INTRODUCTION: Smaller hippocampal volumes similar to those found in schizophrenia (SZ) are frequently observed to a lesser extent in non-psychotic first-degree relatives of patients with the illness, compared to control subjects. In this study, subdivisions of the hippocampal formation and their association with verbal and visual learning and memory were assessed in persons at familial high risk (FHR) for SZ.
The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw = 0.992), as compared to the case of more dehydrating conditions (aw = 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance (13)C polarization transfer solid-state NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with \~ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.
A new technique has been developed using NMR chemical shift imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.
Friedreich ataxia (FRDA) is a common inherited ataxia, caused by an expanded GAA repeat sequence in the Frataxin (FXN) gene. The proprioceptive system, which enters the cerebellum through the cerebellar peduncles, is a primary focus of pathology. In this study, we investigate the relationship of clinical and genetic data with diffusion-tensor imaging (DTI) indices reflecting white matter integrity of the cerebellar peduncles. Nine FRDA patients underwent DTI. After between-subject registration using tract-based spatial statistics, a white matter atlas was used for computing average values of DTI indices in the regions of interest. These were the inferior, middle and superior cerebellar peduncles (ICP, MCP, SCP). For Bonferroni correction, significance threshold was set to p 0.0056. We found that radial diffusivity (D(⊥)) within the ICP significantly correlated with scores on the Friedreich Ataxia Rating Scale (FARS, Spearman’s ρ = 0.883, p = 0.0016, all two-sided) and, at trend level, with number of trinucleotide repeats (ρ = 0.812, p = 0.008). D(⊥) in the SCP correlated with scores on the Scale for the Assessment and Rating of Ataxia (SARA, ρ = 0.867, p = 0.0025). These findings support the role of DTI, and especially D(⊥), as an informative biomarker in FRDA.
OBJECTIVE: EEG source localization is demonstrated in three cases of acute traumatic brain injury (TBI) with progressive lesion loads using anatomically faithful models of the head which account for pathology. METHODS: Multimodal magnetic resonance imaging (MRI) volumes were used to generate head models via the finite element method (FEM). A total of 25 tissue types-including 6 types accounting for pathology-were included. To determine the effects of TBI upon source localization accuracy, a minimum-norm operator was used to perform inverse localization and to determine the accuracy of the latter. RESULTS: The importance of using a more comprehensive number of tissue types is confirmed in both health and in TBI. Pathology omission is found to cause substantial inaccuracies in EEG forward matrix calculations, with lead field sensitivity being underestimated by as much as ≈ 200% in (peri-) contusional regions when TBI-related changes are ignored. Failing to account for such conductivity changes is found to misestimate substantial localization error by up to 35 mm. CONCLUSIONS: Changes in head conductivity profiles should be accounted for when performing EEG modeling in acute TBI. SIGNIFICANCE: Given the challenges of inverse localization in TBI, this framework can benefit neurotrauma patients by providing useful insights on pathophysiology.
We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia.
PURPOSE OF REVIEW: We review diffusion tensor imaging (DTI) studies that investigate white matter abnormalities in patients with chronic schizophrenia, first episode schizophrenia, and those who are at genetic risk for developing schizophrenia. Additionally, we include studies that combine DTI and functional MRI (fMRI) to investigate brain connectivity abnormalities. RECENT FINDINGS: Schizophrenia is a complex mental disorder with a peak age of onset in early adulthood. Abnormalities in white matter tracts, which connect brain regions into functional networks, are most likely relevant for understanding structural and functional brain abnormalities in schizophrenia. Dysconnectivity between brain regions, in fact, is thought to underlie cognitive abnormalities in schizophrenia but little is known about how alterations at the functional level relate to abnormalities in anatomical connectivity. DTI has become one of the most popular tools in brain research to address such questions. Here we review white matter abnormalities using DTI with the aim of understanding dysconnectivity of brain regions and their implications in schizophrenia. SUMMARY: Advances in DTI and in combining DTI with fMRI provide new insight into anatomical and functional connections in the brain, and for studying dysconnectivity in schizophrenia.
INTRODUCTION: Cognitive and emotional functioning is mediated by frontal-subcortical feedback loops. The striatum, a component of this circuitry, thus is a possible neural substrate of schizophrenia. Striatum volume, however, is believed to be differentially influenced by neuroleptic treatment due to an anterior-posterior D2 receptor density gradient. We thus rigorously parcellated it into subregions in order to assess whether neuroleptic effect on group differences is regionally specific. METHODS: 29 chronic, male, schizophrenia patients and 28 male, normal controls (NCs), group-matched for handedness, age, and parental SES, underwent structural brain imaging on a 1.5 Tesla GE system. We manually measured the volume, normalized for intracranial contents, of the striatum parcellated into anatomic subregions and their corresponding limbic, associative and sensorimotor functional subregions and performed clinical correlations. RESULTS: First, we found a localized bilateral enlargement of the posterior putamen in medicated chronic schizophrenia. Second, we showed associative striatal subregion volumes correlated with executive function in schizophrenia subjects and, to a lesser extent, in NCs. Third, we showed associative striatal subregions inversely correlated with negative symptoms but conversely, the ventral/limbic striatum did not correlate with positive or negative clinical symptoms. DISCUSSION: Our novel parcellation strategy, based on rigorous delineation of the ventral striatum, allowed for the demonstration of localized volumetric differences between schizophrenia and NCs. Furthermore, by parcellating the striatum into functional subregions we demonstrated significant positive correlations between the volume of the associative striatum and executive functioning in schizophrenia, adding further support to the importance of its role in the pathophysiology of schizophrenia.
A unique pentanuclear cluster within a zeolite-type polymer ([Cu5(μ4-Br)(μ3-Br)2(μ2-Br)2](μ2-MeSPr)3)n (1; void space >81%) and a luminescent 1D ([Cu(μ3-I)]4(MeSPr)3)n polymer, 2, are formed when MeSPr reacts with CuBr and CuI.
