Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue.

Malignant and normal human breast tissue were compared by evaluating two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) maps of frozen tissue samples. Image analyzing software was used to scan and process 34 gels. Eight (8/34) of these gels (4 malignant breast tumor samples, 4 normal tissue samples) were selected on the basis of gel and image quality to build a database to identify and measure the expression of a previously unidentified proteome. Growth factor receptor proteins (GFRs), including ERBB2 (HER2) and ERBB3 (HER3), were expressed in the malignant tissue samples. Growth factor receptor proteins were not expressed in the normal tissue. Also, expression of PS2-protein (pS2) was detected in neither malignant nor normal tissue. In benign breast samples a higher intensity of protein expression could be observed for maspin, desmoglein 3 and keratin 8 than in malignant samples. Other proteins expressed in malignant breast tissue include mitogen-activated protein kinase 3 (MK03), heat shock protein 27 kDa (HS27), growth factor receptor-bound protein (GRB2), cathepsin D, G1/S specific cyclin E1 (CGEI), glucose transporter type 5 (GTR5), and a number of as yet unidentified proteins.     

Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax: A systematic review and cumulative meta-analysis

AIM: To assess the effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in refractory hepatic hydrothorax (RHH) in a systematic review and cumulative meta-analysis.METHODS: A comprehensive literature search was conducted on MEDLINE, EMBASE, and PubMed covering the period from January 1970 to August 2014. Two authors independently selected and abstracted data from eligible studies. Data were summarized using a random-effects model. Heterogeneity was assessed using the I² test.RESULTS: Six studies involving a total of 198 patients were included in the analysis. The mean (SD) age of patients was 56 (1.8) years. Most patients (56.9%) had Child-Turcott-Pugh class C disease. The mean duration of follow-up was 10 mo (range, 5.7-16 mo). Response to TIPSS was complete in 55.8% (95%CI: 44.7%-66.9%), partial in 17.6% (95%CI: 10.9%-24.2%), and absent in 21.2% (95%CI: 14.2%-28.3%). The mean change in hepatic venous pressure gradient post-TIPSS was 12.7 mmHg. The incidence of TIPSS-related encephalopathy was 11.7% (95%CI: 6.3%-17.2%), and the 45-d mortality was 17.7% (95%CI: 11.34%-24.13%).CONCLUSION: TIPSS is associated with a clinically relevant response in RHH. TIPSS should be considered early in these patients, given its poor prognosis.     

Performance of a New Blunt-Tip Coaxial Needle for Percutaneous Biopsy and Drainage of “Hard-To-Reach” Targets

Aim

To present a new blunt-tip coaxial needle (SoftGuard) applied to access “hard-to-reach” targets undergoing percutaneous image-guided biopsy or drainage.

Materials and Methods

All consecutive patients presenting between August and December 2016 with “hard-to-reach” (<10 mm from a critical nearby structure such as vessels, nerves, bowel or adjacent parenchymal organs) solid lesions requiring biopsy (group A) or abscesses requiring drainage for sepsis (group B) were prospectively included. The individual features of each patient and lesion as well as technical and clinical data were collected and analysed.

Results

Twenty-six patients (18 males, 8 females, mean age 59.81 ± 17.53 years) were enrolled in group A and nine (6 males, 3 females, mean age 58.33 ± 13.8 years) in group B. Technical success was achieved in 92.3% of cases from group A and 100% of cases from group B. Five (19.2%) minor complications were noted in group A (four small self-limiting pneumothoraces and one small self-limiting peri-pancreatic haematoma). There were no complications in group B. Histological results in group A accounted for 95% sensitivity, 100% specificity and 95.2% diagnostic accuracy. In group B, mean post-operative C-reactive protein was 41 ± 48.3 mg/L in comparison with 155 ± 117.5 mg/L at baseline (P = 0.004).

Conclusions

The SoftGuard blunt-tip needle is a safe and effective tool when applied as a coaxial working cannula for percutaneous biopsy or drainage of “hard-to-reach” targets.

     

RENEB – Running the European Network of biological dosimetry and physical retrospective dosimetry

Abstract

Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios.

Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015.

Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.     

Numerical simulation of orthodontic bone remodeling

Orthodontic tooth movement is the result of alveolar bone remodeling due to response to mechanical stimulus at the interface with periodontal ligament. Therefore, periodontal ligament plays a critical role in the orthodontic tooth movement. The present study sought to develop a numerical model capable of simulating orthodontic bone remodeling. A three-dimensional finite elements model of mandibular incisor has been constructed based on CT data from a 15-year-old boy prior to orthodontic treatment. Simulations of orthodontic tooth movement were performed for tooth translation (bodily movement). The normal strain of periodontal ligament was assumed to be the key mechanical stimulus for alveolar bone remodeling. As bone remodeling is an iterative procedure, tooth position and the geometry of tooth supporting structures were updated at each iteration. The results indicated that the total amount of tooth movement after a 30-day therapy period was approximately 0.9 mm, which was in good agreement with clinical observations. Therefore, orthodontic bone remodeling, and consequently, orthodontic tooth movement can be simulated using finite elements method. These simulations can be used in treatment planning strategy and predicting clinical tooth movement.     

