Depressive symptoms and glycated hemoglobin A1c: A reciprocal relationship in a prospective cohort study

Background The aim of this study was to evaluate the dynamic association between depressive symptoms and glycated hemoglobin A1c (HbA1c) levels using data from the English Longitudinal Study of Ageing (ELSA). Method The sample was comprised of 2886 participants aged ≥50 years who participated in three clinical assessments over an 8-year period (21% with prediabetes and 7% with diabetes at baseline). Structural equation models were used to address reciprocal associations between depressive symptoms and HbA1c levels and to evaluate the mediating effects of lifestyle-related behaviors and cardiometabolic factors. Results We found a reciprocal association between depressive symptoms and HbA1c levels: depressive symptoms at one assessment point predicted HbA1c levels at the next assessment point (standardized β = 0.052) which in turn predicted depressive symptoms at the following assessment point (standardized β = 0.051). Mediation analysis suggested that both lifestyle-related behaviors and cardiometabolic factors might mediate the association between depressive symptoms and HbA1c levels: depressive symptoms at baseline predicted lifestyle-related behaviors and cardiometabolic factors at the next assessment, which in turn predicted HbA1c levels 4 years later. A similar association was observed for the other direction: HbA1c levels at baseline predicted lifestyle-related behaviors and cardiometabolic factors at the next assessment, which in turn predicted depressive symptoms 4 years later. Conclusions Our results suggest a dynamic relationship between depressive symptoms and HbA1c which might be mediated by both lifestyle and cardiometabolic factors. This has important implications for investigating the pathways which could link depressive symptoms and increased risk of diabetes.ELSA is funded by the US National Institute on Aging (NIA) and a consortium of UK Government departments. N.S. was supported by grants from the Canadian Institutes of Health Research (MOP-84574 and MOP-130552). S.D. is supported by a fellowship from the Fonds de recherche du Québec – Santé, Canada and R.B. is supported by a fellowship from the Canadian Institutes of Health Research.ELSA is funded by the US National Institute on Aging (NIA) and a consortium of UK Government departments. N.S. was supported by grants from the Canadian Institutes of Health Research (MOP-84574 and MOP-130552). S.D. is supported by a fellowship from the Fonds de recherche du Québec – Santé, Canada and R.B. is supported by a fellowship from the Canadian Institutes of Health Research

Expression of phospho-ERK1/2 and PI3-K in benign and malignant gallbladder lesions and its clinical and pathological correlations

Abstract Background An increasing number of studies have shown that ERK and PI3-K/AKT signaling pathways are involved in various human cancers including hepatocellular carcinoma and cholangiocarcinoma. However, few studies have examined gallbladder cancer specimens, and little is known about the clinical and pathological significance of ERK1/2 and PI3-K/AKT signaling changes in gallbladder adenocarcinoma. In this study, we examined phospho-ERK1/2 (p-ERK1/2) and PI3K expression and analyzed its clinicopathological impact in gallbladder adenocarcinoma. Methods Immunohistochemistry was used to detect and compare the frequency of p-ERK1/2 and PI3-K expression in gallbladder adenocarcinoma, peri-tumor tissues, adenomatous polyps, and chronic cholecystitis specimens. Results The positive staining for p-EKR1/2 and PI3-K were 63/108 (58.3%) and 55/108 (50.9%) in gallbladder adenocarcinoma; 14/46 (30.4%) and 5/46 (10.1%) in peri-tumor tissues; 3/15 (20%) and 3/15 (20%) in adenomatous polyps; and 4/35 (11.4%) and 3/35 (8.6%) in chronic cholecystitis. The positive rate of p-ERK1/2 or PI3-K in gallbladder adenocarcinoma was significantly higher than that in peri-tumor tissue (both, P P P P P P P P = 0.062) was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased p-ERK1/2 expression was an independent prognostic predictor in gallbladder carcinoma (P = 0.028). Conclusion Increased expression of p-ERK1/2 and PI3K might contribute to gallbladder carcinogenesis. p-ERK1/2 over-expression is correlated with decreased survival and therefore may serve as an important biological marker in development of gallbladder adenocarcinoma.</p

Schwannoma-like pleomorphic adenoma of the parotid

Pleomorphic adenoma is the most common benign salivary gland tumour. It can occur in any salivary gland, but is most frequently found in the parotid gland. Chondroid metaplasia is a frequent finding in pleomorphic adenoma. Other forms of metaplasia have been described, but are encountered less frequently. We report a rare case of unusual pleomorphic adenoma of the parotid gland with schwannoma-like feature

