Cryptogenic NORSE: Its distinctive clinical features and response to immunotherapy.

OBJECTIVE: To report the distinctive clinical features of cryptogenic new-onset refractory status epilepticus (C-NORSE) and the C-NORSE score based on initial clinical assessments. METHODS: A retrospective study was conducted for 136 patients with clinically suspected autoimmune encephalitis who underwent testing for autoantibodies to neuronal surface antigens between January 1, 2007, and August 31, 2016. Eleven patients with C-NORSE were identified. Their clinical features were compared with those of 32 patients with anti-NMDA receptor encephalitis (NMDARE). RESULTS: The clinical outcome of 11 patients (median age, 27 years; 7 [64%] women) with C-NORSE was evaluated after a median follow-up of 11 months (range, 6-111 months). Status epilepticus was frequently preceded by fever (10/11 [91%]). Brain MRIs showed symmetric T2/fluid-attenuated inversion recovery hyperintensities (8/11 [73%]) and brain atrophy (9/11 [82%]). Only 2 of the 10 treated patients responded to the first-line immunotherapy, and 4 of the 5 patients treated with IV cyclophosphamide responded to the therapy. The long-term outcome was poor in 8 patients (73%). Compared with 32 patients with NMDARE (median age, 27 years; 24 [75%] women), those with C-NORSE had more frequent prodromal fever, status epilepticus, ventilatory support, and symmetric brain MRI abnormalities, had less frequent involuntary movements, absent psychobehavioral symptoms, CSF oligoclonal bands, or tumor association, and had a worse outcome. The C-NORSE score was higher in patients with C-NORSE than those with NMDARE. CONCLUSIONS: Patients with C-NORSE have a spectrum of clinical-immunological features different from those with NMDARE. The C-NORSE score may be useful for discrimination between them. Some patients could respond to immunotherapy.

Effects of a Public Education Campaign on the Association Between Knowledge of Early Stroke Symptoms and Intention to Call an Ambulance at Stroke Onset: The Acquisition of Stroke Knowledge (ASK) Study.

BACKGROUND: An immediate ambulance call offers the greatest opportunity for acute stroke therapy. Effectively using ambulance services requires strengthening the association between knowledge of early stroke symptoms and intention to call an ambulance at stroke onset, and encouraging the public to use ambulance services. METHODS: The present study utilized data from the Acquisition of Stroke Knowledge (ASK) study, which administered multiple-choice, mail-in surveys regarding awareness of early stroke symptoms and response to a stroke attack before and after a 2-year stroke education campaign in two areas subject to intensive and moderate intervention, as well as in a control area, in Japan. In these three areas, 3833 individuals (1680, 1088 and 1065 participants in intensive intervention, moderate intervention, and control areas, respectively), aged 40 to 74 years, who responded appropriately to each survey were included in the present study. RESULTS: After the intervention, the number of correctly identified symptoms significantly associated with intention to call an ambulance (P < 0.05) increased (eg, from 4 to 5 correctly identified symptoms), without increasing choice of decoy symptoms in the intensive intervention area. Meanwhile, in other areas, rate of identification of not only correct symptoms but also decoy symptoms associated with intention to call an ambulance increased. Furthermore, the association between improvement in the knowledge of stroke symptoms and intention to call an ambulance was observed only in the intensive intervention area (P = 0.009). CONCLUSIONS: Our results indicate that intensive interventions are useful for strengthening the association between correct knowledge of early stroke symptoms and intention to call an ambulance, without strengthening the association between incorrect knowledge and intention to call an ambulance.

Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation.

BACKGROUND: Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation. RESULTS: We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum. CONCLUSIONS: The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns.

Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage specification cascade in the non-differentiating social amoeba, Acytostelium subglobosum.

Separation of somatic cells from germ-line cells is a crucial event for multicellular organisms, but how this step was achieved during evolution remains elusive. In Dictyostelium discoideum and many other dictyostelid species, solitary amoebae gather and form a multicellular fruiting body in which germ-line spores and somatic stalk cells differentiate, whereas in Acytostelium subglobosum, acellular stalks form and all aggregated amoebae become spores. In this study, because most D. discoideum genes known to be required for stalk cell differentiation have homologs in A. subglobosum, we inferred functional variations in these genes and examined conservation of the stalk cell specification cascade of D. discoideum mediated by the polyketide differentiation-inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we confirmed that two of the three genes were functional equivalents, while DIF-methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1 production in this species. On the other hand, the molecular function of an A. subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with that of D. discoideum and inhibition of polyketide synthesis caused developmental arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These results suggest that non-DIF-1 polyketide cascades involving downstream transcription factors are required for fruiting body development of A. subglobosum.

General applicability of synthetic gene-overexpression for cell-type ratio control via reprogramming.

Control of the cell-type ratio in multistable systems requires wide-range control of the initial states of cells. Here, using a synthetic circuit in E. coli, we describe the use of a simple gene-overexpression system combined with a bistable toggle switch, for the purposes of enabling the wide-range control of cellular states and thus generating arbitrary cell-type ratios. Theoretically, overexpression induction temporarily alters the bistable system to a monostable system, in which the location of the single steady state of cells can be manipulated over a wide range by regulating the overexpression levels. This induced cellular state becomes the initial state of the basal bistable system upon overexpression cessation, which restores the original bistable system. We experimentally demonstrated that the overexpression induced a monomodal cell distribution, and subsequent overexpression withdrawal generated a bimodal distribution. Furthermore, as designed theoretically, regulating the overexpression levels by adjusting the concentrations of small molecules generated arbitrary cell-type ratios.

Effects of intensive and moderate public education on knowledge of early stroke symptoms among a Japanese population: the Acquisition of Stroke Knowledge study.

BACKGROUND AND PURPOSE: To assess the effects of intensive and moderate public education on knowledge of early stroke symptoms among a general Japanese population. METHODS: Information on early stroke symptoms was distributed by leaflet 12× and by booklet twice in an intensive intervention area >22 months, and by leaflet and booklet once each in a moderate intervention area. No distribution occurred in the control area. Before and after the intervention, a mailed survey was conducted in the 3 areas. A total of 2734 individuals, aged 40 to 74 years, who did not select all 5 correct symptoms of stroke in the preintervention survey were eligible for our analysis. RESULTS: The numbers of correct answers selected about stroke symptoms did not differ significantly among the 3 areas in the preintervention survey (P=0.156). In the postintervention survey, the proportions of participants who selected sudden 1-sided numbness or weakness (94.2% in the intensive intervention area, 88.3% in the moderate intervention area, and 89.2% in the control area; P<0.001) and sudden severe headache (76.8%, 70.1%, and 70.4%, respectively; P<0.001) differed significantly among the 3 areas. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for correctly choosing all 5 symptoms were 1.35 (1.07-1.71) in the intensive intervention area and 0.96 (0.74-1.24) in the moderate intervention area compared with the control area. CONCLUSIONS: Our findings suggest that frequent distribution of leaflets and booklets significantly improved the short-term knowledge of community residents about early symptoms of stroke.

Public awareness of early symptoms of stroke and information sources about stroke among the general Japanese population: the Acquisition of Stroke Knowledge Study.

BACKGROUND: It is important that the general population be aware of the early symptoms, since it has been shown that early arrival to hospitals leads better prognosis of stroke patients. However, the general population is not well informed about the early symptoms of stroke. This study was conducted to clarify which stroke symptoms are less well known and which information sources are related to awareness of stroke symptoms. METHODS: A multiple-choice, mail-in survey involving 5,540 randomly selected residents, aged 40-74 years, of 3 cities in Japan was conducted. Their knowledge about stroke symptoms and their information sources were surveyed; information sources were classified as mass media (television/newspaper/radio) and personal communication sources (posters/leaflets/internet/health professionals/family and/or friends). 'Awareness' was defined as selecting all 5 of the correct stroke symptoms from among 10 listed symptoms with decoy choices. The estimated fraction of the possible impact due to each source on the whole population was also calculated by odds ratios (ORs) and the proportion of respondents who selected each source (Pe). The combined effects of mass media and personal communication sources on awareness were also assessed. RESULTS: Of the 5,540 residents, only 23% selected all 5 correct symptoms. Visual disturbance was the least known of the 5 symptoms (35%). All sources were positively related to awareness, with ORs (Pe) of: television, 1.58 (72.5%); newspaper, 1.79 (48.0%); radio, 1.74 (13.3%); posters, 1.73 (7.6%); leaflets, 1.50 (24.7%); Internet, 1.66 (5.6%); health professionals, 1.33 (34.8%), and family/friends, 1.21 (44.6%). The estimated fraction of the possible impact due to each source was higher for mass media (television, 0.31 and newspaper, 0.28) than personal communication sources (Internet, 0.04 and leaflets, 0.12). Mass media only and mass media/personal communication sources were significantly associated (ORs: 1.66, 2.75, respectively). CONCLUSIONS: As a single method of public education, television could be the most effective strategy. Moreover, the combined approach involving mass media and personal communication sources might have a synergistic effect. Less well-known symptoms, such as visual disturbances, should be noted in public education campaigns.

