Development of Magnetic Resonance-Compatible Head Immobilization Device and Initial Experience of Magnetic Resonance-Guided Radiation Therapy for Central Nervous System Tumors.

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

The Role of Extracellular Vesicles in the Treatment of Prostate Cancer.

Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.

Ginsenosides Decrease ß-Amyloid Production via Potentiating Capacitative Calcium Entry.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid ß-peptide (Aß). Studies have indicated that Ca2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca2+ entry (CCE), a refilling mechanism of intracellular Ca2+, resulting in increased Aß production. In contrast, constitutive activation of CCE could decrease Aß production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aß levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aß-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aß production by examining the effects of various ginsenosides on CCE levels. Aß-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aß-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydipherryl borate (2APB), an inhibitor of CCE. 2APB alone increased Aß42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aß42 production. Our results indicate that ginsenosides decrease Aß production via potentiating CCE levels, confirming a close relationship between CCE levels and Aß production. Since CCE levels are closely related to Aß production, modulating CCE could be a novel target for AD therapeutics.

Optical and UV Shielding Properties of Inorganic Nanoparticles Embedded in Polymethyl Methacrylate Nanocomposite Freestanding Films.

Polymethyl methacrylate (PMMA) is an interesting polymer employed in various applications due to its outstanding properties. However, its electrical and mechanical properties can be further improved by incorporating nanoparticles, and in particular, PMMA nanocomposite with nanoparticles provides various multifunctional properties. This work reports PMMA nanocomposite preparation and structural and optical characterizations incorporating carbon nanotubes (CNTs), TiO2 nanoparticles, and carbon quantum dots (CQDs). CNT/PMMA, TiO2/PMMA, and CQD/PMMA nanocomposite freestanding films were prepared using a simple solution method. Various properties of the prepared composite films were analyzed using scanning electron microscopy, X-ray diffraction, photoluminescence, Fourier transform infrared, and UV-Vis and Raman spectroscopy. Optical parameters and photocatalytic dye degradation for the films are reported, focusing on the properties of the materials. The CNT/PMMA, TiO2/PMMA, and CQD/PMMA films achieved, respectively, good electrical conductivity, photodegradation, and fluorescence compared with other composite films.

Incidence of atrial fibrillation in patients with renal infarction: A retrospective cohort analysis of the Korean national health insurance registry.

BACKGROUND: Regarding the pathophysiology of renal infarction (RI), cardioembolic causes could have large proportion. However, there are notable variations in prevalence of atrial fibrillation (AF) among patients with RI across different studies, ranging from 17 to 65%. The primary objective of this study is to analyze the incidence of AF in patients with RI. METHODS: This nationwide retrospective cohort study enrolled 5200 patients with RI from the Korean National Institute of Health Services database spanning the years 2013 to 2019. The study accessed the AF incidence rate within 12 months in patients without a prior history of AF. Events occurring within 3 months of RI diagnosis were excluded to mitigate cases diagnosed during the initial screening or those with AF diagnoses that were potentially overlooked in the past. RESULTS: AF occurred in 19.1% of patients with RI over the entire period (median: 2.5 years, interquartile range 1.04-4.25 years). The majority of AF cases (16.1%) occured within the first year, resulting in an overall incidence rate of 7.0 per 100 person-years. Patients with newly developed AF were, on average, older than those who did not develop AF (64.1 vs. 57.3 years, P < 0.001). The independent predictors of AF were identified as age, male sex, higher body mass index, current smoking, ischemic heart disease, and heart failure. CONCLUSIONS: Physicians should consider the implementation of active rhythm monitoring for patients with RI to identify potential occurrence of subclinical AF, even if not initially diagnosed during the initial screening after RI diagnosis.

Healthcare service use and medical outcomes of tracheostomy-dependent children: a nationwide study.

BACKGROUND: Despite the rising trend of tracheostomies in children, there is a lack of comprehensive resources for families to navigate the challenges of living with a tracheostomy, emphasising the need for evidence-based support in understanding postoperative care and long-term adjustments. This study aimed to examine the pattern of using healthcare services and nationwide medical outcomes in children who underwent a tracheotomy before the age of 2 years. METHODS: This retrospective study used the National Health Insurance System database from 2008 to 2016 and included all children codified with tracheotomy procedure codes before their second birthday. Healthcare utilisation, such as medical costs, number of hospital visits, home healthcare nursing and medical diagnoses on readmission, in the first 2 years after tracheotomy was evaluated. Multivariable logistic regression analysis was used to determine the factors affecting mortality. RESULTS: In total, 813 patients were included in this study. Their use of healthcare services and the accompanying expenses were higher than the national medians for similar age groups; however, both metrics decreased in the second year. The major causes of admission within 2 years of surgery were respiratory and neurological diseases. The mortality rate within 2 years was 37.8%. Higher risks of mortality were associated with having two or more complex chronic conditions. Use of home healthcare nursing services was associated with a lower mortality risk. CONCLUSION: Paediatric patients with more complex chronic conditions tended to have higher mortality rates within 2 years after surgery. However, receiving home healthcare nursing was significantly associated with a reduced risk of death. Many causes of hospitalisation may be preventable with education and supportive care. Therefore, further research for establishing an integrated care system for these patients and their caregivers is required.

Tonicity-induced cargo loading into extracellular vesicles.

The current challenge in using extracellular vesicles (EVs) as drug delivery vehicles is to precisely control their membrane permeability, specifically in the ability to switch between permeable and impermeable states without compromising their integrity and functionality. Here, we introduce a rapid, efficient, and gentle loading method for EVs based on tonicity control (TC) using a lab-on-a-disc platform. In this technique, a hypotonic solution was used for temporarily permeabilizing a membrane ("on" state), allowing the influx of molecules into EVs. The subsequent isotonic washing led to an impermeable membrane ("off" state). This loading cycle enables the loading of different cargos into EVs, such as doxorubicin hydrochloride (Dox), ssDNA, and miRNA. The TC approach was shown to be more effective than traditional methods such as sonication or extrusion, with loading yields that were 4.3-fold and 7.2-fold greater, respectively. Finally, the intracellular assessments of miRNA-497-loaded EVs and doxorubicin-loaded EVs confirmed the superior performance of TC-prepared formulations and demonstrated the impact of encapsulation heterogeneity on the therapeutic outcome, signifying potential opportunities for developing novel exosome-based therapeutic systems for clinical applications.

Can DNA Methylation Profiling Classify Histologic Subtypes and Grades in Soft Tissue Sarcoma?

BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.

Recent updates on treatment patterns in patients with treated attention-deficit/hyperactivity disorders from a nationwide real-world database in South Korea.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) is steadily increasing across Korea. We analyzed ADHD patients with ADHD medications (Rx) characteristics and treatment patterns compared to patients without Rx and identified the differences between pediatric-/adult- and active-/transient-patients with Rx. Using a nationwide claims dataset from 2020 to 2021, we conducted a prevalence-based cross-sectional study and analyzed the recent patients' characteristics and patterns among ADHD patients. Among 132 017 ADHD patients with Rx, differences from 20 312 without Rx across all characteristics except sex. We found significant differences in characteristics and treatment patterns between pediatric-/adult- and active-/transient-patients with Rx. Age-specific sex ratios notably diverged in pediatric patients (61.2%), but remained similar in adults, revealing significant psychiatric comorbidities differences. Active-patients peaked at 6-11 years (41.4%), while transient-patients at 18-30 years (36.1%). Predominantly, methylphenidate (89.7%), atomoxetine (27.8%), and clonidine (2.8%) were prescribed, with 85% experiencing treatment changes within methylphenidate formulations. In pediatric patients, extended-release methylphenidate was preferred (56.1%), adults favored oral delivery system methylphenidate (71.5%), and active-patients had higher treatment rates than transient-patients across all patterns, with low monotherapy rates. This study provides epidemiologic insights into recent characteristics and treatment patterns of ADHD patients with Rx in Korea, providing valuable evidence for identifying those actively receiving ADHD treatment in future healthcare policy decisions.

Alix-normalized exosomal programmed death-ligand 1 analysis in urine enables precision monitoring of urothelial cancer.

Anti-programmed death-ligand 1 (PD-L1) Ab-based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD-L1 expression. Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD-L1/Alix ratio to normalize exosomal PD-L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD-L1, and Alix on individual exosomes. On-disc ELISA was used to evaluate PD-L1 and Alix-normalized PD-L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On-disc ELISA was more reliable for detecting exosomal PD-L1 expression than standard plate ELISA-based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD-L1 in urine samples from patients with urothelial cancer.

Care of patients undergoing withdrawal of life-sustaining treatments: an ICU nurse perspective.

BACKGROUND: Intensive care unit (ICU) nurses working in South Korea report experiencing uncertainty about how to care for patients undergoing withdrawal of life-sustaining treatments (WLT). A lack of consensus on care guidelines for patients with WLT contributes to uncertainty, ambiguity, and confusion on how to act appropriately within current law and social and ethical norms. To date, little has been discussed or described about how ICU nurses construct meaning about their roles in caring for dying patients in the context of wider social issues about end-of-life care and how this meaning interacts with the ICU system structure and national law. We aimed to better understand how ICU nurses view themselves professionally and how their perceived roles are enabled and/or limited by the current healthcare system in South Korea and by social and ethical norms. METHODS: This qualitative descriptive study was conducted using in-depth, semi-structured interviews and discourse analysis using Gee's Tools of Inquiry. Purposive sampling was used to recruit ICU nurses (n = 20) who could provide the most insightful information on caring for patients undergoing WLT in the ICU. The interviews were conducted between December 2021 and February 2022 in three university hospitals in South Korea. RESULTS: We identified four categories of discourses: (1) both "left hanging" or feeling abandoned ICU nurses and patients undergoing WLT; (2) socially underdeveloped conversations about death and dying management; (3) attitudes of legal guardians and physicians toward the dying process of patients with WLT; and (4) provision of end-of-life care according to individual nurses' beliefs in their nursing values. CONCLUSION: ICU nurses reported having feelings of ambiguity and confusion about their professional roles and identities in caring for dying patients undergoing WLT. This uncertainty may limit their positive contributions to a dignified dying process. We suggest that one way to move forward is for ICU administrators and physicians to respond more sensitively to ICU nurses' discourses. Additionally, social policy and healthcare system leaders should focus on issues that enable and limit the dignified end-of-life processes of patients undergoing WLT. Doing so may improve nurses' understanding of their professional roles and identities as caretakers for dying patients.

Residual pure intralymphatic carcinoma component only (lymphovascular tumor emboli without invasive carcinoma) after neoadjuvant chemotherapy is associated with poor outcome: Not pathologic complete response.

Residual pure intralymphatic carcinoma (PIC) component only after neoadjuvant chemotherapy (NAC) is lymphovascular tumor emboli without invasive carcinoma and extremely rare form of residual tumor after NAC. Although several studies have been published, the prognostic influence of residual PIC component only had not been fully evaluated. This study aims to evaluate the clinicopathologic features and the prognostic value of residual PIC component only. We reviewed the 251 patients with no residual invasive carcinoma in breast after NAC and found 12 patients with residual PIC component only after NAC. Five cases were triple negative, 6 were HER2 positive, and 1 was estrogen receptor positive and HER2 negative. The extent of PIC component ranged from 0.18 to 50.00 mm. The detailed microscopic PIC component findings did not significantly correlate with regional lymph node metastasis, local recurrence, or distant metastasis (p > 0.05). In multivariate survival analysis, the presence of lymph node metastasis and pretreatment ki-67 labeling index more than 50 % was statistically associated with greater risk of relapse [Cox proportional hazards ratio (HR) = 3.236, 95 % confidence interval (CI), 1.461-7.280, p = 0.004; HR = 3.046, 95 % CI, 1.421-6.529, p = 0.004, respectively) and residual PIC component only tended to be associated with greater risk of relapse (HR = 2.378, 95 % CI, 0.853-6.631; p = 0.098), but not reached to statistically significance. In patients without lymph node metastasis, the presence of residual PIC component only was associated with worse disease-free survival (p = 0.004). Although the number of published studies still limited, residual residual PIC component only after NAC is associated with poor outcome, and it should not be considered as pathological complete response.

Nicotinamide adenine dinucleotide phosphate oxidase 2 deletion attenuates polyhexamethylene guanidine-induced lung injury in mice.

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes.

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Amygdala electrical stimulation for operant conditioning in rat navigation.

There have been several attempts to navigate the locomotion of animals by neuromodulation. The most common method is animal training with electrical brain stimulation for directional cues and rewards; the basic principle is to activate dopamine-mediated neural reward pathways such as the medial forebrain bundle (MFB) when the animal correctly follows the external commands. In this study, the amygdala, which is the brain region responsible for fear modulation, was targeted for punishment training. The brain regions of MFB, amygdala, and barrel cortex were electrically stimulated for reward, punishment, and directional cues, respectively. Electrical stimulation was applied to the amygdala of rats when they failed to follow directional commands. First, two different amygdala regions, i.e., basolateral amygdala (BLA) and central amygdala (CeA), were stimulated and compared in terms of behavior responses, success and correction rates for training, and gene expression for learning and memory. Then, the training was performed in three groups: group R (MFB stimulation for reward), group P (BLA stimulation for punishment), and group RP (both MFB and BLA stimulation for reward and punishment). In group P, after the training, RNA sequencing was conducted to detect gene expression and demonstrate the effect of punishment learning. Group P showed higher success rates than group R, and group RP exhibited the most effective locomotion control among the three groups. Gene expression results imply that BLA stimulation can be more effective as a punishment in the learning process than CeA stimulation. We developed a new method to navigate rat locomotion behaviors by applying amygdala stimulation.

Drosophila melanogaster as potential alternative animal model for evaluating acute inhalation toxicity.

Drosophila melanogaster (D. melanogaster) is a promising model biological system. It has a short life cycle and can provide a substantial number of specimens suitable for comprehensive genetic and molecular analyses in a short time. In this study, we investigated the acute inhalation toxicity of methylisothiazolinone (MIT) and chloromethylisothiazolinone (CMIT) in a D. melanogaster model. During exposure, environmental conditions, mass median aerodynamic and geometric standard diameters were measured. After inhalation exposure, the survival rate, climbing ability, and bang sensitivity were measured on days 1, 2, and 7. Notably, the survival rate of flies decreased in an exposure concentration-dependent manner. Climbing ability and bang sensitivity were also altered in the MIT/CMIT group, compared with the negative control group. Overall, these results provide a reliable D. melanogaster model system for inhalation toxicity study.

In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months.

Importance: Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking. Objective: To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age. Design, Setting, and Participants: This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely. Exposure: In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed. Main Outcomes and Measures: Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay. Results: A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07). Conclusions and Relevance: Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

Factors influencing the intention for lung cancer screening in high-risk populations for lung cancer.

Objective: Utilizing low-dose computed tomography for lung cancer screening has proven effective in reducing lung cancer mortality among high-risk individuals. This study aimed to investigate the health beliefs, knowledge of lung cancer, and cancer prevention behaviors in adults at high risk for lung cancer, with the goal of identifying predictors influencing their intention to undergo lung cancer screening. Methods: The study utilized a descriptive cross-sectional design. Online questionnaires, including assessments of lung cancer screening health beliefs, knowledge of lung cancer, cancer prevention behaviors, intention to undergo lung cancer screening, and participant characteristics, were distributed to 186 individuals at high risk of lung cancer through a survey link. The data collection period spanned from April 26 to May 3, 2023. Analytical procedures encompassed descriptive statistics, independent t-test, one-way ANOVA, Pearson's correlations, and hierarchical multiple regression. Results: The mean score for the intention to undergo lung cancer screening in our study was 3.66 out of 5. The regression model explaining the intention to undergo lung cancer screening accounted for 34.7% of the variance. Significant factors identified included stress level (ß = 0.20, P = 0.002), perceived risk (ß = 0.13, P = 0.040), self-efficacy (ß = 0.35, P < 0.001), and engagement in cancer prevention behavior (ß = 0.26, P < 0.001). Conclusions: Healthcare providers should implement psychological interventions and provide education about cancer screening for high-risk individuals, aiming to enhance their perceived risk and self-efficacy, thus promoting a higher likelihood of undergoing screening.

Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Platelet Membrane-Enclosed Bioorthogonal Catalysis for Combating Dental Caries.

Platelets have shown promise as a means to combat bacterial infections, fostering the development of innovative therapeutic approaches. However, several challenges persist, including cargo loading issues, limited efficacy against biofilms, and concerns regarding the impact of payloads on the platelet carriers. Here, human platelet membrane vesicles (h-PMVs) encapsulating supramolecular metal catalysts (SMCs) as "nanofactories" to convert prodrugs into antimicrobial compounds within close proximity to bacteria are introduced. Having established the feasibility and effectiveness of the SMCs within h-PMVs, referred to as the PLT-reactor, to activate pro-antibiotic drugs (pro-ciprofloxacin and pro-moxifloxacin) using model organisms (Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923), the investigation is subsequently extended to oral biofilms, with a particular emphasis on Streptococcus mutans 3065. This "bind and kill" strategy demonstrates the potent antimicrobial specificity of the PLT-reactor through localized antibiotic production. h-PMVs play a pivotal role by enabling precise targeting of pathogenic biofilms on natural teeth while minimizing potential hemolytic effects. The finding indicates that platelet membrane-cloaked surfaces exhibit robust, multifaceted, and pathogen-specific binding affinity with excellent biocompatibility, making them a promising alternative to antibody-based therapies for infectious diseases.