Association between dry eye and periodontal disease in community-dwelling Japanese adults: data from the Uonoma cohort study.

BACKGROUND: While research has explored the risk of periodontal disease in various eye conditions, the link between dry eye and periodontal disease remains underexplored, especially in Japanese adults. This study aims to investigate the association between dry eye and periodontal disease in community-dwelling Japanese adults. METHODS: This study is a subset of the Uonuma cohort study, which includes Japanese adults aged 40 years and older residing in the Uonuma area of Niigata Prefecture, Japan. Participants completed a self-administered, paper-based questionnaire. Statistical analyses, including the chi-square test, independent t test, ANOVA test, and logistic regressions, were employed to assess the association of periodontal disease with independent variables. RESULTS: Among 36,488 participants (average age 63.3 years, 47.4% men), 39.3% had a history of periodontal disease, and gender differences were statistically significant (p < 0.001). Significant associations were found between periodontal disease and dry eye diagnosis or symptoms. Univariable logistic regression revealed links between periodontal disease and age, gender, living status, alcohol consumption, remaining teeth, bite molar availability, and history of dry eye disease or symptoms. Multiple-adjusted regression found that doctor-diagnosed dry eye was associated with a higher likelihood of periodontal disease (odds ratio, 1.12; 95% confidence interval, 1.03-1.22). Participants who never experienced dryness or foreign body sensation had lower ORs of periodontal disease than those who always experienced such symptoms across all models. CONCLUSION: A significant correlation was found between dry eye and periodontal disease in Japanese adults. Regular check-ups, early detection, and effective management of both conditions are strongly recommended.

[A case in which endoscopic ultrasound-guided transrectal drainage was effective for pelvic abscess].

The patient, a 33-year-old female, presented to her local doctor with lower abdominal pain. She was referred to our hospital for a plain CT scan, which revealed signs of ileitis. Because acute appendicitis could not be ruled out, the patient was hospitalized. On the third day of hospitalization, she underwent laparoscopic appendicectomy for perforated appendicitis. However, the inflammatory response persisted despite continued antibacterial treatment; we diagnosed this to be due to the formation of a postoperative residual abscess. Since drainage of the abscess was deemed necessary, the patient underwent EUS-guided transrectal drainage on the 26th day of hospitalization. The patient had a favorable postoperative course and was discharged on the 31st day of hospitalization. Along with some literature review, this report details a case in which transrectal drainage under ultrasound endoscopy was effective in treating a pelvic abscess. We report a case of a pelvic abscess that was drained through the rectum under EUS guidance and an internal and external fistula tube was placed. The abscess resolved without complications.

Which modality is better to diagnose high-grade transformation in retroperitoneal liposarcoma? Comparison of computed tomography, positron emission tomography, and magnetic resonance imaging.

BACKGROUND: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. METHODS: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). RESULTS: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775-0.984; p < 0.001), maximum standardized uptake value (SUVmax) of 2.9 (AUC = 0.865 95% CI 0.792-0.980; p < 0.001), while MRI failed to differentiate DDLS. The cutoff values for distinguishing FNCLCC grades 1 and 2/3 were a mean CT value of 24 HU (AUC = 0.858, 95% CI 0.731-0.985; p < 0.001) and SUVmax of 2.9 (AUC = 0.885, 95% CI 0.792-0.978; p < 0.001). MRI had no sufficient power to separate these grades. CONCLUSIONS: Contrast-enhanced CT and PET were useful for predicting DDLS and FNCLCC grade 2/3, while MRI was inferior to these two modalities.

Subpolar marginal seas fuel the North Pacific through the intermediate water at the termination of the global ocean circulation.

The mechanism by which nutrients in the deep ocean are uplifted to maintain nutrient-rich surface waters in the subarctic Pacific has not been properly described. The iron (Fe) supply processes that control biological production in the nutrient-rich waters are also still under debate. Here, we report the processes that determine the chemical properties of intermediate water and the uplift of Fe and nutrients to the main thermocline, which eventually maintains surface biological productivity. Extremely nutrient-rich water is pooled in intermediate water (26.8 to 27.6 σθ) in the western subarctic area, especially in the Bering Sea basin. Increases of two to four orders in the upward turbulent fluxes of nutrients were observed around the marginal sea island chains, indicating that nutrients are uplifted to the surface and are returned to the subarctic intermediate nutrient pool as sinking particles through the biological production and microbial degradation of organic substances. This nutrient circulation coupled with the dissolved Fe in upper-intermediate water (26.6 to 27.0 σθ) derived from the Okhotsk Sea evidently constructs an area that has one of the largest biological CO2 drawdowns in the world ocean. These results highlight the pivotal roles of the marginal seas and the formation of intermediate water at the end of the ocean conveyor belt.

Oral Health and Nutritional Intake in Community-Dwelling 90-Year-Old Japanese People: A Cross-Sectional Study.

INTRODUCTION: This study aimed to determine the relationship between dentition, mastication, salivation and nutritional intake in 90-year-old Japanese people. METHODS: This cross-sectional study included 84 participants (39 men and 45 women) aged 90 years. We used questionnaires to collect demographic information, smoking status, nutritional intake and higher-level functional capacity. Nutritional intake was assessed using the validated Brief-Type Self-Administered Diet History Questionnaire, and higher-level functional capacity was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) questionnaire. Oral examinations, masticatory performance tests, stimulated salivary flow rate (SSF) tests, blood tests, blood pressure tests and body mass index (BMI) assessments were conducted. Univariable and multivariable linear regression analyses were performed. RESULTS: Multivariable linear regression analyses adjusted for sex, education, TMIG-IC and BMI ≤20 kg/m2 showed that participants with masticatory performance <173 mg/dL had lower intake of folic acid and vitamin A than those with masticatory performance ≥173 mg/dL. SSF was positively associated with intake of vitamin A. The number of teeth was positively associated with the intake of ß-carotene. With smaller effect sizes, masticatory performance, SSF and number of teeth were also associated with the intake of various micronutrients and carbohydrates. CONCLUSION: Lower masticatory performance, lower SSF and fewer teeth were associated with a lower intake of several micronutrients, such as vitamin A, ß-carotene and folic acids, in Japanese individuals of advanced age. Oral health practitioners should pay careful attention to the nutritional intake of older people with poor mastication, dry mouth and severe tooth loss.

Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01).

OBJECTIVE: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. SUMMARY OF BACKGROUND DATA: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. METHODS: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. RESULTS: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. CONCLUSIONS: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.

Ultrafast time-resolved single-shot birefringence microscopy for laser-induced anisotropy.

The interaction between ultrashort laser pulses and materials in the ultrafast time domain, especially regarding the effect of laser polarization, has attracted much attention. In this study, ultrafast time-resolved single-shot birefringence microscopy is performed to observe laser-induced anisotropy. The birefringences of the optical Kerr effect and laser-induced anisotropic nanostructures by femtosecond laser pulses in silica glass are measured, and their slow axis is confirmed to correspond to the linear polarization angle of the pump light. We discuss the time variations of these birefringences in the picosecond time domain.

Interaction between serum vitamin C levels and smoking on the periodontal condition in older adults.

BACKGROUND AND OBJECTIVES: Several epidemiological studies have reported that smokers have a higher prevalence and severity of periodontal disease than do nonsmokers, and that smoking negatively affects nutritional status and is associated with a reduced intake of antioxidants, particularly vitamin C. The present investigation aimed to examine the relationship between serum vitamin C levels and smoking and its influence on the periodontal condition in older adults. MATERIALS AND METHODS: A total of 353 respondents met the inclusion criteria and were enrolled in the present study. The periodontal status of the study participants was determined through examinations of one or more residual teeth, which included a measurement of the probing pocket depth (PPD) and clinical attachment level (CAL) at six regions of each tooth. Blood samples were collected during the dental examinations and then sent to a laboratory to evaluate serum vitamin C and cotinine levels. A serum cotinine concentration of 100 ng/ml was considered a relevant threshold for active smoking. After dividing the participants into two groups according to serum cotinine levels, Poisson regression analysis was carried out to compare vitamin C levels with the prevalence rate ratio (PRR) for periodontal condition markers for each group based on serum cotinine levels. RESULTS: We evaluated differences in the PRR of serum vitamin C tertiles between participants with high (≥100 ng/ml) or low (<100 ng/ml) serum cotinine levels after adjusting for sex, the use of interdental brushes or dental floss, and the number of teeth. A negative tendency between the PRR of vitamin C tertiles for the PPD or CAL was seen for both groups. Especially, a bigger difference was observed in the group with high serum cotinine levels. The PRR of the first tertiles in the high serum cotinine group was 5.03, compared with 2.69 in the low serum cotinine group (relative risk: 1.9). CONCLUSION: The results of this study suggest a potential association between vitamin C levels and the periodontal condition, which may be influenced by smoking status.

