(A)symmetries in Memory and Directed Forgetting of Political Stimuli.

As political information becomes increasingly prevalent in all forms of media, it is becoming increasingly important to understand when and why biases in remembering such information occur. Using an item-method directed forgetting procedure, we conducted two online experiments to determine the efficacy of admonitions to forget politically charged stimuli that were either congruent or incongruent with participants' political beliefs. Participants viewed slideshows wherein each item combined the face of a famous politician (Donald Trump or Joe Biden) with a word that was positive, negative, or neutral in emotional valence. Each slide was followed by an instruction to remember or forget. After a brief filler task, a recognition test assessed their memory for both remember and forget slides and (in Experiment 2) assessed their beliefs about the truth of each word/face pairing and beliefs about the accuracy of their memory. The results showed that for both liberal and conservative participants, politically congruent stimuli were more conducive to recognition memory and more resistant to directed forgetting than politically incongruent or neutral stimuli. There were small asymmetries wherein conservatives showed greater biases in memory and other cognitive measures. We discuss possible explanations of the results and their implications.

Making judgments of learning enhances memory by inducing item-specific processing.

A judgment of leaning (JOL) has been investigated to understand self-regulated learning. However, asking participants to make JOLs may increase memory by creating a reactivity effect. In two experiments, we examined whether making JOLs would enhance memory by inducing item-specific processing. We compared a JOL task with two other tasks that are known to induce item-specific processing: pleasantness rating (Experiment 1) and single imagery (Experiment 2; creating vivid mental images). Participants learned a categorized or uncategorized list of words. Memory should be enhanced when the list promotes relational processing and the task induces item-specific processing. As expected, when the list was categorized, recall was higher in the JOL and item-specific processing conditions (pleasantness rating and single imagery) than in the control condition. Furthermore, recall was similar between the JOL and item-specific processing conditions. When the list was uncategorized, there was no difference in recall among the JOL, item-specific processing, and control conditions. Making JOLs enhances memory by inducing item-specific processing. We concluded that researchers need to carefully consider how making a JOL influences memory when investigating self-regulated study behaviors.

Reducing negative emotional memories by retroactive interference.

Because negative emotional memories are often disruptive, we conducted two experiments to reduce these memories by using a retroactive interference (RI) paradigm. In both experiments, participants were presented with highly negative pictures (List 1) followed by highly negative, moderately negative, or neutral pictures (List 2) or a rest period. Then, following a filler task, participants took a surprise free recall test, recalling pictures from List 1 in Experiment 1 and from both List 1 and List 2 in Experiment 2. In both experiments, recall of List 1 was reduced by List 2, indicating that RI was present. Furthermore, in Experiment 1, RI was similar between moderately negative and highly negative List 2 whereas in Experiment 2, RI was greater for highly negative List 2 than moderately negative List 2. These results showed that RI can be used to reduce negative emotional memories by making these memories inaccessible.

Learning style, judgements of learning, and learning of verbal and visual information.

The concept of learning style is immensely popular despite the lack of evidence showing that learning style influences performance. This study tested the hypothesis that the popularity of learning style is maintained because it is associated with subjective aspects of learning, such as judgements of learning (JOLs). Preference for verbal and visual information was assessed using the revised Verbalizer-Visualizer Questionnaire (VVQ). Then, participants studied a list of word pairs and a list of picture pairs, making JOLs (immediate, delayed, and global) while studying each list. Learning was tested by cued recall. The results showed that higher VVQ verbalizer scores were associated with higher immediate JOLs for words, and higher VVQ visualizer scores were associated with higher immediate JOLs for pictures. There was no association between VVQ scores and recall or JOL accuracy. As predicted, learning style was associated with subjective aspects of learning but not objective aspects of learning.

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition).

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

Treatment and management of thyroid storm: analysis of the nationwide surveys: The taskforce committee of the Japan Thyroid Association and Japan Endocrine Society for the establishment of diagnostic criteria and nationwide surveys for thyroid storm.

OBJECTIVE: Thyroid storm (TS) is a life-threatening endocrine emergency. This study aimed to achieve a better understanding of the management of TS by analyzing therapeutic modalities and prognoses reported by nationwide surveys performed in Japan. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective analyses were performed on clinical parameters, outcomes, and treatments in 356 TS patients. RESULTS: Patient disease severities assessed via Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores significantly correlated with mortality. Free triiodothyronine (FT3) and the FT3/free thyroxine (FT4) ratio inversely correlated with disease severity. Methimazole (MMI) was used in the majority of patients (78·1%), and there were no significant differences in mortality or disease severity between those treated with MMI and those receiving propylthiouracil (PTU). Patients who received inorganic iodide (KI) demonstrated higher disease severity but no change in mortality compared to those who did not. Patients treated with corticosteroids (CSs) demonstrated significantly higher disease severity and mortality than those who were not. Disease severity in patients treated with intravenous administration of beta-adrenergic antagonists (AAs) was significantly higher than those treated with oral preparations, although no significant difference in mortality was observed between these groups. In addition, mortality was significantly higher in patients treated with non-selective beta-AAs as compared with other types of beta-AAs. CONCLUSION: In Japan, MMI was preferentially used in TS and showed no disadvantages compared to PTU. In severe TS, multimodal treatment, including administration of antithyroid drugs, KI, CSs and selective beta1 -AAs may be preferable to improve outcomes.

