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Roving eye movement (RoEM), commonly seen in unconscious patients with significant cortical dysfunction but without apparent brainstem damage, has unclear prognostic significance. We describe a case of presumed hypoglycemic encephalopathy with RoEM, where the patient emerged from a 4‐day coma. While previous reports often associate RoEM cases with poor prognosis, cases with favorable outcomes exist, particularly among young patients or those with reversible conditions. Our findings highlight the variable neurological prognosis of RoEM, suggesting the possibility of improved consciousness and neurological recovery in certain pathologies, thus enhancing our understanding of RoEM's implications. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 70-year-old Japanese woman with antiphospholipid antibody syndrome (APS) who experienced recurrent cerebral infarctions despite standard treatment. The patient was treated with hydroxychloroquine (HCQ) in addition to anticoagulant therapy, which successfully prevented further strokes for 18 months. The article highlights the potential effectiveness of HCQ in reducing thrombotic events in APS patients and suggests that combination therapy with HCQ may be beneficial for those who do not respond to conventional treatments. The findings provide hope for challenging cases of APS. [Extracted from the article]

Bed mattresses are rated as products to cause a fire hazard because of their very high heat release rate among indoor combustibles. In this study, fire growth rate and flame height were measured through a series of combustion experiments on a full scale in order to provide information regarding mattress fire characteristics. The experiments were conducted in an open space, and bed mattresses as the test samples were installed at different installation heights (0~515 mm). The experiment results revealed that the higher the bed mattress was installed, the higher the fire growth rate, the heat release rate, and the flame height. Additionally, the time of the mattress to reach 1 MW was evaluated as the category "medium" in the NFPA 72 standards. The flame heights showed a good coincidence compared to the existing flame height model equations, proving the applicability of the model to the mattress combustion. [ABSTRACT FROM AUTHOR]

The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network. [ABSTRACT FROM AUTHOR]

Some case reports showed that dopaminergic dysfunction is a causative factor of PLMT: PLMT variants associated with Parkinson's disease [[2]] and dopamine antagonist-induced PLMT [[3]]. Dear Editor, Painful legs and moving toes (PLMT) is a rare syndrome characterized by severe pain localized in legs and irregular involuntary toe movement [[1]], and it is an incapacitating syndrome due to the lack of an effective pain therapy [[1]]. [Extracted from the article]

Aim Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. Methods We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. Results Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. Conclusion Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely. [ABSTRACT FROM AUTHOR]

Background Acute decompensated heart failure (ADHF) is a leading cause of hospitalization among the elderly. Discussion of optimal management of ADHF in older patients is a growing health care priority. The aim of this study was to examine the clinical profile, management, and mortality in patients admitted with ADHF according to age. Methods We analyzed 4824 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry from April 2007 to December 2011. Patient characteristics, management, and in-hospital outcomes were compared among four age groups (< 65, 65–74, 75–84, and ≥ 85 years). Results The mean age of the overall population was 73 years; approximately 20% were aged ≥ 85 years. Older patients were more likely to be women and have preserved left ventricular ejection fraction (LVEF) and decreased renal function. Intravenous treatments were well administered in both young and elderly patients irrespective of LVEF. Invasive procedures were less frequently performed in the eldest group. The median length of hospital stay was 21 days, and in-hospital cardiac death in the eldest group was four-fold higher than that in the youngest group (2.2% vs. 8.9%, P < 0.001). Conclusions Clinical characteristics of ADHF differ considerably with age, and cardiac death increases linearly with age. Despite a higher rate of preserved systolic function in very-elderly individuals aged ≥ 85 years, in-hospital mortality was higher, suggesting that more suitable treatments for the elderly might be needed. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in the medial septal nucleus in vitro and in vivo. The precursor, HCNP-pp, is a multifunctional protein participating in important signaling pathways, such as MAPK/ERK kinase (MEK) and G-protein-coupled receptor kinase 2 (GRK2). We recently demonstrated that HCNP-pp colocalizes with collapsin response mediator protein-2 (CRMP-2) at presynaptic terminals in the hippocampus, suggesting that HCNP-pp may play an important role in presynaptic function in association with CRMP-2. To clarify the involvement of phosphorylation in regulating the interaction between HCNP-pp and CRMP-2, we investigated the colocalization of HCNP-pp with unphosphorylated- and/or phosphorylated-CRMP-2 (pCRMP-2) at presynaptic terminals. We further determined if the phosphorylation of CRMP-2 affects the binding between those proteins. Here, we demonstrate that HCNP-pp predominantly colocalizes and associates with unphosphorylated and/or pSer-522-CRMP-2 at presynaptic terminals in the hippocampus. Interestingly, HCNP-pp does not associate with pThr-509/514-CRMP-2, which is primarily localized at postsynaptic terminals. These findings suggest that HCNP-pp, in association with unphosphorylated and/or pSer522-CRMP-2, plays an important role in presynaptic function in the mature hippocampus. [Copyright &y& Elsevier]

The article focuses on a study which reports the presence of pink-pigmented facultative methylotrophs (PPFMs) bacteria on the leaves of various vegetables grown in farms. It mentions the formation of pink pigmented colonies for vegetable leaves which were tested for PPFMs on agar plates containing methanol as sole carbon source. The herb Perilla frutescens viridis reportedly gave highest counts of presence of PPFMs bacteria which accounts for presence of 15 percent of microbes on its leaves.

