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Background: Chest X-rays (CXRs) are pivotal in clinical diagnostics, particularly in assessing cardiomegaly through the cardiothoracic ratio (CTR). This systematic review and meta-analysis evaluate the efficacy of artificial intelligence (AI) in automating CTR determination to enhance patient care and streamline diagnostic processes. They are concentrated on comparing the performance of AI models in determining the CTR against human assessments, identifying the most effective models for potential clinical implementation. This study was registered with PROSPERO (no. CRD42023437459). No funding was received. Methods: A comprehensive search of medical databases was conducted in June 2023. The search strategy adhered to the PICO framework. Inclusion criteria encompassed original articles from the last decade focusing on AI-assisted CTR assessment from standing-position CXRs. Exclusion criteria included systematic reviews, meta-analyses, conference abstracts, paediatric studies, non-original articles, and studies using imaging techniques other than X-rays. After initial screening, 117 articles were reviewed, with 14 studies meeting the final inclusion criteria. Data extraction was performed by three independent investigators, and quality assessment followed PRISMA 2020 guidelines, using tools such as the JBI Checklist, AMSTAR 2, and CASP Diagnostic Study Checklist. Risk of bias was assessed according to the Cochrane Handbook guidelines. Results: Fourteen studies, comprising a total of 70,472 CXR images, met the inclusion criteria. Various AI models were evaluated, with differences in dataset characteristics and AI technology used. Common preprocessing techniques included resizing and normalization. The pooled AUC for cardiomegaly detection was 0.959 (95% CI 0.944-0.975). The pooled standardized mean difference for CTR measurement was 0.0353 (95% CI 0.147-0.0760). Significant heterogeneity was found between studies (I 2 89.97%, p < 0.0001), with no publication bias detected. Conclusions: Standardizing methodologies is crucial to avoid interpretational errors and advance AI in medical imaging diagnostics. Uniform reporting standards are essential for the further development of AI in CTR measurement and broader medical imaging applications.

Objectives : The purpose of this study is to evaluate the performance of our deep learning algorithm in calculating cardiothoracic ratio (CTR) and thus in the assessment of cardiomegaly or pericardial effusion occurrences on chest radiography (CXR). Methods : From a database of 8000 CXRs, 13 folders with a comparable number of images were created. Then, 1020 images were chosen randomly, in proportion to the number of images in each folder. Afterward, CTR was calculated using RadiAnt Digital Imaging and Communications in Medicine (DICOM) Viewer software (2023.1). Next, heart and lung anatomical areas were marked in 3D Slicer. From these data, we trained an AI model which segmented heart and lung anatomy and determined the CTR value. Results : Our model achieved an Intersection over Union metric of 88.28% for the augmented training subset and 83.06% for the validation subset. F1-score for subsets were accordingly 90.22% and 90.67%. In the comparative analysis of artificial intelligence (AI) vs. humans, significantly lower transverse thoracic diameter (TTD) ( p < 0.001), transverse cardiac diameter (TCD) ( p < 0.001), and CTR ( p < 0.001) values obtained using the neural network were observed. Conclusions : Results confirm that there is a significant correlation between the measurements made by human observers and the neural network. After validation in clinical conditions, our method may be used as a screening test or advisory tool when a specialist is not available, especially on Intensive Care Units (ICUs) or Emergency Departments (ERs) where time plays a key role.

Background : A reliable assessment of liver volume, necessary before transplantation, remains a challenge. Our work aimed to assess the differences in the evaluation and measurements of the liver between independent observers and compare different formulas calculating its volume in relation to volumetric segmentation. Methods : Eight researchers measured standard liver dimensions based on 105 abdominal computed tomography (CT) scans. Based on the results obtained, the volume of the liver was calculated using twelve different methods. An independent observer performed a volumetric segmentation of the livers based on the same CT examinations. Results : Significant differences were found between the formulas and in relation to volumetric segmentation, with the closest results obtained for the Heinemann et al. method. The measurements of individual observers differed significantly from one another. The observers also rated different numbers of livers as enlarged. Conclusions : Due to significant differences, despite its time-consuming nature, the use of volumetric liver segmentation in the daily assessment of liver volume seems to be the most accurate method.

Purpose: The aim of our study is to evaluate the impact of ultrasound probe mechanical pressure on the stiffness of the gastrocnemius muscle in a healthy paediatric population. As far as we know, there has been no previous qualitative in vivo study on the impact of probe pressure on muscle shear-wave elastography results with objective evaluation of compression in the paediatric population., Material and Methods: In this cohort study, a group of 22 children (mean age 8.99 years, SD 2.74, 11 males) underwent elastography of the gastrocnemius muscle of the dominant leg. A custom-made, 3-dimensional printed probe cover was used to measure the mechanical pressure of the probe on tissues., Results: The obtained results were related to the age, sex, BMI, and calf circumference of the subjects. We observed a significant difference in the stiffness parameter at a pressure of 1 N, with a further increase if force was increased ( p < 0.001). A significant, very weak positive correlation of age and stiffness was observed ( p < 0.001, r 2 = 0.022). There was no significant correlation of stiffness, BMI, and calf circumference., Conclusions: The use of compression during muscle elastography in children causes a significant bias in results, regardless of age, sex, BMI, or calf size., Competing Interests: The authors report no conflicts of interest., (© Pol J Radiol 2024.)

