High Dose Research Articles

Safety and Efficacy of Atogepant for the Preventive Treatment of Migraines in Adults: A Systematic Review and Meta-Analysis

Background: Migraine is a common neurological condition marked by unilateral recurrent pulsating headaches, often associated with systemic signs and symptoms. Recently, calcitonin gene-related peptide (CGRP) antagonists, including atogepant, an oral CGRP receptor antagonist, have emerged as effective and safe treatments. The current study sought to assess the efficacy and safety of atogepant for preventing episodic migraines in adults. Methods: A comprehensive search, following PRISMA guidelines, was conducted using PubMed, Web of Science, and Cochrane Library to identify randomized, double-blind, placebo-controlled trials published up to June 2024. Results: The studies included adult participants with episodic migraine treated with atogepant. The primary outcomes assessed were changes in mean monthly migraine days (MMDs) and monthly headache days (MHDs) over 12 weeks. Secondary outcomes included reduction in acute medication use, 50% responder rates, and adverse events. A meta-analysis using a random-effects model was performed to evaluate efficacy and safety. Six trials with 4569 participants were included. Atogepant significantly reduced mean monthly migraine days (MMDs) and monthly headache days (MHDs) compared to placebo at all doses (10 mg, 30 mg, 60 mg), with the 60 mg dose showing the greatest reduction (mean difference: −1.48 days, p < 0.001). Significant reductions in acute medication use and improved 50% responder rates were also observed for all doses. The safety profile of atogepant was favorable, with common adverse events being mild to moderate, such as constipation and nausea. There were no significant differences in serious adverse events between the atogepant and placebo groups. Conclusions: Atogepant is an effective and well-tolerated option for preventing episodic migraines, showing significant reductions in migraine frequency and acute medication use. However, further studies are necessary to assess its long-term safety and efficacy, especially at higher doses, and to investigate its potential role in personalized treatment strategies for migraine prevention.

Multispectral UAV-Based Disease Identification Using Vegetation Indices for Maize Hybrids

In the future, the cultivation of maize will become more and more prominent. As the world’s demand for food and animal feeding increases, remote sensing technologies (RS technologies), especially unmanned aerial vehicles (UAVs), are developing more and more, and the usability of the cameras (Multispectral-MS) installed on them is increasing, especially for plant disease detection and severity observations. In the present research, two different maize hybrids, P9025 and sweet corn Dessert R78 (CS hybrid), were employed. Four different treatments were performed with three different doses (low, medium, and high dosage) of infection with corn smut fungus (Ustilago maydis [DC] Corda). The fields were monitored two times after the inoculation—20 DAI (days after inoculation) and 27 DAI. The orthomosaics were created in WebODM 2.5.2 software and the study included five vegetation indices (NDVI [Normalized Difference Vegetation Index], GNDVI [Green Normalized Difference Vegetation Index], NDRE [Normalized Difference Red Edge], LCI [Leaf Chlorophyll Index] and ENDVI [Enhanced Normalized Difference Vegetation Index]) with further analysis in QGIS. The gathered data were analyzed using R-based Jamovi 2.6.13 software with different statistical methods. In the case of the sweet maize hybrid, we obtained promising results, as follows: the NDVI values of CS 0 were significantly higher than the high-dosed infection CS 10.000 with a mean difference of 0.05422 *** and a p value of 4.43 × 10−5 value, suggesting differences in all of the levels of infection. Furthermore, we investigated the correlations of the vegetation indices (VI) for the Dessert R78, where NDVI and GNDVI showed high correlations. NDVI had a strong correlation with GNDVI (r = 0.83), a medium correlation with LCI (r = 0.56) and a weak correlation with NDRE (r = 0.419). There was also a strong correlation between LCI and GNDVI, with r = 0.836. NDRE and GNDVI indices had the correlation coefficients with a CCoeff. of r = 0.716. For hybrid separation analyses, useful results were obtained for NDVI and ENDVI as well.

Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials

BackgroundConsidering the increasing prevalence of obesity/overweight, its treatment or prevention with new interventions can greatly help health and reduce its adverse effects in people. One of these new interventions is investigating the effect of Survodutide as a dual agonist of glucagon and GLP-1 receptors, which seems to be able to influence weight loss processes in different ways. In this study, we investigated the effect of injectable Survodutide on weight loss.MethodsIn order to identify all randomized controlled trials that investigated the effects of Survodutide on factores related to obesity, a systematic search was conducted in the original databases using predefined keywords until August 2024. The pooled weighted mean difference and 95% confidence intervals were computed using the random-effects model.ResultsThe Findings from 18 treatment arms with 1029 participants indicated significant reductions in weight (WMD: -8.33 kg; 95% CI: -10.80, -5.86; I2 = 99.6%), body mass index (BMI) (WMD:-4.03 kg/m2; 95% CI: -4.86, -3.20; I2 = 72.7%), and waist circumferences (WC) (WMD: -6.33 cm; 95% CI: -8.85 to -3.81; I2 = 99.5%) following the Survodutide injection compared to the control group. Subgroup analysis reveals that longer interventions (more than 16 weeks) and higher doses (more than 2 mg/week) of Survodutide are associated with more significant reductions in weight and WC. These results were also observed in the meta-regression analysis.ConclusionsThe results of this meta-analysis show that Survodutide is effective in reducing weight, BMI and waist circumference, especially with longer interventions and higher doses.

Comparative Study of pH-Responsive and Aggregation Stability of Bosutinib-Loaded Nanogels Comprising Gelatin Methacryloyl, Carboxymethyl Dextran, and Hyaluronic Acid for Controlled Drug Delivery in Colorectal Cancer: An Extensive In Vitro Investigation.

This study investigates the use of pH-responsive nanogels for delivering Bosutinib (BOSU) in colon cancer treatment. Nanogels were formulated using three polymers: hyaluronic acid (HA), carboxymethyl dextran (CMD), and gelatin methacryloyl (GelMA). These nanogels achieved high drug entrapment efficiencies (80-90%) through polymer mixing with BOSU, followed by EDC/NHS cross-linking and sonication. The nanogels were stable, with negative zeta potentials (-20 to -30 mV) and particle sizes between 100 and 200 nm. Fourier-transform infrared analysis confirmed successful methacrylation in GelMA nanogels. Sustained BOSU release at pH 5.0 was observed, resembling tumor environments, compared to slower release at normal pH (7.4). Cytotoxicity tests showed 70-80% cell survival reduction in HCT116 colon cancer cells at higher doses, and GelMA-BOSU nanogels notably reduced cell migration. Antiangiogenic effects were confirmed in a chick chorioallantoic membrane model, highlighting the potential of these nanogels for targeted BOSU delivery in colon cancer therapy.

Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.

This study aimed to investigate the dose and trough concentration (Cmin) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma Cmins, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 Cmins of 113 pediatric patients were detected. The median Cmins were 1.0 and 1.3 mg/L for tablets and injections, respectively (P < 0.05). The median doses required to achieve the target Cmin were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect Cmins of tablets, while age, gender, and BMI were found to be correlated with Cmins of injections. IFD breakthrough occurred in 9.2% of patients with a median Cmins of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median Cmins of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.

Radiotherapy as a metastasis directed therapy for liver oligometastases - comparative analysis between CT-guided interstitial HDR brachytherapy and two SBRT modalities performed on double-layer and single layer LINACs

IntroductionSurgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis.Material and methodsPatients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups.ResultsCT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT.ConclusionsCT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies.

Paclitaxel-Coated Versus Sirolimus-Coated Eluting Balloons for Percutaneous Coronary Interventions: Pharmacodynamic Properties, Clinical Evidence, and Future Perspectives

Drug-coated balloons (DCBs) have emerged as an increasingly valuable option for the treatment of coronary artery disease (CAD). Percutaneous coronary intervention (PCI) with DCBs enables the localized delivery of antiproliferative drugs directly to the target coronary lesion, avoiding the need for permanent scaffold implantation. Historically, paclitaxel-coated balloons (PCBs) have been the most used device in this context. Paclitaxel interferes with intracellular microtubule function, leading to cell cycle arrest. However, its cytotoxicity at a higher dosage and narrow therapeutic range has raised some safety concerns. To address these issues, sirolimus-coated balloons (SCBs) have been introduced as an alternative. Sirolimus acts as a cytostatic agent with potent anti-inflammatory and antiproliferative properties and is characterized by a wider therapeutic range, potentially offering a safer profile. Several experimental and clinical studies comparing the safety and efficacy of PCBs versus SCBs have yielded mixed results. Recently, a novel DCB (SirPlux Duo), which simultaneously releases both paclitaxel and sirolimus, has been tested in a porcine coronary model with promising results. In this review, we will elucidate the mechanisms of action of paclitaxel and sirolimus, examine contemporary preclinical and clinical evidence comparing PCB and SCB angioplasty, and discuss novel devices that may enhance the safety and efficacy of PCI with DCBs.

Criteria for Re-Irradiation.

The treatment options for patients with progressive malignant tumors despite primary radiotherapy are often limited. In selected cases, re-irradiation can be offered. This article concerns the selection criteria and results of re-irradiation for certain types of cancer. This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to glioblastoma, head and neck tumors, and prostatic carcinoma. The published studies of re-irradiation are few in number and often of limited methodological quality. For glioblastoma, a randomized controlled trial (RCT) found that adding re-irradiation to treatment with bevacizumab yielded no significant improvement in either median progression-free survival or median overall survival (hazard ratio [HR] 0.73; p = 0.05 and HR 0.98; p = 0.46, respectively). Re-irradiation is a treatment option for locoregional recurrences of head and neck tumors after primary radiotherapy, but it carries a risk of serious side effects. For unresectable recurrences of nasopharyngeal carcinoma, an RCT has shown that hyperfractionated re-irradiation is more effective than normofractionated re-irradiation (overall survival: HR 0.54, p = 0.014). For locally recurrent prostatic carcinoma after radiotherapy, re-irradiation can yield good oncologic outcomes with an acceptable level of urogenital and gastrointestinal side effects (5-year recurrence-free survival: stereotactic body radiation therapy (SBRT), 58%; high dose rate (HDR) brachytherapy, 77%; versus salvage prostatectomy, 72%). RCTs on this topic are lacking. Re-irradiation is a treatment option for selected cancer patients. As the available scientific evidence is limited, multidisciplinary collaboration and participatory decision-making are particularly important.

Investigation of serpentine entrainment reduction in pentlandite flotation using eco-friendly sodium alginate in suspension dispersion systems

Magnesium silicates pose severe environmental issues in hydrometallurgical processes. Copper-nickel sulfide ores are the primary source for nickel production, but their increasingly complex properties make separation difficult, causing slimy magnesium silicate minerals to be entrained into the concentrate with the foam, leading to magnesium contamination. Studies have found that sodium alginate (SA), as an environmentally friendly polymer reagent, can effectively inhibit serpentine. This work investigates the effect of SA on the flotation behavior of pentlandite and serpentine in a sodium hexametaphosphate (SHMP) system. Sedimentation tests show that only a low dosage of SA can effectively settle serpentine, while excessive SA disperses serpentine. Flotation tests indicate that SA can further increase the difference in recovery rates between pentlandite and serpentine based on SHMP. Results from artificial mixed ore tests demonstrate that the recovery rate of serpentine decreases from 51.22% to 37.37% with the addition of SA, with minimal impact on the recovery rate of pentlandite. To explain the impact of the SA adsorption process on the mineral states, the following tests and analyses were conducted: TOC and QCM-D results indicate that SA mainly adsorbs onto serpentine, forming rigid adsorption at low dosages and flexible adsorption at high dosages. Zeta potential tests reveal changes in the surface potential of the minerals, explaining the transition from electrostatic attraction to electrostatic repulsion between pentlandite and serpentine. FTIR and XPS results show that SA chemically reacts with the Mg and Si sites on the serpentine surface through its -COO- groups. In summary, in the SHMP system, the use of gel adsorption and the chemical interaction of SA to coagulate and depress serpentine reduces its entrainment into the concentrate, achieving efficient separation of pentlandite and serpentine. However, high dosages of SA do not yield satisfactory results.

