropology studied what people think and psychology studied how people think. Recent research, however, shows that content and process cannot be neatly segregated, because cultural differences in what people think affect how people think. To achieve a deeper understanding of the relation between process and content, research must integrate the methodological insights from both anthropology and psychology. We review previous research and describe new studies in the domain of folk biology which examine the cognitive consequences of different conceptualizations of nature and the place of humans within it. The focus is on cultural differences in framework theories (epistemological orientations) among Native Americans (Menominee) and European American children and adults living in close proximity in rural Wisconsin. Our results show that epistemological orientations affect memory organization, ecological reasoning, and the perceived role of humans in nature. This research also demonstrates that cultural differences in framework theories have implications for understanding intergroup conflict over natural resources and are relevant to efforts to improve science learning, especially among Native American children.     

Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients

CONTEXT: The mechanism and significance of diminished glucocorticoid negative feedback in schizophrenia is unknown but is more commonly observed in schizophrenic patients with primary polydipsia. Polydipsic patients, especially those who are also hyponatremic, exhibit other neuroendocrine abnormalities that have been linked to hippocampal pathology. OBJECTIVE: The objective of the study was to determine the effect of cortisol on plasma ACTH under conditions thought to be most sensitive to hippocampal influences. DESIGN: The design was repeated measures. SETTING: The study was conducted at an inpatient clinical research center. PARTICIPANTS: Participants included eight polydipsic hyponatremic and eight polydipsic normonatremic as well as six schizophrenic patients without water imbalance. Eight healthy community volunteers matched for age and gender were also studied. INTERVENTION: Metyrapone (750 mg) was administered orally at 1430 and 1900 h. Beginning at 1930 h, hydrocortisone was infused over 150 min at 0.03 mg/kg.h. Blood samples and other measures were obtained at 20-min intervals from 1850 to 2320 h. MAIN OUTCOME MEASURES: Plasma ACTH and cortisol were measured. RESULTS: ACTH levels did not decline significantly during the cortisol infusion in the polydipsic hyponatremic group. For any given level of cortisol, ACTH levels were higher in the hyponatremic group. Although levels declined after cortisol in the other three groups, the decline was greatest in patients without water imbalance. CONCLUSIONS: The marked impairment in glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients is consistent with hippocampal mineralocorticoid dysfunction.