Age, gender, and financial literacy in Japan.
The aim of this study is to investigate the association between financial literacy and age as well as gender differences in financial literacy. We analyse a sample of 25,000 individuals from 'The Financial Literacy Survey 2016' conducted by the Central Council for Financial Services Information (Bank of Japan). The analysis focuses on the relationship of age and financial literacy as well as that of age and self-rated financial knowledge. To consider factors accounting for gender differences in financial literacy, we use the Blinder-Oaxaca decomposition method. To further our understanding of financial literacy, we conduct additional analyses on financial behaviour and attitude. Although age is associated with increased financial literacy (Men, β: 0.249, standard error [SE]: 0.030; Women, 0.354, SE: 0.026), the growth rate decreases among the older respondents (Men, β: -0.002, SE: 0.000; Women, -0.003, SE: 0.000). However, the association between age and self-rated financial knowledge among men moves in the opposite direction (Age, β: -0.021, SE: 0.009, Age2, β: 0.000, SE: 0.000). Furthermore, female respondents are likely to be less financially literate than their male counterparts (β: -0.586, SE: 0.095) due to gender differences in the distribution of the factors that affect financial literacy (specifically education), their responses to financial literacy, and the interactions of these effects. In contrast to knowledge-based financial literacy, financial behaviour and attitudes among women are more preferable to those among men, namely, more premeditated. Financial literacy increases until about one's early 60s, after which it declines, while confidence in financial literacy reflects the inverse trend, especially among men. Additionally, men are more financially literate than women; however, these differences could be mitigated through education. Meanwhile, financial behaviour and attitudes among men are less premeditated. Thus, policies are needed that can help older adults with their financial decision-making, enhance women's financial literacy, and improve men's financial behaviours and attitudes.


A patient perspective of complementary and integrative medicine (CIM) for migraine treatment: a social media survey.
To survey persons with migraine who use social media about Complementary and Integrative Medicine (CIM) for the treatment of migraine. CIM encompasses medical treatments that are not part of but are used in concert with mainstream medicine. Between 28 and 82% of people with migraine use non-drug approaches, and approximately 50% of people with migraine do not discuss non-drug treatments with their healthcare providers (HCPs). It is important for providers to be conversant with CIM treatments and the available evidence-based data. To further this effort, people with migraine were surveyed directly through social media to identify CIM practices in which they engage. In collaboration with the American Migraine foundation (AMF) and Yakkety Yak, a digital marketing agency, we conducted a cross-sectional survey study. Participants were recruited from the Move Against Migraine (MAM) Facebook group which has 20,000+ members. The goals of the survey were to assess the attitudes toward CIM among this group, to identify which CIM modalities are being used and to determine what patients considered to be the most effective CIM modalities. While Yakkety Yak posted the survey link on the group page, the survey itself was hosted on Qualtrics, a confidential survey service. 372 MAM members (approximately 2%) responded to the questionnaire, of which 335 reported using CIM; between 114 and 139 (34-42%) found CIM modalities to be at least mildly effective. Of note, 164 (49%) reported using cannabis derivatives or cannabinoids, specifically with, 64/164 (39%) reporting that cannabis was not effective for them. This study provides an initial investigation into the demographic and practice patterns of migraine patients who use CIM. While this sampling may not reflect CIM use across all individuals with migraine, it does strongly suggest the need for better education on the role of, and evidence for, CIM among headache care providers, and the need to ask patients specifically about their use of and interest in CIM.


A case of conversion of a NIPRO ventricular assist system to an EVAHEART left ventricular assist system.
Bridge to bridge (BTB) is a promising strategy for the treatment of end-stage heart failure that involves the left ventricular assist system (LVAS). We describe our experience with the conversion of an extracorporeal ventricular assist system (VAS), the NIPRO VAS, to an implantable LVAS, the EVAHEART LVAS. A 32-year-old man underwent a NIPRO VAS implantation as a bridge to decision for a condition consistent with Interagency Registry for Mechanically Assisted Circulatory Support profile 1. He was later diagnosed with secondary cardiomyopathy due to cardiac sarcoidosis. During the period in which he had NIPRO VAS support, no significant bacterial cultures were obtained from the cannula-piercing site, and no systemic infection occurred. Approximately 5 months after the NIPRO VAS implantation, he underwent an EVAHEART LVAS implantation as a BTB. The procedure required technical modifications, including the anastomosis of outflow grafts, trimming of the apical cuff, and creation of a pump pocket. The operation was completed uneventfully. The patient completed the discharge program for awaiting heart transplantation at home. Approximately 6 months after the EVAHEART LVAS implantation, he continues to do well without any complications, including infection, and visits our hospital as an outpatient. Conversion to an implantable LVAS can be beneficial in carefully selected patients after ascertaining the operative indications and operation timing.


Aprotinin pretreatment diminishes postischemic myocardial contractile dysfunction in dogs.
We evaluated the effect of aprotinin, administered before the onset of acute regional myocardial ischemia, on reversible contractile dysfunction induced by ischemia and reperfusion in pentobarbital-anesthetized dogs. Animals were randomized to receive either aprotinin 30,000 kallikrein inactivator units (KIU)/kg and 7000 KIU x kg(-1) x hr(-1) (n = 8) or equivalent volumes of 0.9% sodium chloride (n = 7) IV 60 min before a 15-min interruption of circumflex coronary artery blood flow and then reperfusion. There were no intra- or intergroup differences in hemodynamic variables or regional myocardial mechanics (sonomicrometry) before onset of ischemia. Immediately before reperfusion, systolic dysfunction characterized by significantly decreased percent systolic shortening was present in the circumflex coronary artery area of both study groups. After reestablishment of perfusion, aprotinin animals had preserved percent systolic shortening whereas saline animals exhibited regional systolic dysfunction. Regional myocardial contractility as assessed by the slope Mw of the preload recruitable stroke work relation was preserved during reperfusion in animals who received aprotinin but depressed in the control group. We conclude that functional recovery from myocardial ischemia-reperfusion injury at normothermia is improved by IV administration of aprotinin before the onset of acute regional myocardial ischemia in physiologically intact dogs. Administration of clinically relevant doses of aprotinin IV before the onset of regional myocardial ischemia, in contrast to control conditions, preserved regional systolic function and contractility at baseline values after reestablishment of myocardial perfusion in dogs.


Canine hemangiosarcoma treated with standard chemotherapy and minocycline.
Standard treatments for canine hemangiosarcoma include surgery and chemotherapy with doxorubicin, but in spite of treatment most dogs with this disease die within 6 months of diagnosis. Tumor growth and metastasis are angiogenesis dependent. Antiangiogenic drugs such as minocycline may provide therapeutic benefits in cancer patients. The purpose of this prospective study was to evaluate the efficacy of chemotherapy with doxorubicin and minocycline, an antiangiogenic agent, in dogs with hemangiosarcoma. Eighteen dogs with histologically confirmed hemangiosarcoma of any stage were treated with doxorubicin, cyclophosphamide, and minocycline. Complete staging was performed before and during the treatment period to assess remission status and response to therapy. No statistically significant difference was found in survival between the dogs treated with chemotherapy and minocycline, and historical controls consisting of dogs that received chemotherapy alone. Postmortem examination revealed widespread metastasis, suggesting that minocycline is ineffective as a single antiangiogenic agent in canine hemangiosarcoma.


Different polyketide folding modes converge to an identical molecular architecture.
Metabolic diversity is being studied intensively by evolutionary biologists, but so far there has been no comparison of biosynthetic pathways leading to a particular secondary metabolite in both prokaryotes and eukaryotes. We have detected the bioactive anthraquinone chrysophanol, which serves as a chemical defense in diverse eukaryotic organisms, in a bacterial Nocardia strain, thereby permitting the first comparative biosynthetic study. Two basic modes of folding a polyketide chain to fused-ring aromatic structures have so far been described: mode F (referring to fungi) and mode S (from Streptomyces). We have demonstrated that in eukaryotes (fungi, higher plants and insects), chrysophanol is formed via folding mode F. In actinomycetes, by contrast, the cyclization follows mode S. Thus, chrysophanol is the first polyketide synthase product that is built up by more than one polyketide folding mode.


[The course of pregnancy and labor in women with combined anemia of pregnancy and late gestosis].
The course of pregnancy in anemia of pregnancy current with late gestosis is characterized by an early development of fetoplacental insufficiency, a greater risk for hypertrophy of the fetus, hemorrhage during the third and early postpartum period, septic puerperal complications. Early correction of the above pathological states can diminish the number of disorders induced by them in the organism of the mother and fetus alike.


Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization.
Piperlongumine (PL), a natural alkaloid isolated from longer pepper plants, is recently found to be a potent selective anti-cancer compound. We first tested its anti-cancer effects on bladder cancer, the fifth most common and aggressive cancer worldwide, to further explore the therapeutic spectrum and molecular mechanisms of PL. PL significantly suppressed bladder cancer cell proliferation, the transition of G2/M phase to next phase, migration/invasion in vitro and bladder cancer growth/development in vivo. PL markedly elevated reactive oxygen species (ROS) and the administration of antioxidants abolished PL induced cell proliferation inhibition, G2/M phase arrest and migration suppression on bladder cancer cells. In vivo studies demonstrated that PL inhibited epithelial mesenchymal transition with profoundly decreased level of Slug, β-catenin, ZEB1 and N-Cadherin. Further, we first reported PL effects on cytoskeleton with prominently reduced lamellipodia formation and decreased F-actin intensity in bladder cancer cells. Taken together, our results first revealed that PL suppressed bladder cancer proliferation and migration in vivo and in vitro, suggesting novel mechanism underlying PL's anti-cancer effect and providing a new anticancer drug strategy for bladder cancer therapy.


[Priorities for health improvement in the medical personnel of phthisiatric service in the Primor'ie Territory].
The authors analyze occupational morbidity rates in the medical personnel of tuberculosis facilities in the Primorsky Territory, as well as the location of the institutions (workrooms) and the influence of occupational factors on medical workers. The nature of work and working conditions in the medical workers of a tuberculosis facility where they are exposed to occupational hazards in practically 100% of cases necessitate effective measures to promote and preserve their health. The absence of standard buildings and premises for tuberculosis facilities and the low efficiency of rehabilitative sanatorium-and-spa treatment, health improvement, and the prevention of occupational diseases are one of the problems of a tuberculosis service in the Primorsky Territory. The findings serve as the basis for the development of an approach to preventing occupational diseases and recovering the health status among the medical workers who have experienced tuberculosis.


Evaluation of moxifloxacin-hydroxyapatite composite graft in the regeneration of intrabony defects: A clinical, radiographic, and microbiological study.
The formation of new connective periodontal attachment is contingent upon the elimination or marked reduction of pathogens at the treated periodontal site. An anti-microbial agent, i.e. moxifloxacin has been incorporated into the bone graft to control infection and facilitate healing during and after periodontal therapy. By purposive sampling, 15 patients with at least two contralateral vertical defect sites were selected. The selected sites in each individual were divided randomly into test and control sites according to split-mouth design. Test site received moxifloxacin-hydroxyapatite composite graft and control site received hydroxyapatite-placebo gel composite graft. Probing depth (PD) and Clinical attachment level (CAL) were assessed at baseline, 3, 6, 9, and 12 months. Bone probing depth (BPD) and hard tissue parameters such as amount of defect fill, percentage of defect fill, and changes in alveolar crest were assessed at baseline, 6, and 12 months. Changes in subgingival microflora were also assessed by culturing the subgingival plaque samples at baseline and at 3-month follow-up. The clinical, radiographic, and microbiological data obtained were subjected to statistical analysis using descriptive statistics, paired sample t-test, independent t-test, and contingency test. On intragroup comparison at test and control sites, there was a significant improvement in all clinical and radiographic parameters. However, on intergroup comparison of the same, there was no statistically significant difference between test and control sites at any interval. Although test sites showed slightly higher amount of bone fill, it was not statistically significant. There was a significant reduction in the counts of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis at both sites from baseline to 3 months. In addition, there was a significant reduction at test sites as compared to control sites at 3-month follow-up (P = 0.003 and P = 0.013). The reduction in microbial counts found in test sites at 3-month follow-up could not bring similar significant improvements in the clinical and radiographic parameters though the test sites showed slightly higher bone fill.


Enhancing light extraction mechanisms of GaN-based light-emitting diodes through the integration of imprinting microstructures, patterned sapphire substrates, and surface roughness.
Analysis of the various light extraction efficiency enhancement mechanisms for the GaN-based light emitting diodes (LEDs) was investigated. Experiments utilized the imprinting technique to fabricate pyramid and inverted pyramid microstructures. Roughness treatment was then integrated with these imprinting structures on patterned sapphire substrate (PSS) LEDs. An approximate 33% improvement in light output power was obtained using the pyramid profile when compared with the planar LED. This was nearly 15% higher than that of the inverted pyramid profile. The roughness effect provided an approximate 5% efficiency enhancement. The total light enhanced efficiency increased to 85.9% by integrating the imprinting pyramid structure, PSS, and surface roughness.


Prophylactic gastrectomy for CDH1 mutation carriers.
Gastric cancer is difficult to diagnose at an early stage. Signs and symptoms of the disease often only occur when advanced or metastatic disease is present. A very small number of gastric cancers are hereditary. The mutation to the E-cadherin gene has high penetrance and confers a lifetime risk of gastric cancer of 80% for carriers. Because of the high penetrance of the mutation and the difficulty of diagnosing gastric cancer at an early stage, carriers of the mutation may be candidates for prophylactic gastrectomy. Although limited data are available about the complications and outcomes associated with prophylactic gastrectomy, nurses should be knowledgeable about prophylactic surgery for hereditary cancers and prepared to answer patients' questions about their prevention.


Unknown aspect of the old disease: does dyslipidemia in systemic AA amyloidosis differ from the dyslipidemia in primary glomerulonephritis?
To investigate the nature of dyslipidemia and its diversity in patients with systemic AA amyloidosis. The reports of the kidney biopsies performed due to nephrotic proteinuria (>3.5 g/day/1.73 m(2)) with preserved renal function [glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)] were reviewed. Clinical and laboratory data of the patients with systemic AA amyloidosis and primary glomerulonephritis (PG) were analyzed. A total of 104 (systemic AA amyloidosis: 43, PG: 61) patients were included in the study. Proteinuria and GFR levels were similar in both the groups. Patients with systemic AA amyloidosis group had lower serum albumin (p = 0.002), lower hemoglobin levels (p = 0.001), higher platelet counts (p = 0.002) and higher C-reactive protein levels (p = 0.001) compared to patients in PG group. Although the frequency of dyslipidemia was similar in the groups (86.0 vs. 93.4%), patients with systemic amyloidosis had both lower values of LDL-C (4.56 ± 2.05 vs. 5.49 ± 2.23 mmol/L, p = 0.028) and HDL-C (1.19 ± 0.36 vs. 1.35 ± 0.39 mmol/L, p = 0.035). Serum lipid levels were correlated with serum total protein, albumin and proteinuria levels in PG group. However, in the systemic amyloidosis group, only one clear correlation between serum lipid and hemoglobin levels was estimated. A multivariate analysis demonstrated that LDL-C was independently associated with the etiology of nephrotic proteinuria, serum total protein, serum albumin (inversely) and hemoglobin levels. Although dyslipidemia is closely associated with serum total protein, albumin and proteinuria in patients with PG, there is no clear such association in patients with systemic amyloidosis. Correlation between serum lipid and hemoglobin levels in this group and other findings point out that probably complex mechanisms take place in dyslipidemia of nephrotic syndrome caused by systemic AA amyloidosis.


Effect of muscle metaboreflex activation on central hemodynamics and cardiac function in humans.
We sought to determine how the mode of muscle metaboreflex activation influences the central hemodynamic response and cardiac inotropic and lusotropic function in healthy humans. Ten healthy males performed (i) isometric handgrip (IHG) with and without post-exercise ischemia (PEI) to examine the influence of isolated muscle metaboreflex activation and (ii) rhythmic handgrip (RHG) with and without ischemia to examine the influence of enhanced muscle metaboreflex activation. Heart rate (HR) and blood pressure (BP) were continuously monitored. Stroke volume (SV, Doppler echocardiography) was measured, cardiac output (CO = HR × SV) and total peripheral resistance (TPR = mean BP/CO) calculated, and indices of left ventricular systolic and diastolic function were obtained (tissue Doppler imaging). During isolated muscle metaboreflex activation with PEI following IHG, mean BP (+23 ± 3 mm Hg) and TPR were elevated from baseline (p < 0.05), whereas HR, SV, and CO were unchanged. Enhanced muscle metaboreceptor activation during ischemic RHG augmented the increase in mean BP, CO, and HR (p < 0.05 ischemic vs. free-flow RHG), whereas SV and TPR were unchanged from baseline. Neither isolated (PEI) nor enhanced muscle metaboreflex activation altered left ventricular systolic function (systolic myocardial velocity), but left atrial systolic function (late diastolic myocardial velocity) was enhanced. These findings indicate that the mode of muscle metaboreceptor activation (during vs. post handgrip) determines whether the resultant pressor response is flow (CO) or vasoconstriction (TPR) mediated, and that although left ventricular systolic function is unchanged, enhanced left atrial systolic function likely aids the preservation of SV during muscle metaboreflex engagement.


[Evaluation of sandfly control measures].
Collections of sandflies were made between May 2005 and April 2006. The results were compared with those from collections undertaken between April 2001 and September 2002, in order to evaluate the measures used to decrease the density of these insects in Recanto Marista, municipality of Doutor Camargo, State of Paraná. The collections were carried out by Falcão traps inside domiciles and hen sheds, from 10 p.m. to 2 a.m. once a week, four times a month. In 2005 and 2006, 213,195 sandflies were collected (average of 1,113.8 per hour), compared with 199,821 (average of 1,653.5 per hour) in 2001 and 2002. Nyssomyia neivai predominated (75.4%) in all the ecotopes. Nyssomyia neivai, Nyssomyia whitmani, Migonemyia migonei and Pintomyia fischeri accounted for 99.7% of all the sandflies collected. The ecotope of hencoops accounted for 88.7% of the sandflies collected. It was observed that the sandfly density had decreased between the 2001-2002 and 2005-2006 collections, especially in homes.


Correction of count losses due to deadtime on a DST-XLi (SmVi-GE) camera during dosimetric studies in patients injected with iodine-131.
In dosimetric studies performed after therapeutic injection, it is essential to correct count losses due to deadtime on the gamma camera. This note describes four deadtime correction methods, one based on the use of a standard source without preliminary calibration, and three requiring specific calibration and based on the count rate observed in different spectrometric windows (20%, 20% plus a lower energy window and the full spectrum of 50-750 keV). Experiments were conducted on a phantom at increasingly higher count rates to check correction accuracy with the different methods. The error was less than +7% with a standard source, whereas count-rate-based methods gave more accurate results. On the assumption that the model was paralysable, preliminary calibration allowed an observed count rate curve to be plotted as a function of the real count rate. The use of the full spectrum led to a 3.0% underestimation for the highest activity imaged. As count losses depend on photon flux independent of energy, the use of the full spectrum during measurement allowed scatter conditions to be taken into account. A protocol was developed to apply this correction method to whole-body acquisitions.


Ambient particulate air pollution and microRNAs in elderly men.
Ambient particulate matter (PM) has been associated with mortality and morbidity for cardiovascular disease. MicroRNAs control gene expression at a posttranscriptional level. Altered microRNA expression has been reported in processes related to cardiovascular disease and PM exposure, such as systemic inflammation, endothelial dysfunction, and atherosclerosis. Polymorphisms in microRNA-related genes could influence response to PM. We investigated the association of exposure to ambient particles in several time windows (4-hour to 28-day moving averages) and blood leukocyte expression changes in 14 candidate microRNAs in 153 elderly males from the Normative Aging Study (examined 2005-2009). Potential effect modification by six single nucleotide polymorphisms (SNPs) in three microRNA-related genes was investigated. Fine PM (PM2.5), black carbon, organic carbon, and sulfates were measured at a stationary ambient monitoring site. Linear regression models, adjusted for potential confounders, were used to assess effects of particles and SNP-by-pollutant interaction. An in silico pathway analysis was performed on target genes of microRNAs associated with the pollutants. We found a negative association for pollutants in all moving averages and miR-1, -126, -135a, -146a, -155, -21, -222, and -9. The strongest associations were observed with the 7-day moving averages for PM2.5 and black carbon and with the 48-hour moving averages for organic carbon. The association with sulfates was stable across the moving averages. The in silico pathway analysis identified 18 pathways related to immune response shared by at least two microRNAs; in particular, the "high-mobility group protein B1/advanced glycosylation end product-specific receptor signaling pathway" was shared by miR-126, -146a, -155, -21, and -222. No important associations were observed for miR-125a-5p, -125b, -128, -147, -218, and -96. We found significant SNP-by-pollutant interactions for rs7813, rs910925, and rs1062923 in GEMIN4 and black carbon and PM2.5 for miR-1, -126, -146a, -222, and -9, and for rs1640299 in DGCR8 and SO4 for miR-1 and -135a. Exposure to ambient particles could cause a downregulation of microRNAs involved in processes related to PM exposure. Polymorphisms in GEMIN4 and DGCR8 could modify these associations.


Upregulation of PD-L1 Expression by Prostaglandin E2 and the Enhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection.
Bovine mycoplasmosis caused by Mycoplasma bovis results in pneumonia and mastitis in cattle. We previously demonstrated that the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E2 (PGE2) suppressed immune responses and upregulated PD-L1 expression in Johne's disease, a bacterial infection in cattle. In this study, we investigated the role of PGE2 in immune dysfunction and the relationship between PGE2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE2 and PD-L1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE2 levels were positively correlated with the proportions of PD-L1+ monocytes in M. bovis-infected cattle. Additionally, plasma PGE2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE2 could be one of the inducers of PD-L1 expression and could be involved in immunosuppression during M. bovis infection. In vitro blockade assays using anti-bovine PD-L1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE2 and the PD-1/PD-L1 pathway.


Familial pericentric inversion of chromosome 19, inv(19) (p13q13) with a note on genetic counseling of pericentric inversion carriers.
An inmate of a hospital for the mentally retarded was found during a cytogenetic screening programme to have karyotype 46,XY,inv(19)(p13q13)mat. Clinical, cytogenetic and family findings are presented and it is concluded that the chromosomes abnormality was probably not the cause of the patient's retardation. The problem of genetic counseling of inversion carriers is examined in some detail and estimates of risk are given.


[Traffic accidents and alcohol consumption in an emergency unit of La Paz, Bolivia].
The aim of this quantitative, descriptive, observational, cross-sectional study was to characterize the distribution and characteristics of motor vehicle accidents related to alcohol consumption. The sample was composed of 62 drivers and pedestrians, over 15 years old, who were involved in motor vehicle accidents involving alcohol, and were attended at the Emergency Unit of the Clinical Hospital of La Paz - Bolivia. A survey designed by the researchers to collect partner-demographic data and morbidity of the victim was applied and data that evaluated the alcohol consumption of the driver responsible for the accident was collected. The results demonstrated that 71% of the victims were men; 32.3% were between 21 and 30 years old; 29% were students and 25.8% were the drivers. This study shows the characterization of victims, alcohol consumption and accidents.


An ecologically sensitive measure of executive cognition (the Breakfast Task) improves prediction of functional outcome in schizophrenia.
Previous work has found that the Breakfast Task (BT), a computerized, ecologically informed executive ability measure, is sensitive to group differences in aging, acquired brain injury, and Parkinson's disease. We investigated whether this measure improves the prediction of functional status over and above standard measures of general intellectual ability, relationship perception, life skills, and symptom severity in individuals with schizophrenia. Regression analyses were conducted to evaluate the joint and incremental validity of the BT in predicting functional disability scores on the World Health Organization Disability Assessment Scale (WHODAS 2.0). Analyses with combined patient (n = 25) and control (n = 32) participants showed that participant status (patients versus control) was the only significant predictor of functional outcome. However, in the patient data, the proportion of variance accounted for improved significantly (model R2 of 4% vs. 25%) when BT scores were added to a model containing clinical (Brief Psychiatric Rating Scale), social (Relationships Across Domains), intellectual (Wechsler Abbreviated Scale of Intelligence), and life skills (Canadian Objective Assessment of Life Skills) measures. Results suggest that the BT, a tool that captures complex executive functioning, improves the prediction of disability in patients with schizophrenia and has potential assessment applications.


Feasibility of social network analysis to study outcomes of children with medical complexity.
Since most care for children with medical complexity (CMC) is delivered daily in communities by multiple caregiving individuals, that is, caregiving networks, tools to assess and intervene across these networks are needed. This study evaluated the feasibility of applying social network analysis (SNA) to describe caregiving networks. Because hospitalization is among the most frequently used outcomes for CMC, exploratory correlations between network characteristics and CMC hospital use were evaluated. Within 3 weeks, the goal network enrollment was achieved, and all feasibility measures were favorable. Network characteristics correlated with hospital use, that is, smaller, denser networks, with more closed-loop communication correlated with fewer hospital days. Networks with more professional caregivers also correlated with fewer hospital days. SNA is a feasible tool to study CMC caregiving networks. Preliminary data support rigorous hypothesis testing using SNA methods. Network-based interventions to improve CMC health may be an important future direction.


Imaging of intracoronary thrombus.
The identification of intracoronary thrombus and atherothrombosis is central to the diagnosis of acute myocardial infarction, with the differentiation between type 1 and type 2 myocardial infarction being crucial for immediate patient management. Invasive coronary angiography has remained the principal imaging modality used in the investigation of patients with myocardial infarction. More recently developed invasive intravascular imaging approaches, such as angioscopy, intravascular ultrasound and optical coherence tomography, can be used as adjunctive imaging modalities to provide more direct visualisation of coronary atheroma and the causes of myocardial infarction as well as to improve the sensitivity of thrombus detection. However, these invasive approaches have practical and logistic constraints that limit their widespread and routine application. Non-invasive angiographic techniques, such as CT and MRI, have become more widely available and have improved the non-invasive visualisation of coronary artery disease. Although they also have a limited ability to reliably identify intracoronary thrombus, this can be overcome by combining their anatomical and structural characterisation of coronary anatomy with positron emission tomography. Specific radiotracers which bind with high specificity and sensitivity to components of thrombus, such as activated platelets, fibrin and factor XIIIa, hold promise for the non-invasive detection of intracoronary thrombus. The development of these novel non-invasive approaches has the potential to inform clinical decision making and patient management as well as to provide a non-invasive technique to assess the efficacy of novel antithrombotic therapies or interventional strategies. However, these have yet to be realised in routine clinical practice.


Metrology with Unknown Detectors.
The best possible precision is one of the key figures in metrology, but this is established by the exact response of the detection apparatus, which is often unknown. There exist techniques for detector characterization that have been introduced in the context of quantum technologies but apply as well for ordinary classical coherence; these techniques, though, rely on intense data processing. Here, we show that one can make use of the simpler approach of data fitting patterns in order to obtain an estimate of the Cramér-Rao bound allowed by an unknown detector, and we present applications in polarimetry. Further, we show how this formalism provides a useful calculation tool in an estimation problem involving a continuous-variable quantum state, i.e., a quantum harmonic oscillator.


Spectral analysis of left ventricular area variability as a tool to improve the understanding of cardiac autonomic control.
Spectral analysis of the fluctuations in heart rate (HR) or blood pressure (BP) has been extensively used as a tool for the noninvasive assessment of autonomic control of the heart. The recently developed echocardiographic acoustic quantification allows noninvasive continuous measurement of the left ventricular cross-sectional area (LVA) signal. In this study, we investigated whether the LVA signal, and more specifically its fluctuations, can be reliably subjected to spectral analysis, and whether the results of such analysis may improve the understanding of the cardiovascular control mechanisms. Our results show that the general pattern of power spectra of LVA fluctuations, as well as their reproducibility, is similar to the power spectra of HR and BP fluctuations. Analysis of LVA signals obtained in normal subjects at rest as well as under vagal blockade and under held respiration, and in patients with known autonomic dysfunction, showed significant differences between groups and states. The effects of age, related to the reduction in parasympathetic activity, were not evident in the spectral content of the LVA and BP signals. The high frequency LVA fluctuations are mainly of mechanical origin, since they were eliminated by breath-holding. We observed an increase in the high frequency LVA fluctuations under vagal blockade, indicating that under normal (control) conditions, these high frequency fluctuations are attenuated by parasympathetic activity. The enhancement in high frequency fluctuations in LVA observed in diabetic patients can thus be attributed to reduced parasympathetic activity. The analysis of LVA variability may be used as a tool for basic research and, possibly, as a quantitative clinical measure for specific disease states.


Kawasaki disease: echocardiographic features in 91 cases presenting in the United Kingdom.
Ninety-one patients with Kawasaki disease were examined by cross sectional echocardiography between 1980 and 1988. In the 75 patients evaluated during the acute phase of the illness (the first month), the first echocardiographic examination was carried out at a mean time of 16 days (range 5-30) and coronary arterial lesions were seen in 21 (28%). Two patients with medium sized aneurysms had myocardial infarctions, and one died. Coronary arterial lesions persisted in 17 (23%) patients, most often in younger children. The remaining 16 patients were examined from one month to four years after their acute illnesses, and this group did not have coronary arterial abnormalities. Seven patients with coronary artery lesions have reached school age and require regular echocardiographic examination and exercise electrocardiography. Selective coronary arteriography may be indicated in some patients to identify coronary artery stenosis, which the Japanese experience has shown may progress for several years after the acute illness.


Molecular dynamics of ionic polymer-metal composites.
Ionic polymer-metal composites (IPMCs) constitute a promising class of soft, active materials with potentially ubiquitous use in science and engineering. Realizing the full potential of IPMCs calls for a deeper understanding of the mechanisms underpinning their most intriguing characteristics: the ability to deform under an electric field and the generation of a voltage upon mechanical deformation. These behaviours are tightly linked to physical phenomena at the level of atoms, including rearrangements of ions and molecules, along with the formation of sub-nanometre thick double layers on the surface of the metal electrodes. Several continuum theories have been developed to describe these phenomena, but their experimental and theoretical validation remains incomplete. IPMC modelling at the atomistic scale could beget valuable support for these efforts, by affording granular analysis of individual atoms. Here, we present a simplified atomistic model of IPMCs based on classical molecular dynamics. The three-dimensional IPMC membrane is constrained by two smooth walls, a simplified analogue of metal electrodes, impermeable only to counterions. The electric field is applied as an additional force acting on all the atoms. We demonstrate the feasibility of simulating counterions' migration and pile-up upon the application of an electric field, similar to experimental observations. By analysing the spatial configuration of atoms and stress distribution, we identify two mechanisms for stress generation. The presented model offers new insight into the physical underpinnings of actuation and sensing in IPMCs. This article is part of the theme issue 'Progress in mesoscale methods for fluid dynamics simulation'.


International strategy in cancer epidemiology: Japan's involvement in global projects and future role.
In recent years, collaboration among researchers in the field of cancer epidemiology has been accelerating in various forms. Here, we review recent trends in international collaborative research activities in the cancer epidemiology field in Japan. These include not only support for other countries with less developed cancer statistics infrastructures, but also large-scale compilations and international comparisons through collaborative studies, as well as integration with analytical epidemiology and clinical research. Formation of international cohort consortia and estimates of cancer and risk factors in each country have contributed to raising the skill levels of cancer epidemiologists as well as to expanding research networks and activities among cancer epidemiologists. Molecular and genome epidemiological studies on cancer have progressed over decades and these continue to increase in size and dimension. Application of evidence from this area in prevention is still underway and needs further effort. Japanese epidemiologists have great potential to assume international leadership roles by taking advantage of the uniqueness, originality and characteristics of Japanese cohorts.


Gap junctions and direct intercellular communication between rat uterine smooth muscle cells.
We have tested the hypothesis that an increase in direct intercellular communication accompanies the development of gap junctions (GJs) between rat uterine smooth muscle cells at parturition. Intercellular communication in these tissues was studied by exposing one portion of small strips of myometrium to 2-[3H]deoxy-D-glucose (2-DG) and determining the longitudinal distribution of tracer after a 5-h period of diffusion. The distribution of 2-DG was greater in parturient compared with ante- and postpartum tissues. Similarly, the apparent diffusion coefficient of 2-DG was almost 10-fold greater in delivering tissues (1.86 X 10(-6) cm2/s) than before (0.199 X 10(-6) cm2/s) or after (0.296 X 10(-6) cm2/s) parturition. Control experiments indicated that the redistribution of 2-DG was dependent on the presence of GJs and was the result of intracellular and direct cell-to-cell diffusion. The appearance of GJs is the myometrium at term facilitates direct intercellular communication between uterine smooth muscle cells during labor. This improved communication may be responsible for synchronizing and coordinating electrical, metabolic, and contractile activity in the uterine wall and, hence, the effective expulsion of fetuses.


Coronavirus disease (COVID-19) and neonate: What neonatologist need to know.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.


"It Is Hard to Be a Woman With Schizophrenia": Randomized Controlled Trial of a Brief Video Intervention to Reduce Public Stigma in Young Adults.
Objective: Women with schizophrenia encounter specific gender-related stressors that may affect their recovery process. They are more susceptible to victimization and tend to experience more shame and stigma about their illness. Confronting stigma early in the illness could enhance treatment seeking. No studies have examined the efficacy of stigma-reducing interventions focused on public stigma toward women living with schizophrenia or have tested the effect of gender-specific content therein. Methods: We compared the efficacy at post-intervention and 30-day follow-up of 2 brief (~80-second) videos, with and without gender-related content, and a non-intervention control, in 1,181 young adults, between September and November 2021. The videos feature an empowered young woman living with schizophrenia who describes struggling with her psychotic illness to attain recovery and hope. Results: A 3 × 3 group-by-time analysis of variance showed decreased mean stigma scores over time in the two intervention arms relative to controls across all 5 public stigma domains: social distance (F = 17.1, P < .001), stereotyping (F = 25.0, P < .001), separateness (F = 8.3, P < .001), social restriction (F = 16.6, P < .001), and perceived recovery (F = 7.8, P < .001). Linear mixed modeling showed a greater intervention effect for women in the gender-related video group in social distance, stereotyping, and separateness. Conclusions: Greater stigma reduction among women in the gender-related video group underscores the importance of tailoring the narrative to specific experiences related to socio-demographic characteristics, especially among members of marginalized groups. This attenuation may result in greater identification and solidarity with the presenter. Future studies should explore other socially oppressed groups, including Black, Latinx, Asian, and LGBTQ+ communities.


Parasitic pneumonia.
With few exceptions, the parasitic pneumonias most commonly encountered in the Western Hemisphere are diseases of compromised hosts; patients with AIDS are at particular risk. Pneumocystis carinii pneumonia occurs eventually in 80% of AIDS patients; bronchoalveolar lavage is quite sensitive in establishing this diagnosis. Toxoplasma gondii pneumonia, seen most often in the patient with AIDS, is characterized by multisystem involvement. Strongyloides stercoralis infection is endemic in the Southeastern United States. Pulmonary strongyloidiasis is seen in patients receiving glucocorticoids or chemotherapy, and in patients with AIDS or other causes of T cell dysfunction. Larvae may be seen on Gram's stains or wet mounts of sputum. Ascaris and hookworm infections may present with pulmonary infiltrates and eosinophilia during the larval migration phase. Dirofilaria, Paragonimus, and Entamoeba histolytica involvement of the lung are less common and require a good epidemiologic history and clinical suspicion for diagnosis.


Concurrent inspiratory muscle and cardiovascular training differentially improves both perceptions of effort and 5000 m running performance compared with cardiovascular training alone.
To examine whether inspiratory muscle training (IMT) is a useful additional technique with which to augment cardiovascular exercise training adaptations. 16 healthy untrained males agreed to participate in the study and were randomly assigned to training (TRA; n = 8) and placebo (PLA; n = 8) groups. Pre- and post-training measurements of spirometry and maximal inspiratory mouth pressure (MIP) were taken in addition to i) maximal aerobic power (VO(2max)) and ii) 5000 m run time-trial. All subjects completed the same 4 week cardiovascular training programme which consisted of three running sessions (CV1: 5 x 1000 m, CV2: 3 x 1600 m, SP1: 20 min run) in each of the 4 weeks. IMT was performed daily by both groups using an inspiratory muscle trainer (POWERbreathe). TRA completed 30 maximal inspirations while PLA inspired 30 times against a negligible resistance. Mean MIP increased significantly in both groups (TRA: 14.5 (SD 6.8)% change, PLA: 7.8 (7.4)% change) from pre- to post-training (p<0.01) but was not significantly related to changes in running performance. Mean CV1 training-repetition runs improved similarly in both groups, but RPE evaluations were significantly reduced in TRA (15.7 (0.7)) compared with PLA (16.6 (0.8)) at week 4 (p<0.05). Pre- to post-training changes in VO(2max) were well-matched between both TRA (+2.1 (2.3)%) and PLA (+1.3 (2.4)%) while post-intervention 5000 m performance was significantly augmented in TRA compared with PLA (TRA: 4.3 (1.6)%, PLA: 2.2 (1.9)%, p<0.05). The addition of IMT to a cardiovascular training programme augments 5000 m running performance but exerts no additional influence over VO(2max) compared with a cardiovascular-training group. This is probably due to IMT-induced reduction in perceived effort at high ventilatory rates, which is of greater consequence to longer duration time-trial performances than incremental tests of VO(2max).


Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies.
Post-traumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder that constitutes a major health care burden. Despite evidence supporting a genetic predisposition to PTSD, the precise genetic loci remain unclear. Herein we review the current state and limitations of genetic research on PTSD. Although recent years have seen an exponential increase in the number of studies examining the influence of candidate genes on PTSD diagnosis and symptomatology, most studies have been characterized by relatively low rates of PTSD, with apparent inconsistencies in gene associations linked to marked differences in methodology. We further discuss how current advances in the genetics field can be applied to studies of PTSD, emphasizing the need to adapt a genome-wide approach that facilitates discovery rather than hypothesis testing. Genome-wide association studies offer the best opportunity to identify novel "true" risk variants for the disorder that in turn has the potential to inform our understanding of PTSD etiology.


Renaissance CFO emerges in response to market pressures.
A 1995 survey of chief financial officers (CFOs) in healthcare organizations finds that as the healthcare industry reshapes itself through mergers, acquisitions, and downsizing, the CFOs of the mid-1990s also are reshaping themselves into "Renaissance CFOs." They are acquiring new skills and expertise beyond the traditional area of finance. About one-third of the CFOs who took part in the February 1995 survey, which updates similar surveys in 1992 and 1990, said they are working to enhance their knowledge of managed care because they expect to assume responsibility for managed care as part of their expanding CFO responsibilities. Other new areas survey respondents said they expect to oversee before the decade's end are financial costing and pricing and physician relations. The 1995 CFO survey was commissioned by HFMA and Executive Risk Management Associates, Inc., and was conducted by Elrick & Lavidge, Inc. Previous CFO profile surveys have included analysis of CFO compensation data. This year, however, a separate, more indepth survey of CFO compensation was commissioned by HFMA; the findings of this survey will be presented in the October issue of HFM.


Addressing the operational problems in a composting and recycling plant.
The Istanbul composting and recycling plant, constructed in 2001, is one of the few composting plants in Turkey. During test operations of the plant, it was reported that the weight of the oversize materials (OM) above a 80-mm sieve was about 40% of the total incoming waste. They mainly consist of plastic bags that were full of garbage, which resulted in operational problems in the plant. In this paper, the composition of OM was determined and evaluated, particularly to find the economic losses in the plant. It was determined that approximately 58% of the OM transferred to the landfill area due to operational failures and interruptions could be used at the plant with improved operational conditions. Otherwise, the plant would realize an annual economic loss of about 640,800 US$. Compost quality in the plant has been satisfactory, but source separated collection, at least the separation of the wet from the dry fraction, is needed to increase the amount of compost and recovered materials.


An Insight in the Reproductive Biology of Therophilus javanus (Hymenoptera, Braconidae, and Agathidinae), a Potential Biological Control Agent against the Legume Pod Borer (Lepidoptera, Crambidae).
Therophilus javanus is a koinobiont, solitary larval endoparasitoid currently being considered as a biological control agent against the pod borer Maruca vitrata, a devastating cowpea pest causing 20-80% crop losses in West Africa. We investigated ovary morphology and anatomy, oogenesis, potential fecundity, and egg load in T. javanus, as well as the effect of factors such as age of the female and parasitoid/host size at oviposition on egg load. The number of ovarioles was found to be variable and significantly influenced by the age/size of the M. vitrata caterpillar when parasitized. Egg load also was strongly influenced by both the instar of M. vitrata caterpillar at the moment of parasitism and wasp age. The practical implications of these findings for improving mass rearing of the parasitoid toward successful biological control of M. vitrata are discussed.


Benzene-1,3,5-triyl tribenzoate.
The title compound, C27H18O6, commonly known as phloroglucinol tribenzoate, is a standard unit for the family of benzyl ether dendrimers. The central phloroglucinol residue is close to planar, with out-of-plane distances for the three oxygen atoms of up to 0.095 (3) Å, while the three attached benzoate groups are approximately planar. One benzoate group is twisted [C-C-O-C torsion angle = 98.2 (3)°] from the central plane, with its carbonyl O atom 2.226 (4) Å above that plane, while the other two benzoate groups are twisted in the opposite direction [C-C-O-C torsion angles = 24.7 (2) and 54.8 (2)°], so that their carbonyl O atoms are on the other side of, and closer to the central plane, with distances from the plane of 1.743 (4) and 1.206 (4) Å. One benzoate group is disordered between two conformers, with occupancies of 86.9 (3) and 13.1 (3)%, related by a 143 (1)° rotation about the bond to the central benzene ring. The phenyl groups of the two conformers occupy the same space. The mol-ecule packs in the crystal with two of the three benzoate phenyl rings stacked parallel to symmetry-related counterparts, with perpendicular distances of 3.715 (5) and 3.791 (5) Å. The parallel rings are slipped away from each other, however, with centroid-centroid distances of 4.122 (2) and 4.363 (2) Å, respectively.


Clinicopathologic analysis of patients with adult rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) in adults (age > or = 16 years) is rare, accounting for less than 3% of adult soft tissue sarcomas. There is little information describing the disease biology or clinicopathologic factors that influence survival in adults with RMS. The objective of this study was to define the factors in patients with adult RMS that predict outcome, disease progression, and survival. Eighty-four adult patients with a pathologic diagnosis of RMS that was confirmed by immunohistochemistry were identified by a prospective inpatient data base during the period 1982--1999 and were analyzed for disease specific survival and metastasis free survival using the Kaplan-Meier actuarial method. Statistical significance was evaluated using the log-rank test for univariate influence and a Cox regression model for multivariate influence. The median disease specific survival was 22 months. Patient age, extent of disease, tumor size at the time of diagnosis, and margin status after resection were significant predictors of disease specific survival. Patients who underwent a complete resection had a significantly longer median survival (105 months) compared with any other subgroup of patients. The histologic subtype did not predict patient survival but did vary with patient age. Most notably, the proportion of the pleomorphic subtype increased with advancing age, accounting for 42% of RMS in patients over the age of 40 years. The most important predictors of outcome in patients with adult RMS are patient age, tumor size, extent of disease, and margin status after resection. In contrast to patients with pediatric RMS, no association was noted between survival and histologic subtype in this group of patients with adult RMS. All histologic subtypes of RMS are aggressive malignancies with poor disease specific survival despite aggressive multimodality management.


Calcium-induced modification of protein conformation demonstrated by immunohistochemistry: What is the signal?
A recent study by Morgan et al. on the mechanism of the heating antigen retrieval (AR) has raised an interesting issue concerning calcium-induced modification of protein conformation demonstrated by immunohistochemistry (IHC). The current study is based on calcium-induced modification of thrombospondin (TSP) and Ki-67, as demonstrated by IHC using seven monoclonal antibodies (MAbs) to TSP and an MAb MIB1. Experiments were carried out on frozen tissue sections of bladder carcinoma and lymph node. Frozen sections were incubated with solutions of 50 mM CaCl2 and/or 10 mM EDTA at 4C overnight before formalin or acetone fixation for TSP and Ki-67, respectively. Sections were then fixed in 10% neutral buffered formalin or acetone before immunostaining. Seven MAbs to TSP, named Ab1 to 7 representing clone numbers of A4.1, D4.6, C6.7, A6.1, B5.2, A2.5, and HB8432, respectively, and MIB1 were utilized as primary antibodies. ABC was used as the detection system and AEC as the chromogen for immunohistochemical staining. An extracellular immunostaining pattern represented a positive result for TSP, and nuclear staining for MIB1. Frozen sections preincubated in 50 mM CaCl2 overnight at 4C showed significant loss of staining and/or altered staining pattern for six of the seven antibodies to TSP and MIB1 compared to positive controls not exposed to CaCl2. Lack of immunostaining of TSP and MIB1 attributable to exposure to CaCl2 could be partially recovered by incubating the frozen sections in EDTA. Calcium-induced modification of protein structure was demonstrated more than 10 years ago on the basis of immunochemical techniques. In this study, similar calcium-induced modification of protein was detectable by IHC in frozen tissue sections, suggesting that calcium-induced modification of protein structure may occur independently of fixation-induced modification. The fact that calcium binding may affect IHC staining is not surprising in view of the fact that antibody/antigen interactions are protein structure-dependent. However, in this experiment the change occurred before and independent of formalin fixation and does not necessarily imply a role for calcium in AR. There may be a valuable role for the use of chemical modification in visualization of protein structure changes in tissue sections by IHC. (J Histochem Cytochem 47:463-469, 1999)


Heat Transfer and Hydrodynamic Properties Using Different Metal-Oxide Nanostructures in Horizontal Concentric Annular Tube: An Optimization Study.
Numerical studies were performed to estimate the heat transfer and hydrodynamic properties of a forced convection turbulent flow using three-dimensional horizontal concentric annuli. This paper applied the standard k-ε turbulence model for the flow range 1 × 104 ≤ Re ≥ 24 × 103. A wide range of parameters like different nanomaterials (Al2O3, CuO, SiO2 and ZnO), different particle nanoshapes (spherical, cylindrical, blades, platelets and bricks), different heat flux ratio (HFR) (0, 0.5, 1 and 2) and different aspect ratios (AR) (1.5, 2, 2.5 and 3) were examined. Also, the effect of inner cylinder rotation was discussed. An experiment was conducted out using a field-emission scanning electron microscope (FE-SEM) to characterize metallic oxides in spherical morphologies. Nano-platelet particles showed the best enhancements in heat transfer properties, followed by nano-cylinders, nano-bricks, nano-blades, and nano-spheres. The maximum heat transfer enhancement was found in SiO2, followed by ZnO, CuO, and Al2O3, in that order. Meanwhile, the effect of the HFR parameter was insignificant. At Re = 24,000, the inner wall rotation enhanced the heat transfer about 47.94%, 43.03%, 42.06% and 39.79% for SiO2, ZnO, CuO and Al2O3, respectively. Moreover, the AR of 2.5 presented the higher heat transfer improvement followed by 3, 2, and 1.5.


RhoE Fine-Tunes Inflammatory Response in Myocardial Infarction.
Inflammatory response after myocardial infarction (MI) is essential for cardiac healing, whereas excessive and prolonged inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanistic insight of these tightly controlled inflammatory processes has a significant impact on post-MI recovery and therapy. Here, we uncover the critical role of small GTPase RhoE in post-MI recovery and its clinical implication. Three genetic mouse lines are used: global RhoE knockout, cardiomyocyte-specific RhoE heterozygous, and cardiomyocyte-specific RhoE overexpression mice. A set of molecular signaling experiments, including bimolecular fluorescence complementation, immunoprecipitation, electrophoretic mobility shift assay, and mRNA microarray analysis, were conducted. Permanent ligation of the left anterior descending artery was performed, followed by the assessments of cardiac function, inflammation, and survival in the first week after MI. Finally, we examined the correlation of the expression levels of RhoE in MI patient heart and patient prognosis. RhoE deficiency turns on a group of proinflammatory gene expressions in mouse heart. Mice with cardiomyocyte-specific haploinsufficiency exhibit excessive inflammatory response with deleterious cardiac function after MI. A profound increase in nuclear factor-κB activity is detected in the mutant heart and the isolated cardiomyocytes. We further find that the expression of RhoE is upregulated in response to MI. Mechanistically, RhoE interacts with p65 and p50 individually in cytosol and blocks their nuclear translocation. RhoE also occupies the dimerization domain of p65 and subsequently disrupts the heterodimerization between p65 and p50. Cardiac RhoE overexpression inhibits nuclear factor-κB activity, restrains post-MI inflammation, and improves cardiac function and survival. Consistently, we find that the expression level of RhoE is elevated in the heart of patients with MI and that the patients with a higher expression level of RhoE exhibit a better prognosis in cardiac function recovery. The study uncovers RhoE as a new fine-tuning factor modulating MI-induced inflammation and promoting injured heart recovery. RhoE may serve as a new potential biomarker for the assessment of MI patient prognosis. Manipulation of RhoE could be as a potential therapeutic approach for MI and other inflammatory diseases.


Vasodilatory mechanisms in contracting skeletal muscle.
Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction and stabilizes within approximately 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise to the sustained elevation during steady-state exercise. Exercise hyperemia is therefore thought to be the result of an integrated response of more than one vasodilator mechanism. To date, the identity of vasoactive substances involved in the regulation of exercise hyperemia remains uncertain. Numerous vasodilators such as adenosine, ATP, potassium, hypoxia, hydrogen ion, nitric oxide, prostanoids, and endothelium-derived hyperpolarizing factor have been proposed to be of importance; however, there is little support for any single vasodilator being essential for exercise hyperemia. Because elevated blood flow cannot be explained by the failure of any single vasodilator, a consensus is beginning to emerge for redundancy among vasodilators, where one vasoactive compound may take over when the formation of another is compromised. Conducted vasodilation or flow-mediated vasodilation may explain dilation in vessels (i.e., feed arteries) not directly exposed to vasodilator substances in the interstitium. Future investigations should focus on identifying novel vasodilators and the interaction between vasodilators by simultaneous inhibition of multiple vasodilator pathways.


Sparse network modeling and metscape-based visualization methods for the analysis of large-scale metabolomics data.
Recent technological advances in mass spectrometry, development of richer mass spectral libraries and data processing tools have enabled large scale metabolic profiling. Biological interpretation of metabolomics studies heavily relies on knowledge-based tools that contain information about metabolic pathways. Incomplete coverage of different areas of metabolism and lack of information about non-canonical connections between metabolites limits the scope of applications of such tools. Furthermore, the presence of a large number of unknown features, which cannot be readily identified, but nonetheless can represent bona fide compounds, also considerably complicates biological interpretation of the data. Leveraging recent developments in the statistical analysis of high-dimensional data, we developed a new Debiased Sparse Partial Correlation algorithm (DSPC) for estimating partial correlation networks and implemented it as a Java-based CorrelationCalculator program. We also introduce a new version of our previously developed tool Metscape that enables building and visualization of correlation networks. We demonstrate the utility of these tools by constructing biologically relevant networks and in aiding identification of unknown compounds. http://metscape.med.umich.edu. Supplementary data are available at Bioinformatics online.


Caregiver's burden, depression and support as predictors of post-stroke depression: a cross-sectional survey.
To examine the effects of caregiver's burden, depression, and support on post-stroke depression (PSD), cross-sectional data were obtained from an epidemiologic survey of 225 stroke survivors and their caregivers living in Seoul, Korea. Multivariate analyses showed that, taking the clinical status of patients into account, caregiver's burden, depression and support were related to higher PSD. Perceived burden exerts adverse effects on PSD through its influence on the depression in caregivers. Hence, the care of stroke survivors that incorporates the care of caregivers is likely to reduce the risk of post-stroke depression in patients.


Theory of fishnet negative-index optical metamaterials.
We theoretically study fishnet metamaterials at optical frequencies. In contrast with earlier works, we provide a microscopic description by tracking the transversal and longitudinal flows of energy through the fishnet mesh composed of intersecting subwavelength plasmonic waveguides. The analysis is supported by a semianalytical model based on surface-plasmon coupled-mode equations, which provides accurate formulas for the fishnet refractive index, including the real-negative and imaginary parts. The model simply explains how the surface plasmons couple at the waveguide intersections, and it shines new light on the fishnet negative-index paradigm at optical frequencies. Extension of the theory for loss-compensated metamaterials with gain media is also presented.


[16p11.2 Microdeletion: first report in Argentina].
The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder. This microdeletion is associated with variable clinical outcome, the phenotypical spectrum ranges from intellectual disability and/or multiple congenital anomalies, autism, learning and speech problems, to a normal Microdeleción 16p11.2: primeros casos reportados en Argentina 16p11.2 Microdeletion: first report in Argentina phenotype. Genomic testing that determines copy number of sequences, such as chromosomal microarray, is used to identify this microdeletion. However, the prediction of the individual phenotype of a patient based only on the location of such deletion remains a challenge, regarding the existence of many genomic variants that might hinder the interpretation of possible functional effects between most of the contributing genes to that region. We describe the clinical findings in two subjects with heterozygous microdeletions at 16p11.2, highlighting the phenotypic and behavioural findings that conditioned the diagnostic strategy. We also discuss the implications of diagnosis, in practical counselling situations.


Rationale for an intraperitoneal gemcitabine chemotherapy treatment for patients with resected pancreatic cancer.
Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Long-term survival is rare even though there is a potentially curative R0 resection. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional and hepatic sites of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a strong pharmacologic basis. The exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 500 times the exposure that occurs within the plasma. By analogy to another lethal disease, ovarian cancer, intraperitoneal gemcitabine chemotherapy used following potentially curative resection is supported. Data that shows a superiority of multiagent chemotherapy to gemcitabine monotherapy has not been reported. A standardized treatment with intraoperative chemotherapy monitoring of gemcitabine would greatly facilitate further improvements in pancreas cancer treatment and lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this review is to present the recent available medical information and patents applicable to patients with resected pancreatic cancer.


Retinoid receptor expression and its correlation to retinoid sensitivity in non-M3 acute myeloid leukemia blast cells.
All-trans-retinoic acid (ATRA) has significantly improved the treatment results in acute promyelocytic leukemia (M3). In non-M3 acute myeloid leukemia (AML), the effects are less clear, and there is a pronounced heterogeneity in the sensitivity to the growth-inhibitory effects of retinoids in leukemic cells from different non-M3 AML patients. Retinoids exert their effects through a number of nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)]. In this study, we determined the expression of RAR alpha, RAR beta, RAR gamma, and RXR alpha by real-time PCR in four cell lines and in blast cells from patients with non-M3 AML before and after ATRA incubation. All four receptors were expressed in cells from all 18 tested patient samples and in four myeloid cell lines. In the majority of the patient samples as well as in the cell lines, there was a pattern of high expression of RAR alpha and RXR alpha and low expression of RAR beta and RAR gamma. There was no correlation between the basal expression of any of the retinoid receptors and sensitivity to ATRA. A 24-h exposure to ATRA increased the expression of RAR alpha, RAR beta, RAR gamma, and RXR alpha in 46%, 77%, 30%, and 38% of the samples, respectively. The mean increase in receptor expression was most pronounced for RAR beta and RXR alpha. There was a significant correlation between an increase in RAR beta expression in response to ATRA and sensitivity to ATRA (P < 0.014). No such correlations were found for RAR alpha, RAR gamma, and RXR alpha. The expression of the monocytoid marker CD14 was significantly correlated with increased expression of RAR alpha (P = 0.03). We conclude that RAR alpha, RAR beta, RAR gamma, and RXR alpha are expressed in non-M3 AML blast cells and that ATRA-induced expression of RAR beta may be a marker for retinoid sensitivity.


Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial.
Prophylaxis with either intravenous (i.v.) factor VIII (FVIII) or FIX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia. To evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B. In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000 μg kg(-1) ) or s.c. (50-3000 μg kg(-1) ) doses of concizumab were administered to healthy volunteers (n = 28) and hemophilia patients (n = 24). Concizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1 + 2. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-∞ of 33 960 h μg mL(-1) and a maximum mean concentration of 247 μg mL(-1) was measured at the highest dose. Concizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed, supporting further study into the potential use of s.c. concizumab for hemophilia treatment.


The Value of Active Ultrasound Surveillance for Patients With Small Testicular Lesions.
This study aimed to determine whether active ultrasound surveillance may obviate the need for surgical resection in selected patients with small testicular lesions (STLs). A retrospective 11-year review was conducted of adults who were diagnosed with an STL on scrotal ultrasonography and who either had orchiectomy or sonographic follow-up during a period of at least 3 months. A total of 101 subjects were enrolled. Ultrasound findings, clinical features, histopathology/follow-up imaging were recorded. Logistic regression analysis was performed to select independent risk factors for the diagnosis of malignancy. Seventeen (16.8%) subjects underwent immediate surgery, 8 (7.9%) of 101 underwent surgery after ultrasound follow-up, and 76 (75.3%) of 101 were followed with ultrasound only. The follow-up period ranged from 1 to 7 months in the 8 patients who ultimately underwent surgery after ultrasound follow-up and from 6 to 84 months in the 76 patients followed up with ultrasound only. All 15 malignant cases underwent immediate surgery without follow-up sonography. The frequency of lesions, either benign at surgery or stable on ultrasound, was 85.1% (86 of 101; 95% confidence interval, 77%-91%). Logistic regression analysis showed that lesion size was the only independent risk factor for malignancy in hypoechoic STLs (P < 0.05). Most of the STLs were stable on serial sonograms and likely benign. Active ultrasound surveillance may be an appropriate management strategy in patients with STLs.


Cloning, partial sequence, expression, and antigenic analysis of the filamentous hemagglutinin gene of Bordetella pertussis.
The gene coding for the filamentous hemagglutinin (FHA), one of the main factors involved in mediating adherence of Bordetella pertussis to ciliated host cells, was cloned in Escherichia coli, and the 3,500-base-pair nucleotide sequence encoding the amino-terminal region was determined. Molecular cloning, together with the characterization of recombinant FHA-related proteins produced in E. coli, revealed that the primary translation product is a protein of about 370 kilodaltons (kDa). The mature 220-kDa FHA polypeptide secreted by B. pertussis is most probably generated by proteolytic processing that eliminates a carboxy-terminal portion of about 150 kDa. The 1,087 amino-terminal residues of the predicted FHA sequence showed a number of remarkable features. Extensive homology to the Serratia marcescens and Proteus mirabilis hemolysin proteins was found between amino acids 91 and 205 of the FHA sequence, suggesting involvement of this FHA domain in host cell binding or secretion of FHA from B. pertussis. In addition, two regions containing repetitive amino acid sequences were identified. One region, extending from residues 382 to 664, was formed by six repeats, and a second, extending from residues 701 to 912, contained three repeats. The reactivities of several recombinant FHA-derived proteins with a panel of monoclonal antibodies identified at least four epitopes composing an immunoreactive domain present in the carboxy-terminal moiety of the mature FHA.


A topology-based metric for measuring term similarity in the gene ontology.
The wide coverage and biological relevance of the Gene Ontology (GO), confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.


Diagnosis of intra vascular catheter-related infection.
The use of central vascular catheters (CVC) is associated with a substantial number of complications, amongst which infections predominate. A diagnosis of CVC-related infection usually requires catheter removal for culture. Semiquantitative (roll-plate method) and quantitative methods (flush, vortex, centrifugation or sonication methods) are the most reliable diagnostic methodologies requiring catheter removal, because of their greater specificity. The roll-plate method is the simplest and most commonly used technique. This method only samples the external surface of the catheter, and is particularly indicated for recently inserted catheters in which extraluminal colonisation is the primary mechanism of infection. Luminal culture techniques, such as the quantitative methods, may be more relevant for catheters that have been in place for a long period of time. However, in up to 85% of removed CVC the culture is negative, and other diagnostic techniques that do not require catheter removal have been proposed, including paired quantitative blood cultures, endoluminal brushing, and differential time to positivity (DTP) of paired blood cultures. DTP, that compares the time to positivity for qualitative cultures of blood samples simultaneously drawn from the CVC and a peripheral vein, appears to be the most reliable in the routine clinical practice since many hospitals use automatic devices for qualitative blood culture positivity detection. More recently catheter-sparing direct diagnostic methods, which include Gram stain and acridin-orange leucocyte cytospin (AOLC) test, appeared to be especially useful because of the rapidity of results and the ability to distinguish different microorganisms, allowing early targeted antimicrobial therapy.


The ortholog of human ataxin-2 is essential for early embryonic patterning in C. elegans.
Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2) gene, is a protein of unknown function. Ataxin-2 interacts with ataxin-2-binding-protein 1 (A2BP1), a member of a novel family of putative RNA-binding proteins. Because the sequences of ataxin-2 and A2BP1 are evolutionarily conserved, we investigated functional aspects and expression pattern in the nematode Caenorhabditis elegans. Human ataxin-2 has 20.1% amino acid identity and 43.9% similarity to its C. elegans ortholog, designated ATX-2, that encodes a predicted 1026 aa protein. One of the worm orthologs of human A2BP1 is the numerator element FOX-1, with an overall 29.8% aa identity. We studied the expression pattern of atx-2 using the endogenous promotor coupled with a GFP expression vector. Atx-2 was widely expressed in the adult worm with strong expression in muscle and nervous tissue. It was also heavily expressed in the embryo. In order to elucidate the function of atx-2 and fox-1, we conducted RNA interference (RNAi) studies. The interfering dsRNA was introduced into larval L4 stage worms of the N2 strain by microinjection or soaking. DsRNA representing the full-length atx-2 gene resulted in arrested embryonic development in the offspring of all 58 microinjected worms. Nomarski imaging showed embryos in different stages of developmental arrest, indicating an essential role of atx-2 for early embryonic development. When fox-1 was targeted by RNAi, there was a marked reduction in the number of eggs per worm. The results presented here underline previous findings about the interaction of human ataxin-2 and A2BP1.


β-Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis.
Cholestatic liver diseases result from impaired bile flow and are characterized by inflammation, atypical ductular proliferation, and fibrosis. The Wnt/β-catenin pathway plays a role in bile duct development, yet its role in cholestatic injury remains indeterminate. Liver-specific β-catenin knockout mice and wild-type littermates were subjected to cholestatic injury through bile duct ligation or short-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet. Intriguingly, knockout mice exhibit a dramatic protection from liver injury, fibrosis, and atypical ductular proliferation, which coincides with significantly decreased total hepatic bile acids (BAs). This led to the discovery of a role for β-catenin in regulating BA synthesis and transport through regulation of farnesoid X receptor (FXR) activation. We show that β-catenin functions as both an inhibitor of nuclear translocation and a nuclear corepressor through formation of a physical complex with FXR. Loss of β-catenin expedited FXR nuclear localization and FXR/retinoic X receptor alpha association, culminating in small heterodimer protein promoter occupancy and activation in response to BA or FXR agonist. Conversely, accumulation of β-catenin sequesters FXR, thus inhibiting its activation. Finally, exogenous suppression of β-catenin expression during cholestatic injury reduces β-catenin/FXR complex activation of FXR to decrease total BA and alleviate hepatic injury. We have identified an FXR/β-catenin interaction whose modulation through β-catenin suppression promotes FXR activation and decreases hepatic BAs, which may provide unique therapeutic opportunities in cholestatic liver diseases. (Hepatology 2018;67:955-971).


ChartSeer: Interactive Steering Exploratory Visual Analysis With Machine Intelligence.
During exploratory visual analysis (EVA), analysts need to continually determine which subsequent activities to perform, such as which data variables to explore or how to present data variables visually. Due to the vast combinations of data variables and visual encodings that are possible, it is often challenging to make such decisions. Further, while performing local explorations, analysts often fail to attend to the holistic picture that is emerging from their analysis, leading them to improperly steer their EVA. These issues become even more impactful in the real world analysis scenarios where EVA occurs in multiple asynchronous sessions that could be completed by one or more analysts. To address these challenges, this work proposes ChartSeer, a system that uses machine intelligence to enable analysts to visually monitor the current state of an EVA and effectively identify future activities to perform. ChartSeer utilizes deep learning techniques to characterize analyst-created data charts to generate visual summaries and recommend appropriate charts for further exploration based on user interactions. A case study was first conducted to demonstrate the usage of ChartSeer in practice, followed by a controlled study to compare ChartSeer's performance with a baseline during EVA tasks. The results demonstrated that ChartSeer enables analysts to adequately understand current EVA status and advance their analysis by creating charts with increased coverage and visual encoding diversity.


Population size affects vital rates but not population growth rate of a perennial plant.
Negative effects of habitat fragmentation on individual performance have been widely documented, but relatively little is known about how simultaneous effects on multiple vital rates translate into effects on population viability in long-lived species. In this study, we examined relationships between population size, individual growth, survival and reproduction, and population growth rate in the perennial plant Phyteuma spicatum. Population size positively affected the growth of seedlings, the survival of juveniles, the proportion of adults flowering, and potential seed production. Analyses with integral projection models, however, showed no relationship between population size and population growth rate. This was due to the fact that herbivores and pathogens eliminated the relationship between population size and seed production, and that population growth rate was not sensitive to changes in the vital rates that varied with population size. We conclude that effects of population size on vital rates must not translate into effects on population growth rate, and that populations of long-lived organisms may partly be able to buffer negative effects of small population size on vital rates that have a relatively small influence on population growth rate. Our study illustrates that we need to be cautious when assessing the consequences of habitat fragmentation for population viability based on effects on only one or a few vital rates.


Testing a passive tracking index for monitoring the endangered Ethiopian wolf.
The endangered Ethiopian wolf is considered the rarest canid in Africa. The species faces many threats and is particularly vulnerable to diseases such as rabies. A simple, low-technology means to monitor populations would greatly facilitate conservation efforts, through early detection of population changes and behavior, and signaling a need for intervention. We tested a passive tracking index methodology, which has been a valuable tool for indexing canids and other species around the world. The method uses counts of track intrusions into plots placed in the animals' routes of travel as the basis for calculating an index. Unlike for other species, for which the placement of tracking plots on dirt roads has been extremely successful, we found in our first trial that this approach did not adequately intersect the wolves' activity patterns. The low vegetation associated with Afro-alpine habitats offered little benefit for the wolves to travel roads. However, in our second trial among molerat colonies, a focus of wolf foraging activity, we found plot placement on molerat mounds was efficient for collecting Ethiopian wolf plot intrusions for index calculations. This plot placement method coupled with the passive tracking index calculations might offer resource managers a cost efficient tool that requires minimal equipment to monitor Ethiopian wolf populations on the Sanetti Plateau and other Afro-alpine habitats. Plot placement on roads in other Ethiopian wolf habitats where cross-country travel is more difficult might still be a viable means to collect track data, but would require further testing.


A comparison of paralysing agents in double-contrast barium meal examinations.
One hundred and fourteen patients attending for barium meal examination were randomly allocated to receive Buscopan (hyoscine N-butylbromide, Boehringer Ingelheim; 20 mg) or glucagon (0.5 mg) as paralysing agents, or sterile water as control. The radiographs were analysed with regard to (a) gastric and duodenal distension and coating and (b) early or delayed filling of the duodenum with barium, in order to assess claims that paralysing agents influence radiographic quality. It was found that both duodenal distension and coating were better with Buscopan and glucagon than with water but there was no difference between Buscopan and glucagon in producing these effects. Relaxants produced no significant effect on distension or coating of the stomach. Glucagon prolonged the time of some examinations but gave better visualisation of the stomach, which was less frequently obscured by contrast in the duodenum.


Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus.
Epstein-Barr virus (EBV) is the prototypical γ-herpesvirus and an obligate human pathogen that infects mainly epithelial cells and B cells, which can result in malignancies. EBV infects these target cells by fusing with the viral and cellular lipid bilayer membranes using multiple viral factors and host receptor(s) thus exhibiting a unique complexity in its entry machinery. To enter epithelial cells, EBV requires minimally the conserved core fusion machinery comprised of the glycoproteins gH/gL acting as the receptor-binding complex and gB as the fusogen. EBV can enter B cells using gp42, which binds tightly to gH/gL and interacts with host HLA class II, activating fusion. Previously, we published the individual crystal structures of EBV entry factors, such as gH/gL and gp42, the EBV/host receptor complex, gp42/HLA-DR1, and the fusion protein EBV gB in a postfusion conformation, which allowed us to identify structural determinants and regions critical for receptor-binding and membrane fusion. Recently, we reported different low resolution models of the EBV B cell entry triggering complex (gHgL/gp42/HLA class II) in "open" and "closed" states based on negative-stain single particle electron microscopy, which provide further mechanistic insights. This review summarizes the current knowledge of these key players in EBV entry and how their structures impact receptor-binding and the triggering of gB-mediated fusion.


Gd-Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1.
The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasis. Our previous study found that Gd@C82(OH)22 can suppress pancreatic cancer by inhibiting MMP-2/9 expression. In this study, we further explored the epigenetic mechanism of Gd@C82(OH)22 in human pancreatic cancer metastasis. Gd@C82(OH)22 suppressed tumor metastasis through down-regulation of metastasis-associated protein 1 (MTA1), HDAC1, HIF-1α, and MMP-2/9 and up-regulation of reversion-cysteine protein with the Kazal motif (RECK). The level of acetylation was increased in the promoter region of the RECK gene after Gd@C82(OH)22 treatment. The interaction of MTA1, HDAC1, and HIF-1α was inhibited by Gd@C82(OH)22. Furthermore, large-scale molecular dynamics simulations revealed Gd@C82(OH)22 could serve as an effective HDAC inhibitor to the protein-protein association between HDAC1 and MTA1, especially through MTA1's SANT and ELM2 dimerization domains. Our findings implicate Gd@C82(OH)22 as a novel HDAC inhibitor acting to increase RECK expression by suppressing the MTA1/HDAC1 co-repressor complex. Gd@C82(OH)22 may serve as a potential HDAC1 inhibitor to suppress pancreatic cancer cell invasion and metastasis both in vitro and in vivo. According to computer analysis and experimental validation, Gd@C82(OH)22 activates RECK expression by inhibiting the interaction of HDAC1 and MTA1.


Survival following primary surgery for oral cancer.
The main aims of this article are to report the overall and disease-specific survival of a consecutive series of patients presenting with oral cancer from 1992 to 2002 and to relate survival to clinical and pathological factors. The article uses population-based age-sex mortality rates in the North-West of England to highlight differences in overall and disease-specific survival. 541 patients with oral squamous cell carcinoma presented to the Regional Maxillofacial Unit from 1992 to 2002. Curative treatment favoured radical primary surgery, 10% (52) received primary radiotherapy. These patients were on average 8 years older with more advanced tumours and overall poorer survival at 5 years, 23% (SE 7%). The remainder of the results refer to 489 patients who had primary curative surgery, 40% (194) of whom received adjuvant radiotherapy. The overall survival (OS) was 56% (SE 2%) and the disease-specific survival (DSS) was 74% (SE 2%). There was a local recurrence rate of 10% (50) and the loco-regional recurrence rate was 21% (103). The second primary rate was 7% (35). Survival figures had improved over the 10-year period from 63% DSS for the first 4 years of the study (1992-1995) compared to 81% for the last 3 years (2000-2002). In stepwise Cox regression the two predictors selected for disease-specific survival were pN status and margins (both p<0.001). Age-sex mortality rates for the North-West indicate that 15.0% of the 489 primary surgery patients might have been expected to die within 5 years if they were typical of the general population and the observed difference between all causes and oral-cancer specific survival was 18.3%. These data emphasise the value of disease-specific survival as an indicator of successful treatment in a cohort that tends to be elderly, from social deprived backgrounds, with life styles and comorbidity that influence overall survival.


Immune and inflammatory responses of Australian firefighters after repeated exposures to the heat.
When firefighters work in hot conditions, altered immune and inflammatory responses may increase the risk of a cardiac event. The present study aimed to establish the time course of such responses. Forty-two urban firefighters completed a repeat work protocol in a heat chamber (100 ± 5°C). Changes to leukocytes, platelets, TNFα, IL-6, IL-10, LPS and CRP were evaluated immediately post-work and also after 1 and 24 h of rest. Increases in core temperatures were associated with significant increases in leukocytes, platelets and TNFα directly following work. Further, platelets continued to increase at 1 h (+31.2 ± 31.3 × 10(9) l, p < 0.01) and remained elevated at 24 h (+15.9 ± 19.6 × 10(9) l, p < 0.01). Sustained increases in leukocytes and platelets may increase the risk of cardiac events in firefighters when performing repeat work tasks in the heat. This is particularly relevant during multi-day deployments following natural disasters. Practitioner Summary: Firefighters regularly re-enter fire affected buildings or are redeployed to further operational tasks. Should work in the heat lead to sustained immune and inflammatory changes following extended rest periods, incident controllers should plan appropriate work/rest cycles to minimise these changes and any subsequent risks of cardiac events.


The Human Vaccines Project: A roadmap for cancer vaccine development.
Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited by most vaccines tested, but their clinical efficacy remains modest. We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines.


Anion and proton transport in chromaffin granules.
Both intact chromaffin granules and ghosts behave as osmometers in response to the relative internal and external concentrations of solutes. The permeability properties of the granule membrane can therefore be studied by measuring the osmotic consequences of ion permeation. These include lysis of intact granules and shrinking or swelling of ghosts. This approach has been used to identify at least two types of selective anion transport sites in the membrane. One is observed in the presence of K+ ionophores and appears to be electrogenic in nature. It is insensitive to a group of compounds known to inhibit anion transport in erythrocytes. The other site is sensitive to those inhibitors and is involved with electroneutral cotransport with protons. This proton entry can be driven by either the proton-pumping ATPase of the granule membrane or by a simple inward concentration gradient of protons. The proton entry-coupled anion transport site may be structurally related to the ATPase itself based on parallel anion and inhibitor sensitivities of the site and the enzyme. One or both of the anion transport sites described here may play a role in regulating exocytosis from cells based on a chemiosmotic mechanism that has been postulated to be responsible for this process.


Synthetic efforts toward the spiroketal core of spirangien A.
Synthetic studies toward the spiroketal core of spirangien A are described. Two synthetic approaches were developed. Both of them use a diastereoselective aldol addition of a lithium enolate derived from a methyl ketone on an aldehyde. In the first approach, the introduction of the (E)-trisubstituted terminal olefin was achieved by using an iron-catalyzed cross-coupling between an alkyl iodide and a vinyl Grignard reagent and a randomly protected spiroketal was obtained. In the second approach, a highly functionalized spiroketal carbamate, which includes 13 stereogenic centers, was successfully isolated.