Increased left atrial volume index is associated with more cardiovascular events in patients with acute coronary syndrome: HIJ-PROPER study findings.

AIM: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). METHODS: In this sub-analysis of the HIJ-PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut-off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. RESULTS: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut-off point of 34 mL/m2 . Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow-up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19-7.22; P = .014). The tendency was similar after adjusting for several confounders (P = .025). CONCLUSION: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. CLINICAL TRIAL REGISTRATION: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742).

Independent contribution of optical attenuation length in ultrafast laser-induced structural change.

Although laser irradiation with femtosecond pulses is known to generate crystallization and morphological changes, the contribution of optical parameters to material changes is still in discussion. Here, we compare two structures irradiated near Si-L2,3 edges by an extreme ultraviolet femtosecond pulse. Our result implies that, despite the femtosecond irradiation regime, these values of the optical attenuation length between the wavelengths of 10.3-nm and 13.5-nm differ by one order of magnitude. From the structural comparison, the original crystalline state was maintained upon irradiation at 13.5-nm, on the other hand, transition to an amorphous state occurred at 10.3-nm. The difference in optical attenuation length directly influence to the decision of material crystallization or morphological changes, even if the irradiation condition is under the femtosecond regime and same pulse duration. Our result reveals the contribution of optical attenuation length in ultrafast laser-induced structural change.

Greater Change in the Eicosapentaenoic Acid to Arachidonic Acid Ratio Is Associated With Decreased Incidence of Cardiovascular Events in Acute Coronary Syndrome Patients With Elevated Triglyceride Levels.

BACKGROUND: This study investigated whether the percentage change (%Δ) in the eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio is associated with cardiovascular event rates among acute coronary syndrome (ACS) patients receiving contemporary lipid-lowering therapy other than polyunsaturated fatty acids (PUFAs).Methods and Results:This post hoc subanalysis of the HIJ-PROPER study included PUFA-naïve patients for whom EPA/AA ratio data were available at baseline and after 3 months. Patients were categorized into 2 groups based on the median %ΔEPA/AA ratio: Group 1, change less than the median; and Group 2, change greater than or equal to the median. The 3-year rates of the primary endpoint, a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina pectoris, were compared between the 2 groups. The median %ΔEPA/AA ratio in Groups 1 and 2 was -26.2% (n=482 patients [49.9%]) and 42.2% (n=483 patients [50.1%]), respectively. At the 3-year follow-up, the occurrence of the primary endpoint was significantly lower in Group 2 than in Group 1 (29/483 [6.0%] vs. 53/482 [11.0%]; hazard ratio 0.53, 95% confidence interval 0.33-0.82; P=0.005). The same trend was observed after adjusting for patient factors (P=0.02). CONCLUSIONS: Among ACS patients receiving contemporary lipid-lowering therapy other than PUFAs, a greater change in the EPA/AA ratio was associated with a lower incidence of cardiovascular events.

A population-based cross-sectional study of the association between periodontitis and arterial stiffness among the older Japanese population.

OBJECTIVE: To investigate the potential association between periodontitis and arterial stiffness among the older Japanese population. BACKGROUND: The prevalence of periodontitis is increasing in Japanese older adults. Arterial stiffness increases the risks of cardiovascular events and death, morbidity, and dementia. METHODS: This secondary analysis of data from a cross-sectional study evaluated the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue that was estimated by a full-mouth periodontal examination. Severe periodontitis was defined per the parameters provided by the Centers for Disease Control/American Academy of Periodontology. The Cardio-Ankle Vascular Index (CAVI) was used for measuring the overall stiffness of the artery, and higher CAVI indicated increased arterial stiffness. An ordinal logistic regression model was used to evaluate the association between periodontitis and arterial stiffness. RESULTS: The analysis included 185 Japanese adults [35% men; age, mean (standard deviation) 80.2 (4.4) years]. The average PISA and the prevalence of severe periodontitis were 64.4 mm2 and 27.6%, respectively; 54 (29.2%), 56 (30.3%), and 75 (40.5%) participants were stratified to the CAVI < 9, 9 ≤ CAVI <10, and CAVI ≥ 10 groups, respectively. After adjusting for potential confounders, the odds ratio of the prevalence and severity of arterial stiffness evaluated using CAVI was 1.06 [95% confidence interval (CI) 1.01 to 1.10] for PISA per 10 mm2 and 2.12 (95% CI 1.09 to 4.11) for severe periodontitis. CONCLUSION: Periodontitis was associated with arterial stiffness among Japanese older adults. Further studies are needed to investigate whether arterial stiffness is an intermediate factor in the pathway between periodontitis and systemic diseases, including cardiovascular disease and dementia.

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.

Association between anemia and mortality in patients with acute coronary syndrome treated with percutaneous coronary intervention and contemporary lipid-lowering therapy.

Despite a clear correlation between anemia and mortality in patients with the acute coronary syndrome (ACS), anemia as a mortality predictor in patients with ACS-receiving early invasive strategy and contemporary lipid-lowering therapy has not been examined. Therefore, we aimed to evaluate the association between anemia and mortality in ACS patients treated with acute revascularization and contemporary lipid-lowering treatment. This was a post-hoc study of the Heart Institute of Japan-Proper level of Lipid-Lowering with Pitavastatin and Ezetimibe in acute coronary syndrome study, in which ACS patients with dyslipidemia were randomized to receive either pitavastatin and ezetimibe or pitavastatin monotherapy. The success rate of primary percutaneous coronary intervention (PCI) was 95.2%. Eligible patients were divided into two groups: patients with anemia (anemia group) or without anemia (non-anemia group). Anemia was defined using the World Health Organization definition hemoglobin < 12 g/dL for women and < 13 g/dL for men. We compared the mortality between the two groups using propensity scores derived from 17 baseline variables. We identified 1721 eligible patients, including 420 (24.4%) in the anemia group and 1301 (75.6%) in the non-anemia group. One-to-one propensity score-matching created 381 pairs. Both unmatched and matched analyses found significantly high mortality in the anemia group compared to the non-anemia group (unmatched 12.3% vs. 3.8%, log-rank p < 0.01; matched 11.5% vs. 6.3%, log-rank p = 0.01). In ACS patients treated with an early invasive strategy era with a high PCI success rate and concurrent contemporary lipid-lowering management, all-cause mortality was still significantly higher in anemic patients than in non-anemic patients.Trial registration: Clinical trial registration URL: http://www.umin.ac.jp/ctr . Unique identifier: UMIN00000274.

Association between elevated left ventricular mass index and increased cardiovascular events in patients with acute coronary syndrome: A sub-analysis of the HIJ-PROPER study.

AIM: This study aimed to assess the association between left ventricular mass index (LVMI) and cardiovascular events in patients with acute coronary syndrome (ACS) under standard ACS management. METHODS AND RESULTS: This study is the sub-analysis of the HIJ-PROPER study. A total of 299 patients who had echocardiographic LVMI data were included in the current analysis. The participants were divided into four groups according to the LVMI quartile [quartile 1 (Q1), 77 (25.8%); quartile 2 (Q2), 73 (24.4%); quartile 3 (Q3), 74 (24.7%); and quartile 4 (Q4), 75 (25.1%)]. The incidence of cardiovascular events was compared among the four groups. The primary endpoint was defined as the composite endpoint of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. Mean LVMI in the four groups was 68.1±8.6, 86.2±3.8, 101.1±4.9, and 126.0±18.5 g/m2 , respectively. The primary endpoint was noted in 4, 4, 7, and 14 patients in Q1, Q2, Q3, and Q4, corresponding to an incidence of 5.2%, 5.5%, 9.5%, and 18.7%, respectively (p = 0.03 for difference among four groups). The cumulative incidence of the primary endpoint was significantly higher in patients in Q4 than in those in Q1 and Q2 [hazard ratio (HR) 3.75; 95% confidence interval (CI), 1.23-11.4; p = 0.02 for Q4 vs Q1; HR 3.43; 95% CI, 1.13-10.4; p = 0.03 for Q4 vs Q2]. This tendency was noted even after adjusting for patient characteristics and echocardiography parameters (p = 0.039 for Q4 vs Q1). CONCLUSION: Elevated LVMI was associated with increased cardiovascular events in patients with ACS under standard management. Adequately powered studies are warranted to validate these findings.

Cancer-Associated Mutations in Endometriosis without Cancer.

BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. CONCLUSIONS: We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.

Ezetimibe Markedly Reduces Hepatic Triglycerides and Cholesterol in Rats Fed on Fish Oil by Increasing the Expression of Cholesterol Efflux Transporters.

Besides diet therapy, hypolipidemic pharmacological therapy may be a crucial component of nonalcoholic fatty liver disease (NAFLD) treatment. Ezetimibe may be a promising drug for treatment of NAFLD. n-3 polyunsaturated fatty acids, which are abundant in fish oil, reduce serum and hepatic cholesterol and triglycerides in rodents. The aim of this study was to examine the combined effects of dietary fish oil and ezetimibe on lipid metabolism in rats. Seven-week-old male Sprague-Dawley rats were allocated to four different diets containing 1) 10% soybean oil (C), 2) 10% fish oil (F), 3) 10% soybean oil + 0.005% ezetimibe, and 4) 10% fish oil + 0.005% ezetimibe (F+E) for 4 weeks, when the liver, jejunum, blood, and fecal samples were collected. Compared with the C group, the F+E diet decreased hepatic triglycerides and cholesterol 84% and 86%, but it did not increase fecal cholesterol. In liver, the expression of lipogenic enzymes was decreased in the F+E diet, whereas ß-oxidation-related genes were not increased. Abcg5/g8 mRNA expression was increased 1380%/442% when ezetimibe was added to the F diet. These gene expression changes are related to the decrease in hepatic lipids. In jejunum, Abcg5/g8 mRNA was increased 244%/841% when ezetimibe was added to the F diet. Hepatic induction of Abcg5/8 rather than intestinal induction correlates with the marked decrease in liver cholesterol when ezetimibe was added to the F diet. These data suggest that fish oil diet and ezetimibe in combination may be a beneficial therapy for NAFLD by increasing hepatic Abcg5/g8 and decreasing lipogenic genes. SIGNIFICANCE STATEMENT: There is currently no single treatment for NAFLD. Thus, lifestyle modifications including dietary regulation and physical activity are also important options. In this study, ezetimibe, a cholesterol absorption inhibitor, was evaluated for the treatment of liver steatosis in rats fed on the different diets. We found that ezetimibe and fish oil in combination markedly improved fatty liver by increasing cholesterol efflux transporters. The combination therapy of fish oil agents and ezetimibe may be effective for NAFLD.

Surface processing of PMMA and metal nano-particle resist by sub-micrometer focusing of coherent extreme ultraviolet high-order harmonics pulses.

We demonstrate sub-micrometer processing of two kinds of thin films, polymethyl methacrylate (PMMA) and metal nano-particle resist, by focusing high-order harmonics of near-IR femtosecond laser pulses in the extreme ultraviolet (XUV) wavelength region (27.2-34.3 nm) on the thin film samples using an ellipsoidal focusing mirror. The ablation threshold fluences for the PMMA sample and the metal nano-particle resist per XUV pulse obtained by the accumulation of 200 XUV pulses were determined to be 0.42mJ/cm2 and 0.17mJ/cm2, respectively. The diameters (FWHM) of a hole created by the ablation on the PMMA film at the focus were 0.67 µm and 0.44 µm along the horizontal direction and the vertical direction, respectively. The fluence dependence of the Raman microscope spectra of the processed holes on the PMMA sample showed that the chemical modification, in which C=C double bonds are formed associated with the scission of the PMMA polymer chains, is achieved by the irradiation of the XUV pulses.

Facephenes and rainbows: Causal evidence for functional and anatomical specificity of face and color processing in the human brain.

Neuroscientists have long debated whether some regions of the human brain are exclusively engaged in a single specific mental process. Consistent with this view, fMRI has revealed cortical regions that respond selectively to certain stimulus classes such as faces. However, results from multivoxel pattern analyses (MVPA) challenge this view by demonstrating that category-selective regions often contain information about "nonpreferred" stimulus dimensions. But is this nonpreferred information causally relevant to behavior? Here we report a rare opportunity to test this question in a neurosurgical patient implanted for clinical reasons with strips of electrodes along his fusiform gyri. Broadband gamma electrocorticographic responses in multiple adjacent electrodes showed strong selectivity for faces in a region corresponding to the fusiform face area (FFA), and preferential responses to color in a nearby site, replicating earlier reports. To test the causal role of these regions in the perception of nonpreferred dimensions, we then electrically stimulated individual sites while the patient viewed various objects. When stimulated in the FFA, the patient reported seeing an illusory face (or "facephene"), independent of the object viewed. Similarly, stimulation of color-preferring sites produced illusory "rainbows." Crucially, the patient reported no change in the object viewed, apart from the facephenes and rainbows apparently superimposed on them. The functional and anatomical specificity of these effects indicate that some cortical regions are exclusively causally engaged in a single specific mental process, and prompt caution about the widespread assumption that any information scientists can decode from the brain is causally relevant to behavior.

Periodontitis, periodontal inflammation, and mild cognitive impairment: A 5-year cohort study.

BACKGROUND AND OBJECTIVES: Identification of modifiable factors for mild cognitive impairment (MCI) is important since individuals with MCI are at a high risk of dementia and disability. Previous studies have suggested a potential association between periodontitis and cognitive impairment, but the results remain inconclusive. We designed a 5-year longitudinal study to explore the association between MCI and periodontitis and periodontal inflammation in older adults. METHODS: This study included 179 community-dwelling dentate individuals (62 men and 117 women, average age: 80.1 years). A full-mouth periodontal examination at six sites per tooth was performed at baseline. Case definitions provided by the European Workshop in Periodontology Group C (EWP definition) and the Centers for Disease Control/American Academy of Periodontology (CDC/AAP definition) were used to define severe periodontitis. Additionally, the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue, was calculated using clinical periodontal parameters. Follow-up cognitive examinations for MCI diagnosis were performed by neurologists 1, 2, 3, and 5 years after baseline. Odds ratios (ORs) for MCI according to the presence of periodontitis and periodontal inflammation at baseline were calculated using multilevel mixed-effects logistic regression. RESULTS: At baseline, 56.4% and 27.4% of the participants had severe periodontitis by the EWP and CDC/AAP definitions, respectively. After adjusting for follow-up period and other baseline health characteristics (age, sex, smoking status, educational level, physical activity level, obesity, depression, and diabetes), severe periodontitis by either definition was significantly associated with MCI (for the EWP definition: adjusted OR = 3.58, 95% confidence interval [CI] = 1.45-8.87; for the CDC/AAP definition: adjusted OR = 2.61, 95% CI = 1.08-6.28). Periodontal inflammation assessed by PISA was also significantly associated with a higher OR for MCI (adjusted OR = 1.05, 95% CI = 1.01-1.10, per 10-mm2 increase in PISA). CONCLUSION: Severe periodontitis and periodontal inflammation were associated with incident MCI among older community-dwelling men and women.