• The control volume model is used to model the dynamic processes of the evacuees and derive the evacuation times. • The model can be used to simulate different evacuation scenarios of the super high rise buildings. • The parameters of walking speeds and specific flows influence the processes of evacuation significantly. • The influence of coefficient value of specific exit/stair flow is obvious. Issues of safety evacuation of super high-rise buildings for emergencies have been attracting a lot of studies, especially after the disaster of WTC 9/11. In this study, the numerical results and dynamic processes of mass evacuation of a super high rise building are investigated by using the control volume model. The evacuation process of this model is divided into five stages and based on the assumptions of homogeneous flow with merge flow ratio where the exit flows from different floors meet and merge together. The super high-rise building, Taipei 101 is chosen for the object of evacuation simulation building, which is about 508 m tall. Seven scenarios, which content as total building evacuation and phased evacuation, are analyzed by using various values of the parameters which influenced the evacuation process in the building including walking speed, coefficient of flow rate, and merge flow ratio etc. The numerical results of mass evacuation are found to be in good agreement with the result of the National Fire Protection Association (NFPA) first-order approximation and indicate that the evacuation processes are highly dependent on the parameters of walking speed and specific flow. Furthermore, the dynamic characteristics of the evacuation process at each time-step for each floor are presented and discussed. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion Dual antiplatelet therapy (DAPT) with clopidogrel is one of the initial treatment regimens for early neurological deterioration (END) in branch atheromatous disease (BAD). However, its effectiveness is affected by cytochrome P450 2C19 polymorphism. Prasugrel, with reduced cytochrome P450 2C19 interactions, has been approved for cerebrovascular diseases in Japan.To explore the efficacy of DAPT with prasugrel and with clopidogrel in preventing END.Patients with BAD, admitted within 48 h of symptom onset between June 2022 and September 2023, were enrolled. The primary endpoint was the proportion of patients with END within 7 days, which was defined as an increase of 1 point or more on the National Institutes of Health Stroke Scale (NIHSS). Patients meeting specific magnetic resonance imaging (MRI) criteria, including lesions of ≥15 mm in the lenticulostriate artery (LSA) region or infarcts extending to the ventral side of the paramedian pontine region, were included. The patients were randomly assigned to the clopidogrel with loading and prasugrel without loading groups and administered common medications.The study included 9 and 10 patients in clopidogrel and prasugrel groups, of whom 56% and 50% had END, respectively. The prasugrel group had earlier exacerbations after admission (days 0–1) than that of the clopidogrel group (days 1–2). The bleeding complications of both groups were not significantly different.The two groups had similar proportions of patients with END, suggesting comparable efficacies of both drugs for patients with BAD. [ABSTRACT FROM AUTHOR]

We herein describe a 45-year-old man with posterior neck pain and severe dysphagia secondary to retropharyngeal calcific tendinitis. Brain stem infarction as a result of vertebral artery dissection was suspected, but head magnetic resonance imaging showed no acute ischemic lesion. Sagittal T2-weighted neck magnetic resonance imaging showed a retropharyngeal fluid collection from C2 to C8, and neck computed tomography showed calcification at the tendon of the longus colli muscle. Based on these characteristic imaging findings, retropharyngeal calcific tendinitis was diagnosed. Neurologists should remember that retropharyngeal calcific tendinitis can cause neck pain and severe dysphagia, and mimic brain stem infarction as a result of vertebral artery dissection. [ABSTRACT FROM AUTHOR]

