Feature Integration in the Mapping of Multi-Attribute Visual Stimuli to Responses

In the human visual system, different attributes of an object, such as shape and color, are separately processed in different modules and then integrated to elicit a specific response. In this process, different attributes are thought to be temporarily “bound” together by focusing attention on the object; however, how such binding contributes to stimulus-response mapping remains unclear. Here we report that learning and performance of stimulus-response tasks was more difficult when three attributes of the stimulus determined the correct response than when two attributes did. We also found that spatially separated presentations of attributes considerably complicated the task, although they did not markedly affect target detection. These results are consistent with a paired-attribute model in which bound feature pairs, rather than object representations, are associated with responses by learning. This suggests that attention does not bind three or more attributes into a unitary object representation, and long-term learning is required for their integration

Combined immunohistochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer

BACKGROUND: It is important to discriminate between primary and secondary lung cancer. However, often, the discriminating diagnosis of primary lung acinar adenocarcinoma and lung metastasis of colorectal cancer based on morphological and pathological findings is difficult. The purpose of this study was to evaluate the clinical usefulness of immunohistochemistry of β-catenin, cytokeratin (CK) 7, and CK20 for the discriminating diagnosis of lung cancer. METHODS: We performed immunohistochemistry of β-catenin, CK7, and CK20 in 19 lung metastasis of colorectal cancer samples, 10 corresponding primary colorectal cancer samples and 11 primary lung acinar adenocarcinoma samples and compared the levels of accuracy of the discriminating diagnosis by using antibodies against these antigens. RESULTS: Positive staining of β-catenin was observed in all the lung metastasis of colorectal cancer samples as well as in the primary colorectal cancer samples but in none of the primary lung acinar adenocarcinoma samples. Positive staining of CK7 was observed in 90.9% of the primary lung acinar adenocarcinoma samples and in 5.3% of the lung metastasis of colorectal cancer samples, but in none of the primary colorectal cancer samples. Positive staining of CK20 was observed in all the primary colorectal cancer samples and in 84.2% of the lung metastasis of colorectal cancer samples, but in none of the primary lung acinar adenocarcinoma samples. CONCLUSION: Combined immunohistochemistry of β-catenin, CK7, and CK20 is useful for making a discriminating diagnosis between lung metastasis of colorectal cancer and primary lung acinar adenocarcinoma. This method will enable accurate diagnosis of a lung tumor and will be useful for selecting appropriate therapeutic strategies, including chemotherapeutic agents and operation methods

Impact of Gender on In-hospital Mortality in Patients with Acute Myocardial Infarction in Nagasaki

Acute myocardial infarction (AMI) is one of the leading causes of death in Japan. Immediate reperfusion therapy, includingcoronary intervention, improves patient prognosis. Despite this, females are said to be more prone to poor prognosis. A regional AMI registry in Nagasaki prefecture has been instituted recently that will evaluate whether female gender might predict short-term in-hospital death. Seventeen regional AMI centers enrolled all AMI patients from September 2014 through March 2016. A propensity score (PS) was derived using logistic regression to model the probability of females as a total function of the potential confounding covariates. Two types of PS techniques were used: PS matching and PS stratification. The consistency of in-hospital death was determined between PS matched patients of both genders. Based on PS, patients were ranked and stratified into five groups for the PS stratification. Out of 996 patients, 67 (6.7%) died during hospitalization: 31 (10.4%) out of 298 females and 36 (5.2%) out of 698 males (p < 0.0025). The proportion of cardiac and non-cardiac related death was almost same between genders (25 and 6 in female, 29 and 7 in male, respectively). Among 196 PS matched patients, there was a consistency between genders regarding in-hospital deaths (McNemar test, p = 0.6698). The 717 propensity scored patients had no significant differences between genders among propensity quintiles (Cochran-Mantel-Heanszel test, p = 0.7117). We found that gender alone is not an indicator of short-term in-hospital death in acute myocardial infarction patients

Phosphodiesterase-III Inhibitor Prevents Hemorrhagic Transformation Induced by Focal Cerebral Ischemia in Mice Treated with tPA

The purpose of the present study was to investigate whether cilostazol, a phosphodiesterase-III inhibitor and antiplatelet drug, would prevent tPA-associated hemorrhagic transformation. Mice subjected to 6-h middle cerebral artery occlusion were treated with delayed tPA alone at 6 h, with combined tPA plus cilostazol at 6 h, or with vehicle at 6 h. We used multiple imaging (electron microscopy, spectroscopy), histological and neurobehavioral measures to assess the effects of the treatment at 18 h and 7 days after the reperfusion. To further investigate the mechanism of cilostazol to beneficial effect, we also performed an in vitro study with tPA and a phosphodiesterase-III inhibitor in human brain microvascular endothelial cells, pericytes, and astrocytes. Combination therapy with tPA plus cilostazol prevented development of hemorrhagic transformation, reduced brain edema, prevented endothelial injury via reduction MMP-9 activity, and prevented the blood-brain barrier opening by inhibiting decreased claudin-5 expression. These changes significantly reduced the morbidity and mortality at 18 h and 7 days after the reperfusion. Also, the administration of both drugs prevented injury to brain human endothelial cells and human brain pericytes. The present study indicates that a phosphodiesterase-III inhibitor prevents the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells.

We previously examined the effect of brain microvascular endothelial cell (MVEC) transplantation on rat white matter infarction, and found that MVEC transplantation promoted remyelination of demyelinated axons in the infarct region and reduced apoptotic death of oligodendrocyte precursor cells (OPCs). We also found that the conditioned medium (CM) from cultured MVECs inhibited apoptosis of cultured OPCs. In this study, we examined contribution of extracellular vesicles (EVs) contained in the CM to its inhibitory effect on OPC apoptosis. Removal of EVs from the CM by ultracentrifugation reduced its inhibitory effect on OPC apoptosis. To confirm whether EVs derived from MVECs are taken up by cultured OPCs, we labeled EVs with PKH67, a fluorescent dye, and added them to OPC cultures. Many vesicular structures labeled with PKH67 were found within OPCs immediately after their addition. Next we examined the effect of MVEC-derived EVs on OPC behaviors. After 2 days in culture with EVs, there was significantly less pyknotic and more BrdU-positive OPCs when compared to control. We also examined the effect of EVs on motility of OPCs. OPCs migrated longer in the presence of EVs when compared to control. To examine whether these effects on cultured OPCs are shared by EVs from endothelial cells, we prepared EVs from conditioned media of several types of endothelial cells, and tested their effects on cultured OPCs. EVs from all types of endothelial cells we examined reduced apoptosis of OPCs and promoted their motility. Identification of the molecules contained in EVs from endothelial cells may prove helpful for establishment of effective therapies for demyelinating diseases

TEACCH-based group social skills training for children with high-functioning autism: a pilot randomized controlled trial.

[Background]Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted. [Methods]Eleven children with HFA, aged 5–6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent–child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS). [Results]Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers’ satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not. [Conclusion]We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses

Thrombosed Stanford Type A Dissection of the Aorta in an Elderly Patient Following a Fall

Physical or mental exertion is an important antecedent to dissection. A fall is one of the causes of hip fracture in the elderly population. We report the case of a 78-year-old woman who was diagnosed to have a thrombosed aortic dissection after a fall. We wish to emphasize with this case report that aortic dissection should be considered in the differential diagnosis of patients who complain of chest discomfort after a tumbling over

Removal of EVs from MVEC-CM reduced its effects on cultured OPCs.

<p>OPCs were cultured in MVEC-CM or EV-dep-MVEC-CM for 3 days (or overnight for cell motility assay). As control, OPCs were cultured in fresh serum-free medium. (A) Phase contrast images. Scale bar, 50 μm. (B) OPCs were stained with Hoechst 33342, and the nuclear morphology was observed. The number of pyknotic nuclei (red arrowheads) in MVEC-CM was smaller when compared to that of EV-dep-MVEC-CM. Scale bar, 50 μm. (C) After labeling with 10 μM BrdU for the last 4 h of culture, cells were fixed and stained with an anti-BrdU antibody. Cell nuclei were stained with propidium iodide (PI, red). Many BrdU-positive cells (green) were observed in MVEC-CM. Scale bar, 50 μm. (D) Phase contrast images of OPC migration 16 h after plating (<i>Insets</i>: OPC aggregates 1 h after plating). Scale bar, 200 μm. (E) All nuclei (pyknotic or non-pyknotic) were counted in a field of microscope and the fraction of pyknotic nuclei was determined, and results are shown as mean ± SE (N = 8 in each condition). Treatment with MVEC-CM significantly inhibited apoptotic cell death of OPCs. ***p<0.001 against control. #p<0.05 against EV-dep-MVEC-CM. (F) All cells were counted in a field of microscope and the fraction of BrdU-positive cells was determined, and results are shown as mean ± SE (N = 8 in each condition). The proportion of BrdU-positive cells in MVEC-CM was significantly larger when compared to EV-dep-MVEC-CM. *p<0.05 against control and MVEC-CM. (G) The distance of OPC migration in MVEC-CM was significantly larger when compared to EV-dep-MVEC-CM. Results are shown as mean ± SE (N = 4 in each condition). ***p<0.001 against control. ###p<0.001 against EV-dep-MVEC-CM. These experiments were repeated three times, and similar results were obtained each time. Typical experiments are shown here.</p

MVEC-EVs promoted OPC survival, proliferation and motility.

<p>EVs isolated from MVEC-CM were suspended in fresh serum-free medium at 50 μg/ml of proteins and added to OPC culture, which were maintained for 2 days (or overnight for cell motility assay). As control, OPCs were cultured in fresh serum-free medium without EVs. (A) Phase contrast images. Scale bar, 50 μm. (B) OPCs were stained with Hoechst 33342, and the nuclear morphology was observed. The proportion of pyknotic nuclei (red arrowheads) in OPCs with MVEC-EVs was smaller when compared to control. Scale bar, 50 μm. (C) After labeling with BrdU for the last 4 h of culture, cells were fixed and stained with an anti-BrdU antibody. Cell nuclei were stained with propidium iodide (PI, red). Many BrdU-positive cells (green) were observed in the presence of MVEC-EVs. Scale bar, 50 μm. (D) Phase contrast images of OPC migration 16 h after plating (<i>Insets</i>: OPC aggregates at 1 h after plating). Scale bar, 200 μm. (E) The proportion of pyknotic nuclei in the presence of MVEC-EVs was significantly smaller when compared to control. Results are shown as mean ± SE (N = 8 in each condition). ***p<0.001. (F) The proportion of BrdU-positive cells in the presence of MVEC-EVs was significantly larger when compared to control. Results are shown as mean ± SE (N = 8 in each condition). ***p<0.001. (G) The distance of OPC migration in the presence of MVEC-EVs was significantly larger when compared to control. Results are shown as mean ± SE (N = 4 in each condition). ***p<0.001. These experiments were repeated three times, and similar results were obtained each time. Typical experiments are shown here.</p