As the number of smartphones increases, so does the number of medical apps. Medical mobile applications are widely used in many medical fields by both patients and doctors. However, there are still few approved mobile applications that can be used in the diagnostic-therapeutic process and radiological apps are affected as well. We conducted our research by classifying radiological applications from the Google Play® store into appropriate categories, according to our own qualification system developed by researchers for the purposes of this study. In addition, we also evaluated apps from the App Store®. The radiology application rating system we created has not been previously used in other articles. Out of 228 applications from the Google Play store, only 6 of them were classified as "A" category with the highest standard. Apps from the App Store (157) were not categorized due to the lack of download counts, which was necessary in our app-rating system. The vast majority of applications are for educational purposes and are not used in clinical practice. This is due to the need of obtaining special permits and certificates from relevant institutions in order to use them in medical practice. We recommend applications from the Google Play store that have been classified in the "A" category, evaluating them as the most valuable. App Store apps data is described and presented in the form of diagrams and tables., (© 2023. The Author(s).)

Background: On March 11, 2020, coronavirus disease (COVID-19) was declared a global threat by the World Health Organization (WHO). It quickly became apparent that reducing inpatient mortality rates and early phase prediction of possible deterioration or severe disease course relied on finding more specific biomarkers., Objectives: This retrospective study assessed initial clinical, laboratory and radiological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and explored their impact on mortality and the course of the disease. Such efforts aimed to facilitate the identification of high-risk patients and to improve the formulation of treatment plans for these individuals., Material and Methods: The cohort comprised 111 consecutive adult inpatients diagnosed with COVID-19 and hospitalized in the Internal Medicine Ward of the University Clinical Center of prof. K. Gibiński of the Medical University of Silesia in Katowice, Poland, a COVID-19 Treatment Unit, between November 16, 2020 and February 15, 2021. All available clinical, laboratory and radiological findings were extracted from electronic records and assessed as possible risk factors for poor prognosis., Results: Clinicasl and radiological features with higher frequency in COVID-19 non-survivors included older age, history of smoking, concomitant cardiovascular diseases, low oxygen saturation (SpO2), and high infection risk assessed on admission as well as high opacity score, percentage of opacity and percentage of high opacity in computed tomography. Non-survivors had decreased serum lymphocytes, monocytes, calcium, magnesium, and hemoglobin oxygen saturation. They also had increased red cell distribution width (RDW), C-reactive protein (CRP), procalcitonin, alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), D-dimer, troponin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, as well as a base deficit., Conclusions: This retrospective study identified several markers associated with a fatal course of COVID-19. The early assessment of SARS-CoV-2-infected inpatients should consider these markers.

In recent years, deep neural networks have enabled countless innovations in the field of image classification. Encouraged by success in this field, researchers worldwide have demonstrated how to use Convolutional Neural Network techniques in medical imaging problems. In this article, the results were obtained through the use of the EfficientNet in the task of classifying 14 different diseases based on chest X-ray images coming from the NIH (National Institutes of Health) ChestX-ray14 dataset. The approach addresses dataset imbalances by introducing a custom split to ensure fair representation. Binary cross entropy loss is utilized to handle the multi-label difficulty. The model architecture comprises an EfficientNet backbone for feature extraction, succeeded by sequential layers including GlobalAveragePooling, Dense, and BatchNormalization. The main contribution of this paper is a proposed solution that outperforms previous state-of-the-art deep learning models average area under the receiver operating characteristic curve-AUC-ROC (score: 84.28%). The usage of the transfer-learning technique and traditional deep learning engineering techniques was shown to enable us to obtain such results on consumer-class GPUs (graphics processing units).

Diagnostic imaging has become an integral part of the healthcare system. In recent years, scientists around the world have been working on artificial intelligence-based tools that help in achieving better and faster diagnoses. Their accuracy is crucial for successful treatment, especially for imaging diagnostics. This study used a deep convolutional neural network to detect four categories of objects on digital chest X-ray images. The data were obtained from the publicly available National Institutes of Health (NIH) Chest X-ray (CXR) Dataset. In total, 112,120 CXRs from 30,805 patients were manually checked for foreign objects: vascular port, shoulder endoprosthesis, necklace, and implantable cardioverter-defibrillator (ICD). Then, they were annotated with the use of a computer program, and the necessary image preprocessing was performed, such as resizing, normalization, and cropping. The object detection model was trained using the You Only Look Once v8 architecture and the Ultralytics framework. The results showed not only that the obtained average precision of foreign object detection on the CXR was 0.815 but also that the model can be useful in detecting foreign objects on the CXR images. Models of this type may be used as a tool for specialists, in particular, with the growing popularity of radiology comes an increasing workload. We are optimistic that it could accelerate and facilitate the work to provide a faster diagnosis.

This study aimed at characterizing some adaptive changes in Plantago lanceolata L. exposed to harsh conditions of a desert-like environment generating physiological stress of limited water availability and exposure to strong light. It was clearly shown that the plants were capable of adapting their root system and vascular tissues to enable efficient vegetative performance. Soil analyses, as well as nitrogen isotope discrimination data show that P. lanceolata leaves in a desert-like environment had better access to nitrogen (nitrite/nitrate) and were able to fix it efficiently, as compared to the plants growing in the surrounding forest. The arbuscular mycorrhiza was also shown to be well-developed, and this was accompanied by higher bacterial frequency in the root zone, which might further stimulate plant growth. A closer look at the nitrogen content and leaf veins with a higher number of vessels and a greater vessel diameter made it possible to define the changes developed by the plants populating sandy habitats as compared with the vegetation sites located in the nearby forest. A determination of the photosynthesis parameters indicates that the photochemical apparatus in P. lanceolata inhabiting the desert areas adapted slightly to the desert-like environment and the time of day, with some changes of the reaction center (RC) size (photosystem II, PSII), while the plants' photochemical activity was at a similar level. No differences between the two groups of plants were observed in the dissipation of light energy. The exposure of plants to harsh conditions of a desert-like environment increased the water use efficiency (WUE) value in parallel with possible stimulation of the β -carboxylation pathway.

Background: The COVID-19 pandemic, which affected the entire global population, had an impact on our health and quality of life. Many people had complications, were hospitalised or even died due to SARS-CoV-2 infection. The health systems of many countries had to radically change their way of functioning and scientists around the world worked intensively to develop a vaccine for the SARS-CoV-2 virus., Aim: The aim of this work is to assess the quality of life of patients who were hospitalised for COVID-19, using the SF-36 questionnaire., Methods: Between May and August 2022, we conducted a telephone assessment of quality of life in patients who were hospitalised for COVID-19 at the Temporary Hospital in Pyrzowice (Silesia, Poland), between November 2021 and January 2022., Results: Quality of life was significantly lower in women ( p = 0.040), those with DM2 ( p = 0.013), CKD ( p = 0.041) and the vaccinated ( p = 0.015)., Conclusions: People with chronic kidney disease, diabetes mellitus and women had a lower quality of life after COVID-19 disease. However, people who were vaccinated for SARS-CoV-2 had a lower quality of life than non-vaccinated people did. This is possibly due to the higher mean age, and probably the higher disease burden, in the vaccinated group.

Machine learning (ML), artificial neural networks (ANNs), and deep learning (DL) are all topics that fall under the heading of artificial intelligence (AI) and have gained popularity in recent years. ML involves the application of algorithms to automate decision-making processes using models that have not been manually programmed but have been trained on data. ANNs that are a part of ML aim to simulate the structure and function of the human brain. DL, on the other hand, uses multiple layers of interconnected neurons. This enables the processing and analysis of large and complex databases. In medicine, these techniques are being introduced to improve the speed and efficiency of disease diagnosis and treatment. Each of the AI techniques presented in the paper is supported with an example of a possible medical application. Given the rapid development of technology, the use of AI in medicine shows promising results in the context of patient care. It is particularly important to keep a close eye on this issue and conduct further research in order to fully explore the potential of ML, ANNs, and DL, and bring further applications into clinical use in the future.

Glutathione transferases (GSTs) are a class of phase II detoxifying enzymes catalysing the conjugation of glutathione (GSH) to endogenous and exogenous electrophilic molecules, with microsomal glutathione transferase 1 (MGST1) being one of its key members. MGST1 forms a homotrimer displaying third-of-the-sites-reactivity and up to 30-fold activation through modification of its Cys-49 residue. It has been shown that the steady-state behaviour of the enzyme at 5 °C can be accounted for by its pre-steady-state behaviour if the presence of a natively activated subpopulation (~ 10%) is assumed. Low temperature was used as the ligand-free enzyme is unstable at higher temperatures. Here, we overcame enzyme lability through stop-flow limited turnover analysis, whereby kinetic parameters at 30 °C were obtained. The acquired data are more physiologically relevant and enable confirmation of the previously established enzyme mechanism (at 5 °C), yielding parameters relevant for in vivo modelling. Interestingly, the kinetic parameter defining toxicant metabolism, k cat /K M , is strongly dependent on substrate reactivity (Hammett value 4.2), underscoring that glutathione transferases function as efficient and responsive interception catalysts. The temperature behaviour of the enzyme was also analysed. Both the K M and K D values decreased with increasing temperature, while the chemical step k 3 displayed modest temperature dependence (Q 10 : 1.1-1.2), mirrored in that of the nonenzymatic reaction (Q 10 : 1.1-1.7). Unusually high Q 10 values for GSH thiolate anion formation (k 2 : 3.9), k cat (2.7-5.6) and k cat /K M (3.4-5.9) support that large structural transitions govern GSH binding and deprotonation, which limits steady-state catalysis., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The point shear wave elastography and supersonic shear imaging methods were compared regarding incorrect measurements during the liver examinations. A report-based, single-center, retrospective analysis of 425 liver elastography examinations was performed. A lower success ratio was observed for the point shear wave elastography method, as well as the older and obese patients pre-dominated in non-diagnostic studies. In our center experience, it is easier to obtain diagnostic data using the supersonic shear imaging method. However, further investigation of the subject is needed., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inter-recti distance (IRD) measurement using musculoskeletal USI has been used in physiotherapy research, in particular, to investigate pregnancy-related diastasis recti abdominis (DRA) and to seek its effective treatment methods. Severe and untreated diastasis may result in the formation of umbilical or epigastric hernias., Objective: This study aimed to systematically map physiotherapy-related research articles that included descriptions of IRD measurement procedures using USI to present their similarities and differences, and formulate recommendations on the procedure., Design: A scoping review was conducted according to PRISMA-ScR guidelines, including 49 of 511 publications from three major databases. Publications were selected and screened by two independent reviewers whose decisions were consulted with a third reviewer. The main synthesized data items were: the examinees' body position, breathing phase, measurement sites, and DRA screening methods. The final conclusions and recommendations were the result of a consensus between seven reviewers from four research centers., Results: Studies used 1-5 measurement sites that were differently determined. IRD was measured at the umbilicus (n = 3), at its superior (n = 16) and/or inferior border (n = 9), and at different levels: between 2 and 12 cm above the umbilicus, or a third of the distance and halfway between the umbilicus and xiphoid (n = 37); between 2 and 4.5 cm below the umbilicus or halfway between the umbilicus and pubis (n = 27). Different approaches were used to screen subjects for DRA., Conclusions: The discrepancies between the measurement procedures prevent between-study comparisons. The DRA screening method should be standardized. IRD measurement protocol standardization has been proposed., Critical Relevance Statement: This scoping review indicates that the inter-recti distance measurement procedures using ultrasound imaging differ between studies, preventing between-study comparisons. Based on the results synthesis, the measurement protocol standardization has been proposed., Key Points: The inter-recti distance measurement procedures using USI differ between studies. Proposed standardization concerns body position, breathing phase, measurements number per location. Determination of measurement locations considering individual linea alba length is suggested. Recommended locations: umbilical top, ½ of umbilical top-xiphoid, ¼ of umbilical top-xiphoid/pubis distances. Diastasis recti abdominis diagnostic criteria are needed for proposed measurement locations., (© 2023. The Author(s).)

The present study aimed to meta-analyze and evaluate the certainty of evidence for resin infiltration of proximal carious lesions in primary and permanent teeth. While resin infiltration has been shown efficacious for caries management, the certainty of evidence remains unclear. The protocol was registered with PROSPERO (CRD42018080895), and PRISMA guidelines have been followed. The databases PubMed, Embase, and Cochrane CENTRAL were systematically screened, complemented by hand searches and cross-referencing. Eleven relevant articles were identified and included, i.e., randomized controlled trials (RCTs) comparing the progression of resin infiltrated proximal caries lesions (combined with non-invasive measures) in primary or permanent teeth with non-invasive measures. Random-effects meta-analyses and trial sequential analyses (TSA) were performed for per-protocol (PP), intention-to-treat (ITT), and best/worst case (BC/WC) scenarios. Six included trials assessed lesions in permanent teeth and five trails assessed lesions in primary teeth. The trials had a high or unclear risk of bias. Risk of caries progression was significantly reduced for infiltrated lesions in the PP, ITT, and BC scenarios in both permanent teeth and primary teeth, but not in the WC scenario. According to the TSA, firm evidence was reached for all of the scenarios except the WC. In conclusion, there is firm evidence for resin infiltration arresting proximal caries lesions in permanent and primary teeth.

Objectives: The study aimed to analyze the effect of BNT162b2 vaccination among Polish healthcare workers in terms of serologic response and adverse events., Material and Methods: A questionnaire survey covered data in the period January 1-March 31, 2021 gathered in 2 hospitals in Wielkopolska, Poland. Additionally, serological analysis (SARS-CoV-2 anti-S protein IgG) was performed., Results: A total of 617 medical workers were vaccinated with BNT162b2 (Comirnaty, Pfizer). Data from the questionnaires were received from all of the staff after the first and the second dose. No severe side effects were observed. The most common side effect following the first and second doses of vaccination was pain at the injection site. After the first dose, 3 (1.4 %) women aged 18-55 years, 5 women (3.9 %), and 3 men (8.3 %) aged >55 years had negative SARS-CoV-2 anti-S protein IgG result. After the second dose, all those who agreed to have antibodies tested responded to vaccination with positive SARS-CoV-2 anti-S protein IgG results., Conclusions: Vaccination tolerance was good in the studied population; no severe side effects were observed. After the second dose, all tested healthcare workers responded to vaccination with antibody production. Int J Occup Med Environ Health. 2022;35(6):761-66., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

The study analyzes the correlation between the indications and results of head CT examinations in search of evidence of the excessive use of this diagnostic method. In total, 1160 referrals for urgent head CT were analyzed retrospectively, including the following parameters: patients' sex and age, type of scan (C-, C+, angio-CT), description of symptoms and presence of diagnostic target. Pathologies identified by the radiologist were assigned to four classes, regarding the severity of diagnosed conditions. The analysis of the CT results has shown that over half (55.22%) of the examinations revealed no deviations or showed chronic, asymptomatic lesions. As many as 73.71% referrals constituted group 0 in terms of the lack of a diagnostic target of a specific pathology. The presence of specific clinical targeting in a referral correlated significantly with a higher frequency of acute diagnosis. Contrast-enhanced follow-up examinations allowed the unequivocal classification of patients into extreme classes (I or IV) and accurate identification of patients requiring urgent or chronic treatment. Excessive use of diagnostic imaging is harmful, not only to patients, who often are unnecessarily exposed to radiation, but also to the quality of healthcare, since it increases the costs and radiologists' workload.

Despite the growing popularity of mobile devices, they still have not found widespread use in medicine. This is due to the procedures in a given place, differences in the availability of mobile devices between individual institutions or lack of appropriate legal regulations and accreditation by relevant institutions. Numerous studies have been conducted and compared the usability of mobile solutions designed for diagnostic images evaluation on various mobile devices and applications with classic stationary descriptive stations. This study is an attempt to compare the usefulness of currently available mobile applications which are used in the medical industry, focusing on imaging diagnostics. As a consequence of the healthcare sector's diversity, it is also not possible to design a universal mobile application, which results in a multitude of software available on the market and makes it difficult to reliably compile and compare studies included in this systematic review. Despite these differences, it was possible to identify both positive and negative features of portable methods analyzing radiological images. The mobile application of the golden mean in hospital infrastructure should be widely available, with convenient and simple usage. Our future research will focus on development in the use of mobile devices and applications in the medical sector.

