Potential neural embedding of parental social standing

Socioeconomic disadvantage during childhood and adolescence predicts poor mental and physical health and premature death by major medical diseases in adulthood. However, the neural pathways through which socioeconomic factors may exert a developmental influence on health and longevity remain largely unknown. This fMRI study provides novel evidence of a unique relationship between the perception that one's parents had a relatively low social standing--a putative indicator of early socioeconomic disadvantage--and greater amygdala reactivity to threatening facial expressions. This relationship was not explained by several possible confounders, including sex, ethnicity, dispositional emotionality, symptoms of depression and anxiety, parental education and participants' perceptions of their own social standing. The amygdala expresses marked developmental plasticity and plays instrumental roles in processing emotional information, regulating emotion-related behaviors and orchestrating biobehavioral stress responses throughout life. Thus, these findings may provide insight into the neurodevelopmental pathways impacting socioeconomic disparities in health.     

Association between amygdala reactivity and a dopamine transporter gene polymorphism

Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [¹⁵O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.     

Fabrication of a three-dimensional temporomandibular joint model for arthrocentesis and arthroscopy simulation

Arthrocentesis and arthroscopy are relatively safe treatments for arthrogenic temporomandibular disorders. Hands-on training in both procedures is essential for surgeons to become competent. In this study, a three-dimensional (3D) temporomandibular joint (TMJ) prototype was developed at a relatively low cost, and arthrocentesis and arthroscopy were performed successfully on the model. Despite its limitations, this model is a viable adjunct to TMJ surgical training and can be fabricated easily by any training centre with a 3D printer.     

Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum

Background

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder with considerable phenotypic variability, mainly affects the eyes, skin and cardiovascular system, characterised by dystrophic mineralization of connective tissues. It is caused by mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance‐associated protein 6).

Objective

To investigate the mutation spectrum of ABCC6 and possible genotype–phenotype correlations.

Methods

Mutation data were collected on an international case series of 270 patients with PXE (239 probands, 31 affected family members). A denaturing high‐performance liquid chromatography‐based assay was developed to screen for mutations in all 31 exons, eliminating pseudogene coamplification. In 134 patients with a known phenotype and both mutations identified, genotype–phenotype correlations were assessed.

Results

In total, 316 mutant alleles in ABCC6, including 39 novel mutations, were identified in 239 probands. Mutations were found to cluster in exons 24 and 28, corresponding to the second nucleotide‐binding fold and the last intracellular domain of the protein. Together with the recurrent R1141X and del23–29 mutations, these mutations accounted for 71.5% of the total individual mutations identified. Genotype–phenotype analysis failed to reveal a significant correlation between the types of mutations identified or their predicted effect on the expression of the protein and the age of onset and severity of the disease.

Conclusions

This study emphasises the principal role of ABCC6 mutations in the pathogenesis of PXE, but the reasons for phenotypic variability remain to be explored.     

Genetic variants affecting the neural processing of human facial expressions: evidence using a genome-wide functional imaging approach

Human faces present crucial visual information for social interaction. Specialized brain regions are involved in the perception of faces, with the fusiform face area (FFA) a key neuronal substrate. Face processing is genetically controlled, but by which specific genes is unknown. A genome-wide approach identified common single nucleotide polymorphisms (SNPs) associated with areas of increased brain activity in response to affective facial expressions, measured with functional magnetic resonance imaging. SNPs in 20 genetic regions were linked with neural responses to negative facial expressions in a Norwegian sample (n=246), which included patients with mental illness. Three genetic regions were linked with FFA activation in a further discovery experiment using positive facial expressions and involving many of the same individuals (n=284). Two of these three regions showed significant association with right FFA activation to negative facial expressions in an independent North American replication sample of healthy Caucasians (n=85, 3q26.31, P=0.004; 20p12.3, P=0.045). The activation patterns were particularly striking for the SNP in 3q26.31, which lies in a gene TMEM212; only the FFA was activated. The specialized function of this brain region suggests that TMEM212 could contribute to the innate architecture of face processing.     

Feasibility of optical coherence tomography imaging to characterize renal neoplasms: limitations in resolution and depth of penetration

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Optical coherence tomography has been used for the diagnosis of retinal disease and has been used experimentally for imaging of vascular plaques, gastrointestinal pathology, bladder cancer, prostate cancer, and recently to examine benign kidney microanatomy. It has not been previously used to image kidney cancer. This study presents the first data on the utility of OCT in the imaging for renal neoplasms. It found that OCT was most successful in distinguishing AML and TCC from normal parenchyma. OCT had more limited success at differentiating oncocytoma. Clear cell tumors and other renal cancer subtypes had a more heterogenous appearance, precluding reliable identification using OCT. The study shows that higher resolution versions of OCT, such as OCM, will be needed to allow optical coherence imaging to reach clinical utility in the assessment of renal neoplasms.

OBJECTIVEs

? To determine the appearance of normal and neoplastic renal tissue when imaged with optical coherence tomography (OCT). ? To preliminarily assess the feasibility of using OCT to differentiate normal and neoplastic renal tissue.

PATIENTS AND METHODS

? After radical or partial nephrectomy in 20 subjects, normal renal parenchyma and neoplastic tissue samples were obtained. ? The tissue was evaluated with light microscopy and using a bench‐top laboratory OCT system with a lateral resolution of 10 µm. ? OCT images were compared with histological slides to evaluate the ability of OCT to differentiate renal neoplasms.

RESULTS

? Pathological subtypes included eight clear‐cell, three papillary and two chromophobe renal carcinomas; two oncocytomas; one angiomyolipoma (AML); two transitional cell carcinomas (TCCs); and one haematoma. ? Using OCT, benign renal parenchyma showed recognizable glomeruli and tubules. ? TCC had a distinctive appearance on OCT whereas AML showed a unique identifiable signature because of its fat content. Oncocytomas had a lobulated appearance, which appeared subtly different from renal carcinoma. ? Renal carcinoma lacked recognizable anatomical elements and had a heterogeneous appearance making differentiation from normal parenchyma at times difficult. ? Subtypes of renal cancer appeared to vary on OCT imaging although discrimination was unreliable.

CONCLUSIONS

? OCT imaging for renal neoplasms was most successful in distinguishing AML and TCC from normal parenchyma and malignant tumours. Oncocytoma differed subtly from renal carcinoma, making distinction more challenging. ? Clear‐cell tumours and other renal carcinoma subtypes had a heterogeneous appearance on OCT, which precluded reliable differentiation from normal parenchyma and between renal carcinoma subtypes. ? Higher resolution versions of optical coherence imaging, such as optical coherence microscopy, will be necessary to achieve clinical utility.     

Is bariatric surgery effective for co-morbidity resolution in the super-obese patients?

Background

Type 2 diabetes (T2D), obstructive sleep apnea (OSA), hypertension (HTN), and hyperlipidemia (HLD) are common co-morbidities that are strongly associated with obesity.