Search

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]

Frozen microspheres of hydrogen (pellets) will be one of the target types for the future hadron physics experiment PANDA at FAIR (GSI, Darmstadt, Germany) []. Pellets with a diameter of 25- μm are generated about 3 meters above the interaction region, to which they travel with a velocity around 80 m/s inside a narrow pipe. 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 possibilities to reconstruct particle tracks and events e.g. in charmonium decay studies. One would also like to suppress background events that do not originate in a pellet, but e.g. may occur in rest gas, that is present in the beam pipe. A solution is provided by the presented pellet tracking system together with a target operation mode that provides one and only one pellet in the interaction region most of the time. The goal is to track individual pellets in order to know their position with a resolution of a few tenths of a millimeter at the time of an interaction. The system must also be highly efficient and provide tracking information for essentially all pellets that pass the interaction region. Presented results from the design studies show that the goals can be fulfilled by this solution. [ABSTRACT FROM AUTHOR]

The cross-sections of the pd $ \rightarrow$3He $ \eta$ , pd $ \rightarrow$3He $ \pi^{0}_{}$ $ \pi^{0}_{}$ $ \pi^{0}_{}$ and pd $ \rightarrow$3He $ \pi^{+}_{}$ $ \pi^{-}_{}$ $ \pi^{0}_{}$ reactions have been measured at the beam kinetic energies Tp= 1360 MeV and Tp= 1450 MeV using the CELSIUS/WASA detector setup. At both energies, the differential cross-section $\tfrac{{d\sigma }} {{d\Omega }}$ of the $ \eta$ meson in the pd $ \rightarrow$3He $ \eta$ reaction shows a strong forward-backward asymmetry in the CMS. The ratio between the pd $ \rightarrow$3He $ \pi^{+}_{}$ $ \pi^{-}_{}$ $ \pi^{0}_{}$ and pd $ \rightarrow$3He $ \pi^{0}_{}$ $ \pi^{0}_{}$ $ \pi^{0}_{}$ cross-sections has been analysed in terms of isospin amplitudes. The reconstructed invariant-mass distributions of the $ \pi$ $ \pi$ , 3He $\displaystyle \pi$ and 3He2 $ \pi$ systems provide hints on the role of nucleon resonances in the 3 $ \pi$ production process. [ABSTRACT FROM AUTHOR]

The production of η mesons at an excess energy of 72 MeV has been studied in the reaction pp → pp(η)γγ. It is shown that a simple model with Pp final states included reproduces observed differential distributions better than the same model restricted to Ss, Sd and Ds final states. The strong influence of the Pp states could be taken as an indication of ρ dominance within an one boson exchange model for the excitation of N*(1535). [ABSTRACT FROM AUTHOR]

The two-pion production in pp-collisions has been investigated in exclusive measurements from threshold up to Tp = 1.36 GeV. Total and differential cross sections have been obtained for the channels pnπ+π0, ppπ+π-, ppπ0π0 and also nnπ+π+. For intermediate incident energies Tp > 1 GeV, i.e. in the region, which is beyond the Roper excitation but at the onset of ΔΔ excitation the total ppπ0π0 cross section falls behind theoretical predictions by as much as an order of magnitude near 1.2 GeV, whereas the nnπ+π+ cross section is a factor of five larger than predicted. A model-unconstrained isospin decompostion of the cross section points to a significant contribution of an isospin 3/2 resonance other than the Δ(1232). As a possible candidate the Δ(1600) is discussed. [ABSTRACT FROM AUTHOR]

The reaction pn → dπ0π0 constitutes the most fundamental system for the study of the ABC effect - a puzzling threshold enhancement in the ππ invariant mass spectrum of the ππ system in double-pionic fusion to nuclear bound states. The first exclusive measurements of this reaction have now been carried out at CELSIUS-WASA. They exhibit a striking low-mass enhancement in the ππ invariant mass spectrum, prove it to be a σ-channel phenomenon and falsify conventional theoretical models, which predict an associated high-mass enhancement not present in the new exclusive data. In the kinematically complete data sample we observe a ΔΔ excitation, where the interaction between the two Δ obviously plays a crucial role for the generation of the ππ low-mass enhancement. [ABSTRACT FROM AUTHOR]

At CELSIUS-WASA the two-pion production in proton-proton collisisons has been measured exclusively from threshold up to the energy regime, where both of the collision partners are expected to be excited to the Δ state. The measurements constitute the first kinematically complete data samples of solid statistics in this energy range. Most of the data have been obtained for the π+π- and π0π0channels. Whereas at near-threshold energies the differential distributions can be succesfully explained by chiral dynamics and Roper excitation, respectively, the data for the π+π- channel in the ΔΔ region can be described only, if the special configuration (ΔΔ)0+ is assumed. The data for the π0π0 channel moreover exhibit a low-mass enhancement in the π0π0 invariant mass spectrum, which is reminiscent of the ABC-effect found in double-pionic fusion to light nuclei. [ABSTRACT FROM AUTHOR]

The ABC effect - a puzzling threshold enhancement in the ππ invariant mass spectrum of double-pionic fusion to nuclear bound states - has been investigated since 40 years by inclusive measurements without providing a conclusive interpretation. First exclusive measurements to this topic have now been carried out at CELSIUS-WASA. They confirm a huge ππ threshold enhancement, prove it to be of scalar-isoscalar nature, i.e., a σ-channel phenomenon and reveal the theoretically predicted high-mass enhancement in inclusive spectra to be of πππ rather than of ππ nature - falsifying thus corresponding model predictions for the ABC effect. From the kinematically complete data samples we infer that the interaction between the two Δ particles created in this process is of crucial importance. [ABSTRACT FROM AUTHOR]

Electron emission from micro-protrusions on the surface of metal electrodes is crucial for vacuum breakdown. The emission characteristics of cathode micro-protrusions and the impact of the space charge effect are investigated in this study, with a comparison to the Murphy–Good (MG) theory analysis. Precise calculations of the emission current density and the Nottingham effect are achieved. A thermal-field emission model for copper micro-protrusion is established to analyze emission characteristics and clarify the mismatches between the results of simulations and MG theory. The results indicate that, for copper micro-protrusions, before breakdown, the emission current is primarily field emission, with thermal emission constituting only 7% of the total. The Nottingham effect results in consistent heating during this phase. The field enhancement factor obtained through the MG theory (γ MG) is slightly smaller than that derived from the geometric model (γ geom). This is because γ geom reflects the characteristics of the apex of the protrusion, while γ MG reflects the characteristics of the entire electron emission region. The space charge effect bends the MG plot curve and decreases its slope, making it impossible to analyze the emission current using MG theory at this point, which is consistent with the theoretical derivations recorded in the current literature. [ABSTRACT FROM AUTHOR]

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]

The π0π0 production in pp-collisions has been investigated in exclusive and kinematically complete measurements from threshold up to Tp = 1.4 GeV. For incident energies Tp > 1 GeV, i.e. in the region beyond the Roper excitation, the ΔΔ excitation process takes over. The data are well explained by the t-channel ΔΔ process dominated by pion exchange. There is no low-mass enhancement (ABC effect) in the π0π0-invariant mass distribution beyond that given by the conventional t-channel ΔΔ process. This is also true for the limiting case, where the protons are in the quasi-bound 2He state. [ABSTRACT FROM AUTHOR]

The ABC effect, a low-mass enhancement in the invariant ππ mass, is observed in double-pionic fusion reactions leading to a bound nuclear system in the final state. From previous measurements there have been indications that this phenomenon is resctricted to the σ channel of the ππ system. With exclusive measurements of the pp → dπ+π0 reaction at Tp = 1.1 GeV we demonstrate that, indeed, the ABC effect does not occur in the vector-isovector ππ channel (ρ channel) despite the fact that the ΔΔ excitation is oberved to be the dominant reaction process. We also show that this reaction is well described by a t-channel ΔΔ excitation with the subsequent decay into the vector-isovector ππ channel given by the ρ channel operator. [ABSTRACT FROM AUTHOR]

In most investigations the Roper resonance is sensed only very indirectly via complex partial-wave analyses. We find indications for its excitation in the invariant nπ+ mass spectrum of the pp → npπ+ reaction at M ≈ 1360 MeV with a width of ≈ 150 MeV . The values fit very favorably to the most recent phase shift results as well as to the observations at BES. In the near-threshold two-pion production pp → ppπ0π0 , where the Roper excitation and its subsequent decays via the routes N * → Δπ → Nππ and N * → Nσ are the only dominant processes, we find its direct decay into the Nσ channel to be the by far dominating decay process --in favor of a monopole excitation of the Roper resonance. [ABSTRACT FROM AUTHOR]

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]

Neuronal loss in the ipsilateral thalamus after focal cortical infarction participates in post-stroke cognitive deficits, and enhanced angiogenesis in the thalamus is expected to reduce neuronal damage. We hypothesize that novel translocator protein (TSPO) ligand, 2-Cl-MGV-1, can promote angiogenesis, attenuate neuronal loss in the thalamus, and ameliorate post-stroke cognitive deficits. Cortical infarction was induced by distal middle cerebral artery occlusion (dMCAO) in stroke-prone renovascular hypertensive rats. 2-Cl-MGV-1 or dimethyl sulfoxide was administered 24 h after dMCAO and then for 6 or 13 days. Spatial learning and memory were assessed using the Morris water maze. Neuronal loss, TSPO expression, angiogenesis, and intrinsic pathway were determined by immunofluorescence and immunoblotting 7 and 14 days after dMCAO. Cortical infarction caused post-stroke cognitive deficits and secondary neuronal loss with gliosis in the ipsilateral thalamus within 14 days of dMCAO. Increased angiogenesis and elevated expression of vascular TSPO were detected in the ipsilateral thalamus, and treatment with 2-Cl-MGV-1 enhanced angiogenesis by stimulating the PI3K-AKT-mTOR pathway. The effects of 2-Cl-MGV-1 on angiogenesis coincided with reduced neuronal loss in the thalamus and contributed to improvements in post-stroke cognitive deficits. Our findings suggest that 2-Cl-MGV-1 stimulates angiogenesis, ameliorates neuronal loss in the thalamus, and improves post-stroke cognitive deficits. [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]

Purpose: To calculate the frequency of infection and acute urinary retention (AUR) following transperineal (TP) prostate biopsy at a single high-volume academic institution and determine risk factors for developing these post-biopsy conditions. Methods: Men undergoing TP prostate biopsy from 2012 to 2022 at our institution were retrospectively identified and chart reviewed. TP biopsies were performed with TR ultrasound (TRUS) guidance with anesthesia using a brachytherapy grid template. TRUS volumes were recorded during the procedure, and magnetic resonance imaging (MRI) volumes were calculated using the ellipsoid formula. When available, MRI volume was used for all analysis, and when absent, TRUS volume was used. AUR was defined as requiring urinary catheter placement within 72 h post-biopsy for inability to urinate. Univariable analysis was performed and variables with p < 0.1 and/or established clinical relevance were included in a backward binary logistic regression to produce an optimized model that fit the data without collinearity between variables. Results: A total of 767 TP biopsies were completed in the study window. The frequency of infection was 1.83% (N = 14/767). The total frequency of AUR was 5.48% (N = 42/767). On multivariable regression, patients who went into AUR were five times as likely to develop infection (p = 0.020). Patients with infection post-TP biopsy were four times as likely to develop AUR (p = 0.047) and with prostates > 61.21 cc were three times as likely (p = 0.019). Conclusion: According to our model, AUR is the greatest risk factor for infection post-TP biopsy. With regard to AUR risks, infection post-biopsy and prostate size > 61.21 cc are the greatest risk factors. [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]

Background: Periprocedural prophylaxis in medicine encompasses the set of measures (physical, chemical, and pharmacological) used to reduce the risk of infection. Antibiotic prophylaxis (AP) refers to the administration of a short-term regimen of antibiotics shortly before a medical procedure to reduce the risk of infectious complications that can result from diagnostic and therapeutic interventions. The outspreading growth of multidrug-resistant bacterial species and changes in the bacterial local ecosystem have impeded the development of a unique scheme of AP in urology. Objectives: To review the literature and current guidelines regarding AP for urological diagnostic and therapeutic procedures, and to define agents, timing, and occasions when administering pharmacological prophylaxis. Secondly, according to current literature, to open new scenarios where AP can be useful or useless. Results: Major gaps in evidence still exist in this field. AP appears useful in many invasive procedures and some sub-populations at risk of infectious complications. AP is not routinely recommended for urodynamic exams, diagnostic cystoscopy, and extracorporeal shock-wave lithotripsy. The available data regarding the use of AP during the transperineal prostate biopsy are still unclear; conversely, in the case of the transrectal approach AP is mandatory. AP is still considered the gold standard for the prevention of postoperative infective complications in the case of ureteroscopy, percutaneous nephrolithotomy, endoscopic resection of bladder tumor, endoscopic resection of the prostate, and prosthetic or major surgery. Conclusion: The review highlights the complexity of determining the appropriate candidates for AP, emphasizing the importance of considering patient-specific factors such as comorbidities, immunocompetence, and the nature of the urologic intervention. The evidence suggests that a one-size-fits-all approach may not be suitable, and a tailored strategy based on the specific procedure and patient characteristics is essential. [ABSTRACT FROM AUTHOR]

Copyright of Jinekoloji-Obstetrik & Neonatoloji Tip Dergisi is the property of T.C. Saglik Bakanligi Ankara Sehir Hastanesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Objective: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, “PI-RADS 5 patients”). Materials and methods: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. Results: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63–74) and 8.9 ng/ml (IQR 6.0–13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74–0.83). Conclusion: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present. [ABSTRACT FROM AUTHOR]

Introduction: Prostate mpMRI was introduced in 2011 as a secondary test and subsequently integrated into a prostate cancer (PCa) diagnostics unit representing a population of approximately 550,000 people. The following represents an audit of its step-wise introduction between 2 index years, 2009 and 2018, focusing on the activity, patient outcomes and economic benefits. Patients and methods: The 2 distinct years were selected for relying on a transrectal ultrasound biopsy pathway in 2009 to an mpMRI-based pathway in 2018. All referrals were retrospectively screened and compared for age, PSA levels, DRE findings, biopsy history, biopsy and mpMRI allocation data. Cost analysis was determined using local unit procedure costs. Results: Patients referred included 648 in 2009 and 714 in 2018. mpMRI seldomly informed decision to biopsy in 2009 (9.8%), while in 2018 it was performed in the pre-biopsy setting in 87.9% cases and enabled biopsy avoidance in 137 patients. In 2018, there was a 31.8% decrease in the number of biopsies in patients without previous PCa diagnosis, coupled with an increase in diagnostic rates of csPCa, from 28.6 to 49.0% (p < 0.0001) and a reduction in negative biopsy rates from 52.3 to 33.8%. mpMRI had a positive impact on the system with reduced patient morbidity and post-procedural complications. The estimated overall cost savings amount to approximately £75,000/year for PCa diagnosis and £11,000/year due to reduced complications. Conclusion: Our evaluation shows the mpMRI-based pathway has improved early detection of csPCa and reduction of repeat biopsies, resulting in significant financial benefits for the local healthcare system. [ABSTRACT FROM AUTHOR]