Polystyrene nanoplastics-induced intestinal barrier disruption via inflammation and apoptosis in zebrafish larvae (Danio Rerio).

Plastics are one of the most pervasive materials on Earth, to which humans are exposed daily. Polystyrene (PS) is a common plastic packaging material. However, the impact of PS on human health remains poorly understood. Therefore, this study aimed to identify intestinal damage induced by PS nanoplastics (PS-NPs) in zebrafish larvae which have a high homology with humans. Four days post fertilization (dpf), zebrafish larvae were exposed to 0-, 10-, and 50-ppm PS-NPs for 48 h Initially, to ascertain if 100 nm PS-NPs could accumulate in the gastrointestinal (GI) tract of zebrafish larvae, the larvae were exposed to red fluorescence-labeled PS-NPs, and at 6 dpf, the larvae were examined using a fluorescence microscope. Analysis of the fluorescence intensity revealed that the GI tract of larvae exposed to 50-ppm exhibited a significantly stronger fluorescence intensity than the other groups. Nonfluorescent PS-NPs were then used in further studies. Scanning electron microscopy (SEM) confirmed the spherical shape of the PS-NPs. Fourier-transform infrared spectroscopy (FT-IR) analysis revealed chemical alterations in the PS-NPs before and after exposure to larvae. The polydispersity index (PDI) value derived using a Zetasizer indicated a stable dispersion of PS-NPs in egg water. Whole-mount apoptotic signal analysis via TUNEL assay showed increased apoptosis in zebrafish larval intestines exposed to 50-ppm PS-NPs. Damage to the intestinal tissue was assessed by Alcian blue (AB) and hematoxylin and eosin (H&E) staining. AB staining revealed increased mucin levels in the zebrafish larval intestines. Thin larval intestinal walls with a decrease in the density of intestinal epithelial cells were revealed by H&E staining. The differentially expressed genes (DEGs) induced by PS-NPs were identified and analyzed. In conclusion, exposure to PS-NPs may damage the intestinal barrier of zebrafish larvae due to increased intestinal permeability, and the in vivo gene network may change in larvae exposed to PS-NPs.

Geriatric Nutritional Risk Index and 30-Day Postoperative Mortality in Geriatric Burn Patients.

INTRODUCTION: The geriatric nutritional risk index (GNRI) can easily identify malnutrition-associated morbidity and mortality. We investigated the association between preoperative GNRI and 30-d mortality in geriatric burn patients who underwent surgery. METHODS: The study involved geriatric burn patients (aged ≥ 65 y) who underwent burn surgery between 2012 and 2022. The GNRI was computed using the following formula: 1.489 × serum albumin concentration (mg/L) + 41.7 × patient body weight/ideal body weight. Patients were dichotomized into the high GNRI (≥ 82) and low GNRI (< 82) groups. GNRI was evaluated as an independent predictor of 30-d postoperative mortality. The study also evaluated the association between GNRI and sepsis, the need for continuous renal replacement therapy (CRRT), major adverse cardiac events (MACE), and pneumonia. RESULTS: Out of 270 patients, 128 (47.4%) had low GNRI (< 82). Multivariate Cox regression analysis revealed that low GNRI was significantly associated with 30-d postoperative mortality (hazard ratio: 1.874, 95% confidence interval [CI]: 1.146-3.066, P = 0.001). Kaplan-Meier analysis revealed that the 30-day mortality rate differed significantly between the low and high GNRI groups (log-rank test, P < 0.001). The 30-d postoperative mortality (hazard ratio: 2.677, 95% CI: 1.536-4.667, P < 0.001) and the incidence of sepsis (odds ratio [OR]: 2.137, 95% CI: 1.307-3.494, P = 0.004), need for CRRT (OR: 1.919, 95% CI: 1.101-3.344, P = 0.025), MACE (OR: 1.680, 95% CI: 1.018-2.773, P = 0.043), and pneumonia (OR: 1.678, 95% CI: 1.019-2.764, P = 0.044), were significantly higher in the low GNRI group than in the high GNRI group. CONCLUSIONS: Preoperative low GNRI was associated with increased 30-d postoperative mortality, sepsis, need for CRRT, MACE, and pneumonia in geriatric burn patients.

Drug-Coated Balloon Angioplasty in Patients Undergoing Complex Percutaneous Coronary Intervention.

Background: There are limited clinical data on drug-coated balloon (DCB)-based percutaneous coronary intervention (PCI) compared with drug-eluting stent (DES)-only PCI in patients with complex coronary artery lesions. Objectives: The goal of the current study was to investigate the efficacy of DCB in patients undergoing PCI for complex coronary artery lesions. Methods: From an institutional registry of patients with de novo complex coronary artery lesions, 126 patients treated with DCB-based PCI were compared with 234 propensity score-matched patients treated with DES-only PCI. Complex coronary artery lesions were defined as the presence of at least 1 of the following: bifurcation, chronic total occlusion, unprotected left main disease, long lesion ≥38 mm, multivessel disease, lesion requiring ≥3 devices, or severe calcification. The primary endpoint was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Results: Baseline characteristics were comparable between the 2 groups. DCB-based PCI showed a comparable risk of TVF vs DES-based PCI (7.6% vs 8.1%; HR: 0.81; 95% CI: 0.33-1.99; P = 0.638). The risks of cardiac death (5.0% vs 5.7%; HR: 0.78; 95% CI: 0.24-2.49), target vessel-related myocardial infarction (0.9% vs 1.3%; HR: 2.65; 95% CI: 0.26-27.06), and target vessel revascularization (3.5% vs 2.0%; HR: 1.30; 95% CI: 0.30-5.67) were also comparable between the 2 groups. Conclusions: DCB-based PCI showed comparable risks of TVF vs those of DES-only PCI in patients with complex coronary artery lesions. DCB might be considered as a suitable alternative device to DES in patients undergoing complex PCI. (Long-term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815).

Public Perception Towards Drug Abuse in South Korea: The Effects of Overconfidence and Affirmation.

OBJECTIVE: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse. METHODS: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse. RESULTS: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569). CONCLUSION: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

Clinical prediction nomogram for steroid-induced ocular hypertension risk in patients with intravitreal dexamethasone implant.

Background: Recognizing the risk factors and understanding the mechanisms underlying steroid-induced ocular hypertension (SIOH) are vital to prevent potent vision loss and ensure the safety and effectiveness of dexamethasone (DEX) injections. The study aimed to develop a novel nomogram for predicting the risk of SIOH and determining safety zones for steroid injections. Methods: This single-center, retrospective, case-control study included a total of 154 eyes with available measured axial length that had undergone AS-OCT and DEX implantation at the Yonsei University Health System. The eyes were categorized into the SIOH (n = 39) and post-steroid normal IOP (n = 115) groups. We measured intraocular pressure (IOP) for all eyes prior to DEX implantation, at 1 week post-implantation, and at 1, 2, 3, 6, and 12 months thereafter. We used AS-OCT to analyze the trabecular meshwork (TM) height and ocular parameters. Results: The predictive nomogram, including TM height, yielded an AUC of 0.807 (95 % confidence interval [CI], 0.737-0.877) and demonstrated significantly higher predictive accuracy than that of previous nomograms, which did not consider TM height and had an AUC of 0.644 (95 % CI, 0.543-0.745) (p = 0.031). The calibration plot demonstrated a strong predictive accuracy for a predicted value of approximately 0.4. We established cutoff values to ensure different levels of sensitivity and specificity within the safety zone following DEX implantation. Conclusion: Our improved nomogram incorporating TM height as a newly identified risk factor, established a safety threshold for intravitreal DEX implantation, helping identify safe individuals from those who require caution.

Transcutaneous electrical nerve stimulation and catheter-related bladder discomfort following transurethral resection of bladder tumour: A randomised controlled trial.

BACKGROUND: Catheter-related bladder discomfort (CRBD) is problematic in patients with a urinary catheter. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic modality used to relieve various types of pain. OBJECTIVES: We evaluated the effect of TENS on CRBD after transurethral resection of bladder tumours (TURBT). DESIGN: A randomised controlled trial. SETTING: A large university tertiary hospital, from October 2022 to March 2023. PATIENTS: Patients requiring urinary catheterisation after TURBT. INTERVENTION: In this randomised controlled trial, patients were randomly allocated to the TENS (n  = 56) or control (n  = 56) groups. CRBD manifests as a burning sensation with an urge to void or discomfort in the suprapubic area. Moderate to severe CRBD was defined as patients self-reporting CRBD symptoms with or without behavioural response, including attempts to remove the urinary catheter, intense verbal reactions, and flailing limbs. TENS was performed from the end of surgery to 1 h postoperatively. MAIN OUTCOME MEASURE: The primary endpoint was considered moderate to severe CRBD immediately postoperatively. Secondary endpoints included moderate to severe CRBD at 1, 2 and 6 h postoperatively. Additionally, postoperative pain, patient satisfaction, and TENS-related adverse effects were evaluated. RESULTS: Moderate to severe CRBD immediately postoperatively was significantly less frequent in the TENS group than in the control group: 10 (17.9%) vs. 34 (60.7%); P < 0.001; relative risk (95% CI) = 0.294 (0.161 to 0.536); absolute risk reduction = 0.43; number needed to treat = 2.3. Moderate to severe CRBD differed between the two groups at 1 h postoperatively: 1 (1.8%) vs. 16 (28.6%); P < 0.001; relative risk = 0.06 (95% CI 0.01 to 0.46); absolute risk reduction = 0.27; number needed to treat = 3.7. The TENS group exhibited a significantly lower score for postoperative pain at 1 h (1.8 ±â€Š0.6 vs. 2.2 ±â€Š0.4; P < 0.001, mean difference (95% CI) = 0.4 (0.2 to 0.6) and a higher score for patient satisfaction, 5.0 (4.0 to 6.0) vs. 3.0 (3.0 to 4.0); P < 0.001; median difference (95% CI) = 2.0 (1.0 to 2.0). CONCLUSIONS: TENS reduced moderate to severe CRBD, decreased postoperative pain, and increased patient satisfaction after TURBT. CLINICAL TRIAL REGISTRY: Clinical Research Information Service (KCT0007450). VISUAL ABSTRACT: http://links.lww.com/EJA/B12.

4-Color Flow Cytometric Crossmatch Using Whole Blood Lysis.

BACKGROUND: In lymphocyte crossmatch using flow cytometry (flow cytometric crossmatch, FCXM), the conventional tricolor FCXM protocol requires a mononuclear cell isolation step. To develop a new, more streamlined protocol, we introduced whole blood lysis (WBL) and CD45 fluorescence-triggered acquisition using 4-color flow cytometry. METHODS: A total of 186 donor/recipient pairs for transplantation were classified into donor-specific human leukocyte antigen (HLA) alloantibody-positive (DSA+, n = 78) and DSA-negative (DSA-, n = 108) groups. The latter group was reclassified into blood group ABO-incompatible (ABOi, n = 56) and ABO-compatible (n = 52) subgroups. The WBL FCXM protocol with CD45 V500-C was optimized using a FACSLyric cytometer (BD Biosciences) with 3 lasers. Measurements for T cells or B cells were calculated as a mean fluorescence intensity (MFI) ratio (test divided by control). WBL FCXM was compared with conventional FCXM in each group. RESULTS: WBL FCXM showed no difference quantitatively compared with conventional FCXM, except for the B cell FCXM in the DSA- group (B cell MFI ratio: 1.06 ± 0.44 and 0.92 ± 0.41, respectively [P = .0001]). There was no ABO antibody interference in the ABOi subgroup. Similar results were observed in the qualitative determinations of FCXM as follows: 1) In the DSA+ group, the sensitivity of B cell WBL FCXM (96.2%) showed no difference compared with that of conventional FCXM (91.0%, P = .2188) and 2) In the DSA- group, the specificity of T cell WBL FCXM (96.3%) showed no difference compared with that of conventional FCXM (98.1%, P = .6250). WBL FCXM reduced the turnaround time by 50 min compared with that by conventional FCXM. CONCLUSIONS: WBL FCXM demonstrated comparable assay performance to that of conventional FCXM. Because this new FCXM protocol is simple and does not compromise assay sensitivity, it has the potential to replace the conventional method in histocompatibility laboratory settings.

Evaluation of the Modal Parameters of a Unidirectional Carbon-Based Composite Structure Using the Influential Factor of Static Loading.

Static loading can significantly alter the dynamics of unidirectional carbon-based composites (UCBCs), with modal parameters varying depending on the orientation of the carbon fibers. In this study, the sensitivity of modal parameters of UCBC structures under uniaxial static loading was investigated. The theoretical static load influential factor was derived from a linearized UCBC model and corresponded to the transformed decoupled response over the mass-normalized static load. Three rectangular UCBC specimens (carbon fiber orientation of 0°, 45°, and 90°) were prepared under fixed-fixed boundary conditions using a jig fixture. Uniaxial static loads between 0 N and 1000 N were applied, and the first three modes of the UCBC specimens were analyzed. An isotropic SUS304 specimen was used as a reference. The linearization assumption about the UCBC structure was preliminarily validated with the Modal Assurance Criterion (MAC). A high influential factor was found for the UCBC specimen when carbon fibers were aligned with the static load direction at the first two resonance frequencies. Therefore, the proposed influential factor is an efficient indicator for determining the sensitivity of the dynamic response of a UCBC structure over a static load case. The variations in the influential factors for the UCBC specimens were more pronounced than for the isotropic specimens.

Collision Tumor of the Ovary: Adult Granulosa Cell Tumor and Mesonephric-like Adenocarcinoma.

Collision tumors of the ovaries are rare, with only a few reports in the literature. Adult granulosa cell tumors are a relatively common primary tumor component of previously reported collision tumors. The combination of serous and mucinous tumors with adult granulosa cell tumors has been reported in several cases. On the other hand, mesonephric-like adenocarcinomas are rare neoplasms that commonly arise in the uterine corpus and ovaries. In this report, we present the case of a collision tumor composed of an adult granulosa cell tumor and mesonephric-like adenocarcinoma of the ovary in a 63-year-old woman. The initial magnetic resonance imaging findings showed a cystic mass with an internal hemorrhage, which suggested an adult granulosa cell tumor, and a solid mass with different enhancements. Microscopically, the tumor had two distinct components: An adult granulosa cell tumor and a mesonephric-like adenocarcinoma. Recognizing collision tumors consisting of slow-growing and aggressive tumors may prove beneficial in future diagnostic and treatment strategies.

Current practices of cervical epidural block for cervical radicular pain: a multicenter survey conducted by the Korean Pain Society.

Background: Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea. Methods: Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail. Results: Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group. Conclusions: This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.

Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage â ¡A Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy.

PURPOSE: This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. METHODS: This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. RESULTS: Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. CONCLUSION: AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.

Successful treatment with rituximab in anti-phospholipid syndrome nephropathy associated with systemic lupus erythematosus: A case report and literature review.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency.

Predictive factors for perinatal bacterial transmission from colonized mothers to delivered very-low-birth-weight infants: a retrospective cohort study.

This study investigated the predictive factors for perinatal bacterial transmission in very-low-birth-weight infants (VLBWIs) born to mothers with a history of intrapartum colonization. We retrospectively reviewed the medical records of 173 VLBWIs, wherein pathogens were confirmed in maternal cultures obtained from the blood, urine, and vagina during the intrapartum period from 2013 to 2020. Newborns were categorized based on microbiological tests, including gastric aspirates, endotracheal aspirates, blood, and skin/nasal swab cultures collected immediately after birth. Infants whose cultures matched their maternal pathogens were categorized into the "transmission group" (n = 45), while those who tested negative were assigned to the "control group" (n = 128). The predominant maternal-colonizing pathogen observed was Escherichia coli (30.6%), which also emerged as the primary colonizing pathogen in neonates (35.6%). Transmission group had higher incidences of maternal leukocytosis, chorioamnionitis, and cervical cerclage. Regarding neonatal characteristics, the transmission group demonstrated lower initial base excesses (- 6.3 ± 3.9 vs. - 9.2 ± 4.9, P < 0.05) and higher C-reactive protein levels (0.1 ± 0.3 vs. 0.4 ± 0.8, P < 0.05). Notably, regarding major neonatal outcomes, transmission group had higher mortality rates and incidences of severe intraventricular hemorrhage. These findings may be useful for making decisions when considering antibiotic treatment for infants with a history of maternal colonization.

Highly efficient CRISPR/Cas9-RNP mediated CaPAD1 editing in protoplasts of three pepper (Capsicum annuum L.) cultivars.

Parthenocarpy, characterized by seedless fruit development without pollination or fertilization, offers the advantage of consistent fruit formation, even under challenging conditions such as high temperatures. It can be induced by regulating auxin homeostasis; PAD1 (PARENTAL ADVICE-1) is an inducer of parthenocarpy in Solanaceae plants. However, precise editing of PAD1 is not well studied in peppers. Here, we report a highly efficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein (RNP) for CaPAD1 editing in three valuable cultivars of pepper (Capsicum annuum L.): Dempsey, a gene-editable bell pepper; C15, a transformable commercial inbred line; and Younggo 4, a Korean landrace. To achieve the seedless pepper trait under high temperatures caused by unstable climate change, we designed five single guide RNAs (sgRNAs) targeting the CaPAD1 gene. We evaluated the in vitro on-target activity of the RNP complexes in three cultivars. Subsequently, we introduced five CRISPR/Cas9-RNP complexes into protoplasts isolated from three pepper leaves and compared indel frequencies and patterns through targeted deep sequencing analyses. We selected two sgRNAs, sgRNA2 and sgRNA5, which had high in vivo target efficiencies for the CaPAD1 gene across the three cultivars and were validated as potential off-targets in their genomes. These findings are expected to be valuable tools for developing new seedless pepper cultivars through precise molecular breeding of recalcitrant crops in response to climate change.

Achyranthis radix Extract Enhances Antioxidant Effect of Placenta-Derived Mesenchymal Stem Cell on Injured Human Ocular Cells.

Age-related ocular diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy are major causes of irreversible vision impairment in the elderly. Conventional treatments focus on symptom relief and disease slowdown, often involving surgery, but fall short of providing a cure, leading to substantial vision loss. Regenerative medicine, particularly mesenchymal stem cells (MSCs), holds promise for ocular disease treatment. This study investigates the synergistic potential of combining placenta-derived MSCs (PD-MSCs) with Achyranthis radix extract (ARE) from Achyranthes japonica to enhance therapeutic outcomes. In a 24-h treatment, ARE significantly increased the proliferative capacity of PD-MSCs and delayed their senescence (* p < 0.05). ARE also enhanced antioxidant capabilities and increased the expression of regeneration-associated genes in an in vitro injured model using chemical damages on human retinal pigment epithelial cell line (ARPE-19) (* p < 0.05). These results suggest that ARE-primed PD-MSC have the capability to enhance the activation of genes associated with regeneration in the injured eye via increasing antioxidant properties. Taken together, these findings support the conclusion that ARE-primed PD-MSC may serve as an enhanced source for stem cell-based therapy in ocular diseases.

Stem Cell-Derived Extracellular Vesicle-Bearing Injectable Hydrogel for Collagen Generation in Dermis.

Despite the remarkable advances of dermal fillers that reduce wrinkles caused by dermis thickness reduction, they still lack effective hydrogel systems that stimulate collagen generation along with injection convenience. Here, we develop a stem cell-derived extracellular vesicle (EV)-bearing thermosensitive hydrogel (EVTS-Gel) for effective in vivo collagen generation. The TS-Gel undergoes sol-gel transition at 32.6 °C, as demonstrated by the storage and loss moduli crossover. Moreover, the TS-Gel and the EVTS-Gel have comparable rheological properties. Both hydrogels are injected in a sol state; hence, they require lower injection forces than conventional hydrogel-based dermal fillers. When locally administered to mouse skin, the TS-Gel extends the retention time of EVs by 2.23 times. Based on the nature of the controlled EV release, the EVTS-Gel significantly inhibits the dermis thickness reduction caused by aging compared to the bare EV treatment for 24 weeks. After a single treatment, the collagen layer thickness of the EVTS-Gel-treated dermis becomes 2.64-fold thicker than that of the bare EV-treated dermis. Notably, the collagen generation efficacy of the bare EV is poorer than that of the EVTS-Gel of a 10× lesser dose. Overall, the EVTS-Gel shows potential as an antiaging dermal filler for in vivo collagen generation.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma.

PURPOSE: To identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study. METHODS: A total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of Cirrus OCT. RESULTS: Thirty-two eyes displayed choroidal MvD (62.7 [95% CI 58.4-67.0] years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV ≥ 1400 cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P = .023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P = .025). CONCLUSIONS: In NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Dual Stimuli-Responsive Nanoprecursor of Ascorbic Acid and Quinone Methide Disrupting Redox Homeostasis for Cancer Treatment.

Disrupting the redox balance through reactive oxygen species (ROS) generation and intracellular glutathione (GSH) depletion presents a promising strategy for cancer therapy. Megadoses of ascorbic acid (AA) can induce oxidative stress in cancer cells, leading to cell death. However, achieving enhanced oxidative stress using ultrahigh doses of AA is challenging because of the intricate delivery of high-concentration AA to the targeted sites while the cancer cells could also re-establish more robust redox homeostasis by upregulating antioxidants such as GSH. Recently, quinone methide and its analogues (QMs) have been recognized as effective GSH scavengers, offering a new dimension to accelerate oxidative stress. In this study, we formulated a dual stimuli-responsive nanoprecursor of AA and QM using gold nanoparticles. The nanoprecursor can release AA in response to the intracellular acidic pH in tumor cells, elevating the intracellular ROS levels and triggering the production of ample QMs to quench excessive GSH. This positive feedback mechanism significantly amplifies oxidative stress and disrupts redox homeostasis in cancer cells at a relatively low concentration of AA, leading to selective apoptosis without affecting normal cells. These results highlight the potential of the nanoprecursor as an effective anticancer therapeutic.

Tubular adenoma arising in tubular colonic duplication: a case report.

Colonic duplication constitutes a rare congenital anomaly, characterized by the presence of hollow cystic or tubular structures exhibiting an epithelial-lined intestinal wall. Diagnostic challenges persist due to its low incidence and manifestation of nonspecific symptoms such as abdominal pain or constipation, resulting in a reluctance to pursue surgical resection. As associated malignancies in colonic duplication are rare, the inherent malignant potential of these anomalies remains undetermined. Additionally, despite reported instances of associated malignancies in colonic duplication, there is an absence of reports in the literature detailing tubular adenoma within these cases. The histologic features of the presented case are particularly noteworthy, situated at the precancerous stage, intimating potential progression towards adenocarcinoma within colonic duplication.