Type I interferon alters invasive extravillous trophoblast function.

Inappropriate type I interferon (IFN) signaling during embryo implantation and placentation is linked to poor pregnancy outcomes. Here, we evaluated the consequence of elevated type I IFN exposure on implantation using a biomimetic model of human implantation in an organ-on-a-chip device. We found that type I IFN reduced extravillous trophoblast (EVT) invasion capacity. Analyzing single-cell transcriptomes, we uncovered that IFN truncated endovascular EVT emergence in the implantation-on-a-chip device by stunting EVT epithelial-to-mesenchymal transition. Disruptions to the epithelial-to-mesenchymal transition is associated with the pathogenesis of preeclampsia, a life-threatening hypertensive disorder of pregnancy. Strikingly, unwarranted IFN stimulation induced genes associated with increased preeclampsia risk and a preeclamptic gene-like signature in EVTs. These dysregulated EVT phenotypes ultimately reduced EVT-mediated endothelial cell vascular remodeling in the implantation-on-a-chip device. Overall, our work indicates IFN signaling can alter EVT epithelial-to-mesenchymal transition progression which results in diminished EVT-mediated spiral artery remodeling and a preeclampsia gene signature upon sustained stimulation. Our work implicates unwarranted type I IFN as a maternal disturbance that can result in abnormal EVT function that could trigger preeclampsia.

The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model.

BACKGROUND: Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture. OBJECTIVES: We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site. METHODS: The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants. The groups included implant only (n = 10); implant plus bacterial inoculation (n = 14); implant, bacterial inoculation, and patch loaded with gentamycin placed on the ventral side of the implant (n = 10), and implant, bacterial inoculation, and patch loaded with gentamycin and triamcinolone acetonide (n = 9). Histologic and immunohistochemical analyses were performed 8 weeks after implantation. RESULTS: The 2 drugs were sequentially released from the dual drug-releasing patch and exhibited different release profiles. Compared to the animals with bacterial inoculation, those with the antibiotic-only and the dual drug-releasing patch exhibited thinner capsules and lower myofibroblast activity and inflammation, indicating better tissue integration and less foreign body response. These effects were more pronounced with the dual drug-releasing patch than with the antibiotic-only patch. CONCLUSIONS: The 3D-printed dual drug-releasing patch effectively reduced inflammation and capsule formation in a rat model of silicone breast reconstruction. The beneficial effect of the dual drug-releasing patch was better than that of the antibiotic-only patch, indicating its therapeutic potential as a novel approach to preventing capsular contracture while reducing concerns of systemic side effects.

The ability of the geriatric nutritional risk index to predict the risk of heart diseases in Korean adults: a Korean Genome and Epidemiology Study cohort.

Introduction: The predictive ability of nutritional risk index on cardiovascular outcomes in middle-aged and non-hospitalized adults has not yet been reported. This study investigated whether the Geriatric Nutritional Risk Index (GNRI), an index for assessing the risk of developing malnutrition, could predict heart disease in middle-aged Korean adults. Methods: The cohort used in this study consisted of 3,783 participants selected from 10,030 Korean adults who participated in the Ansan-Ansung cohort study as part of the Korean Genome and Epidemiology Study. The GNRI was determined based on serum albumin level, proportion of current weight, and ideal body weight. Participants were then divided into two groups: GNRI ≤98 and > 98, which corresponded to the risk of malnutrition and normal, respectively. The major outcome of this study was coronary artery disease (CAD) or congestive heart failure (CHF) during a 15-year-follow period. Results: During the follow-up period spanning 2004-2018, 136 events of heart disease occurred. Using a Kaplan-Meier analysis, event-free rates were found to be associated with 90.5% on a GNRI ≤98 and 96.6% on a GNRI >98 (p < 0.0009). GNRI ≤98 showed a 3.2-fold (hazard ratio, 3.22; 95% credit interval, 1.49-6.96; p = 0.0029) increase in the incidence of heart disease, including CAD or CHF, compared with GNRI >98, after controlling for potential confounders. Conclusion: Malnutrition risk confers a significantly increased risk for heart disease in middle-aged Koreans. Further studies with larger cohorts are needed to verify the efficacy of the GNRI in predicting disease risk in adults with pre-disease.