In vitro cytotoxicity assessment of carbonaceous gels for bone marrow mesenchymal stem cells

The current work aimed to elucidate the potential applications of the carbonaceous gels and assess the in vitro cytotoxicity of these gels when suspended in a culture medium and exposed to bone marrow mesenchymal stem cells. Cellular viability, cell cycle distribution, apoptotic cell death, and mitochondrial membrane potential in bone marrow mesenchymal stem cells co-incubated with different concentrations of carbonaceous gels (0.1, 1, 10, 50, and 100μg/mL) were evaluated. Flow cytometry and immunofluorescence were used to investigate apoptosis and cell cycle distribution. The expression of associated apoptotic proteins was analysed using Western Blot. Although the co-incubation of carbonaceous gels did not significantly affect cell viability, high dosages (100μg/mL) of these gels led to cellular dysfunction. Specifically, cells exposed to high concentrations of these gels exhibited G2-phase arrest and increased levels of reactive oxygen species. However, the reported impacts did not cause considerable cell death. At the same time, carbonaceous gels did not significantly induce apoptosis. Compared to other carbon nanomaterials, carbonaceous gels' biotoxicity was relatively low, suggesting their potential for various biological applications. Nonetheless, caution should be exercised when considering the concentration of carbonaceous gels for future medical applications.

Population pharmacokinetics of fluconazole for prevention or treatment of invasive candidiasis in Chinese young infants.

The dosing of fluconazole for young infants remains empirical because of the limited pharmacokinetic (PK) data. We aimed to establish a population PK model and assess the systematic exposure-response of commonly used regimens of fluconazole in Chinese infants.We included infants with a postnatal age of less than 120 days and received intravenous fluconazole. Both scheduled and scavenged plasma samples were collected, and fluconzaole concentration was determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using Phoenix NLME, and then Monte Carlo simulation was conducted to predict the probability of target attainment (PTA) of empirically used regimens of both prophylactic and therapeutic purposes.Based on 304 plasma samples from 183 young infants, fluconazole concentration data was best described by a one-compartment model with first-order elimination. Gestational Age (GA), postnatal age (PNA), and body weight (BW) were included in the final model as CL = 0.02*(GA/214)2.77*(PNA/13)0.24*exp(nCL); V = 1.56*(BW/1435)0.90*exp(nV). Model validation revealed the final model had qualified stability and acceptable predictive properties. Monte Carlo simulation indicated that under the same minimum inhibitory concentration (MIC) value and administration regimen, PTA decreased with GA and PNA. The commonly used prophylactic regimens can meet the clinical need, while higher doses might be needed for treatment of invasive candidiasis.This population PK model of fluconazole discriminated the impact of GA and PNA on CL and BW on V. Dosing adjustment was needed according to the GA and PNA of infants to achieve targeted exposures.

Zolpidem-related euphoria, addiction and detoxification: A case report and review of the literature.

Zolpidem, a non-benzodiazepine sedative-hypnotic, is considered safer for the treatment of insomnia compared to benzodiazepines. However, in recent years, there have been growing reports of Zolpidem dependence, addiction, and withdrawal symptoms. We reported a case of Zolpidem addiction and successful detoxification, reviewed similar cases in the literature, and proposed a potential mechanism underlying Zolpidem addiction. The patient was a 46-year-old Tibetan woman who had been using Zolpidem intermittently to treat insomnia for at least 8 years. She was overweight, with a BMI of 28.04 kg/m², and had hypertension, diabetes, a 20-year smoking history, and several years of alcohol abuse, often seeking instant gratification. She voluntarily increased both the dosage and frequency of Zolpidem, experiencing euphoria, anxiolysis, and increased appetite at higher doses, which led her to gradually escalate her dosage to 280 mg per day in divided doses. However, upon stopping Zolpidem, she experienced withdrawal symptoms, including insomnia, tension, and palpitations. She was diagnosed with a combination of hypnotic use disorder, anxiety disorder, hypertension, and diabetes. She underwent diazepam replacement therapy, along with antianxiety medications and mindfulness-based cognitive therapy, to address Zolpidem addiction. After 13 days of inpatient treatment, the patient successfully quit Zolpidem. During a 3-month follow-up, she returned to work and remained free from Zolpidem use. We speculate that Zolpidem addiction is likely linked to the drug's euphoric effects and certain patient characteristics, such as sensation-seeking behavior. A comprehensive approach, involving both pharmacological and psychological interventions, is essential for an effective detoxification strategy for Zolpidem addiction.

Cobalt-modified digestate-derived biochar enhances kitchen waste anaerobic dry digestion: Performance, microbial mechanisms, and metabolic pathways

To achieve simultaneous in-situ high-value utilization of digestate and efficient resource recovery of kitchen waste (KW). In this work, Co-modified digestate-derived biochar (DDB-Co) was prepared for the first time, the effects of DDB-Co on KW mesophilic dry anaerobic digestion were investigated, and the underlying mechanisms were elucidated. The results showed that the specific surface area of DDB-Co increased to 98.7 m2/g, which was 37.4 % higher than that of the unmodified group (DDB). DDB-Co exhibited a dose-dependent effect on biogas production from the KW dry digestion, with the optimal dose of 4.0 g/L (calculated on a solid content) DDB-Co yielding 205.3 mL/(g·VS) of biogas, representing an 80.9 % increase compared to the CK group. However, higher doses, such as 8.0 g/L DDB-Co, reduced the cumulative biogas production. Mechanistic analysis indicated that 4.0 g/L DDB-Co facilitated the dissolution of particulate organic matter and accelerates the conversion process of volatile fatty acids (VFA) in KW, thereby preventing excessive acidification. Microbial community structure analysis revealed that DDB-Co reduced microbial richness and diversity but selectively enriched microorganisms such as Lactobacillus and Methanothrix, accelerating the direct interspecific electron transfer (DIET) reaction rate and increasing biogas production. Metagenomic analysis demonstrated that DDB-Co primarily upregulated the relative abundances of key enzymes in the acetate decarboxylation methanogenesis pathway, such as acetate kinase (ackA), phosphate acetyltransferase (pta), and acetyl-CoA synthetase (acs), enhancing biogas yield and maintaining system stability. The findings of this work expand the high-value utilization pathways for digestate and provide an alternative solution for the efficient resource recovery of KW.

Effect of Beta-Alanine Supplementation on Maximal Intensity Exercise in Trained Young Male Individuals: A Systematic Review and Meta-Analysis.

Beta-alanine is a nonessential amino acid that is commonly used to improve exercise performance. It could influence the buffering of hydrogen ions produced during intense exercise and delay fatigue, providing a substrate for increased synthesis of intramuscular carnosine. This systematic review evaluates the effects of beta-alanine supplementation on maximal intensity exercise in trained, young, male individuals. Six databases were searched on August 10, 2023, to identify randomized, double-blinded, placebo-controlled trials investigating the effect of chronic beta-alanine supplementation in trained male individuals with an age range of 18-40years. Studies evaluating exercise performance through maximal or supramaximal intensity efforts falling within the 0.5-10min duration were included. A total of 18 individual studies were analyzed, employing 18 exercise test protocols and 15 outcome measures in 331 participants. A significant (p = .01) result was observed with an overall effect size of 0.39 (95% confidence interval [CI] [0.09, 0.69]), in favor of beta-alanine supplementation versus placebo. Results indicate significant effects at 4weeks of supplementation, effect size 0.34 (95% CI [0.02, 0.67], p = .04); 4-10min of maximal effort, effect size 0.55 (95% CI [0.07, 1.04], p = .03); and a high beta-alanine dosage of 5.6-6.4g per day, effect size 0.35 (95% CI [0.09, 0.62], p = .009). The results provide insights into which exercise modality will benefit the most, and which dosage protocols and durations stand to provide the greatest ergogenic effects. This may be used to inform further research, and professional or recreational training design, and optimization of supplementation strategies.

Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora

Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS-Pg), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS-Pg lasting for ten weeks. The results demonstrated that FCS-Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS-Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS-Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter, Bilophila and Firmicutes compared with HFD group. Moreover, FCS-Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS-Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.

