Optimized method development and validation for determining donepezil in rat plasma: A liquid-liquid extraction, LC-MS/MS, and design of experiments approach.

Donepezil (DPZ), a piperidine-based reversible cholinesterase inhibitor, finds extensive use in treating Alzheimer's disease (AD). Originally designed as an oral formulation, DPZ encounters drawbacks such as a brief duration of action and reduced treatment effectiveness in elderly patients with memory impairment or difficulty swallowing medications. To address these issues and improve patient compliance, researchers are actively exploring alternative DPZ formulations. Consequently, reliable methods are necessary to quantitate DPZ in biological samples for in vivo assessment. Therefore, we propose an efficient, sensitive, wide-dynamic, and cost-effective method for quantitating DPZ in rat plasma. Our method employs liquid-liquid extraction (LLE) followed by liquid chromatography and tandem mass spectrometry, enabling in vivo evaluation of novel DPZ formulations. Notably, our method requires only 20 µL of rat plasma and employs icopezil as the internal standard-a cost-effective compound with chemical similarity to DPZ. We meticulously optimized LLE conditions, taking into account factor interactions through design of experiments (DOE). Our rapid and straightforward extraction and purification involved using 500 µL of pure methyl tert-butyl ether to extract DPZ from the sample within five minutes. The dynamic range of the method extends from 0.5 ng/mL to 1,000 ng/mL, demonstrating excellent sensitivity and suitability for pharmacokinetic studies across diverse DPZ formulations. Following the FDA guidelines, we rigorously validated the developed method, evaluating selectivity, linearity (with a coefficient of determination ≥0.9999), accuracy (ranging from 96.0% to 109.6%), precision (≤13.9%), matrix effect (92.2% to 103.8%), recovery (98.5% to 106.8%), the lower limit of quantitation (0.5 ng/mL), and stability. Finally, we effectively employed the validated method for the long-term pharmacokinetic assessment of a DPZ formulation. We expect that this approach will make a substantial contribution to the advancement of new DPZ formulations, ultimately benefiting individuals afflicted by AD.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

The potential for drug incompatibility and its drivers - A hospital wide retrospective descriptive study.

OBJECTIVE: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data. METHODS: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission. RESULTS: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs. CONCLUSIONS: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings.

Validation of analytical methods for newly regulated veterinary drug residues in livestock and fishery products with maximum residue limits in Republic of Korea.

Veterinary drugs play a crucial role in the treatment of various animal diseases. However, their residues, stemming from issues, such as withdrawal period lapses, overuse, or abuse, can jeopardize food safety and human health. This study addresses recent regulations in Korea concerning specific veterinary drugs (anacolin, ephedrine, menichlopholan, piperonyl butoxide, and etisazole HCl) and their ongoing discussions. This study aimed to validate two pre-developed methods for quantifying residues in livestock and fishery products using QuEChERS and liquid chromatography-tandem mass spectrometry. Both methods exhibited excellent linearity, recoveries (70.3-119%), and coefficient of variations (1.3-28%), along with low limits of detection and quantification (0.3-4 ng/g and 1-12 ng/g). This study is significant for its contribution to the detection of veterinary drugs in livestock and fishery products, given the limited research available on the methods for analyzing these substances.

Anatomical topology of extrahippocampal projections from dorsoventral CA pyramidal neurons in mice.

The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Among these, CA PNs are known to project beyond the hippocampus into various limbic areas, critically influencing cognitive and affective behaviors. Despite accumulating evidence of these extrahippocampal projections, the specific topological patterns-particularly variations among CA PN types and between their dorsal and ventral subpopulations within each type-remain to be fully elucidated. In this study, we utilized cell type-specific Cre mice injected with fluorescent protein-expressing AAVs to label each CA PN type distinctly. This method further enabled the dual-fluorescence labeling of dorsal and ventral subpopulations using EGFP and tdTomato, respectively, allowing a comprehensive comparison of their axonal projections in an animal. Our findings demonstrate that CA1 PNs predominantly form unilateral projections to the frontal cortex (PFC), amygdala (Amy), nucleus accumbens (NAc), and lateral septum (LS), unlike CA2 and CA3 PNs making bilateral innervation to the LS only. Moreover, the innervation patterns especially within LS subfields differ according to the CA PN type and their location along the dorsoventral axis of the hippocampus. This detailed topographical mapping provides the neuroanatomical basis of the underlying functional distinctions among CA PN types.