Impact of emotional state and suicidal intentions on suicide attempts among Korean adolescents with household financial difficulties following the outbreak of COVID-19: A cross-sectional study.

The recent prolonged coronavirus disease-2019 pandemic has brought an economic crisis to various households, leading to negative mental health such as depression, anxiety, traumatic distress, and suicide risk among adolescents. Adolescents with household financial difficulties due to the coronavirus disease-2019 pandemic show high suicidal tendencies and attempts such as suicidal ideation and plans, their suicidal ideation and plans increase the risk of suicide attempts in South Korea. The purpose of this study was to determine the effects of emotional state and suicidal tendencies on suicide attempts among adolescents with household financial difficulties in early pandemic. This was a secondary data analysis study using statistical data from the 16th (2020) Korea Youth Risk Behavior Web-based Survey. Among 54,948 who participated in the survey, 16,839 (30.6%) adolescents who had household financial difficulties were included in final analysis. Descriptive statistics, chi-squared test, and logistic regression analysis were conducted to analyze data. The strengthening the reporting of observational studies in epidemiology checklist was used for reporting this study. 16,839 adolescents (mean age 15.68 ± 1.76 years; 8709, 51.7% male) who experienced household financial difficulties in the prior year revealed 3 percent (508) had attempted suicide. Suicide attempts differed according to several characteristics and were significantly associated with sex, residence type, drinking experience, depressive mood, perceived happiness, suicidal ideation, and suicide planning. The findings indicate high-risk adolescents with household financial difficulties need a multi-dimensional safety network, suicide screening, and emotional interventions during the pandemic.

Synthesis of 1-(4-(dimethylamino)phenyl)-3,4-diphenyl-1H-pyrrole-2,5-dione analogues and their anti-inflammatory activities in lipopolysaccharide-induced BV2 cells.

A series of thalidomide analogues, where the fused benzene ring in the phthalimide moiety was converted into two separated diphenyl rings in maleimide moiety and N-aminoglutarimide moiety was replaced by substituted phenyl moiety, were synthesized and evaluated for their NO inhibitory activities on BV2 cells stimulated with lipopolysaccharide (LPS). Among the synthesized compounds, the dimethylaminophenyl analogue 1s (IC50 = 7.1 µM) showed significantly higher inhibitory activity than the glutarimide analogue 1a (IC50 > 50 µM) and suppressed NO production dose-dependently without cytotoxicity. In addition, 1s inhibited the production of pro-inflammatory cytokines and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by blocking nuclear factor-kappa B (NF-κB) and p38 MAPK pathways. These results demonstrated that 1s showed good anti-inflammatory activity and could become a leading compound for the treatment of neuroinflammatory diseases.

AD-1 Small Molecule Improves Learning and Memory Function in Scopolamine-Induced Amnesic Mice Model through Regulation of CREB/BDNF and NF-κB/MAPK Signaling Pathway.

