Lipin expression is attenuated in adipose tissue of insulin-resistant human subjects and increases with peroxisome proliferator-activated receptor gamma activation

Lipin-alpha and -beta are the alternatively spliced gene products of the Lpin1 gene, whose product lipin is required for adipocyte differentiation. Lipin deficiency causes lipodystrophy, fatty liver, and insulin resistance in mice, whereas adipose tissue lipin overexpression results in increased adiposity but improved insulin sensitivity. To assess lipin expression and its relation to insulin resistance in humans, we examined lipin-alpha and -beta mRNA levels in subjects with normal or impaired glucose tolerance. We found higher expression levels of both lipin isoforms in lean, insulin-sensitive subjects. When compared with normal glucose-tolerant subjects, individuals with impaired glucose tolerance were more insulin resistant, demonstrated higher levels of intramyocellular lipids (IMCLs), and expressed approximately 50% lower levels of lipin-alpha and -beta. In addition, there was a strong inverse correlation between adipose tissue lipin expression and muscle IMCLs but no evidence for an increase in muscle lipid oxidation. After treatment of the impaired glucose-tolerant subjects with insulin sensitizers for 10 weeks, pioglitazone (but not metformin) resulted in a 60% increase in the insulin sensitivity index (Si) and a 32% decrease in IMCLs (both P < 0.01), along with an increase in lipin-beta (but not lipin-alpha) expression by 200% (P < 0.005). Lipin expression in skeletal muscle, however, was not related to obesity or insulin resistance. Hence, high adipose tissue lipin expression is found in insulin-sensitive subjects, and lipin-beta expression increases following treatment with pioglitazone. These results suggest that increased adipogenesis and/or lipogenesis in subcutaneous fat, mediated by the LPIN1 gene, may prevent lipotoxicity in muscle, leading to improved insulin sensitivity.     

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy

Background Context

Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy.

Cholestatic pruritus: a retrospective analysis on clinical characteristics and treatment response

Background: Chronic cholestatic pruritus (ChP) is caused by various hepatobiliary disorders. This retrospective study describes the distribution of underlying diseases, clinical characteristics and treatment efficacy in a consecutive collective of patients with ChP. Patients and methods: Extensive data from 60 patients with ChP (30 women, 30 men; mean age: 58.0 ± 17.0 years) were retrospectively statistically analyzed concerning demographic data, pruritus characteristics, and response to therapy. Results: In this study population, 40.0% of the patients suffered from hepatitis B or C. Regarding the overall population, pruritus started in 50% of patients after diagnosis of the underlying hepatobiliary disorder. Only in patients with immune‐mediated liver diseases did pruritus more often occur before diagnosis (p < 0.05). Only 23.3% of the patients reported an initial palmoplantar pruritus. Along with other drugs, anticonvulsants proved to be an effective treatment regime. Conclusions: In this study, viral pathogenesis was the most common cause of ChP. Other underlying diseases were represented to a lower extent in the total study population. Overall, the collected clinical parameters in each group were comparable. Thus, it was difficult to draw conclusions on the pathogenesis.     

Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices

BACKGROUND: Keloid scars represent a pathological response to cutaneous injury. Overproliferation of fibroblasts and overproduction of collagen characterize these abnormal scars. The pathology of these scars remains poorly understood. The role of epithelial-mesenchymal interactions in keloid pathogenesis and scar contracture has recently been explored. OBJECTIVES: To test our hypothesis that epithelial-mesenchymal interactions play a major role in modulating keloid scar contracture. METHODS: A coculture model was employed wherein keloid and normal keratinocytes were cocultured with keloid or normal fibroblasts, and the conditioned media from day 5 cocultures were collected to study the effect of the paracrine secretions on contraction of an in vitro fibroblast-populated collagen lattice (FPCL) model. RESULTS: Keloid keratinocyte/keloid fibroblast coculture conditioned media brought about increased contraction of the collagen lattice compared with non-cocultured conditioned media. When keloid fibroblasts populated the collagen lattice, significantly increased lattice contraction was induced compared with lattices populated by normal fibroblasts. The addition of antitransforming growth factor (TGF)-beta neutralizing antibody to the conditioned media produced an attenuation of the contraction of the FPCLs. When keloid and normal fibroblasts were cultured on chamber slides and treated with conditioned media from coculture and non-coculture series, immunohistochemical analysis demonstrated an increased expression of alpha-smooth muscle actin (a marker for fibroblast differentiation into myofibroblasts) in fibroblasts exposed to conditioned media from coculture. CONCLUSIONS: These data indicate that epithelial-mesenchymal interactions are likely to play a major role in scar contracture and scar pathogenesis, and underscore the role of TGF-beta1 as a key player in keloid pathogenesis.     

Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts

The pulmonary circulation represents a unique vascular bed, receiving 100% of the cardiac output while maintaining low blood pressure. Multiple different cell types, including endothelium, smooth muscle, and fibroblasts, contribute to normal vascular function, and to the vascular response to injury. Our understanding of the basic cell biology of these various cell types, and the roles they play in vascular homeostasis and disease, remains quite limited despite several decades of study. Recent advances in approaches that enable the mapping of cell origin and the study of the molecular basis of structure and function have resulted in a rapid accumulation of new information that is essential to vascular biology. A recent National Institutes of Health workshop was held to discuss emerging concepts in lung vascular biology. The findings of this workshop are summarized in this article.     

Highly sensitive p-type 4H-SiC van der Pauw sensor

This paper presents for the first time a p-type 4H silicon carbide (4H-SiC) van der Pauw strain sensor by utilizing the strain induced effect in four-terminal devices. The sensor was fabricated from a 4H-SiC (0001) wafer, using a 1 μm thick p-type epilayer with a concentration of 10¹⁸ cm⁻³. Taking advantage of the four-terminal configuration, the sensor can eliminate the need for resistance-to-voltage conversion which is typically required for two-terminal devices. The van der Pauw sensor also exhibits an excellent repeatability and linearity with a significantly large output voltage in induced strain ranging from 0 to 334 ppm. Various sensors aligned in different orientations were measured and a high sensitivity of 26.3 ppm⁻¹ was obtained. Combining these performances with the excellent mechanical strength, electrical conductivity, thermal stability, and chemical inertness of 4H-SiC, the proposed sensor is promising for strain monitoring in harsh environments.

This paper presents for the first time a p-type 4H silicon carbide (4H-SiC) van der Pauw strain sensor by utilizing the strain induced effect in four-terminal devices.