Amputation for histiocytic sarcoma in a cat.

A 9-year-old spayed female domestic shorthair cat presented with a skin lesion of the left tarsus. The lesion was biopsied and, based on the microscopic appearance and immunohistochemical characteristics, histiocytic sarcoma was diagnosed. Amputation was performed with improved demeanor seen postoperatively. However, between 44 and 60 days following the surgery, relapse of skin lesions appeared in multiple locations, including at the previous amputation site, and euthanasia was elected. This is the first report of a histiocytic sarcoma treated with amputation in a cat.

[Drinking/smoking habits and knowledge regarding heavy drinking/ smoking as a risk factor of stroke among Japanese general population].

OBJECTIVE: We examined the knowledge regarding heavy drinking and smoking as risk factors of stroke according to drinking/smoking habits among randomly selected Japanese general population. METHODS: The Japan Stroke Association and co-researchers have performed a large-scale educational intervention to improve knowledge concerning stroke from 2006 to 2008. Prior to above-mentioned intervention, we conducted mail-surveillance on knowledge about stroke in 11,306 randomly selected residents aged 40 to 74. We assessed the relationship between drinking/smoking habits and knowledge regarding heavy drinking and smoking as risk factors by using the chi-square test and multiple logistic regression analysis adjusting for age, sex, area, employment, living situation, history of stroke and other stroke related diseases, history of liver disease, family history of stroke and drinking (non-drinker / ex-drinker / occasional drinker / habitual drinker) / smoking habits (non-smoker / ex-smoker / current smoker). RESULTS: Total 5,540 subjects (49.0%) participated in this study. Ex-smokers and current smokers had better knowledge regarding smoking as a risk factor of stroke than non-smokers (odds ratio and 95% confidence intervals: 1.89, 1.55-2.31, 1.76, 1.45-2.12, respectively). CONCLUSION: There was no difference between habitual drinkers and non-drinkers in their knowledge, whereas current smokers had greater knowledge regarding smoking than nonsmokers. Accordingly, it is suggested that it will be necessary for habitual drinkers to be enlightened regarding heavy drinking as a risk factor of stroke and for current smokers to be provided with information regarding not only these risks but also the specific strategies for invoking behavioral changes.

Interdigitation and vesicle-to-micelle transformation induced by a local anesthetic tetracaine in phospholipids bilayers.

The phase transitions of distearoyl- (DSPC), dipalmitoyl- (DPPC) and dimyristoyl-phosphatidylcholine (DMPC) bilayer membranes were observed by means of differential scanning calorimetry as a function of the concentration of a local anesthetic tetracaine hydrochloride (TC.HCl). The depression of both temperatures of the main- and pre-transition, which is accompanied by a decrease in enthalpy changes for both transitions, was observed initially by the addition of TC.HCl. Bilayer interdigitation, which is accompanied by an increase in enthalpy change for the main transition from the interdigitated gel phase to the liquid crystalline phase, was followed by disappearance of the pretransition. The TC.HCl concentration necessary for the bilayer interdigitation was found to be 10, 21 and 6 mmol kg(-1) for DSPC, DPPC and DMPC bilayers, respectively, which was not consistent with the order of acyl-chain length of lipids. Biphasic interactions for the interdigitation, that is, repulsive interaction between polar head groups and van der Waals attractive interaction between hydrophobic chains of lipids, were discussed. On the other hand, vesicle-to-micelle transformation, which is accompanied by a cooperative decrease in enthalpy change for the main transition, was observed at higher concentration of TC.HCl and was confirmed by the vesicle size determined by the dynamic light scattering. The longer the acyl-chain length of lipids, the higher the TC.HCl concentration necessary for the vesicle-to-micelle transformation.

Interaction modes of long-chain fatty acids in dipalmitoylphosphatidylcholine bilayer membrane: contrast to mode of inhalation anesthetics.

The effects of long-chain fatty acids (four saturated and two unsaturated fatty acids, one derivative) on phase transitions of dipalmitoylphosphatidylcholine (DPPC) bilayer membranes were examined in the low concentration region, and the results were compared with those for an inhalation anesthetic. The effects of all fatty acids on the pre- and main-transition temperatures of the DPPC bilayer membrane appeared in the concentration range of microM order while that of the anesthetic appeared in the mM order. The appearance modes of these ligand actions were significantly different from one another. The three differential partition coefficients of the ligands between two phases of the DPPC bilayer membrane were evaluated by applying the thermodynamic equation to the variation of the phase-transition temperatures. The DPPC bilayer membranes showed the different receptivity for the ligands; the saturated fatty acids had an affinity for gel phase whereas unsaturated fatty acids and an anesthetic had an affinity for liquid-crystalline phase to the contrary. In particular, the receptivity for the ligands in the gel phase markedly changed depending on kinds of ligands. The interaction modes between the DPPC and fatty acid molecules in the gel phase were considered from the hexagonal lattice model. The disappearance compositions of the pretransition by the fatty acids coincided with the compositions at which the membrane is all covered by the units in each of which two fatty acids molecules are regularly distributed in the hexagonal lattice in a different way, and the distribution depended on the chain length and existence of a double bond for the fatty acids. The interpretation did not hold for the case of the anesthetic at all, which proved that a number of anesthetic molecules act the surface region of the bilayer membrane nonspecifically. The present study clearly implies that DPPC bilayer membranes have high ability to recognize kinds of ligand molecules and can discriminate among them with specific interaction by the membrane states.

Spontaneous epidural hematoma due to skull metastasis of hepatocellular carcinoma.

Although "spontaneous" epidural hematomas are rare, they can occur in patients with metastatic skull tumors. We describe a case caused by skull metastasis of hepatocellular carcinoma (HCC), and review the relevant literature. In patients with HCC, potential skull metastasis should be kept in mind, since skull metastases from HCC seem to often cause devastating epidural hematoma.

Impact of the approval of intravenous recombinant tissue plasminogen activator therapy on the processes of acute stroke management in Japan: the Stroke Unit Multicenter Observational (SUMO) Study.

BACKGROUND AND PURPOSE: The Ministry of Health, Labor, and Welfare of Japan approved the use of recombinant tissue-type plasminogen activator (rt-PA) for the treatment of acute ischemic stroke in October 2005. The impact of the regulatory approval of rt-PA on the processes of acute stroke management was examined. METHODS: A prospective, multicenter, observational study was conducted between December 2004 and December 2005 in 84 Japanese institutes, including 24 institutes with a stroke unit. We enrolled 4620 consecutive patients who were hospitalized within 72 hours after the onset of completed ischemic stroke; 1089 of them were hospitalized after rt-PA was approved. The patients' characteristics and the processes of stroke management were compared before and after rt-PA approval. RESULTS: Age, gender, stroke subtype, time from onset to hospital visit, and National Institutes of Health Stroke Scale score on admission were similar between the 2 periods. With approval, the percentage of patients treated with intravenous rt-PA therapy increased from 0.7% to 2.6% (P<0.001). The rate increased from 0.9% to 5.2% in institutes with a stroke unit (P<0.001) but did not increase in other institutes (P=0.587). Within 24 hours of stroke onset, conventional MRI (P=0.003), diffusion-weighted MRI (P<0.001), magnetic resonance angiography (P=0.001), carotid ultrasound (P=0.004), measurement of prothrombin time or activated partial thromboplastin time (P=0.034), and measurement of blood sugar (P=0.015) were performed more frequently after rt-PA approval. CONCLUSIONS: The present results indicate that the approval of intravenous rt-PA therapy resulted in dramatic changes in the processes of management for acute stroke patients.

A case of 'lymphomatosis cerebri' diagnosed in an early phase and treated by whole brain radiation: case report and literature review.

'Lymphomatosis cerebri' (LC) is a term indicating a diffusely infiltrating form of primary central nervous system lymphoma (PCNSL) without evidence of a mass lesion. Not infrequently, diagnostic confusion is caused by its presentation on cranial magnetic resonance images (MRI), which is characterized by diffuse leukoencephalopathy without contrast enhancement. In this report, we describe a 53-year-old, immunocompetent man who had an insidiously progressive dementia and right weakness. On serial MRI in 4 months duration, diffuse white matter lesions without contrast enhancement gradually progressed, which was clinically consistent with his worsening condition. Biopsy specimen demonstrated nondestructive, diffusely infiltrating, large B-cell lymphoma, diagnosing LC. After the biopsy, corticosteroids were initiated, which dramatically alleviated his symptoms. Afterwards, he was treated by whole brain irradiation (total 36Gy) and discharged without noticeable deficits. Diagnosis of LC requires additional examinations generally not performed in the other white matter disorders. In suspected cases, biopsy should be performed to avoid deferring adequate cytostatic treatment.

Effect of anticholesterol therapy on soluble ICAM-1 in chronic stroke patients with hyperlipidemia.

OBJECTIVE: We examined the effects of drug therapy with pravastatin (P) or bezafibrate (B) and diet (D) therapy on serum lipids and soluble intercellular adhesion molecule-1 (sICAM-1) in hyperlipidemic cerebrovascular disease (CVD) patients in the chronic stage. METHODS: This study included 36 patients (28 with cerebral infarction and hyperlipidemia and eight with cerebral hemorrhage and hyperlipidemia) divided into three groups: Group P (12 patients), Group B (10 patients), and Group D (14 patients). Before and after treatment, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and sICAM-1 levels were measured. RESULTS: In Group P, Group B and Group D, TC levels were decreased by 30% (p < 0.005), 21% (p < 0.01), and 21% (p < 0.001), LDL-C levels were decreased by 38% (p < 0.005), 18% (not significant), and 25% (p < 0.005) and TG levels were decreased by 27% (p < 0.05), 53% (p < 0.005) and 22% (p < 0.05), respectively. sICAM-1 levels were decreased by 20% (p < 0.005) in Group P, but were not decreased in Group B or Group D. There was no correlation between deltaTC and delta sICAM-1 (r = 0.172). CONCLUSION: Administration of pravastatin significantly reduced sICAM-1 levels, independently of its decreasing effect on TC and TG in chronic CVD patients. Pravastatin may exert anti-atherosclerotic activity via two distinct mechanisms.

[Evaluation of 18F-FDG PET in acute ischemic stroke: assessment of hyper accumulation around the lesion].

PURPOSE: Although pathophysiology of cerebrovascular disease has been reported previously, few clinical studies of glucose metabolism in acute stroke have been published. Purpose of this study is to evaluate glucose metabolism in acute stroke patients by 18F-FDG PET. SUBJECTS AND METHODS: Twenty-four patients with acute ischemic stroke were involved in this study. All subjects underwent MRI (conventional T1- and T2-weighted images, diffusion-weighted imaging, and MR angiography), CT and 18F-FDG PET. 18F-FDG PET was performed within 1 to 7 days after the first episode. 18F-FDG PET images were visually evaluated as well as MRI and CT images. RESULTS: Four patients out of 24 showed no abnormal 18F-FDG accumulation, while MRI demonstrated abnormal signal area and abnormal vascular findings that suggested acute stroke. Decreased 18F-FDG accumulation corresponding with abnormal signal area on MR images was noted in 20 cases. In 7 cases among these 20 with decreased 18F-FDG, hyper accumulation of 18F-FDG was recognized around the decreased accumulation area. CONCLUSION: Increased 18F-FDG accumulation (increased glucose metabolization) around the lesion may be due to: 1) acceleration of anaerobic glycolysis, 2) activated repair process of damaged brain tissue, i.e., phagocytosis and gliosis, and 3) neuronal excitation by excito-toxic amino acids which can be released after ischemia.