Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFq. Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyms. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD. (C) 2011 Elsevier B.V. All rights reserved.

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children`s growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling. The trials were registered at www.clinicaltrials.gov as #NCT00598481 and #NCT00599781. (Blood. 2009; 114: 3216-3226)

Analysis of placenta vascularization in patients with uterine altered artery Doppler flow velocity exams

Background: One of the frequent questions in obstetric practice is to determine placental vascular changes that may account for abnormal Doppler flow velocity alterations in maternal uterine vessels from women and fetuses without pregnancy pathology. Methods: A retrospective morphometric study was realized using 27 placentas from patients submitted for Doppler flow velocity exam during pregnancy. The placentas were morphologically examined using hematoxylin-eosin staining. Measurements of villi were made with the use of a video camera coupled to a common light microscope and a computer with automatic image analyzing software. Results: Of the 27 placentas, 13 (48%) were of patients showing unaltered Doppler and 14 (52%) showing altered Doppler. The number of stem villi vessels was significantly larger in the placentas of patients with Doppler exam alterations (P = 0.003). This group also presented greater stem villi vessel thickness, although without significant difference. The number of intermediary and terminal villi vessels was greater in the placentas of patients with altered Doppler exams (P < 0.001), and a greater terminal villi area was observed in these cases (P < 0.001). Conclusion: The morphological proof that uterine artery Doppler flow velocity exam alterations are associated with placental vascular alterations demonstrates the importance of this exam during prenatal care, even in the absence of maternal-fetal alterations.

The Stability of the Blood Oxygenation Level-Dependent Functional MRI Response to Motor Tasks Is Altered in Patients With Chronic Ischemic Stroke

Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)

Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.

Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues

Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

Bacterial Adhesion on Smooth and Rough Titanium Surfaces After Treatment With Different Instruments

Background: Newly formed biofilm after implant debridement may challenge the long-term stability of peri-implant therapy. This in vitro study aimed to assess the roughness and adherence of Streptococcus sanguinis after treatment of smooth and rough titanium surfaces with an erbium-doped: yttrium, aluminum, and garnet (Er:YAG) laser, metal and plastic curets, and an air-powder abrasive system. Methods: Forty titanium disks with smooth-machined surfaces and 40 with sand-blasted and acid-etched surfaces were divided into the following treatment groups: Er:YAG laser; plastic curet; metal curet, and air-powder abrasive system. The surface roughness (roughness average [Raj) before and after treatments was determined using a profilometer. S. sanguinis (American Type Culture Collection 10556) was grown on treated and untreated specimens, and the amounts of retained bacteria on the surfaces were measured by the culture method. Rough and smooth surfaces with and without a suspension of S. sanguinis were also analyzed using scanning electron microscopy (SEM). Results: For smooth surfaces, the roughest surfaces were produced by metal curets (repeated - measures analysis of variance [ANOVA] and Tukey test; P<0.05). The rough-surface profile was not altered by any of the treatments (repeated-measures ANOVA; P>0.05). Rough surfaces treated with metal curets and air-powder abrasion showed the lowest level of bacteria] adhesion (two-way ANOVA and Tukey test; P<0.05). SEM analysis revealed distinct surface profiles produced by all devices. Conclusions: Metal curets are not recommended for smooth titanium surface debridement due to severe texture alteration. Rough surfaces treated with a metal curet and the air-powder abrasive system were less susceptible to bacterial adhesion, probably due to texture modification and the presence of abrasive deposits. J Periodontol 2009;80: 1824-1832.

Altered beta-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip

beta-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of beta-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of beta-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using beta-catenin antibody. beta-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for beta-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of beta-catenin on studied cases point to pathway alterations. Results demonstrated that beta-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations. (C) 2011 Elsevier Inc. All rights reserved.