Relationship Between Regional Brain Volumes and Cognitive Performance in the Healthy Aging: An MRI Study Using Voxel-Based Morphometry

The presence of cognitive impairment is a frequent complaint among elderly individuals in the general population. This study aimed to investigate the relationship between aging-related regional gray matter (rGM) volume changes and cognitive performance in healthy elderly adults. Morphometric magnetic resonance imaging (MRI) measures were acquired in a community-based sample of 170 cognitively-preserved subjects (66 to 75 years). This sample was drawn from the "Sao Paulo Ageing and Health" study, an epidemiological study aimed at investigating the prevalence and risk factors for Alzheimer's disease in a low income region of the city of Sao Paulo. All subjects underwent cognitive testing using a cross-culturally battery validated by the Research Group on Dementia 10/66 as well as the SKT (applied on the day of MRI scanning). Blood genotyping was performed to determine the frequency of the three apolipoprotein E allele variants (APOE epsilon 2/epsilon 3/epsilon 4) in the sample. Voxelwise linear correlation analyses between rGM volumes and cognitive test scores were performed using voxel-based morphometry, including chronological age as covariate. There were significant direct correlations between worse overall cognitive performance and rGM reductions in the right orbitofrontal cortex and parahippocampal gyrus, and also between verbal fluency scores and bilateral parahippocampal gyral volume (p < 0.05, familywise-error corrected for multiple comparisons using small volume correction). When analyses were repeated adding the presence of the APOE epsilon 4 allele as confounding covariate or excluding a minority of APOE epsilon 2 carriers, all findings retained significance. These results indicate that rGM volumes are relevant biomarkers of cognitive deficits in healthy aging individuals, most notably involving temporolimbic regions and the orbitofrontal cortex.

Sural nerve involvement in experimental hypertension: morphology and morphometry in male and female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)

Background: The sural nerve has been widely investigated in experimental models of neuropathies but information about its involvement in hypertension was not yet explored. The aim of the present study was to compare the morphological and morphometric aspects of different segments of the sural nerve in male and female spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats aged 20 weeks (N = 6 in each group) were investigated. After arterial pressure and heart rate recordings in anesthetized animals, right and left sural nerves were removed and prepared for epoxy resin embedding and light microscopy. Morphometric analysis was performed with the aid of computer software, and took into consideration the fascicle area and diameter, as well as myelinated fiber number, density, area and diameter. Results: Significant differences were observed for the myelinated fiber number and density, comparing different genders of WKY and SHR. Also, significant differences for the morphological (thickening of the endoneural blood vessel walls and lumen reduction) and morphometric (myelinated fibers diameter and G ratio) parameters of myelinated fibers were identified. Morphological exam of the myelinated fibers suggested the presence of a neuropathy due to hypertension in both SHR genders. Conclusions: These results indicate that hypertension altered important morphometric parameters related to nerve conduction of sural nerve in hypertensive animals. Moreover the comparison between males and females of WKY and SHR allows the conclusion that the morphological and morphometric parameters of sural nerve are not gender related. The morphometric approach confirmed the presence of neuropathy, mainly associated to the small myelinated fibers. In conclusion, the present study collected evidences that the high blood pressure in SHR is affecting the sural nerve myelinated fibers.

Sperm head morphometry in ejaculates of adult marmosets (Callithrix jacchus): a model for studying sperm subpopulations and among-donor variations

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a nonhuman primate model (Callithrix jacchus), using an objective computer analysis system and principal component analysis (PCA) methods to establish the relationship between the subpopulation distribution observed and among-donor variation. The PCA method revealed a stable number of principal components in all donors studied, that represented more than 85% of the cumulative variance in all cases. After cluster analysis, a variable number (from three to seven) sperm morphometric subpopulations were identified with defined sperm dimensions and shapes. There were differences in the distribution of the sperm morphometric subpopulations (P < 0.001) in all ejaculates among the four donors analyzed. In conclusion, in this study, computerized sperm analysis methods combined with PCA cluster analyses were useful to identify, classify, and characterize various head sperm morphometric subpopulations in nonhuman primates, yielding considerable biological information. In addition, because all individuals were kept in the same conditions, differences in the distribution of these subpopulations were not attributed to external or management factors. Finally, the substantial information derived from subpopulation analyses provided new and relevant biological knowledge which may have a practical use for future studies in human and nonhuman primate ejaculates, including identifying individuals more suitable for assisted reproductive technologies. (c) 2012 Elsevier Inc. All rights reserved.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Allometric growth of a common Nassariidae (Gastropoda) in south-east Brazil

The allometric growth of two groups of Nassarius vibex on beds of the bivalve Mytella charruana on the northern coast of the State of Sao Paulo, was evaluated between September 2006 and February 2007 in the bed on Camaroeiro Beach, and from March 2007 to June 2007 at Cidade Beach. The shells from Camaroeiro were longer and wider and had a smaller shell aperture than those from Cidade; a principal components analysis also confirmed different morphometric patterns between the areas. The allometric growth of the two groups showed great variation in the development of individuals. The increase of shell width and height in relation to shell length did not differ between the two areas. Shell aperture showed a contrasting growth pattern, with individuals from Camaroeiro having smaller apertures. The methodology based on Kullback-Leibler information theory and the multi-model inference showed, for N. vibex, that the classic linear allometric growth was not the most suitable explanation for the observed morphometric relationships. The patterns of relative growth observed in the two groups of N. vibex may be a consequence of different growth and variation rates, which modifies the development of the individuals. Other factors such as food resource availability and environmental parameters, which might also differ between the two areas, should also be considered.

Influence of biliary anastomosis on recovery from secondary biliary cirrhosis

Objective The influence of choledochoduodenostomy and choledochojejunostomy on the repair of hepatic lesions secondary to biliary obstruction is not well known. The aim of the present study was to compare the effects of choledochoduodenostomy and choledochojejunostomy on the recovery of these lesions in rats with biliary obstruction. Methods Rats subjected to 4 weeks of biliary obstruction underwent choledochoduodenostomy (n=10) or choledochojejunostomy (n=10). The following variables were measured: total bilirubin, alkaline phosphatase, aminotransferases, and albumin. Hepatic mitochondrial energy metabolism was evaluated by calculating the respiratory control ratio and the oxidative phosphorylation index. Hepatic morphometry was used to estimate the mass of the hepatocytes, bile ducts, and fibrosis, as well as the hepatic stellate cell count. Results After choledochoduodenostomy and choledochojejunostomy, there was a regression in cholestasis and a reduction in the oxidative phosphorylation index. However, the total bilirubin, alkaline phosphatase, albumin, and respiratory control ratio values improved only after choledochojejunostomy. The mass of the liver, spleen, and fibrosis was reduced after both choledochoduodenostomy and choledochojejunostomy, but the number of hepatic stellate cells increased. After choledochojejunostomy, the hepatic mass recovered completely, and the spleen mass was significantly reduced compared with that after choledochoduodenostomy. After both choledochoduodenostomy and choledochojejunostomy, enterobiliary reflux, biliary contamination, and an exacerbation in hepatic inflammation developed. Conclusion Choledochojejunostomy was more effective than choledochoduodenostomy, but both techniques induced enterobiliary reflux and biliary contamination, which may explain the maintenance of hepatic alterations, especially after choledochoduodenostomy. Eur J Gastroenterol Hepatol 24: 1039-1050 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections

Aims: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. Methods and results: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. Conclusions: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

Molecular phylogeny and morphometric analyses reveal deep divergence between Amazonia and Atlantic Forest species of Dendrophryniscus

Dendrophryniscus is an early diverging clade of bufonids represented by few small-bodied species distributed in Amazonia and the Atlantic Forest. We used mitochondrial (414 bp of 12S, 575 bp of 16S genes) and nuclear DNA (785 bp of RAG-1) to investigate phylogenetic relationships and the timing of diversification within the genus. These molecular data were gathered from 23 specimens from 19 populations, including eight out of the 10 nominal species of the genus as well as Rhinella boulengeri. Analyses also included sequences of representatives of 18 other bufonid genera that were publically available. We also examined morphological characters to analyze differences within Dendrophryniscus. We found deep genetic divergence between an Amazonian and an Atlantic Forest clade, dating back to Eocene. Morphological data corroborate this distinction. We thus propose to assign the Amazonian species to a new genus, Amazonella. The species currently named R. boulengeri, which has been previously assigned to the genus Rhamphophryne, is shown to be closely related to Dendrophryniscus species. Our findings illustrate cryptic trends in bufonid morphological evolution, and point to a deep history of persistence and diversification within the Amazonian and Atlantic rainforests. We discuss our results in light of available paleoecological data and the biogeographic patterns observed in other similarly distributed groups. (C) 2011 Elsevier Inc. All rights reserved.

Voxelwise evaluation of white matter volumes in first-episode psychosis

The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n = 40) relative to controls (n = 89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.

Comparative analysis of shell occupation by two southern populations of the hermit crab Loxopagurus loxochelis (Decapoda, Diogenidae)

The present study aimed to comparatively verify the relation between the hermit crabs and the shells they use in two populations of Loxopagurus loxochelis. Samples were collected monthly from July 2002 to June 2003, at Caraguatatuba and Ubatuba Bay, Sao Paulo, Brazil. The animals sampled had their sex identified, were weighed and measured; their shells were identified, measured and weighed, and their internal volume determined. To relate the hermit crab's characteristics and the shells' variables, principal component analysis (PCA) and a regression tree were used. According to the PCA analysis, the three gastropod shells most frequently used by L. loxochelis varied in size. The regression tree successfully explained the relationship between the hermit crab's characteristics and the internal volume of the inhabited shell. It can be inferred that the relationship between the morphometry of an individual hermit crab and its shell is not straightforward and it is impossible to explain only on the basis of direct correlations between the body's and the shell's attributes. Several factors (such as the morphometry and the availability of the shell, environmental conditions and inter- and intraspecific competition) interact and seem to be taken into consideration by the hermit crabs when they choose a shell, resulting in the diversified pattern of shell occupancy shown here and elsewhere.

Rice oil as a soybean oil replacement in weanling pig diets

The motivation for including oils in the diets of weanling pigs is to increase dietary energy density to meet the pigs' energy requirements. The purpose of this study was to determine the digestible and metabolizable energy values of semi-refined rice oil (RO) and refined soybean oil (SO) for weanling pigs (Experiment 1), as well as to evaluate how replacing SO with RO in weanling pig diets affects performance, intestinal histology, organ morphometry and the occurrence of diarrhea (Experiment 2). In Experiment 1,21 barrows, averaging 19.63 +/- 0.37 kg body weight (BW), were used in a randomized complete block design experiment, with seven replications per treatment and one pig per experimental unit (metabolism cage). The treatments consisted of a reference diet and two test diets. The test diets were obtained by using 90% of the reference diet and 10% of RO or SO. The experimental period consisted of a 7 days adaptation period, followed by a 5 days collection period of feces and urine. The values of the apparent digestible energy, apparent metabolizable energy and N-corrected apparent metabolizable energy of the oils were, respectively, 26.24, 25.78 and 26.01 MJ kg(-1) for RO and 31.74, 31.35 and 31.51 MJ kg(-1) for SO. In Experiment 2, 120 weaned pigs, castrated males and females, averaging 6.74 +/- 0.42 kg BW, were used in a randomized complete block design experiment, with eight replications per treatment and three pigs per experimental unit (pen) to evaluate the effects of five replacement levels of SO with RO in isonutritive weanling pig diets. The treatments were as follows: 4:0 basal diet with 4% of SO; 3:1 basal diet with 3% of SO and 1% of RO; 2:2 basal diet with 2% of SO and 2% of RO; 1:3 basal diet with 1% of SO and 3% of RO; and 0:4 basal diet with 4% of RO. No effects of the replacement levels were observed in the weanling pigs' performance, organ morphometry or in their occurrence of diarrhea. However, a quadratic effect on the villus width and a cubic effect on the villus height:crypt depth ratio were observed in the duodenum. Therefore, if the determined values of energy are used in the feed formulation, refined soybean oil can be replaced with semi-refined rice oil in weanling pig diets without affecting their growth performance. (C) 2011 Elsevier B.V. All rights reserved.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma

Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

Background: Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. Methods: Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology. Results: Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity. Conclusions: Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.