Cognitive decline and memory impairment induced by oxidative brain damage are the critical pathological hallmarks of Alzheimer's disease (AD). Based on the potential neuroprotective effects of AD-1 small molecule, we here explored the possible underlying mechanisms of the protective effect of AD-1 small molecule against scopolamine-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, scopolamine administration resulted in increased AChE activity, MDA levels, and decreased antioxidant enzymes, as well as the downregulation of the antioxidant response proteins of Nrf2 and HO-1 expression; however, treatment with AD-1 small molecule mitigated the generation of oxidant factors while restoring the antioxidant enzymes status, in addition to improving antioxidant protein levels. Similarly, AD-1 small molecule significantly increased the protein expression of neuroprotective markers such as BDNF and CREB and promoted memory processes in scopolamine-induced mice. Western blot analysis showed that AD-1 small molecule reduced activated microglia and astrocytes via the attenuation of iba-1 and GFAP protein expression. We also found that scopolamine enhanced the phosphorylation of NF-κB/MAPK signaling and, conversely, that AD-1 small molecule significantly inhibited the phosphorylation of NF-κB/MAPK signaling in the brain regions of hippocampus and cortex. We further found that scopolamine promoted neuronal loss by inducing Bax and caspase-3 and reducing the levels of the antiapoptotic protein Bcl-2. In contrast, AD-1 small molecule significantly decreased the levels of apoptotic markers and increased neuronal survival. Furthermore, AD-1 small molecule ameliorated scopolamine-induced impairments in spatial learning behavior and memory formation. These findings revealed that AD-1 small molecule attenuated scopolamine-induced cognitive and memory dysfunction by ameliorating AChE activity, oxidative brain damage, neuroinflammation, and neuronal apoptosis.

Effect of bacterial resistant zwitterionic derivative incorporation on the physical properties of resin-modified glass ionomer luting cement.

Biofilms induce microbial-mediated surface roughening and deterioration of cement. In this study, zwitterionic derivatives (ZD) of sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethyl phosphorylcholine, were added in concentrations of 0, 1, and 3% to three different types of commercially available resin-modified glass ionomer cement (RMGIC) (RMC-I: RelyX Luting 2, RMC-II: Nexus RMGI, and RMC-III: GC FujiCEM 2). The unmodified RMGICs served as the control group for comparison. The resistance of Streptococcus mutans to ZD-modified RMGIC was evaluated with a monoculture biofilm assay. The following physical properties of the ZD-modified RMGIC were assessed: wettability, film thickness, flexural strength, elastic modulus, shear bond strength, and failure mode. The ZD-modified RMGIC significantly inhibited biofilm formation, with at least a 30% reduction compared to the control group. The addition of ZD improved the wettability of RMGIC; however, only 3% of the SBMA group was statistically different (P < 0.05). The film thickness increased in proportion to the increasing ZD concentrations; there was no statistical difference within the RMC-I (P > 0.05). The experimental groups' flexural strength, elastic modulus, and shear bond strength showed an insignificant decrease from the control group; there was no statistical difference within the RMC-I (P > 0.05). The mode of failure differed slightly in each group, but all groups showed dominance in the adhesive and mixed failure. Thus, the addition of 1 wt.% ZD in RMGIC favorably enhanced the resistance to Streptococcus mutans without any tangible loss in flexural and shear bond strength.

Vascular Cast to Program Antistenotic Hemodynamics and Remodeling of Vein Graft.

The structural stability of medical devices is established by managing stress distribution in response to organ movement. Veins abruptly dilate upon arterial grafting due to the mismatched tissue property, resulting in flow disturbances and consequently stenosis. Vascular cast is designed to wrap the vein-artery grafts, thereby adjusting the diameter and property mismatches by relying on the elastic fixity. Here, a small bridge connection in the cast structure serves as an essential element to prevent stress concentrations due to the improved elastic fixity. Consequently, the vein dilation is efficiently suppressed, healthy (laminar and helical) flow is induced effectively, and the heathy functions of vein grafting are promoted, as indicated by the flow directional alignment of endothelial cells with arterialization, muscle expansion, and improved contractility. Finally, collaborative effects of the bridge drastically suppress stenosis with patency improvement. As a key technical point, the advantages of the bridge addition are validated via the computational modeling of fluid-structure interaction, followed by a customized ex vivo set-up and analyses. The calculated effects are verified using a series of cell, rat, and canine models towards translation. The bridge acted like "Little Dutch boy" who saved the big mass using one finger by supporting the cast function.

Urine Cytology Rarely Escalates Clinical Management in the Surveillance of Non-muscle-Invasive Bladder Cancer.

INTRODUCTION: The use of urine cytology in the surveillance of non-muscle invasive bladder cancer (NMIBC) is widely variable in clinical practice. We studied the impact of surveillance urine cytology on clinical decision making during NMIBC surveillance. METHODS: A retrospective chart review was conducted on patients surveilled for clinical NMIBC from 2013 to 2020 with at least one follow-up cytology result after diagnosis. Patients were classified into risk categories according to American Urological Association (AUA) NMIBC guidelines. Data were obtained regarding tumor recurrence pathology and the frequency and findings of surveillance cystoscopies and urine cytologies. Positive (suspicious, malignant) and negative (atypical or negative for malignant cells) cytology results were correlated with cystoscopy and pathology findings when obtained within 3 months of the cytology specimen to determine if cytology impacted plan of care. RESULTS: Two hundred fourteen patients with NMIBC were followed for a median of 34 months, with 1045 urine cytologies collectively obtained over the surveillance period. There were no positive urine cytologies among patients with low-risk NMIBC; therefore, cytology did not change management in this cohort. The potential for cytology to escalate management for patients of any risk group (ie, positive cytology in the absence of positive cystoscopy or pathology findings) occurred in 30 (2.9%) cases. However, clinical decision making was only altered in 4 cases (0.4% of all cytologies). CONCLUSIONS: Less than 1% of urine cytology specimens collected during NMIBC surveillance impacted clinical management, none of whom had low-risk disease. The use of urine cytology for surveillance of low-risk NMIBC should continue to be strongly discouraged, as it did not change management in any such cases.

Synthesis of 1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-2-morpholinoethane-1,2-dione analogues and their inhibitory activities with reduced cytotoxicity in lipopolysaccharide-induced BV2 cells.

A series of rimonabant analogues, where the N-aminopiperidine moiety was replaced by various amines and an additional carbonyl group, were synthesized and their inhibition of nitric oxide (NO) production was evaluated in lipopolysaccharide (LPS)-induced BV2 microglial cells. Among the synthesized compounds, the morpholine analogue 7y (IC50 = 4.71 ±â€¯0.11 µM) showed significantly higher inhibitory activity than rimonabant (IC50 = 16.17 ±â€¯0.56 µM), and suppressed NO production dose-dependently without cytotoxicity. In addition, 7y inhibited the expression of iNOS, COX-2 and pro-inflammatory cytokines and attenuated LPS-induced activation of nuclear factor-kappa B (NF-κB) and ERK MAPK phosphorylation in BV2 cells. These results demonstrated that 7y exerted anti-inflammatory effects by ERK pathway in BV2 cells, which can be used for the prevention and treatment of neuroinflammatory diseases.

Relationship between Androgen Deprivation Therapy and Normal-Tension Glaucoma in Patients with Prostate Cancer: A Nationwide Cohort Study.

PURPOSE: This study assessed the relationship between newly developed normal-tension glaucoma (NTG) and androgen deprivation therapy (ADT) in patients with prostate cancer. MATERIALS AND METHODS: A retrospective population-based cohort study was performed. During the period between 2008 and 2017, a total of 218203 prostate cancer patients were identified in a nationwide claims database in the Republic of Korea. The final analysis included 170874 patients (42909 in the ADT group, 127965 in the control group) after applying the inclusion and exclusion criteria. The incidences of NTG according to ADT duration were compared with controls. Exact matching was conducted to adjust comorbidities between cohorts. Cox proportional hazard regression models were performed after controlling for latent confounding factors, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of NTG according to ADT were obtained. RESULTS: In the matched cohort, the ADT group was associated with a significantly reduced risk of NTG in multivariable analysis compared to the control group. The risk of NTG decreased in patients who underwent ADT for less than 2 years (HR=0.824; 95% CI, 0.682-0.995; p=0.0440) and in those using ADT over 2 years (HR=0.796; 95% CI, 0.678-0.934; p=0.0051), compared to the controls. CONCLUSION: Medical castrations for patients with prostate cancer results in a lower incidence of newly diagnosed NTG compared to no ADT. These findings suggest that testosterone may be involved in the pathogenesis of NTG.

