Search Results (2,982)

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management. Full article

Background/Objectives: Body-surface-area-based dosing of continuous-infusion 5-fluorouracil does not account for inter-individual pharmacokinetic variability. This pilot study explored whether patient-level representative plasma 5-fluorouracil exposure within the target area under the concentration–time curve (AUC) range was associated with clinical outcomes. It evaluated a prototype immunochromatographic assay as a preliminary monitoring tool. Methods: Fifteen patients with unresectable advanced or recurrent colorectal cancer who received continuous-infusion 5-fluorouracil-based chemotherapy were prospectively evaluated between 1 January 2017 and 30 April 2018. Plasma 5-fluorouracil levels were measured during eight treatment cycles at three time points in each cycle. Representative AUC values were calculated using median concentrations across cycles and interpreted as exploratory patient-level exposure indices. Tumor response, grade ≥2 adverse events, progression-free survival, and overall survival were assessed descriptively. Results: The median representative AUC was 24.3 mg·h/L. Eight patients (53.3%) were within the target range of 20–30 mg·h/L, whereas seven (46.7%) were outside it. Disease control was observed in 7 of 8 patients (87.5%) within the target range and in 3 of 7 patients (42.9%) outside it. Grade ≥2 adverse events were less frequent in the target-range group (2/8, 25.0%) than in the outside-range group (6/7, 85.7%; p = 0.041). Progression-free survival was numerically longer in the target-range group (17.2 vs. 9.2 months, p = 0.36), while overall survival did not differ clearly (p = 0.76); these survival analyses were exploratory. The prototype immunochromatographic assay showed a favorable correlation with the My-5FU assay (R2 = 0.762), but Bland–Altman analysis showed relatively wide limits of agreement. Conclusions: Target plasma 5-fluorouracil exposure was associated with lower clinically relevant toxicity and may support favorable tumor control in this pilot cohort. The prototype immunochromatographic method demonstrated preliminary feasibility for rapid plasma 5-FU monitoring but requires further validation before routine dose adjustment. Full article

To investigate the resin infusion molding process for novel dry fiber-reinforced epoxy composite wing skin, dry fiber preforms were fabricated via an automated fiber placement (AFP) system, and the out-of-plane permeability of the preforms at different lay-up speeds was measured using the ultrasonic transmission method to determine the optimal lay-up parameters. A scaled-down composite wing skin structure was modeled and meshed via numerical simulation, and different resin infusion schemes were simulated and analyzed using PAM-RTM software. The optimal infusion scheme was determined by comparing the infusion time, infusion pressure and defect formation during resin flow for different schemes, and the wing skin component was fabricated through the vacuum-assisted resin infusion (VARI) process. Results indicate that the infusion time predicted by PAM-RTM simulation is 3883 s, while the actual measured value in the VARI process is 3611 s with an error of approximately 7% within a reasonable range. Both simulation and actual wing skin fabrication exhibited no significant defects, validating the accuracy of the three-dimensional permeability measurement of dry fiber preforms as well as the reliability of the simulation results. Full article

This paper focuses on the early Qing monk-painter Hongren 弘仁, systematically exploring the pathways through which the Chan Buddhist “emptiness contemplation” is manifested in his landscape paintings. As a representative monk-painter, Hongren produced works that profoundly embody the Chan contemplation of emptiness, yielding a singular style defined by austere coldness, minimalist simplicity, and profound quietude. Transcending conventional stylistic descriptions in art history and essentialist philosophical deductions, this study adopts a comprehensive empirical approach that integrates poetry, calligraphy, painting, and seals (shi-shu-hua-yin 诗书画印). By adopting an interdisciplinary perspective of philosophy, religion, and art history, this study argues that Hongren’s landscapes are not merely subjective emotional expressions or aesthetic pursuits; rather, they constitute a visual extension and a spiritual externalization of his emptiness contemplation. Through a multi-layered analysis of his form, brushwork, composition, and artistic conception, combined with the mutual corroboration of poetic inscriptions on paintings and textual inscriptions on seals, this paper reveals how the Chan philosophy of “emptiness contemplation” is reflected within his artistic language. While Hongren’s style is the cumulative result of various factors such as the Ming-Qing dynasty transition, his personal life, the inheritance of painting techniques, and the regional culture of Mount Huang, this paper specifically takes Chan thought as its analytical starting point, focusing on its unique expression in his work. Hongren’s path of “Painting-Chan” (hua chan 画禅) not only infused early Qing painting with a sublime spiritual power but also provides a vital religious exegesis of the deep-seated Chinese tradition of “Technique Ascending to the Dao” (ji jin yu dao 技进于道). Full article

Background/Objectives: Postoperative agitation (PA) and postoperative pain in pediatric patients following sevoflurane anesthesia are challenging clinical scenarios. This study aimed to evaluate the effects of intraoperative dexmedetomidine infusion compared to fentanyl infusion on the prevention of postoperative agitation and analgesic efficacy in children undergoing tonsillectomy and/or adenoidectomy. Methods: After ethical committee approval, a total of 85 pediatric patients (age range: 2–13 years) in the ASA I-II group were included in the study. Patients were randomized into two groups: the dexmedetomidine group (Group D, n = 40) and the fentanyl group (Group F, n = 45). Postoperative pain was monitored in the recovery unit (PACU) using the FLACC (face, legs, activity, cry, consolability) scale, and agitation was monitored using the PAED (pediatric anesthesia emergence delirium) scale. FLACC and PAED were monitored at 5, 10, 15, 30 min, and 2 and 4 h postoperatively. Results: Demographic data and surgical durations were similar between groups (p > 0.05). The dexmedetomidine group had lower FLACC pain scores at 10 and 15 min (uncorrected trends), but only the difference at 30 min remained statistically significant after Bonferroni correction (p = 0.0001; Cohen’s d = 0.85). Although PAED scores were numerically lower in Group D, no statistically significant difference was found. While an observational trend toward lower agitation was noted, it did not reach statistical significance. Extubation times and hemodynamic parameters were similar in both groups. Conclusions: The intraoperative use of dexmedetomidine in tonsillectomy and adenoidectomy procedures provides superior analgesia compared to fentanyl, particularly in the first 30 min postoperatively, without prolonging recovery time. Full article

Background: Although guidelines emphasize proper insertion techniques and tip positioning, catheter-related thrombosis (CRT) remains a common and clinically significant complication of peripherally inserted central catheters (PICCs) and midline catheters (MCs). In this context, the use of pharmacological prophylaxis is still debated. This study aims to assess the incidence of CRT in patients receiving anticoagulant therapy (therapeutic or prophylactic) and antiplatelet therapy. Methods: This retrospective study was conducted at a tertiary care hospital and included adult patients from March 2021 to May 2023. Six potential confounders were analyzed: anticoagulation status (none, prophylaxis, therapeutic), antiplatelet therapy, tip position (PICCs vs. MCs), number of lumens, CRT risk factors, and drug infusion requiring central access. CRT was diagnosed in symptomatic patients using compression ultrasonography. Propensity score weighting and logistic regression were employed to estimate odds ratios (OR) and average treatment effects. Results: A total of 1431 patients were enrolled. PICCs and therapeutic anticoagulant therapy were highly protective against CRT (OR 0.068 [95% CI 0.013–0.2] and OR 0.007 [95% CI 0.001–0.046], respectively). Prophylactic anticoagulant therapy (OR 0.328 [95% CI 0.200–0.519]) and antiplatelet therapy (OR 0.342 [95% CI 0.182–0.595]) also showed protective effects. At the same time, neither the number of lumens, the presence of risk factors, nor the infusion of irritating drugs was independently associated with CRT. Conclusions: The use of anticoagulant drugs (both prophylactic and therapeutic), antiplatelet therapy, and PICC use significantly lowered the risk of CRT. The findings support personalized prevention strategies and underscore the need for a well-designed randomized controlled trial to validate these findings. Full article

Background/Objectives: This study evaluated whether a low-carbohydrate diabetes-specific enteral formula improves glycemic control and insulin requirement compared with a standard enteral formula in critically ill patients with type 2 diabetes mellitus (T2DM) under pandemic-related product accessibility constraints. Methods: This retrospective observational study included adult ICU patients with T2DM receiving enteral nutrition between August 2021 and August 2023. Patients were grouped according to enteral formula type as standard enteral formula or diabetes-specific enteral formula. All patients received continuous nasogastric enteral feeding according to routine ICU practice. Glycemic control was managed using intravenous insulin infusion protocols. One hundred eligible patients were analyzed. Results: Fifty patients were included in each group. Baseline characteristics were broadly comparable, although differences in BMI and feeding rate were observed. Mean glucose level, daily insulin requirement, hypoglycemia, hyperglycemia, and glycemic variability were similar between groups (all p > 0.05). However, the number and percentage of days within the target glycemic range were higher in the diabetes-specific formula group (both p = 0.021). Clinical outcomes were comparable between groups. In multivariable analysis, mean glucose level independently predicted insulin requirement and glycemic variability, whereas formula type did not. Product-related costs were lower in the diabetes-specific formula group (all p < 0.001). Conclusions: Diabetes-specific enteral formula did not improve mean glucose level or insulin requirement in critically ill patients with T2DM, although it was associated with better maintenance of the target glycemic range and lower product-related costs. Enteral formula choice should therefore be individualized rather than routinely determined by diabetes status alone. Full article

Purpose: The aim of this study is to describe a slit-modified 23-gauge infusion trocar designed to enable early postoperative hypotony-free sclerotomy closure by allowing scleral suturing prior to complete trocar removal, and to report initial clinical outcomes in eyes with proliferative diabetic retinopathy with or without vitreous hemorrhage (PDR + H and PDR). Methods: A standard 23-gauge metallic (titanium) trocar was modified by creating a longitudinal slit that permitted passage of a suture needle while the trocar remained partially engaged within the scleral tunnel. At the end of pars plana vitrectomy, a transscleral suture was placed through the slit with the knot prepared prior to trocar removal, followed by simultaneous trocar extraction and suture tightening. Eighteen consecutive patients undergoing vitrectomy for PDR (fourteen with vitreous hemorrhage [PDR + H]; four without) were included. Intraocular pressure (IOP) was recorded preoperatively, immediately after sclerotomy closure (postoperative baseline), and at 8 and 24 h postoperatively. The study was designed as an exploratory pilot feasibility and safety evaluation of a slit-modified infusion trocar in 23-gauge vitrectomy. The primary outcomes were postoperative IOP stability and wound leakage. Secondary outcomes included early hypotony, postoperative hemorrhage, choroidal effusion, and the need for additional suturing. Results: All procedures were completed without intraoperative complications. The mean IOP was 14.83 ± 2.50 mmHg preoperatively, 13.33 ± 1.53 mmHg immediately after closure, 14.17 ± 3.01 mmHg at 8 h, and 15.17 ± 1.79 mmHg at 24 h. No cases of wound leakage or early postoperative hypotony were observed in either subgroup. One eye exhibited a transient IOP increase at 8 h; no choroidal effusion, postoperative hemorrhage, or need for secondary suturing occurred. Endotamponade consisted of balanced salt solution (BSS) in eight eyes, SF6 in seven eyes, silicone oil in two eyes, and air in one eye. Conclusions: The slit-modified infusion trocar enables secure, hypotony-free closure of the infusion sclerotomy by eliminating the open-wound interval during trocar removal. This simple biomedical device modification provides stable early postoperative IOP across different tamponade agents and appears safe and feasible in high-risk eyes with PDR. Full article

Background and Objectives: FLOT is a highly effective first-line treatment for metastatic gastric cancer and offers a favorable safety profile. Clinical studies investigating the FLOT regimen have reported varying outcomes depending on the infusion duration and have highlighted possible differences in complication rates and the efficacy of neoadjuvant therapy. The choice between 24 h or 48 h infusion durations for fluorouracil can be influenced by several factors, such as the patient’s overall health status, their tolerance to treatment, and the specific treatment protocol determined by the medical team. In this study, we aimed to evaluate the effects of different infusion durations (24 and 48 h) on clinical response, toxicity, and survival in patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. Materials and Methods: This retrospective multicenter study included 113 patients with gastric or gastroesophageal junction adenocarcinoma who received neoadjuvant FLOT chemotherapy (24 h infusion: n = 28; 48 h infusion: n = 85). Propensity score matching (PSM) was performed to balance baseline characteristics, yielding a matched cohort of 90 patients. The primary endpoints were the pathologic complete response (pCR) and toxicity. Secondary endpoints included disease-free survival (DFS) and overall survival (OS). Results: Significant baseline imbalances existed (cT stage p < 0.001). After PSM, the balance improved (cT stage p = 0.009). In the matched cohort, pCR 11.1% (24 h) vs. 12.1% (48 h), p > 0.99. The median DFS was 27.4 mo (24 h) vs. NR (48 h), p = 0.847. The median OS was 32.8 mo in both, p = 0.797. Multivariate analysis (baseline variables) indicates that infusion duration is not prognostic (DFS HR = 0.77, p = 0.453; OS HR = 0.72, p = 0.328). Power was ~10% for a 1% pCR difference. Conclusions: The 24 h infusion protocol was associated with similar outcomes to the 48 h protocol after PSM adjustment. However, residual confounding persists (cT stage p = 0.009 despite PSM), and the combination of this study’s retrospective design and severe underpowering (~10%) precludes definitive conclusions. As a result, the findings are hypothesis-generating. Full article

Background: Traditional refills of intrathecal infusion pumps rely on manual palpation and the use of external templates, a method that can be challenging in patients with anatomical variations or a high body mass index. Ultrasound guidance has emerged as a precision-based alternative. This study aimed to evaluate the impact of the ultrasound-guided technique versus the conventional template-based technique on patient satisfaction. Methods: A quasi-experimental before-and-after study was conducted on a cohort of 45 chronic pain patients. Immediate satisfaction with procedure duration (IPP-SQ), overall treatment efficacy (CRES-4), and pain interference via the Brief Pain Inventory (BPI) were assessed. Results: The use of ultrasound was associated with significantly higher satisfaction regarding procedure duration, with a mean score of 5.00 (95% CI: 4.35–5.65) compared to 3.22 (95% CI: 2.70–3.75) with the traditional method (p < 0.001). Overall satisfaction (CRES-4) also improved significantly (12.4 vs. 11.3; p = 0.001). Regarding patient-reported outcome measures (PROMs), the mean pain intensity in the subsequent week was lower following the ultrasound technique (mean difference −0.48; p = 0.040). Technically, no first-attempt failures were recorded under ultrasound guidance in this sample, compared to a 20% re-attempt rate observed with the manual method. Conclusions: The transition from the traditional method to ultrasound-guided refill optimizes technical precision and substantially enhances the patient experience. By reducing pain and increasing satisfaction, ultrasound guidance proves to be a valuable resource for improving procedural precision, representing an advancement toward a more personalized medicine approach. Full article

The genus Leonurus L. is renowned for its diverse secondary metabolites with significant pharmacological value; however, the chemical biodiversity and biological potential of its indigenous members in Türkiye remain largely unexplored. This study investigates four species (L. cardiaca, L. quinquelobatus, L. glaucescens, and L. persicus) to elucidate their phytochemical architecture and therapeutic capacities. Characterization of the ethanol, methanol, and aqueous (5% infusion) extracts via HPLC-MS/MS identified verbascoside, genkwanin, and caffeoylquinic acids as the major representative bioactive constituents across the studied Leonurus species. The extracts exhibited measurable biological activity, with L. cardiaca displaying the highest antioxidant profile (EC₅₀ 0.117 ± 0.01 mg/mL for DPPH, 2.731 ± 0.01 mM/Trolox for ABTS), correlating with its phenolic content. Notably, the extracts demonstrated notable anticandidal activity (MIC 0.1–1 mg/mL) and negligible to moderate antibacterial effects, alongside varying levels of susceptibility against breast (MCF7) and glioma (C6) cancer cell lines. These effects showed differentiation in toxicity compared to lung (A549) cells. This investigation provides scientific evidence supporting the traditional medicinal use of Leonurus species while highlighting their potential as standardized sources for the pharmaceutical and nutraceutical sectors. Our results lay a robust foundation for future bioactivity-guided isolation studies to further elucidate the molecular mechanisms behind their differential biological effects. Full article

Background and Aims: Automated insulin delivery (AID) systems are standard of care for type 1 diabetes mellitus (T1DM). Tubeless AID systems may improve treatment acceptance, but real-world European data in patients transitioning from multiple daily injections (MDI) or open-loop patch pump therapy are limited. This study evaluated real-world glycemic, safety, and quality-of-life (QoL) outcomes after transition to a tubeless automated closed-loop system (Omnipod 5^®, OP5^®). Research Design and Methods: In this prospective, multicenter observational study, adults with T1DM transitioned from MDI or open-loop continuous subcutaneous insulin infusion to OP5^® and were followed for 180 days. Continuous glucose monitoring-derived metrics and validated patient-reported outcome measures were assessed. Subgroup analyses were performed by prior therapy. Results: Of the 94 enrolled participants, 88 completed the study. At 180 days, HbA1c decreased from 7.5% to 7.1% (p < 0.001), and time in range increased from 59.0% to 68.0% (p < 0.001) without increased hypoglycemia. The proportion achieving TIR_70–180 ≥ 70% rose from 12.5% to 43.2%. Improvements were greater among prior MDI users. Treatment satisfaction and diabetes-related QoL improved significantly. The mean time in automated mode was 90.9%. Conclusions. Transition to tubeless AID significantly improved glycemic and psychosocial outcomes, supporting its effectiveness in routine clinical practice. Full article

This study examines the influence of scale effects on the thermomechanical and structural performance of chemically cured, glass-fibre-reinforced polyester composites. Two reinforcement architectures—plain 0/90° fabric and biaxial fabric—were analysed to assess differences in resin flow, curing behaviour, and mechanical characteristics. Differential Scanning Calorimetry (DSC) was employed to characterise cross-linking kinetics at 15 °C, 19 °C, and 25 °C, demonstrating that higher cure temperatures markedly accelerate gelation and cross-linking. Composite plates were manufactured by Light Resin Transfer Moulding (L-RTM), and static tensile tests were conducted in accordance with PN-EN ISO 527-4. The results confirm that reinforcement architecture strongly affects processability and mechanical performance. The 0/90° fabric provided superior resin permeability and shorter infusion times, whereas the biaxial fabric required higher injection pressure and exhibited longer curing duration. Statistical analysis based on Weibull’s brittle strength theory verified the presence of scale effects: larger specimens displayed lower nominal strength due to a higher probability of internal flaws. Multiple regression modelling further revealed relationships between geometric and mechanical parameters: maximum (destructive) stress, Rm, was the dominant factor influencing both specimen thickness and number of layers, while deformation at maximum stress (εm) primarily determined specimen length. These findings highlight the necessity of accounting for size-dependent behaviour when designing and testing polymer composites. Considering scale effects enables more reliable extrapolation from laboratory-scale tests to full-scale components, thereby improving predictability and structural reliability in engineering applications. Full article

Cisplatin-induced ototoxicity is a permanent, bilateral sensorineural hearing loss occurring in up to 80% of treated patients. Its defining and clinically challenging feature is the progressive worsening of auditory function that continues well after chemotherapy has ended, a trajectory that cannot be explained by cumulative dose alone. This article is a comprehensive review of the present research studies on mechanisms that are responsible for this post-treatment progression. The cochlea, unlike other organs, appears to be unable to eliminate platinum (the active divalent metal ion released from cisplatin and responsible for its cytotoxic and ototoxic effects): traces of it can be found in human temporal bone tissue even more than 18 months after last infusion, and bone might serve as a long-term systemic reservoir. Within the inner ear, platinum accumulates preferentially in the stria vascularis, impairing endocochlear potential and outer hair cell function. Retained platinum sustains cascading effects including sustained NOX3-dependent oxidative stress, mitochondrial dysfunction, ongoing genotoxic injury to non-regenerative cells, and the early loss of ribbon synapses that precipitates delayed spiral ganglion neurodegeneration. Pharmacogenetic variability in platinum transport and antioxidant metabolism further modulates individual susceptibility. These findings support lifelong audiological surveillance and provide a basis for designing strategies that can protect hearing without compromising the essential anticancer efficacy of cisplatin therapy. Full article

Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency and poor glycemic control. Over the last 20 years, researchers have investigated mesenchymal stem cell infusion and the transplantation of stem cell-derived β cells and islet tissues. This review aims to comprehensively discuss the latest advances in the field of stem cell use in diabetes, including clinical studies and preclinical experiments aiming at improving the efficacy and safety of stem cell use. Full article