Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

White-matter hyperintensities in first-episode psychosis.

BACKGROUND: White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. AIMS: To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. METHOD: T(2)-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons. RESULTS: There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. CONCLUSIONS: White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings.

Pulmonary paracoccidioidomycosis.

Paracoccidioidomycosis (formerly known as South American blastomycosis) is produced by the thermally dimorphic fungus Paracoccidioides brasiliensis. Most often this mycosis runs a chronic progressive course affecting preferentially the lungs followed by the skin, mucous membranes, adrenals, and reticuloendothelial organs. Acute-subacute presentations can be observed in children and immunosuppressed patients. Occasionally, self-limited infections have been documented. Two types of clinical presentations are described, the acute-subacute (juvenile) and the chronic (adult) forms of the disease. Paracoccidioidomycosis predominates in adult males (13:1); this gender difference is not observed in children or adolescents. The mycosis is limited geographically to various Latin American countries, with the greatest number of cases originating in Brazil, The fungus's natural habitat has not been precisely defined, although it is supposed to be a soil-inhabiting microorganism. No outbreaks have been reported. P. brasiliensis is capable of entering into prolonged periods of latency as is demonstrated by its diagnosis in patients who have moved outside the recognized endemic areas. This review updates clinicians and laboratory workers on the characteristics of a mycosis seldom reported outside of the Latin American countries.

Grey matter abnormalities in Brazilians with first-episode psychosis.

BACKGROUND: In low- and middle-income countries people with schizophrenia are reported to experience better outcomes than those in high-income countries. AIMS: To examine structural brain differences in people with first-episode psychosis and controls in Brazil. METHOD: Magnetic resonance imaging using voxel-based morphometry was performed on 122 people with first-episode psychosis and 94 controls. RESULTS: There were significant decreases in grey matter in the left superior temporal and inferior prefrontal cortices, insula bilaterally and the right hippocampal region in first-episode psychosis (P<0.05, corrected for multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited a similar pattern of decrease in grey matter relative to controls. CONCLUSIONS: Structural abnormalities reported in psychosis in high-income countries are also present in first-episode psychosis in Brazil.

Volumetric reduction of the corpus callosum in Alzheimer's disease in vivo as assessed with voxel-based morphometry.

Several recent magnetic resonance imaging studies have employed voxel-based morphometry (VBM) to detect regional gray matter volume abnormalities in Alzheimer's disease (AD). However, investigations of corpus callosum (CC) abnormalities in AD using this automated methodology have been scarce, and no VBM study investigated correlations between regional CC atrophy and cognitive measurements in AD subjects at mild disease stages. We used VBM to compare the topography of CC volume differences between 14 AD subjects (MMSE 14-25) and 14 healthy volunteers. Images were acquired using a 1.5-Telsa scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. Significant CC atrophy was detected in the antero-superior portion of the splenium, the isthmus, the anterior and posterior portions of the CC body, and the rostral portion of the genu. Voxels showing peak statistical difference were all left-sided (P<0.001, uncorrected for multiple comparisons). A cluster of significant positive correlation with MMSE scores was seen on the left anterior CC body. Our results confirm previous findings of diffuse volumetric CC reductions early in the course of AD, and warrant further evaluation of the relevance of atrophic changes in anterior CC portions to the cognitive impairments that characterize the disorder.

A 1HMRS study of the anterior cingulate gyrus in euthymic bipolar patients.

INTRODUCTION: The anterior cingulate region has been implicated in the pathophysiology of mood disorders. Studies have reported anatomical and functional abnormalities in this region in bipolar disorder patients. Few neurochemical studies have evaluated this region, especially on medicated bipolar patients. Lithium has been reported to increase NAA levels but not by all studies. We used proton magnetic spectroscopy ((1)HMRS) to measure the levels of N-acetyl-L-aspartate (NAA) and choline (Cho) relative to creatine (Cr) in the anterior cingulate of euthymic medicated bipolar subjects. METHODS: (1)HMRS was performed using a GE Signa 1.5 Tesla scanner in 13 euthymic bipolar patients who were taking lithium for at least four weeks before the scan and in 15 normal controls. The (1)HMRS signal was collected from an 8 cm(3) voxel placed in the anterior cingulate. Data analysis was performed with the automated PROBE/SV quantification tool. RESULTS: NAA/Cr and Cho/Cr ratios were not significantly different between patients and controls (NAA/Cr: 1.60 +/- 0.34 in patients, 1.68 +/- 0.34 in controls; Cho/Cr: 1.13 +/- 0.13 in patients, 1.11 +/- 0.20 in controls). CONCLUSIONS: We did not find a significant difference in the NAA/Cr and Cho/Cr ratio between bipolar patients and healthy controls. Chronic administration of psychotropic drugs could have had an effect on NAA/Cr levels of bipolar patients.

Widespread electrical cortical dysfunction in schizophrenia.

The purpose of this study was to compare slow cortical electrical activity between healthy and schizophrenic individuals using 123-channel EEG and current density reconstruction (CDR). Twenty-nine healthy subjects and 14 drug-free patients performed three visual paired-associate tasks (verbal, pictorial and spatial). We modeled the generators of the slow potentials (SPs) at their peak amplitude by Lp-norm minimization using individual MRIs to model the volume conductor and source. Activity in each architectonic area of Brodmann was scored with respect to individual maximum current by a percentile method. Resulting scores by cortical area were analyzed by multivariate analysis of variance (MANOVA) with planned comparisons, to search for differences among levels. Results showed a multifocal pattern of current density foci comprising the SP generators, including frontal and posterior cortices in all subjects. A few cortical areas, not exclusively frontal, were observed to significantly differ between groups. Moreover, changes in patients' frontal activity were not exclusively to lower scores or 'hipofrontality': overall effects (all tasks collapsed) included increased electrical activity in right area 10, left 38 and 47 bilaterally, and decreased activity in right area 6 and left areas 39, 21 and 19. A few additional areas showed significantly altered activity only in particular tasks. We conclude that the present method, by preserving individual anatomical and functional information, indicates bidirectional patterns of altered electrical activity in specific cortical association areas in schizophrenia, which are not compatible with the exclusive 'hipofrontality' hypothesis. Our results agree with the hypothesis of schizophrenia as a syndrome resulting from abnormalities in multiple encephalic foci.

Gadolinium-enhanced three-dimensional MR angiography of Takayasu arteritis.

Takayasu arteritis is a form of large vessel vasculitis with a possible autoimmune origin that may cause stenosis of the aorta and its major branches. Six types of Takayasu arteritis are recognized; the type depends on whether the ascending aorta, descending thoracic aorta, abdominal aorta, aortic cervicobrachial branches, or renal arteries are affected. The coronary and pulmonary arteries are also sometimes involved. Clinical features of the disease include diminished or absent pulses, claudication, hypertension, and mesenteric angina. Conventional angiography has been the standard imaging tool for diagnosis and evaluation of Takayasu arteritis, although it demonstrates only the lumen of the vessel. Less invasive cross-sectional methods such as computed tomographic angiography and, more recently, three-dimensional magnetic resonance (MR) angiography can effectively demonstrate thickening of the vessel wall, which may be the earliest manifestation of the disease, occurring before stenosis and dilatation. MR imaging in particular allows better soft-tissue differentiation and can show other signs of inflammation, including mural edema and increased mural vascularity. Other advantages of MR imaging are the lack of iodinated contrast material or ionizing radiation.

Inter- and intrareader variability in the interpretation of two radiographic classification systems for juvenile rheumatoid arthritis.

OBJECTIVE: To evaluate the inter- and intrareader variability for interpretation of a modified Larsen's radiographic classification system for juvenile rheumatoid arthritis (JRA) focused on osteochondral lesions and a conventional Larsen's classification system, compared to a reference MR scoring system of corresponding images. MATERIALS AND METHODS: Seventy-five radiographs of 60 children with JRA, performed within a short interval of time from the MR examinations, were independently evaluated by three experienced radiologists, three diagnostic imaging residents and three rheumatologists, in two separate sessions, according to the two different classification methods, blinded to the corresponding MR images. RESULTS: The inter- and intrareader concordance rates between the two radiographic classification systems and the MR-related radiographs were respectively poor and poor/moderate. The interobserver range of weighted kappa values for the conventional and the modified Larsen's system respectively was 0.25-0.37 vs 0.19-0.39 for radiologists, 0.25-0.37 vs 0.18-0.30 for residents and 0.19-0.51 vs 0.17-0.29 for rheumatologists. The intrareader rate ranged from 0.17-0.55 for radiologists, 0.2-0.56 for residents, and 0.14-0.59 for rheumatologists. CONCLUSION: Although the proposal of a new radiographic classification system for JRA focused on osteochondral abnormalities sounds promising, the low inter- and intrareader concordance rates with an MR-related radiographic system makes the clinical applicability of such a radiographic system less suitable.

The generators of slow potentials obtained during verbal, pictorial and spatial tasks.

The purpose of this study was to test whether slow cortical electrical activity is specific to performance on verbal, pictorial and spatial tasks. Twenty-nine healthy subjects were required to compare pairs of visual stimuli separated by a delay of 2.5 s in a S1-S2 contingent negative variation-type paradigm. Slow potentials (SPs) were recorded by high-resolution EEG (123 channels) and their generators modeled by current density reconstruction using individual MRIs as source space models. Activity in each architectonic area of Brodmann was scored with respect to individual maximum current by a percentile method. Results showed a multifocal pattern of current density foci comprising the SP generators, including frontal and posterior cortices in all subjects, with the most active areas being common to the three tasks. In spite of the intersubject variability in the sets of active areas for each given task, a few cortical areas were observed to discriminate between tasks in a statistically significant way: the verbal task corresponded to stronger electrical activity in right area 45 than the other tasks; the spatial to weaker activity in right area 38 and left area 5 than the other tasks; the pictorial, compared to the spatial task, to stronger activity in left area 39; the verbal, compared to the spatial task, to stronger activity in left area 10, and compared to the pictorial, to weaker activity in right area 20. The present method of SP analysis may aid in the functional mapping of human association cortices in individual cases. We discuss our results emphasizing intersubject variability in cortical activity patterns and the possibility of finding more universal patterns.

Multifocal slow potential generation revealed by high-resolution EEG and current density reconstruction.

In this work we used high-resolution EEG (123 channels) and current density reconstruction (CDR) to analyze the generators of slow potentials (SPs) in 31 healthy individuals. SPs were obtained during a task-performance feedback anticipation paradigm. The task consisted of a visual paired-associate memory test, with correct performance on single trials indicated by pleasant visual stimuli and incorrect performance by an unpleasant sound. We used realistic models of each subject's head based on their magnetic resonance images (MRIs) to estimate the potentials in the intracranial compartments and to define the source space using individual cortical geometry. Source reconstruction was performed by an Lp-norm minimization algorithm. Results showed a multifocal pattern of current density foci in various association cortices, including prefrontal areas 9 and 10 of Brodmann in all subjects. Posterior cortical areas also contributed importantly to the SP, for instance extrastriate area 19 and parietal area 7, in 90% of the subjects. According to our modeling, we conclude that even the pure stimulus-anticipation SP obtained here, as opposed to traditional motor-task contigent negative variation (CNVs), is not exclusively prefrontal in origin, being generated by multiple association areas. We discuss our results with respect to new possibilities in large-scale cortical physiology and with respect to their application in psychiatry.

[Reliability of volumetric measures of mesial temporal structures]. / Confiabilidade de medidas volumétricas de estruturas temporais mesiais.

RATIONALE: The development of reliable techniques for volumetric measurement of mesial temporal structures (amygdala, hippocampus and parahippocampal gyrus) on magnetic resonance imaging (MRI) can provide data for the study of neuropsychiatric disorders, mainly temporal lobe epilepsy, Alzheimer's disease and schizophrenia. METHOD: We investigated these techniques performing intraobserver and interobserver reliability study concerning normal controls, epilepsy and Alzheimer's disease patients using the intra-class correlation coefficient. RESULTS: Intra-observer reliability of evaluated structures ranged from 0.93 to 0.99 (p<0.001). Inter-observer reliability ranged from 0.70 to 0.95 (p < or = 0.001). CONCLUSION: The results suggest that the technique of MRI morphometry of mesial temporal regions can be considered a reliable tool which may help in the investigation of neuropsychiatric disorders, since used by adequately trained clinicians and researchers.