Multiresponsive Polymer Nanocomposite Liquid Crystals Having Heterogeneous Phase Transitions for Battery-Free Temperature Maintenance Indicators.

Multiresponsive functional materials that respond to more than one external stimulus are promising for novel photonic, electronic, and biomedical applications. However, the design or synthesis of new multiresponsive materials is challenging. Here, this work reports a facile method to prepare a multiresponsive colloidal material by mixing a liquid-crystalline 2D nanocolloid and a functional polymer colloid. For this purpose, electrically sensitive exfoliated α-ZrP 2D nanocolloids and thermosensitive block copolymer colloids that are dispersed well in water are mixed. In the liquid-crystalline nanocomposite, nematic, antinematic, or isotropic assemblies of α-ZrP, nanoparticles can be electrically and selectively obtained by applying electric fields with different frequencies; furthermore, their rheology is thermally and reversibly controlled through thesol-gel-sol transition. The nanocomposite exhibits a solid gel phase within a predesigned gel temperature range and a liquid sol phase outside this range. These properties facilitate the design of a simple display device in which information can be electrically written and thermally stabilized or erased, and using the device, a battery-free temperature maintenance indication function is demonstrated. The proposed polymer nanocomposite method can enrich the physical properties of 2D nanocolloidal liquid crystals and create new opportunities for eco-friendly, reusable, battery-free electro-optical devices.

Factors influencing suicidal tendencies during COVID-19 pandemic in Korean multicultural adolescents: a cross-sectional study.

BACKGROUND: There is concern that the COVID-19 pandemic has had a negative impact on the psychological wellbeing of many populations, including increase of fear, anxiety, and uncertainty. Since the start of the COVID-19 pandemic, adolescents specifically have experienced direct and indirect impacts on their mentally, resulting in severe depression, self-harm and suicide. This study aimed to identify factors influencing suicidal tendencies and the mental health status of multicultural adolescents in Korea during the COVID-19 pandemic. METHODS: This cross-sectional study was conducted with 784 multicultural adolescents (Korean fathers and foreign mothers) who participated in the 16th national Korean Youth Risk Behaviour online survey. Research variables were measured using self-reported questionnaires for mental health and suicidal tendencies. Data was analysed using SPSS 26.0 program. RESULTS: The factors influencing suicidal tendencies (contemplating suicide, suicidal plans, and suicide attempts) were sexual intercourse experience (adjusted odds ratio [aOR], 7.67, 5.04, 7.10), depressive mood (aOR 1.03, 0.98, 0.97, 0.90), and unhappiness (aOR 13.00, 7.28, 5.56). CONCLUSIONS: In conclusion, the factors that affect suicidal tendencies showed sexual intercourse experience, depressive mood and unhappiness. Screening for suicidal tendencies and suicide prevention programs that consider the significant factors that affect suicidal tendencies should be developed for multicultural adolescents. School health professions and mental health counselors at schools need to emphasize the mental health and psychosocial support needs of senior high school students.

Proton Pump Inhibitors and Risk of Cardiovascular Disease: A Self-Controlled Case Series Study.

INTRODUCTION: We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control. METHODS: We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables. RESULTS: In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome. DISCUSSION: Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

Factors influencing nursing students' participatory behaviour during COVID-19.

Background: Because nursing students are important human resources for future public health, their participatory behaviours related to preventive health during a pandemic were explored. Aim: This study examines the impact of nursing students' risk communication, anxiety, and their perception of risk on their participatory behaviour during COVID-19. Methods: Data were collected from 180 South Korean nursing students in six provinces via an online survey and were analysed using independent t-test, ANOVA, Pearson's correlation coefficient, and multiple regression. The SPSS WIN 25.0 program was employed. Findings: Perceiving information to influence oneself was a significant predictor of each participatory behaviour. Risk communication was not identified as a factor influencing health-related participatory behaviour. However, the influence of information is a concept derived from risk communication. Discussion: Risk communication for behaviour change needs to be designed so that communication targets recognise the impact of risk. Promoting pro-social behaviour in the nursing curriculum is important because it will make the students more sensitive to information that can have a dangerous impact on others. Conclusion: It is important to create health-related risk communications by considering the perspective of perception of influence.

A microphysiological model of human trophoblast invasion during implantation.

Successful establishment of pregnancy requires adhesion of an embryo to the endometrium and subsequent invasion into the maternal tissue. Abnormalities in this critical process of implantation and placentation lead to many pregnancy complications. Here we present a microenigneered system to model a complex sequence of orchestrated multicellular events that plays an essential role in early pregnancy. Our implantation-on-a-chip is capable of reconstructing the three-dimensional structural organization of the maternal-fetal interface to model the invasion of specialized fetal extravillous trophoblasts into the maternal uterus. Using primary human cells isolated from clinical specimens, we demonstrate in vivo-like directional migration of extravillous trophoblasts towards a microengineered maternal vessel and their interactions with the endothelium necessary for vascular remodeling. Through parametric variation of the cellular microenvironment and proteomic analysis of microengineered tissues, we show the important role of decidualized stromal cells as a regulator of extravillous trophoblast migration. Furthermore, our study reveals previously unknown effects of pre-implantation maternal immune cells on extravillous trophoblast invasion. This work represents a significant advance in our ability to model early human pregnancy, and may enable the development of advanced in vitro platforms for basic and clinical research of human reproduction.

Piperine and Its Metabolite's Pharmacology in Neurodegenerative and Neurological Diseases.

Piperine (PIP) is an active alkaloid of black and long peppers. An increasing amount of evidence is suggesting that PIP and its metabolite's could be a potential therapeutic to intervene different disease conditions including chronic inflammation, cardiac and hepatic diseases, neurodegenerative diseases, and cancer. In addition, the omnipresence of PIP in food and beverages made this compound an important investigational material. It has now become essential to understand PIP pharmacology and toxicology to determine its merits and demerits, especially its effect on the central nervous system (CNS). Although several earlier reports documented that PIP has poor pharmacokinetic properties, such as absorption, bioavailability, and blood-brain barrier permeability. However, its interaction with metabolic enzyme cytochrome P450 superfamily and competitive hydrophobic interaction at Monoamine oxide B (MAO-B) active site have made PIP both a xenobiotics bioenhancer and a potential MAO-B inhibitor. Moreover, recent advancements in pharmaceutical technology have overcome several of PIP's limitations, including bioavailability and blood-brain barrier permeability, even at low doses. Contrarily, the structure activity relationship (SAR) study of PIP suggesting that its several metabolites are reactive and plausibly responsible for acute toxicity or have pharmacological potentiality. Considering the importance of PIP and its metabolites as an emerging drug target, this study aims to combine the current knowledge of PIP pharmacology and biochemistry with neurodegenerative and neurological disease therapy.

Androgen Deprivation Therapy in Patients with Prostate Cancer is Associated with the Risk of Subsequent Alzheimer's Disease but Not with Vascular Dementia.

PURPOSE: We aimed to investigate the association between androgen deprivation therapy (ADT) and the risk of dementia according to subtypes of dementia in men with prostate cancer. MATERIALS AND METHODS: We performed a nationwide population-based cohort study using the nationwide claims database in Korea. A total of 195,308 men with newly diagnosed prostate cancer were identified between January 2008 and December 2017, and 132,700 men were selected for analysis after applying inclusion and exclusion criteria. The patients were divided into ADT and non-ADT groups. To adjust for imbalances in relevant comorbidities between the groups, exact matching was performed. Study events included newly developed Alzheimer's disease, vascular dementia, and overall dementia. Cox proportional hazard regression models were used. RESULTS: After exact matching, 44,854 men with prostate cancer were selected for the main analysis. In age-adjusted Cox regression analysis, the ADT group was significantly associated with increased risks for overall dementia (hazard ratio [HR], 1.070; 95% confidence interval [CI], 1.009-1.134; p=0.0232) and Alzheimer's disease (HR, 1.086; 95% CI, 1.018-1.160; p=0.0127), compared to the non-ADT group. No difference in vascular dementia risk was observed between the two groups (HR, 0.990; 95% CI, 0.870-1.126; p=0.8792). CONCLUSIONS: The risk of overall dementia increased in men who received ADT. According to dementia subtypes, ADT was associated with an increased risk of Alzheimer's disease, but not with vascular dementia.