ABDGAN: Arbitrary Time Blur Decomposition Using Critic-Guided TripleGAN.

Recent studies have proposed methods for extracting latent sharp frames from a single blurred image. However, these methods still suffer from limitations in restoring satisfactory images. In addition, most existing methods are limited to decomposing a blurred image into sharp frames with a fixed frame rate. To address these problems, we present an Arbitrary Time Blur Decomposition Triple Generative Adversarial Network (ABDGAN) that restores sharp frames with flexible frame rates. Our framework plays a min-max game consisting of a generator, a discriminator, and a time-code predictor. The generator serves as a time-conditional deblurring network, while the discriminator and the label predictor provide feedback to the generator on producing realistic and sharp image depending on given time code. To provide adequate feedback for the generator, we propose a critic-guided (CG) loss by collaboration of the discriminator and time-code predictor. We also propose a pairwise order-consistency (POC) loss to ensure that each pixel in a predicted image consistently corresponds to the same ground-truth frame. Extensive experiments show that our method outperforms previously reported methods in both qualitative and quantitative evaluations. Compared to the best competitor, the proposed ABDGAN improves PSNR, SSIM, and LPIPS on the GoPro test set by 16.67%, 9.16%, and 36.61%, respectively. For the B-Aist++ test set, our method shows improvements of 6.99%, 2.38%, and 17.05% in PSNR, SSIM, and LPIPS, respectively, compared to the best competitive method.

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

P53 Status Influences the Anti-proliferative Effect Induced by IFITM1 Inhibition in Estrogen Receptor-positive Breast Cancer Cells.

BACKGROUND/AIM: Interferon-induced trans-membrane protein 1 (IFITM1) is known to be involved in breast cancer progression. We aimed to investigate its role in estrogen receptor (ER)-positive breast cancer cells with wild-type p53 and tamoxifen-resistant breast cancer cells. MATERIALS AND METHODS: The ER-positive breast cancer cell lines, MCF-7 with wild-type p53 and T47D with mutant p53, were used. We established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. RESULTS: IFITM1 inhibition in MCF-7 cells significantly decreased cell growth and migration. MCF-7 cells with suppression of IFITM1 using siRNA or ruxolitinib showed reduced cell viability after tamoxifen treatment compared with that in the control MCF-7 cells. Unexpectedly, mRNA and protein levels of IFITM1 were decreased in TamR cells compared with those in MCF-7 cells. TamR cells with suppression of IFITM1 using siRNA or ruxolitinib showed no change in cell viability after treatment with tamoxifen. P53 knockdown using siRNA reduced the mRNA levels of IRF9 and increased mRNA and protein levels of SOCS3 in MCF-7 cells, suggesting that loss or mutation of p53 can affect the induction of IFITM1 via the JAK/STAT signaling pathway in breast cancer. Furthermore, MCF-7 cells with p53 knockdown using siRNA showed no decrease in cell viability after tamoxifen treatment or IFITM1 inhibition, indicating that p53 status may be important for cell death after tamoxifen treatment or IFITM1 inhibition. CONCLUSION: IFITM1 inhibition may enhance the sensitivity to tamoxifen based on p53-dependent enhancement of IFN signaling in wild-type p53, ER-positive breast cancer cells.

Deep learning for predicting rehospitalization in acute heart failure: Model foundation and external validation.

AIMS: Assessing the risk for HF rehospitalization is important for managing and treating patients with HF. To address this need, various risk prediction models have been developed. However, none of them used deep learning methods with real-world data. This study aimed to develop a deep learning-based prediction model for HF rehospitalization within 30, 90, and 365 days after acute HF (AHF) discharge. METHODS AND RESULTS: We analysed the data of patients admitted due to AHF between January 2014 and January 2019 in a tertiary hospital. In performing deep learning-based predictive algorithms for HF rehospitalization, we use hyperbolic tangent activation layers followed by recurrent layers with gated recurrent units. To assess the readmission prediction, we used the AUC, precision, recall, specificity, and F1 measure. We applied the Shapley value to identify which features contributed to HF readmission. Twenty-two prognostic features exhibiting statistically significant associations with HF rehospitalization were identified, consisting of 6 time-independent and 16 time-dependent features. The AUC value shows moderate discrimination for predicting readmission within 30, 90, and 365 days of follow-up (FU) (AUC:0.63, 0.74, and 0.76, respectively). The features during the FU have a relatively higher contribution to HF rehospitalization than features from other time points. CONCLUSIONS: Our deep learning-based model using real-world data could provide valid predictions of HF rehospitalization in 1 year follow-up. It can be easily utilized to guide appropriate interventions or care strategies for patients with HF. The closed monitoring and blood test in daily clinics are important for assessing the risk of HF rehospitalization.

Determination of Flunixin and 5-Hydroxy Flunixin Residues in Livestock and Fishery Products Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Flunixin is a veterinary nonsteroidal anti-inflammatory agent whose residues have been investigated in their original form within tissues such as muscle and liver. However, flunixin remains in milk as a metabolite, and 5-hydroxy flunixin has been used as the primary marker for its surveillance. This study aimed to develop a quantitative method for detecting flunixin and 5-hydroxy flunixin in milk and to strengthen the monitoring system by applying to other livestock and fishery products. Two different methods were compared, and the target compounds were extracted from milk using an organic solvent, purified with C18, concentrated, and reconstituted using a methanol-based solvent. Following filtering, the final sample was analyzed using liquid chromatography- tandem mass spectrometry. Method 1 is environmentally friendly due to the low use of reagents and is based on a multi-residue, multi-class analysis method approved by the Ministry of Food and Drug Safety. The accuracy and precision of both methods were 84.6%-115% and 0.7%-9.3%, respectively. Owing to the low matrix effect in milk and its convenience, Method 1 was evaluated for other matrices (beef, chicken, egg, flatfish, and shrimp) and its recovery and coefficient of variation are sufficient according to the Codex criteria (CAC/GL 71-2009). The limits of detection and quantification were 2-8 and 5-27 µg/kg for flunixin and 2-10 and 6-33 µg/kg for 5-hydroxy flunixin, respectively. This study can be used as a monitoring method for a positive list system that regulates veterinary drug residues for all livestock and fisheries products.

Tricaprylin-based drug crystalline suspension for intramuscular long-acting delivery of entecavir with alleviated local inflammation.

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 µm), crystallinity (melting point of 160-165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS-injected site, drug aggregates of up to 500 µm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS-injected site, with >4 weeks remaining of the oily vehicle in micro-computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long-acting delivery, with improved local tolerability.

Biocatalysis enables the scalable conversion of biobased furans into various furfurylamines.

Biobased furans have emerged as chemical building blocks for the development of materials because of their diverse scaffolds and as they can be directly prepared from sugars. However, selective, efficient, and cost-effective scalable conversion of biobased furans remains elusive. Here, we report a robust transaminase (TA) from Shimia marina (SMTA) that enables the scalable amination of biobased furanaldehydes with high activity and broad substrate specificity. Crystallographic and mutagenesis analyses provide mechanistic insights and a structural basis for understanding SMTA, which enables a higher substrate conversion. The enzymatic cascade process established in this study allows one-pot synthesis of 2,5-bis(aminomethyl)furan (BAMF) and 5-(aminomethyl)furan-2-carboxylic acid from 5-hydroxymethylfurfural. The biosynthesis of various furfurylamines, including a one-pot cascade reaction for BAMF generation using whole cells, demonstrates their practical application in the pharmaceutical and polymer industries.

Dual Adjuvant-Loaded Peptide Antigen Self-Assembly Potentiates Dendritic Cell-Mediated Tumor Immunotherapy.

Clinical translation of current cancer vaccine research has been hampered by limited antitumor immune responses due to inefficient antigen delivery and presentation, suboptimal DC and T cell activation. Biomaterial-based nanovaccine offers targeted antigen delivery, protection from degradation in vivo, and prolonged tumor therapeutic efficacy. This study introduces a lipid-coated deoxycholic acid-survivin nanoassembly (DA-L-DSA). Survivin, overexpressed in several cancer cells and involved in cancer cell growth and immune evasion, is selected as a tumor-associated antigen. An major histocompatibility complex class I binding epitope of survivin is engineered into the nanoassembly. R848, TLR 7/8 agonist, and SD-208, TGF-beta receptor1 kinase inhibitor, are coencapsulated into the nanoassembly as potent adjuvants to boost DC maturation and enhance antigen presentation. The DA-L-DSA effectively stimulates the maturation of dendritic cells, migrates into lymph nodes, and enhances T-cell activation and Th1 response. A substantial influx of cytotoxic T lymphocytes into primary tumors is observed in a murine melanoma model and demonstrates anti-metastatic effects in a spontaneous breast cancer metastasis model. Furthermore, DA-L-DSA exhibits a remarkable synergistic effect in the combination therapy with immune checkpoint inhibitors alleviating immunosuppressive tumor microenvironment. Taken together, these findings suggest DA-L-DSA as a promising immuno-therapeutic platform that could be applicable to diverse intractable cancers.

Effects of physical inactivity behavior during COVID-19 pandemic on physical fitness, body composition, inflammatory cytokine, and immunocytes in older adults: A retrospective and prospective study.

The prolonged period of COVID-19 has ingrained physical inactivity as a habit, leading to a reluctance to move. This has resulted in a decline in physical fitness and the loss of a healthy body composition. While this trend is particularly noticeable among the older adults, its impact on the immune cell defense system, which is crucial for minimizing viral infections, remains unclear. This study aimed to investigate the physical fitness, body composition, cytokines and immunocytes of older adults who engaged in physical activity (PA) before the COVID-19 pandemic but had to stop it due to the lockdown. A total of 172 older adults aged 61 to 85 years participated in this study: 90 in non-PA group (NPAG, 34 men and 56 women), and 82 in PA group (PAG, 29 men and 53 women). Physical inactivity was 45.13 ± 5.67 weeks in the NPAG and 1.70 ± 0.43 weeks in the PAG. Although there was no significant difference in calorie intake, PA volume showed a significant decrease in NPGA (P < 0.001). VO2max, strength, and sit-ups decreased in NPAG, whereas they maintained or increased in PAG (Ps < 0.001). NPAG experienced an increase in fat mass (∼33.0 %), along with a decrease in muscle mass (∼10.4 %), but PAG showed slight increases (∼1.1 % vs. ∼1.5 %, Ps < 0.001). Interleukin-6 (∼38.9 %), tumor necrosis factor-α (∼38.3 %), and C-reactive protein (∼33.6 %) increased, whereas immunocytes decreased in NPAG (Ps < 0.001). In contrast, those in PAG showed the opposite phenomenon. This study indicates that even during the COVID-19 situation, maintaining active PA in the older adults helps retain beneficial physical fitness and body composition, reduces inflammatory factors, and contributes to preserving or enhancing the function of immunocytes.

Femoral artery occlusion induced vasculopathy following herpes zoster: a case report.

