The role of ultrasound in breast screening

Ultrasound is a valuable diagnostic tool commonly used by Radiologists in breast screening. The current paper outlines the main functions that Ultrasound performs, differences between mammography and Ultrasound and why it is a topic worthy of ergonomic and psychological research. Finally, a summary of the various methodological approaches to studying Ultrasound usage and interpretation are outlined which will be used to inform the development of a new Ultrasound training application to be used by trainee radiologists

Calculation of the pole-face windings compensation at injection

<div><p>Background</p><p>Hydrogen sulfide (H₂S), produced by the activity of cystathionine-gamma-lyase (CSE), is a key mediator of inflammation in sepsis. The liver sinusoidal endothelial cells (LSECs) are important target and mediator of sepsis. The aim of this study was to investigate the role of CSE-derived H₂S on inflammation and LSECs fenestrae in caecal-ligation and puncture (CLP)-induced sepsis using CSE KO mice.</p><p>Methods</p><p>Sepsis was induced by CLP, and mice (C57BL/6J, male) were sacrificed after 8 hours. Liver, lung, and blood were collected and processed to measure CSE expression, H₂S synthesis, MPO activity, NF-κB p65, ERK1/2, and cytokines/chemokines levels. Diameter, frequency, porosity and gap area of the liver sieve were calculated from scanning electron micrographs of the LSECs.</p><p>Results</p><p>An increased CSE expression and H₂S synthesizing activity in the liver and lung of wild-type mice following CLP-induced sepsis. This was associated with an increased liver and lung MPO activity, and increased liver and lung and plasma levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and the chemokines MCP-1 and MIP-2α. Conversely, CSE KO mice had less liver and lung injury and reduced inflammation following CLP-induced sepsis as evidenced by decreased levels of H₂S synthesizing activity, MPO activity, and pro-inflammatory cytokines/chemokines production. Extracellular-regulated kinase (ERK1/2) and nuclear factor-κB p65 (NF-κB) became significantly activated after the CLP in WT mice but not in CSE KO mice. In addition, CLP-induced damage to the LSECs, as indicated by increased defenestration and gaps formation in the LSECs compared to WT sham control. CSE KO mice showed decreased defenestration and gaps formation following sepsis.</p><p>Conclusions</p><p>Mice with CSE (an H₂S synthesising enzyme) gene deletion are less susceptible to CLP-induced sepsis and associated inflammatory response through ERK1/2-NF-κB p65 pathway as evidenced by reduced inflammation, tissue damage, and LSECs defenestration and gaps formation.</p></div

CSE Protein Expression and H₂S-Synthesizing Activity Following CLP Induced Sepsis.

<p>(A-B) Liver CSE protein expression and (C-D) lung CSE protein expression. Liver and lung CSE protein expression was increased following CLP induced sepsis compared to sham control (liver: P<0.001 vs. sham control; lung P<0.01 vs. sham control) and no CSE protein expression was detected in CSE KO mice. Results were normalized with GAPDH and expressed as the relative fold increase of CSE protein expression compared with sham control. For western blot results, each lane represents a separate animal. The blots shown were representative of all animals in each group with similar results. (E) Liver H₂S synthesizing activity. H₂S synthesizing activity was increased following increased CSE protein expression in WT CLP induced sepsis mice compared to sham controls and CSE KO mice had significantly lower H₂S synthesizing activity compared to WT sepsis mice. Data represent the mean±standard deviation (n = 8). Data were analysed for Gaussian or Normal distribution using Shapiro-Wilk test. One-way ANOVA with post hoc Tukey’s test was performed to compare multiple groups. Statistical significance was assigned as *P<0.05; **P<0.01; ***P<0.001; and ****P<0.0001.</p

Effect of CSE Gene Deletion on Liver and Lung MPO Activity and Organ Injury in Mice Following CLP Induced Sepsis.

<p>(A) Liver MPO activity and (B) Lung MPO activity. Following CLP induced sepsis, liver and lung MPO activity levels were increased in WT sepsis mice compared to sham operation controls. CSE gene deletion decreased significantly liver and lung MPO activity following CLP induced sepsis compared to WT sepsis mice. Results were expressed as the relative fold increase of MPO activity compared with sham operation controls. (C) Representative images of the liver H&E sections revealed extensive capsular inflammation and lobular necrosis in CLP induced sepsis in the WT mice compared to sham control. The CSE KO mice showed a lower capsular inflammation and lobular necrosis. (D) Representative images of the lung H&E sections. Histological examination of the lung sections reveal marked leukocyte infiltration and alveolar thickening following CLP induced sepsis in the WT mice compared to sham operation controls. This effect was substantially reduced in the CLP induced CSE KO mice. Scale bar is 50 μm. Data represent the mean±standard deviation (n = 8). Data were analysed for Gaussian or Normal distribution using Shapiro-Wilk test. Liver and lung MPO activity data were analysed using One-way ANOVA with post hoc Tukey’s test whereas liver and lung histology scores were analysed with non-parametric Kruskal-Wallis test to compare multiple groups. Statistical significance was assigned as *P<0.05; and **P<0.01.</p

Effect of CSE Gene Deletion on Lung Pro-inflammatory Cytokines and Chemokines.

<p>(A) Lung TNF-α, (B) Lung IL-6, (C) Lung IL-1β, (D) Lung MCP-1 and (E) Lung MIP-2α. CLP induced sepsis significantly increased the lung cytokines TNF-α (P<0.05), IL-6 (P<0.001) and IL-1β (P<0.001) and the chemokines MCP-1 (P<0.001) and MIP-2α (P<0.01) in WT mice compared to sham operation controls. Knockdown of the CSE gene protects mice against lung injury by reducing pro-inflammatory TNF-α (P<0.01), IL-6 (P<0.05), IL-1β (P<0.05), MCP-1 (P<0.05) and MIP-2α (P<0.05) following CLP induced sepsis compared to WT sepsis mice. Results were expressed in ng/mg of protein. Data represent the mean±standard deviation (n = 8). Data were analysed for Gaussian or Normal distribution using Shapiro-Wilk test. One-way ANOVA with post hoc Tukey’s test was performed to compare multiple groups. Statistical significance was assigned as *P<0.05; **P<0.01: and ***P<0.001.</p

Effect of CLP Induced Sepsis and CSE Gene Deletion on Liver Sieve Injury in Mice.

<p>(A) Representative images of the LSECs micrographs of scanning electron microscopy of perfusion fixed liver sections after 8 hours CLP or sham operation (voltage and magnification: 15kV x15000; n = 8) and (B) Average graph area in the LSECs. Scanning electron microscopy studies revealed that LSECs injury was increased following 8 hours CLP surgery in WT mice as evidenced by increased gaps formation in LSECs. CSE KO mice had significantly fewer gaps compared to WT sepsis mice. Data represent the mean±standard deviation (n = 8). Data were analysed for Gaussian or Normal distribution using Shapiro-Wilk test. One-way ANOVA with post hoc Tukey’s test was performed to compare multiple groups. Statistical significance was assigned as ****P<0.0001.</p

Effect of CSE Gene Deletion on Liver Pro-inflammatory Cytokine and Chemokine Levels Following CLP Induced Sepsis.

<p>(A) Liver TNF-α, (B) Liver IL-6, (C) Liver IL-1β, (D) Liver MCP-1 and (E) Liver MIP-2α. CLP induced sepsis significantly increased the liver cytokines TNF-α (P<0.05), IL-6 (P<0.05) and IL-1β (P<0.0001) and the chemokines MCP-1 (P<0.0001) and MIP-2α (P<0.0001) in WT mice compared to sham operation controls. Knockdown of the CSE gene protects mice against liver injury by reducing pro-inflammatory TNF-α (P<0.01), IL-6 (P<0.01), IL-1β (P<0.05), MCP-1 (P<0.01) and MIP-2α (P<0.001) following CLP induced sepsis compared to WT sepsis mice. Results were expressed in ng/mg of protein. Data represent the mean±standard deviation (n = 8). Data were analysed for Gaussian or Normal distribution using Shapiro-Wilk test. One-way ANOVA with post hoc Tukey’s test was performed to compare multiple groups. Statistical significance was assigned as *P<0.05; **P<0.01: ***P<0.001; and ****P<0.0001.</p