Challenging Diagnostics of Biofilm Associated Periprosthetic Infection in Immunocompromised Patient: A Clinical Case

Abstract BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of joint arthroplasty. The identification of microorganisms in biofilm-related PJI is challenging yet significant stage of the treatment process. Medical microbiology methods, such as pure culture isolation, remain the gold standard. However, the error rate of classical methods may vary from 10% to as high as 42% due to the inability to detect bacteria growing within biofilms. Other methods of detection are being explored to improve the management of PJI. AIM: Accurate identification of PJI contributing microorganisms in a patient with acute postoperative PJI after total hip joint arthroplasty and systemic lupus erythematosus in anamnesis. METHODS: We used microbial culture methods followed by scanning electron microscopy (SEM). RESULTS: Perioperative an intraoperative cultural analysis of 8 different culture samples of tissue and prosthetic origin was insufficient for bacterial or fungal detection. Scanning electron microscopy revealed detailed biofilm visualisation on the surface of the prosthetic component. The biofilm exterior was composed of microbial clusters made of 10 or more cells with either pear- or bottle-shaped morphology, 3-6 mcm in length and 1.5-3 mcm in diameter. Rod-shaped microorganisms of 0.7-1 mcm length and up to 0.5 mcm in diameter were found adjacent to these clusters. CONCLUSION: Additional methods for PJI agents’ detection are time-and cost-effective in the case of the challenging diagnostics of biofilm-related PJI, particularly in immunocompromised patients. Using combined diagnostic approaches increases the accuracy of detection, justifies treatment strategies and improves clinical outcomes

Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer

Background: Inflammatory breast cancer (IBC) is a rare and understudied disease, with 40% of cases presenting with human epidermal growth factor receptor 2 (HER2)-positive subtype. The goals of this study were to (i) assess the pathologic complete response (pCR) rate of short-term neoadjuvant dual-HER2-blockade and paclitaxel, (ii) contrast baseline and on-treatment transcriptional profiles of IBC tumor biopsies associated with pCR, and (iii) identify biological pathways that may explain the effect of neoadjuvant therapy on tumor response. Patients and Methods: A single-arm phase II trial of neoadjuvant trastuzumab (H), pertuzumab (P), and paclitaxel for 16 weeks was completed among patients with newly diagnosed HER2-positive IBC. Fresh-frozen tumor biopsies were obtained pretreatment (D1) and 8 days later (D8), following a single dose of HP, prior to adding paclitaxel. We performed RNA-sequencing on D1 and D8 tumor biopsies, identified genes associated with pCR using differential gene expression analysis, identified pathways associated with pCR using gene set enrichment and gene expression deconvolution methods, and compared the pCR predictive value of principal components derived from gene expression profiles by calculating and area under the curve for D1 and D8 subsets. Results: Twenty-three participants were enrolled, of whom 21 completed surgery following neoadjuvant therapy. Paired longitudinal fresh-frozen tumor samples (D1 and D8) were obtained from all patients. Among the 21 patients who underwent surgery, the pCR and the 4-year disease-free survival were 48% (90% CI 0.29-0.67) and 90% (95% CI 66-97%), respectively. The transcriptional profile of D8 biopsies was found to be more predictive of pCR (AUC = 0.91, 95% CI: 0.7993-1) than the D1 biopsies (AUC = 0.79, 95% CI: 0.5905-0.9822). Conclusions: In patients with HER2-positive IBC treated with neoadjuvant HP and paclitaxel for 16 weeks, gene expression patterns of tumor biopsies measured 1 week after treatment initiation not only offered different biological information but importantly served as a better predictor of pCR than baseline transcriptional analysis

Improving the Effectiveness of Training the On-board Object Detection System for a Compact Unmanned Aerial Vehicle

The model of object detector and the criterion of leaning effectiveness of the model were proposed. The model contains 7 first modules of the convolutional Squeezenet network, two convolutional multiscale layers and the information­extreme classifier. The multiplicative convolution of the particular criteria that takes into account the effectiveness of detection of objects in the image and accuracy of the classification analysis was considered as the criterion of learning effectiveness of the model. In this case, additional use of the orthogonal matching pursuit algorithm in calculating high­level features makes it possible to increase the accuracy of the model by 4 %. The training algorithm of object detector under conditions of a small size of labeled training datasets and limited computing resources available on board of a compact unmanned aerial vehicle was developed. The essence of the algorithm is to adapt the high­level layers of the model to the domain application area, based on the algorithms of growing sparse coding neural gas and simulated annealing. Unsupervised learning of high­level layers makes it possible to use effectively the unlabeled datasets from the domain area and determine the required number of neurons. It is shown that in the absence of fine tuning of convolutional layers, 69 % detection of objects in the images of the test dataset Inria Aerial Image was ensured. In this case, after fine tuning based on the simulated annealing algorithm, 95 % detection of the objects in test images is ensured. It was shown that the use of unsupervised pretraining makes it possible to increase the generalizing ability of decision rules and to accelerate the iteration process of finding the global maximum during supervised learning on the dataset of limited size. In this case, the overfitting effect is eliminated by optimal selection of the value of hyperparameter, characterizing the measure of coverage of the input data of by network neurons

Identifying Changes in the Milking Rubber of Milking Machines During Testing and Under Industrial Conditions

Milking rubber is the only part of the milking equipment that comes into direct contact with the cow's teats. The task is to establish the high-quality technical and technological characteristics of the rubber liners for milking machines. It has been established that milking rubber after 600‒650 hours of operation acquires significant deflection in the range of 5.5±0.03–3.7±0.04 mm while a teat cup deformation varies within 1.3±0.02–3.5±0.05 mm. A positive correlation dependence of the milking rubber elasticity on the deformation of its teat cup (r=+0.948) has been found.The method of passing the electric discharge was used to assess the readiness of milking rubber for use, whereby a variation coefficient of υ˂10 % was determined for the milking rubber DD 00.041A AO «Bratslav», which makes it possible to estimate the product quality.It was found that the change in the mass and volume of milking rubber over 72 hours of its treatment with the liquid SZHR-3 at t=150 °C exceeds the indicators obtained in contact with the liquid Skydrol LD-4 by more than 2.5 times. A positive correlation dependence of the milking rubber mass on its volume (r=+0.965) has been established.It was found that at a rubber tension in the range of 0 to 90 N the duration of the deformation loss experienced by the milking rubber shell was not long; it is 0.05‒0.06 s. With an increase in the service life of milking rubber to 4 months, there is a decrease in its tension, from 56‒60 N to 43‒45 N, which adversely affects the maximum speed of milk yield – it decreases by 1.5 times.A positive correlation dependence of the milking rubber service life on the level of its bacterial insemination (r=+0.960) has been establishe

Determining A Technique for Transmitting Measuring Data on the Spatial Positioning of the Piercing Head in Small-size Installations During Controlled Soil Piercing

For laying of underground utility systems in urban conditions by the method of horizontally directed soil piercing, small-sized units are designed. Such units should have measurement systems for determining the spatial position of the piercing head. In known systems, the surface layer of the soil is used as a data transmission line for transmitting measurement information.This method of transmitting information signals in urban conditions is not very acceptable. Ground-based objects reflect electromagnetic radiation of the head transmitter which leads to distortion of the directional diagram of the emitter and complicates the reliable reception of measurement information.It was proposed to use an autonomous measuring system with an operating frequency of 5 GHz based on Wi-Fi technologies and an unconventional method of transmitting measurement information using hollow steel bars in the piercing unit itself. This transmission line has periodic discontinuities because of the bar design. These discontinuities accumulate as the piercing head advances. For the basic vibration type Н11, more accurate analytical expressions were obtained for calculating the power transfer coefficient of the measurement signal in such non-uniform lines. It was shown that inhomogeneity of the transmission line in comparison with its surface resistance does not significantly affect the transmission coefficient.For example, damping in the line increased by 1.2 dB with the maximum length of inhomogeneity of 5 mm and the total length of jointed bars of 50 m. It has been theoretically proven that the range of soil piercing with reliable signal reception can be up to 50 meters.The proposed method for transmitting information signals makes it possible to reduce the transmitter power, ensure noise immunity of the measuring system, and reliable reception of the measuring information throughout the entire piercing pat

Identifying Changes in the Milking Rubber of Milking Machines During Testing and Under Industrial Conditions

Milking rubber is the only part of the milking equipment that comes into direct contact with the cow's teats. The task is to establish the high-quality technical and technological characteristics of the rubber liners for milking machines. It has been established that milking rubber after 600‒650 hours of operation acquires significant deflection in the range of 5.5±0.03–3.7±0.04 mm while a teat cup deformation varies within 1.3±0.02–3.5±0.05 mm. A positive correlation dependence of the milking rubber elasticity on the deformation of its teat cup (r=+0.948) has been found.The method of passing the electric discharge was used to assess the readiness of milking rubber for use, whereby a variation coefficient of υ˂10 % was determined for the milking rubber DD 00.041A AO «Bratslav», which makes it possible to estimate the product quality.It was found that the change in the mass and volume of milking rubber over 72 hours of its treatment with the liquid SZHR-3 at t=150 °C exceeds the indicators obtained in contact with the liquid Skydrol LD-4 by more than 2.5 times. A positive correlation dependence of the milking rubber mass on its volume (r=+0.965) has been established.It was found that at a rubber tension in the range of 0 to 90 N the duration of the deformation loss experienced by the milking rubber shell was not long; it is 0.05‒0.06 s. With an increase in the service life of milking rubber to 4 months, there is a decrease in its tension, from 56‒60 N to 43‒45 N, which adversely affects the maximum speed of milk yield – it decreases by 1.5 times.A positive correlation dependence of the milking rubber service life on the level of its bacterial insemination (r=+0.960) has been establishe

Improving the Algorithm of Choosing Spacing and Number of Stiff Supports Against A Concentrated Force in Steel-concrete Beams

A steel-concrete beam was taken as the study object. The algorithm of selecting the number of stiff supports for the steel-concrete beam loaded with a concentrated lateral force in the middle of the span has been refined. Stiff supports served to join the steel strip with concrete to ensure their joint performance. The algorithm was refined based on the condition of equality of the longitudinal force in the steel strip from the action of the calculated load and the maximum longitudinal force obtained after setting the supports. In this case, the longitudinal forces in all stiff supports, as well as the spacing of the stiff supports should be the same. A disadvantage of the known algorithm consists in the complexity of determining the coefficient φb2 taking into account the effect of long-term concrete creep on the element deformation without cracks. This coefficient fluctuates widely and depends on many factors. Besides, it is also insufficiently studied. Calculations for determining the number and spacing of stiff supports in a steel-concrete beam were conducted according to the proposed algorithm and in the Lira software package. The forces acting on the supports and spacing of the supports were the same. The force acting in the support was 8941.5 N. When selecting characteristics of the steel-concrete beam, maximum longitudinal force in the steel strip was obtained. The longitudinal force amounted to 35726 N. The same longitudinal force was obtained from the diagram of longitudinal forces obtained after setting the supports. This study was aimed at improving the design of steel-concrete beams. A rational number and placement of stiff supports ensure savings: the required amount of building materials is reduced and their cost is reduced due to cutting labor costs for their manufacture and operatio

Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles

Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs