Enzyme activity and electrophoretic pattern of isoenzymes of amylase, catalase and peroxidase in photo- and gibberellin-induced plants of Impatiens balsamina L. var. rose

Floral buds were induced either by 8 h photoperiods or by the application of GA3 and GA13 in Impatiens balsamina. Total enzyme activity was not directly related to floral morphogenesis although some interesting qualitative correlations existed. Thus, the presence of a new isoenzyme of amylase (RF 0·05) may be related to flower formation since it was present only in the induced plants and not in the vegetative ones, regardless of whether the flowering was caused by inductive photoperiods or by gibberellin treatment. Catalase activity, as well as its isoenzyme forms, could not be detected in the stem and the isoenzyme profile in leaves did not alter with photoperiodic or gibberellin treatment. Treatment with gibberellins induced the synthesis of new isoenzymes of peroxidase but inductive photoperiods did not. The enzyme profiles in relation to photoperiod and gibberellin application are discussed

Aging display's effect on interpretation of digital pathology slides

It is our conjecture that the variability of colors in a pathology image effects the interpretation of pathology cases, whether it is diagnostic accuracy, diagnostic confidence, or workflow efficiency. In this paper, digital pathology images are analyzed to quantify the perceived difference in color that occurs due to display aging, in particular a change in the maximum luminance, white point, and color gamut. The digital pathology images studied include diagnostically important features, such as the conspicuity of nuclei. Three different display aging models are applied to images: aging of luminance & chrominance, aging of chrominance only, and a stabilized luminance & chrominance (i.e., no aging). These display models and images are then used to compare conspicuity of nuclei using CIE deltaE2000, a perceptual color difference metric. The effect of display aging using these display models and images is further analyzed through a human reader study designed to quantify the effects from a clinical perspective. Results from our reader study indicate significant impact of aged displays on workflow as well as diagnosis as follow. As compared to the originals (no-aging), slides with the effect of aging simulated were significantly more difficult to read (p-value of 0.0005) and took longer to score (p-value of 0.02). Moreover, luminance+chrominance aging significantly reduced inter-session percent agreement of diagnostic scores (p-value of 0.0418)

Biomarkers differentiate drug-induced liver injury from other liver injury: PONDER study

Background and Aim: Drug-induced liver injury (DILI) is a known complication of volatile anesthetic (VA) agents, and, despite being rare, DILI can be serious. One mechanism of VA-DILI occurs via interleukin 4 (IL-4)driven upregulation of cytochrome P450-2E1, leading to the formation of drug metabolites (haptens) that trigger IL-4-driven antigen-specific T cells and autoantibodies. Our group has developed biomarkers for liver injury and have examined this in patients before and after VA exposure. The aim of this prospective study was to determine the early markers of VA-DILI. Methods: We prospectively followed patients having a VA general anesthetic (sevoflurane and/or desflurane) and compared them with those who received regional or total intravenous anesthesia. Exclusion criteria were known liver disease or any episode of significant hypotension. Baseline data on patient demographics and comorbidities were collected, and blood was analyzed for liver biochemistry, macrophage activation markers (CD206, CD163), and IgG1 and IgG4 antibodies to JHDN5 (the CYP2E1 epitope) and trifluoroacetyl (TFA), the VA drug hapten. Follow-up blood samples were taken 48 h postoperatively and compared with baseline results. DILI was defined as an alanine aminotransferase (ALT) level greater than two times the upper limit of normal (ULN) and post-review agreement by an expert panel, taking into account the pattern of liver function test result derangement and intraoperative events. Results: Of 229 patients recruited, 16 developed an ALT level > 2 × ULN. Twelve were considered likely to have VA-DILI, including four with an ALT rise >3 × ULN. There was a trend to associate VA-DILI with obesity (RR, 2.98; P = 0.063); however, the association with dyslipidemia (RR, 1.47; P = 0.72), male sex (RR, 1.18; P = 0.76), history of atopy (RR, 1.16; P = 0.79), and heavy ethanol consumption (RR, 1.09; P = 0.89) was not statistically significant. Prior VA exposure was not a risk factor (RR, 0.89; P = 0.83). There was a rise in CD206 and decline in CD163 from baseline in all patients. However, in the patients with VA-DILI, the levels were significantly different from all other groups. TFA IgG1 and IgG4 antibodies were elevated in the VA-DILI group when compared with controls. Conclusion: Recognizing that our results may be skewed by our cohort, this work suggests the known immunological pathway mediated by IL-4 in response to an injury: rise in CD206 to stimulate an inflammatory response, and decrease in CD163 to modulate the response. The increase in TFA IgG1 and IgG4 antibodies in the VA-DILI group is consistent with metabolism and the heightened immune response in those who develop DILI. At this early juncture, JHDN5 IgG4 autoantibodies were not detected. Ongoing work is looking at other DILI, and how these markers can be used in DILI

Synthesis and antiinflammatory activity of some 3-(2-thiazolyl)-1 ,2-benzisothiazoles

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Characterization of a submicro-X-ray fluorescence setup on the B16 beamline at Diamond Light Source

An X-ray fluorescence setup has been tested on the B16 beamline at the Diamond Light Source synchrotron with two different excitation energies (12.7 and 17 keV). This setup allows the scanning of thin samples (thicknesses up to several micrometers) with a sub-micrometer resolution (beam size of 500 nm × 600 nm determined with a 50 µm Au wire). Sensitivities and detection limits reaching values of 249 counts s−1 fg−1 and 4 ag in 1000 s, respectively (for As Kα excited with 17 keV), are presented in order to demonstrate the capabilities of this setup. Sample measurements of a human bone and a single cell performed at B16 are presented in order to illustrate the suitability of the setup in biological applications.</jats:p

Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study

Copyright \ua9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.Background: Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreement between readers, estimated linear weighted kappas between 2 panels, compared them with published pairwise kappa estimates, and addressed how agreement or disagreement might impact the precision and validity of the surrogate efficacy endpoint in NASH trials. Methods: Two panels, each comprising 3 liver fellowship-trained pathologists who underwent NASH histology training, independently evaluated scanned whole slide images, scoring fibrosis, inflammation, hepatocyte ballooning, and steatosis from baseline and month 18 biopsies for 100 patients from the precirrhotic NASH study REGENERATE. The consensus score for each parameter was defined as agreement by ≥2 pathologists. If consensus was not reached, all 3 pathologists read the slide jointly to achieve a consensus score. Results: Between the 2 panels, the consensus was 97%-99% for steatosis, 91%-93% for fibrosis, 88%-92% for hepatocyte ballooning, and 84%-91% for inflammation. Linear weighted kappa scores between panels were similar to published NASH CRN values. Conclusions: A panel of 3 trained pathologists independently scoring 4 NASH CRN histology parameters produced high consensus rates. Interpanel kappa values were comparable to NASH CRN metrics, supporting the accuracy and reproducibility of this method. The high concordance for fibrosis scoring was reassuring, as fibrosis is predictive of liver-specific outcomes and all-cause mortality

Precision scans of the pixel cell response of double sided 3D pixel detectors to pion and x-ray beams

hree-dimensional (3D) silicon sensors offer potential advantages over standard planar sensors for radiation hardness in future high energy physics experiments and reduced charge-sharing for X-ray applications, but may introduce inefficiencies due to the columnar electrodes. These inefficiencies are probed by studying variations in response across a unit pixel cell in a 55μm pitch double-sided 3D pixel sensor bump bonded to TimePix and Medipix2 readout ASICs. Two complementary characterisation techniques are discussed: the first uses a custom built telescope and a 120GeV pion beam from the Super Proton Synchrotron (SPS) at CERN; the second employs a novel technique to illuminate the sensor with a micro-focused synchrotron X-ray beam at the Diamond Light Source, UK. For a pion beam incident perpendicular to the sensor plane an overall pixel efficiency of 93.0±0.5% is measured. After a 10o rotation of the device the effect of the columnar region becomes negligible and the overall efficiency rises to 99.8±0.5%. The double-sided 3D sensor shows significantly reduced charge sharing to neighbouring pixels compared to the planar device. The charge sharing results obtained from the X-ray beam study of the 3D sensor are shown to agree with a simple simulation in which charge diffusion is neglected. The devices tested are found to be compatible with having a region in which no charge is collected centred on the electrode columns and of radius 7.6±0.6μm. Charge collection above and below the columnar electrodes in the double-sided 3D sensor is observed

Transseptal puncture for left atrial ablation: Risk factors for cardiac tamponade and a proposed causative classification system

AIMS: Cardiac tamponade is a high morbidity complication of transseptal puncture (TSP). We examined the associations of TSP‐related cardiac tamponade (TRCT) for all patients undergoing left atrial ablation at our center from 2016 to 2020. METHODS AND RESULTS: Patient and procedural variables were extracted retrospectively. Cases of cardiac tamponade were scrutinized to adjudicate TSP culpability. Adjusted multivariate analysis examined predictors of TRCT. A total of 3239 consecutive TSPs were performed; cardiac tamponade occurred in 51 patients (incidence: 1.6%) and was adjudicated as TSP‐related in 35 (incidence: 1.1%; 68.6% of all tamponades). Patients of above‐median age [odds ratio (OR): 2.4 (1.19–4.2), p = .006] and those undergoing re‐do procedures [OR: 1.95 (1.29–3.43, p = .042] were at higher risk of TRCT. Of the operator‐dependent variables, choice of transseptal needle (Endrys vs. Brockenbrough, p > .1) or puncture sheath (Swartz vs. Mullins vs. Agilis vs. Vizigo vs. Cryosheath, all p > .1) did not predict TRCT. Adjusting for operator, equipment and demographics, failure to cross the septum first pass increased TRCT risk [OR: 4.42 (2.45–8.2), p = .001], whilst top quartile operator experience [OR: 0.4 (0.17–0.85), p = .002], transoesophageal echocardiogram [TOE prevalence: 26%, OR: 0.51 (0.11–0.94), p = .023], and use of the SafeSept transseptal guidewire [OR: 0.22 (0.08–0.62), p = .001] reduced TRCT risk. An increase in transseptal guidewire use over time (2016: 15.6%, 2020: 60.2%) correlated with an annual reduction in TRCT (R (2) = 0.72, p < .001) and was associated with a relative risk reduction of 70%. CONCLUSIONS: During left atrial ablation, the risk of TRCT was reduced by operator experience, TOE‐guidance, and use of a transseptal guidewire, and was increased by patient age, re‐do procedures, and failure to cross the septum first pass

Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

<p>Abstract</p> <p>Background</p> <p>We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.</p> <p>Methods</p> <p>Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.</p> <p>Results</p> <p>Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.</p> <p>Conclusion</p> <p>Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.</p