Fundamental cracking performance of asphalt-filler mastics with hydrated lime

This study evaluates the impact of hydrated lime (HL) on the cracking performance at intermediate temperature of asphalt-filler mastics, specifically as a partial replacement for limestone filler (LF). HL, is an active filler known for its multiple benefits in asphalt applications. The Double Edge Notched Tension (DENT) test was used to assess fracture properties, including specific total work of fracture, plastic work of failure, essential work of fracture, and average critical tip opening displacement. The results revealed several key findings: a notable loss of ductility and toughness with increasing HL dosages, a stiffening effect evidenced by increased peak loads and reduced failure deformation, and a decrease in the specific total work of fracture, indicating a loss of fracture energy. However, an enhancement in fracture resistance to plastic deformation is observed with HL addition, although identifying trends at high dosages remains challenging due to complex interactions between HL and LF. Furthermore, using low volumetric concentrations of HL minimizes the adverse impact on fracture performance while leveraging its other beneficial active filler properties. These findings suggest that while HL can improve certain fracture properties, optimal dosages are crucial to avoid adverse effects. Overall, this paper provides an updated and comprehensive study of the fracture of mastics at intermediate temperatures, which adds up to the understanding of asphalt-filler interactions, which can potentially lead to further investigations, such as how the partial replacement of LF with HL affects asphalt mixtures’ performance-related characteristics, particularly the fatigue cracking resistance.

Amlodipine-induced gingival hyperplasia in a Nepalese patient experiencing high dosages: a case report

Introduction and importance: Amlodipine is a third-generation calcium channel blocker used in the treatment of hypertension. One of the side effects associated with amlodipine is gingival hyperplasia mostly occurring at a higher dose (10 mg). There are very few cases of gingival hyperplasia associated with amlodipine at a lower dose (5 mg) or short-term administration. Case presentation: A 51-year-old male patient with diagnosed hypertension sought medical attention for gingival swelling and bleeding from the gums while brushing. He had been under amlodipine 5 mg for 12 months, which was increased to 10 mg for the last 2 months. The history and physical examination were consistent with amlodipine-induced gingival hyperplasia. The first line of treatment consisted of discontinuation of amlodipine and substitution with another class of anti-hypertensive. Clinical discussion and conclusion: The presented case highlights the challenge of balancing economic considerations with potential side effects in the use of amlodipine for hypertension in low-income countries like Nepal. Given its availability at no cost or minimal expense, amlodipine is often initiated as a first-line therapy. However, the decision to increase the dosage to 10 mg/day, influenced by economic constraints and the drug’s affordability, raises the risk of gingival hyperplasia. This case emphasizes the importance of physicians being mindful of potential adverse effects when prescribing higher doses of amlodipine and underscores the need for continued vigilance in managing hypertension in resource-limited settings.

BP05 Presentation Time: 4:36 PM: Dosimetric Impact of Inter-Fractional Applicator Lengthening in High-Dose Rate Interstitial Breast Brachytherapy

BP05 Presentation Time: 4:36 PM: Dosimetric Impact of Inter-Fractional Applicator Lengthening in High-Dose Rate Interstitial Breast Brachytherapy

GPP06 Presentation Time: 11:15 AM: Recurrence Patterns and Prognostic Features among Patients with Vaginal Cancer Treated Definitively with Intraoperative Magnetic Resonance Imaging and High-Dose Rate Brachytherapy

GPP06 Presentation Time: 11:15 AM: Recurrence Patterns and Prognostic Features among Patients with Vaginal Cancer Treated Definitively with Intraoperative Magnetic Resonance Imaging and High-Dose Rate Brachytherapy

Examining the association between trenbolone, psychological distress, and aggression among males who use anabolic-androgenic steroids

Introduction: The link between anabolic-androgenic steroid (AAS) use and psychosocial effects such as aggression and violence is contentious. Few studies differentiate between types of AAS. This study focuses on trenbolone to assess its psychological risks and effects on aggression compared to other AAS. We hypothesised that there would be a positive relationship between trenbolone dosage and both psychological distress and aggression among people who use AAS. Methods: Using purposive and snowball sampling of people using AAS, we conducted an online survey to investigate the relationship between trenbolone use and other AAS use. Participants completed sections on demographics, trenbolone and other illicit drug use, the Kessler Psychological Distress Scale, and the Buss and Perry Aggression Questionnaire. Data were analysed using multinominal and multivariable regression. Results: The study included 282 males using AAS. Over 33% (n=93) reported currently using trenbolone, with 55.3% (n=156) of participants reporting having used trenbolone in the past, and 11.7% (n=33) reporting having never used trenbolone. Those who had never used trenbolone were not significantly different on age, height, weight, and BMI compared to those who had. After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression. Conclusion: The study highlights trenbolone's association with increased verbal aggression among males using AAS, particularly at higher doses. Further research should continue to differentiate between AAS types and the accompanying health harms.