Detection of Neodymium-Rich Phase for Development of Coercivity in Neodymium-Iron-Boron-Based Alloys with Submicron-Sized Grains Using Positron Lifetime Spectroscopy

In order to evaluate the relationship between positron lifetime and microstructure, which contributes to the development of coercivity in hydrogenation-disproportionation-desorption-recombination (HDDR)-processed Nd-Fe-B-based alloys, detailed studies of positron lifetime spectroscopy were performed on HDDR-processed Nd-Fe-B-based alloys during desorption-recombination (DR) treatment. After the onset of coercivity, the change in positron lifetime closely corresponded to the change in intrinsic coercivity (H cJ ) with the progress of DR treatment. This result can be explained in terms of the grain size of the recombined Nd 2 Fe 14 B phases and the diffusion length of positrons, which annihilate in the matrix before reaching the grain boundary. Furthermore, positron lifetime spectroscopy was able to detect small changes in the grain boundary region very sensitively compared with thermal desorption spectroscopy (TDS) and X-ray diffraction (XRD). These changes in the grain boundary region caused the onset of coercivity attributed to the formation of Nd-rich intergranular phases. These results indicate that formation of a small amount of the Nd-rich intergranular phase during the DR process, which could be detected by positron lifetime spectroscopy, contributes to the onset of coercivity, even if NdH x phases remain

Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity

The adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death. We have found that ASC activation induced caspase-8-dependent apoptosis or CA-074Me (cathepsin B inhibitor)-inhibitable necrosis depending on the cell type. Unlike necroptosis, another necrotic cell death, ASC-mediated necrosis, was neither RIP3-dependent nor necrostatin-1-inhibitable. Although acetyl-YVAD- chloromethylketone (Ac-YVAD-CMK) (caspase-1 inhibitor) did not inhibit ASC-mediated necrosis, comprehensive gene expression analyses indicated that caspase-1 expression coincided with the necrosis type. Furthermore, caspase-1 knockdown converted necrosis-type cells to apoptosis-type cells, whereas exogenous expression of either wild-type or catalytically inactive caspase-1 did the opposite. Knockdown of caspase-1, but not Ac-YVAD-CMK, suppressed the monocyte necrosis induced by Staphylococcus and Pseudomonas infection. Thus, the catalytic activity of caspase-1 is dispensable for necrosis induction. Intriguingly, a short period of caspase-1 knockdown inhibited IL-1β production but not necrosis, although longer knockdown suppressed both responses. Possible explanations of this phenomenon are discussed. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Mechanism and repertoire of ASC-mediated gene expression

金沢大学がん研究所Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an adaptor molecule that mediates inflammatory and apoptotic signals. Although the role of ASC in caspase-1-mediated IL-1beta and IL-18 maturation is well known, ASC also induces NF-kappaB activation and cytokine gene expression in human cells. In this study, we investigated the molecular mechanism and repertoire of ASC-induced gene expression in human cells. We found that the specific activation of ASC induced AP-1 activity, which was required for optimal IL8 promoter activity. ASC activation also induced STAT3-, but not STAT1-, IFN-stimulated gene factor 3- or NF-AT-dependent reporter gene expression. The ASC-mediated AP-1 activation was NF-kappaB-independent and primarily cell-autonomous response, whereas the STAT3 activation required NF-kappaB activation and was mediated by a factor that can act in a paracrine manner. ASC-mediated AP-1 activation was inhibited by chemical or protein inhibitors for caspase-8, caspase-8-targeting small-interfering RNA, and p38 and JNK inhibitors, but not by a caspase-1 inhibitor, caspase-9 or Fas-associated death domain protein (FADD) dominant-negative mutants, FADD- or RICK-targeting small-interfering RNAs, or a MEK inhibitor, indicating that the ASC-induced AP-1 activation is mediated by caspase-8, p38, and JNK, but does not require caspase-1, caspase-9, FADD, RICK, or ERK. DNA microarray analyses identified 75 genes that were induced by ASC activation. A large proportion of them was related to transcription (23%), inflammation (21%), or cell death (16%), indicating that ASC is a potent inducer of inflammatory and cell death-related genes. This is the first report of ASC-mediated AP-1 activation and the repertoire of genes induced downstream of ASC activation

トクシマ コウケツアツ トウニョウビョウ study : コウケツアツ トウニョウビョウ ガッペイレイ ニ カンスル リンショウテキ ケントウ

Hypertension is frequently complicated by diabetes mellitus and vice versa. Since these ２ disorders are important risk factors for atherosclerotic cardiovascular diseases, appropriate disease control is required. To understand the present state of treatment, we investigated hypertensive patients complicated by diabetes mellitus and vice versa who were under treatment by cardiology and diabetes specialists in Tokushima Prefecture, and evaluated the details of treatment and the state of disease control. The subjects consisted of １８２ hypertensive patients complicated by diabetes mellitus （Group C） who were under treatment by cardiology specialists and ２０５ diabetic patients complicated by hypertension （Group D） who were under treatment by diabetes specialists. When patient backgrounds were evaluated, patient age and BMI were significantly higher in Group C than in Group D, although HbA１c levels were significantly higher in Group D than in Group C. Calcium antagonists were most frequently used for the treatment of hypertension in both groups （７０．９％ in Group C and ６５．４％ in Group D）, and the percentage of patients who were treated with β‐blockers was significantly higher in Group C than in Group D （２８．６％ in Group C vs.８．８％ in Group D, p＜０．０００５）. The percentage of patients who fulfilled the criteria of blood pressure recommended by the Guidelines for the Management of Hypertension （JSH２０００） was ２１．６％ in Group C and ２２．９％ in Group D. When the type of antidiabetics was investigated, SU derivatives were most frequently used for the treatment of diabetes mellitus in both groups （４７．２％ in Group C and ５０．２％ in Group D, n.s.）, followed by the use of α‐GI, insulin, and biguanide in descending order. The percentage of patients who were treated with those types of antidiabetics did not significantly differ between the two groups. The percentage of patients who showed HbA１c levels below ６．５％ was significantly higher in Group C than in Group D （４０．７％ in Group C vs．２１．９％ in Group D p＜０．００５）. However, the percentage of patients who showed HbA１c levels of ８．０％ or higher was significantly higher in Group D than in Group C （１８．９％ in Group C vs. ３６．８％ in Group D, p＜０．０００１）. In addition, the percentage of patients in whom total cholesterol levels were successfully controlled based on the Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases （JAS２００２） did not significantly differ between the two groups （４９．７％ in Group C vs. ４５．０％ in Group D）. These findings suggest that the group at high-risk of atherosclerosis, such as hypertensive patients complicated by diabetes mellitus and vice versa, is not successfully managed. Therefore, more appropriate disease control is required in the future

Comparison of supraglottic airway versus endotracheal intubation for the pre-hospital treatment of out-of-hospital cardiac arrest

10.1186/cc10483Critical Care155R23

Comparison of supraglottic airway versus endotracheal intubation for the pre-hospital treatment of out-of-hospital cardiac arrest

Introduction: Both supraglottic airway devices (SGA) and endotracheal intubation (ETI) have been used by emergency life-saving technicians (ELST) in Japan to treat out-of-hospital cardiac arrests (OHCAs). Despite traditional emphasis on airway management during cardiac arrest, its impact on survival from OHCA and time dependent effectiveness remains unclear.Methods: All adults with witnessed, non-traumatic OHCA, from 1 January 2005 to 31 December 2008, treated by the emergency medical services (EMS) with an advanced airway in Osaka, Japan were studied in a prospective Utstein-style population cohort database. The primary outcome measure was one-month survival with neurologically favorable outcome. The association between type of advanced airway (ETI/SGA), timing of device placement and neurological outcome was assessed by multiple logistic regression.Results: Of 7,517 witnessed non-traumatic OHCAs, 5,377 cases were treated with advanced airways. Of these, 1,679 were ETI while 3,698 were SGA. Favorable neurological outcome was similar between ETI and SGA (3.6% versus 3.6%, P = 0.95). The time interval from collapse to ETI placement was significantly longer than for SGA (17.2 minutes versus 15.8 minutes, P < 0.001). From multivariate analysis, early placement of an advanced airway was significantly associated with better neurological outcome (Adjusted Odds Ratio (AOR) for one minute delay, 0.91, 95% confidence interval (CI) 0.88 to 0.95). ETI was not a significant predictor (AOR 0.71, 95% CI 0.39 to 1.30) but the presence of an ETI certified ELST (AOR, 1.86, 95% CI 1.04 to 3.34) was a significant predictor for favorable neurological outcome.Conclusions: There was no difference in neurologically favorable outcome from witnessed OHCA for ETI versus SGA. Early airway management with advanced airway regardless of type and rhythm was associated with improved outcomes.Kajino, K., Iwami, T., Kitamura, T. et al. Comparison of supraglottic airway versus endotracheal intubation for the pre-hospital treatment of out-of-hospital cardiac arrest. Crit Care 15, R236 (2011). https://doi.org/10.1186/cc1048

トクシマ コウケツアツ トウニョウビョウ study 2011 : コウケツアツ トウニョウビョウ ガッペイ レイ ニ カンスル タシセツ ケンキュウ

Cardiologists and diabetologists in Tokushima Prefecture investigated patients with hypertension and diabetes mellitus on treatment in２０１１. The findings were compared with our year‐２００４ data. The study population comprised ２３６ patients with hypertension and diabetes mellitus being treated by cardiologists（C２０１１group）, and ３９５ patients with the same condition being treated by diabetologists（D２０１１group）. The mean number of antihypertensives used per patient was１．９for the C２０１１group and１．６for the D２０１１group. In these two groups, calcium antagonists were the most frequently used drugs. Renin-angiotensin system（RAS）inhibitors were used in７１．５％ of the patients in the C２０１１group and７０．０％ in the D２０１１group. The ratio of patients meeting the blood pressure criteria of the Japan Hypertension Society Guidelines was ２１．６％ for the C２００４group,２２．９％ for the D２００４group,２９．１％ for the C２０１１group, and１８．２％ for the D２０１１group. The mean number of antidiabetics used per patient was１．３for the two groups, glimepiride being most frequently used（３８．５％ for the C２０１１group,５８．１％ for the D２０１１group）, followed by α-glucosidase inhibitors and pioglitazone. Frequency of use of biguanide increased compared with２００４. The ratio of patients with HbA１c＜６．５％ was４０．７％ for the C２００４group, ２１．９％ for the D２００４ group, ４６．５％ for the C２０１１ group, and ４９．０％ for the D２０１１ group ; a significant improvement was observed in the D２０１１group compared with the D２００４group. The serum cholesterol control rate was４９．７％ for the C２００４group,４５．０％ for the D２００４group,６０．９％ for the C２０１１group, and５６．５％ for the D２０１１group. The ratio of patients achieving good control for all three parameters（blood pressure, blood glucose level, serum lipid level）was low at７．６％ for the C２００４group,６．７％ for the D２００４group,９．４％ for the C２０１１group, and９．０％ for the D２０１１ group. This managerial situation for the condition is unsatisfactory, necessitating efforts for even better control

An association between systolic blood pressure and stroke among patients with impaired consciousness in out-of-hospital emergency settings

Background: Stroke is difficult to diagnose when consciousness is disturbed. However few reports have discussed the clinical predictors of stroke in out-of-hospital emergency settings. This study aims to evaluate the association between initial systolic blood pressure (SBP) value measured by emergency medical service (EMS) and diagnosis of stroke among impaired consciousness patients. Methods: We included all patients aged 18 years or older who were treated and transported by EMS, and had impaired consciousness (Japan Coma Scale ≧ 1) in Osaka City (2.7 million), Japan from January 1, 1998 through December 31, 2007. Data were prospectively collected by EMS personnel using a study-specific case report form. Multiple logistic regressions assessed the relationship between initial SBP and stroke and its subtypes adjusted for possible confounding factors. Results: During these 10 years, a total of 1,840,784 emergency patients who were treated and transported by EMS were documented during the study period in Osaka City. Out of 128,678 with impaired consciousness, 106,706 who had prehospital SBP measurements in the field were eligible for our analyses. The proportion of patients with severe impaired consciousness significantly increased from 14.5% in the =200 mmHg SBP group (P for trend =200 mmHg group versus the SBP 101-120 mmHg group was 5.26 (95% CI 4.93 to 5.60). The AOR of the SBP > =200 mmHg group versus the SBP 101-120 mmHg group was 9.76 in subarachnoid hemorrhage (SAH), 16.16 in intracranial hemorrhage (ICH), and 1.52 in ischemic stroke (IS), and the AOR of SAH and ICH was greater than that of IS. Conclusions: Elevated SBP among emergency patients with impaired consciousness in the field was associated with increased diagnosis of stroke

Effect of aspirin treatment on serum levels of lipoprotein (a) : analysis from the apolipoprotein (a) isoforms

We have found that aspirin lowers elevated serum lipoprotein(a) [Lp(a)] levels via reduction of the transcriptional activity of apolipoprotein(a) [apo(a)] gene with suppression of apo(a) mRNA expression. In the present study, we evaluated the effect of aspirin treatment on serum Lp(a) level and analyzed its relation to type of apo(a) isoform. Serum levels of Lp(a) were measured by turbidimetric immunoassay before and after the oral administration of aspirin therapy (81 mg/day) in 57 patients with coronary artery disease or cerebral infarction. Apo(a) isoforms were determined by immunoblotting method. In patients with high serum Lp(a) levels (more than 30 mg/dl), aspirin reduced serum Lp(a) levels to approximately 80 % of the baseline after one month. Their levels sustained significantly low even after six months. The effect of aspirin in reducing elevated serum Lp(a) levels were stronger in patients with smaller-sized type or double-band type of apo(a) isoforms. The transcriptional efficiency of apo(a) gene is thought to be increased in patients with these apo(a) isoforms. Therefore, these findings suggest that aspirin reduces apo(a) gene transcription preferentialy in patients with high transcriptional efficiency of this gene

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies