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step before optimization of radiation dose. • Following the implementation of the program, the mean RS and CTDIvol were below or equal to the organizational reference levels in all countries.

• Engaging a multidisciplinary team can enhance the use of an RDIM system for CT dose management in a multinational healthcare environment. • Deep dive of baseline data and standardization of CT practices by defining organizational clinical indication CT protocols with RPIDs is an essential step before optimization of radiation dose. • Following the implementation of the program, the mean RS and CTDIvol were below or equal to the organizational reference levels in all countries.

To determine the accuracy of CT-guided percutaneous transthoracic needle lung biopsy (PTNB) for the diagnosis of malignancy and the associated complication rates in patients with idiopathic pulmonary fibrosis (IPF).

This retrospective study included 91 CT-guided PTNBs performed in 80 patients with IPF from April 2003 through December 2016. Data regarding patients, target lesions, procedures, complications, and pathological reports were collected, and the final diagnosis was made. The diagnostic accuracy, sensitivity, specificity, percentage of nondiagnostic results, and complication rates were determined. Multivariable logistic regression analyses were performed to identify risk factors for nondiagnostic results and major complications.

Three biopsies (technical failure [n = 2] and undetermined final diagnosis [n = 1]) were excluded from the diagnostic accuracy calculation. The diagnostic accuracy, sensitivity, and specificity were 89% (78/88), 90% (62/69), and 84% (16/19), respectively. The percentage ic results of CT-guided PTNB. • The complication rate may be high, especially in cases where the biopsy needle passes through honeycomb lesions.

• In patients with idiopathic pulmonary fibrosis (IPF), CT-guided percutaneous transthoracic needle lung biopsy (PTNB) showed a relatively reasonable accuracy for the diagnosis of malignancy. • Target lesion size ≤ 3 cm and biopsy needle tip placement outside the target lesion were risk factors for nondiagnostic results of CT-guided PTNB. • The complication rate may be high, especially in cases where the biopsy needle passes through honeycomb lesions.

To review the effectiveness and safety of chemical ablation using ethanol or OK-432 for the treatment of TGDCs (thyroglossal duct cysts).

MEDLINE and EMBASE databases were searched up to May 29, 2020, to identify studies reporting the safety and efficacy of chemical ablation using ethanol or OK-432 for the treatment of TGDCs. The search query consisted of synonyms of thyroglossal duct cysts and ethanol or OK-432 ablation. The pooled success and complication rates were calculated using the inverse variance method to calculate weights, and pooled proportions were determined using the DerSimonian-Laird random-effects method.

Seven original articles including a total of 129 patients were included. The efficacy of chemical ablation was acceptable, with a pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). Repeat ethanol ablation achieved a pooled success rata pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). • Repeat ethanol ablation was also feasible, with a pooled success rate of 47% (95% CI, 24-71%). • The chemical ablation procedures were safe, with a pooled major complication rate of 0.9% (95% CI, 0.1-5.8%).Hoxa2 genes provide critical patterning signals during development, and their regulation and function have been extensively studied. We report a previously uncharacterized significant sequence divergence of a highly conserved hindbrain hoxa2b enhancer element in the family syngnathidae (pipefishes, seahorses, pipehorses, seadragons). We compared the hox cis-regulatory element variation in the Gulf pipefish and two species of seahorse against eight other species of fish, as well as human and mouse. We annotated the hoxa2b enhancer element binding sites across three species of seahorse, four species of pipefish, and one species of ghost pipefish. Finally, we performed in situ hybridization analysis of hoxa2b expression in Gulf pipefish embryos. We found that all syngnathid fish examined share a modified rhombomere 4 hoxa2b enhancer element, despite the fact that this element has been found to be highly conserved across all vertebrates examined previously. Binding element sequence motifs and spacing between binding elements have been modified for the hoxa2b enhancer in several species of pipefish and seahorse, and that the loss of the Prep/Meis binding site and further space shortening happened after ghost pipefish split from the rest of the syngnathid clade. We showed that expression of this gene in rhombomere 4 is lower relative to the surrounding rhombomeres in developing Gulf pipefish embryos, reflecting previously published functional tests for this enhancer. Our findings highlight the benefits of studying highly derived, diverse taxa for understanding of gene regulatory evolution and support the hypothesis that natural mutations can occur in deeply conserved pathways in ways potentially related to phenotypic diversity.Local accumulation of xenobiotics in human and animal tissues may cause adverse effects. Large differences in their concentrations may exist between individual cell types, often due to the expression of specific uptake and export carriers. Here we established a two-photon microscopy-based technique for spatio-temporal detection of the distribution of mycotoxins in intact kidneys and livers of anesthetized mice with subcellular resolution. selleck chemicals llc The mycotoxins ochratoxin A (OTA, 10 mg/kg b.w.) and aflatoxin B1 (AFB1, 1.5 mg/kg b.w.), which both show blue auto-fluorescence, were analyzed after intravenous bolus injections. link2 Within seconds after administration, OTA was filtered by glomeruli, and enriched in distal tubular epithelial cells (dTEC). A striking feature of AFB1 toxicokinetics was its very rapid uptake from sinusoidal blood into hepatocytes (t1/2 ~ 4 min) and excretion into bile canaliculi. Interestingly, AFB1 was enriched in the nuclei of hepatocytes with zonal differences in clearance. In the cytoplasm of pericentral hepatocytes, the half-life (t1/2~ 63 min) was much longer compared to periportal hepatocytes of the same lobules (t1/2 ~ 9 min). In addition, nuclear AFB1 from periportal hepatocytes cleared faster compared to the pericentral region. These local differences in AFB1 clearance may be due to the pericentral expression of cytochrome P450 enzymes that activate AFB1 to protein- and DNA-binding metabolites. In conclusion, the present study shows that large spatio-temporal concentration differences exist within the same tissues and its analysis may provide valuable additional information to conventional toxicokinetic studies.Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species. Humans are frequently exposed to PAs via ingestion of PA-containing herbal products or PA-contaminated foods. PAs require metabolic activation to form pyrrole-protein adducts and pyrrole-DNA adducts which lead to cytotoxicity and genotoxicity. Individual PAs differ in their metabolic activation patterns, which may cause significant difference in toxic potency of different PAs. This review discusses the current knowledge and recent advances of metabolic pathways of different PAs, especially the metabolic activation and metabolism-mediated cytotoxicity and genotoxicity, and the risk evaluation methods of PA exposure. In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.Cells respond to protein-damaging (proteotoxic) stress by activation of the Heat Shock Response (HSR). The HSR provides cells with an enhanced ability to endure proteotoxic insults and plays a crucial role in determining subsequent cell death or survival. The HSR is, therefore, a critical factor that influences the toxicity of protein stress. While named for its vital role in the cellular response to heat stress, various components of the HSR system and the molecular chaperone network execute essential physiological functions as well as responses to other diverse toxic insults. The effector molecules of the HSR, the Heat Shock Factors (HSFs) and Heat Shock Proteins (HSPs), are also important regulatory targets in the progression of neurodegenerative diseases and cancers. Modulation of the HSR and/or its extended network have, therefore, become attractive treatment strategies for these diseases. Development of effective therapies will, however, require a detailed understanding of the HSR, important features of which continue to be uncovered and are yet to be completely understood. link3 We review recently described and hallmark mechanistic principles of the HSR, the regulation and functions of HSPs, and contexts in which the HSR is activated and influences cell fate in response to various toxic conditions.Over the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future.Radioactive iodine released in nuclear accidents may accumulate in the thyroid and by irradiation enhances the risk of cancer. Radioiodine uptake into the gland can be inhibited by large doses of stable iodine or perchlorate. Nutritional iodine daily intake may impact thyroid physiology, so that radiological doses absorbed by the thyroid as well as thyroid blocking efficacy may differ in Japanese with a very rich iodine diet compared to Caucasians. Based on established biokinetic-dosimetric models for the thyroid, we derived the parameters for Caucasians and Japanese to quantitatively compare the effects of radioiodine exposure and the protective efficacy of thyroid blocking by stable iodine at the officially recommended dosages (100 mg in Germany, 76 mg in Japan) or perchlorate. The maximum transport capacity for iodine uptake into the thyroid is lower in Japanese compared to Caucasians. For the same radioiodine exposure pattern, the radiological equivalent thyroid dose is substantially lower in Japanese in the absence of thyroid blocking treatments.

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