Allelic Exchange and Mutant Selection Demonstrate that Common Clinical embCAB Gene Mutations Only Modestly Increase Resistance to Ethambutol in Mycobacterium tuberculosis

Mutations within codon 306 of the Mycobacterium tuberculosis embB gene modestly increase ethambutol (EMB) MICs. To identify other causes of EMB resistance and to identify causes of high-level resistance, we generated EMB-resistant M. tuberculosis isolates in vitro and performed allelic exchange studies of embB codon 406 (embB406) and embB497 mutations. In vitro selection produced mutations already identified clinically in embB306, embB397, embB497, embB1024, and embC13, which result in EMB MICs of 8 or 14 μg/ml, 5 μg/ml, 12 μg/ml, 3 μg/ml, and 4 μg/ml, respectively, and mutations at embB320, embB324, and embB445, which have not been identified in clinical M. tuberculosis isolates and which result in EMB MICs of 8 μg/ml, 8 μg/ml, and 2 to 8 μg/ml, respectively. To definitively identify the effect of the common clinical embB497 and embB406 mutations on EMB susceptibility, we created a series of isogenic mutants, exchanging the wild-type embB497 CAG codon in EMB-susceptible M. tuberculosis strain 210 for the embB497 CGG codon and the wild-type embB406 GGC codon for either the embB406 GCC, embB406 TGC, embB406 TCC, or embB406 GAC codon. These new mutants showed 6-fold and 3- to 3.5-fold increases in the EMB MICs, respectively. In contrast to the embB306 mutants, the isogenic embB497 and embB406 mutants did not have preferential growth in the presence of isoniazid or rifampin (rifampicin) at their MICs. These results demonstrate that individual embCAB mutations confer low to moderate increases in EMB MICs. Discrepancies between the EMB MICs of laboratory mutants and clinical M. tuberculosis strains with identical mutations suggest that clinical EMB resistance is multigenic and that high-level EMB resistance requires mutations in currently unknown loci.Ethambutol (EMB) is a first-line antituberculosis drug that is often used in combination with other drugs to treat tuberculosis and to prevent the emergence of drug resistance. EMB also has a place in the treatment of drug-resistant and multidrug-resistant tuberculosis (2). The recent global increase in the incidence of drug-resistant tuberculosis has produced many strains that are resistant to EMB. Therefore, it is prudent to test isolates from all tuberculosis patients for their EMB susceptibility, especially when EMB is used to treat multidrug-resistant tuberculosis. Unfortunately, conventional culture-based EMB susceptibility test methods have poor intertest and interlaboratory reproducibilities (8, 21). This has made it difficult to firmly rule out the presence of EMB resistance by the use of conventional assays. Culture-based Mycobacterium tuberculosis drug susceptibility tests are also quite slow (12, 20).Genetic tests for EMB resistance are potentially more rapid and more accurate than conventional culture-based resistance testing. Genetic assays identify resistance by detecting mutations that encode EMB resistance on the M. tuberculosis chromosome, principally within the embB gene (5, 17, 25). The results of genetic assays can be available within hours; they have high interassay reproducibilities and have the potential to have high sensitivities (5, 25). However, genetic testing for EMB resistance has been hindered by a persistent uncertainty concerning the role of specific mutations in EMB resistance. Initially, the role of mutations within codon 306 of the embB gene (embB306) was questioned. Although embB306 mutations were present in 30 to 68% of EMB-resistant clinical isolates (1, 13, 22), some studies had noted a widespread presence of embB306 mutations in EMB-susceptible isolates (1, 7, 9). The role of embB306 mutations was firmly established to be a cause of low- and moderate-level (two to seven times the MIC for the wild type) EMB resistance in a recent allelic exchange study (19). However, that study also demonstrated that embB306 mutations do not in themselves cause high-level (MICs > 20 μg/ml) EMB resistance. Furthermore, the cause of EMB resistance in the 32 to 70% of clinical EMB-resistant M. tuberculosis isolates that did not have embB306 mutations remained an open question.Several clinical studies have suggested that other mutations in the embCAB operon are responsible for at least some of the remaining EMB-resistant tuberculosis cases. The most commonly occurring embCAB mutations other than embB306 have been found in embB406 and embB497. Importantly, these two mutations have been detected in clinical isolates with high-level EMB resistance (11, 14). However, other studies identified embB406 mutations in EMB-susceptible clinical isolates (7, 15, 23). Other mutations in the embB and embC genes have also been identified in EMB-resistant clinical M. tuberculosis isolates (6, 22, 23), but at low frequencies, making it difficult to firmly establish associations with EMB resistance. Thus, the actual role of non-embB306 mutations in EMB resistance has not been proven.In the study described here, we examined the role of embB mutations outside of the embB306 codon in EMB resistance. Using in vitro-selected mutants and allelic exchange techniques, our results demonstrate that non-embB306 mutations in the embCAB operon play an important role in EMB resistance, but like mutations in embB306, these mutations confer only a low to a moderate increase in EMB MICs. Our study strongly suggests that unrecognized mycobacterial gene targets for EMB resistance and high-level resistance remain to be discovered.     

A survey of suicide by burning in Tehran, Iran

To identify the characteristics of completed suicide by burning in Tehran. A retrospective analysis of data obtained from Tehran's Legal Medicine Organization and judiciary system over 5-years (from 2002 to 2006). During the 5 years, 374 decedents (64.2% female and 35.8% male) were diagnosed as suicide by self-burning, and the annual incidence rate was 0.9 per 100,000 general population-years. The most at risk group was young females. Sixty-five decedents (17.4%) had died at the scene of incidents. The location at the time of attempted suicide in all female victims and 75.4% of male decedents was home. Sixty-one percent of decedents were married and 26.2% of them had no education. Most victims were residents of suburban areas. The annual incidence rate of self-burning suicide in Tehran was found to be lower than other Iran's geographic areas, although it was higher than developed countries. Self-burning was more frequent in females than in males and was noted mainly in young age groups' residents of suburban areas with low level of education. These characteristics suggest that social factors are the main drive leading to an unacceptably high rate of suicide by self-burning among women in Tehran.