Alzheimer’s disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals world-wide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an in vitro thioflavin T assay with Aβ1–42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1–40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1–42 fibrillization (IC50: 0.26 μM), as well as on disassembling preformed Aβ1–42 fibrils (EC50: 0.59 μM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1–42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1–42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1–42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1–42 fibrillization and disaggregation of preformed mature Aβ1–42 fibrils.

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.
Anisotropy ; Caudate Nucleus ; Connectome ; Diffusion ; Epilepsies, Partial* ; Epilepsy ; Globus Pallidus ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Prospective Studies ; Putamen ; Thalamus

BACKGROUND/AIMS: The eradication of Helicobacter pylori (H. pylori) is an effective treatment in gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with H. pylori infection. However, the treatment strategy in gastric MALT lymphoma patients who are H. pylori-negative or unresponsive to H. pylori eradication therapy remains controversial. In this study, we investigated the clinical efficacy of treatments other than H. pylori eradication therapy in these groups of patients. METHODS: This was a retrospective single-center study based on the medical records of patients diagnosed with gastric MALT lymphoma at Yeungnam University Medical Center between January 2005 and December 2016. Patients were treated with H. pylori eradication therapy, chemotherapy, or radiotherapy according to their H. pylori infection status and stage of gastric MALT lymphoma. RESULTS: Of the 68 eligible patients, 50 were enrolled in the study. Of the 42 patients with H. pylori-positive gastric MALT lymphoma, 36 (81.7%) were treated with H. pylori eradication therapy as primary treatment and 25 (69.4%) achieved a complete response (CR). Patients without a CR after H. pylori eradication therapy (n=11, 30.6%) received radiotherapy as a secondary treatment. Two patients with H. pylori-positive gastric MALT lymphoma and eight with H. pylori-negative gastric MALT lymphoma received radiotherapy as the primary treatment. CR was achieved in all 21 patients treated with radiotherapy as primary or secondary treatment. The 5-year progression-free survival rate after radiotherapy was 92.9%. CONCLUSIONS: Radiotherapy may be a worthwhile treatment option in patients with H. pylori-negative MALT lymphoma or H. pylori-positive MALT lymphoma that is not responsive to H. pylori eradication therapy.
Academic Medical Centers ; Disease-Free Survival ; Drug Therapy ; Helicobacter pylori* ; Helicobacter* ; Humans ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Medical Records ; Radiotherapy* ; Retrospective Studies ; Stomach Neoplasms ; Treatment Outcome*

The incidence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is increasing worldwide, but the diagnosis is difficult. Most patients are asymptomatic or complain of nonspecific gastrointestinal symptoms. As the endoscopic features of gastric MALT lymphoma are variable and nonspecific, the possibility of this condition may be overlooked during esophagogastroduodenoscopy, and it remain undiagnosed. Therefore, this condition needs to be considered when an abnormal mucosa is observed during this procedure. Biopsy performed during endoscopy is the primary diagnostic test, but false negative results are possible; large numbers of samples should be collected from both normal and abnormal mucosae. Endoscopic ultrasonography is useful to assess the depth of invasion and to predict the treatment response. After treatment, follow-up tests are required every 3 months until complete remission is achieved, and annually thereafter. Early diagnosis of gastric MALT lymphoma is difficult, and its diagnosis and follow-up require wide experience and competent endoscopic technique.
Biopsy ; Diagnosis ; Diagnostic Tests, Routine ; Early Diagnosis ; Endoscopy ; Endoscopy, Digestive System ; Endoscopy, Gastrointestinal ; Endosonography ; Follow-Up Studies ; Humans ; Incidence ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone ; Mucous Membrane ; Stomach Neoplasms

BACKGROUND: Heatstroke is one of the most serious heat-related illnesses. However, establishing public policies to prevent heatstroke remains a challenge. This study aimed to investigate the most relevant climate elements and their warning criteria to prevent outdoor heatstroke (OHS).METHODS: We investigated heatstroke patients from five major hospitals in Daegu metropolitan city, Korea, from June 1 to August 31, 2011 to 2016. We also collected the corresponding regional climate data from Korea Meteorological Administration. We analyzed the relationship between the climate elements and OHS occurrence by logistic regression.RESULTS: Of 70 patients who had heatstroke, 45 (64.3%) experienced it while outdoors. Considering all climate elements, only mean heat index (MHI) was related with OHS occurrence (p=0.019). Therefore, the higher the MHI, the higher the risk for OHS (adjusted odds ratio, 1.824; 95% confidence interval, 1.102–3.017). The most suitable cutoff point for MHI by Youden’s index was 30.0°C (sensitivity, 77.4%; specificity, 73.7%).CONCLUSION: Among the climate elements, MHI was significantly associated with OHS occurrence. The optimal MHI cutoff point for OHS prevention was 30.0°C.
Climate ; Daegu ; Heat Stroke ; Hot Temperature ; Humans ; Incidence ; Korea ; Logistic Models ; Meteorology ; Odds Ratio ; Public Policy ; Sensitivity and Specificity

OBJECTIVE: This study was conducted to evaluate scorecards for early recognition of high-risk patients of delirium in the emergency department (ED). METHODS: Data from 399 consecutive patients aged 65 years or older between January 1, 2015 and December 31, 2015 were retrospectively analyzed. Delirium was identified by reviewing medical records and was confirmed by a psychiatrist. The study population was divided into a training and validation group. Predisposing factors were evaluated and validated by multivariate logistic regression analysis and a calibration plot, after which a scorecard was constructed using these factors and applying points to double odds to each regression coefficient. RESULTS: Dementia, transfer from a long-term care facility, acute acid-base imbalance, moderate pain, and stroke were independent predisposing factors for delirium in ED, with assigned scores in the scorecard of 3, 2, 2, 2, and 2, respectively. The total score of the scorecard for delirious patients was significantly higher than that for non-delirious patients in both the training and validation groups. The coefficient of determination (R²) of the calibration plot was 0.74 and 0.68 in the training and validation group, respectively. In the receiver operation characteristic curve, the cut-off point of the scorecard for delirium was 2.5 and the sensitivity, specificity, and accuracy were 75.0%, 87.8%, and 86.7% in training group, while they were 76.9%, 85.1%, and 84.2% in the validation group, respectively. CONCLUSION: The scorecard was a useful screening tool for early recognition of patients with a high-risk of developing delirium in the ED.
Acid-Base Imbalance ; Calibration ; Causality ; Delirium ; Dementia ; Emergencies ; Emergency Service, Hospital ; Humans ; Logistic Models ; Long-Term Care ; Mass Screening ; Medical Records ; Psychiatry ; Retrospective Studies ; Sensitivity and Specificity ; Stroke

It is well known that the presence of arachnoid cysts (ACs) in young patients is a risk factor for developing a chronic subdural hematoma (CSDH) after a minor head injury. Although there have been controversies with the treatment, most authors recommend only draining the CSDH if the AC is asymptomatic. This judgement is based on the facts that this surgical approach has shown good clinical outcomes, and the AC usually remains unchanged after the surgery. Our case demonstrates that the AC of a young patient who developed a CSDH after a minor head injury completely disappeared after a burr hole drainage of the CSDH. Although the chances of an AC disappearing are low, this case shows that an AC might disappear after only draining a CSDH when a rupture of the AC membrane is identified. In such cases, we recommend first draining only the CSDH for the treatment of AC-associated CSDHs.
Arachnoid Cysts ; Arachnoid ; Craniocerebral Trauma ; Drainage ; Hematoma, Subdural, Chronic ; Humans ; Membranes ; Risk Factors ; Rupture