Total flow intensity, active flow intensity and volume related flow intensity as new quantitative metrics in optical coherence tomography angiography

Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal

Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine

Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-hours later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system

Isomorphisms of algebras of Colombeau generalized functions

We show that for smooth manifolds X and Y, any isomorphism between the special algebra of Colombeau generalized functions on X, resp. Y is given by composition with a unique Colombeau generalized function from Y to X. We also identify the multiplicative linear functionals from the special algebra of Colombeau generalized functions on X to the ring of Colombeau generalized numbers. Up to multiplication with an idempotent generalized number, they are given by an evaluation map at a compactly supported generalized point on X.Comment: 10 page

Lymph node metastases displaying lower Ki-67 immunostaining activity than the primary breast cancer

The aim of the study was to verify by Ki-67 immunostaining if any difference exists in the cell proliferating fraction between primary breast tumors (PTs) and matching positive axillary lymph nodes (ALNs). PATIENTS AND METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 160 node-positive breast carcinomas and in their respective lymph node metastases. RESULTS: An increase of Ki-67 immunoreactive cells in ALN compared with that of PTs was observed in 84% of cases (ALN: mean 17%, PTs: mean 8%; p < 0.001), whereas 16% of the cases showed Ki-67 value two to six times lower in the ALNs than in the corresponding PTs (ALN: mean 3.2%, PTs mean 12.5%; p < 0.005). The decrease of Ki-67 positive cells in the ALN was independent from the histotype and the histological grade of the tumor. CONCLUSION: A different cell proliferation fraction between PTs and matching positive ALNs was demonstrated and underlined that the existence of a group of patients with decreased number of Ki-67 immunoreactive cells in lymph node metastases compared with that of the primary tumors could be taken into account in the choice of therapeutic strategy

Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas