Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. METHODS: l-carnitine (2 g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. RESULTS: Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. CONCLUSIONS: Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.

Long non-coding RNAs (lncRNAs) play a critical role in a variety of human diseases such as cancer. Here, to elucidate a novel function of a lncRNA called LINC00173, we investigated its binding partner, target gene, and its regulatory mechanism in lung adenocarcinoma, including the A549 cell line and patients. In the A549 cell line, RNA immunoprecipitation (RIP) assays revealed that LINC00173 efficiently binds to SNAIL. RNA-seq and RT-qPCR analyses revealed that the expression of FHIT was decreased upon LINC00173 depletion, indicating that FHIT is a target gene of LINC00173. Overexpression of SNAIL suppressed and depletion of SNAIL increased the expression of FHIT, indicating that SNAIL negatively regulates FHIT. The downregulation of FHIT expression upon LINC00173 depletion was restored by additional SNAIL depletion, revealing a LINC00173-SNAIL-FHIT axis for FHIT regulation. Data from 501 patients with lung adenocarcinoma also support the existence of a LINC00173-SNAIL-FHIT axis, as FHIT expression correlated positively with LINC00173 (p = 1.75 × 10-6) and negatively with SNAIL (p = 7.00 × 10-5). Taken together, we propose that LINC00173 positively regulates FHIT gene expression by binding to SNAIL and inhibiting its function in human lung adenocarcinoma. Thus, this study sheds light on the LINC00173-SNAIL-FHIT axis, which may be a key mechanism for carcinogenesis and progression in human lung adenocarcinoma.

[Validation of Method for Nitrite Determination in Foods].

In general, nitrite in food is extracted under slightly alkaline conditions, deproteinized, and analyzed by a colorimetric method using color development by diazotization. However, depending on the sample, the sample solution may become cloudy and difficult to filter by the deproteinization treatment of the analytical method. Recently, an improved analytical method that solves these problems has been reported. Therefore, a validation study was performed on the improved analytical method was performed. The concentrations of sodium nitrite added to cod roe, fish sausage, and ham, which were not labeled with sodium nitrite, were set at the upper limits of the standards for use. We set the target values of 70-120% for trueness, less than 15% for intralaboratory reproducibility, and less than intralaboratory reproducibility for repeatability. As a result, the target values were met for the three samples verified: 88-92% for trueness, 2.0-3.0% for repeatability, and 3.2-4.3% for intralaboratory reproducibility. In addition, an interlaboratory study was conducted by eight institutes on the improved analytical method for nitrite. At each institution, sodium nitrite was added to the same three samples as in the validation study, at concentrations equivalent to twice the lower limit of quantification and the upper limit of the standards for use and analyzed in triplicate. The estimated trueness from the obtained analyses ranged from 82 to 95%, the repeatability ranged from 2.3 to 5.8%, and the inter-room reproducibility ranged from 3.5 to 11%. Thus, the improved analytical method could be useful for determining nitrite in foods.

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan.

BACKGROUND: Anticardiolipin antibodies (aCL) and anti-ß2 -glycoprotein I antibodies (aß2 GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aß2 GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays. METHODS: We evaluated two manual and three automated assays for aCL and aß2 GPI of IgG- and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well-defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve. RESULTS: A variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between-year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aß2 GPI-IgG and aCL-IgG were generally high (AUC: 0.84-0.93); whereas those for IgM-class assays were low (AUC: 0.57-0.67), implicating its utility is limited to rare IgG negative APS cases. CONCLUSION: To ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.

Sensor histidine kinases mediate ABA and osmostress signaling in the moss Physcomitrium patens.

To survive fluctuating water availability on land, terrestrial plants must be able to sense water stresses, such as drought and flooding. The plant hormone abscisic acid (ABA) and plant-specific SNF1-related protein kinase 2 (SnRK2) play key roles in plant osmostress responses. We recently reported that, in the moss Physcomitrium patens, ABA and osmostress-dependent SnRK2 activation requires phosphorylation by an upstream RAF-like kinase (ARK). This RAF/SnRK2 module is an evolutionarily conserved mechanism of osmostress signaling in land plants. Surprisingly, ARK is also an ortholog of Arabidopsis CONSTITUTIVE RESPONSE 1 (CTR1), which negatively regulates the ethylene-mediated submergence response of P. patens, indicating a nexus for cross-talk between the two signaling pathways that regulate responses to water availability. However, the mechanism through which the ARK/SnRK2 module is activated in response to water stress remains to be elucidated. Here, we show that a group of ethylene-receptor-related sensor histidine kinases (ETR-HKs) is essential for ABA and osmostress responses in P. patens. The intracellular kinase domain of an ETR-HK from P. patens physically interacts with ARK at the endoplasmic reticulum in planta. Moreover, HK disruptants lack ABA-dependent autophosphorylation of the critical serine residue in the activation loop of ARK, leading to loss of SnRK2 activation in response to ABA and osmostress. Collectively with the notion that ETR-HKs participate in submergence responses, our present data suggest that the HK/ARK module functions as an integration unit for environmental water availability to elicit optimized water stress responses in the moss P. patens.

Measurement of coagulation factor antibody levels is useful for diagnosis and determining therapeutic efficacy in hemorrhagic patients with autoantibodies to coagulation factor VIII and factor V: results from a single center in Japan.

Coagulation factor inhibitors (CFIs) sometimes cause fatal bleeding conditions. Determination of an inhibitor titer (INH-titer) using the Bethesda method is essential for diagnosing diseases associated with CFIs and examining the effects of immunosuppressive therapy. We reviewed 17 cases with CFIs (acquired hemophilia A, n = 11; FV inhibitor, n = 6) to examine the usefulness of determining quantities of an autoantibody to a coagulation factor (CF-IgG) by ELISA for diagnosis and therapeutic efficacy, as compared with INH-titer. One patient with an INH-titer and no evidence of CF-IgG was lupus anticoagulant (LA)-positive, and thus the positive INH-titer may have been a false positive caused by LA. Although INH-titer alone was insufficient to correctly identify patients with CFI, determination of CF-IgG appeared to be useful. In addition, even after INH-titer disappearance, hemorrhagic conditions recurred when CF-IgG was detected. These findings suggest that the presence of a clearance antibody against the coagulation factor might reduce the activity of that coagulation factor even after disappearance of the corresponding neutralizing antibody. Although the diagnosis and therapeutic efficacy can also be determined by INH-titer disappearance and improvement of corresponding coagulation factor activity, determination of CF-IgG by ELISA can improve the accuracy of these assessments.

Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis.

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

Comparative evaluation of reagents for measuring protein S activity: possibility of harmonization.

Patients with congenital protein S (PS) deficiency show a hereditary predisposition for thrombosis, and PS deficiency is prevalent among Japanese populations. Diagnosis is based on symptoms of thrombosis and reduced PS activity. Three reagents that use different measurement principles for determining PS activity are available in Japan. This study aimed to confirm the possibility of harmonization of these three reagents to establish a universal standard for PS activity in Japanese populations. Commercial normal plasma and plasma samples obtained from healthy individuals and healthy pregnant women were tested at three facilities using three reagents for measuring PS: STA-Staclot Protein S (STA-PS), HemosIL Protein S (Clotting) (IL-PS), and a total PS assay (SNT-PS). The within-run precision of each reagent was good, as each had a coefficient of variation of ≤ 3.8%. The dilution linearity for each reagent was also good. The correlation coefficient was 0.94 for STA-PS vs. IL-PS, 0.93 for SNT-PS vs. STA-PS, and 0.90 for SNT-PS vs. IL-PS, indicating a good correlation. Although the three reagents available in Japan for measuring PS activity use different measurement methods, each showed good performance, and large differences were not observed between the obtained values. Harmonization among them appears possible.

Characterization of fibrin/fibrinogen degradation products reagents and their utility in critical care patients with enhanced fibrinolysis.

INTRODUCTION: Fibrin/fibrinogen degradation products (FDP) values reflect coagulation and fibrinolysis status, and FDP levels are helpful for diagnosis and classification of disseminated intravascular coagulation (DIC). FDP measurement has always played a key role in diagnosing DIC, a phenomenon that has recently gained renewed attention because of its occurrence in coronavirus disease 2019 (COVID-19) patients. Although the evaluation of FDP is crucial for the management of critical care, the variability among FDP reagents is unclear. In this study, we aimed to compare LIASAUTO P-FDP with three FDP reagents and investigate their characteristics. METHODS: In total, 172 plasmas samples were used in the correlation. The sample data were divided into three groups including negative, no and positive discrepancy based on the discrepancy percentages calculated from each correlation between LIASAUTO P-FDP and other three reagents. D-dimer, plasmin-α2 plasmin inhibitor complex (PIC), fibrin monomer complex (FMC), fibrinogen (Fbg) and Plasmin-α2 Plasmin Inhibitor (α2 PI) were measured and included in data analysis. RESULTS: The positive discrepancy groups showed higher D-dimer, PIC and FMC values than the negative discrepancy groups. The data indicated that LIASAUTO P-FDP had higher reactivity to D-dimer than other reagents and the values were elevated in the fibrinolysis-enhanced samples with various FDP fragments. CONCLUSION: LIASAUTO P-FDP displayed the reactivity towards various fibrin/fibrinogen degradation products, and it might be useful for DIC diagnosis because the fibrinolytic status differed in the DIC types and stages.

Novel assay based on diluted prothrombin time reflects anticoagulant effects of direct oral factor Xa inhibitors: Results of multicenter study in Japan.

BACKGROUND: Direct oral anticoagulants targeting factor Xa (DXaIs) are administered as prophylaxis for various venothrombotic diseases without routine monitoring required. However, assessment of their anticoagulant effects is necessary to prevent severe events, including major bleeding and/or refractory thrombosis. OBJECTIVES: We examined the correlation of ratio of inhibited thrombin generation (RITG), determined using a novel assay based on dilute prothrombin time (dPT), with coagulant markers and laboratory test results to show drug effects. In addition, RITG usefulness as a confirmation test for DXaI therapy was investigated. METHODS: Citrated plasma samples were obtained from patients treated with rivaroxaban (n = 882), apixaban (n = 1214), or edoxaban (n = 820) at 4 different institutions in Japan. Laboratory tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and plasma concentrations of DXaIs, were conducted, with drug concentrations divided into peak and trough groups, within and after 5 h of administration. RESULTS: In each DXaI group, RITG was positively correlated with PT, APTT, and drug concentration, and negatively with D-dimer. RITG fluctuation during the peak and trough periods reflected the anticoagulant activity characteristic of each DXaI, which was different from blood concentration fluctuations. RITG showed a significant decrease in cases with thrombosis, while that was increased in those with hemorrhage. CONCLUSION: We developed RITG, a novel measurement method based on dPT. RITG represents residual coagulation ability in plasma samples, and is useful for assessment of bleeding and thrombotic tendencies in DXaI patients. RITG can be utilized to confirm the effectiveness of oral anticoagulation therapy with DXaI agents.

Knockdown of long noncoding RNA dreh facilitates cell surface GLUT4 expression and glucose uptake through the involvement of vimentin in 3T3-L1 adipocytes.

Glucose uptake in adipocytes is crucial for regulating systemic metabolism. Long noncoding RNAs (lncRNAs), defined as being transcripts with lengths exceeding 200 nucleotides that are not translated, are recently identified regulators of cellular functions. Previously, we have shown that an lncRNA, "down-regulated expression by hepatitis B virus X" (dreh), is involved in glucose transport in skeletal muscle cells. Here, we aimed to examine the involvement of dreh in glucose transport in 3T3-L1 adipocytes. Expression analysis showed that dreh was expressed in 3T3-L1 fibroblasts and adipocytes. Knockdown of dreh expression using its specific siRNAs lowered the glucose concentration of the medium and facilitated [3H]-2-deoxyglucose transport in adipocytes. Additionally, dreh silencing enhanced the protein expression of glucose transporter (GLUT4) in the plasma membrane of adipocytes. Treatment with siRNA against vimentin attenuated the glucose-lowering effect of dreh depletion. These results suggest that the repression of dreh facilitates glucose transport via increased GLUT4 expression in the plasma membrane through the involvement of vimentin in 3T3-L1 adipocytes. In conclusion, dreh is the first observed lncRNA that regulates glucose transport in adipocytes and could serve as a novel therapeutic target for diabetes by modulating adipocyte function. Considering the new function of dreh, we propose that dreh be renamed "down-regulated expression-related hexose/glucose transport enhancer."

Magnesium-dependent activated partial thromboplastin time assay-Simple method for lupus anticoagulant detection.

INTRODUCTION: Detection of lupus anticoagulant (LA), an antiphospholipid (aPL) antibody, in a clotting time test is an important finding for diagnosis of antiphospholipid syndrome (APS). However, confirmation of LA requires several different testing procedures, some of which can be difficult and require time. We report here a simple and highly specific method for detecting LA. MATERIALS AND METHODS: We examined 66 plasma samples obtained from LA-positive (LA) and 75 from LA-negative (non-LA) subjects, which included patients with acquired hemophilia and coagulation disorders, as well as from 43 healthy volunteer samples as normal controls. Activated partial thromboplastin time (APTT) was determined by adding 20 mmol of CaCl2 (Ca-APTT) or 25 mmol of a mixture of Mg and Ca (Mg-APTT). The ratio of Mg-APTT/Ca-APTT was then calculated and used as the Mg/Ca Index. RESULTS: The Mg/Ca Index value for the LA group was significantly lower than that for the non-LA and normal control groups (P < .0001). When the cutoff value of the Mg/Ca Index was less than 1.00, the sensitivity of LA determination using the Mg-APTT assay was 80.3%, while specificity was 100%. CONCLUSION: Our findings indicate that the present Mg-APTT assay is a simple yet highly specific method for LA detection.

Dreh, a long noncoding RNA repressed by metformin, regulates glucose transport in C2C12 skeletal muscle cells.

AIMS: The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells. MAIN METHODS: Metformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells. KEY FINDINGS: Metformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes. SIGNIFICANCE: The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes.

Lupus anticoagulant-hypoprothrombinemia syndrome and similar diseases: experiences at a single center in Japan.

Patients with lupus anticoagulant (LA), a thrombotic risk factor, along with decreased prothrombin (FII) activity are classified as lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) and occasionally show bleeding symptoms, although this is not essential for diagnosis. We treated 20 cases of LAHPS over a 3-year period. Median FII activity was 20.9% and the anti-prothrombin antibody (anti-II Ab), shown by ELISA findings, was detected in 55%. Bleeding symptoms were observed in 20%, although that finding was not correlated with FII activity or anti-FII Ab quantity. We also observed 21 LA cases with decreased activity of coagulation factors other than FII, which we have designated LAHPS-like syndrome (LLS). Among LLS patients, anti-FII Ab and bleeding symptoms were seen in 47.6% and 14.3%, respectively. Our findings suggest that bleeding in LAHPS and LLS cannot be explained only by FII activity decreased by anti-FII Ab. Low FVIII activity and the anti-FVIII antibody (anti-FVIII Ab) were detected in some LAHPS and LLS patients, making it difficult to distinguish those from acquired hemophilia A cases. Detection of anti-FVIII Ab quantity by ELISA may be useful for accurate determination, as that was not performed in our LAHPS or LLS patients.

Preoperative weight loss program involving a 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer.

INTRODUCTION: The increased visceral fat in patients with obesity can increase the technical difficulty of surgery. This study was performed to evaluate a preoperative 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer. METHODS: This prospective single-center study involved patients with obesity who were planning to undergo laparoscopic gastrectomy for gastric cancer. Obesity was defined according to the Japanese criteria: BMI ≥25 kg/m2 or waist circumference ≥85 cm in men and ≥90 cm in women. The patients underwent a preoperative 20-day very low-calorie diet and received nutritional counseling. Weight loss, body composition, visceral fat mass, and operative outcomes were evaluated. RESULTS: Thirty-three patients were enrolled from September 2013 to August 2015. Their median age was 71 years, and 78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8-82.5 kg) and 26.0 kg/m2 (range, 23.5-31.0 kg/m2 ), respectively. The patients achieved a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8-5.1), corresponding to 3.2 kg (95%CI: 2.7-3.7 kg). Body fat mass was significantly decreased by a mean of 2.5 kg (95%CI: 1.9-3.1), whereas skeletal muscle mass was unaffected (mean: -0.20 kg [95%CI: -0.55-0.15]). The visceral fat mass reduction rate was high as 16.8% (range, 11.6%-22.0%). All patients underwent laparoscopic gastrectomy as planned. Severe postoperative morbidity (Clavien-Dindo grade ≥III) was seen in only one patient (3.0%). CONCLUSION: The preoperative 20-day very low-calorie diet weight loss program is promising for the treatment of obesity before laparoscopic gastrectomy for gastric cancer.

Basic Evaluation of the Newly Developed "Lias Auto P-FDP" Assay and the Influence of Plasmin-α2 Plasmin Inhibitor Complex Values on Discrepancy in the Comparison with "Lias Auto D-Dimer Neo" Assay.

BACKGROUND: Laboratory determination of fibrin/fibrinogen degradation products (FDP) levels, along with that of the D-dimer, is important for assessing the fibrinolytic situation. Recently, we developed a new FDP reagent "Lias Auto P-FDP", which can detect various FDP fragments. The purpose of this study was to evaluate the basic performance of the newly developed Lias Auto P-FDP and compare it with Lias Auto D-Dimer Neo assay. METHODS: The within-run precision of Lias Auto P-FDP and Lias Auto D-Dimer was determined 20 times in low and high value controls. The between-day precision was evaluated five times a day for five days. The linearity study was performed by diluting high value samples for 2 - 10-fold and 2 - 8-fold. The comparative study was performed using 172 patient samples with elevated FDP values. For the discrepancy analysis, the samples were divided into three groups by the discrepancy percentage between the FDP and D-dimer values. The groups were defined as follows: lower discrepancy group, less than -20%; no discrepancy group, -20% to 20%; upper discrepancy group, more than 20%. RESULTS: The coefficient of variation % (CV%) in within-run and between-day precision were within 3.8% for both FDP and the D-dimer. The correlation coefficients were more than 0.999 and the linearity was high. In the comparative study, the values of FDP were higher than that of the D-dimer in all samples. The median FDP and D-dimer values of lower discrepancy, no discrepancy, and upper discrepancy groups were 11.8, 20.3, and 51.4, and 8.0, 11.3, and 13.1, respectively. FDP showed an increasing tendency but D-Dimer showed constant values. Thus, the possible cause of discrepancy between FDP and D-dimer values were the elevated FDP values. In addition, the values of plasmin-α2 plasmin inhibitor complex (PIC) in the upper discrepancy group were higher than that of the lower and no discrepancy groups, indicating progression of fibrinolysis. CONCLUSIONS: In this study, we evaluated the newly developed Lias Auto P-FDP reagent and confirmed that the basic performance was acceptable. FDP was elevated in samples with high PIC values, which indicated progression of fibrinolysis. Determination of fibrinolysis conditions by FDP measurement is important.

Effectiveness of educational program using printed educational material on care burden distress among staff of residential aged care facilities without medical specialists and/or registered nurses: Cluster quasi-randomization study.

AIM: Behavioral and psychological symptoms of dementia are an important source of distress for caregivers. The aim of the present study was to evaluate the effectiveness of educational intervention using printed educational material for reducing distress induced by behavioral and psychological symptoms of dementia among caregivers working at facilities without medical specialists and/or registered nurses. METHODS: A cluster quasi-randomized, controlled comparative trial was carried out at 17 facilities in Japan. Our intervention was an educational program administered at baseline using printed educational material for the care staff. The primary outcome was evaluated using the Japanese version of the Neuropsychiatric Inventory Questionnaire. The secondary outcome measures were caregiver burnout evaluated using the Japanese version of the Maslach Burnout Inventory and the care dependency of residents measured using the Japanese version of the Care Dependency Scale. RESULTS: The total Neuropsychiatric Inventory Questionnaire score decreased significantly in the intervention group (F [1355] = 6.57, P = 0.01), and the difference between the intervention and control groups was also significant (F [1355] = 4.78, P = 0.03). There were no significant changes in the Maslach Burnout Inventory or Care Dependency Scale scores in the intervention group, while the Maslach Burnout Inventory subscale (personal accomplishment) score decreased significantly in the control group. CONCLUSIONS: Our intervention achieved a significant reduction of distress among caregivers working at care homes without medical specialists and/or registered nurses. The findings of this research show that educational intervention can make a valuable contribution to training programs for care staff. Geriatr Gerontol Int 2018; 18: 487-494.

Acute arterial occlusion due to left ventricular thrombus of Takotsubo cardiomyopathy in a young adult: a case report.

BACKGROUND: Thromboembolism is a rare complication of Takotsubo cardiomyopathy. Importantly, an acute arterial occlusion needs rapid diagnosis and urgent treatment to help save the patient's life. Here, we report a case of arterial occlusion due to ventricular thrombus of Takotsubo cardiomyopathy. CASE PRESENTATION: A woman in her 30s, without previous medical history, felt sudden strong pain on her right leg and was diagnosed with right femoral arterial occlusion. An emergency operation was subsequently performed to take out thrombus. The patient's oxygenation deteriorated to 93% of hemoglobin saturation just after extubation and exacerbated in the intensive care unit. Transthoracic echocardiography revealed Takotsubo cardiomyopathy-like left ventricular wall motion abnormalities and left ventricular thrombus. Heparin treatment was immediately started. After 10 days, the thrombus disappeared and the left ventricular wall motion improved and she was discharged from the hospital. CONCLUSIONS: The patient's acute arterial occlusion in this case report was mainly caused by thrombus of cardiac origin. We suggest to routinely check echocardiography reports before surgery and perform anesthetic management carefully to better control the patient's blood pressure and heart rhythm.