Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Dislodgement resistance of calcium silicate-based materials from root canals with varying thickness of dentine.

AIM: To evaluate the dislodgement resistance of DiaRoot BioAggregate and Biodentine from canals in roots with varying amounts of remaining dentine thickness. METHODOLOGY: A total of 90 maxillary incisor teeth with similar dimensions were used. The teeth were extracted for periodontal reasons from adult subjects aged between 52 and 61 years. They were decoronated at the cemento-enamel junction. Simulated internal cavities with a depth of 3 mm were performed by widening the canals on the coronal thirds of the roots, leaving varying amounts of remaining dentine thickness. The canals were enlarged progressively using round diamond burs until the desired dentine wall thickness was obtained. The samples were divided into three main groups (n = 30 each) according to the dentine thickness as follows: group 1: dentine thickness of 0.75 mm, group 2: dentine thickness of 1.50 mm and group 3: dentine thickness of 2.25 mm. Then, these main groups were further divided into two subgroups (n = 15 each) according to the filling material (DiaRoot BioAggregate or Biodentine). Horizontal root slices of 1 mm were obtained from each specimen. Vertical loading was applied to the filling materials at a cross-head speed of 1 mm min-1 using a universal testing machine. The force that led to dislodgement of the filling was recorded in Newtons. The resistance to dislodgement was calculated in megapascals (MPa) by dividing the load in Newtons by the area of the bonded interface. The data were statistically analysed with two-way anova with Tukey's honestly significant difference (HSD) test. RESULTS: Biodentine had significantly higher resistance to dislodgement than DiaRoot BioAggregate (P < 0.001). The specimens with thinner remaining dentine had lower dislodgement resistance compared to those with dentine thicknesses of 1.50 and 2.25 mm (P < 0.001). The lowest mean value for dislodgement resistance was obtained from the DiaRoot BioAggregate group with 0.75 mm dentine thickness (2.72 ± 0.90 MPa). CONCLUSION: The dislodgement resistance of Biodentine and DiaRoot BioAggregate from root dentine was influenced by remaining dentine thickness, which determines dentinal tubular density.

Iatrogenic or fracture-related nerve injuries in supracondylar humerus fracture: is treatment necessary for nerve injury?

BACKGROUND: Supracondylar humerus fractures are very common types of elbow fractures in children between the ages of three and ten years. Totally displaced supracondylar humerus fractures can be associated with neurovascular injuries, and treatment can be complicated by iatrogenic neurovascular injury, compartment syndrome, malunion, and elbow stiffness. AIM: The aim of this study was to describe the clinical outcome of nerve injuries associated with supracondylar humerus fractures in children observed over a period of seven years. PATIENTS AND METHODS: Children with displaced supracondylar humerus fracture who were treated with closed reduction and percutaneous cross K-wire fixation were reviewed retrospectively at the Medical School Hospital of Yuzuncu Yil University from May 2004 to October 2012. RESULTS: There were 91 patients available for follow-up. Nerve injury was observed in 11 (12.1%) of 91 patients with supracondylar humerus fractures. In 10 (90.1%) of these 11 cases, nerve functions recovered completely (excellent outcome) and in one (9.9%) case partial recovery was seen (good outcome). CONCLUSIONS: Iatrogenic or fracture-related nerve injury in a supracondylar humerus fracture is a benign condition which may be resolved spontaneously and observation appears to be a good and valuable method for treatment of this complication.

The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

Thrombopoietic cytokines in patients with iron deficiency anemia with or without thrombocytosis.

Iron deficiency anemia is a cause of reactive thrombocytosis. A moderate increase in platelet numbers is common but sometimes counts may exceed 1,000 x 10(9)/l. The mechanisms causing reactive thrombocytosis are unclear. In this study, we evaluated 15 women with iron deficiency anemia and thrombocytosis (platelets >450 x 10(9)/l) and 16 women with iron deficiency anemia with normal platelet counts. Serum samples were taken before oral iron replacement therapy, after 1 and 3 months and at the end of replacement therapy. Thrombopoietin, erythropoietin (EPO), leukemia inhibitory factor, interleukin-6 and interleukin-11 levels were assayed. There was no change in the levels of thrombopoietic cytokines except for EPO. The correlation between high EPO levels and high platelet counts may suggest that EPO increases platelet counts, but the same EPO level changes can also be demonstrated in women with iron deficiency anemia but normal initial platelet counts. The fact that the levels of other cytokines remained unchanged during treatment suggests that either these cytokines have no effect on reactive thrombocytosis or the change in platelet counts in our patients is in a narrow range and is thus not affected by the cytokine levels.

Age and origin of carlsbad cavern and related caves from 40Ar/39Ar of alunite

40Ar/39Ar dating of fine-grained alunite that formed during cave genesis provides ages of formation for the Big Room level of Carlsbad Cavern [4.0 to 3.9 million years ago (Ma)], the upper level of Lechuguilla Cave (6.0 to 5.7 Ma), and three other hypogene caves (11.3 to 6.0 Ma) in the Guadalupe Mountains of New Mexico. Alunite ages increase and are strongly correlative with cave elevations, which indicates an 1100-meter decline in the water table, apparently related to tectonic uplift and tilting, from 11.3 Ma to the present. 40Ar/39Ar dating studies of the hypogene caves have the potential to help resolve late Cenozoic climatic, speleologic, and tectonic questions.

The underlying cellular mechanism of fibrosis.

Fibrosis is a common sequela of various exogenous insults to a variety of parenchymal tissues. The underlying mechanisms of the induction and progression of fibrosis both at the molecular and cellular level have not been clarified so far. In the present study the cellular processes that ultimately may lead to interstitial fibrosis are described using the model of radiation-induced terminal differentiation in the fibroblast/fibrocyte cell system. The data reported herein will provide evidence that exogenously induced changes in the proliferation and differentiation pattern of the fibroblast/fibrocyte cell system based on either autocrine and/or paracrine mediators represent the underlying cellular mechanism of fibrosis. Using co-culture systems of parenchymal cells (fibroblasts and type II pneumocytes), the intercellular communication via cytokines, which may lead to fibrosis have been studied. TGF beta 1 could be described as one key modulator of these cellular processes.

Montmorillonite: electron-optical observations.

Fine-grained micas are consistent impurities in Camp-Berteaux (Morocco) and Wyoming montmorillonities. These micas give selected-area electron diffraction spot patterns with triclinic, monoclinic, and hexagonal symmetries similar tO those reported previously for monmorillonites. Camp-Berteaux montmorillonite appears as folded and flexible polycrystalline aggregates with pronounced texturing along the [02],[11], and[1i] directions. Wyoming montmorillonite displays better crystallinity and larger crystallite size, and its structure is no longer truly "turbostratic".