This systematic review focuses on using artificial intelligence (AI) to detect COVID-19 infection with the help of X-ray images. Methodology : In January 2022, the authors searched PubMed, Embase and Scopus using specific medical subject headings terms and filters. All articles were independently reviewed by two reviewers. All conflicts resulting from a misunderstanding were resolved by a third independent researcher. After assessing abstracts and article usefulness, eliminating repetitions and applying inclusion and exclusion criteria, six studies were found to be qualified for this study. Results : The findings from individual studies differed due to the various approaches of the authors. Sensitivity was 72.59%-100%, specificity was 79%-99.9%, precision was 74.74%-98.7%, accuracy was 76.18%-99.81%, and the area under the curve was 95.24%-97.7%. Conclusion : AI computational models used to assess chest X-rays in the process of diagnosing COVID-19 should achieve sufficiently high sensitivity and specificity. Their results and performance should be repeatable to make them dependable for clinicians. Moreover, these additional diagnostic tools should be more affordable and faster than the currently available procedures. The performance and calculations of AI-based systems should take clinical data into account., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that mainly affects developed countries, but the number of cases in developing countries is increasing. We conducted a narrative review on the potential application of ultrasound elastography in the diagnosis and monitoring of UC, as this newly emerging method has promising results in other gut diseases. This review fulfilled the PRISMA Statement criteria with a time cut-off of June 2022. At the end of the review, of the 1334 identified studies, only five fulfilled all the inclusion criteria. Due to the small number of studies in this field, a reliable assessment of the usefulness of ultrasound elastography is difficult. We can only conclude that the transabdominal elastography examination did not significantly differ from the standard gastrointestinal ultrasonography examination and that measurements of the frontal intestinal wall should be made in the longitudinal section. The reports suggest that it is impossible to estimate the clinical scales used in disease assessment solely on the basis of elastographic measurements. Due to the different inclusion criteria, measurement methodologies, and elastographic techniques used in the analysed studies, a reliable comparative evaluation was impossible. Further work is required to assess the validity of expanding gastrointestinal ultrasonography with elastography in the diagnosis and monitoring of UC.

Epilepsy is one of the most frequent serious brain disorders. Approximately 30,000 of the 150,000 children and adolescents who experience unprovoked seizures are diagnosed with epilepsy each year. Magnetic resonance imaging is the method of choice in diagnosing and monitoring patients with this condition. However, one very effective tool using MR images is volBrain software, which automatically generates information about the volume of brain structures. A total of 57 consecutive patients (study group) suffering from epilepsy and 34 healthy patients (control group) who underwent MR examination qualified for the study. Images were then evaluated by volBrain. Results showed atrophy of the brain and particular structures-GM, cerebrum, cerebellum, brainstem, putamen, thalamus, hippocampus and nucleus accumbens volume. Moreover, the statistically significant difference in the volume between the study and the control group was found for brain, lateral ventricle and putamen. A volumetric analysis of the CNS in children with epilepsy confirms a decrease in the volume of brain tissue. A volumetric assessment of brain structures based on MR data has the potential to be a useful diagnostic tool in children with epilepsy and can be implemented in clinical work; however, further studies are necessary to enhance the effectiveness of this software.

Background: Complications of cystic fibrosis-associated liver disease (CFLD) are a leading nonpulmonary cause of death. Noninvasive tests enabling early detection of liver changes, especially in children are sought. The aim of the study was to assess the scale of liver fibrosis with the use of elastography in paediatric patients with diagnosed cystic fibrosis (CF) and its comparison with other tests (APRI and Fibrotest)., Methods: We examined 41 children, in the age range 2-21 years, with diagnosed CF. The analysis a included clinical picture, laboratory parameters of liver damage, and cholestasis. Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrotest were done in all patients. Liver stiffness measurements were acquired using shear-wave elastography (SWE)., Results: CFLD was diagnosed in 16/41 patients (39%). Abnormal elastography was observed in 19/41 patients (46.3%), and in 5/41 (12.2%), the changes were advanced (F4). Abnormal elastography was observed in 12/16 (75%) of the patients with CFLD, and in 7/25 (28%), there were no lesions observed in the liver in the course of cystic fibrosis. In all patients with F4, we observed abnormal results of the APRI and Fibrotest. In most patients with small changes in elastography, we found normal results of the APRI and Fibrotest., Conclusion: Elastography seems to be a noninvasive examination useful in everyday clinical work in detecting early liver changes and monitoring of progression in paediatric patients with diagnosed cystic fibrosis, ahead of changes in laboratory tests. The cost-effectiveness of this test, the possibility of its repetition, and its availability are additional benefits., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Sabina Wiecek et al.)

The common ice plant, Mesembryanthemum crystallinum L., has recently been found as a good candidate for phytoremediation of heavy-metal polluted soils. This semi-halophyte is a C 3 /CAM (Crassulacean acid metabolism) intermediate plant capable of tolerating extreme levels of cadmium in the soil. The aim of the work was to obtain and characterize novel, Cd-tolerant microbial strains that populate the root zone of M. crystallinum performing different types of photosynthetic metabolism and growing in Cd-contaminated substrates. The plants exhibiting either C 3 or CAM photosynthesis were treated for 8 days with different CdCl 2 doses to obtain final Cd concentrations ranging from 0.82 to 818 mg⋅kg -1 of soil d.w. The CAM phase was induced by highly saline conditions. After treatment, eighteen bacterial and three yeast strains were isolated from the rhizosphere and, after preliminary Cd-resistance in vitro test, five bacterial strains were selected and identified with a molecular proteomics technique. Two strains of the species Providencia rettgeri (W6 and W7) were obtained from the C 3 phase and three (one Paenibacillus glucanolyticus S7 and two Rhodococcus erythropolis strains: S4 and S10) from the CAM performing plants. The isolates were further tested for Cd-resistance (treatment with either 1 mM or 10 mM CdCl 2 ) and salinity tolerance (0.5 M NaCl) in model liquid cultures (incubation for 14 days). Providencia rettgeri W7 culture remained fully viable at 1 mM Cd, whereas Rh. erythropolis S4 and S10 together with P. glucanolyticus S7 were found to be resistant to 10 mM Cd in the presence of 0.5 M NaCl. It is suggested that the high tolerance of the common ice plant toward cadmium may result from the synergic action of the plant together with the Cd/salt-resistant strains occurring within rhizospheral microbiota. Moreover, the isolated bacteria appear as promising robust microorganisms for biotechnological applications in bio- and phytoremediation projects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Supel, Śliwa-Cebula, Miszalski and Kaszycki.)