BACKGROUND: Reactivation of the varicella zoster virus (VZV) results in herpes zoster (HZ), which is a painful unilateral rash with a typical dermatomal distribution. HZ may be followed by postherpetic neuralgia (PHN), vasculopathy, myelopathy, retinal necrosis, and cerebellitis. Vasculopathy can cause ischemic stroke, aneurysms, arterial dissection, transient ischemic attack, and rarely, peripheral arterial disease (PAD). The possible mechanism is that the VZV travels to the arteries through the sensory ganglia, leading to inflammation and pathological vascular remodeling, which result in vasculopathy. CASE DESCRIPTION: Here, we describe a rare case of femoral artery occlusion induced vasculopathy 5 years after HZ. A 65-year-old woman visited our pain clinic with persistent pain following HZ that occurred 3 months earlier. She had several rash scars on the right thigh along with a continuous throbbing, shooting, and sharp pain. The patient was diagnosed with PHN and prescribed with medications that relieved the leg pain. The symptoms remained stationary for almost 5 years. She presented again with complaints of a paroxysmal tingling sensation in the right thigh and claudication due to increased pain, which had begun 6 months prior. She reported leg pain after walking for 10 minutes. Lumbar spine magnetic resonance imaging (MRI) revealed foraminal stenosis at the level of right L2, with no abnormality below L2. Subsequently, the patient was evaluated for vascular diseases. Lower extremity ultrasonography and computed tomography (CT) angiography revealed stenosis and thrombotic occlusions in the right superficial femoral and tibial arteries as well as the left middle femoral and tibial arteries. Surgical revascularization via percutaneous angioplasty was performed bilaterally. The leg pain was relieved after the procedure and the claudication improved. CONCLUSIONS: Peripheral artery occlusion is a rare phenomenon following HZ. In cases involving changes in HZ symptoms, further evaluation is required for potential vasculopathy.

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.

Polycaprolactone-MXene coating for controlling initial biodegradation of magnesium implant via near-infrared light.

The mechanical strength of magnesium implants undergoes a rapid decline after implantation due to bioabsorption, which can lead to the risk of rupture. To ensure sustained mechanical strength and initiate bioabsorption selectively upon specific external stimuli until the bone regains sufficient support, we developed a biosafe near-infrared light (NIR)-sensitive polymer coating using polycaprolactone (PCL) and Ti3C2 (MXenes). The synthetic MXene powders were characterized using SEM, EDS, and XRD, and the amount of MXenes had a proliferation-promoting effect on MC3T3-E1, as observed through cell assays. The PCL-MXene coating was successfully prepared on the magnesium surface using the casting coating method, and it can protect the magnesium surface for up to 28 days by decreasing the corrosion ratio. However, the coating can be easily degraded after exposure to NIR light for 20 minutes to expose the magnesium substrate, especially in a liquid environment. Meanwhile, the magnesium implant with the PCL-MXene coating has no cytotoxicity toward MC3T3-E1. These findings can provide a new solution for the development of controlled degradation implants.

Treatment Strategy of Unruptured Intracranial Aneurysms in Octogenarian Patients: A Single-Institution Experience.

AIM: To share our clinical insights into octogenarian patients with unruptured intracranial aneurysms (UIAs) and evaluate the treatment strategies for this demographic. MATERIAL AND METHODS: A retrospective analysis was conducted on data from 134 patients with a follow-up exceeding 6 months, all enrolled in this study. We assessed the incidence rates (IRs) of aneurysm growth and rupture, along with potential predictors of aneurysm growth. RESULTS: Among the 134 patients, 99 (73.9%) underwent conservative management, 25 (18.7%) received coiling, and 10 (7.5%) underwent clipping. The mean age of the cohort was 81.8 years. The middle cerebral artery was the most common location for aneurysms. The mean aneurysm size was 4.9 mm, with sizes significantly larger in the treatment groups (coiling and clipping) compared to the observation group (4.4 mm in the observation group; 5.9 and 7.4 mm in the coiling and clipping groups, respectively). The proportion of aneurysms with a daughter sac was higher in the treatment groups compared to the observation group (6.1% vs. 44% [coiling] and 50% [clipping]). The IR of aneurysm growth was 5.9 per 100 person-years, and that of aneurysm rupture was 0.8 per 100 person-years. No factors were statistically significant for aneurysm growth. CONCLUSION: Age alone, especially in individuals over 80 years old, may not be a contraindication for UIA treatment. We recommend considering treatment in octogenarians with high-risk aneurysm features, such as a large aneurysm and the presence of a daughter sac, as the complication rates are low.