TB therapeutic drug monitoring - analysis of opportunities in Romania and Ukraine.

INTRODUCTION: Therapeutic drug monitoring (TDM) could improve TB treatment outcomes by avoiding drug toxicity or underdosing. In this study, we describe the patient burden in three TB centres in Romania and Ukraine with a TDM indication, as per the current guidelines, in order to estimate the feasibility of implementing TDM.METHODS: A retrospective multi-centre study was conducted at the Iasi Lung Hospital (Iasi, Romania), Bucharest Marius Nasta Institute (Bucharest, Romania) and Chernivtsi TB Centre (Chernivtsi, Ukraine) in adult hospitalised TB patients.RESULTS: A total of 927 participants were admitted, of whom 37.8% had at least one indication for TDM, the most frequent being slow response to TB treatment (202/345, 58.6%); 55.5% had at least one cavity present on chest X-ray. Patients with a TDM indication stayed in the hospital for a median of 67 days and took on average 2 months more to reach a successful TB outcome.CONCLUSION: TDM could be a valuable tool to improve management of selected TB patients. The decision on whether to perform TDM is often delayed by 2 months due to waiting for culture results after treatment initiation. A randomised control trial should be performed in order to define TDM's precise role in TB therapy.

Knowledge, attitudes and practices related to the COVID-19 outbreak among Romanian adults with cancer: a cross-sectional national survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic outbreak forced cancer care providers to face different challenges in terms of prevention and treatment management due to specific precautions implemented for oncological patients. We aimed to describe the level of knowledge, attitude and practices (KAP) among cancer patients, with the purpose to provide an image of the impact of COVID-19 and evaluate the effectiveness of pandemic response measures. PATIENTS AND METHODS: We developed a cross-sectional multicentric study that targeted adults with active cancer during the COVID-19 outbreak, aiming to describe KAP related to COVID-19 among Romanian oncological patients. A questionnaire investigating 64 items on KAP related to the novel coronavirus was designed and applied in seven Romanian hospitals. The group of participants consisted of 1585 oncological patients who completed the questionnaire during the outbreak (April-May 2020). RESULTS: Only 172 patients (10.8%) had very good knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection symptoms, treatment options and incubation period. Only 44.3% of patients identified diarrhoea as a sign of COVID-19. About one-third of patients (32.6%) declared that they are 'very worried' about getting infected with the novel coronavirus. More than two-thirds of participants (68%) considered that having cancer represents an additional risk for infection with SARS-CoV-2, but 27.8% would rather not vaccinate against SARS-CoV-2 should a vaccine be available. A small percentage (8.8%) believed that the risk of infection justifies delaying/stopping oncological treatment until after the pandemic. Around half of the participants (55.5%) declared being compliant with all the protective measures against coronavirus infection listed in the questionnaire. CONCLUSION: Romanian oncological patients have a less than expected knowledge about SARS-CoV-2, appropriate prevention behaviours, with limited trust in their efficacy, optimistic attitudes towards COVID-19 and low level of trust in information sources. Good COVID-19 knowledge was associated with appropriate practices towards COVID-19 and optimistic attitudes.

Extracorporeal shock waves lithotripsy versus retrograde ureteroscopy: is radiation exposure a criterion when we choose which modern treatment to apply for ureteric stones?

The aim of this study is to compare two major urological procedures in terms of patient exposure to radiation. We evaluated 175 patients, that were subjected to retrograde ureteroscopy (URS) and extracorporeal shock waves lithotripsy (ESWL) for lumbar or pelvic ureteral lithiasis, at two urological departments. The C-arm Siemens (produced in 2010 by Siemens AG, Germany) was used for ureteroscopy. The radiological devices of the lithotripters used in this study in the two clinical centers had similar characteristics. We evaluated patient exposure to ionizing radiation by using a relevant parameter, the air kerma-area product (PKA; all values in cGy cm(2)), calculated from the radiation dose values recorded by the fluoroscopy device. PKA depends on technical parameters that change due to anatomical characteristics of each case examined, such as body mass index (BMI), waist circumference, and stone location. For the patients subjected to ESWL for lumbar ureteral lithiasis the mean of PKA (cGy cm(2)) was 509 (SD=180), while for those treated for pelvic ureteral lithiasis the mean of PKA was 342 (SD=201). In the URS group for lumbar ureteral lithiasis, the mean of PKA (cGy cm(2)) was 892 (SD=436), while for patients with pelvic ureteral lithiasis, the mean of PKA was 601 (SD=429). The patients treated by URS had higher exposure to ionizing radiation dose than patients treated by ESWL. The risk factors of higher radiation doses were obesity, exposure time, and localization of the stones.

Radicals in the Bray-Liebhafsky oscillatory reaction.

This study investigates the formation of free radicals in the Bray-Liebhafsky (BL) oscillatory reaction. The results indicate that radicals are produced during both monotonous and oscillatory dynamics observed as the change of the electron paramagnetic signal (EPR) of the spin-probe TEMPONE. EPR spin-trapping with DEPMPO suggested that the most abundant radical produced in the BL reaction is an iodine-centered radical. The EPR spectrum of the DEPMPO/iodine-centered radical adducts has not been previously reported. This study may aid in establishing a more realistic reaction mechanism of the BL reaction and related chemical oscillators.

Role of free radicals in modeling the iodide-peroxide reaction mechanism.

The mechanism of monotonous decomposition of hydrogen peroxide by iodide in acidic medium is investigated at room temperature. For this purpose, O(2) pressure, I(-), I(2), and I(3)(-) concentrations are simultaneously monitored, establishing a useful framework for better understanding of the reaction mechanism and testing various models. The possibility of nonradical and radical approaches to describe experimental data is examined. Results suggest that the best description of experimentally recorded components is obtained by introducing free radicals into the model of the reaction.

U-Compare bio-event meta-service: compatible BioNLP event extraction services.

BACKGROUND: Bio-molecular event extraction from literature is recognized as an important task of bio text mining and, as such, many relevant systems have been developed and made available during the last decade. While such systems provide useful services individually, there is a need for a meta-service to enable comparison and ensemble of such services, offering optimal solutions for various purposes. RESULTS: We have integrated nine event extraction systems in the U-Compare framework, making them intercompatible and interoperable with other U-Compare components. The U-Compare event meta-service provides various meta-level features for comparison and ensemble of multiple event extraction systems. Experimental results show that the performance improvements achieved by the ensemble are significant. CONCLUSIONS: While individual event extraction systems themselves provide useful features for bio text mining, the U-Compare meta-service is expected to improve the accessibility to the individual systems, and to enable meta-level uses over multiple event extraction systems such as comparison and ensemble.

Oxygen centered radicals in iodine chemical oscillators.

The existence of free radicals in iodine-based oscillatory systems has been debated for some time. Recently, we have reported the presence of reactive oxygen species (ROS) in the iodide-peroxide system in acidic medium, which is common to all iodine--based oscillatory systems ( J. Phys. Chem. A 2011 , 115 , 2247--2249 ). In this work, the goal was to identify the ROS produced in this system using an EPR spin trap which can distinguish between hydroxyl (HO(•)) and hydroperoxyl (HOO(•)) radicals. The formation of the hydroperoxyl radical was observed and a possible explanation for the low EPR signal of hydroxyl radical was proposed.

Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology.

BACKGROUND: Interferon-gamma (IFN-γ) is vital in vaccine-induced immune defense against bacterial and viral infections and tumor. Our recent study demonstrated the power of a literature-based discovery method in extraction and comparison of the IFN-γ and vaccine-mediated gene interaction networks. The Vaccine Ontology (VO) contains a hierarchy of vaccine names. It is hypothesized that the application of VO will enhance the prediction of IFN-γ and vaccine-mediated gene interaction network. RESULTS: In this study, 186 specific vaccine names listed in the Vaccine Ontology (VO) and their semantic relations were used for possible improved retrieval of the IFN-γ and vaccine associated gene interactions. The application of VO allows discovery of 38 more genes and 60 more interactions. Comparison of different layers of IFN-γ networks and the example BCG vaccine-induced subnetwork led to generation of new hypotheses. By analyzing all discovered genes using centrality metrics, 32 genes were ranked high in the VO-based IFN-γ vaccine network using four centrality scores. Furthermore, 28 specific vaccines were found to be associated with these top 32 genes. These specific vaccine-gene associations were further used to generate a network of vaccine-vaccine associations. The BCG and LVS vaccines are found to be the most central vaccines in the vaccine-vaccine association network. CONCLUSION: Our results demonstrate that the combined usages of biomedical ontologies and centrality-based literature mining are able to significantly facilitate discovery of gene interaction networks and gene-concept associations. AVAILABILITY: VO is available at: http://www.violinet.org/vaccineontology; and the SVM edit kernel for gene interaction extraction is available at: http://www.violinet.org/ifngvonet/int_ext_svm.zip.

A potential source of free radicals in iodine-based chemical oscillators.

The iodide-peroxide system in an acidic medium was investigated as a potential source of free radicals in iodine-based chemical oscillators. The radicals were detected by EPR spin-trapping using spin-trap 5-(tert-butoxycarbonyl)-5-methyl-1-pyrroline N-oxide (BMPO), which forms stable spin-adducts with oxygen-centered radicals. The iodide-peroxide system is introduced as an easily available laboratory source of free radicals.

Literature-based discovery of IFN-gamma and vaccine-mediated gene interaction networks.

Interferon-gamma (IFN-gamma) regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-gamma-related gene interaction network from a large amount of IFN-gamma research reported in the literature, a literature-based discovery approach was applied with a combination of natural language processing (NLP) and network centrality analysis. The interaction network of human IFN-gamma (Gene symbol: IFNG) and its vaccine-specific subnetwork were automatically extracted using abstracts from all articles in PubMed. Four network centrality metrics were further calculated to rank the genes in the constructed networks. The resulting generic IFNG network contains 1060 genes and 26313 interactions among these genes. The vaccine-specific subnetwork contains 102 genes and 154 interactions. Fifty six genes such as TNF, NFKB1, IL2, IL6, and MAPK8 were ranked among the top 25 by at least one of the centrality methods in one or both networks. Gene enrichment analysis indicated that these genes were classified in various immune mechanisms such as response to extracellular stimulus, lymphocyte activation, and regulation of apoptosis. Literature evidence was manually curated for the IFN-gamma relatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.

Energy dynamics in theBray-Liebhafsky oscillatory reaction.

Energy dynamics of the well-stirred, isothermally conducted Bray-Liebhafsky reaction is followed by monitoring the population of the first two vibration states of hydrogen peroxide. Excitations are detected by Raman spectroscopy showing periodical changes of the energy flow through the system, matching the periodicity of chemical oscillations. Well before chemical oscillation, rearrangement of energy provokes excessive excitation of the first vibration state of hydrogen peroxide followed by the phase-shifted excitation of the second state. The observed populations of excited states highly exceed equilibrium values, suggesting that the nonequilibrium distribution of energy related to the peculiar hydrogen bond network dynamics may be an important part of the reaction mechanism.

A rapid and facile synthesis of nanofibrillar polyaniline using microwave radiation.

We present the first fast and facile microwave assisted synthesis of polyaniline (PANI) nanofibers ("MWA synthesis"). Under conventional synthesis (CS), the polymer was produced with 79.7% yield after 5 h at ambient temperature. However, under microwave irradiation, the nanofibers were produced with yield of 76.2% after only 5 min, i.e., with 78.8% after 20 min at ambient temperature. The FTIR and Raman spectra show the PANI structure in all samples either synthesized conventionally or in the microwave. SEM and TEM confirm the nanofibrillar morphology.

Introducing meta-services for biomedical information extraction.

We introduce the first meta-service for information extraction in molecular biology, the BioCreative MetaServer (BCMS; http://bcms.bioinfo.cnio.es/). This prototype platform is a joint effort of 13 research groups and provides automatically generated annotations for PubMed/Medline abstracts. Annotation types cover gene names, gene IDs, species, and protein-protein interactions. The annotations are distributed by the meta-server in both human and machine readable formats (HTML/XML). This service is intended to be used by biomedical researchers and database annotators, and in biomedical language processing. The platform allows direct comparison, unified access, and result aggregation of the annotations.

Identifying gene-disease associations using centrality on a literature mined gene-interaction network.

MOTIVATION: Understanding the role of genetics in diseases is one of the most important aims of the biological sciences. The completion of the Human Genome Project has led to a rapid increase in the number of publications in this area. However, the coverage of curated databases that provide information manually extracted from the literature is limited. Another challenge is that determining disease-related genes requires laborious experiments. Therefore, predicting good candidate genes before experimental analysis will save time and effort. We introduce an automatic approach based on text mining and network analysis to predict gene-disease associations. We collected an initial set of known disease-related genes and built an interaction network by automatic literature mining based on dependency parsing and support vector machines. Our hypothesis is that the central genes in this disease-specific network are likely to be related to the disease. We used the degree, eigenvector, betweenness and closeness centrality metrics to rank the genes in the network. RESULTS: The proposed approach can be used to extract known and to infer unknown gene-disease associations. We evaluated the approach for prostate cancer. Eigenvector and degree centrality achieved high accuracy. A total of 95% of the top 20 genes ranked by these methods are confirmed to be related to prostate cancer. On the other hand, betweenness and closeness centrality predicted more genes whose relation to the disease is currently unknown and are candidates for experimental study. AVAILABILITY: A web-based system for browsing the disease-specific gene-interaction networks is available at: http://gin.ncibi.org.

Excessive excitation of hydrogen peroxide during oscillatory chemical evolution.

The peculiar reaction dynamics of the Bray-Liebhafsky chemical oscillator is connected with the nonequilibrium periodic excitations of hydrogen peroxide embedded in a hydrogen-bonded water network. This was indicated by Raman spectroscopy that showed periodic, isothermal, and excessive excitation of the symmetric vibration of hydrogen peroxide. Since such an excessive excitation should be the result of a specific nonequilibrium energy distribution with the active participation of water, understanding this process can be of considerable importance in other systems in which water is the main constituent.

[Extraperitoneal transomphalic drainage of the posthydatid hepatic restant cavity by coelioscopic approach]. / Drenajul transomfalic extraperitoneal al cavitatii restante hepatice posthidatice pe cale laparoscopica.

Being often biliary contaminated and suppurative, the hydatid hepatic cyst is in fact a real parasitic abscess. So far its surgical approach represents the only credible possibility of treatment. Authors impart their experience regarding the external drainage of the restant posthydatid cavity, by using a completely extraperitoneal way of bringing out the drain, by means of the round ligament, an original method conceived and put into practice by Prof. D. Burlui in 1968. This technique is simple, without risks or complications, possible for most of the parasite hepatic locations, especially for the central segments, for which this method is superior to other surgical procedures. The greatest advantage of the extraperitoneal transomphalic route of the drain is the absence of the peritoneal losses and so the impossibility of biliary leakage occurrence. The radiological and the ultrasonic controls confirm the reduction and finally total fibrosis and disappearance of the remaining cavity, about two months after the surgery. In this moment the drainage may be suppressed. In December 2001, we added to this method an other original variant: the coelioscopic approach of the extraperitoneal transomphalic drainage of the restant posthydatid cavity, representing the aim of this paper.

[Carcinoid tumors, leiomyosarcoma and invasive adenocarcinoma metastasis of the Treitz angle]. / Tumori carcinoide, leiomiosarcom si metastaza invaziva de adenocarcinom, ale unghiului duodeno-jejunal Treitz.

Our paper studies the quite rare occurrence of the digestive superior occlusive pathology, namely some causes which might induce partial or even total obstruction of the digestive tract, at the distal anatomical limits of the duodenum, also known as the Treitz angle. The first two described cases were carcinoid tumors, obstructive and ulcerated in the lumen of the same angle. The last two cases were an obstructive leiomyosarcoma and an invasive mesenteric metastasis from a right colon cancer, which cause a total external compression of the Treitz angle, clinically manifested as a complete food intolerance, as a first symptom. Concerning the clinical evolution, these are totally different lesions, malign, metastasis and neuroendocrine tumors, which occurred at the same level, had a totally different clinical evolution and surgical approach, only three of them developing at good postoperative course. The imaging, clinical and pathological diagnosis problems, the different specific surgical solutions, the postoperative care and finally the rarity of this level of obstruction of the small bowel, are the aim of this paper.