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Search Results (377)

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Keywords = low dose protocols

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10 pages, 211 KB  
Article
Spinal Analgesia Versus Intravenous Low-Dose Oxycodone for Pain Management After Robotic Hysterectomy: Preliminary Results from an ERAS Institution
by Elisa Peano, Roberta Rosso, Katia Audisio, Giuseppe Coletta, Andrea Puppo and Barbara Franzoso
J. Clin. Med. 2025, 14(19), 6957; https://doi.org/10.3390/jcm14196957 - 1 Oct 2025
Abstract
Background: Robotic hysterectomy and Enhanced Recovery After Surgery (ERAS) are two significant improvements in gynecologic surgery, both associated with decreased postoperative pain and faster recovery. Spinal analgesia guarantees excellent pain coverage; however, its appropriateness in robotic procedures is still controversial. The aim of [...] Read more.
Background: Robotic hysterectomy and Enhanced Recovery After Surgery (ERAS) are two significant improvements in gynecologic surgery, both associated with decreased postoperative pain and faster recovery. Spinal analgesia guarantees excellent pain coverage; however, its appropriateness in robotic procedures is still controversial. The aim of the study was to compare postoperative pain control after robotic hysterectomy in patients receiving spinal analgesia versus intravenous low-dose oxycodone. Methods: Consecutive patients undergoing robotic hysterectomy from January 2022 to July 2023 were included in the analysis. Until August 2022, patients received spinal analgesia, while from September 2022, low-dose oxycodone was administered intraoperatively. All patients were managed following the ERAS protocol. Primary outcomes were the VAS pain score and opioid rescue use, while secondary outcomes included postoperative nausea and vomiting (PONV), mobilization, oral intake, and length of hospital stay (LOS). Results: Of 114 patients, 67 (58.8%) received spinal analgesia and 47 (41.2%) received intravenous low-dose oxycodone. No differences were reported in the VAS pain score at day 0 (1.5 ± 1.6 vs. 1.6 ± 2.2, p = 0.78) and day 1 (2.0 ± 2.1 vs. 1.3 ± 1.8, p = 0.07). At day 2, the VAS pain score was 1.4 ± 1.6 in the spinal analgesia group and 0.7 ± 1.0 in the oxycodone group (p = 0.01). No differences were reported in the need for opioid rescue at days 1 and 2 (p = 1.00). At day 0, 26 patients (38.8%) experienced PONV in the spinal analgesia group versus 8 (17.0%) in the oxycodone group (p = 0.01). Conclusions: Patients receiving intraoperative low-dose oxycodone experienced comparable satisfactory postoperative pain control with a lower incidence of PONV when compared to the spinal analgesia group. Full article
(This article belongs to the Section Obstetrics & Gynecology)
15 pages, 1489 KB  
Article
Ozone Saline Solution Polarizes Microglial Cells Towards an Anti-Inflammatory Phenotype
by Federica Armeli, Beatrice Mengoni, Martina Menin, Gregorio Martínez-Sánchez, Mauro Martinelli, Maurizio Maggiorotti and Rita Businaro
Molecules 2025, 30(19), 3932; https://doi.org/10.3390/molecules30193932 - 30 Sep 2025
Abstract
Ozone (O3) therapy has demonstrated antioxidant and anti-inflammatory properties, but the systemic administration of ozonated saline solution (O3SS) remains underexplored. This study evaluates the cytotoxicity, antioxidant response, and immunomodulatory effects of O3SS on murine microglial (BV2) and [...] Read more.
Ozone (O3) therapy has demonstrated antioxidant and anti-inflammatory properties, but the systemic administration of ozonated saline solution (O3SS) remains underexplored. This study evaluates the cytotoxicity, antioxidant response, and immunomodulatory effects of O3SS on murine microglial (BV2) and human endothelial (HUVEC) cells. Cells were exposed to increasing doses of O3 (1, 5, or 10 μg/NmL) dissolved in saline. Viability assays showed that low doses (1 and 5 μg/NmL) enhanced cell proliferation without cytotoxicity, while the highest dose (10 μg/NmL) reduced viability and increased cell death. O3SS treatment upregulated antioxidant genes, including Nrf2 and SOD1, and decreased reactive oxygen species in lipopolysaccharide (LPS)-stimulated microglia. Additionally, O3SS modulated microglial phenotype by reducing pro-inflammatory markers (iNOS, IL-1β) and increasing anti-inflammatory markers (Arg-1, IL-10). Immunofluorescence confirmed enhanced Arg-1 protein expression, indicating a shift toward an anti-inflammatory state. These results suggest that low-dose O3SS activates cellular antioxidant defenses and promotes an anti-inflammatory microglial phenotype, supporting its potential as a safe systemic O3 therapy. Further studies are warranted to confirm in vivo efficacy and optimize clinical protocols. Full article
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16 pages, 1497 KB  
Article
Clinical and Molecular Characteristics of 100 Atypical Teratoid Rhabdoid Tumor Patients from Low- and Middle-Income Countries
by Noha A. Ismail, Shaimaa Aboubakr, Amal Mosaab, Eslam Maher, Hanafy Hafez, Hala Taha, Dina Yassin, Amal Refaat, Mohamed S. Zaghloul, Mohamed El-Beltagy, Abdelrahman Enayat, Volker Hovestadt, Olfat Ahmed, Mark W. Kieran, Ahmed El-Hemaly, Shahenda EI-Naggar and Alaa El-Haddad
Cancers 2025, 17(18), 3077; https://doi.org/10.3390/cancers17183077 - 20 Sep 2025
Viewed by 273
Abstract
Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and [...] Read more.
Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and outcome data for 100 newly diagnosed ATRT patients aged <18 years treated at the Children’s Cancer Hospital, Egypt, from 2008 to 2022. They were treated uniformly as per the Dana-Farber Cancer Institute modified IRS-III protocol. Molecular subgroups (MYC, SHH, and TYR) were determined via a DNA methylation array for patients who had sufficient DNA material available for the methylation analysis. Treatment toxicities were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: The median age at diagnosis was 1.88 years (IQR 0.99, 3.01); 28% were under 1 year of age, 45% were between 1 and 3 years old, and 26% were above 3 years of age. At diagnosis, 39% of patients had metastatic disease. A total of 60% of patients had gross residual disease following surgical excision. In multivariable analysis, age < 1 year and metastatic disease had a significant impact on event-free survival (EFS) (p = 0.047 and p = 0.002, respectively); however, only metastatic disease had a significantly negative effect on overall survival (OS) and cumulative incidence of relapse (CIR) (p = 0.002 for OS and p < 0.001 for CIR). DNA methylation was performed for 69 patients who were classified as having a TYR (n = 13), SHH (n = 34), MYC (n = 17), or non-ATRT diagnosis (n = 5). In the cohort of the 64 patients with ATRT defined by methylation, no significant survival differences were observed. Treatment-related deaths were reported in 28% of our studied group. Gram-negative septicemia was the most common cause of toxic death. The 5-year EFS and OS of the whole cohort were 12% and 13%, respectively. Conclusions: In this cohort, no significant survival differences were observed among the methylation subgroups. The higher treatment-related mortality in our cohort compared to the original protocol’s toxic-related deaths suggested that intensive and lengthy chemotherapy regimens may need modification for our population. The need for a short intensified approach, including a limited induction cycle followed by an intensified high-dose consolidation therapy, may be more appropriate for our patients with low socioeconomic status to avoid a repeated and prolonged course of protracted neutropenia. Full article
(This article belongs to the Special Issue Current Concept and Management of Pediatric ATRTs)
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11 pages, 404 KB  
Article
Successful Oral Immunotherapy (OIT) Due to Anti-IgE Protection
by Mehrak Yoosefi Moridani, Susanne Lau and Kirsten Beyer
J. Clin. Med. 2025, 14(18), 6612; https://doi.org/10.3390/jcm14186612 - 19 Sep 2025
Viewed by 293
Abstract
Background/Objectives: Oral immunotherapy with peanut protein powder is difficult to initiate in patients with a very low reactivity threshold to peanuts. For this specific group, an add-on treatment with omalizumab (anti-IgE monoclonal antibody) is helpful to tolerate the initial steps. Methods: [...] Read more.
Background/Objectives: Oral immunotherapy with peanut protein powder is difficult to initiate in patients with a very low reactivity threshold to peanuts. For this specific group, an add-on treatment with omalizumab (anti-IgE monoclonal antibody) is helpful to tolerate the initial steps. Methods: After failed initiation in three children, an off-label approval from the individuals’ insurance was necessary for the premedication with anti-IgE ahead of a second approach at our center. Currently, the European countries have no approval from the European Medicines Agency (EMA) for the treatment of food allergies with omalizumab. Results: Under anti-IgE protection, our patients have restarted the oral immunotherapy without anaphylactic reactions and have reached the maintenance dose within the treatment protocol. Conclusions: For a few patients with initial anaphylactic reactions due to doses below the first treatment step (3 mg peanut protein powder), a premedication with omalizumab is not only safe but also reduces side effects, in particular anaphylactic reactions, and the time to reach the hundredfold higher maintenance dose (300 mg peanut protein powder). Full article
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13 pages, 582 KB  
Review
Exploring Manual Interventions for Infantile Colic: A Scoping Review of the Evidence
by Roberto Tedeschi and Federica Giorgi
Children 2025, 12(9), 1246; https://doi.org/10.3390/children12091246 - 17 Sep 2025
Viewed by 309
Abstract
Background: Infantile colic affects up to 40% of otherwise healthy infants and can severely distress caregivers. Manual therapies are increasingly employed as non-pharmacological options, yet their effectiveness and safety remain uncertain. Methods: A scoping review was conducted in accordance with Joanna Briggs Institute [...] Read more.
Background: Infantile colic affects up to 40% of otherwise healthy infants and can severely distress caregivers. Manual therapies are increasingly employed as non-pharmacological options, yet their effectiveness and safety remain uncertain. Methods: A scoping review was conducted in accordance with Joanna Briggs Institute methodology and reported following PRISMA-ScR. Five databases (MEDLINE, CENTRAL, Scopus, PEDro, Web of Science) were searched from December 2024 to May 2025 without restrictions at the search stage; however, only English-language randomised controlled trials published from 2012 onwards were included at the eligibility stage to ensure consistency and focus on the most recent body of evidence. Randomised controlled trials (RCTs) evaluating hands-on interventions for infants ≤ 6 months with colic were eligible. Two reviewers independently screened records, charted data, and grouped outcomes narratively. Results: Seven RCTs investigated abdominal massage, paediatric Tuina, craniosacral therapy, chiropractic manipulation, osteopathic light touch, reflexology, and acupressure. Five trials reported statistically or clinically significant reductions in daily crying (0.6–6.6 h) compared with usual care or sham. Three studies also documented meaningful gains in sleep duration (1.1–2.8 h). Parent-reported satisfaction improved in most interventions. No serious adverse events were recorded, although safety monitoring was inconsistently reported. Substantial heterogeneity in diagnostic criteria, outcome measures, and intervention dose precluded meta-analysis. Conclusions: Low-force manual therapies may offer modest short-term relief for colicky infants and improve parental experience, with an apparently favourable safety profile. However, methodological variability and small sample sizes limit certainty. Standardised protocols, objective outcome measures, and robust adverse-event surveillance are priorities for future research. Full article
(This article belongs to the Section Pediatric Nursing)
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21 pages, 13587 KB  
Article
Quantitative Evaluation of Low-Dose CT Image Quality Using Deep Learning Reconstruction: A Comparative Study of Philips Precise Image and GE TrueFidelity
by Jina Shim, Youngjin Lee and Kyuseok Kim
J. Imaging 2025, 11(9), 317; https://doi.org/10.3390/jimaging11090317 - 16 Sep 2025
Viewed by 371
Abstract
Reducing radiation exposure in CT imaging is critical, particularly in routine and repeat examinations. Deep learning image reconstruction (DLIR) has emerged as a key approach for maintaining diagnostic quality at low-dose acquisition settings. This study compared two DLIR algorithms of Philips Precise Image [...] Read more.
Reducing radiation exposure in CT imaging is critical, particularly in routine and repeat examinations. Deep learning image reconstruction (DLIR) has emerged as a key approach for maintaining diagnostic quality at low-dose acquisition settings. This study compared two DLIR algorithms of Philips Precise Image (PI) and GE TrueFidelity (TF) under an 80 kVp low-dose CT scenario, using the AAPM CIRS-610 phantom to replicate clinical imaging conditions. The phantom’s linearity, high-resolution, and artifact modules were scanned with Philips CT 5300 and GE Revolution CT scanners at low-dose parameters. Images were reconstructed using five DLIR presets, including PI (Smoother, Standard, Sharper) and TF (Middle, High), and evaluated with eight quantitative metrics, including SNR, CNR, nRMSE, PSNR, SSIM, FSIM, UQI, GMSD, and gradient magnitude. TF-High delivered the highest SNR (115.0–118.0 across modules), representing a 54–57% improvement over PI-Smoother, and achieved superior PSNR and the lowest GMSD, reflecting better preservation of structure in low-dose images. PI-Sharper provided the strongest gradient magnitude, emphasizing fine edge detail. Under low-dose CT conditions, TF-High offered the optimal balance of noise suppression and structure fidelity, while PI-Sharper highlighted fine detail enhancement. These findings show that DLIR settings must be tailored to clinical needs when operating under low-dose imaging protocols. Full article
(This article belongs to the Section Medical Imaging)
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23 pages, 1270 KB  
Article
A Pilot, Randomised, Placebo-Controlled, Double-Blind Trial of a Single Oral Dose of Ivermectin for Post-Exposure Prophylaxis of SARS-CoV-2
by Kylie M. Wagstaff, Mark S. Stein, Alan Herschtal, Jean-Jacques Rajter, Juliana Cepelowicz Rajter, Michele Sallaberger, Alexia Smileski, Amala Kanagalingam and David A. Jans
Pharmaceutics 2025, 17(9), 1205; https://doi.org/10.3390/pharmaceutics17091205 - 16 Sep 2025
Viewed by 474
Abstract
Background: The efficacy of a single oral dose of Ivermectin as prophylaxis for SARS-CoV-2 is uncertain. This trial sought to evaluate the effectiveness of a single oral low dose of Ivermectin to prevent SARS-CoV-2 infection or reduce symptoms if infection did occur. Methods: [...] Read more.
Background: The efficacy of a single oral dose of Ivermectin as prophylaxis for SARS-CoV-2 is uncertain. This trial sought to evaluate the effectiveness of a single oral low dose of Ivermectin to prevent SARS-CoV-2 infection or reduce symptoms if infection did occur. Methods: Asymptomatic community-dwelling adults were enrolled in this study within 72 h of close contact with a case of SARS-CoV-2. Participants were randomised, stratified by vaccination status and exposure site, to a single oral 200 µg/kg dose of Ivermectin or placebo. The primary outcome was conversion to a positive polymerase chain reaction (PCR) or rapid antigen test (RAT) for SARS-CoV-2 within 14 days of close contact. Secondary outcomes were restricted to those who met the primary outcome. They included the following: days alive free of symptoms in the 14 (DAFS1-14) and 28 (DAFS1-28) days following intervention and days from close contact until a positive PCR or RAT for SARS-CoV-2. Results: A total of 536 participants registered for this trial. Of these, 86 met inclusion criteria and were randomised. 68 adhered to the trial protocol and were included in the analysis. A total of 11/36 (Ivermectin arm) and 11/32 (placebo arm) met the primary outcome. After controlling for age and prior SARS-CoV-2 infection, the estimate (95% confidence interval (95% CI)) of the effect of Ivermectin (compared to placebo) on the absolute value of the proportion of participants converting to a positive PCR or RAT was −0.051 (−0.26 to 0.16), p = 0.63. After controlling for prior SARS-CoV-2 infection, age, body mass index, hypertension and lung disease, the average treatment effect (Ivermectin versus placebo) on DAFS1-14 was 2.5 days (95%CI 1.1 to 4.5), p = 0.036, and for DAFS1-28, was 2.3 days (95% CI 0.7 to 3.3), p = 0.35. The mean (standard deviation) number of days from close contact until a positive PCR or RAT was 5.0 (4.1) days for the Ivermectin group versus 2.6 (0.8) days for the placebo group. After controlling for age and prior SARS-CoV-2 infection, the average treatment effect (95%CI), Ivermectin versus placebo, on days from close contact until a positive PCR or RAT was 2.3 days (95% CI 1.1 to 3.4), p = 0.033. Conclusions: We did not demonstrate that a single oral low dose of Ivermectin administered to asymptomatic adults within 72 h of close contact with a case of SARS-CoV-2 prevents conversion to a positive PCR or RAT. However, the trial had a small sample size and does not exclude a clinically meaningful effect of Ivermectin on conversion to a positive PCR or RAT. Amongst those who did convert to a positive PCR or RAT, the use of Ivermectin significantly lengthened the time from close contact to conversion and increased the number of days alive free of symptoms following intervention. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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16 pages, 1088 KB  
Review
Radiation-Free Percutaneous Coronary Intervention: Myth or Reality?
by Sotirios C. Kotoulas, Andreas S. Triantafyllis, Nestoras Kontogiannis, Pavlos Tsinivizov, Konstantinos Antoniades, Ibraheem Aqeel, Eleni Karapedi, Angeliki Kolyda and Leonidas E. Poulimenos
J. Cardiovasc. Dev. Dis. 2025, 12(9), 339; https://doi.org/10.3390/jcdd12090339 - 3 Sep 2025
Viewed by 1515
Abstract
Background: Radiation exposure in the cardiac catheterization laboratory remains a critical occupational hazard for interventional cardiologists and staff, contributing to orthopedic injuries, cataracts, and malignancy. In parallel, procedural complexity continues to increase, demanding both precision and safety. Robotic-assisted percutaneous coronary intervention (R-PCI), alongside [...] Read more.
Background: Radiation exposure in the cardiac catheterization laboratory remains a critical occupational hazard for interventional cardiologists and staff, contributing to orthopedic injuries, cataracts, and malignancy. In parallel, procedural complexity continues to increase, demanding both precision and safety. Robotic-assisted percutaneous coronary intervention (R-PCI), alongside advanced shielding systems and imaging integration, has emerged as a transformative strategy to minimize radiation and enhance operator ergonomics. Objective: This state-of-the-art review synthesizes the current clinical evidence and technological advances that support a radiation-reduction paradigm in percutaneous coronary intervention (PCI), with a particular focus on the role of R-PCI platforms, procedural modifications, and emerging shielding technologies. Methods: We reviewed published clinical trials, registries, and experimental studies evaluating robotic PCI platforms, contrast and radiation dose metrics, ergonomic implications, procedural efficiency, and radiation shielding systems. Emphasis was given to the integration of CT-based imaging (coronary computed tomography angiography—CCTA, fractional flow reserve computed tomography—FFR-CT) and low-dose acquisition protocols. Results: R-PCI demonstrated technical success rates of 81–100% and clinical success rates up to 100% in both standard and complex lesions, with significant reductions in operator radiation exposure (up to 95%) and procedural ergonomic burden. Advanced shielding technologies offer radiation dose reductions ranging from 86% to nearly 100%, while integration of (CCTA), (FFR-CT), and Artificial Intelligence (AI) -assisted procedural mapping facilitates further fluoroscopy minimization. Robotic workflows, however, remain limited by lack of device compatibility, absence of haptic feedback, and incomplete integration of physiology and imaging tools. Conclusions: R-PCI, in combination with shielding technologies and imaging integration, marks a shift towards safer, radiation-minimizing interventional strategies. This transition reflects not only a technical evolution but a philosophical redefinition of safety, precision, and sustainability in modern interventional cardiology. Full article
(This article belongs to the Special Issue Emerging Trends and Advances in Interventional Cardiology)
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18 pages, 1793 KB  
Review
Letrozole at the Crossroads of Efficacy and Fetal Safety in Ovulation Induction: A Narrative Review
by Aris Kaltsas, Anna Efthimiou, Christos Roidos, Vasileios Tzikoulis, Ioannis Georgiou, Alexandros Sotiriadis, Athanasios Zachariou, Michael Chrisofos, Nikolaos Sofikitis and Fotios Dimitriadis
Biomedicines 2025, 13(9), 2051; https://doi.org/10.3390/biomedicines13092051 - 22 Aug 2025
Viewed by 1927
Abstract
Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse [...] Read more.
Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article
(This article belongs to the Special Issue Maternal-Fetal and Neonatal Medicine)
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13 pages, 1240 KB  
Article
Bioequivalence and Pharmacokinetics of Low-Dose Anagrelide 0.5 mg Capsules in Healthy Volunteers
by Ahmet Inal, Zafer Sezer, Onur Pinarbasli, Burcu Bulut, Martin Reinsch, Wolfgang Martin, Mumtaz M. Mazicioglu and Selma Alime Koru
Biomedicines 2025, 13(8), 1993; https://doi.org/10.3390/biomedicines13081993 - 15 Aug 2025
Viewed by 629
Abstract
Objectives: Anagrelide, an oral phosphodiesterase-3 inhibitor, is widely used to treat thrombocythemia. Evaluating the bioequivalence of low-dose formulations is essential to ensure consistent therapeutic outcomes while minimizing adverse effects, particularly cardiovascular events such as palpitations, tachycardia, and potential arrhythmias, which are known [...] Read more.
Objectives: Anagrelide, an oral phosphodiesterase-3 inhibitor, is widely used to treat thrombocythemia. Evaluating the bioequivalence of low-dose formulations is essential to ensure consistent therapeutic outcomes while minimizing adverse effects, particularly cardiovascular events such as palpitations, tachycardia, and potential arrhythmias, which are known concerns with anagrelide therapy. This study aimed to compare the pharmacokinetics and bioavailability of a newly developed 0.5 mg anagrelide capsule with the reference product under fasting conditions y. Materials and Methods: In a randomized, open-label, two-period crossover design, 42 healthy Turkish male volunteers received a single oral dose (0.5 mg) of either the test or reference anagrelide capsule, with a seven-day washout period between treatments. Serial blood samples were collected over a 10 h post-dose period. Plasma concentrations of anagrelide were analyzed using a validated LC-MS/MS method. Key pharmacokinetic parameters (AUC0–t, AUC0–∞, Cmax, tmax, λz, t½, AUC–extrapol) were calculated and subjected to ANOVA-based bioequivalence analysis. Results: A total of 42 healthy male participants (mean age: 34.1 ± 8.9 years; BMI: 25.7 ± 2.9 kg/m2) completed the study without any protocol deviations. Pharmacokinetic analysis demonstrated that the test and reference formulations of anagrelide 0.5 mg were bioequivalent. The mean AUC0–t values were 4533.3 ± 2379.3 pg·h/mL for the test formulation and 4515.0 ± 2392.3 pg·h/mL for the reference (p > 0.05), while the mean Cmax values were 1997.1 ± 1159.2 pg/mL and 2061.3 ± 1054.0 pg/mL, respectively (p > 0.05). The 90% confidence intervals for the geometric mean ratios of AUC0–t (94.09–104.75%), Cmax (85.62–104.03%), and AUC0–∞ (94.50–105.10%) were all within the predefined bioequivalence range of 80–125%, with corresponding point estimates of 99.28%, 94.37%, and 99.66%, respectively. Intra-subject variability was 14.68% for AUC0–t and 26.98% for Cmax. No statistically significant differences were observed between the formulations for any of the primary or secondary pharmacokinetic parameters (ANOVA, p > 0.05). Regarding safety, 13 treatment-emergent adverse events were reported in 11 participants (26.2%), mostly moderate-intensity headaches, all of which resolved without complications. No serious adverse events occurred, confirming the tolerability of both formulations. Conclusions: This study demonstrates that the test and reference formulations of low-dose 0.5 mg anagrelide are bioequivalent under fasting conditions, with similar safety and tolerability profiles. The findings support the use of the test product as a safe and effective alternative. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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14 pages, 2199 KB  
Article
Low-Cost Production of Brazilian Mahogany Clones Based on Indole-3-Butyric Acid Use, Clonal Mini-Hedge Nutrition and Vegetative Propagule Type
by Rafael Barbosa Diógenes Lienard, Annanda Souza de Campos, Lucas Graciolli Savian, Barbara Valentim de Oliveira, Felippe Coelho de Souza and Paulo André Trazzi
Forests 2025, 16(8), 1292; https://doi.org/10.3390/f16081292 - 7 Aug 2025
Viewed by 458
Abstract
Swietenia macrophylla King, commonly known as Brazilian mahogany, is a high-value neotropical tree species currently threatened due to intensive logging in previous decades. Technologies aimed at clonal production are essential for this species’ conservation and sustainable use at times of climate change and [...] Read more.
Swietenia macrophylla King, commonly known as Brazilian mahogany, is a high-value neotropical tree species currently threatened due to intensive logging in previous decades. Technologies aimed at clonal production are essential for this species’ conservation and sustainable use at times of climate change and increasing demand for ecological restoration. The aim of the present study is to develop a low-cost protocol for mahogany clonal propagation through mini-cutting by assessing clonal mini-hedge nutrition, vegetative propagule type and indole-3-butyric acid (IBA) application effects on rooting and early clone growth. The experiment was conducted in nursery under controlled conditions based on using basal and apical mini-cuttings rooted in a low-cost mini-greenhouse subjected to three nutrient solution concentrations (50%, 100%, and 200%) and five IBA doses (0–8000 ppm). The mini-cutting technique proved efficient and led to over 90% survival after the hardening phase. The 200% nutrient solution concentration allowed balanced performance between cutting types and optimized clonal yield. IBA concentration at 4000 ppm accounted for higher root percentages at the bottom of the tube and the trend towards higher dry biomass production at 160 days. The results highlighted mini-cutting’s potential as a viable mahogany conservation and sustainable production technique. It also supported tropical forestry sector adaptation to challenges posed by climate change. Full article
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23 pages, 1967 KB  
Article
Evaluation of Myocardial Protection in Prolonged Aortic Cross-Clamp Times: Del Nido and HTK Cardioplegia in Adult Cardiac Surgery
by Murat Yücel, Emre Demir Benli, Kemal Eşref Erdoğan, Muhammet Fethi Sağlam, Gökay Deniz, Hakan Çomaklı and Emrah Uğuz
Medicina 2025, 61(8), 1420; https://doi.org/10.3390/medicina61081420 - 6 Aug 2025
Viewed by 628
Abstract
Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic [...] Read more.
Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. Full article
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11 pages, 239 KB  
Article
Targeted Antibiotic Prophylaxis in Percutaneous Nephrolithotomy: Results of a Protocol Based on Preoperative Urine Culture and Risk Assessment
by Felipe Osorio-Ospina, Gonzalo Bueno-Serrano, María Pilar Alcoba-García, Juan Tabares-Jiménez, Blanca Gómez-Jordana-Mañas, Elena García-Criado, Joaquin Ruiz-de-Castroviejo, Xabier Pérez-Aizpurua, Jaime Jorge Tufet-I-Jaumot, Raúl González-Páez, Jose Carlos Matta-Pérez, Beatriz Yanes-Glaentzlin, Juan Francisco Jiménez-Abad, José Maria Alcázar Peral, Nerea Carrasco Antón, Elizabet Petkova-Saiz and Carmen González-Enguita
J. Clin. Med. 2025, 14(15), 5249; https://doi.org/10.3390/jcm14155249 - 24 Jul 2025
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Abstract
Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the [...] Read more.
Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the use of a single antibiotic dose tailored to culture sensitivity in these cases is limited but emerging. Methods: We conducted a retrospective observational study including 187 PCNL procedures performed between 2021 and 2023 under an individualized antibiotic prophylaxis protocol. Patients with negative or contaminated urine cultures received a single empirical dose, while those with recent positive cultures received a single dose based on antimicrobial susceptibility testing. Postoperative complications—including fever, sepsis, and a composite outcome—were analyzed through multivariable logistic regression, comparing high- and low-risk patients. Results: A total of 67.9% of procedures were performed in patients meeting at least one high-risk criterion, including a positive preoperative urine culture in 32.1%. The overall incidence of infectious complications was 11.9% (fever 8.7%, sepsis 3.2%), with no significant differences between risk groups. A low concordance was observed between preoperative and intraoperative urine cultures (Spearman = 0.3954). Conclusions: A single preoperative antibiotic dose adjusted to the antibiogram, even in patients with a positive urine culture, was not associated with increased infectious complications. This approach is an initial step that supports a rational and individualized prophylactic strategy aligned with the goals of antimicrobial stewardship programs (ASPs). Full article
(This article belongs to the Special Issue Targeted Treatment of Kidney Stones)
19 pages, 2186 KB  
Article
Optimizing Rooting and Growth of Salvia rosmarinus Cuttings in Soilless Systems Affected by Growth Regulators
by Georgios Lykokanellos, Ioannis Lagogiannis, Aglaia Liopa-Tsakalidi, Sofia Anna Barla and Georgios Salachas
Plants 2025, 14(14), 2210; https://doi.org/10.3390/plants14142210 - 17 Jul 2025
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Abstract
This study investigated how propagation systems, growth regulators, and hormone formulations interactively affect the rooting and subsequent growth of rosemary (Salvia rosmarinus Spenn) cuttings. A three factorial (3 × 2 × 7) experiment was conducted under a fully controlled greenhouse environment, incorporating [...] Read more.
This study investigated how propagation systems, growth regulators, and hormone formulations interactively affect the rooting and subsequent growth of rosemary (Salvia rosmarinus Spenn) cuttings. A three factorial (3 × 2 × 7) experiment was conducted under a fully controlled greenhouse environment, incorporating three soilless propagation systems (mist, float, aeroponics), two rooting hormone formulations (powder and gel-based IBA), and two growth regulators (paclobutrazol and daminozide) at three concentrations each. Significant differences (p < 0.001) were found in shoot height, root length, and number of lateral roots. The float system combined with powder hormone and no retardants achieved the highest shoot height (mean = 16.7 cm), while aeroponics with powder hormone and daminozide 1000 ppm promoted the greatest root branching (mean = 12.2 lateral roots per cutting). Root length was maximized (mean = 15.9 cm) under float systems with daminozide 1000 ppm. High doses of both growth regulators negatively affected all parameters across systems. Post-transplantation monitoring confirmed that cuttings from float and mist systems treated with powder hormone and low or no growth retardants exhibited superior establishment and net growth over 60 days. These findings demonstrate the critical importance of pairing hormone type, regulator concentration, and propagation system, providing actionable protocols for nursery managers aiming to enhance Salvia rosmarinus propagation in commercial practice. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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22 pages, 3768 KB  
Article
MWB_Analyzer: An Automated Embedded System for Real-Time Quantitative Analysis of Morphine Withdrawal Behaviors in Rodents
by Moran Zhang, Qianqian Li, Shunhang Li, Binxian Sun, Zhuli Wu, Jinxuan Liu, Xingchao Geng and Fangyi Chen
Toxics 2025, 13(7), 586; https://doi.org/10.3390/toxics13070586 - 14 Jul 2025
Viewed by 2650
Abstract
Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating [...] Read more.
Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article
(This article belongs to the Section Drugs Toxicity)
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