Predictability of Cardiovascular Risk Scores for Carotid Atherosclerosis in Community-Dwelling Middle-Aged and Elderly Adults.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40-74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19-1.28) and 1.36 (95% CI, 1.28-1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19-1.29) and 1.38 (95% CI, 1.30-1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375-0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835-0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study.

Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.

Associations of genetic markers of diabetes mellitus with carotid atherosclerosis: a community-based case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). METHODS: We used a case-control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10-16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. RESULTS: Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18-1.44; p = 4.7 × 10-7) and 1.47 (95% CI 1.74-9.40; p = 6.1 × 10-5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. CONCLUSIONS: We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis.

Using Deep-Learning-Based Artificial Intelligence Technique to Automatically Evaluate the Collateral Status of Multiphase CTA in Acute Ischemic Stroke.

BACKGROUND: Collateral status is an important predictor for the outcome of acute ischemic stroke with large vessel occlusion. Multiphase computed-tomography angiography (mCTA) is useful to evaluate the collateral status, but visual evaluation of this examination is time-consuming. This study aims to use an artificial intelligence (AI) technique to develop an automatic AI prediction model for the collateral status of mCTA. METHODS: This retrospective study enrolled subjects with acute ischemic stroke receiving endovascular thrombectomy between January 2015 and June 2020 in a tertiary referral hospital. The demographic data and images of mCTA were collected. The collateral status of all mCTA was visually evaluated. Images at the basal ganglion and supraganglion levels of mCTA were selected to produce AI models using the convolutional neural network (CNN) technique to automatically predict the collateral status of mCTA. RESULTS: A total of 82 subjects were enrolled. There were 57 cases randomly selected for the training group and 25 cases for the validation group. In the training group, there were 40 cases with a positive collateral result (good or intermediate) and 17 cases with a negative collateral result (poor). In the validation group, there were 21 cases with a positive collateral result and 4 cases with a negative collateral result. During training for the CNN prediction model, the accuracy of the training group could reach 0.999 ± 0.015, whereas the prediction model had a performance of 0.746 ± 0.008 accuracy on the validation group. The area under the ROC curve was 0.7. CONCLUSIONS: This study suggests that the application of the AI model derived from mCTA images to automatically evaluate the collateral status is feasible.

Combined effects of hypertension, hyperlipidemia, and diabetes mellitus on the presence and severity of carotid atherosclerosis in community-dwelling elders: A community-based study.

BACKGROUND: Hypertension, hyperlipidemia, and diabetes mellitus (DM) are common cardiovascular disease (CVD) comorbidities and well-known major determinants of atherosclerosis. However, their combined effects and relative contributions have not been well explored. This study aimed to characterize the characteristics of carotid atherosclerosis and dissect the relative effects of these common CVD comorbidities on the presence and severity of carotid atherosclerosis in community-dwelling elderly individuals. METHODS: We enrolled 817 elders from communities in northern Taiwan. We evaluated their cardiovascular risk profiles and scanned their extracranial carotid arteries using high-resolution ultrasonography systems. RESULTS: The prevalence rates for hypertension, hyperlipidemia, and DM were 45.4%, 37.1%, and 16.8%, respectively. Sixty-two (7.6%) and 188 (23.0%) elderly had all three and two of these common CVD comorbidities, respectively. The prevalent rates of carotid plaque and moderate-to-severe atherosclerosis were 62.9% and 35.5%, respectively. The percentages of one or more common CVD comorbidities in elders with carotid plaque and moderate-to-severe atherosclerosis were 78.2% and 83.1%, respectively. Multivariate analyses showed that the number of common CVD comorbidities was the most predictive determinant. Multivariable-adjusted odds ratios (ORs) per comorbidity for the presence of carotid plaque and advanced carotid atherosclerosis were 1.52 (95% CI, 1.28-1.81) and 1.57 (95% CI, 1.28-1.93), respectively. Models containing hypertension and DM were the second most predictive. Combinatory analyses showed distinct relationship patterns between carotid atherosclerosis and hypertension, hyperlipidemia, and DM. Hypertension was significantly correlated with higher ORs for the presence of carotid plaque and advanced carotid atherosclerosis but not for hyperlipidemia. CONCLUSION: Carotid plaques are highly prevalent in community-dwelling elders. The number of common CVD comorbidities was the most predictive determinant of carotid plaques and advanced carotid atherosclerosis. Our results indicate that to reduce the impact of atherosclerotic diseases, blood pressure controls precede the control of blood lipids and glucose in the community-dwelling elders.

Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study.

Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (< 65 and ≥ 65 years old). This observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with a follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. SIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (< 65, ≥ 65 years), and different follow-up years. After excluding 128 individuals (< 20 years or ≥ 85 years old) and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years among thyroid cancer patients, the observed number of new CHD events was 70; IS, 30; and AF, 20, respectively. The SIR was significantly higher for CHD (SIR, 1.57; 95% confidence interval [CI] 1.2-1.93) among thyroid cancer patients compared with the age- and sex-specific standardized population. However, the association between thyroid cancer and the risks of IS (SIR, 0.74; 95% CI 0.47-1), cardiovascular disease (SIR, 0.88; 95% CI 0.7-1.05), and atrial fibrillation (SIR, 0.74; 95% CI 0.42-1.06) were insignificant. Moreover, stratification by age < 65 or age ≥ 65 years old and by sex for CHD suggested that the diagnosis of thyroid cancer in the young may attenuate the CHD risk (SIR, 2.08; 95% CI 1.5-2.66), and the CVD risk was constant among both men (SIR, 1.63; 95% CI 1.03-2.24) and women (SIR, 1.53; 95% CI 1.06-1.99). The patients had persistent higher CHD risk for 5 years after cancer diagnosis. Thyroid cancer survivors have a substantial CHD risk, even at long-term follow-up, especially in those patients < 65 years old. Further research on the association between thyroid cancer and CHD risk is warranted.

Association of Common Variants in OLA1 Gene with Preclinical Atherosclerosis.

Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case-control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima-media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3'-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.

Prevalences of diabetes mellitus and carotid atherosclerosis and their relationships in middle-aged adults and elders: a community-based study.

BACKGROUND/PURPOSE: Atherosclerosis and diabetes mellitus (DM) are both severe chronic diseases that cause huge burdens on patients' families and societies. Connections between the two diseases have brought high attention recently, however, population-based study with large sample size was few. The study aimed to explore the relationship between carotid atherosclerosis and DM. METHODS: We enrolled 3908 adults aged 40-74 years from communities and measured their cardio-metabolic profiles and scanned their carotid arteries bilaterally. RESULTS: The overall prevalence rates of carotid plaque and DM were 34.4 and 10.7%, respectively. The age-specific prevalence rates of DM and carotid plaque were nearly linearly correlated in both sexes (both Pearson's correlation coefficient r > 0.97). The prevalence rates of carotid plaque, total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3 were 53.6, 24.8, 19.1, and 28.6%, respectively, in DM patients and were 32.1, 9.4, 9.8, and 11.2%, respectively, in non-DM controls. After adjustment for other conventional risk factors, the multivariable-adjusted OR of having carotid plaque was 1.60 (95% CI 1.27-2.01) and were 2.06 (95% CI 1.55-2.75), 1.33 (95% CI 0.99-1.78), and 2.03 (95% CI 1.55-2.65) for total plaque number ≥3, maximum diameter stenosis ≥30%, and plaque score ≥3, respectively. CONCLUSION: We demonstrated that prevalences of DM were linearly correlated with prevalences of carotid plaque and DM patients had higher prevalence rates of carotid plaque and more advanced carotid atherosclerosis than non-DM controls. Our results indicated the need to address the role of DM in atherosclerosis development.

Common Genetic Variants on Bone Morphogenetic Protein Receptor Type IB (BMPR1B) Gene Are Predictive for Carotid Intima-Media Thickness.

BACKGROUND: Bone morphogenetic proteins (BMP) 2 and 4 are implicated in the development of atherosclerosis. However, the relationships between the proteins, their main receptors and carotid intima-media thickness (cIMT), a predictive preclinical phenotype of atherosclerosis, have not been established. Methods and Results: We screened and validated the relationships of single-nucleotide polymorphisms (SNPs) on BMP2, BMP4, BMPR1A, BMPR1B, and BMPR2 with thicker cIMT by 2 independent case-control studies that used different subject selection methods. Among 200 screened SNPs, 12 on BMPR1B were regarded as candidate genetic markers (P-value <5.0×10-4). After combining the discovery and validation studies and adjusting for traditional cardiovascular risk factors, rs4456963*G, rs4235438*T, rs2522530*T, and rs3796433*C showed significant higher odds ratios (ORs) of having thicker cIMT (adjusted ORs: 1.50-1.56; all P-values <2.5×10-4). Multivariate analyses showed that rs4456963 and rs3796433 were significantly independent determinants of cIMT thickening. The corresponding multivariate-adjusted ORs for rs4456963*G and rs3796433*C alleles were 1.50 (95% confidence interval (CI): 1.22-1.84) and 1.50 (95% CI: 1.23-1.82), respectively. Interaction between rs4456963 and rs3796433 was evident by the significantly higher OR (8.16, 95% CI: 3.12-21.3) for subjects with the GG-CC genotype. The rs4456963*G and rs3796433*C showed positively linear trends with severity of carotid atherosclerosis. CONCLUSIONS: We identified 2 SNPs on BMPR1B showing significantly independent correlations with thicker cIMT. The study provides invaluable evidence supporting that BMPR1B is closely related to carotid atherosclerosis and a potential target for the development of therapeutic agents for atherosclerotic disease.

Segment-specific prevalence of carotid artery plaque and stenosis in middle-aged adults and elders in Taiwan: A community-based study.

BACKGROUND: Plaque in carotid arteries (CAs) is a major factor of systemic atherosclerosis and cardiovascular disease (CVD). The left and right CAs have different anatomic and geometric features and may influence the predictability of CVD. However, the site- and segment-specific prevalence of carotid plaques (CP) and study on severity of carotid atherosclerosis with CVD risks was very limited. METHODS: We enrolled 1539 healthy residents aged 40-to-74 years from two northern districts in Taiwan. All volunteers received high resolution B-mode carotid ultrasound scans and CVD risk factors evaluations. RESULTS: The prevalence rate of extracranial CP was 21.9% in females and 33.8% in males. Carotid bifurcation is the most affected segment. As compared with the right CAs, the age-sex-adjusted matched odds ratio of having plaques in the left CAs was 1.32 (95% confidence interval = 1.02-1.73). The proportions of subjects had a total plaque number≥2, maximum stenosis≥30%, and plaque score≥3 were 8.9, 10.3, and 7.2%, respectively, in females and were 17.7, 17.2, and 15.1%, respectively, in males. Among subjects with moderate and severe carotid atherosclerosis, the mean ± SD of estimated 10-year CVD risk was 19.1 ± 14.6% and more than 65% of them need intensive blood pressure, lipids, or sugar controls. CONCLUSION: We found that bifurcation was the most prevalent segment, and left CAs was more likely to form plaque than right CAs. The major CVD risk factors were highly prevalent and the estimated CVD risks were high in subjects with more advanced carotid atherosclerosis. The study provides further direction for CVD prevention and treatment.

Associations of Common Genetic Variants on IL-17 Genes and Carotid Intima-Media Thickness.

AIM: Atherosclerosis is a chronic inflammatory process of the arterial wall and carotid intima-media thickness (cIMT) is regarded as its early marker. Several members of the IL-17 family are involved in pro-inflammatory functions. The specific aim of the study was to explore the relationships of common genetic variants on IL-17 genes with cIMT thickening. METHODS: In the discovery stage, 146 SNPs on 11 IL-17 genes were screened for their relationships with cIMT by a case-control study that enrolled 284 and 464 subjects who had thicker and normal cIMT, respectively. Findings were replicated by an independent case-control study that enrolled 282 subjects who had thicker cIMT and 282 age-sex-matched subjects who had normal cIMT. RESULTS: Among 134 eligible SNPs in the discovery study, only IL-17RC rs279545 was significantly correlated with cIMT (p=6.9×10-5). The rs279545 and 2 nearby linked SNPs rs55847610 and rs3846167 were included in the validation study. We found that the rs279545＊G, rs55847610＊G, and rs3846167＊C were correlated with significantly higher likelihoods of having thicker cIMT. The corresponding multivariate-adjusted ORs were 1.462 (95% CI: 1.055-2.027), 1.481 (95% CI:1.090-2.013), and 1.589 (95% CI: 1.147-2.200), respectively. Analyses of rs279545-rs55847610 haplotypes showed that the multivariate-adjusted OR for A-A haplotype was significantly decreased (OR=0.665, 95% CI: 0.487-0.908) and for G-G haplotype was significantly increased (OR=1.539, 95% CI: 1.097-2.161). CONCLUSIONS: We first correlated cIMT, a preclinical clinical cardiovascular marker, with IL-17RC, the key molecule in the IL-17 signaling pathway. Our results indicated that IL-17RC may play critical role in the development of atherosclerotic diseases.

Fusarium Brain Abscess in a Patient with Diabetes Mellitus and Liver Cirrhosis.

PURPOSE: Invasive mycosis caused by the Aspergillus, Fusarium, and Mucor can be fetal, especially in the immunocompromised patients with central nervous system (CNS) involvement. Here we present a case of CNS Fusarium infection, and this is the first reported case of Fusarium brain abscess in Taiwan. CASE REPORT: A 65-year-old woman presented with fever and conscious disturbance for 3 days. Neurological examination showed stupor consciousness, neck stiffness, multiple cranial nerves palsy, and bilateral Babinski signs. Magnetic resonance imaging showed multifocal lesions involving medulla oblongata, pons, bilateral cerebral peduncles, and bilateral cerebellar peduncles. Cerebrospinal fluid (CSF) study revealed neutrophil predominant pleocytosis, but both blood and CSF culture were negative. We treated patient with ceftriaxone and vancomycin initially as empiric therapy for suspected bacterial meningoencephalitis. However, chronic sinusitis with fungal ball and brain abscess were later found. Despite antifungal treatment and surgical intervention, patient expired 3 months after admission. Fungal culture of the brain abscess disclosed Fusarium species 2 weeks after her death. CONCLUSION: CNS Fusarium infection should be considered when an immunocompromised patient presenting with fever, conscious change, cranial nerve palsies, and angioinvasion suggested by brain imaging. To properly manage the disease, early effective antifungal therapy and neurosurgical intervention are important.

Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer's Disease Inhibiting Aggregation of Aß: In Silico and in Vitro Studies.

Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Aß aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aß aggregation and protect cells against Aß induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer's disease.

Recurrent nonconvulsive status epilepticus in a patient with progressive left hemispheric leukoencephalopathy after a remote viral meningoencephalitis.

Nonconvulsive status epilepticus (NCSE), defined as changes in behavior and/or mental processes from baseline with continuous epileptiform discharges, remains a diagnostic and treatment challenge. Here, we present a 68-year-old female who developed 3 episodes of NCSE 10 years after a viral meningoencephalitis which gradually progressed to left hemispheric leukoencephalopathy. In this case, we hypothesize that immune-mediated mechanisms and perhaps genetic predisposition played a role in epileptogenesis, and these will be discussed. This article is part of a Special Issue entitled "Status Epilepticus".

The Role of the Renin-Angiotensin System in Amyloid Metabolism of Alzheimer's Disease.

UNLABELLED: The etiology of Alzheimer's disease (AD) remains unclear. Epidemiologic studies suggest hypertension plays a contributing role to AD. Recently, several experimental and observational studies showed interaction between the renin-angiotensin system and amyloid-ß, a key pathologic feature of AD, with diverse results. This article reviews molecular, genetic, experimental and clinical data to clarify the impact on an AD patient with angiotensin converting enzyme inhibitor and angiotensin II receptor blocker therapy, with some guidance for the direction of possible future research. KEY WORDS: Alzheimer's disease; Amyloid-ß; Renin angiotensin system.