Distorted time perception in patients with neurocognitive impairment.

Background: Time perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). Methods: Overall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. Results: Time perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. Conclusions: Patients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

Cancer risks of patients with Graves' disease who received antithyroid drugs as initial treatment: A nationwide population-based analysis.

BACKGROUND: Population-based studies that examining the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared to controls. METHODS: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD who received antithyroid drugs as initial treatment and 57,173 age and sex matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HR) with 95% confidence intervals (CI) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. RESULTS: The risk of biliary tract and pancreatic cancers (HR: 1.41, 95% CI: 1.24-1.60), thyroid cancer (HR: 15.51, 95% CI: 12.29-19.57), prostate cancer (HR: 1.48, 95% CI: 1.28-1.71), and ovarian cancer (HR: 1.31, 95% CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 - < 2 years) (HR: 19.35, 95% CI: 7.66-48.87) compared to that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. CONCLUSION: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

The Role of Direct Oral Anticoagulants in Managing Myeloproliferative Neoplasms Patients.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with one-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (HR=3.48), concomitant antiplatelet use (HR = 2.57), and cytoreduction (HR=2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion: Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Therapeutic Potential of Lactiplantibacillus plantarum FB091 in Alleviating AlcoholInduced Liver Disease through Gut-Liver Axis.

Alcoholic liver disease (ALD) poses a significant global health burden, often requiring liver transplantation and resulting in fatalities. Current treatments, like corticosteroids, effectively reduce inflammation but carry significant immunosuppressive risks. This study evaluates Lactiplantibacillus plantarum FB091, a newly isolated probiotic strain, as a safer alternative for ALD treatment. Using an in vivo mouse model, we assessed the effects of L. plantarum FB091 on alcohol-induced liver damage and gut microbiota composition. Alcohol and probiotics administration did not significantly impact water/feed intake or body weight. Histopathological analysis showed that L. plantarum FB091 reduced hepatocellular ballooning and inflammatory cell infiltration in liver tissues and mitigated structural damage in colon tissues, demonstrating protective effects against alcohol-induced damage. Biomarker analysis indicated that L. plantarum FB091 decreased aspartate aminotransferase levels, suggesting reduced liver damage, and increased alcohol dehydrogenase activity, indicating enhanced alcohol metabolism. Additionally, cytokine assays revealed a reduction in pro-inflammatory TNF-α and an increase in anti-inflammatory IL-10 levels in colon tissues of the L. plantarum FB091 group, suggesting an anti-inflammatory effect. Gut microbiota analysis showed changes in the L. plantarum FB091 group, including a reduction in Cyanobacteria and an increase in beneficial bacteria such as Akkermansia and Lactobacillus. These changes correlated with the recovery and protection of liver and colon health. Overall, L. plantarum FB091 shows potential as a therapeutic probiotic for managing ALD through its protective effects on liver and colon tissues, enhancement of alcohol metabolism, and beneficial modulation of gut microbiota. Further clinical studies are warranted to confirm these findings in humans.

HN1-mediated activation of lipogenesis through Akt-SREBP signaling promotes hepatocellular carcinoma cell proliferation and metastasis.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, with more than 800,000 deaths each year, and its 5-year survival rate is less than 12%. The role of the HN1 gene in HCC has remained elusive, despite its upregulation in various cancer types. In our investigation, we identified HN1's heightened expression in HCC tissues, which, upon overexpression, fosters cell proliferation, migration, and invasion, unveiling its role as an oncogene in HCC. In addition, silencing HN1 diminished the viability and metastasis of HCC cells, whereas HN1 overexpression stimulated their growth and invasion. Gene expression profiling revealed HN1 silencing downregulated 379 genes and upregulated 130 genes, and suppressive proteins associated with the lipogenic signaling pathway networks. Notably, suppressing HN1 markedly decreased the expression levels of SREBP1 and SREBP2, whereas elevating HN1 had the converse effect. This dual modulation of HN1 affected lipid formation, hindering it upon HN1 silencing and promoting it upon HN1 overexpression. Moreover, HN1 triggers the Akt pathway, fostering tumorigenesis via SREBP1-mediated lipogenesis and silencing HN1 effectively curbed HCC tumor growth in mouse xenograft models by deactivating SREBP-1, emphasizing the potential of HN1 as a therapeutic target, impacting both external and internal factors, it holds promise as an effective therapeutic strategy for HCC.

A facile strategy for synthesizing isosorbide-based polyurethane structural adhesives and core-shell rubber.

A structural adhesive series of biomass-based polyurethane (Biomass-PU) is synthesized using polypropylene glycol (PPG2000), isosorbide-based polyol (RPO300) as polyols, isophorone diisocyanate (IPDI) as an isocyanate and 4-tert-butylphenol (BP) as a capping agent. Three different equivalent ratios of PPG2000/RPO300, 9/1 (Biomass-PU1), 7/3 (Biomass-PU2), and 1/1 (Biomass-PU3), are evaluated to determine the effect of isosorbide-based polyol content on the properties and the optimizing formulation of biomass-PU structure adhesive. The 9/1 ratio of PPG2000/RPO300 substantially leads to the improvement of impact strength by up to 35 MPa, and the PPG2000/RPO300 = 9/1 ratio exhibits better thermal properties and impact strength than those of other ratios. To achieve more compatibility between biomass-PU structure adhesive and core-shell rubber (CSR) toughener, novel CSRs are successfully synthesized using acryl-PU as a shell and biomass-based PU as a core. The chemical structure of biomass-PU structure adhesives is analyzed through FT-IR Spectroscopy and NCO% titration. Thermal properties are evaluated using TGA and DSC analysis. Their molecular weights are measured by GPC. Also, the core-shell rubber (CSR) with a polyurethane shell is prepared to reinforce the impact strength of Biomass-PU structure adhesive.

Evaluation and characteristic analysis of SSRs from the transcriptomic sequences of Perilla crop (Perilla frutescens L.).

Perilla crop is a self-fertilizing annual plant, cultivated and used mainly in East Asia. Perilla frutescens var. frutescens seeds are rich in unsaturated fatty acids, which have health benefits, and Perilla frutescens var. crispa leaves are rich in anthocyanins. However, genomic analysis such as whole genome sequencing or genetic mapping has not been performed on Perilla crop. This current study confirms the abundance and diversity of 15,991 simple sequence repeats (SSRs) classified in previous studies in the Perilla genome, selects and designs 1,538 SSR primer sets, and confirms which SSR primer sets exhibit high polymorphism. Of the 15,991 SSRs classified, there were 9,910 (62%) dinucleotide repeats, 5,652 (35.3%) trinucleotide repeats, and 429 (2.7%) tetranucleotide repeats. Among these, the most identified was (CT)n with a total of 4,817. The 15,991 SSRs had 4 to 26 repeats. Four repeats were the most frequent with 11,084 (69.3%). A total of 1,538 SSR primers were selected and designed to confirm polymorphism, of which 157 showed persistent and clear polymorphism. Among these 157 SSR primer sets, 98 (62.4%) were dinucleotide repeats, 39 (24.8%) were trinucleotide repeats, and 20 (12.7%) were tetranucleotide repeats. Among 549 SSR primers that showed polymorphism, trinucleotide repeats showed persistent polymorphism at a high rate. Therefore, when developing SSR primer sets for Perilla crop in the future, it is recommended that trinucleotide repeats be selected first. These research results will be helpful in future genomic analysis and development of SSR primers in Perilla crop.

In Vitro and In Silico Analysis of PTP1B Inhibitors from Cleistocalyx operculatus Leaves and Their Effect on Glucose Uptake.

As part of our ongoing research on new anti-diabetic compounds from ethnopharmacologically consumed plants, two previously undescribed lupane-type triterpenoids (1 and 2) with dicarboxylic groups, an undescribed nor-taraxastane-type triterpenoid (3), and 14 known compounds (4-17) were isolated from the leaves of Cleistocalyx operculatus. Extensive spectroscopic analysis (IR, HRESIMS, 1D, and 2D NMR) was used for structure elucidation, while the known compounds were compared to reference data reported in the scientific literature. All the isolates (1-17) were evaluated for their inhibitory effects on the protein tyrosine phosphatase 1B (PTP1B) enzyme. Compounds 6, 9, and 17 showed strong PTP1B inhibitory activities. The mechanism of PTP1B inhibition was studied through enzyme kinetic experiments. A non-competitive mechanism of inhibition was determined using Lineweaver-Burk plots for compounds 6, 9, and 17. Additionally, Dixon plots were employed to determine the inhibition constant. Further insights were gained through a structure-activity relationship study and molecular docking analysis of isolated compounds with the PTP1B crystal structure. Moreover, all isolates (1-17) were tested for their stimulatory effects on the uptake of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) in differentiated 3T3-L1 adipocyte cells. Compounds 6, 13, and 17 exhibited strong glucose absorption stimulation activity in a dose-dependent manner.

Incidence and pattern of second primary cancer in patients diagnosed with primary cancer.

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

Versatile effects of galectin-1 protein-containing lipid bilayer coating for cardiovascular applications.

Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices. Inspired by the role of galectin-1 (Gal-1) in selective functions on multiple cells and immunomodulatory processes, we prepared a biologically target-specific surface coated with the lipid bilayer containing Gal-1 (Gal-1-SLB) and investigate the proof of the biological effects. First, lipoamido-dPEG-acid was deposited on a gold-coated substrate to form a self-assembled monolayer and then conjugated dioleoylphosphatidylethanolamine (DOPE) onto that to produce a lower leaflet of the supported lipid bilayer (SLB) before fusing membrane-derived vesicles extracted from B16-F10 cells. The Gal-1-SLB showed the expected anti-fouling activity by revealing the resistance to protein adsorption and bacterial adhesion. In vitro studies showed that the Gal-1-SLB can promote endothelial function and inhibit smooth muscle cell proliferation. Moreover, Gal-1- SLB presents potential function for endothelial cell migration and angiogenic activities. In vitro macrophage culture studies showed that the Gal-1-SLB attenuated the LPS-induced inflammation and the production of macrophage-secreted inflammatory cytokines. Finally, the implanted Gal-1-SLB reduced the infiltration of immune cells at the tissue-implant interface and increased markers for M2 polarization and blood vessel formation in vivo. This straightforward surface coating with Gal-1 can be a useful strategy for modulating the vascular and immune cells around a blood-contacting device.

Association mapping analysis (AMA) for morpho-agronomic traits and leaf aromatic compounds using SSR markers in three types of Perilla crop collected from South Korea.

BACKGROUND: Perilla is a representative leafy vegetable in South Korea. As K-Food (Korean food) is in the spotlight around the world, there is also increasing interest in Western countries in Perilla crop, an annual plant belonging to the Lamiaceae family. OBJECTIVE: To discover comprehensive information, including genetic and phylogenetic relationships among the 80 native Perilla accessions, using three types of data: simple sequence repeat (SSR) marker data, volatiles profile data, and morpho-agronomic data. METHODS: This study conducted genotypic and phenotypic analyses on 80 Perilla accessions of three types (cultivated var. frutescens, weedy var. frutescens, weedy var. crispa) from South Korea. Five groups (G1-G5) of the 80 Perilla accessions of the three types were differentiated into two different clusters [genotype-based clustering (GTC) and phenotype-based clustering (PTC)] based on an aroma sensory phenotypic test. RESULTS: A total of 314 alleles were confirmed using 55 Perilla SSR primer sets, and genetic variation in the 80 Perilla accessions was evaluated. Among the three statistical analysis methods, principal coordinate analysis (PCoA) and GTC using data of the 55 Perilla SSR markers revealed perfectly consistent results, whereas PTC produced a total of six clusters. The 10 Perilla SSR markers associated with and significantly correlated with both biochemical and morphological characteristics were selected. CONCLUSIONS: These findings are expected to provide valuable information for developing global South Korean Perilla cultivars for further studies in Perilla crop breeding programs.

Orthodontic treatment outcome predictive performance differences between artificial intelligence and conventional methods.

OBJECTIVES: To evaluate an artificial intelligence (AI) model in predicting soft tissue and alveolar bone changes following orthodontic treatment and compare the predictive performance of the AI model with conventional prediction models. MATERIALS AND METHODS: A total of 1774 lateral cephalograms of 887 adult patients who had undergone orthodontic treatment were collected. Patients who had orthognathic surgery were excluded. On each cephalogram, 78 landmarks were detected using PIPNet-based AI. Prediction models consisted of 132 predictor variables and 88 outcome variables. Predictor variables were demographics (age, sex), clinical (treatment time, premolar extraction), and Cartesian coordinates of the 64 anatomic landmarks. Outcome variables were Cartesian coordinates of the 22 soft tissue and 22 hard tissue landmarks after orthodontic treatment. The AI prediction model was based on the TabNet deep neural network. Two conventional statistical methods, multivariate multiple linear regression (MMLR) and partial least squares regression (PLSR), were each implemented for comparison. Prediction accuracy among the methods was compared. RESULTS: Overall, MMLR demonstrated the most accurate results, while AI was least accurate. AI showed superior predictions in only 5 of the 44 anatomic landmarks, all of which were soft tissue landmarks inferior to menton to the terminal point of the neck. CONCLUSIONS: When predicting changes following orthodontic treatment, AI was not as effective as conventional statistical methods. However, AI had an outstanding advantage in predicting soft tissue landmarks with substantial variability. Overall, results may indicate the need for a hybrid prediction model that combines conventional and AI methods.

Does artificial intelligence predict orthognathic surgical outcomes better than conventional linear regression methods?

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) model in predicting orthognathic surgical outcomes compared to conventional prediction methods. MATERIALS AND METHODS: Preoperative and posttreatment lateral cephalograms from 705 patients who underwent combined surgical-orthodontic treatment were collected. Predictors included 254 input variables, including preoperative skeletal and soft-tissue characteristics, as well as the extent of orthognathic surgical repositioning. Outcomes were 64 Cartesian coordinate variables of 32 soft-tissue landmarks after surgery. Conventional prediction models were built applying two linear regression methods: multivariate multiple linear regression (MLR) and multivariate partial least squares algorithm (PLS). The AI-based prediction model was based on the TabNet deep neural network. The prediction accuracy was compared, and the influencing factors were analyzed. RESULTS: In general, MLR demonstrated the poorest predictive performance. Among 32 soft-tissue landmarks, PLS showed more accurate prediction results in 16 soft-tissue landmarks above the upper lip, whereas AI outperformed in six landmarks located in the lower border of the mandible and neck area. The remaining 10 landmarks presented no significant difference between AI and PLS prediction models. CONCLUSIONS: AI predictions did not always outperform conventional methods. A combination of both methods may be more effective in predicting orthognathic surgical outcomes.

Subchronic particulate matter exposure underlying polyhexamethylene guanidine phosphate-induced lung injury: Quantitative and qualitative evaluation with chest computed tomography.

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Serum cortisol and neuroticism for post-traumatic stress disorder over 2 years in patients with physical injuries.

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

Assessing the Predictive Validity of Early Post-injury CAPS-5 for Later Posttraumatic Stress Disorder Diagnosis.

Abstract.Objective: The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a widely recognized tool with exceptional reliability and validity in evaluating and diagnosing PTSD. This study aimed to determine the predictive values of CAPS-5 assessed early postinjury for subsequent development of PTSD during a 2-year follow-up period.Methods: Patients with moderate to severe physical injuries were recruited from a trauma center at a university hospital in South Korea between June 2015 and January 2021. At baseline, 1,142 patients underwent evaluations using CAPS-5 for the diagnosis of acute stress disorder (ASD) along with total scores. They were followed up for PTSD using the CAPS-5 evaluations at 3, 6, 12, and 24 months post-baseline. Area under receiver operating curve (AUROC) analyses were conducted to identify predictive values of the CAPS-5 for later PTSD development.Results: CAPS-5 diagnosis of ASD at baseline displayed fair to failed performance (AUROCs: 0.555-0.722) for predicting follow-up PTSD. However, CAPS-5 scores of ≥15 exhibited good to fair predictive accuracy (AUROCs: 0.767-0.854) for later PTSD development. Notably, for patients with intentional injuries or a history of previous trauma, a higher CAPS-5 score of ≥16 showed improved predictive accuracy.Conclusion: A CAPS-5 score of ≥15 would be an effective and practical cutoff for early prediction of PTSD following physical injuries. In cases of intentional injuries or a documented trauma history, a cutoff of ≥16 may offer enhanced predictive precision. Future research in diverse settings and populations is needed to confirm the generalizability of our findings.

Immunogenicity of a novel inactivated canine adenovirus type 2 variant vaccine for dogs.

Purpose: The immunogenicity of vaccines containing the canine adenovirus (CAdV) type 2 (CAdV-2) variant has not yet been reported. We prepared a novel inactivated CAdV-2 variant vaccine using the CAV2232-41 strain, and evaluated its safety and immunogenicity in raccoon dogs. Materials and Methods: The growth kinetics of CAV2232-41 were determined using Madin-Darby Canine Kidney (MDCK) cells. The nucleotide sequences of CAV2232 and CAV2232-41 were determined by next-generation sequencing. To generate the CAdV-2 variant vaccine, CAV2232-41 propagated in the MDCK cells was inactivated with 0.1% formaldehyde. Two vaccines were prepared by blending inactivated CAV2232-41 with Cabopol and Rehydragel adjuvants. Safety and immunogenicity of the CAV2232C and CAV2232R vaccines were evaluated in guinea pigs. Safety and immunogenicity of the CAV2232C vaccine were also evaluated in raccoon dogs. The virus neutralizing antibody (VNA) titer against CAV2232-41 was measured in sera collected from immunized guinea pigs and raccoon dogs. Results: CAV2232-41 showed the highest viral titer on days 4-6 post-inoculation and had a deletion in the E3 gene, which was confirmed as a CAdV-2 variant. Guinea pigs inoculated with CAV2232C showed slightly higher VNA titers than those inoculated with CAV2232R 2 weeks after booster vaccination. Raccoon dogs immunized with the CAV2232C vaccine developed high mean VNA titers, while non-vaccinated raccoon dogs were antibody-negative. Conclusion: The CAV2232C vaccine is safe and induces a protective VNA titer in raccoon dogs.

Choroidal thickening induced by pioglitazone in diabetic patients.

Purpose: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients. Methods: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroid vascular index. Patients were categorized into a high dose group if their pioglitazone dose was 30mg or more per day, and a low dose group if it was 15mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location. Results: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone in all subjects (6.70µm, 13.65µm, each). When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both the high (4.48µm, 0.84µm, each) and low dose groups (6.85µm, 21.45µm, each), with a greater change observed in low dose group (p<0.05, respectively). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00µm, 13.15µm, each) and nasal regions (6.43µm, 19.24µm, each), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53µm) (p<0.05, respectively). The largest increase in choroidal thickness was observed in the nasal side. Conclusion: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.