High-resolution DCE-MRI of the pituitary gland using radial k-space acquisition with compressed sensing reconstruction

BACKGROUND AND PURPOSE: The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS: A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with goldenangle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS: Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS: This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging

Ocular changes in primary hypothyroidism

<p>Abstract</p> <p>Background</p> <p>To determine the ocular changes related to hypothyrodism in newly diagnosed patients without orbitopathy.</p> <p>Findings</p> <p>Thirty-three patients diagnosed to have primary overt hypothyroidism were enrolled in the study. All subjects were assigned to underwent central corneal thickness (CCT), anterior chamber volume, depth and angle measurements with the Scheimpflug camera (Pentacam, Oculus) and cup to disc ratio (C/D), mean retinal thickness and mean retinal nerve fiber layer (RNFL) thickness measurements with optical coherence tomography (OCT) in addition to ophthalmological examination preceeding the replacement therapy and at the 1^st, 3^rdand 6^thmonths of treatment.</p> <p>The mean age of the patients included in the study were 40.58 ± 1.32 years. The thyroid hormone levels return to normal levels in all patients during the follow-up period, however the mean intraocular pressure (IOP) revealed no significant change. The mean CCT was 538.05 ± 3.85 μ initially and demonstrated no statistically significant change as the anterior chamber volume, depth and angle measurements did. The mean C/D ratio was 0.29 ± 0.03 and the mean retinal thickness was 255.83 ± 19.49 μ initially and the treatment did not give rise to any significant change. The mean RNFL thickness was also stable during the control visits, so no statistically significant change was encountered.</p> <p>Conclusions</p> <p>Neither hypothyroidism, nor its replacement therapy gave rise to any change of IOP, CCT, anterior chamber parameters, RNFL, retinal thickness and C/D ratio.</p

Link Mining for Kernel-based Compound-Protein Interaction Predictions Using a Chemogenomics Approach

Virtual screening (VS) is widely used during computational drug discovery to reduce costs. Chemogenomics-based virtual screening (CGBVS) can be used to predict new compound-protein interactions (CPIs) from known CPI network data using several methods, including machine learning and data mining. Although CGBVS facilitates highly efficient and accurate CPI prediction, it has poor performance for prediction of new compounds for which CPIs are unknown. The pairwise kernel method (PKM) is a state-of-the-art CGBVS method and shows high accuracy for prediction of new compounds. In this study, on the basis of link mining, we improved the PKM by combining link indicator kernel (LIK) and chemical similarity and evaluated the accuracy of these methods. The proposed method obtained an average area under the precision-recall curve (AUPR) value of 0.562, which was higher than that achieved by the conventional Gaussian interaction profile (GIP) method (0.425), and the calculation time was only increased by a few percent

Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity.

hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP

Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C\u3eT polymorphism in non-small cell lung carcinoma

BACKGROUND: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC. METHODS: Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP. RESULTS: We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders. CONCLUSIONS: Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function

The role of disulfide bond replacements in analogues of the Tarantula toxin ProTx-II and their effects on inhibition of the voltage-gated sodium ion channel Nav1.7

Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Nav1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues. We have also investigated the folding and disulfide bridging patterns arising from different methods of oxidation of the linear peptide precursor. Finally, we report the X-ray crystal structure of ProTx-II to atomic resolution; to our knowledge this is the first crystal structure of an ICK spider venom peptide not bound to a substrate

Prognostic significance of early recurrence: a conditional survival analysis in patients with resected colorectal liver metastasis

AbstractBackgroundFor patients undergoing liver resection for colorectal metastases, specific clinico‐pathological variables have been shown to be prognostic at baseline. This study analyses how the prognostic capability of these variables changes in a conditional survival model.MethodsRetrospective review of a prospectively maintained database of patients who underwent an R0 resection of colorectal liver metastases from 1994 to 2004 at a single institution.ResultsIn total, 807 patients were identified, with an 87‐month median follow‐up for survivors. Five‐ and 10‐year disease‐specific survivals (DSS) were 68% and 55%, respectively. The probability of further survival increased as the survival time increased. For 3‐year survivors (n = 504), DSS were no longer significantly different between patients with a low (0–2) or high (3–5) clinical risk score (CRS, P = 0.19). On multivariate analysis, independent predictors of DSS for 3‐year survivors were recurrence within the first 3 years after a liver resection, a pre‐operative carcinoembryonic antigen (CEA) >200 ng/ml and disease‐free interval <12 months prior to the diagnosis of liver metastasis. However, for those patients who were recurrence free at 1 year, no clinico‐pathological variables retained prognostic significance.DiscussionAfter 3 years of DSS and 1 year of recurrence‐free survival, baseline clinico‐pathological variables have a limited ability to predict future survival. Early post‐operative recurrence appears to be the most useful single clinical feature in estimating conditional DSS