Search Results (766)

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

The growing popularity of Personal Light Electric Vehicles (PLEVs), such as e-scooters, has revolutionized urban mobility by offering compact, cost-effective, and environmentally friendly transportation solutions. However, safety concerns, including inadequate infrastructure, poor protective measures, and high accident rates, remain critical challenges. This paper presents the design and development of an innovative self-balancing microvehicle under the H2020 LEONARDO project, which aims to address these challenges through advanced engineering and user-centric design. The vehicle combines features of monowheels and e-scooters, integrating cutting-edge technologies to enhance safety, stability, and usability. The design adheres to European regulations, including Germany’s eKFV standards, and incorporates user preferences identified through representative online surveys of 1500 PLEV users. These preferences include improved handling on uneven surfaces, enhanced signaling capabilities, and reduced instability during maneuvers. The prototype features a lightweight composite structure reinforced with carbon fibers, a high-torque motorized front wheel, and multiple speed modes tailored to different conditions, such as travel in pedestrian areas, use by novice riders, and advanced users. Braking tests demonstrate deceleration values of up to 3.5 m/s², comparable to PLEV market standards and exceeding regulatory minimums, while smooth acceleration ramps ensure rider stability and safety. Additional features, such as identification plates and weight-dependent motor control, enhance compliance with local traffic rules and prevent misuse. The vehicle’s design also addresses common safety concerns, such as curb navigation and signaling, by incorporating large-diameter wheels, increased ground clearance, and electrically operated direction indicators. Future upgrades include the addition of a second rear wheel for enhanced stability, skateboard-like rear axle modifications for improved maneuverability, and hybrid supercapacitors to minimize fire risks and extend battery life. With its focus on safety, regulatory compliance, and rider-friendly innovations, this microvehicle represents a significant advancement in promoting safe and sustainable urban mobility. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

In the decommissioning of nuclear facilities, activated steel often contains radionuclides such as ⁵⁵Fe and ⁶³Ni, which are categorized as hard-to-measure due to their emission of only low-energy beta particles or X-rays. In samples exhibiting very low radioactivity, close to background levels, a large quantity of steel must undergo extensive physical and chemical processing to achieve the Minimum Detectable Activity Concentration (MDC) necessary for clearance, recycling, or reuse. Italian regulations set particularly stringent clearance levels for these radionuclides (1 Bq/g for both ⁵⁵Fe and ⁶³Ni), significantly lower than those specified in the EU Directive 2013/59 (1000 Bq/g for ⁵⁵Fe and 100 Bq/g for ⁶³Ni). Additionally, Italian authorities may enforce even stricter limits depending on specific circumstances. The analytical challenge is compounded by the presence of large amounts of non-radioactive Fe and Ni, which can cause color quenching, further extending analysis times. This study presents a reliable and optimized method for the quantitative determination of ⁵⁵Fe and ⁶³Ni in steel samples with activity levels approaching regulatory thresholds. The methodology was specifically developed and applied to steel from the Frascati Tokamak Upgrade (FTU) facility, under decommissioning by ENEA. The optimization process demonstrated that achieving the required MDCs necessitates acquisition times of approximately 5 days for ⁵⁵Fe and 6 h for ⁶³Ni, ensuring compliance with stringent regulatory requirements and supporting efficient laboratory workflows. Full article

Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3⁺ T cell frequencies, especially CD3^+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3⁺. All treatments diminished CD19⁺/IL-10⁺ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression. Full article

Background: Asparaginase (ASPase) plays an important role in the therapy of acute lymphoblastic leukemia (ALL). Serum ASPase activity (SAA) can be modified and even abolished by host immune responses; therefore, current treatment guidelines recommend to monitor SAA during treatment administration. The SAA monitoring schedule needs to be carefully planned to reduce the number of samples without hampering the possibility of measuring pharmacokinetics (PK) parameters in individual patients. Complex modelling approaches, not easily applicable in common practice, have been applied in previous studies to estimate ASPase PK parameters. This study aimed to estimate PK parameters by using a simplified approach suitable for real-world settings with limited sampling. Methods: Our study was based on 434 patients treated in Italy within the AIEOP-BFM ALL 2009 trial. During the induction phase, patients received two doses of pegylated ASPase and were monitored with blood sampling at five time points, including time 0. PK parameters were estimated by using the individually available SAA measurements with simple modifications of the classical non-compartmental PK analysis. We also took the opportunity to develop and validate a series of limited sampling models to predict ASPase exposure. Results: During the induction phase, average ASPase activity at day 7 was 1380 IU/L after the first dose and 1948 IU/L after the second dose; therapeutic SAA levels (>100 IU/L) were maintained until day 33 in 90.1% of patients. The average AUC and clearance were 46,937 IU/L × day and 0.114 L/day/m², respectively. The database was analyzed for possible associations of PK parameters with biological characteristics of the patients, finding only a limited dependence on sex, age and risk score; however, these differences were not sufficient to allow any dose or schedule adjustments. Thereafter the possibility of further sampling reduction by using simple linear models to estimate the AUC was also explored. The most simple model required only two samplings 7 days after each ASPase dose, with the AUC being proportional to the sum of the two measured activities A(7) and A(21), calculated by the formula AUC = 14.1 × [A(7) + A(21)]. This model predicts the AUC with 6% average error and 35% maximum error compared to the AUC estimated with all available measures. Conclusions: Our study demonstrates the feasibility of a direct estimation of PK parameters in a real-life situation with limited and variable blood sampling schedules and also offers a simplified method and formulae easily applicable in clinical practice while maintaining a reliable pharmacokinetic monitoring. Full article

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms. Full article

Traditional PMUT ultrasonic ranging systems usually possess a large measurement blind area under the integrated transmit–receive mode, dramatically limiting its distance measurement in confined spaces, such as when determining the clearance of large bearing components. Here, a broadband PMUT rangefinder was designed by integrating six types of different cells with adjacent resonant frequencies into an array. Through overlapping and coupling of the bandwidths from the different cells, the proposed PMUTs showed a wide –6 dB fractional bandwidth of 108% in silicon oil. Due to the broadening of bandwidth, the device could obtain the maximum steady state with less excitation (5 cycles versus 14 cycles) and reduce its residual ring-down (ca. 6 μs versus 15 μs) compared with the traditional PMUT array with the same cells, resulting in a small blind area. The pulse–echo ranging experiments demonstrated that the blind area was effectively reduced to 4.4 mm in air or 12.8 mm in silicon oil, and the error was controlled within ±0.3 mm for distance measurements up to 250 mm. In addition, a specific ultrasound signal processing circuit with functions of transmitting, receiving, and processing ultrasonic waves was developed. Combining the processing circuit and PMUT device, the system was applied to determine the axial clearance of the main bearing in a tunneling machine. This work develops broadband PMUTs with a small blind area and high resolution for distance measurement in narrow and confined spaces, opening up a new path for ultrasonic ranging technology. Full article

Background/Objectives: This study focuses on the motion planning and control of an active ankle–foot orthosis (AFO) that leverages biomechanical insights to mitigate footdrop, a deficit that prevents safe toe clearance during walking. Methods: To adapt the motion of the device to the user’s walking speed, a geometric model was used, together with real-time measurement of the user’s gait cycle. A geometric speed-adaptive model also scales a trapezoidal ankle-velocity profile in real time using the detected gait cycle. The algorithm was tested at three different walking speeds, with a prototype of the AFO worn by a test subject. Results: At walking speeds of 0.44 and 0.61 m/s, reduced tibialis anterior (TA) muscle activity was confirmed by electromyography (EMG) signal measurement during the stance phase of assisted gait. When the AFO was in assistance mode after toe-off (initial and mid-swing phase), it provided an average of 48% of the estimated required power to make up for the deliberate inactivity of the TA muscle. Conclusions: Kinematic analysis of the motion capture data showed that sufficient foot clearance was achieved at all three speeds of the test. No adverse effects or discomfort were reported during the experiment. Future studies should examine the device in populations with footdrop and include a comprehensive evaluation of safety. Full article

In chronic kidney disease (CKD), various disorders occur that worsen with the progression of CKD. These include increased levels of hormones such as adiponectin, leptin, and prolactin, changes in feedback loops and metabolism, and decreased renal clearance, contributing to significant morbidity and mortality. We conducted a cross-sectional observational study on 157 randomly selected patients with various stages of chronic kidney disease, 29% of whom had diabetes. We recorded clinical and usual laboratory data. We determined muscle mass and adipose tissue mass using bioimpedance. In addition, we measured serum prolactin levels, tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin-1 beta (IL-1β). N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated as a marker of cardiac function. We evaluated the relation between prolactin, TNF-α, IL-6, IL-1β, and NT-proBNP by bivariate and multivariate analysis. In bivariate analysis, we recorded associations of prolactin with inflammatory markers: TNF-α (r = 0.65, p < 0.001), IL-6 (r = 0.66, p < 0.001), and IL-1β (r = 0.25, p = 0.002). In multivariate analysis we observed that serum prolactin values are associated with IL-1β [median (25th–75th percentile): [−0.001 (−0.001; −0.00003), p = 0.037], muscle mass [−0.03 (−0.04; −0.01), p = 0.003], and NT-proBNP [0.0001 (0.0001; 0.0001)] p < 0.001 In conclusion, in chronic kidney disease, prolactin is associated with inflammatory markers (IL-1β, TNF-α, IL-6), and nutritional status. Additionally, prolactin has been linked to NT-ProBNP, a marker of cardiac function. Full article

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, resulting in α-galactosidase A (α-Gal A) deficiency and progressive accumulation of globotriaosylceramide (Gb3). Current therapies, such as enzyme replacement and chaperone therapy, have limitations, including incomplete biodistribution and mutation-specific efficacy. Gene therapy using adeno-associated virus (AAV) vectors presents a promising alternative. Methods: In this study, we assessed the dose-dependent effects of AAV8 and AAV9 vectors encoding human GLA in Gla knockout (Gla^−/y) mice by measuring α-Gal A activity and monitoring safety. To evaluate therapeutic efficacy, symptomatic Fabry mice (G3S^Tg/+Gla^−/y) were used. Results: AAV9-GLA produced significantly higher and more sustained enzyme activity than AAV8-GLA across plasma, liver, heart, and kidney. In symptomatic mice, AAV9-GLA achieved superior reductions in serum Gb3 and lyso-Gb3 levels, greater Gb3 clearance in heart and kidney tissues, and improved proteinuria. Anti-GLA IgG titers remained below threshold for the first four weeks and increased modestly by week eight, indicating a limited humoral immune response. No significant clinical signs or weight loss were observed in Gla^−/y mice over the 3.5-month study period, supporting the favorable safety profile of AAV-mediated gene therapy. Conclusions: These findings demonstrate that AAV9 provides enhanced biodistribution and therapeutic efficacy compared to AAV8, supporting its potential for the treatment of Fabry disease. Full article

Porcine small intestinal submucosa (SIS) extracellular matrix (ECM) has emerged as a widely researched biological scaffold in regenerative medicine. This meta-analysis examines 205 peer-reviewed studies published from 1993 to 2025, emphasizing the biochemical composition, decellularization techniques, biomedical applications, and validation methods associated with SIS-ECM. Findings reveal a dominant focus on wound healing and cardiovascular repair, reflecting the scaffold’s mechanical adaptability and bioactivity. Research has evolved from basic compositional analyses to complex, application-specific investigations that incorporate in vivo models and functional outcome measures. Decellularization methods vary significantly, trending toward hybrid, multi-step protocols that preserve ECM integrity while ensuring cellular clearance. While the results are encouraging, a notable transparency issue persists, with only a third of studies providing full methodological details, which restricts reproducibility. Frequently utilized validation methods encompass mechanical testing, histology, DNA quantification, and growth factor retention. This review emphasizes the critical requirement for standardized guidelines in preparation and reporting to guarantee the safe and effective clinical application of SIS-ECM. Through continuous refinement and collaboration among various disciplines, SIS-ECM has the potential to serve as a next-generation scaffold for a range of regenerative uses. Full article

The integration of tilted photovoltaic strings on large, flat roofs, typical of industrial and commercial buildings, raises complex design challenges, particularly regarding wind-induced loads. This study presents a comprehensive wind tunnel investigation aimed at evaluating the aerodynamic effects on rooftop PV strings under various representative configurations and the correlation between characteristic geometric parameters such as tilt angle, bottom clearance, row spacing, and wind direction. Following a literature review, a detailed 1:10 scaled model with geometric adjustment capabilities was developed and eventually tested in a boundary-layer wind tunnel. High-resolution pressure measurements were processed to derive force and moment resultants normalised by reference wind pressure. Envelopes of force/moment resultants are presented for each representative geometric configuration and for each wind exposure angle. The results present severe variations in local wind actions, particularly significant at the strings’ free ends and for oblique wind angles. The severe underestimation of local wind loads by standard codes is discussed. The findings underline the importance of detailed wind-load assessment for both new constructions and retrofits, suggesting that reliance solely on code provisions might result in unsafe designs. Full article

Introduction: Pediatric prosthetic knee joints must be appropriately scaled from adult designs to ensure proper gait biomechanics. However, direct dimensional scaling without considering the biomechanical implications may lead to functional discrepancies. This study aimed to evaluate whether using a linear scaling factor can effectively adapt a knee for pediatric use. The study assessed whether such an approach yields a viable pediatric prosthetic knee joint by applying a fixed scaling factor and analyzing the resultant knee geometry. Methods: The linear scaling factor was determined based on the pylon tube diameter, a key constraint in compact pediatric knee design. Given a pediatric pylon diameter of 22 mm, the length of the tibial link was set to 22 mm, yielding a scaling factor of 0.6875 when compared to the adult-sized knee. This scaling factor was used to determine the dimensions of the pediatric four-bar (scaled) knee joint. Static geometric analysis was conducted using GeoGebra^® to model the lower-body segment lengths. The knee joint’s performance was evaluated based on stance and swing phase parameters. These metrics were compared between the scaled knee and a commercial pediatric knee. Results: The geometric analysis revealed that while using the linear scaling factor maintained proportional relationships, certain biomechanical parameters deviated from the expected pediatric norms. The scaled knee achieved a toe clearance of 13.5 mm compared to 19.7 mm in the commercial design and demonstrated a swing-phase heel clearance of 11.6 mm versus 13.3 mm, maintaining negative x/y ratios at heel contact and showing significant stability in push-off moments, while the stance flexion angle remained within an acceptable range. The heel contact and push-off ratios (x/y) were found to be comparable, with the scaled model achieving values of −1.21 and −0.59, respectively. The stance flexion angle measured 10.6°, closely aligning with the commercial reference. Conclusions: Using a linear scaling factor provides a straightforward method for adapting adult prosthetic knee designs to pediatric use. However, deviations in key biomechanical parameters indicate that further experimental study may be required to validate the applicability of the scaled knee joint for pediatric users. Future work should explore dynamic simulations and experimental validations to refine the design further and ensure optimal gait performance. Full article

Background: Organic anion transporter 3 (OAT3) in the kidney proximal tubule cells plays a critical role in renal clearance of numerous endogenous metabolites and exogenous drugs and toxins. In this study, we discovered that epidermal growth factor (EGF) regulates the expression and activity of OAT3 through palmitoylation, a novel mechanism that has never been described in the OAT field. Methods/Results: Our results showed that treatment of OAT3-expressing cells with EGF led to a ~40% increase in OAT3 expression and OAT3-mediated transport of estrone sulfate, a prototypical substrate for OAT3. EGF-stimulated OAT3 transport activity was abrogated by H-89, a protein kinase A (PKA) inhibitor, indicating that an EGF-PKA signaling pathway is involved in the regulation of OAT3. We also showed that treatment of OAT3-expressing cells with EGF resulted in an enhancement of OAT3 palmitoylation, a novel type of post-translational modification for OATs, and such an enhancement was blocked by H-89, suggesting that the EGF-PKA signaling pathway participated in the modulation of OAT3 palmitoylation. Palmitoylation was catalyzed by a group of palmitoyltransfereases, and we showed that OAT3 palmitoylation and expression were inhibited by 2-BP, a general inhibitor for palmitoyltransfereases. We also explored the relationship among EGF/PKA signaling, OAT palmitoylation, and OAT transport activity. We treated OAT3-expressing cells with EGF or Bt2-cAMP, a PKA activator, in the presence and absence of 2-BP, followed by the measurement of OAT3-mediated transport of estrone sulfate. We showed that both EGF- and Bt2-cAMP-stimulated OAT3 transport activity were abolished by 2-BP, suggesting that palmitoylation mediates the regulation of EGF/PKA on OAT3. Finally, we showed that osimertinib, an anti-cancer drug/EGFR inhibitor, blocked EGF-stimulated OAT3 transport activity. Conclusions: In summary, we provided the first evidence that palmitoylation transduces the EGF/PKA signaling pathway to the modulation of OAT3 expression and function. Our study also provided an important implication that during comorbidity therapies, EGFR inhibitor drugs could potentially decrease the transport activity of renal OAT3, which would subsequently alter the therapeutic efficacy and toxicity of many co-medications that are OAT3 substrates. Full article