Scope and Anaphoric Links in Dynamic Discourse Representation Theory

PACLIC 23 / City University of Hong Kong / 3-5 December 200

Anti-amyloidogenic effect of menaquinone-7 on betaamyloid production and aggregation

Purpose: To investigate the beneficial effects of menaquinone-7 (MK-7), an isoform of vitamin K2, against beta-amyloid (Aβ) production and aggregation in Alzheimer's disease using in vitro assays. Methods: The cytotoxicity of MK-7 was determined by MTT assay. The amount of Aβ produced and secreted into the supernatant by APP-CHO cells treated with MK-7 was evaluated by ELISA. The expression of β-secretases and ADAM10, a representative α-secretase, was determined using western blot analysis. The production of sAPPβ and sAPPα fragments generated by β-secretases and αsecretase, respectively, were also determined by western blot analysis. The effect on Aβ aggregation was assessed using Thioflavin T (Th T) assay. Results: MK-7 (up to 75 nM) significantly decreased Aβ production in APP-CHO cells. This was accompanied by decreased expression of β-secretase and lower production of sAPPβ (p < 0.05). However, expression of ADAM10 and production of sAPPα were not significantly affected. In contrast, MK-7 significantly decreased Aβ aggregation in a dose-dependent manner (p < 0.05). Conclusion: MK-7 exerts anti-amyloidogenic effects via decreased production and lower aggregation of Aβ into oligomers and fibrils. Therefore, dietary supplementation with MK-7 may be beneficial for the prevention of Alzheimer’s disease

Photometric Properties of the Near-contact Binary GW Geminorum

New multiband CCD photometry is presented for the eclipsing binary GW Gem; the $RI$ light curves are the first ever compiled. Four new minimum timings have been determined. Our analysis of eclipse timings observed during the past 79 years indicates a continuous period increase at a fractional rate of +(1.2$\pm$0.1)$\times10^{-10}$, in excellent agreement with the value $+1.1\times10^{-10}$ calculated from the Wilson-Devinney binary code. The new light curves display an inverse O'Connell effect increasing toward longer wavelengths. Hot and cool spot models are developed to describe these variations but we prefer a cool spot on the secondary star. Our light-curve synthesis reveals that GW Gem is in a semi-detached, but near-contact, configuration. It appears to consist of a near-main-sequence primary star with a spectral type of about A7 and an evolved early K-type secondary star that completely fills its inner Roche lobe. Mass transfer from the secondary to the primary component is responsible for the observed secular period change.Comment: 20 pages, including 5 figures and 6 tables, accepted for publication in PAS

Immune microenvironment in ductal carcinoma in situ: a comparison with invasive carcinoma of the breast

Abstract Background The immune microenvironment in ductal carcinoma in situ (DCIS) and its significance are not well established. This study was conducted to evaluate the immune microenvironment of DCIS including the composition of tumor-infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells and to compare it with that of invasive breast cancer. Materials and methods A total of 671 cases including three different disease groups of pure DCIS, DCIS with microinvasion (DCIS-M), and invasive carcinoma were included in this study. CD4+, CD8+, and FOXP3+ TIL subsets and PD-L1+ immune cells were detected with immunohistochemistry using tissue microarrays and were analyzed in relation to clinicopathologic characteristics and different disease groups. Results In pure DCIS, high infiltrations of CD4+, CD8+, and FOXP3+ T cells and the presence of PD-L1+ immune cells were associated with high nuclear grade, comedo-type necrosis, hormone receptor (HR) negativity, and high Ki-67 proliferation index. All immune cell infiltrations were higher in invasive carcinoma than in pure DCIS regardless of the HR status. While CD4+ T cells were more abundant than CD8+ T cells in pure DCIS, CD8+ T cells were dominant in invasive carcinoma, especially in HR-negative tumors. Within individual cases of invasive carcinoma with DCIS component, all immune cell subset infiltration was higher in the invasive component than in the DCIS component; however, CD4+ TIL infiltration did not differ between the two components in HR-negative tumors. Comparing pure DCIS, DCIS-M, and DCIS associated with invasive carcinoma (DCIS-INV), CD4+ TIL infiltration revealed a gradual increase from pure DCIS to DCIS-M and DCIS-INV in the HR-negative group, whereas FOXP3+ TIL infiltration was significantly increased in DCIS-INV than in pure DCIS in the HR-positive group. The high infiltration of FOXP3+ TIL and the presence of PD-L1+ immune cells were associated with tumor recurrence in patients with pure DCIS. Conclusions Our study showed that the immune microenvironment differs significantly not only between DCIS and invasive carcinoma but also between pure DCIS, DCIS-M, and DCIS-INV depending on the HR status

Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes

This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes

Multiple Fibromas of Tendon Sheath: Unusual Presentation

Fibroma of the tendon sheath is an uncommon soft tissue tumor presenting as a solitary, slow-growing, firm, painless, small nodule, which shows strong attachment to the tendon or tendon sheath. It is usually localized on fingers and hand tendons in adults between the age of 20 and 40 years old. This case concerns a 61-year-old man presenting with a 5-year history of multiple cutaneous nodules on both palms and soles. Skin biopsy confirmed fibroma of the tendon sheath. Blood tests showed a high titer of rheumatoid factor and positivity to anti-nuclear antibody. No case of fibroma of the tendon sheath occurring multifocally on both palms and soles has been previously reported. Herein, we report on a very rare case of multiple fibromas of the tendon sheath arising from palms and soles, which supports the pathogenetic hypothesis that this tumor may be a reactive process rather than a true neoplasm

Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway

Non-alcoholic Fatty Liver Disease and the Risk of Incident Atrial Fibrillation in Young Adults:A Nationwide Population-Based Cohort Study

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease including cardiovascular. However, the association between NAFLD and the risk of incident atrial fibrillation (AF), especially in young adults, remains unclear. We aimed to evaluate the association between NAFLD as assessed by the fatty liver index (FLI) and the risk of AF in young adults. METHODS: We identified individuals aged 20–39 years who underwent health examinations conducted by the Korean National Health Insurance Corporation between January 2009 and December 2012. Individuals with significant liver disease, heavy alcohol consumption, or prevalent AF were excluded. We categorized based on FLI: <30, 30 to <60, and ≥60. Incident AF was evaluated as the primary outcome. RESULTS: We included 5,333,907 subjects (mean age, 31 ± 5 years; men, 57%). During a mean follow-up of 7.4 ± 1.1 years, 12,096 patients had newly diagnosed AF (incidence rate 0.31 per 1,000 person-years). After adjustment, subjects with FLI 30 to <60 and FLI ≥60 showed a higher risk of AF compared to those with FLI <30 (hazard ratio [HR] 1.21, 95% confidence interval [CI, 1.15–1.27] and HR 1.47, 95% CI [1.39–1.55], p < 0.001, respectively). In women, the increased AF risk was accentuated in the higher FLI group than in the individuals with FLI <30, compared with men (p-for-interaction = 0.023). A higher incident AF risk in the higher FLI groups was consistently observed in various subgroups. CONCLUSION: Among young adults, NAFLD assessed using FLI was positively correlated with the AF risk. These findings support the evidence of AF screening in young adults with high FLI scores

Habitual Alcohol Intake and Risk of Atrial Fibrillation in Young Adults in Korea

IMPORTANCE: Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. OBJECTIVE: To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. DESIGN, SETTING, AND PARTICIPANTS: Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (<105 g per week), moderate (105-210 g per week), and heavy (≥210 g per week) drinking, respectively. Data were analyzed from May to June 2021. EXPOSURE: Amount of alcohol intake in 4 years. MAIN OUTCOMES AND MEASURES: The primary outcome was incident atrial fibrillation during the follow-up period. RESULTS: A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-to-mild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47, CI 1.18-1.83). CONCLUSIONS AND RELEVANCE: Persistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years