Pseudocirrhosis: A Case Series with Clinical and Radiographic Correlation and Review of the Literature.

BACKGROUND AND AIMS: Pseudocirrhosis is a poorly understood acquired morphologic change of the liver that occurs in the setting of metastatic malignancy and radiographically resembles cirrhosis. Pseudocirrhosis has been primarily described in metastatic breast carcinoma, with few case reports arising from other primary malignancies. We present 29 cases of pseudocirrhosis, including several cases from primary malignancies not previously described. METHODS: Radiologic, clinical, demographic, and biomedical data were collected retrospectively and analyzed. We compared clinical and radiologic characteristics and outcomes between patients with pseudocirrhosis arising in metastatic breast cancer and non-breast primary malignancies. RESULTS: Among the 29 patients, 14 had breast cancer and 15 had non-breast primaries including previously never reported primaries associated with pseudocirrhosis, melanoma, renal cell carcinoma, appendiceal carcinoid, and cholangiocarcinoma. Median time from cancer diagnosis to development of pseudocirrhosis was 80.8 months for patients with primary breast cancer and 29.8 months for non-breast primary (p = 0.02). Among all patients, 15 (52%) had radiographic features of portal hypertension. Radiographic evidence of portal hypertension was identified in 28.6% of breast cancer patients, compared to 73.3% of those with non-breast malignancies (p = 0.03). CONCLUSION: Pseudocirrhosis has most commonly been described in the setting of metastatic breast cancer but occurs in any metastatic disease to the liver. Our study suggests that portal hypertensive complications are more common in the setting of non-breast primary cancers than in metastatic breast cancer. Prior exposure to multiple chemotherapeutic agents, and agents known to cause sinusoidal injury, is a common feature but not essential for the development of pseudocirrhosis.

DIAGNOSTIC PATTERNS OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize prevalence estimates by race, age, sex, and comorbidity (diabetes and hypertension) within the Medicare beneficiary demographic. METHODS: In this US population-based retrospective cohort analysis, the Vision and Eye Health Surveillance System was analyzed for a 100% sample of Medicare Fee-For-Service beneficiary populations of Asians and non-Hispanic Whites between 2014 and 2018. Exclusionary criteria included beneficiaries younger than 40 years. Prevalence rate ratios, defined as prevalence rate for Asians divided by prevalence rate for non-Hispanic Whites, were calculated using multivariate negative binomial regression or Pearson-scaled Poisson regression, stratified by age, sex, and comorbidity. RESULTS: A total of 21,892,200 Medicare beneficiaries fulfilled the inclusionary criteria in 2018. Of the entire cohort, 3.2% of the beneficiaries (N = 714,500) were Asian. For beneficiaries aged 40 to 64 years, Asian male (prevalence rate ratios 1.73, 95% confidence interval 1.64-1.83, P < 0.0001) and female (prevalence rate ratios 1.34, 95% confidence interval 1.28-1.41, P < 0.0001) beneficiaries had an increased prevalence rate of all age-related macular degeneration relative to non-Hispanic Whites. Significant time-wise increases in prevalence rate ratios were observed within several age groups, sexes, and comorbidities (race-time interaction coefficients P < 0.05 ). CONCLUSION: This analysis highlights increased age-related macular degeneration prevalence estimates within the Asian American demographic relative to non-Hispanic Whites. Furthermore, specific Asian subpopulations are experiencing accelerated prevalence rates over time.

Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

Cardiolipin-deficient cells have decreased levels of the iron-sulfur biogenesis protein frataxin.

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays an important role in mitochondrial bioenergetics. Previous studies in the yeast model have indicated that CL is required for optimal iron homeostasis, which is disrupted by a mechanism not yet determined in the yeast CL mutant, crd1Δ. This finding has implications for the severe genetic disorder, Barth syndrome (BTHS), in which CL metabolism is perturbed because of mutations in the CL-remodeling enzyme, tafazzin. Here, we investigate the effects of tafazzin deficiency on iron homeostasis in the mouse myoblast model of BTHS tafazzin knockout (TAZ-KO) cells. Similarly to CL-deficient yeast cells, TAZ-KO cells exhibited elevated sensitivity to iron, as well as to H2O2, which was alleviated by the iron chelator deferoxamine. TAZ-KO cells exhibited increased expression of the iron exporter ferroportin and decreased expression of the iron importer transferrin receptor, likely reflecting a regulatory response to elevated mitochondrial iron. Reduced activities of mitochondrial iron-sulfur cluster enzymes suggested that the mechanism underlying perturbation of iron homeostasis was defective iron-sulfur biogenesis. We observed decreased levels of Yfh1/frataxin, an essential component of the iron-sulfur biogenesis machinery, in mitochondria from TAZ-KO mouse cells and in CL-deleted yeast crd1Δ cells, indicating that the role of CL in iron-sulfur biogenesis is highly conserved. Yeast crd1Δ cells exhibited decreased processing of the Yfh1 precursor upon import, which likely contributes to the iron homeostasis defects. Implications for understanding the pathogenesis of BTHS are discussed.

Shape and texture-based radiomics signature on CT effectively discriminates benign from malignant renal masses.

OBJECTIVES: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model. MATERIALS AND METHODS: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC. RESULTS: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively. CONCLUSION: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics. KEY POINTS: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

ENDOPHTHALMITIS AFTER TRANSCONJUNCTIVAL PARS PLANA VITRECTOMY: A 6-year Experience Without Prophylactic Intraoperative Subconjunctival Antibiotics.

PURPOSE: This study aimed to investigate the incidence and risk factors of endophthalmitis after transconjunctival pars plana vitrectomy (PPV) without intraoperative subconjunctival antibiotics. DESIGN: Retrospective, consecutive case series at a single institution. METHODS: Consecutive cases of transconjunctival 25-gauge PPV without intraoperative subconjunctival antibiotics performed by three retina surgeons at a single surgical site at the Dean McGee Eye Institute from 2012 to 2018 were reviewed. RESULTS: Of 4,263 cases of PPV without intraoperative subconjunctival antibiotics, five cases (0.117%, 5/4,263) of post-PPV endophthalmitis were identified. Of these five cases, four cases (80%, 4/5) received combined cataract extraction or secondary intraocular lens implantation at the time of PPV. The incidence of endophthalmitis in isolated PPV was 0.027% (1/3,606 cases), whereas the incidence in combined PPV with anterior segment procedures was 0.608% (4/657 cases). Risk factors for endophthalmitis included diabetes mellitus, which was present in 80% of patients with endophthalmitis (4/5 cases). Causative organisms were identified in four of the five cases (80%), including Staphylococcus epidermidis (N = 3) and Propionibacterium acnes (N = 1). CONCLUSION: Performing transconjunctival PPV alone with standard preparation using povidone-iodine and postoperative topical antibiotics for 1 week without intraoperative subconjunctival antibiotics did not lead to an increase in incidence of postoperative endophthalmitis (1 per 3,606 cases).

Identification of robust and reproducible CT-texture metrics using a customized 3D-printed texture phantom.