Treating breast cancer through novel inhibitors of the phosphatidylinositol 3'-kinase pathway

Recent studies indicate that constitutive signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is a cause of treatment resistance in breast cancer patients. This implies that patients with tumors that exhibit aberrant PI3K signaling may benefit from targeted pathway inhibitors. The first agents to make it to the clinic are the rapamycin analogs. These compounds inhibit the downstream PI3K effector mTOR (mammalian target of rapamycin). A study presented in this issue of Breast Cancer Research suggests that recently developed inhibitors of phosphoinositide-dependent protein kinase 1, a more proximal target of the PI3K pathway, may provide an alternative route to effective PI3K pathway inhibition for breast cancer treatment

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

'SOSORT consensus paper on brace action: TLSO biomechanics of correction (investigating the rationale for force vector selection)'

BACKGROUND: The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies. Heterogeneity of the samples has been suggested as a reason for conflicting results. Besides the obvious theoretical differences between the brace concepts, the variability in the technical factors can also explain the contradictory results between same brace types. This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT. Ultimately, this information could be a foundation for establishing a consensus and framework for future prospective controlled studies. METHODS: A preliminary questionnaire on the topic of 'brace action' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis. A particular case was presented (main thoracic curve with minor lumbar). Several key points emerged and were used to develop a second questionnaire which was discussed and full filed after the SOSORT consensus meeting (Milano, Italy, January 2005). RESULTS: Twenty-one questionnaires were completed. The Chêneau brace was the most frequently recommended. The importance of the three point system mechanism was stressed. Options about proper pad placement on the thoracic convexity were divided 50% for the pad reaching or involving the apical vertebra and 50% for the pad acting caudal to the apical vertebra. There was agreement about the direction of the vector force, 85% selecting a 'dorso lateral to ventro medial' direction but about the shape of the pad to produce such a force. Principles related to three-dimensional correction achieved high consensus (80%–85%), but suggested methods of correction were quite diverse. CONCLUSION: This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment. If the goal of a 'treatment consensus' is realistic and achievable, significantly more effort will be required to reconcile these differences

Imaging of Flaws in Solids by Velocity Inversion

We describe the application of a method for ultrasonic imaging of flaws in solids. These methods greatly extend earlier work along these lines at Rockwell and the Langenberg group in Germany, see [1,2,3,4,5,6,7,8,9,10]. The new inversion methods allow reflector imaging and parameter estimation in progressively more complex media with progressively more realistic source/receiver configurations. This research has been carried out in the context of seismic exploration. However, the problems are sufficiently similar that these more realistic models have direct counterparts in nondestructive testing [11,12,13,14,15,16,17]. In particular, both problems are high frequency inverse scattering problems. High frequency means that the wavelengths are much smaller (by a factor of three or more) than the other length scales of the problem.</p

Exceptionally Preserved Cambrian Trilobite Digestive System Revealed in 3D by Synchrotron-Radiation X-Ray Tomographic Microscopy

The Cambrian ‘Orsten’ fauna comprises exceptionally preserved and phosphatised microscopic arthropods. The external morphology of these fossils is well known, but their internal soft-tissue anatomy has remained virtually unknown. Here, we report the first non-biomineralised tissues from a juvenile polymerid trilobite, represented by digestive structures, glands, and connective strands harboured in a hypostome from the Swedish ‘Orsten’ fauna. Synchrotron-radiation X-ray tomographic microscopy enabled three-dimensional internal recordings at sub-micrometre resolution. The specimen provides the first unambiguous evidence for a J-shaped anterior gut and the presence of a crop with a constricted alimentary tract in the Trilobita. Moreover, the gut is Y-shaped in cross section, probably due to a collapsed lumen of that shape, another feature which has not previously been observed in trilobites. The combination of anatomical features suggests that the trilobite hypostome is functionally analogous to the labrum of euarthropods and that it was a sophisticated element closely integrated with the digestive system. This study also briefly addresses the preservational bias of the ‘Orsten’ fauna, particularly the near-absence of polymerid trilobites, and the taphonomy of the soft-tissue-harbouring hypostome

Metabolite Profiling of Alzheimer's Disease Cerebrospinal Fluid

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine