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Paweł Radkowski,1– 3 Michał Jacewicz,2 Iwona Podlińska,2 Maria Derkaczew2 1Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 3Department of Anaesthesiology and Intensive Care, Hospital zum Heiligen Geist in Fritzlar, Fritzlar, GermanyCorrespondence: Maria Derkaczew, Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland, Email m.derkaczew@gmail.comIntroduction: Patients after chemotherapy and radiotherapy while being operated can suffer from different systemic problems, which may complicate the anesthetic management. Some interactions between muscle relaxants and chemotherapeutics can occur.Aim: This article aims to present the use of muscle relaxants in cancer patients who have undergone chemotherapy and radiotherapy.Material and Methods: Our work is based on the available literature and the authors’ experience.Conclusion: Based on our observations and a thorough examination of the medical literature, it is advisable to exercise significant caution when employing muscle relaxants in individuals undergoing chemotherapy and radiotherapy. All muscle relaxants can behave differently after chemotherapy and radiotherapy, and for this reason, practitioners should familiarize themselves with the pharmacodynamics and pharmacokinetics of their chosen muscle relaxant.Keywords: muscle relaxant, chemotherapy, radiotherapy

Paweł Radkowski,1– 3 Michał Jacewicz,2 Katarzyna Podhorodecka1 1Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 3Hospital zum Heiligen Geist, Fritzlar, GermanyCorrespondence: Paweł Radkowski, Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Żołnierska 18, Olsztyn, 10-561, Poland, Tel +48-882815714, Email k.podhorodecka1@gmail.comIntroduction: Anaesthetising a pregnant woman and during the postpartum period is challenging for most anaesthetists. There are many factors involved, including all the physiological changes that occur in the body of such a woman. Particular attention should be paid to muscle relaxants.Aim: The purpose of this article is to present the use of muscle relaxants in pregnancy and puerperium period.Material and Methods: This work is based on the available literature and the authors’ experience.Conclusion: In our experience and from a broad review of the medical literature, a great deal of caution should be exercised when using muscle relaxants during the anaesthesia of pregnant or postpartum patients. The pharmacodynamic and pharmacokinetic differences in the action of this group of drugs during this period should be known.Keywords: muscle relaxant, pregnancy, puerperium period, anaesthesia

Frozen microspheres of hydrogen (pellets) are used as targets in the hadron physics experiment WASA (Forschungszentrum Jülich, Germany) [1] and will also be used in the future PANDA experiment at FAIR (GSI, Darmstadt, Germany) [2]. The interaction region is defined by the overlap of the pellet stream and the accelerator beam and has a size of a few millimeters. One would like to know the interaction point more precisely, to have better possibility to reconstruct particle tracks and events. One would also like to suppress background events that do not originate in a pellet, but e.g. may occur in residual gas in the beam pipe. A solution is provided by the presented pellet tracking system, for which a prototype [3] has been developed in Uppsala. The goal is to track individual pellets in order to know their position at the time of an interaction. The design of such a system, simulation techniques and results are presented.

Identification of a spinning projectile controlled with gasodynamic engines is shown in this paper. A missile model with a measurement inertial unit was developed from Newton's law of motion and its aerodynamic coefficients were identified. This was achieved by applying the maximum likelihood principle in the wavelet domain. To assess the results, this was also performed in the time domain. The outcomes were obtained for two cases: when noise was not present and when it was included in the data. In all cases, the identification was performed in the passive mode, i.e., no special system identification experiments were designed. In the noise-free case, aerodynamic coefficients were estimated with high accuracy. When noise was included in the data, the wavelet-based estimates had a drop in their accuracy, but were still very accurate, whereas for the time domain approach the estimates were considered inaccurate.

The article presents the analysis of the impact point dispersion reduction using lateral correction thrusters. Two types of control algorithms are used and four sources of uncertainties are taken into account: aerodynamic parameters, thrust curve, initial conditions and IMU errors. The Monte Carlo approach was used for simulations and Circular Error Probable was used as a measure of dispersion. Generic rocket mathematical and simulation model was created in MATLAB/Simulink 2020b environment. Results show that the use of control algorithms greatly reduces the impact point dispersion.

Background/aim: The aim of this study was to evaluate the cancer detection rate (CDR) using magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion-guided transperineal targeted biopsy (TB)., Patients and Methods: We included 401 consecutive patients, of which 161 were biopsy-naïve. All underwent prebiopsy bi-parametric MRI; patients with positive MRI [prostate imaging reporting and data system (PI-RADS≥3)] underwent TB. Biopsy-naïve patients with positive MRI underwent TB and systematic biopsies (SBs). MRI-negative patients underwent SBs. Clinically significant prostate cancer (csPCa) was defined as ISUP ≥2. The added value of SB was defined as an upgrade from a negative biopsy or ISUP of 1 in TB to csPCa in SB., Results: The median (interquartile range) age was 69 (range=63-74) years, and PSA was 6.9 (range=4.5-11) ng/ml. The overall CDR was 65%, with csPCa occurring in 48%. In cases of PI-RADS 5, CDR was 91%, and csPCa was 77%. The added value of SB was 2%., Conclusion: Transperineal TB biopsies using MRI-TRUS fusion yield a high CDR., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

INTRODUCTION    The prevalence of polycystic ovary syndrome (PCOS) among women with type 1 diabetes (T1DM) is higher than in the general population. Both diseases are associated with higher risk of premature atherosclerosis. OBJECTIVES    The aim of our study was to evaluate whether the cardiovascular risks conferred by T1DM and PCOS are additive. PATIENTS AND METHODS   The study group included 78 women divided into 4 groups: 19 women with PCOS and T1DM (T1DM+PCOS), 16 women with T1DM only (T1DM/no‑PCOS), 27 women with PCOS only(PCOS), and 16 healthy women (control group). We evaluated the serum concentrations of cardiovascular disease biomarkers: soluble intercellular adhesion molecule 1 (sICAM‑1) and soluble endothelial‑leukocyte adhesion molecule 1 (sE‑selectin). We also assessed brachial artery flow‑mediated dilation (FMD) and estimated the intima-media thickness of the common carotid artery (CIMT) by ultrasonography. RESULTS    The serum concentrations of sICAM‑1and sE‑selectin were higher in the T1DM+PCOS group compared with women with PCOS only (P = 0.041 and P = 0.002, respectively) and were comparable to those in the T1DM/no‑PCOS group. FMD and CIMT did not differ between the groups. In women with T1DM, sICAM‑1 positively correlated with body mass index (r = 0.34, P = 0.047), CIMT with daily insulin dose (r = 0.37, P = 0.039), and FMD negatively correlated with diabetes duration (r = -0.42, P = 0.02). In a multivariable logistic regression model, the presence of T1DM, with adjustment for sICAM‑1, was the only predictor of sE‑selectin concentrations in the whole study group (odds ratio, 8.03; 95% confidence interval, 2.56-13.49; P = 0.005). CONCLUSIONS    The presence of PCOS does not increase the risk of subclinical vascular disease in young lean women with T1DM.

Shiga toxin is a potent protein toxin produced by Shigella dysenteriae type I strains. In this report we present a procedure for the separation of functionally intact toxin A and B chains and for their reconstitution to form biologically active molecules. In agreement with the findings of others, the isolated A chain was shown to be a potent in vitro inhibitor of eukaryotic protein synthesis. The isolated B chain bound to HeLa cells and competitively inhibited the binding and cytotoxic activity of holotoxin. These findings show that the functional rote of the B chain is to recognize cell surface functional receptors. By labelling the B subunit alone, prior to renaturation of holotoxin, the polypeptide chains were shown to associate noncovalently with a stoichiometry of one A chain and five B chains. [ABSTRACT FROM AUTHOR]

Introduction: Data underline the role of betatrophin in glucose homeostasis. Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR). The aim of our study was to investigate the relationship of serum betatrophin concentrations with indirect indices of IR and insulin secretion in women with PCOS, compared to the control group., Methods: The study group comprised 43 women with PCOS and 16 controls. IR was assessed by HOMA-IR and Matsuda index. Insulin secretion was evaluated with HOMA-B. An oral glucose tolerance test (OGTT) with estimation of serum betatrophin concentrations was performed., Results: Glucose load resulted in an increase in serum betatrophin concentrations in the control group ( p = 0.02). Serum betatrophin concentrations at 120 min of OGTT were lower in women with PCOS than in the control group ( p = 0.02). We observed positive correlations between baseline serum betatrophin concentrations and HOMA-IR ( r = 0.39, p = 0.008), negative correlations with Matsuda index ( r = -0.31, p = 0.004), and a positive relationship with HOMA-B ( r = 0.38, p = 0.01) in women with PCOS. Multiple regression analysis revealed that HOMA-B ( β = 0.47, p = 0.001) was an independent factor connected to serum betatrophin levels in PCOS., Conclusions: Serum concentrations of betatrophin are connected with insulin resistance and beta cell function and did not change after glucose load in women with PCOS.

The process of developing new drugs is arduous and costly, particularly for targets classified as "difficult-to-drug." Macrocycles show a particular ability to modulate difficult-to-drug targets, including protein-protein interactions, while still allowing oral administration. However, the determination of membrane permeability, critical for reaching intracellular targets and for oral bioavailability, is laborious and expensive. In silico methods are a cost-effective alternative, enabling predictions prior to compound synthesis. Here, we present a comprehensive online database (https://swemacrocycledb.com/), housing 5638 membrane permeability datapoints for 4216 nonpeptidic macrocycles, curated from the literature, patents, and bioactivity repositories. In addition, we present a new descriptor, the "amide ratio" (AR), that quantifies the peptidic nature of macrocyclic compounds, enabling the classification of peptidic, semipeptidic, and nonpeptidic macrocycles. Overall, this resource fills a gap among existing databases, offering valuable insights into the membrane permeability of nonpeptidic and semipeptidic macrocycles, and facilitating predictions for drug discovery projects. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as a highly sensitive imaging modality for prostate cancer (PCa), outperforming conventional methods like CT, MRI, and bone scintigraphy. Over the past decade, PSMA-PET has gained widespread clinical adoption, particularly for staging intermediate- and high-risk PCa, detecting biochemical recurrence, and identifying metastatic disease. Its use of targeted radiotracers enables the detection of even small metastases, offering detailed tumor assessments and supporting advanced therapeutic strategies, especially in radioligand therapy for advanced cases. Integrated into leading clinical guidelines, PSMA-PET has significantly impacted diagnostic workflows and treatment planning. This review explores the evolution of PSMA-PET diagnostics and therapy, addressing its benefits, its integration into clinical practice, and its transformative potential. While limitations remain, PSMA-PET represents a critical step forward in the management of prostate cancer. Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [68Ga]- and [18F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care. [ABSTRACT FROM AUTHOR]

Peri-infarct depolarizations (PIDs) contribute to the evolution of focal ischemic lesions. Proposed mechanisms include both increased metabolic demand under conditions of attenuated perfusion and overt vasoconstrictive responses to depolarization. The present studies investigated the relative contributions of metabolic and perfusion effects to PID-associated infarct expansion during middle cerebral artery (MCA) occlusion in the Spontaneously Hypertensive Rat. The initial distribution of ischemic depolarization (ID) was established within minutes after MCA occlusion at a cerebral blood flow threshold of ∼40 mL/100 g per minute, with expansion of the depolarized territory during 3 hours detected in half of the animals. Peri-infarct depolarizations were associated with transient metabolic responses, comparable to those observed after spreading depression, with no evidence of cumulative energy failure after multiple transient depolarizations during 1 hour. Speckle contrast imaging of PID-associated flow transients documented prominent distal hyperemic flow responses that became progressively attenuated in regions of already impaired perfusion, with modest propagated flow decreases more proximal to the ischemic core. However, sporadic PIDs were associated with persistent decrements in perfusion, increasing tissue volume below the threshold for energy failure, ID and infarction. These latter, comparatively rare, events can account for the pattern of stepwise infarct expansion in this model.

Our previous data demonstrated that systemic inflammation evoked by intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg b.w.) induces morphological and biochemical changes in the brain, including alterations of poly(ADP-ribose) polymerase-1 (PARP-1) activity and expression of several genes. In this study, the effect of systemic inflammatory response (SIR) on glutathione redox state and on cognition, spatial memory and locomotor activity was evaluated by using spectrophotometric method, object recognition test, Morris water-maze and open-field tests, respectively. The effect of PARP-1 inhibitor was included in this study. Our data indicated that SIR significantly decreases reduced glutathione (GSH) level, enhances its disulfide form (GSSG) and decreases glutathione reductase activity. Moreover, SIR affects the object recognition and locomotor activity but has negligible effect on spatial memory. PARP-1 inhibitor protects against LPS-evoked recognition impairment and significantly improves spatial memory in LPS-treated mice. The effect of PARP-1 inhibitor could be in part connected with lowering of PARP-1 involvement in regulation of transcription of several pro-inflammatory genes. Moreover, PARP-1 inhibitors may modulate glutamatergic receptor signaling that plays an important role in learning and memory.

Shiga toxin-producing Escherichia coli (STEC) is an important food-borne pathogen that causes hemolytic-uremic syndrome. Following ingestion, STEC cells colonize the intestine and produce Shiga toxins (Stx), which appear to translocate across the intestinal epithelium and subsequently reach sensitive endothelial cell beds. STEC cells produce one or both of two major toxins, Stx1 and Stx2. Stx2-producing STEC is more often associated with disease for reasons as yet undetermined. In this study, we used polarized intestinal epithelial cells grown on permeable filters as a model to compare Stx1 and Stx2 movement across the intestinal epithelium. We have previously shown that biologically active Stx1 is able to translocate across cell monolayers in an energy-dependent, saturable manner. This study demonstrates that biologically active Stx2 is also capable of movement across the epithelium without affecting barrier function, but significantly less Stx2 crossed monolayers than Stx1. Chilling the monolayers to 4 degrees C reduced the amount of Stx1 and Stx2 movement by 200-fold and 20-fold respectively. Stx1 movement was clearly directional, favoring an apical-to-basolateral translocation, whereas Stx2 movement was not. Colchicine reduced Stx1, but not Stx2, translocation. Monensin reduced the translocation of both toxins, but the effect was more pronounced with Stx1. Brefeldin A had no effect on either toxin. Excess unlabeled Stx1 blocks the movement of (125)I-Stx1. Excess Stx2 failed to have any effect on Stx1 movement. Our data suggests that, despite the many common physical and biochemical properties of the two toxins, they appear to be crossing the epithelial cell barrier by different pathways.

Escherichia coli strains producing Shiga toxins (Stx) 1 and 2 colonize the lower gastrointestinal tract in humans and are associated with gastrointestinal and systemic diseases. Stx are detectable in the feces of infected patients, and it is likely that toxin passes from the intestinal tract lumen to underlying tissues. The objective of this study was to develop an in vitro model to study the passage of Stx across intact, polarized cell monolayers. Translocation of biologically active Stx was examined in four cell lines grown on polycarbonate filters. Stx1 translocated across intestinal cell monolayers (CaCo2A and T84 cells) in an energy-requiring and saturable manner, while the monolayers maintained a high level of electrical resistance. Stx1 had no effect on electrical resistance or inulin movement across these cell lines for at least 24 h. Induction of specific Stx receptors with sodium butyrate reduced the proportion of toxin translocated across CaCo2A monolayers but had no major effect on the movement of horseradish peroxidase or [3H]inulin. We have shown that biologically active Stx1 is capable of moving across intact polarized intestinal epithelial cells without apparent cellular disruption, probably via a transcellular pathway. The data also suggest that the presence of Stx receptors on the apical surface of intestinal epithelial cells may offer some protection against the absorption of luminal Stx1.

We reexamined the binding specificity of the Shiga-like toxin variant associated with porcine edema disease, SLT2e, which is reported to be more cytotoxic for Vero cells than for HeLa cells, by using receptor-deficient cells and a liposomal insertion system for purified glycolipids. We found that SLT2e preferentially uses globotetraosylceramide as a receptor but can also cause cytotoxicity by using globotriaosylceramide, the SLT2 receptor. We conclude that the differential cytotoxicity of SLT2e on HeLa and Vero cells is a function of both the receptor preference of the toxin and the specific glycolipid content of the target cells being used.

Shiga-like toxins (SLTs), which are produced by certain strains of Escherichia coli, are composed of enzymatically active A and B subunit multimers responsible for the toxin's binding. We have previously purified large amounts of the SLT-I B subunit by using a hyperexpression vector in Vibrio cholerae under the control of the trc promoter. In this study we examined various expression vectors to maximize yields of the SLT-II B subunit. The SLT-II B subunit has been expressed by using both the T7 promoter and the tac promoter in E. coli. When expressed from a plasmid containing the structural gene for SLT-II B deleted of the leader sequence, SLT-II B was able to form multimers when cross-linked, although SLT-II B production from this plasmid was unreproducible. SLT-II B expressed in all three systems appeared to form unstable multimers, which did not readily bind to a monoclonal antibody which preferentially recognizes B subunit multimers. SLT-II B expression was not increased by moving any of the plasmids into V. cholerae. Polyclonal antibodies raised to SLT-II B in rabbits recognized B subunit in SLT-II holotoxin yet were poorly neutralizing. SLT-II B was also expressed as a fusion protein with maltose-binding protein and could be cleaved from maltose-binding protein with factor Xa. Although the expression vectors were able to make large amounts of SLT-II B, as determined by Western blotting (immunoblotting), the levels of purified SLT-II B subunit were low compared with those obtained previously for SLT-I B subunit, probably because of instability of the multimeric SLT-II B subunit.

Shiga toxin is enterotoxic in rabbit small bowel and binds to the microvillus membrane (MVM). The toxin exhibits specificity for glycolipids possessing a terminal gal-alpha 1----4gal disaccharide, including the neutral glycolipid Gb3 in MVM. Gb3, which is developmentally regulated in the rabbit small bowel, is present in very low concentration until the animals reach day 16 of life. In older animals an increase in Gb3 content is paralleled by an increase in the ability of MVM to bind toxin, which also correlates with the fluid secretion response. Shiga toxin selectively binds to villus cells, which contain Gb3, and not to crypt cells, which do not express Gb3. Targeting of the villus cell by the toxin is consistent with physiologic studies that demonstrate inhibition of villus cell Na+ absorptive pathways, with no effect on crypt cell Cl- secretory mechanisms. These effects are sufficient to account for the enterotoxicity of Shiga toxin in the rabbit model.

Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli. Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury (AKI). Two sphingosine kinase (SphK) isozymes, SphK1 and SphK2, have been shown to be involved in barrier maintenance and renal inflammatory diseases. Therefore, we sought to determine their role in the pathogenesis of HUS. Experimental HUS was induced by the repeated administration of Stx2 in wild-type (WT) and SphK1 (SphK1−/−) or SphK2 (SphK2−/−) null mutant mice. Disease severity was evaluated by assessing clinical symptoms, renal injury and dysfunction, inflammatory status and sphingolipid levels on day 5 of HUS development. Renal inflammation and injury were found to be attenuated in the SphK2−/− mice, but exacerbated in the SphK1−/− mice compared to the WT mice. The divergent outcome appeared to be associated with oppositely altered sphingolipid levels. This study represents the first description of the distinct roles of SphK1−/− and SphK2−/− in the pathogenesis of HUS. The identification of sphingolipid metabolism as a potential target for HUS therapy represents a significant advance in the field of HUS research. [ABSTRACT FROM AUTHOR]

Knowledge about the effect of different prostate biopsy approaches on the prostate cancer detection rate (CDR) in patients with gray-zone prostate-specific antigen (PSA) is limited. We performed this study to compare the CDR among patients who underwent different biopsy approaches and had rising PSA levels in the gray zone. Two hundred and twenty-two patients who underwent transrectal prostate biopsy (TRB) and 216 patients who underwent transperineal prostate biopsy (TPB) between June 2016 and September 2022 were reviewed in this study. In addition, 110 patients who received additional targeted biopsies following the systematic TPB were identified. Clinical parameters, including age, PSA derivative, prostate volume (PV), and needle core count, were recorded. The data were fitted via propensity score matching (PSM), adjusting for potential confounders. TPB outperformed TRB in terms of the CDR (49.6% vs 28.3%, P = 0.001). The clinically significant prostate cancer (csPCa) detection rate was not significantly different between TPB and TRB (78.6% vs 68.8%, P = 0.306). In stratified analysis, TPB outperformed TRB in CDR when the age of patients was 65–75 years (59.0% vs 22.0%, P < 0.001), when PV was 25.00–50.00 ml (63.2% vs 28.3%, P < 0.001), and when needle core count was no more than 12 (58.5% vs 31.5%, P = 0.005). The CDR (P = 0.712) and detection rate of csPCa (P = 0.993) did not significantly differ among the systematic, targeted, and combined biopsies. TPB outperformed TRB in CDR for patients with gray-zone PSA. Moreover, performing target biopsy after systematic TPB provided no additional benefits in CDR. [ABSTRACT FROM AUTHOR]

Hard ticks (Ixodidae) play a critical role in transmitting various tick-borne diseases (TBDs), posing significant global threats to human and animal health. Climatic factors influence the abundance, diversity, and vectorial capacity of tick vectors. It is imperative to have a comprehensive understanding of hard ticks, pathogens, eco-epidemiology, and the impact of climatic changes on the transmission dynamics of TBDs. The distribution and life cycle patterns of hard ticks are influenced by diverse ecological factors that, in turn, can be impacted by changes in climate, leading to the expansion of the tick vector's range and geographical distribution. Vector competence, a pivotal aspect of vectorial capacity, involves the tick's ability to acquire, maintain, and transmit pathogens. Hard ticks, by efficiently feeding on diverse hosts and manipulating their immunity through their saliva, emerge as competent vectors for various pathogens, such as viruses, parasites and bacteria. This ability significantly influences the success of pathogen transmission. Further exploration of genetic diversity, population structure, and hybrid tick vectors is crucial, as they play a substantial role in influencing vector competence and complicating the dynamics of TBDs. This comprehensive review deals with important TBDs in India and delves into a profound understanding of hard ticks as vectors, their biology, and the factors influencing their vector competence. Given that TBDs continue to pose a substantial threat to global health, the review emphasizes the urgency of investigating tick control strategies and advancing vaccine development. Special attention is given to the pivotal role of population genetics in comprehending the genetic diversity of tick populations and providing essential insights into their adaptability to environmental changes. [ABSTRACT FROM AUTHOR]

In recent years, significant efforts have been made to understand oral drug absorption mechanisms and to develop new research models. These studies have been conducted using both in vitro and in vivo models and play a crucial role in determining the rate and extent of drug absorption in the intestines. Specifically, the permeability value (Peff value) is a common measure used to assess drug intestinal passage. Today, there is an increasing need for reliable gastrointestinal absorption models that can be used in preclinical studies to develop new drugs and appropriate dosages. However, collaboration and integration across different disciplines are important for further advancements in this field. Strengthening connections between pharmaceutical, biopharmaceutical, biochemical, and physiological research areas can contribute to a better understanding of drug absorption mechanisms and biopharmaceutical progress. Particularly, the use of animal models that mimic human intestinal drug permeability and the role of human cell culture models in investigating drug absorption in the intestine are highlighted as significant steps in this regard. Such research enables a more detailed examination of intestinal drug diffusion processes, which are crucial for the biopharmaceutical advancement of pharmaceutical compounds. Understanding factors such as the interactions between drug molecules and membrane transport molecules that affect the intestinal Peff value can further advance the assessment and improvement of drug absorption processes. [ABSTRACT FROM AUTHOR]

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavychain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts. [ABSTRACT FROM AUTHOR]

The neuroinflammation is a crucial component of virtually all neurodegenerative disorders, including Alzheimer’s disease (AD). The bacterial lipopolysaccharide (LPS), a potent activator of the innate immune system, was suggested to influence or even trigger the neuropathological alterations in AD. LPS-induced neuroinflammation involves changes in transcription of several genes, thus controlling these molecular processes may be a potentially efficient strategy to attenuate the progression of AD. Since genome-wide association studies showed that the majority of AD-related genetic risk factors (AD-GRF) are connected to the immune system, our aim was to identify AD-GRF affected in the hippocampus by LPS-induced systemic inflammatory response (SIR). Moreover, we analysed the role of bromodomain and extraterminal domain (BET) proteins, the readers of the acetylation code, in controlling the transcription of selected AD-GRF in the brain during neuroinflammation. In our study, we used a mouse model of LPS-induced SIR and mouse microglial BV2 cells. JQ1 was used as an inhibitor of BET proteins. The level of mRNA was analysed using microarrays and qPCR. Our data demonstrated that among the established AD-GRF, only the expression of Cd33 was significantly upregulated in the hippocampus during SIR. In parallel, we observed an increase in the expression of Brd4, a BET family member. JQ1 prevented an LPS-evoked increase in Cd33 expression in the hippocampus of mice. Moreover, JQ1 reduced Cd33 expression in BV2 microglial cells stimulated with blood serum from LPS-treated mice. Our study suggests that LPS-evoked SIR may increase Cd33 gene expression in the brain, and inhibition of BET proteins through suppression of Cd33 expression could be a promising strategy in prevention or in slowing down the progression of neuroinflammation and may potentially affect the pathomechanism of AD. [ABSTRACT FROM AUTHOR]

Membrane permeability is an in vitro parameter that represents the apparent permeability (Papp) of a compound, and is a key absorption, distribution, metabolism, and excretion parameter in drug development. Although the Caco-2 cell lines are the most used cell lines to measure Papp, other cell lines, such as the Madin-Darby Canine Kidney (MDCK), LLC-Pig Kidney 1 (LLC-PK1), and Ralph Russ Canine Kidney (RRCK) cell lines, can also be used to estimate Papp. Therefore, constructing in silico models for Papp estimation using the MDCK, LLC-PK1, and RRCK cell lines requires collecting extensive amounts of in vitro Papp data. An open database offers extensive measurements of various compounds covering a vast chemical space; however, concerns were reported on the use of data published in open databases without the appropriate accuracy and quality checks. Ensuring the quality of datasets for training in silico models is critical because artificial intelligence (AI, including deep learning) was used to develop models to predict various pharmacokinetic properties, and data quality affects the performance of these models. Hence, careful curation of the collected data is imperative. Herein, we developed a new workflow that supports automatic curation of Papp data measured in the MDCK, LLC-PK1, and RRCK cell lines collected from ChEMBL using KNIME. The workflow consisted of four main phases. Data were extracted from ChEMBL and filtered to identify the target protocols. A total of 1661 high-quality entries were retained after checking 436 articles. The workflow is freely available, can be updated, and has high reusability. Our study provides a novel approach for data quality analysis and accelerates the development of helpful in silico models for effective drug discovery. Scientific Contribution: The cost of building highly accurate predictive models can be significantly reduced by automating the collection of reliable measurement data. Our tool reduces the time and effort required for data collection and will enable researchers to focus on constructing high-performance in silico models for other types of analysis. To the best of our knowledge, no such tool is available in the literature. [ABSTRACT FROM AUTHOR]

The accuracy of aerodynamically controlled guided projectile simulations is largely determined by the aerodynamic model employed in flight simulations which impacts vehicle interaction with the surrounding air. In this work, the performance of projectile path following with two distinct aerodynamic models is examined for their possible influence on trajectory following accuracy. The study incorporates the path following guidance algorithm, which enables the object to navigate along a predefined path. The simulation mathematical model is developed in the MATLAB/Simulink environment. In addition, by integrating the path-following algorithm with the two aerodynamic models, the dynamic behaviour of the aerodynamically controlled projectile can be compared. This allows for a more comprehensive analysis of the trajectory and the effects of each model on the desired flight path. Further research can explore the differences between the two models in greater detail and quantify their impact on unmanned projectile trajectory predictions, in addition to further exploring the specific characteristics and limitations of each model. This will involve analysing their assumptions, computational methods, and inputs to identify potential sources of error or uncertainty in the simulations. Moreover, these results have important implications for the design of aerodynamically controlled projectiles as well as a deeper understanding of aerodynamic mathematical modelling in flight simulation. [ABSTRACT FROM AUTHOR]

Ischemic stroke occurs abruptly causing sudden neurologic deficits, and therefore, very little is known about hemodynamic perturbations in the brain immediately after stroke onset. Here, functional ultrasound imaging was used to monitor variations in relative cerebral blood volume (rCBV) compared to baseline. rCBV levels were analyzed brain-wide and continuously at high spatiotemporal resolution (100 μm, 2 Hz) until 70mins after stroke onset in rats. We compared two stroke models, with either a permanent occlusion of the middle cerebral artery (MCAo) or a tandem occlusion of both the common carotid and middle cerebral arteries (CCAo + MCAo). We observed a typical hemodynamic pattern, including a quick drop of the rCBV after MCAo, followed by spontaneous reperfusion of several brain regions located in the vicinity of the ischemic core. The severity and location of the ischemia were variable within groups. On average, the severity of the ischemia was in good agreement with the lesion volume (24 hrs after stroke) for MCAo group, while larger for the CCAo + MCAo model. For both groups, we observed that infarcts extended to initially non-ischemic regions located rostrally to the ischemic core. These regions strongly colocalize with the origin of transient hemodynamic events associated with spreading depolarizations. [ABSTRACT FROM AUTHOR]

Fluidic thrust vectoring (FTV) control is a cutting-edge method used to manipulate the motion of an unmanned air vehicle when traditional control surfaces like elevators are not available. The primary purpose of employing FTV is to make the aircraft less detectable. This research centers around the exploration of the co-flow variation of the FTV concept. In this approach, a secondary jet with a significant velocity is injected into the boundary layer of the primary jet. As a consequence, the primary jet is diverted, leading to the formation of a pitch moment. Numerical simulations were conducted to analyze different ratios of secondary and primary jet velocities, providing valuable insights into the effectiveness of the proposed technique. The test rig, designed with a pitch-constraint dynamic setup, utilized electric ducted fans to generate primary and secondary flows. At 19 m/s primary velocity, the experimental testing shows a maximum vertical force of 0.4 N, producing a deflection of 25°, which is deemed adequate for thrust vectoring. This research builds upon the authors' previous work on characterizing a static co-flow FTV rig. The comparison between the computational fluid dynamics analyses and the experimental results demonstrates agreement in the behavior of the vectored jet. This validation further strengthens the findings presented in this paper. [ABSTRACT FROM AUTHOR]

Centella asiatica (L.) Urb. (Apiaceae) is a renowned medicinal plant being used in the Ayurvedic system for its pharmacological effects on the central nervous system such as rejuvenating, sedative, anxiolytic and memory-enhancing properties. The present study was designed to investigate the effect of Centella asiatica (CA) extract on inflammatory responses induced by lipopolysaccharide (LPS) and resulting changes in cognitive behavior. Adult male Sprague-Dawley rats were divided into 4 groups as control, LPS, CA and LPS + CA. The treatments with LPS (5 mg/kg) were intraperitoneally (i.p) injected on day 4 and CA ethanol extract (200 mg/kg) were given orally for 14 days. Morris Water Maze (MWM) test was performed to assess spatial learning and memory performance. Acute oral toxicity of the extract at the highest dose of 5000 mg/kg was also conducted. Single administration of LPS was able to significantly elicit learning and memory impairment (p <.05) when compared to the control groups. Treatment with CA significantly improved the impaired learning ability in which the LPS + CA rats took the shortest time and route to find the hidden platform (15.85 ± 2.68 s (p <.001); 352.43 ± 88.10 cm (p <.001) on day 5) and induced differential cytokine responses in the blood. No mortality and no significant variation in the body and organ weights between the control and the treated group was observed after 14 days of acute toxicity study. Hematological analysis and biochemical parameters revealed no toxic effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed. Centella asiatica extract exhibited significant learning and memory enhancement potential in animal model. Hence, indicating its putative preventive therapeutic effects in neuroinflammation related diseases. A single dose of lipopolysaccharide (LPS) (5 mg/kg) administered systemically to mimic the consequences of LPS-induced inflammatory responses was able to affect some behavioral modification of spatial memory at the time point of study. The study showed that the learning capability during the training trial was restored or ameliorated with the pre-emptive treatment of Centella asiatica extract (200 mg/kg). Centella asiatica extract improves spatial memory, learning deficits and regulates proinflammatory responses in systemic LPS-treated rats. [ABSTRACT FROM AUTHOR]

Background: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial., Methods: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery., Results: A total of 16 189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability., Conclusion: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The objective of this study was to compare transperineal (TP) versus transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion prostate biopsy (PBx). Consecutive men who underwent prostate MRI followed by a systematic biopsy. Additional target biopsies were performed from Prostate Imaging Reporting & Data System (PIRADS) 3–5 lesions. Men who underwent TP PBx were matched 1:2 with a synchronous cohort undergoing TR PBx by PSA, Prostate volume (PV) and PIRADS score. Endpoint of the study was the detection of clinically significant prostate cancer (CSPCa; Grade Group ≥ 2). Univariate and multivariable analyses were performed. Results were considered statistically significant if p < 0.05. Overall, 504 patients met the inclusion criteria. A total of 168 TP PBx were pair-matched to 336 TR PBx patients. Baseline demographics and imaging characteristics were similar between the groups. Per patient, the CSPCa detection was 2.1% vs 6.3% (p = 0.4) for PIRADS 1–2, and 59% vs 60% (p = 0.9) for PIRADS 3–5, on TP vs TR PBx, respectively. Per lesion, the CSPCa detection for PIRADS 3 (21% vs 16%; p = 0.4), PIRADS 4 (51% vs 44%; p = 0.8) and PIRADS 5 (76% vs 84%; p = 0.3) was similar for TP vs TR PBx, respectively. However, the TP PBx showed a longer maximum cancer core length (11 vs 9 mm; p = 0.02) and higher cancer core involvement (83% vs 65%; p < 0.001) than TR PBx. Independent predictors for CSPCa detection were age, PSA, PV, abnormal digital rectal examination findings, and PIRADS 3–5. Our study demonstrated transperineal MRI/TRUS fusion PBx provides similar CSPCa detection, with larger prostate cancer core length and percent of core involvement, than transrectal PBx. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid power supply system for commercial drones. The proposed hybrid power supply system consists of a lithium polymer battery, a supercapacitor, and a power converter for charging the supercapacitor. In the proposed system, the supercapacitor is pre-charged with a lithium polymer battery through a power converter, and the supercapacitor first supplies the power required for the drone's initial startup and lift-up. Afterward, in the section where the power consumption of the drone is low, the battery and the supercapacitor supply power together, minimizing the stress on the battery. To verify the proposed hybrid power supply system, a computer simulation was conducted, the actual hardware was fabricated, and experiments were performed. [ABSTRACT FROM AUTHOR]

Background: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. Methods: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. Results: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. Conclusions: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS. [ABSTRACT FROM AUTHOR]

Shiga toxins (Stxs), especially the Stx2a subtype, are the major virulence factors involved in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic uremic syndrome (eHUS), a life-threatening disease causing acute kidney injury, especially in children. After oral transmission and colonization in the gut, EHEC release Stx. Intracellular cleavage of the Stx A subunit, when followed by reduction, boosts the enzymatic activity that causes damage to targeted cells. This cleavage was assumed to be mostly mediated by furin during Stx intracellular trafficking. To investigate whether this cleavage could occur in the intestine, even prior to entering target cells, Stx2a A subunit structure (intact or cleaved) was characterized after its exposure to specific host factors present in human stool. The molecular weight of Stx2a A subunit/fragments was determined by immunoblotting after electrophoretic separation under reducing conditions. In this study, it was demonstrated that Stx2a is cleaved by certain human stool components. Trypsin and chymotrypsin-like elastase 3B (CELA3B), two serine proteases, were identified as potential candidates that can trigger the extracellular cleavage of Stx2a A subunit directly after its secretion by EHEC in the gut. Whether the observed cleavage indeed translates to natural infections and plays a role in eHUS pathogenesis has yet to be determined. If so, it seems likely that a host's protease profile could affect disease development by changing the toxin's biological features. [ABSTRACT FROM AUTHOR]