Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Background: and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). Conclusions The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.