Antagomir-92a impregnated gelatin hydrogel microsphere sheet enhances cardiac regeneration after myocardial infarction in rats.

INTRODUCTION: We investigated whether attachment of gelatin hydrogel microsphere (GHM) sheet impregnated with antagomir-92a on the infarcted heart promotes angiogenesis and cardiomyogenesis, and improves cardiac function after myocardial infarction (MI) in rats. METHODS: GHM sheet impregnated with antagomir-92a, its scramble sequence antagomir-control sheet or the sheet alone was attached on the area at risk of MI after the left anterior descending coronary artery ligation. Bromodeoxyuridine (BrdU) was included in the sheet to trace proliferating cells. RESULTS: The antagomir-92a sheet significantly increased capillary density in the infarct border zone 14 days after MI compared to the antagomir-control sheet or the sheet alone, associated with an increase in endothelial cells incorporated with BrdU. The antagomir-92a sheet significantly increased cardiac stem cells incorporated with BrdU 3 days after MI in the infarct border zone. This was associated with an increase in cardiomyocytes incorporated with BrdU 14 days after MI. Scar area was significantly reduced by the antagomir-92a sheet compared to the antagomir-control sheet or the sheet alone (12.8 ± 1.3 vs 25.2 ± 2.2, 24.0 ± 1.7% LV area, respectively) 14 days after MI. LV dilatation was inhibited, and LV wall motion was improved 14 days after MI in rats with the antagomir-92a sheet compared to the antagomir-control sheet or the sheet alone. CONCLUSIONS: These results suggest that attachment of the GHM sheet impregnated with antagomir-92a on the area at risk of MI enhances angiogenesis, promotes cardiomyogenesis, and ameliorates LV function.

Sepiapterin prevents left ventricular hypertrophy and dilatory remodeling induced by pressure overload in rats.

Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO.

Partial dopaminergic denervation-induced impairment in stimulus discrimination acquisition in parkinsonian rats: a model for early Parkinson's disease.

Parkinson's disease (PD) produces progressive nigrostriatal dopamine (DA) denervation resulting in cognitive and motor impairment. However, it is unknown whether cognitive impairments, such as instrumental learning deficits, are associated with the early stage PD-induced mild DA denervation. The current study sought to model early PD-induced instrumental learning impairments by assessing the effects of low dose (5.5µg), bilateral 6OHDA-induced striatal DA denervation on acquisition of instrumental stimulus discrimination in rats. 6OHDA (n=20) or sham (n=10) lesioned rats were tested for stimulus discrimination acquisition either 1 or 2 weeks post surgical lesion. Stimulus discrimination acquisition across 10 daily sessions was used to assess discriminative accuracy, or a probability measure of the shift toward reinforced responding under one stimulus condition (Sd) away from extinction, when reinforcement was withheld, under another (S(d) phase). Striatal DA denervation was assayed by tyrosine hydroxylase (TH) staining intensity. Results indicated that 6OHDA lesions produced significant loss of dorsal striatal TH staining intensity and marked impairment in discrimination acquisition, without inducing akinetic motor deficits. Rather 6OHDA-induced impairment was associated with perseveration during extinction (S(Δ) phase). These findings suggest that partial, bilateral striatal DA denervation produces instrumental learning deficits, prior to the onset of gross motor impairment, and suggest that the current model is useful for investigating mild nigrostriatal DA denervation associated with early stage clinical PD.

Emotional salience and the isolation effect.

When a homogeneous list contains a few items that are different from the rest of the items in the list, these isolated items show enhanced recall compared to the same items in a list where these items are not isolated. This phenomenon, known as the isolation effect, has been explained on the basis of isolated items eliciting salience. In this experiment, negative pictures and neutral pictures were isolated at the early and late part of the list. The salience explanation would predict that participants would pay more attention to these isolated items resulting in higher judgments of learning (JOL) ratings compared to the same items in the control list. Negative pictures showed the isolation effect for both early and late isolation; however, for early isolation, JOL was similar between the isolated and non-isolated pictures indicating that the emotional isolation effect does not require emotional salience.

Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression.

We designed class I/II hybrid inhibitory oligodeoxynucleotides (iODNs), called iSG, and found that the sequence 5'-TTAGGG-3', which has a six-base loop head structure, and a 3'-oligo (dG)3-5 tail sequence are important for potent immunosuppressive activity. Interestingly, splenocytes isolated from ovalbumin (OVA)-immunized mice and treated with iSG3 showed suppression of not only interleukin (IL)-6, IL-12p35, IL-12p40, and interferon (IFN) γ mRNA expression, but also IL-4 and IL-13 mRNA expression. Thus, both Th2 and Th1 immune responses can be strongly suppressed by iODNs in splenocytes from allergen-immunized mice, suggesting usefulness in the treatment of diseases induced by over-active immune activation.

Site-specific antioxidative therapy for prevention of atherosclerosis and cardiovascular disease.

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat.

BACKGROUND: Statins (HMG-CoA reductase inhibitors), are known to improve cardiac function in diabetes-induced cardiovascular disease. We investigated the mechanism by which statins ameliorate cardiac function after myocardial infarction (MI). Simvastatin (S) increased tube formation and migration of HUVEC in vitro. We examined the role of simvastatin on cardiac function in streptozotocin (STZ) induced diabetic rats subjected to MI. METHODS: Rats were randomly assigned to 1) Control (non-diabetic) Sham (CS); 2) Control (non-diabetic) MI (CMI); 3) Control Statin treated Sham (CSS); 4) Control Statin treated MI (CSMI); 5) Diabetic Sham (DS); 6) Diabetic MI (DMI); 7) Diabetic Statin treated Sham (DSS); 8) Diabetic Statin treated MI (DSMI). Two weeks after STZ/saline injection Simvastatin (1mg/kg.b.wt) was gavaged for 15 days (d). MI was induced 30 d after treatment by permanent LAD ligation. RESULTS: The S treated MI groups exhibited increased arteriolar density (23 ± 0.6 vs. 14.8 ± 0.4 counts/mm(2), DSMI vs. DMI) and reduced fibrosis at 30 d post-MI. VEGF measurement by ELISA after 4d post-MI showed increased expression in DSMI group compared to DMI group. Western blot analysis showed decreased Prolyl-4-Hydroxylase 3 (PHD-3) in DSMI group as compared to DMI group. Echocardiographic analysis 4 weeks after post-MI showed significant improvement in ejection fraction (50.11 ± 1.83 vs. 32.46 ± 2.19%; DSMI vs. DMI) and fractional shortening (26.77 ± 1.12 vs.16.36 ± 1.22%; DSMI vs. DMI) in both statin-treated MI groups regardless of diabetic status. CONCLUSION: These results suggest that statin therapy mitigates impairment of angiogenesis and myocardial dysfunction following MI in the diabetic rat through PHD3 inhibition.

Intracoronary followed by intravenous administration of the short-acting ß-blocker landiolol prevents myocardial injury in the face of elective percutaneous coronary intervention.

BACKGROUND: Myocardial injury during elective percutaneous coronary intervention (PCI) is associated with higher subsequent cardiac events and mortality. ß-Blockers have been used to reduce myocardial injury during ischemia and reperfusion. We investigated whether intracoronary followed by intravenous administration of the short-acting ß-blocker landiolol prevents myocardial injury in the face of elective PCI. METHODS AND RESULTS: Patients undergoing elective PCI (n=70) were randomly assigned to the landiolol (n=35) or control (n=35) group. Landiolol or saline was administered into target vessels through a balloon catheter for 1min before and after first balloon inflation followed by continuous intravenous administration for 6h after PCI. The incidence of myocardial injury defined by cardiac troponin-I (cTnI) >/=0.05 ng/ml was 79% of the patients in the control group compared to 56% in the landiolol group (p=0.04). The cTnI level at 24h after PCI tended to be lower in the landiolol group (0.57 ± 1.14 versus 1.27 ± 2.48 ng/ml; p=0.07), while the CK-MB level was not significantly different between the landiolol and control groups. The incidence of peri-procedural myocardial infarction defined by cTnI >/=0.12 ng/ml was significantly (p=0.02) lower in the landiolol group (41%) compared to the control group (70%). There was no incidence of coronary spasm, hypotension, bradycardia or heart failure during and after PCI in the two groups. CONCLUSIONS: Brief intracoronary followed by continuous intravenous administration of landiolol is safe and effective for myocardial protection in the face of elective PCI.

Expression of the immunoreactive buckwheat major allergenic storage protein in Lactococcus lactis.

