Clinicopathological and radiological study of Egyptian β-thalassemia intermedia and β-thalassemia major patients: relation to complications and response to therapy

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian β-thalassemia intermedia (β-TI) patients were compared with 70 β-thalassemia major (β-TM) patients. β-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, β-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in β-TM patients compared with β-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for β-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between β-TI and β-TM. We provide evidence that calls for the use of HU in β-TI patients.     

A CSF and postmortem brain study of D-serine metabolic parameters in schizophrenia

Clinical trials demonstrated that D-serine administration improves schizophrenia symptoms, raising the possibility that altered levels of endogenous D-serine may contribute to the N-methyl D-aspartate receptor hypofunction thought to play a role in the disease. We hypothesized that cerebro-spinal fluid (CSF) D-serine levels are decreased in the patients due to reduced synthesis and/or increased degradation in brain. We now monitored amino acid levels in CSF from 12 schizophrenia patients vs. 12 controls and in postmortem parietal-cortex from 15 control subjects and 15 each of schizophrenia, major-depression and bipolar patients. In addition, we monitored postmortem brain serine racemase and D-amino acid oxidase protein levels by Western-blot analysis. We found a 25% decrease in D-serine levels and D/L-serine ratio in CSF of schizophrenia patients, while parietal-cortex D-serine was unaltered. Levels of L-serine, L-glutamine and L-glutamate were unaffected. Frontal-cortex (39%) and hippocampal (21%) serine racemase protein levels and hippocampal serine racemase/D-amino acid oxidase ratio (34%) were reduced. Hippocampal D-amino-acid-oxidase protein levels significantly correlated with duration of illness (r=0.6, p=0.019) but not age. D-amino acid oxidase levels in patients with DOI>20 years were 77% significantly higher than in the other patients and controls. Our results suggest that reduced brain serine racemase and elevated D-amino acid oxidase protein levels may contribute to the lower CSF D-serine levels in schizophrenia.     

Theory of Mind and Executive Function in Preschoolers with Typical Development Versus Intellectually Able Preschoolers with Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) have difficulties in theory of mind (ToM) and executive function (EF), which may be linked because one domain (EF) affects the other (ToM). Group differences (ASD vs. typical development) were examined in both cognitive domains, as well as EF’s associations and regressions with ToM. Participants included 29 intellectually able preschoolers with ASD and 30 typical preschoolers, aged 3–6 years. EF tasks included planning and cognitive shifting measures. ToM tasks included predicting and explaining affective and location false-belief tasks. The novelty of this study lies in its in-depth examination of ToM explanation abilities in ASD alongside the role of verbal abilities (VIQ). Significant group differences emerged on most EF and ToM measures, in favor of typically developing children. Overall in the study group, EF-planning skills, EF-cognitive shifting and VIQ significantly contributed to the explained variance of ToM measures. Implications are discussed regarding the social-cognitive deficit in ASD.     

Development of a human brain diffusion tensor template

The development of a brain template for diffusion tensor imaging (DTI) is crucial for comparisons of neuronal structural integrity and brain connectivity across populations, as well as for the development of a white matter atlas. Previous efforts to produce a DTI brain template have been compromised by factors related to image quality, the effectiveness of the image registration approach, the appropriateness of subject inclusion criteria, and the completeness and accuracy of the information summarized in the final template. The purpose of this work was to develop a DTI human brain template using techniques that address the shortcomings of previous efforts. Therefore, data containing minimal artifacts were first obtained on 67 healthy human subjects selected from an age-group with relatively similar diffusion characteristics (20–40 years of age), using an appropriate DTI acquisition protocol. Non-linear image registration based on mean diffusion-weighted and fractional anisotropy images was employed. DTI brain templates containing median and mean tensors were produced in ICBM-152 space and made publicly available. The resulting set of DTI templates is characterized by higher image sharpness, provides the ability to distinguish smaller white matter fiber structures, contains fewer image artifacts, than previously developed templates, and to our knowledge, is one of only two templates produced based on a relatively large number of subjects. Furthermore, median tensors were shown to better preserve the diffusion characteristics at the group level than mean tensors. Finally, white matter fiber tractography was applied on the template and several fiber-bundles were traced.