Risk of cardiovascular intervention after androgen deprivation therapy in prostate cancer patients with a prior history of ischemic cardiovascular and cerebrovascular disease: A nationwide population-based cohort study.

BACKGROUND: Androgen deprivation therapy for prostate cancer is known to increase the risk of cardiovascular disease, but there is controversy regarding the cardiovascular risk in patients with preexisting cardiovascular disease. This study assessed the risk of cardiovascular intervention after androgen deprivation therapy in patients with a history of cardiovascular disease, cerebrovascular disease, and cardiovascular intervention. MATERIALS AND METHODS: Between 2008 and 2017, 195,308 men with newly diagnosed prostate cancer were identified from the nationwide claims database in South Korea. Among them, 49,090 men with a history of ischemic cardiovascular and cerebrovascular diseases were analyzed. The patients were divided into the androgen deprivation therapy (n = 14,092) and non-androgen deprivation therapy (n = 34,988) groups. The primary outcome was cardiovascular interventions (percutaneous transluminal angioplasty and coronary bypass surgery). Cox proportional hazard regression models were used to estimate the adjusted hazard ratios and 95% confidence intervals of the events. RESULTS: After balancing the covariates with 1:1 exact matching, the two groups had 10,514 subjects each. Multivariable analysis demonstrated that androgen deprivation therapy was not significantly associated with an increased risk of cardiovascular interventions (hazard ratio, 1.060; 95% confidence interval, 0.923-1.217; P = 0.4104), regardless of the duration of therapy. A history of cardiovascular intervention, diabetes mellitus, antithrombotic medication use, and cardiovascular events significantly increased the risk of cardiovascular intervention. CONCLUSIONS: Androgen deprivation therapy was not associated with cardiovascular intervention in patients with a previous history of cardiovascular disease, regardless of the duration of therapy. Therefore, the cardiovascular risk of androgen deprivation therapy should be reassessed in this population.

A rice gene encoding glycosyl hydrolase plays contrasting roles in immunity depending on the type of pathogens.

Because pathogens use diverse infection strategies, plants cannot use one-size-fits-all defence and modulate defence responses based on the nature of pathogens and pathogenicity mechanism. Here, we report that a rice glycoside hydrolase (GH) plays contrasting roles in defence depending on whether a pathogen is hemibiotrophic or necrotrophic. The Arabidopsis thaliana MORE1 (Magnaporthe oryzae resistance 1) gene, encoding a member of the GH10 family, is needed for resistance against M. oryzae and Alternaria brassicicola, a fungal pathogen infecting A. thaliana as a necrotroph. Among 13 rice genes homologous to MORE1, 11 genes were induced during the biotrophic or necrotrophic stage of infection by M. oryzae. CRISPR/Cas9-assisted disruption of one of them (OsMORE1a) enhanced resistance against hemibiotrophic pathogens M. oryzae and Xanthomonas oryzae pv. oryzae but increased susceptibility to Cochliobolus miyabeanus, a necrotrophic fungus, suggesting that OsMORE1a acts as a double-edged sword depending on the mode of infection (hemibiotrophic vs. necrotrophic). We characterized molecular and cellular changes caused by the loss of MORE1 and OsMORE1a to understand how these genes participate in modulating defence responses. Although the underlying mechanism of action remains unknown, both genes appear to affect the expression of many defence-related genes. Expression patterns of the GH10 family genes in A. thaliana and rice suggest that other members also participate in pathogen defence.