White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain The underlying structural basis of this functional connectivity pattern is still widely unexplored We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure e 7 underlying default mode connectivity We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data Would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus With lateral temporal lobes, medial temporal lobes, and precuneus This was demonstrated at the p<0001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data Out findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based oil distinct pattern of anatomical connectivity within the cerebral white matter (C) 2009 Elsevier Inc All rights reserved

Peritumoral brain edema in benign meningiomas: correlation with clinical, radiologic, and surgical factors and possible role on recurrence

Background: Approximately 60% of meningiomas are associated with peritumoral edema. Various causative factors have been discussed in the literature. The objective of this study was to investigate the correlation of PTBE with clinical, radiologic, and surgical aspects and recurrence of meningiomas. Methods: Sixty-one patients with benign meningiomas were chosen for surgical treatment by the Group of Brain Tumors and Metastasis of the Department of Neurosurgery. All patients underwent complete surgical resection (Simpson grades I and 2), and those with atypical and malignant histopathologic grades were excluded. Tumors located in the cavernous sinus, tuberculum sellae, foramen magnum, ventricles, and petroclival region were excluded. Results: Edema extension had a positive correlation with the higher recurrence rates (P=.042) and with the presence of irregular margins (P<.011) on bivariate analysis. Meningiomas with larger edema sizes also showed correlation with large meningiomas (P=.035), and the ones with smaller edema sizes correlated with the tentorial location (P=.032). Multivariate analysis showed an association between PTBE and the presence of seizures (odds ratio, 3.469), large meningiomas (odds ratio, 15.977), and for each cubic centimeter added to its size, the risk of edema increased 1.082 times (odds ratio). Conclusion: Peritumoral brain edema may be related to the invading potential of meningiomas and may play a role in the recurrence potential of the tumor. As a consequence, it is reasonable to consider the presence of edema as an additional factor to be taken into account when mapping out strategies for the treatment of meningiomas. (C) 2008 Elsevier Inc. All rights reserved.

Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue

In spite of considerable technical advance in MRI techniques, the optical resolution of these methods are still limited. Consequently, the delineation of cytoarchitectonic fields based on probabilistic maps and brain volume changes, as well as small-scale changes seen in MRI scans need to be verified by neuronanatomical/neuropathological diagnostic tools. To attend the current interdisciplinary needs of the scientific community, brain banks have to broaden their scope in order to provide high quality tissue suitable for neuroimaging- neuropathology/anatomy correlation studies. The Brain Bank of the Brazilian Aging Brain Research Group (BBBABSG) of the University of Sao Paulo Medical School (USPMS) collaborates with researchers interested in neuroimaging-neuropathological correlation studies providing brains submitted to postmortem MRI in-situ. In this paper we describe and discuss the parameters established by the BBBABSG to select and to handle brains for fine-scale neuroimaging-neuropathological correlation studies, and to exclude inappropriate/unsuitable autopsy brains. We tried to assess the impact of the postmortem time and storage of the corpse on the quality of the MRI scans and to establish fixation protocols that are the most appropriate to these correlation studies. After investigation of a total of 36 brains, postmortem interval and low body temperature proved to be the main factors determining the quality of routine MRI protocols. Perfusion fixation of the brains after autopsy by mannitol 20% followed by formalin 20% was the best method for preserving the original brain shape and volume, and for allowing further routine and immunohistochemical staining. Taken to together, these parameters offer a methodological progress in screening and processing of human postmortem tissue in order to guarantee high quality material for unbiased correlation studies and to avoid expenditures by post-imaging analyses and histological processing of brain tissue.

Molecular Characterization, Distribution, and Dynamics of Hepatitis C Virus Genotypes in Blood Donors in Colombia

Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the ""Banco Nacional de Sangre de la Cruz Roja Colombiana,`` Bogota, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5`UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5`UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogota around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogota, as is the case in other South American countries. J. Med. Virol. 82: 1889-1898, 2010. (C) 2010 Wiley-Liss, Inc.