Proteins from buckwheat (Fagopyrum esculentum) are strong allergens that can cause serious symptoms, including anaphylaxis, in patients with hypersensitivity. In this study, we successfully developed a modified lactic acid bacterial vector (pNSH) and a recombinant strain of Lactococcus lactis NZ9000 (NZ9000) that produced a major allergenic storage protein of buckwheat, Fagag1 (61.2 kDa, GenBank accession number AF152003), with or without a green fluorescent protein (GFP) tag. GFP fluorescence allows for rapid, simple, and accurate measurement of target protein expression by microscopy or fluorimetry. We describe a convenient method for production of rGFP-Fagag1 fusion and rFagag1 proteins with a good yield in an advantageous probiotic host. We found that in vitro treatment of splenocytes isolated from buckwheat crude protein-immunized mice with rFagag1 increased the expression of allergic inflammation cytokines such as IL-4, IL-13, and IL-17 F. Because it was less antigenic, rGFP-Fagag1 protein from NZ9000 might be of limited use; however, rFagag1 from NZ9000 evoked a robust response as measured by induction of IL-4 and IL-17 F expression levels. The observed allergic activity is indicative of a Th2 cell-mediated immune response and is similar to the effects induced by exposure to buckwheat crude protein. Our results suggest that expression of rFagag1 in NZ9000 may facilitate in vivo applications of this system aimed at improving the specificity of immunological responses to buckwheat allergens.

Fermented soybean powder with rice mold in the absence of salt stimulates the cellular immune system and suppresses the humoral immune response in mice.

The immunomodulatory effect of fermented non-salty soybean powder (NSBP) was investigated in C3H/HeN mice. The number of splenic CD11b(+), CD49b(+), and interferon (IFN)-γ(+)CD4(+) cells increased significantly, while that of interleukin (IL)-4(+)CD4(+) and CD19(+) cells decreased significantly in cultures containing NSBP. Similarly, in the spleen and Peyer's patches of mice fed a diet containing NSBP, the number of IL-12(+)CD11b(+), CD49b(+), and IFN-γ(+)CD4(+) cells increased noticeably, whereas the number of splenic IL-4(+)CD4(+) and CD19b(+) cells was lower compared to mice fed an NSBP-free diet. Superoxide production by peritoneal macrophages was significantly higher in mice fed an NSBP-containing diet. Both intestinal total IgA and serum total IgG levels declined in mice fed the NSBP-containing diet. Microarray analysis of mRNAs extracted from Peyer's patch cells of mice fed the NSBP-containing diet indicated an increase in the expression of several genes related to cellular immune responses, while the expression of genes related to immunoglobulin production decreased. These results indicate that NSBP stimulates the cellular immune response, but suppresses the acquired humoral immune response in C3H/HeN mice.

Anti-allergic properties of a matured fruit extract of the date palm tree (Phoenix dactylifera L.) in mite-sensitized mice.

The effects of oral ingestion of a hot water extract of matured fruit of the date palm tree (Phoenix dactylifera L.) on allergic responses were investigated in mite-sensitized mice. Sneezing and nose rubbing events in mice given a date extract-added diet were significantly lower than in those given an extract-free (control) diet. The serum total and mite antigen-specific immunoglobulin (Ig) E levels, and the number of spleen interleukin-4(+)CD4(+), IgE(+)B220(+) and FcεRIα(+)CD117(+) cells was significantly lower in mice given the date extract-added diet than in those given the control diet. Chlorogenic acid, pelargonin and ferulic acid significantly reduced the number of IgE(+)B220(+) cells, while chlorogenic acid and pelargonin significantly decreased the number of FcεRIα(+)CD117(+) cells in mouse spleen cell cultures. These results suggest that some polyphenols in the date may reduce mite-induced allergic symptoms in mice via a decrease in the number of IgE-producing plasma cells and high-affinity IgE receptor-expressing mast cells.

Emotion, directed forgetting, and source memory.

We investigated the role of emotion on item and source memory using the item method of directed forgetting (DF) paradigm. We predicted that emotion would produce source memory impairment because emotion would make it more difficult to distinguish between to-be-remembered (R items) and to-be-forgotten items (F items) by making memory strength of R and F items similar to each other. Participants were presented with negatively arousing, positively arousing, and neutral pictures. After each picture, they received an instruction to remember or forget the picture. At retrieval, participants were asked to recall both R and F items and indicate whether each item was an R or F item. Recall was higher for the negatively arousing than for the positively arousing or neutral pictures. Further, DF occurred for the positively arousing and neutral pictures, whereas DF was not significant for the negatively arousing pictures. More importantly, the negatively arousing pictures, particularly the ones with violent content, showed a higher tendency of producing misattribution errors than the other picture types, supporting the notion that negative emotion may produce source memory impairment, even though it is still not clear whether the impairment occurs at encoding or retrieval.

Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys.

BACKGROUND: Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. METHODS: We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. RESULTS: We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL. CONCLUSIONS: TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.