Cerebrovascular disease and hippocampal atrophy are differently linked to functional coupling of brain areas: an EEG coherence study in MCI subjects

The working hypothesis of paper is that the functional coupling of brain areas is combined with different neuroradiological substrates and has different clinical manifestations. 31 normal old subjects and 85 subjects with mild cognitive impairment (MCI) underwent EEG recordings and magnetic resonance imaging (MRI). Intrahemispheric and interhemispheric linear EEG coherences were computed. At first, all normal old and MCI subjects were compared. Subsequently, three subgroups of MCI were obtained based on neuroradiological substrate (subcortical cerebrovascular damage, MCI-CVD; cholinergic pathways vascular damage MCI-CHOL; and hippocampal atrophy, MCI-HIPP) and compared with a normal old sample matched for age, education and Mini-Mental State Examination score. The group of MCI subjects compared to normal old subjects shows: 1) decrease of intrahemispheric coherence in fronto-parietal regions (both right and left hemisphere); 2) increase of interhemispheric coherence on frontal regions in delta frequency; and 3) increase of interhemispheric coherence on temporal regions (from delta to alpha3 frequency bands). In the MCI subgroups, hippocampal atrophy is linked to an increase of interhemispheric coherence seen on frontal and temporal regions whereas subcortical CVD is linked to the largest decrease of coherence in fronto-parietal regions. MCI-CVD patients performed worst on Trail Making Test battery whereas MCI-HIPP patients were impaired on Rey word list delayed recall and Rey figure recall.     

Maternal hyperthyroidism in rats impairs stress coping of adult offspring

Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.     

An automated image analysis methodology for classifying megakaryocytes in chronic myeloproliferative disorders

This work describes an automatic method for discrimination in microphotographs between normal and pathological human megakaryocytes and between two kinds of disorders of these cells. A segmentation procedure has been developed, mainly based on mathematical morphology and wavelet transform, to isolate the cells. The features of each megakaryocyte (e.g. area, perimeter and tortuosity of the cell and its nucleus, and shape complexity via elliptic Fourier transform) are used by a regression tree procedure applied twice: the first time to find the set of normal megakaryocytes and the second to distinguish between the pathologies. The output of our classifier has been compared to the interpretation provided by the pathologists and the results show that 98.4% and 97.1% of normal and pathological cells, respectively, have testified an excellent classification. This study proposes a useful aid in supporting the specialist in the classification of megakaryocyte disorders.     

Topsy-turvy heart with associated congenital tracheobronchial stenosis and airway compression requiring surgical reconstruction

We describe a case of "topsy-turvy heart" that necessitated simultaneous left tracheobronchial repair, aortic arch reconstruction, and bronchial stenting in an 11-month-old girl. This case highlights the significant therapeutic dilemmas clinicians are faced with when dealing with conditions having an unknown natural history and unpredictable surgical outcomes, and reinforces the need for these patients to be managed by a multidisciplinary team approach.     

T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies

In the past few years, we have witnessed extraordinary advances in the understanding of the functions of regulatory T (Treg) cells in immunity against pathogens. However, controversy exists over the part that these cells play in determining the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the two main causes of chronic liver inflammation worldwide. Treg-cell responses may be either beneficial or detrimental to those infected with HBV and HCV, by either limiting liver immunopathology or suppressing protective T-cell responses. We review the latest research on CD4 Treg cells, dissect much of the Treg-related HBV and HCV literature, and discuss how new insights in Treg immunobiology apply to human and primate models of HBV and HCV infections. Moreover, we discuss the limitations of the conclusions drawn from current studies on Treg cells, and suggest experimental approaches that can resolve current conflicts and improve our understanding of the roles of Treg-cell subsets in HBV and HCV infections.     

ALS multidisciplinary clinic and survival

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motorneurons, for which there is no effective cure. Because of the multifactorial nature of impairment and disablity in ALS, multidisciplinary clinics (MDC) have been recently introduced in the management of ALS patients; their effects on survival remain, however, largely debated. OBJECTIVE: To compare survival of ALS patients who received their care at MDC with that of patients followed by general neurology clinics. METHODS: Source of the study was a prospective population-based registry of ALS established in Puglia, Southern Italy, in 1997. We examined survival of 126 out of 130 incident ALS cases that were diagnosed during the period 1998-99. RESULTS: 84 patients (67%) were enrolled and followed by MDC and the remaining 42 (33%) by general neurological clinics. No difference in median survival time from the diagnosis was observed between patients followed by ALS multidisciplinary (17.6 months) and general clinics (18 months). No beneficial effect was present among bulbar onset ALS (11.7 versus 23 months). In multivariate analysis management by ALS MDC was associated with only a 10% increase in survival probability at 12 months (HR: 0.91; 95%CI: 0.44-1.89; p = 0.9). CONCLUSIONS: In this population-based series, we found that in Southern Italy management of ALS by multidisciplinary clinics does not improve survival, regardless of site of symptoms onset.     

Differential Regulation of Smac/DIABLO and Hsp-70 during Brain Maturation

The heat shock protein (Hsp) system is a cell defense mechanism constitutively expressed at the basal state and essential for cell survival in response to damaging stimuli. Apoptosis is a physiological cell death program that preserves tissue homeostasis. We investigated the intrinsic pathway of apoptosis at various stages of brain maturation in CD-1 mice, triggered by two mitochondrial proapoptotic proteins, cytochrome c and Smac/DIABLO, and the pathway’s regulation by Hsp-70. Smac/DIABLO and Hsp-70 proteins were upregulated 2-fold and 1.5–3-fold, respectively, after birth. In contrast, in the presence of cytochrome c/2′-deoxyadenosine 5′-triphosphate (dATP), caspase activity in mouse brain cell-free extracts increased 90-fold and 61-fold, at fetal and neonatal stages, whereas no activation was detected 15 days postnatally or at any subsequent times. These results indicate that the activation pattern of the intrinsic pathway of apoptosis undergoes a marked shift during postnatal maturation. Vito Turk and Dale E. Bredesen share senior authorship.