Dynamics of Hepatitis D (delta) virus genotype 3 in the Amazon region of South America

Hepatitis delta virus (HDV) is widely distributed and associated with fulminant hepatitis epidemics in areas with high prevalence of HBV. Several studies performed in the 1980s showed data on HDV infection in South America, but there are no studies on the viral dynamics of this virus. The aim of this study was to conduct an evolutionary analysis of hepatitis delta genotype 3 (HDV/3) prevalent in South America: estimate its nucleotide substitution rate, determine the time of most recent ancestor (TMRCA) and characterize the epidemic history and evolutionary dynamics. Furthermore, we characterized the presence of HBV/HDV infection in seven samples collected from patients who died due to fulminant hepatitis from Amazon region in Colombia and included them in the evolutionary analysis. This is the first study reporting HBV and HDV sequences from the Amazon region of Colombia. Of the seven Colombian patients, five were positive for HBV-DNA and HDV-RNA. Of them, two samples were successfully sequenced for HBV (subgenotypes F3 and Fib) and the five samples HDV positive were classified as HDV/3. By using all HDV/3 available reference sequences with sampling dates (n = 36), we estimated the HDV/3 substitution rate in 1.07 x 10(-3) substitutions per site per year (s/s/y), which resulted in a time to the most recent common ancestor (TMRCA) of 85 years. Also, it was determined that HDV/3 spread exponentially from early 1950s to the 1970s in South America. This work discusses for the first time the viral dynamics for the HDV/3 circulating in South America. We suggest that the measures implemented to control HBV transmission resulted in the control of HDV/3 spreading in South America, especially after the important raise in this infection associated with a huge mortality during the 1950s up to the 1970s. The differences found among HDV/3 and the other HDV genotypes concerning its diversity raises the hypothesis of a different origin and/or a different transmission route. (C) 2011 Elsevier B.V. All rights reserved.

Wilson`s disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

Brain magnetic resonance imaging (MRI) studies on Wilson`s disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.

Influence of vitrification on mouse metaphase II oocyte spindle dynamics and chromatin alignment

Objective: To evaluate influences of vitrification and warming of metaphase II (MII) mouse oocytes on survival, spindle dynamics. spindle morphology, and chromatin alignment on metaphase plates. Design: Experimental animal Study. Setting: University animal laboratory. Animal(s): Eight-week-old B6D2F1 mice. Intervention(s): Denuded MII oocytes were used fresh (control), exposed to vitrification/warming solutions (Sol Expos), or vitrified and warmed (Vitr). Main Outcome Measure(s): Oocyte recovery and survival after warming and the influence of solution exposure and cryopreservation on spindle dynamics and chromatin alignment. Result(s): Cryopreservation of two or 10 oocytes per straw resulted in recovery (100% +/- 0% and 95% +/- 4%, respectively; mean SE) and survival (95% 2% and 98% 2%, respectively). Immediately after warming (Vitr), significantly fewer oocytes assessed with immunocytochemistry contained spindles, compared with control and Sol Expos. When oocytes were placed into a 3 degrees 7C environment for 2 hours after exposure or warming, the ability to recognize spindles by immunocytochemistry was not significantly different between groups. Using live-cell time-lapse imaging with LC-Polscope, similar time-dependent spindle formation dynamics were observed. At 2 hours after collection or treatment, spindle morphology and length were not significantly different between the groups, nor was the incidence of aberrant alignment of chromatin on metaphase plates. Conclusion(s): Immediately after warming of vitrified MII oocytes, beta-tubulin is depolymerized and chromatin remains condensed on the metaphase plate. Within a 2-hour period, beta-tubulin repolymerizes, forming morphologically normal metaphase spindles with properly aligned chromatin.

Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: A preliminary 4-week study

Several studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9 +/- 127.1 pg/mL) compared to pre-treatment (406.3 +/- 69.5 pg/mL) (p = 0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithium`s direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study

Background. Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. Method. Longitudinal regional grey matter volume and ventricle : brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. Results. While there was no longitudinal difference in ventricle : brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. Conclusions. Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Serum brain-derived neurotrophic factor level is reduced in antidepressant-free patients with late-life depression

Objectives. The aim of the present study is to investigate serum BDNF levels in older depressed patients as compared to healthy elderly controls. Methods. Twenty-nine elderly subjects with major depression and 42 healthy older adults were enrolled to this study. All depressed patients were antidepressant-free for at least 1 month prior clinical and laboratorial assessments. Serum BDNF levels were determined by sandwich ELISA. Results. BDNF levels were lower in elderly depressed patients as compared to controls (P = 0.034). Patients with late-onset depression had the lowest BDNF level (median 478.5, interquartile range 373.5-740.9 pg/l) when compared to early-onset depression (median 620.7, interquartile range 366.1-971.9 pg/l) and healthy controls (median 711.3, interquartile range 534.7-1181.0 pg/l) (P < 0.03). Conclusions. Reduced serum BDNF level may be a state marker of late-life depression in non-medicated elderly patients. Our findings provide further evidences that reduced neurotrophic support may have an important role in the physiopathology of late-life depression.