Background: Lead aprons, as a type of individual radiological shields, are designed to protect the body against the negative effects of ionizing radiation. In order for the individual shields to fulfill their task, the weakening of the X-ray beam should be as high as possible. Previous reports have indicated the possibility of significant defects even among newly purchased aprons. The aim of the study was to analyze the influence of storage conditions and usage time on the permeability of lead aprons., Material and Methods: The analysis covered 11 lead aprons used by the staff and patients of the Department of Radiodiagnostics and Interventional Radiology of the Central Clinical Hospital in Katowice, Poland. The dependent variable was the average pixel value, and the grouping variables included the storage method, age and thickness of the apron, and the type of its user., Results: Statistically significant differences were found between the weakening value of the X-ray beam of individual aprons, and their storage conditions and age., Conclusions: Aprons stored in a hanging position show a greater degree of weakening of the X-ray beam, and thus a higher degree of worker protection, compared to aprons stored otherwise. The age of the apron affects its protective properties. Med Pr. 2022;73(1):13-7., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Ultrasonographic elastography is a relatively new imaging modality for the qualitative and quantitative assessments of tissue elasticity. While it has steadily gained use in adult clinical practice, including for liver diseases, breast cancer, thyroid pathologies, and muscle and tendon diseases, data on its paediatric application is still limited. Moreover, diagnosis of muscular diseases in children remains challenging. The gold standard methods, namely biopsy, electroneurography, and electromyography, are often limited owing to their invasive characteristics, possible contraindications, complications, and need for good cooperation, that is, a patient's ability to perform certain tasks during the examination while withstanding discomfort, which is a significant problem especially in younger or uncooperative children. Genetic testing, which has broad diagnostic possibilities, often entails a high cost, which limits its application. Thus, a non-invasive, objective, repeatable, and accessible tool is needed to aid in both the diagnosis and monitoring of muscle pathologies. We believe that elastography may prove to be such a method. The aim of this review was to present the current knowledge on the use of muscle elastography in the paediatric population and information on the limitations of elastography in relation to examination protocols and factors for consideration in everyday practice and future studies.

Background and Objectives : Carotid web (CaW) is an intimal variant of fibromuscular dysplasia and may constitute as one of rare causes of acute ischemic stroke (AIS). The objective of this study was to determine the prevalence of CaW in patients with AIS or transient ischemic attack (TIA) based on head/neck CT angiography (CTA) in a Polish cohort study. Materials and Methods : A retrospective study was performed by analyzing 1480 electronic clinical and imaging data regarding patients with AIS or TIA, hospitalized in the years 2018-2020 in the authors' institution. The final sample consisted of 181 patients who underwent head/neck CTA; aged 67.81 ± 13.51 years (52% were women). All head/neck CTA studies were independently evaluated by two radiologists. The patient's clinical condition was assessed with the National Institutes of Health Stroke Scale (NIHSS, 5.76 ± 4.05 and 2.88 ± 3.38 at admission and at discharge, respectively). Results : 27 patients were identified with CaW. The prevalence of CaW in the final sample (181 pts with good quality CTA) was 14.9%. In the CaW group, 89% patients had AIS, including 26% diagnosed with recurrent and 11% with cryptogenic strokes. There were no significant differences between the presence of CaW and gender, age, NIHSS score, recurrent or cryptogenic stroke. Conclusions: Our study demonstrated that CaW may be an underrecognized entity leading to cerebrovascular events. The diagnosis of CaW depends on a high level of awareness and a comprehensive analysis of the neuroimaging studies. Our findings support the hypothesis that it is worthwhile to perform CTA to determine the etiology of ischemic stroke, particularly if predicting factors were not identified.

One modern imaging technique used in the diagnosis of Crohn's disease (CD) is sonoelastrography of the intestine. Guidelines regarding the use of bowel sonoelastography in CD have still not been specified. The aim of our research was to conduct a systematic review of the use of sonoelastography in the diagnosis, assessment, and monitoring of strictures in the course of CD. A systematic review was conducted according to the PRISMA guidelines statement. The following databases were searched in January 2021: MEDINE via PubMed, Embase and Scopus. The search utilised the following MeSH tags: 'Ultrasound Shear Wave', 'Elastography', 'elastogram', 'elastographies' AND 'Crohn disease'. The inclusion criteria were as follows: from 2010 or later, articles with abstracts, articles in English, human-based studies and original articles. Articles were assessed independently by two reviewers. Out of 181 articles, only 15 met the criteria and were included in the review. Due to a small number of studies and significant methodological differences, the feasibility of using sonoelastography for Crohn's disease must be proven through further research and analysis. In the future, standardised assessment criteria and cut-off points should be established for both strain elastography (SE) and shear wave elastography (SWE).

Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kumashie, Cebula, Hagedorn, Kreppel, Pils, Koch-Nolte, Rissiek and Wirth.)

Background and Objectives: This work focuses on the possibility of using the point shear wave elastography (pSWE) method for detecting biochemical markers in diffuse liver diseases. Additionally, this study addresses the issue of the influence of ultrasound factors on the pSWE quality indicators of the obtained measurements. Materials and Methods: A pSWE examination was performed on 139 patients (69 female and 70 male) diagnosed with diffuse liver disease. The average age for all patients was 50.7 ± 15.0 years (female: 52.7 ± 15.2 years; male: 48.8 ± 14.6 years). Of these 139 patients, 65 met the inclusion criteria regarding biochemical parameters. The pSWE quality indicators were related to abnormalities found in B-mode ultrasound. Results: A strong positive correlation was found between the results of the pSWE and all biochemical indexes analysed, with the exception of age/platelet count (PLT), for which an average correlation was obtained. The greatest correlation was observed between the elastography and King's Score index. There was no correlation observed between elastography and any of the analysed parameters or biochemical indexes considered. The pSWE measurements were impaired by factors such as thick soft tissue, uneven hepatic surface, hepatomegaly and female gender. No statistically significant difference in pSWE quality indicators parameters was found between disease entities. Conclusions: pSWE seems to be a complementary method for detecting biochemical indexes, but its results can be influenced by numerous factors.

Background and objectives: In the paediatric population, hand injuries are one of the most frequent injuries and the second most frequent area of fracture. It is estimated that hand injuries account for up to 23% of the trauma-related causes of emergency department visits. Not only are they a significant factor in health care costs, but they may also lead to detrimental and long-term consequences for the patient. The discrepancy observed between the published studies suggests a geographical variation in their epidemiology. The aim of this study is to determine the localisation of injuries and fractures involving the hand in the paediatric population of the Polish Silesia region. This exploratory cross-sectional study involved 1441 post-traumatic hand X-ray examinations performed at the Department of Diagnostic Imaging of the John Paul II Upper Silesian Child Health Centre in Katowice between January and December 2014. Materials and Methods: The study group consisted of 656 girls and 785 boys who were 11.65 ± 3.50 and 11.51 ± 3.98 years old, respectively (range: 1-18 years). All examinations were evaluated for the location of the injury and presence of fracture(s). Results: Finger injuries were dominant ( n = 1346), with the fifth finger being the most frequently injured ( n = 381). The majority of injuries were observed among children who were 11 years old ( n = 176), with a visible peak in the 11- to 13-year-old group. A total of 625 bone fractures were detected. Fractures of the proximal phalanges ( n = 213) and middle phalanges ( n = 159) were most common, and fifth finger ( n = 189) predominance was again observed. A gender-independent positive correlation was found between patients' age and finger injuries ( p < 0.01) as well as metacarpal injuries ( p < 0.01). There was no correlation between patients' age and fractures in these locations ( p > 0.05). Metacarpal injuries ( p < 0.01), finger injuries ( p < 0.01), fractures ( p = 0.01), and fractures with displacement ( p = 0.03) were more common among males regardless of age. Conclusions: The results indicate that 11-year-old boys are at an increased risk of hand injuries and fractures. The distal and middle phalanges of the right hand, especially of the fifth digit, were the most susceptible to fracture localisation. Thus, injuries in these areas should be perceived as most likely to cause fractures and therefore demand careful examination.

The common ice plant ( Mesembryanthemum crystallinum L.) is a widely studied model due to its tolerance to numerous biotic and abiotic stresses. In this study, carried out in model pots, the plants were treated with variant doses of Cd(II) and Cr(VI) and proved resistant to extreme levels of these heavy metals. Initial toxicity symptoms were observed upon final concentrations of 818 mg Cd kg -1 soil d.w., and 1699 mg Cr kg -1 applied as potassium chromate. Biometric analyses revealed that none of the Cr(VI) doses affected dry weight of the plant organs thus maintaining the shoot-to-root ratio. The Cd and Cr hypertolerance strategies were divergent and resulted in different accumulation patterns. For the case of Cd(II), an excluder-like mechanism was developed to prevent the plant from toxicity. For chromate, high accumulation potential together with Cr(VI) root-to-shoot translocation at sublethal concentrations was revealed (up to 6152 mg Cr kg -1 shoot at 4248 mg Cr kg -1 soil). It is concluded that M. crystallinum reveals considerable phytoremediation capabilities due to unique growth potential in contaminated substrates and is suitable for bioreclamation of degraded soils. The plant is especially applicable for efficient phytoextraction of chromate-contamination, whereas for Cd-affected areas it may have a phytostabilizing effect.

Background: In accordance with the European guidelines on rhinosinusitis and nasal polyps (EPOS 2012), CT is used as the main imaging modality for the assessment intensity of inflammatory lesions.The aim of this study was to measure the differences in the assessment of inflammatory changes in the paranasal sinuses due to different parameters of width (W) and length (L) of the CT window., Material/methods: A retrospective analysis included 44 CT scans of the paranasal sinuses that were performed in adults. All studies were characterized by the presence of inflammatory changes in at least one of the sinuses.Measurements of the same inflammatory lesions were performed sequentially with different CT windows. The results were statistically analyzed., Results: A statistically significant difference was observed between the average measurements that were performed with the use CT windows dedicated for the sinuses and head. A downward trend in the measured values and a shift towards soft tissue values was observed with decreasing window parameters., Conclusions: A major cause of inaccurate examinations of pathological changes in the paranasal sinuses may be due to selection of unsuitable CT windows. Therefore, in order to avoid missing inflammatory lesions in the paranasal sinuses, it is reasonable to use CT windows dedicated for the sinuses or bones., Competing Interests: The authors do not have any disclosures or conflict of interests that they would like to declare in relation to their paper.

Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination-induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response., (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA) exclusively in alveolar type II epithelial cells. This model is characterized by the absence of functional endogenous T cell responses upon OVA neoantigen induction. Standard DNA and protein vaccination protocols resulted in the accumulation of high numbers of antigen-specific CD8 T cells in the lung. However, clearance of antigen-expressing cells was not achieved. To overcome this tolerance, we induced inflammatory conditions by coapplication of the TLR ligands LPS and CpG-ODN during intrapulmonary vaccinations. Both ligands induced high numbers of neoantigen-specific T cells in the lung. However, only coapplication of CpG-ODN was sufficient to establish functional cytotoxic responses resulting in the elimination of neoantigen presenting target cells. Remarkably, CpG-ODN was also crucial for functional memory responses upon re-induction of the neoantigen. The results highlight the need of TLR9 co-stimulation for overcoming tolerization, which might be a key factor for therapeutic interventions.