OBJECTIVE: The objective of this study was to evaluate the robustness and reproducibility of computed tomography-based texture analysis (CTTA) metrics extracted from CT images of a customized texture phantom built for assessing the association of texture metrics to three-dimensional (3D) printed progressively increasing textural heterogeneity. MATERIALS AND METHODS: A custom-built 3D-printed texture phantom comprising of six texture patterns was used to evaluate the robustness and reproducibility of a radiomics panel under a variety of routine abdominal imaging protocols. The phantom was scanned on four CT scanners (Philips, Canon, GE, and Siemens) to assess reproducibility. The robustness assessment was conducted by imaging the texture phantom across different CT imaging parameters such as slice thickness, field of view (FOV), tube voltage, and tube current for each scanner. The texture panel comprised of 387 features belonging to 15 subgroups of texture extraction methods (e.g., Gray-level Co-occurrence Matrix: GLCM). Twelve unique image settings were tested on all the four scanners (e.g., FOV125). Interclass correlation two-way mixed with absolute agreement (ICC3) was used to assess the robustness and reproducibility of radiomic features. Linear regression was used to test the association between change in radiomic features and increased texture heterogeneity. Results were summarized in heat maps. RESULTS: A total of 5612 (23.2%) of 24 090 features showed excellent robustness and reproducibility (ICC ≥ 0.9). Intensity, GLCM 3D, and gray-level run length matrix (GLRLM) 3D features showed best performance. Among imaging variables, changes in slice thickness affected all metrics more intensely compared to other imaging variables in reducing the ICC3. From the analysis of linear trend effect of the CTTA metrics, the top three metrics with high linear correlations across all scanners and scanning settings were from the GLRLM 2D/3D and discrete cosine transform (DCT) texture family. CONCLUSION: The choice of scanner and imaging protocols affect texture metrics. Furthermore, not all CTTA metrics have a linear association with linearly varying texture patterns.

Coalescence, Partial Coalescence, and Noncoalescence of an Aqueous Drop at an Oil-Water Interface under an Electric Field.

Drop-interface interaction under an electric field is relevant in commercial desalters wherein water droplets suspended in oil coalesce under an electric field, move down under gravity, and eventually coalesce with the water pool at the bottom of the desalter. In this work, we report our observation that the transition from coalescence to partial coalescence can be described by a critical electrocapillary number and is independent of the Ohnesorge number. On the other hand, the partial coalescence to noncoalescence transition depends upon both the electrocapillary number and the Ohnesorge number. The bridge during partial coalescence exhibits an electrocapillary-number-independent growth and collapse dynamics, although the transition time for growth to collapse depends upon the electrocapillary number (CaE). Lastly, contrary to previous studies, our results indicate that the secondary droplet size varies as CaE3/2 unlike the CaE1/2 reported in the literature.

Remarkable decrease in the viscosity of waxy crude oil under an electric field.

Uninterrupted transport of waxy crude oil through pipelines remains a pressing concern for the petroleum industry. When the ambient temperature falls below the pour point of the crude, deposition of wax particles may lead to complete blockage of the pipeline. We demonstrate that the application of a DC electric field to waxy crude below its pour point can effectively break the wax network and also reduce the viscosity by up to two orders of magnitude. We have studied the dynamics of the change in viscosity during and after application of an electric field. Three regimes are observed. First is the induction regime, where viscous stresses dominate and the viscosity remains unchanged. During the intermediate and final regimes, the decrease in viscosity follows first order kinetics with rate constants proportional to the strength of the electric field and to the square of the strength, respectively. Microscopic evidence shows that some network connections break during the intermediate regime, whereas in the final regime, further fragmentation of the pieces of the broken network occurs. This is accompanied by aggregation of fine wax fragments. After cessation of the field, the viscosity increases gradually. The rate and the extent of recovery of viscosity depend only on the value of viscosity at the point of cessation of the field. That the breakage of the network occurs, even in the absence of shear, has been demonstrated. Through measurement of the dielectric constants and conductivities of the crude oil and its component phases, we have shown that the wax network experiences compressive Maxwell stress, which is dominated by the electric field within the wax particles.

Texture Analysis of Imaging: What Radiologists Need to Know.

OBJECTIVE: Radiologic texture is the variation in image intensities within an image and is an important part of radiomics. The objective of this article is to discuss some parameters that affect the performance of texture metrics and propose recommendations that can guide both the design and evaluation of future radiomics studies. CONCLUSION: A variety of texture-extraction techniques are used to assess clinical imaging data. Currently, no consensus exists regarding workflow, including acquisition, extraction, or reporting of variable settings leading to poor reproducibility.

Reliability of CT-based texture features: Phantom study.

OBJECTIVE: To determine the intra-, inter- and test-retest variability of CT-based texture analysis (CTTA) metrics. MATERIALS AND METHODS: In this study, we conducted a series of CT imaging experiments using a texture phantom to evaluate the performance of a CTTA panel on routine abdominal imaging protocols. The phantom comprises of three different regions with various textures found in tumors. The phantom was scanned on two CT scanners viz. the Philips Brilliance 64 CT and Toshiba Aquilion Prime 160 CT scanners. The intra-scanner variability of the CTTA metrics was evaluated across imaging parameters such as slice thickness, field of view, post-reconstruction filtering, tube voltage, and tube current. For each scanner and scanning parameter combination, we evaluated the performance of eight different types of texture quantification techniques on a predetermined region of interest (ROI) within the phantom image using 235 different texture metrics. We conducted the repeatability (test-retest) and robustness (intra-scanner) test on both the scanners and the reproducibility test was conducted by comparing the inter-scanner differences in the repeatability and robustness to identify reliable CTTA metrics. Reliable metrics are those metrics that are repeatable, reproducible and robust. RESULTS: As expected, the robustness, repeatability and reproducibility of CTTA metrics are variably sensitive to various scanner and scanning parameters. Entropy of Fast Fourier Transform-based texture metrics was overall most reliable across the two scanners and scanning conditions. Post-processing techniques that reduce image noise while preserving the underlying edges associated with true anatomy or pathology bring about significant differences in radiomic reliability compared to when they were not used. CONCLUSION: Following large-scale validation, identification of reliable CTTA metrics can aid in conducting large-scale multicenter CTTA analysis using sample sets acquired using different imaging protocols, scanners etc.

Differentiation of Predominantly Solid Enhancing Lipid-Poor Renal Cell Masses by Use of Contrast-Enhanced CT: Evaluating the Role of Texture in Tumor Subtyping.

OBJECTIVE: The purpose of this study was to assess the accuracy of a panel of texture features extracted from clinical CT in differentiating benign from malignant solid enhancing lipid-poor renal masses. MATERIALS AND METHODS: In a retrospective case-control study of 174 patients with predominantly solid nonmacroscopic fat-containing enhancing renal masses, 129 cases of malignant renal cell carcinoma were found, including clear cell, papillary, and chromophobe subtypes. Benign renal masses-oncocytoma and lipid-poor angiomyolipoma-were found in 45 patients. Whole-lesion ROIs were manually segmented and coregistered from the standard-of-care multiphase contrast-enhanced CT (CECT) scans of these patients. Pathologic diagnosis of all tumors was obtained after surgical resection. CECT images of the renal masses were used as inputs to a CECT texture analysis panel comprising 31 texture metrics derived with six texture methods. Stepwise logistic regression analysis was used to select the best predictor among all candidate predictors from each of the texture methods, and their performance was quantified by AUC. RESULTS: Among the texture predictors aiding renal mass subtyping were entropy, entropy of fast-Fourier transform magnitude, mean, uniformity, information measure of correlation 2, and sum of averages. These metrics had AUC values ranging from good (0.80) to excellent (0.98) across the various subtype comparisons. The overall CECT-based tumor texture model had an AUC of 0.87 (p < 0.05) for differentiating benign from malignant renal masses. CONCLUSION: The CT texture statistical model studied was accurate for differentiating benign from malignant solid enhancing lipid-poor renal masses.

Synthesis of Naked-eye Detectable Fluorescent 2H-chromen-2-One 2, 6-Dicyanoanilines: Effect of Substituents and pH on Its Luminous Behavior.

A variety of new coumarin derivatives containing C-4 bridged 2,6-dicyanoanilines (4a-4d) were synthesized via multicomponent one pot approach. These novel sensors were characterized by spectral analysis and a series of pH sensing fluorescence studies were performed, the results indicating that the sensors are highly selective and more effective at various pH. The fluorescence colour changes at different pH could be directly detected by naked eyes.

Does Computed Tomography Still Have Limitations to Distinguish Benign from Malignant Renal Tumors for Radiologists?

OBJECTIVES: To evaluate the current accuracy of CT for diagnosing benign renal tumors. MATERIALS AND METHODS: We retrospectively reviewed 905 patients who underwent preoperative CT followed by surgical resection. The final pathology was benign in 156 patients (17%). After exclusions, 140 patients with 163 benign tumors were included and 3 sets of the CT interpretations by radiologists with varying levels of experience were analyzed. RESULTS: The histological breakdown was as follows: oncocytomas (54.6%), angiomyolipomas (AMLs; 30.7%), renal cysts (8.0%), other miscellaneous benign tumors (6.7%). The sensitivities of diagnosing oncocytomas were 3.4, 9.0, and 13.5% in primary radiological reports, second blinded reviews, and third non-blinded reviews, respectively (p = 0.055). The sensitivities of diagnosing AMLs were 46.0, 58.0, and 62.0% in the 3-sets of CT interpretations, respectively (p = 0.246). As for renal cysts, the sensitivities were 69.2, 92.3, and 100% in the 3-sets of CT interpretations, respectively (p = 0.051). In primary reports, the positive predictive values were 95.8% in lipid poor (lp)-AMLs, 60.0% in oncocytomas, 69.2% in renal cysts, respectively (p < 0.05). CONCLUSIONS: Current conventional CT imaging still has limitations in differentiating oncocytomas and lp-AMLs from renal cell carcinomas, even when images were re-examined by experienced radiologists.

Characterization of cells from patient-derived fibrovascular membranes in proliferative diabetic retinopathy.

PURPOSE: Epiretinal fibrovascular membranes (FVMs) are a hallmark of proliferative diabetic retinopathy (PDR). Surgical removal of FVMs is often indicated to treat tractional retinal detachment. This potentially informative pathological tissue is usually disposed of after surgery without further examination. We developed a method for isolating and characterizing cells derived from FVMs and correlated their expression of specific markers in culture with that in tissue. METHODS: FVMs were obtained from 11 patients with PDR during diabetic vitrectomy surgery and were analyzed with electron microscopy (EM), comparative genomic hybridization (CGH), immunohistochemistry, and/or digested with collagenase II for cell isolation and culture. Antibody arrays and enzyme-linked immunosorbent assay (ELISA) were used to profile secreted angiogenesis-related proteins in cell culture supernatants. RESULTS: EM analysis of the FVMs showed abnormal vessels composed of endothelial cells with large nuclei and plasma membrane infoldings, loosely attached perivascular cells, and stromal cells. The cellular constituents of the FVMs lacked major chromosomal aberrations as shown with CGH. Cells derived from FVMs (C-FVMs) could be isolated and maintained in culture. The C-FVMs retained the expression of markers of cell identity in primary culture, which define specific cell populations including CD31-positive, alpha-smooth muscle actin-positive (SMA), and glial fibrillary acidic protein-positive (GFAP) cells. In primary culture, secretion of angiopoietin-1 and thrombospondin-1 was significantly decreased in culture conditions that resemble a diabetic environment in SMA-positive C-FVMs compared to human retinal pericytes derived from a non-diabetic donor. CONCLUSIONS: C-FVMs obtained from individuals with PDR can be isolated, cultured, and profiled in vitro and may constitute a unique resource for the discovery of cell signaling mechanisms underlying PDR that extends beyond current animal and cell culture models.

Contrast-enhanced ultrasound (CEUS) of cystic and solid renal lesions: a review.

Incidentally detected renal lesions have traditionally undergone imaging characterization by contrast-enhanced computer tomography (CECT) or magnetic resonance imaging. Contrast-enhanced ultrasound (CEUS) of renal lesions is a relatively novel, but increasingly utilized, diagnostic modality. CEUS has advantages over CECT and MRI including unmatched temporal resolution due to continuous real-time imaging, lack of nephrotoxicity, and potential cost savings. CEUS has been most thoroughly evaluated in workup of complex cystic renal lesions, where it has been proposed as a replacement for CECT. Using CEUS to differentiate benign from malignant solid renal lesions has also been studied, but has proven difficult due to overlapping imaging features. Monitoring minimally invasive treatments of renal masses is an emerging application of CEUS. An additional promising area is quantitative analysis of renal masses using CEUS. This review discusses the scientific literature on renal CEUS, with an emphasis on imaging features differentiating various cystic and solid renal lesions.

Quantitative assessment of solid renal masses by contrast-enhanced ultrasound with time-intensity curves: how we do it.

PURPOSE: To discuss the evaluation of the enhancement curve over time of the major renal cell carcinoma (RCC) subtypes, oncocytoma, and lipid-poor angiomyolipoma, to aid in the preoperative differentiation of these entities. Differentiation of these lesions is important, given the different prognoses of the subtypes, as well as the desire to avoid resecting benign lesions. METHODS: We discuss findings from CT, MR, and US, but with a special emphasis on contrast-enhanced ultrasound (CEUS). CEUS technique is described, as well as time-intensity curve analysis. RESULTS: Examples of each of the major RCC subtypes (clear cell, papillary, and chromophobe) are shown, as well as examples of oncocytoma and lipid-poor angiomyolipoma. For each lesion, the time-intensity curve of enhancement on CEUS is reviewed, and correlated with the enhancement curve over time reported for multiphase CT and MR. CONCLUSIONS: Preoperative differentiation of the most common solid renal masses is important, and the time-intensity curves of these lesions show some distinguishing features that can aid in this differentiation. The use of CEUS is increasing, and as a modality it is especially well suited to the evaluation of the time-intensity curve.

Contrast-Enhanced Sonography for Monitoring Neoadjuvant Chemotherapy in Soft Tissue Sarcomas.

Neoadjuvant chemotherapy is a mainstay in treating soft tissue sarcomas. Soft tissue sarcomas can show an increase in size and central necrosis, with a decrease in the viable tumor, as an initial response to neoadjuvant chemotherapy. Thus, the maximum tumor diameter may not reliably assess the response to this therapy. Contrast-enhanced sonography may address this limitation. We evaluated 4 patients with soft tissue sarcomas by contrast-enhanced sonography, performed concomitantly with conventional imaging (computed tomography, magnetic resonance imaging, or positron emission tomography). Quantitative analysis was also performed on 1 sarcoma. A viable, enhancing tumor versus tumor necrosis was nearly identical on contrast-enhanced sonography and conventional imaging. Preliminary results demonstrate potential for contrast-enhanced sonographic monitoring of soft tissue sarcomas during neoadjuvant chemotherapy.

Toxicopathological evaluation in Wistar rats (Rattus norvegicus) following repeated oral exposure to acephate.

The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses.

Loss of cardiolipin leads to perturbation of mitochondrial and cellular iron homeostasis.

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays a critical role in mitochondrial bioenergetic functions. The importance of CL in human health is underscored by the observation that perturbation of CL biosynthesis causes the severe genetic disorder Barth syndrome. To fully understand the cellular response to the loss of CL, we carried out genome-wide expression profiling of the yeast CL mutant crd1Δ. Our results show that the loss of CL in this mutant leads to increased expression of iron uptake genes accompanied by elevated levels of mitochondrial iron and increased sensitivity to iron and hydrogen peroxide. Previous studies have shown that increased mitochondrial iron levels result from perturbations in iron-sulfur (Fe-S) cluster biogenesis. Consistent with an Fe-S defect, deletion of ISU1, one of two ISU genes that encode the mitochondrial Fe-S scaffolding protein essential for the synthesis of Fe-S clusters, led to synthetic growth defects with the crd1Δ mutant. We further show that crd1Δ cells have reduced activities of mitochondrial Fe-S enzymes (aconitase, succinate dehydrogenase, and ubiquinol-cytochrome c oxidoreductase), as well as cytosolic Fe-S enzymes (sulfite reductase and isopropylmalate isomerase). Increased expression of ATM1 or YAP1 did not rescue the Fe-S defects in crd1Δ. These findings show for the first time that CL is required for Fe-S biogenesis to maintain mitochondrial and cellular iron homeostasis.