Identification of infants at high‐risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks

Autism spectrum disorder (ASD) is a wide range of disabilities that cause life‐long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for identifying high‐risk ASD infants at as early as six months after birth. This is based on the observation that ASD‐induced abnormalities in white matter (WM) tracts and whole‐brain connectivity have already started to appear within 24 months after birth. In particular, we propose a novel multikernel support vector machine classification framework by using the connectivity features gathered from WM connectivity networks, which are generated via multiscale regions of interest (ROIs) and multiple diffusion statistics such as fractional anisotropy, mean diffusivity, and average fiber length. Our proposed framework achieves an accuracy of 76% and an area of 0.80 under the receiver operating characteristic curve (AUC), in comparison to the accuracy of 70% and the AUC of 70% provided by the best single‐parameter single‐scale network. The improvement in accuracy is mainly due to the complementary information provided by multiparameter multiscale networks. In addition, our framework also provides the potential imaging connectomic markers and an objective means for early ASD diagnosis. Hum Brain Mapp 36:4880–4896, 2015. © 2015 Wiley Periodicals, Inc .     

Filtration leukapheresis: effects of donor stimulation with dexamethasone

Dexamethasone was administered to 51 donors prior to filtration leukapheresis. The results of this maneuver, including the consequences of transfusion, were contrasted with results in 52 donors who did not receive the steroid. Yields of polymorphonuclear leukocytes, the posttransfusion increments in recipients, themorphologic polymorphonuclear leukocytes obtained, and the incidence of donor and recipient reactions were all beneficially influenced by this manipulation. Possible mechanisms responsible for these observations are discussed. It is recommended that dexamethasone stimulation be used in filtration leukapheresis when circumstances do not otherwise contraindicate such a maneuver.     

Periodontal parameters and BANA test in patients with chronic renal failure undergoing hemodialysis

Objectives

The aim of this study was to analyze the periodontal parameters of patients with chronic renal failure.

Material and Methods

The periodontal status of 16 Brazilian patients aged 29 to 53 (41.7±7.2) years with chronic renal failure (CRF) and another matched group of 14 healthy controls with periodontitis was assessed clinically and microbiologically. Probing pocket depth (PPD), gingival recession (GR), dental plaque index (PLI), gingival index (GI), and dental calculus index (CI) were the clinical parameters recorded for the entire dentition (at least 19 teeth), while the anaerobic periodontopathogen colonization in four sites with the highest PPD was evaluated using the BANA test (“PerioScan”; Oral B).

Results

The results for the CRF group and control group, respectively were: PPD: 1.77±0.32 and 2.65±0.53; GR: 0.58±0.56 and 0.51±0.36; PLI: 1.64±0.56 and 1.24±0.67; GI: 0.64±0.42 and 0.93±0.50; CI: 1.17±0.54 and 0.87±0.52. Comparison between groups using the "t" test revealed a significantly increased PPD (p<0.001) in the control group. Comparison of the other clincial parameters by the Mann-Whitney test showed differences only for PLI, which was significantly higher (p<0.05) in the CRF group. Spearman''s test applied to each group showed a positive correlation among all clinical parameters, except for GR (p<0.05). None of the groups showed any correlation between GR and GI, while a significant negative correlation between GR and PPD was observed for the CRF group. The percentage of BANA-positive sites was 35.9% for the CRF group and 35.7% for the control group. The BANA test correlated positively with PPD only in the control group and with GR only in the CRF group.

Conclusions

In spite of a higher PLI and dense anaerobic microbial population even in shallow PPD, patients with CRF exhibited better periodontal conditions than periodontitis patients, which is an evidence of altered response to local irritants.     

Groupwise registration based on hierarchical image clustering and atlas synthesis

Groupwise registration has recently been proposed for simultaneous and consistent registration of all images in a group. Since many deformation parameters need to be optimized for each image under registration, the number of images that can be effectively handled by conventional groupwise registration methods is limited. Moreover, the robustness of registration is at stake due to significant intersubject variability. To overcome these problems, we present a groupwise registration framework, which is based on a hierarchical image clustering and atlas synthesis strategy. The basic idea is to decompose a large‐scale groupwise registration problem into a series of small‐scale problems, each of which is relatively easy to solve using a general computer. In particular, we employ a method called affinity propagation, which is designed for fast and robust clustering, to hierarchically cluster images into a pyramid of classes. Intraclass registration is then performed to register all images within individual classes, resulting in a representative center image for each class. These center images of different classes are further registered, from the bottom to the top in the pyramid. Once the registration reaches the summit of the pyramid, a single center image, or an atlas, is synthesized. Utilizing this strategy, we can efficiently and effectively register a large image group, construct their atlas, and, at the same time, establish shape correspondences between each image and the atlas. We have evaluated our framework using real and simulated data, and the results indicate that our framework achieves better robustness and registration accuracy compared to conventional methods. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington's disease

Background and purpose:

The therapeutic potential of cannabinoids in Huntington''s disease (HD) has been investigated by several groups with complex and sometimes contrasting results. We sought to examine key points of intersection between cannabinoid receptor 1 (CB₁) signalling, survival and the formation of mutant huntingtin aggregates in HD.

Experimental approach:

Using a simplified pheochromocytoma (PC12) cell model of HD expressing exon 1 of wild-type or mutant huntingtin, we assayed cell death and aggregate formation using high-throughput cytotoxicity and image-based assays respectively.

Key results:

CB₁ activation by HU210 conferred a small but significant level of protection against mutant huntingtin-induced cell death. Pertussis toxin uncoupled HU210 from the inhibition of cAMP, preventing rescue of cell death. Phosphorylation of extracellular signal-regulated kinase (ERK) was also critical to CB₁-mediated rescue. Conversely, treatments that elevated cAMP exacerbated mutant huntingtin-induced cell death. Despite opposing effects on HD cell survival, both HU210 and compounds that elevated cAMP increased the formation of mutant huntingtin aggregates. The increase in aggregation by HU210 was insensitive to Pertussis toxin and UO126, suggesting a G-protein alpha subtype s (G_s)-linked mechanism.

Conclusions and implications:

We suggest that the CB₁ receptor, through G-protein alpha subtype i/o (G_i/o)-linked, ERK-dependent signal transduction, is a therapeutic target in HD. However the protective potential of CB₁ may be limited by promiscuous coupling to G_s, the stimulation of cAMP formation and increased aggregate formation. This may underpin the poor therapeutic efficacy of cannabinoids in more complex model systems and suggest that therapies that are selective for the G_i/o, ERK pathway may be of most benefit in HD.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x     

生物标志物与非小细胞肺癌治疗结局相关

血管内皮生长因子（VEGF）和可溶性VEGF受体2（sVEGFR-2）由VEGF通路抑制因子所调控,化疗、VEGFR抑制剂或两者联合治疗是否可引起细胞因子和血管生成因子（CAFs）的改变,而这些改变是否又能预示临床获益？     

Femoral Neck Trabecular Bone: Loss With Aging and Role in Preventing Fracture

Hip fracture risk rises 100‐ to 1000‐fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression. In a buckle, the cortex moves approximately at right angles to the direction of load, thereby distorting its microstructure, eventually to the point of disintegration. By resisting buckling movement, trabecular buttressing would protect the femoral neck cortex against this type of failure but not against crushing. We quantified the effect of aging on trabecular BMD in the femoral neck and assessed its contribution to cortical elastic stability, which determines resistance to buckling. Using CT, we measured ex vivo the distribution of bone in the midfemoral necks of 35 female and 33 male proximal femurs from cases of sudden death in those 20–95 yr of age. We calculated the critical stress σ_cr, at which the cortex was predicted to buckle locally, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall. Using long‐established engineering principles, we estimated the amount by which stability or buckling resistance was increased by the trabecular bone supporting the most stressed cortical sector in each femoral neck. We repeated these measurements and calculations in an age‐ and sex‐matched series of femoral necks donated by women who had suffered intracapsular hip fracture and controls, using histological measurements of cortical thickness to improve accuracy. With normal aging, trabecular BMD declined asymmetrically, fastest in the supero‐lateral one‐half (in antero‐posterior projection) of the trabecular compartment. When viewed axially with respect to the femoral neck, the most rapid loss of trabecular bone occurred in the posterior part of this region (supero‐posterior [S‐P]), amounting to a 42% reduction in women (34% in men) over five decades of adult age. Because local cortical bone thickness declined comparably, age had no significant effect on the relative contributions of cortical and trabecular bone to elastic stability, and trabecular bone was calculated to contribute 40% (in men) and 43% (in women) to the S‐P cortex of its overall elastic stability. Hip fracture cases had reduced elastic stability compared with age‐matched controls, with a median reduction of 49% or 37%, depending on whether thickness was measured histologically or by CT (pQCT; p < 0.002 for both). This effect was because of reduced cortical thickness and density. Trabecular BMD was similar in hip fracture cases and controls. The capacity of the femur to resist fracture in a sideways fall becomes compromised with normal aging because cortical thickness and trabecular BMD in the most compressed part of the femoral neck both decline substantially. This decline is relatively more rapid than that of femoral neck areal BMD. If elastic instability rather than cortical crushing initiates the fracture event, interventions that increase trabecular bone in the proximal femur have great potential to reduce fracture risk because the gradient defining the increase in elastic stability with increasing trabecular BMD is steep, and most hip fracture cases have sufficient trabecular bone for anabolic therapies to build on.