Both soluble and membrane-bound enzymes can catalyze the conversion of lipophilic substrates. The precise substrate access path, with regard to phase, has however, until now relied on conjecture from enzyme structural data only (certainly giving credible and valuable hypotheses). Alternative methods have been missing. To obtain the first experimental evidence directly determining the access paths (of lipophilic substrates) to phase constrained enzymes we here describe the application of a BODIPY-derived substrate (PS1). Using this tool, which is not accessible to cytosolic enzymes in the presence of detergent and, by contrast, not accessible to membrane embedded enzymes in the absence of detergent, we demonstrate that cytosolic and microsomal glutathione transferases (GSTs), both catalyzing the activation of PS1, do so only within their respective phases. This approach can serve as a guideline to experimentally validate substrate access paths, a fundamental property of phase restricted enzymes. Examples of other enzyme classes with members in both phases are xenobiotic-metabolizing sulphotransferases/UDP-glucuronosyl transferases or epoxide hydrolases. Since specific GSTs have been suggested to contribute to tumor drug resistance, PS1 can also be utilized as a tool to discriminate between phase constrained members of these enzymes by analyzing samples in the absence and presence of Triton X-100.

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.

Bacterial resistance against classical antibiotics is a growing problem and the development of new antibiotics is limited. Thus, novel alternatives to antibiotics are warranted. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can be induced by several compounds, including vitamin D and phenyl-butyrate (PBA). Utilizing a luciferase based assay, we recently discovered that the histone deacetylase inhibitor Entinostat is a potent inducer of the CAMP gene encoding the human cathelicidin LL-37. Here we investigate a mechanism for the induction and also find that Entinostat up-regulates human β-defensin 1. Analysis of the CAMP promoter sequence revealed binding sites for the transcription factors STAT3 and HIF-1α. By using short hairpin RNA and selective inhibitors, we found that both transcription factors are involved in Entinostat-induced expression of LL-37. However, only HIF-1α was found to be recruited to the CAMP promoter, suggesting that Entinostat activates STAT3, which promotes transcription of CAMP by increasing the expression of HIF-1α. Finally, we provide in vivo relevance to our findings by showing that Entinostat-elicited LL-37 expression was impaired in macrophages from a patient with a STAT3-mutation. Combined, our findings support a role for STAT3 and HIF-1α in the regulation of LL-37 expression., Competing Interests: R.S., G.H.G., B.A. are co-founders of Akthelia, a company that holds a patent for the use of Entinostat in the treatment of infections; (Strömberg R., Ottoson H., Agerberth B., Gudmundsson G., Miraglia E. & Nylen F. Antimicrobial compounds. Application: WO patent 2014-IB65678 2015063694, 2015).

Thioredoxin-related protein of 14 kDa (TRP14, also called TXNDC17 for thioredoxin domain containing 17, or TXNL5 for thioredoxin-like 5) is an evolutionarily well-conserved member of the thioredoxin (Trx)-fold protein family that lacks activity with classical Trx1 substrates. However, we discovered here that human TRP14 has a high enzymatic activity in reduction of l-cystine, where the catalytic efficiency (2,217 min(-1)⋅µM(-1)) coupled to Trx reductase 1 (TrxR1) using NADPH was fivefold higher compared with Trx1 (418 min(-1)⋅µM(-1)). Moreover, the l-cystine reduction with TRP14 was in contrast to that of Trx1 fully maintained in the presence of a protein disulfide substrate of Trx1 such as insulin, suggesting that TRP14 is a more dedicated l-cystine reductase compared with Trx1. We also found that TRP14 is an efficient S-denitrosylase with similar efficiency as Trx1 in catalyzing TrxR1-dependent denitrosylation of S-nitrosylated glutathione or of HEK293 cell-derived S-nitrosoproteins. Consequently, nitrosylated and thereby inactivated caspase 3 or cathepsin B could be reactivated through either Trx1- or TRP14-catalyzed denitrosylation reactions. TRP14 was also, in contrast to Trx1, completely resistant to inactivation by high concentrations of hydrogen peroxide. The oxidoreductase activities of TRP14 thereby complement those of Trx1 and must therefore be considered for the full understanding of enzymatic control of cellular thiols and nitrosothiols.

The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA&#95;X&#95;CreER(T2) mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b)/OVA257-264-specific OT-I T cells to OVA&#95;X&#95;CreER(T2) mice or generated triple transgenic OVA&#95;X CreER(T2)&#95;X&#95;OT-I mice. OT-I T cells become activated in OVA&#95;X&#95;CreER(T2) mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA&#95;X&#95;CreER(T2)&#95;X&#95;OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA&#95;X&#95;CreER(T2)&#95;X&#95;OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

The human selenoprotein thioredoxin reductase 1 (TrxR1), encoded by the TXNRD1 gene, is a key player in redox regulation. Alternative splicing generates several TrxR1 variants, one of which is v3 that carries an atypical N-terminal glutaredoxin domain. When overexpressed, v3 associates with membranes and triggers formation of filopodia. Here we found that membrane targeting of v3 is mediated by myristoylation and palmitoylation of its N-terminal MGC motif, through which v3 specifically targets membrane rafts. This was suggested by its localization in cholera toxin subunit B-stained membrane areas and also shown using lipid fractionation experiments. Utilizing site-directed mutant variants, we also found that v3-mediated generation of filopodia is independent of the Cys residues in its redox active site, but dependent upon its membrane raft targeting. These results identify v3 as an intricately regulated protein that expands TXNRD1-derived protein functions to the membrane raft compartment.