Increased Brain Membrane Fluidity in Schizophrenia

Recent findings showing significant correlations between phospholipase A2 (PLA2) activity and structural changes in schizophrenic brains contribute to the membrane hypothesis of schizophrenia, which was hampered because a clean functional link between elevated PLA2 activity and brain structure was missing (Neuroimage, 2010; 52: 1314-1327). We measured membrane fluidity parameters and found that brain membranes isolated from the prefrontal cortex of schizophrenic patients showed significantly increased flexibility of fatty acid chains. Our findings support a possible link between elevated PLA2 activity in cortical areas of schizophrenic patients and subsequent alterations of the biophysical parameters of neuronal membranes leading to structural changes in these areas.

A longitudinal study on the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection in Amazonian Brazil, with special reference to its prevalence and incidence

This was a longitudinal study carried out during a period over 2 years with a cohort of 946 individuals of both sexes, aged 1 year and older, from an endemic area of American visceral leishmaniasis (AVL) in Para State, Brazil. The object was to analyze the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection based principally on the prevalence and incidence. For diagnosis of the infection, the indirect fluorescent antibody test (IFAT) and leishmanin skin test (LST) were performed with amastigote and promastigote antigens of the parasite, respectively. The prevalence by LST (11.2%) was higher (p < 0.0001) than that (3.4%) by IFAT, and the combined prevalence by both tests was 12.6%. The incidences by LST were also higher (p < 0.05) than those by IFAT at 6 (4.7% A- 0.6%), 12 (4.7% A- 2.7%), and 24 months (2.9% A- 0.3%). Moreover, there were no differences (p > 0.05) between the combined incidences by both tests on the same point surveys, 5.2%, 6.3%, and 3.6%. During the study, 12 infected persons showed high IFAT IgG titers with no LST reactions: five children and two adults developed AVL (2,560-10,120), and two children and three adults developed subclinical oligosymptomatic infection (1,280-2,560). The combined tests diagnosed a total of 231 cases of infection leading to an accumulated prevalence of 24.4%.

Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats

Several epidemiological studies have linked particulate matter exposure to numerous adverse health effects on the respiratory, cardiovascular, and reproductive systems (Braga et al., 1999; Zanobetti et al., 2000; Anderson et al., 2001; Farhat et al., 2005). More recently, ambient levels of black carbon were associated to impaired cognitive function in children (Suglia et al., 2008), suggesting that the central nervous system (CNS) may be a target of air pollutants. The present study was conducted to (a) determine whether chronic residual oil fly ash (ROFA) exposure promotes behavioral changes and lipid peroxidation in rat brain areas, and (b) determine whether N-acetylcysteine (NAC), a general antioxidant, prevents these effects. Forty-five-day-old male Wistar rats were exposed or not to ROFA by intranasal instillation and were treated or not with NAC (150 mg/kg) ip for 30 days. One day later, rats were submitted to the open field test to evaluate the motor/exploratory activities and emotionality followed by decapitation. Striatum and cerebellum were dissected to determine lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBARS). ROFA instillation induced an increase in lipid peroxidation level in striatum (p = .033) and cerebellum (p = .030), as compared with the control group. NAC treatment blocked these changes. ROFA promoted a decrease in the frequency of peripheral walking (p = .006) and a decrease in exploration (p = .001), which were not blocked by N-acetylcysteine. The present study provides evidence that toxic particles, administered by the respiratory route, induce oxidative stress in structures of the central nervous system, as well as behavioral alterations. The administration of NAC reduces lipid peroxidation at the striatum and cerebellum levels, but does not influence behavioral disturbances.

A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

This prospective study was carried out from October 2003 to December 2005 and involved a cohort of 946 individuals of both genders, aged 1-89 years, from an endemic area for American visceral leishmaniasis (AVL), in Para State, Brazil. The aim of the study was to analyze the dynamics of the clinical and immunological evolution of human Leishmania ( L.) infantum chagasi infection represented by the following clinical-immunological profiles: asymptomatic infection (AI); symptomatic infection (SI = AVL); subclinical oligosymptomatic infection (SOI); subclinical resistant infection (SRI); and indeterminate initial infection (III). Infection diagnosis was determined by the indirect fluorescent antibody test and leishmanin skin test. In total, 231 cases of infection were diagnosed: the AI profile was the most frequent (73.2%), followed by SRI (12.1%), III (9.9%), SI (2.6%) and SOI (2.2%). The major conclusion regarding evolution dynamics was that the III profile plays a pivotal role from which the cases evolve to either the resistant, SRI and AI, or susceptible, SOI and SI, profiles; only one of the 23 III cases evolved to SI, while most evolved to either SRI (nine cases) or SOI (five cases) and eight cases remained as III. (C) 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer`s disease, Huntington`s disease and Parkinson`s disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.