Background: A shorter onset‐to recanalization (O2R) time in mechanical thrombectomy for acute ischemic stroke (AIS) results in better outcomes. Thus, we should reduce the door‐to‐puncture (D2P) time. Aim: To evaluate the effectiveness of a triage system named "Code AIS." We adopted the emergency large vessel occlusion (ELVO) screen as a screening test. Methods: Using the ELVO screening test, Code AIS was invoked when ≥1 positive results were obtained without witnessed seizures. The Code AIS system requires the assembly of neurologists, neurosurgeons, and an endovascular team in the emergency department before a patient arrives at the hospital. In total, 104 consecutive patients who underwent thrombectomy after emergency transport from January 2015 to December 2022 were included. The Code AIS system was initiated on February 17, 2022, and patients were divided into the pre‐Code AIS and Code AIS era groups. D2P time, outcome, and other parameters were compared between the groups. Results: Eighty‐eight and 16 cases were in the pre‐Code AIS and Code AIS era groups, respectively. Background factors, including age, sex, and etiology, did not differ between the groups. The median (interquartile range) time of D2P in the Code AIS era was 60 (41–102) min and significantly shortened compared to 135 (109–161) min in the pre‐Code AIS era (p < 0.001). The proportion of patients with favorable outcomes (modified Rankin Scale score, 0–2) improved significantly from 33% (pre‐Code AIS era) to 63% (Code AIS era) (p = 0.047). Conclusion: Using Code AIS, we succeeded in shortening D2P time and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to develop a novel noninvasive test using an artificial intelligence/neural network system (called HCC‐Scope) to diagnose early‐stage hepatocellular carcinoma (HCC) on the background of nonalcoholic steatohepatitis (NASH). Methods: In total, 175 patients with histologically proven nonalcoholic fatty liver disease and 55 patients with NASH‐HCC were enrolled for training and validation studies. Of the 55 patients with NASH‐HCC, 27 (49.1%) had very early‐stage HCC, and six (10.9%) had early‐stage HCC based on the Barcelona Clinic Liver Cancer staging system. Diagnosis with HCC‐Scope was performed based on 12 items: age, sex, height, weight, AST level, ALT level, gamma‐glutamyl transferase level, cholesterol level, triglyceride level, platelet count, diabetes status, and IgM‐free apoptosis inhibitor of macrophage level. The FMVWG2U47 hardware (Fujitsu Co. Ltd, Tokyo, Japan) and the originally developed software were used. Results: HCC‐Scope had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% for the differential diagnosis between non‐HCC and HCC in a training study with gray zone analysis. It was also excellent in the validation study (95.0% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV with gray zone analysis and 95.2% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV without gray zone analysis). HCC‐Scope had a significantly higher sensitivity (85.3%) and specificity (85.1%) than alpha‐fetoprotein (AFP) level, AFP‐L3 level, des‐gamma‐carboxy prothrombin (DCP) level, and the gender–age–AFP‐L3–AFP–DCP (GALAD) score. Conclusions: HCC‐Scope can accurately differentially diagnose between non‐HCC NASH and NASH‐HCC, including very early‐stage NASH‐HCC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although measurement of stent strut by optical coherence tomography (OCT) is important as an index for evaluating incomplete stent apposition, the effects of drug-eluting stents (DES) polymer on it are unknown. Methods and results: DES and bare-metal stents (BMS) as platforms of DES were implanted in an artificial artery. Thickness of stent strut, defined as a distance from inner surface of the strut to the adjacent surface of the tube, and thickness of high-signal band were measured by OCT. Each measurement of DES was significantly larger comparing with BMS. Conclusion: This in-vitro study demonstrates that DES polymer may influence OCT measurement for the stent strut. [ABSTRACT FROM AUTHOR]

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67–2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25–1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23–1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84–4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63–0.67)]. Conclusions: We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients. [ABSTRACT FROM AUTHOR]

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer's disease and Lewy body dementia. [ABSTRACT FROM AUTHOR]

Anti- N-methyl- d-aspartate receptor (NMDAR) limbic encephalitis is the most common form of paraneoplastic encephalitis that is associated with teratomas. Because tumor removal leads to better clinical outcomes, it is essential to reveal the location of the teratomas. This is the first reported case of anti-NMDAR encephalitis associated with teratoma of the fallopian tube. Salpingo-oophorectomy improved neurological symptoms and immunohistochemical examinations indicated the expression of NMDAR on neuroglial cells within the fallopian tube teratoma. Teratomas of the fallopian tube cause anti-NMDAR encephalitis; the imaging analysis and exploratory laparoscopies of the fallopian tube as well as of the ovary should be considered. Surgical removal of both fallopian tubes and ovaries with a normal appearance should be considered for patients in whom immunotherapy is not effective. [ABSTRACT FROM AUTHOR]

Background: The apoptosis inhibitor of macrophage (AIM) is usually associated with the immunoglobulin M (IgM) pentamer in the blood and is dissociated from IgM in various diseases, including hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH). We aimed to elucidate whether IgM‐free AIM (fAIM) is useful for detecting latent HCC in NASH. Methods: This research consisted of two cohort studies. The levels of serum fAIM, alpha‐fetoprotein (AFP), and des‐gamma carboxy prothrombin (DCP) of 18 NASH patients who developed HCC were measured during the follow‐up period before HCC diagnosis (median, 4.7 years). In total, 199 patients with nonalcoholic fatty liver disease (NAFLD) were included in the HCC survey. The serum fAIM levels were analyzed using enzyme‐linked immunosorbent assays. Results: In the cohort of 18 patients with HCC, 12 had high fAIM at the time of the initial blood sample, three had normal fAIM levels throughout the follow‐up period, and three had fAIM elevated from normal to positive. The positive ratio of fAIM prior to HCC diagnosis remained significantly higher than that of AFP and DCP, and the fAIM ratio gradually increased. In a survey of 199 non‐HCC NAFLD patients, a Cox regression analysis using independent variables, such as AFP, fAIM, age, albumin, bilirubin, and fibrosis stage, revealed that fAIM and AFP were significantly associated with the incidence of HCC. Conclusions: During the development of NASH‐HCC, AIM activation in blood appears to start even before HCC is diagnostically detectable. Thus, the serum IgM‐free AIM levels could be a new, sensitive biomarker for latent NASH‐HCC. [ABSTRACT FROM AUTHOR]

Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer's disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Aim: Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non‐alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus‐related chronic liver disease (CLD‐C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD‐C and investigated the underlying mechanisms. Methods: A total of 760 biopsy‐confirmed NAFLD and 1171 CLD‐C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD‐C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. Results: The median platelet counts (×104/μL) of NAFLD and CLD‐C patients were 20.2 and 18.7 (p = 2.4 × 10−5) in F1; 20.0 and 14.5 (p = 2.1 × 10−12) in F2; 16.9 and 12.3 (p = 8.1 × 10−10) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD‐C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD‐C patients, the IPF value of NAFLD patients was significantly higher than that of CLD‐C patients. Conclusions: NAFLD patients had a significantly higher platelet count than CLD‐C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD‐C may have contributed to this difference. [ABSTRACT FROM AUTHOR]

Hippocampal cholinergic neurostimulating peptide (HCNP) regulates acetylcholine synthesis in the septal hippocampus through the quantitative increase of choline acetyltransferase levels in the septal nucleus both in vitro and in vivo. Additionally, HCNP-precursor protein transgenic (HCNP-pp Tg) mice display depressive behavior. To examine the physiological function of HCNP and/or HCNP-pp on hippocampal neural activity, we investigated whether overexpression of HCNP-pp strengthened the efficiency of neural activity in the hippocampus. Long-term potentiation (LTP) of excitatory synaptic transmission was induced by a tetanic stimulation of the Schaffer collateral-commissural fibers (SCs) in mouse hippocampal slices. LTP in HCNP-pp Tg mice was significantly enhanced when compared with wild-type littermate (WT) mice. This facilitation of LTP in HCNP-pp Tg mice was blocked by atropine or pirenzepine, but not by mecamylamine. In contrast, LTP in WT mice was not affected by atropine, but enhanced by carbachol. However, neither difference in the input–output relationship of field excitatory postsynaptic potentials nor in the facilitation ratio in paired-pulse stimulation of the SCs was observed between HCNP-pp Tg and WT mice, indicating that presynaptic glutamate release in HCNP-pp Tg mice is similar to that of WT mice. These results suggest that muscarinic (M1) modulation of glutamatergic postsynaptic function may be involved in strengthening LTP in HCNP-pp Tg mice. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain.Methods: This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test.Results: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse during memantine intervention.Conclusions: Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy.Trial Registration: UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017. [ABSTRACT FROM AUTHOR]

While recent guidelines for the treatment of acute heart failure syndromes (AHFS) recommend pharmacotherapy with vasodilators in patients without excessively low blood pressure (BP), few reports have compared the relative efficiency of vasodilators on hemodynamics in AHFS patients. The present study aimed to assess the differences in hemodynamic responses between intravenous carperitide and nicorandil in patients with AHFS. Thirty-eight consecutive patients were assigned to receive 48-h continuous infusion of carperitide ( n = 19; 0.0125-0.05 μg/kg/min) or nicorandil ( n = 19; 0.05-0.2 mg/kg/h). Hemodynamic parameters were estimated at baseline, and 2, 24, and 48 h after drug administration using echocardiography. After 48 h of infusion, systolic BP was significantly more decreased in the carperitide group compared with that in the nicorandil group (22.1 ± 20.0 % vs 5.3 ± 10.4 %, P = 0.003). While both carperitide and nicorandil significantly improved hemodynamic parameters, improvement of estimated pulmonary capillary wedge pressure was greater in the carperitide group (38.2 ± 14.5 % vs 26.5 ± 18.3 %, P = 0.036), and improvement of estimated cardiac output was superior in the nicorandil group (52.1 ± 33.5 % vs 11.4 ± 36.9 %, P = 0.001). Urine output for 48 h was greater in the carperitide group, but not to a statistically significant degree (4203 ± 1542 vs 3627 ± 1074 ml, P = 0.189). Carperitide and nicorandil were differentially effective in improving hemodynamics in AHFS patients. This knowledge may enable physicians in emergency wards to treat and manage patients with AHFS more effectively and safely. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in medial septal nucleus in vitro and in vivo. HCNP precursor protein (HCNP-pp) is a multifunctional protein that participates in a number of signaling pathways, including MAPK/extracellular signal and G-protein-coupled receptor kinase 2. We recently demonstrated that the amount of collapsin response mediator protein-2 (CRMP-2) is increased in hippocampus of HCNP-pp transgenic mice. To clarify the interaction between HCNP/HCNP-pp and CRMP-2 and its role in synaptic function, we investigated whether HCNP-pp is localized to the synapse and if it affects protein expression. Here, we demonstrate that HCNP-pp co-localizes with CRMP-2 at presynaptic terminals. Furthermore, HCNP-pp overexpression increases synaptophysin levels. These findings suggest that HCNP-pp, in association with CRMP-2, plays an important role in presynaptic function in the hippocampus. [Copyright &y& Elsevier]

We have investigated solid electrolyte switches that utilize electrochemical reactions (deposition and dissolution) of metallic ions. The switch turns off or on when a metallic bridge electrochemically forms or dissolves in the solid electrolyte. Each state is nonvolatile and the switching is repeatable up to 105 cycles. The promising application is a programmable switch in a field programmable logic because of its small size (<30 nm) and low ON resistance (<100Ω). This paper discusses the electrical characteristics, operation principle, and applications of the solid electrolyte switch. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 165(1): 68–73, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20542 [ABSTRACT FROM AUTHOR]

Aim: Type IV collagen 7S (T4C7S) is a valuable biomarker for detecting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). The conventional T4C7S measurement via radioimmunoassay (T4C7S RIA) has shortcomings of radioisotope usage and longer assay periods. We compared T4C7S RIA with a newly developed, fast T4C7S chemiluminescent enzyme immunoassay (T4C7S CLEIA) and examined the diagnostic accuracies of and correlation between the two techniques. Methods: We evaluated 170 biopsy‐confirmed patients with NAFLD. T4C7S was measured via both T4C7S RIA and T4C7S CLEIA. The correlation between T4C7S RIA and T4C7S CLEIA was analyzed in 305 total serum samples via exploratory research and 47 validation samples. The diagnostic accuracies of T4C7S CLEIA and T4C7S RIA were compared in the sera of patients with NAFLD and test samples. Results: Sera T4C7S levels of T4C7S CLEIA and T4C7S RIA significantly correlated in patients' samples via exploratory (r = 0.914, P = 0.000) and validation (r = 0.929, P = 0.000) research. At a 10% coefficient, T4C7S CLEIA concentration was 0.26 ng/ml in the serum samples, indicating high accuracy at even low concentrations. T4C7S CLEIA revealed distinct changes between each stage and high sensitivity in detecting the F2 stage, indicating a higher sensitivity in detecting low fibrosis stages than T4C7S RIA in patients with NAFLD. Conclusions: The T4C7S CLEIA correlated well with the T4C7S RIA. Favorably, the T4C7S CLEIA has a higher sensitivity and rapid measurement time and requires a small sample volume; thus, it is a promising and popular biomarker for fibrosis stage diagnosis in NAFLD. [ABSTRACT FROM AUTHOR]

Cholinergic neural activation from the medial septal nucleus to hippocampus plays a crucial role in episodic memory as a regulating system for glutamatergic neural activation in the hippocampus. As a candidate regulating factor for acetylcholine synthesis in the medial septal nucleus, hippocampal cholinergic neurostimulating peptide (HCNP) was purified from the soluble fraction of young adult rat hippocampus. HCNP is released from its precursor protein (HCNP-pp), also referred to as phosphatidylethanolamine-binding protein 1. We recently reported that HCNP-pp conditional knockout (KO) mice, in which the HCNP-pp gene was knocked out at 3 months of age by tamoxifen injection, display no significant behavioral abnormalities, whereas HCNP-pp KO mice have a diminished cholinergic projection to CA1 and a decreased of theta activity in CA1. In this study, to address whether HCNP-pp reduction in early life is associated with behavioral changes, we evaluated the behavior of HCNP-pp KO mice in which HCNP-pp was downregulated from an early phase (postnatal days 14–28). As unexpected, HCNP-pp KO mice had no behavioral deficits. However, a significant positive correlation between HCNP-pp and gamma-aminobutyric acid A (GABA A) receptor α3 subunit mRNA expression was found in individuals. This finding suggests involvement of HCNP-pp in regulating GABA A receptor α3 gene expression. • HCNP-pp expression is associated with the MAPK, GSK3β and NF-kB pathways. • HCNP-pp expression correlated with GABA A receptor α3 that is involved in depression. • HCNP-pp function related GABA A could help elucidate the pathogenesis of depression. [ABSTRACT FROM AUTHOR]

Background: Numerous biomarkers have been developed for assessing the presence and severity of liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD). Fibrosis can be assessed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). Here we examined whether diagnostic accuracy and applicability can be further improved by combining various biomarker measurements with LSM.Methods: A total of 278 patients with biopsy-confirmed Japanese NAFLD patients were enrolled. Area under the receiver operator characteristic curve (AUROC) was evaluated for obtaining the optimum interpretation criteria for LSM by VCTE and comparing various biomarkers alone and in combination with LSM.Results: Liver stiffness measurements including cases with interquartile range (IQR)/median (M) < 30% or LSM ≤ 7.1 kPa demonstrated high applicability (90% of patients with NAFLD) and accuracy (AUROC: 0.891) for predicting stage ≥ 3 fibrosis. For all biomarkers tested, the AUROC values for predicting stage ≥ 3 fibrosis were increased when combined with LSM [platelet count, 0.734 vs. 0.912; type-4 collagen 7s (T4C7s), 0.894 vs. 0.921; aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), 0.774 vs. 0.906; AST to platelet ratio index, 0.789 vs. 0.902; FIB-4 index, 0.828 vs. 0.922; NAFLD fibrosis score, 0.800 vs. 0.906; CA index-fibrosis, 0.884 vs. 0.913; FM-fibro index, 0.920 vs. 0.943; FIB-4 index + T4C7s, 0.901 vs. 0.930], demonstrating the advantage of concurrent LSM.Conclusions: While VCTE has slightly limited applicability (90%) for patients with NAFLD, concurrent measurement with certain biomarkers (especially FM-fibro, T4C7s, and FIB-4) greatly improves the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: A diagnostic marker is needed enabling early and specific diagnosis of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH). Our recent findings have indicated that circulating apoptosis inhibitor of macrophage (AIM), which usually associates with IgM pentamer in the blood, is activated by its dissociation from IgM. We investigated the serum levels of IgM-free AIM for AIM activation and its possible relationship with development of HCC in NASH.Methods: Serum levels of IgM-associated and IgM-free AIM were evaluated in patients with non-alcoholic fatty liver, NASH, and NASH-HCC using enzyme-linked immunosorbent assays and immunoblots. Liver biopsy specimens were graded and staged using Brunt's classification.Results: Forty-two patients with fatty liver, 141 with NASH, and 26 with NASH-HCC were evaluated. Patients with stage 4 or grade 3 NASH (with or without HCC) exhibited significantly higher levels of both IgM-free and total AIM than those with fatty liver, whereas the ratio of IgM-free-to-total AIM was equivalent in these groups. Among patients with the same fibrosis stage of NASH, those with HCC had significantly higher IgM-free but not total AIM levels, resulting in a proportional increase in the IgM-free/total AIM ratio. Analysis of the areas under the receiver operating characteristic curves indicated the high sensitivity of the IgM-free AIM for NASH-HCC.Conclusions: Our observations suggest the activation of AIM in blood in the presence of NASH-HCC, with a significant increase in IgM-free AIM levels. IgM-free AIM serum levels appear to be a sensitive diagnostic marker for NASH-HCC. [ABSTRACT FROM AUTHOR]

Background: Recently we reported novel noninvasive scoring systems for diagnosing nonalcoholic steatohepatitis (NASH) and related fibrosis, namely FM-NASH index and FM-fibro index. They are highly accurate, however, they contain some items not widely used in clinical practice and require six or more items to diagnose both NASH and related fibrosis. By focusing on widely used items, we tried to identify convenient markers in common with the both diagnoses.Methods: To explore the markers for NASH and related fibrosis in nonalcoholic fatty liver disease (NAFLD) patients, we used data of 24 clinical items in our previous report. By logistic regression analysis, we identified items suitable for the both diagnoses. We then evaluated their accuracies by area under the receiver operator characteristic curves (AUROCs) on independent validation data.Results: We identified the combination of type IV collagen 7S and aspartate aminotransferase (AST) as the predictor both for NASH and related fibrosis. We developed a scoring system based on the combination and evaluated the prediction accuracy: the AUROCs for training/validation data sets are 0.857/0.769 for NASH and 0.918/0.842 for NASH-related fibrosis. The former was higher than that of NAFIC score, and the latter was higher than those of existing fibrosis markers: BARD score, FIB-4 index and NAFLD fibrosis score but lower than FM-fibro index.Conclusions: The scoring system using type IV collagen 7S and AST named CA index can predict both NASH and related fibrosis in NAFLD patients with sufficient accuracy and could be a convenient diagnostic and screening tool for NASH and related fibrosis. The scoring system needs to be validated in independent larger populations from multiple clinical centers. [ABSTRACT FROM AUTHOR]

Aim Transient elastography (TE) is a non-invasive method for predicting liver fibrosis. However, there are limited data regarding the performance of TE in Japanese patients with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. Methods A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan. The area under the receiver operating characteristic curve of LSM and other non-invasive markers of liver fibrosis were compared to determine the most accurate method of predicting liver fibrosis. Results Liver stiffness measurement significantly correlated with fibrosis stage ( P < 0.001). The areas under the receiver operating characteristic curve of LSM for fibrosis stage ≥1 and ≥3 was 0.85 and 0.91, respectively and were higher than those of the aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, fibrosis-4 index, and NAFLD fibrosis score. The best cut-off values of LSM fibrosis stage ≥1 and ≥3 were 7.2 kPa (sensitivity 78.5%, specificity 78.3%) and 10.0 kPa (sensitivity 89.5%, specificity 87.6%), respectively. The combination of LSM (≥10 kPa) and type IV collagen 7 s (≥6.0 ng/mL) had a specificity of 97.6% for advanced fibrosis. The LSM in patients with high alanine aminotransferase levels or high body mass index was associated with false positive results regarding advanced fibrosis. Conclusions In NAFLD patients, TE has excellent utility for the assessment of liver fibrosis, particularly for advanced stage cases. The cut-off value of LSM by TE for predicting liver fibrosis stage ≥3 is 10.0 kPa in Japanese NAFLD patients. [ABSTRACT FROM AUTHOR]

Abstract: A 62‐year‐old woman presented with left hemiparesis just after finishing lymphatic draining massage involving the four extremities. Diffusion‐weighted magnetic resonance imaging showed an acute infarct in the right precentral gyrus. The diagnosis of paradoxical cerebral embolism was established on the findings of transesophageal echocardiography and detected thrombi in the leg veins. Movement of extant thrombi in the legs to the right atrium, in association with massage, is considered to have contributed to the stroke onset. [ABSTRACT FROM AUTHOR]

Background: Host genetic factors have been suspected to influence histological liver damage in chronic liver disease. The nonsynonymous single-nucleotide polymorphism rs738409 C > G in the patatin-like phospholipase domain-containing 3 gene ( PNPLA3, also known as adiponutrin), encoding the I148 M protein variant, has been identified as a novel genetic marker for hepatic steatosis and fibrosis in nonalcoholic fatty liver disease and alcoholic liver disease. We aimed to determine whether the PNPLA3 rs738409 variant was associated with hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C. Methods: In a cross-sectional study in Japan, we analyzed 276 patients with chronic hepatitis C who underwent liver biopsy. Genotyping for rs738409 was performed using the TaqMan genotyping assay. Results: The frequencies of the rs738409 CC, CG, and GG genotypes were 32.6, 46.4, and 21.0 %, respectively. Multivariate analysis revealed that the GG genotype was independently associated with the presence of steatosis [odds ratio (OR) 2.58, 95 % confidence interval (CI) 1.37-4.84, p = 0.003], severe necroinflammatory activity (OR 2.16, 95 % CI 1.12-4.16, p = 0.02), and advanced fibrosis (OR 2.10, 95 % CI 1.07-4.11, p = 0.03), after adjustment for age, sex, body mass index, and diabetes. Conclusions: The PNPLA3 rs738409 variant influences histological liver damage in Japanese patients with chronic hepatitis C. The G allele homozygotes are at higher risk for hepatic steatosis, severe necroinflammation, and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Aim Although non-alcoholic fatty liver disease ( NAFLD) is the hepatic manifestation of metabolic syndrome, the clinical association between non-alcoholic steatohepatitis ( NASH) and lifestyle-related diseases such as obesity, type 2 diabetes mellitus ( DM), hypertension ( HT) and dyslipidemia ( DL) has not been clarified. We studied the influence of lifestyle-related diseases and age on the development and progression of NAFLD. Methods We enrolled 550 patients with biopsy-proven NAFLD (284 men, 266 women; average age, 52 and 62 years, respectively). The effect of lifestyle-related diseases and age (≤49 vs ≥50 years) on the frequency of NASH and advanced fibrosis (≥stage 3) was studied. Results Prevalence of obesity, DM, HT and DL in male and female NASH patients was 75%/67%, 53%/54%, 66%/77% and 85/79%, respectively. DM patients had a higher frequency of NASH in the older male NAFLD group and a higher frequency of advanced fibrosis in the older female NASH group. With the increasing number of complicating lifestyle-related diseases, the rate of NASH increased in male NAFLD patients. In both sexes, aging resulted in the development of NASH and progression of liver fibrosis. Multivariate logistic regression analysis revealed that age and DM were significantly associated with the development of NASH in male NAFLD patients and progression of fibrosis in female NASH patients. Conclusion Age is strongly associated with the development and progression of NASH. Type 2 DM may play the most crucial role among lifestyle-related diseases in the development and progression of NASH. [ABSTRACT FROM AUTHOR]

Aim Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma ( HCC). We aimed to assess the efficacy and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. Methods In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male; 95% Child-Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. Results Median overall survival was 10.6 months in all patients: 11.7 months in patients aged 80 years and older and 10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort. Conclusion Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction associated with acute decompensated heart failure (ADHF) is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation. Methods and Results: ADHF syndromes registry subjects were evaluated (N = 4,321). Logistic regression modeling calculated adjusted odds ratios (OR) for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure) or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide) to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8%) patients aged 73.3±13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75–3.18, p<0.001), and the prognostic impact of renal dysfunction was similar in subgroup of patients with hypoperfusion- or congestion-dominant clinical profiles (p-value for the interaction ranged from 0.104–0.924, and was always >0.05). Conclusions: Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Background: Randomized controlled trials concerning pulmonary artery catheters (PACs) use have yielded little evidence of their beneficial effects on survival. This study aimed to evaluate the association between PACs and in-hospital mortality in patients with acute heart failure syndromes (AHFS). Methods: The Acute Decompensated Heart Failure Syndromes (ATTEND) Registry is a prospective, observational, multicenter cohort study performed in Japan, since April 2007. We analyzed data from the ATTEND Registry and evaluated the effectiveness of PAC in AHFS treatment using propensity score-matching and the Cox proportional hazards model. Results: Final follow-up examinations of the 4842 patients were conducted in December 2012. During the study period, 813 patients (16.8%) were managed with PACs, of which 502 patients (PAC group) were propensity score-matched with 502 controls (Control group). Of the 1004 score-matched patients, 22 (4.4%) patients from the Control group and 7 (1.4%) from the PAC group died. The risk of all-cause death was lower in the PAC group than that in the Control group [hazard ratio (HR), 0.3; 95% confidence interval (CI), 0.13–0.70; p=0.006]. PAC-guided therapy decreased all-cause mortality in patients with lower systolic blood pressure (SBP≤100mmHg; HR, 0.09; 95% CI, 0.01–0.70; p=0.021) or inotropic therapy (HR, 0.22; 95% CI, 0.08–0.57; p=0.002). Conclusions: This study revealed that appropriate PAC use effectively decreases in-hospital mortality in AHFS patients, particularly those with lower SBP or receiving inotropic therapy, suggesting that real-world PAC use could improve AHFS management. [Copyright &y& Elsevier]

Background: The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. Methods: In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Results: Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Conclusions: Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium <135 mEq/L) was observed in 11.6% of patients. Patients with hyponatremia were of similar age, included fewer men, and had a higher proportion of previous hospitalizations for HF compared to those with normonatremia. On admission, lower heart rates and blood pressures and higher brain natriuretic peptide levels were observed in patients with hyponatremia. During hospitalization, inotrope levels and mechanical device use were significantly higher in patients with hyponatremia. Rates of allcause and cardiac death were significantly higher in patients with hyponatremia, 15.0% and 11.4%, respectively, compared to 5.3% and 3.6%, respectively, in those with normonatremia. In hyponatremic hospitalized patients with HF, cardiac death accounted for 76.2% of all-cause death. In conclusion, the present study demonstrates that in Japan hyponatremia in patients hospitalized with HF is relatively common and is associated with a very high in-hospital mortality. [ABSTRACT FROM AUTHOR]

We propose a three-terminal nanometer metal switch that utilizes a solid electrolyte where a nanoscale metal filament is stretched and retracted. Its operating principle is based on electrochemical reaction and ion migration in the electrolyte. The fabricated device is composed of a solid electrolyte layer (CuS), a gate (Cu), a source (Cu), and a drain (Pt). After the Cu filament is formed between the source and the drain by applying the drain voltage, repeatable on/off switching in the drain current is obtained by controlling the gate voltage. The on/off current ratio can be as high as 10, and the programmable cycle is around 50. Each state can be kept for up to 40 days. Since the gate is separated from the current path, the switching current can be reduced to 10 μA, which is two orders of magnitude smaller than that of a two-terminal switch. In this paper, we present the operating principle and electrical characteristics of the three-terminal switches, and discuss how suitable they are for reconfigurable circuits. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(4): 55-61, 2011; Published online in Wiley Online Library (). DOI 10.1002/ecj.10214 [ABSTRACT FROM AUTHOR]

Both insulin resistance and increased oxidative stress in the liver are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Senescence marker protein-30 (SMP30) was initially identified as a novel protein in the rat liver, and acts as an antioxidant and antiapoptotic protein. Our aim was to determine whether hepatic SMP30 levels are associated with the development and progression of NAFLD. Liver biopsies and blood samples were obtained from patients with an NAFLD activity score (NAS) ≤ 2 ( n = 18), NAS of 3–4 ( n = 14), and NAS ≥ 5 ( n = 66). Patients with NAS ≥ 5 had significantly lower hepatic SMP30 levels (12.5 ± 8.4 ng/mg protein) than patients with NAS ≤ 2 (30.5 ± 14.2 ng/mg protein) and patients with NAS = 3–4 (24.6 ± 12.2 ng/mg protein). Hepatic SMP30 decreased in a fibrosis stage-dependent manner. Hepatic SMP30 levels were correlated positively with the platelet count ( r = 0.291) and negatively with the homeostasis model assessment of insulin resistance ( r = −0.298), the net electronegative charge modified-low-density lipoprotein ( r = −0.442), and type IV collagen 7S ( r = −0.350). The immunostaining intensity levels of 4-hydroxynonenal in the liver were significantly and inversely correlated with hepatic SMP30 levels. Both serum large very low-density lipoprotein (VLDL) and very small low-density lipoprotein (LDL) levels in patients with NAS ≥ 5 were significantly higher than those seen in patients with NAS ≤ 2, and these lipoprotein fractions were significantly and inversely correlated with hepatic SMP30. These results suggest that hepatic SMP30 is closely associated with the pathogenesis of NAFLD, although it is not known whether decreased hepatic SMP30 is a result or a cause of cirrhosis. [ABSTRACT FROM AUTHOR]

The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei. HCNP is processed from the N-terminal region of a 186 amino acid, 21 kD HCNP precursor protein called HCNP-pp (also known as Raf kinase inhibitory protein (RKIP) and phosphatidylethanolamine-binding protein 1 (PEBP1)). In this study, we generated HCNP-pp knockout (KO) mice and assessed their cholinergic septo-hippocampal projection, local field potentials in CA1, and behavioral phenotypes. No significant behavioral phenotype was observed in HCNP-pp KO mice. However, theta power in the CA1 of HCNP-pp KO mice was significantly reduced because of fewer cholineacetyltransferase-positive axons in the CA1 stratum oriens. These observations indicated disruption of cholinergic activity in the septo-hippocampal network. Our study demonstrates that HCNP may be a cholinergic regulator in the septo-hippocampal network. [ABSTRACT FROM AUTHOR]