The benefits from complying with the framework convention on tobacco control: a SimSmoke analysis of 15 European nations.
This article compares the predicted impact of tobacco tax increases alone and as part of a comprehensive tobacco control strategy on smoking prevalence and smoking-attributable deaths (SADs) across 15 European countries. Country-specific population, smoking prevalence and policy data with modified parameter values have been applied to the previously validated SimSmoke model for 10 high-income and 5 middle-income European nations. The impact of past and potential future policies is modelled. Models generally validated well across the 15 countries, and showed the impact of past policies. Without stronger future policies, 44 million lives would be lost due to smoking across the 15 study countries between 2011 and 2040, but effective policies could avert 7.7 million of those premature deaths. Results suggest that past policies have been effective in reducing smoking rates, but there is also a strong potential for future policies consistent with the Framework Convention on Tobacco Control. When specific taxes are increased to 70% of retail price, strong smoke-free air laws, youth access laws and marketing restrictions are enforced, stronger health warnings are implemented, and cessation treatment and media campaigns are supported, smoking prevalence and SADs will fall substantially in European countries.


Back complaints in the elders (BACE); design of cohort studies in primary care: an international consortium.
Although back complaints are common among older people, limited information is available in the literature about the clinical course of back pain in older people and the identification of older persons at risk for the transition from acute back complaints to chronic back pain. The aim of this study is to assess the course of back complaints and identify prognostic factors for the transition from acute back complaints to chronic back complaints in older people who visit a primary health care physician. The design is a prospective cohort study with one-year follow-up. There will be no interference with usual care. Patients older than 55 years who consult a primary health care physician with a new episode of back complaints will be included in this study. Data will be collected using a questionnaire, physical examination and X-ray at baseline, and follow-up questionnaires after 6 weeks and 3, 6, 9 and 12 months. The study 'Back Complaints in the Elders' (BACE) will take place in different countries: starting in the Netherlands, Brazil and Australia. The research groups collaborate in the BACE consortium. The design and basic objectives of the study will be the same across the studies. This consortium is a collaboration between different research groups, aiming to provide insight into the course of back complaints in older people and to identify prognostic factors for the transition from acute back complaints to chronic back complaints in older persons. The BACE consortium allows to investigate differences between older people with back complaints and the health care systems in the different countries and to increase the statistical power by enabling meta-analyses using the individual patient data. Additional research groups worldwide are invited to join the BACE consortium.


FK506-Binding Protein 13 Expression Is Upregulated in Interstitial Lung Disease and Correlated with Clinical Severity. A Potentially Protective Role.
Pulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. We sought to investigate the role of FKBP13 (13-kD FK506-binding protein), an endoplasmic reticulum-resident molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy specimens from 24 patients with idiopathic pulmonary fibrosis and 17 control subjects. FKBP13 expression was found to be elevated in the fibrotic regions of idiopathic pulmonary fibrosis lung tissues and correlated with declining forced vital capacity and dyspnea severity. FKBP13 expression was also increased in lung biopsy specimens of patients with hypersensitivity pneumonitis, rheumatoid arthritis, and sarcoidosis-associated interstitial lung disease. We next evaluated the role of this protein using FKBP13-/- mice in a bleomycin model of pulmonary fibrosis. Animals were assessed for lung function and histopathology at different stages of lung injury including the inflammatory (Day 7), fibrotic (Day 21), and resolution (Day 50) phases. FKBP13-/- mice showed increased infiltration of inflammatory cells and cytokines at Day 7, increased lung elastance and fibrosis at Day 21, and impaired resolution of fibrosis at Day 50. These changes were associated with an increased number of cells that stained positive for TUNEL and cleaved caspase 3 in the FKBP13-/- lungs, indicating a heightened cellular sensitivity to bleomycin. Our findings suggest that FKBP13 is a potential biomarker for severity of interstitial lung diseases and that it has a biologically relevant role in protecting mice against bleomycin-induced injury, inflammation, and fibrosis.


Psychological factors and outcome of electrode implantation for chronic pain.
The utility of using psychological assessments as a basis for predicting pain relief after electrode implantation is examined. Two raters independently reviewed the functional pain protocols of chronic pain patients who were candidates for deep brain (n = 13) or spinal cord (n = 17) electrode implants and predicted whether each would have a good or poor treatment response. At follow-up, five deep brain (39%) and four spinal cord (24%) patients were classified as having good responses to treatment. Predictions of outcome based on psychological data were accurate for 80% of the patients. These results suggest that functional pain assessment is useful as a part of preimplantation screening and emphasize the importance of psychological factors in the outcome of treatment for chronic pain.


Food Insecurity and Micronutrient Status among Ghanaian Women Planning to Become Pregnant.
We examined the association between food insecurity (FIS) and micronutrient status among Ghanaian women planning to become pregnant. A cross-sectional analysis was completed of 95 women aged 18-35 years, living in the Upper Manya Krobo District in the Eastern Region of Ghana. Questionnaires were administered to collect sociodemographic and food security data; weight and height were measured. Blood was drawn from an antecubital vein; one drop was used to assess hemoglobin via Hemocue. Zinc and copper were analyzed using flame atomic spectrophotometry while iron biomarkers, retinol and 25-hydroxyvitamin D were analyzed using ELISA, ultra-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. Logistic regression models were used to determine the relationship between food insecurity (FIS) and micronutrient deficiencies. FIS was reported among 23% of the households, while micronutrient deficiencies ranged from 7-28% irrespective of FIS status. Retinol concentrations were negatively associated with FIS (p = 0.043) after controlling for covariates, although levels were within the normal range in both groups. No statistically significant associations between FIS and micronutrient deficiencies were found. Among those with FIS, 59% were deficient in at least one nutrient with 18% deficient in two nutrients. Unmarried women were at higher risk of FIS (p = 0.017) than married women. FIS was associated with retinol concentrations but not other micronutrient biomarkers in Ghanaian women expecting to become pregnant in the next 6 months.


Patient-Reported Outcome Coordinator Did Not Improve Quality of Life Assessment Response Rates: A Report from the Children's Oncology Group.
Health related quality of life (HRQL) assessments during therapy for pediatric cancer provide valuable information to better understand the patient experience. Our objective was to determine the impact of a patient-reported outcome (PRO) coordinator on HRQL questionnaire completion rates during a pediatric acute myeloid leukemia (AML) trial. AAML1031 is a multicenter Children's Oncology Group therapeutic trial for de novo AML with a secondary aim to assess HRQL of children and adolescents treated with chemotherapy and hematopoietic stem cell transplantation (HSCT). Parents/guardians are the primary respondents and four questionnaires are administered at eight time points. The questionnaires are the PedsQL 4.0 Generic Core Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale, and the Pediatric Inventory for Parents. To improve response rates, a central PRO coordinator was instituted and reminded sites about upcoming and delinquent questionnaires. The proportion of HRQL questionnaires completed were compared prior to, and following institution of the PRO coordinator. This analysis evaluated the first five assessment time points. There were231 families who consented to participate in the HRQL aim. Overall response rates for all questionnaires were 73-83%. At time point 1, within 14 days of chemotherapy initiation, post-PRO coordinator completion rates were significantly higher for three of four questionnaires. However, the effect was not sustained and at time point 4, one month following last chemotherapy or HSCT, completion rates were significantly lower post-PRO coordinator for all four questionnaires. Addition of a central PRO coordinator did not result in sustained improvement in HRQL questionnaire completion rates. Efforts to improve response rates must consider other strategies.


Determination of the detective quantum efficiency of gamma camera systems: a Monte Carlo study.
The purpose of the present work was to investigate the validity of using the Monte Carlo technique for determining the detective quantum efficiency (DQE) of a gamma camera system and to use this technique in investigating the DQE behaviour of a gamma camera system and its dependency on a number of relevant parameters. The Monte Carlo-based software SIMIND, simulating a complete gamma camera system, was used in the present study. The modulation transfer function (MTF) of the system was determined from simulated images of a point source of (99m)Tc, positioned at different depths in a water phantom. Simulations were performed using different collimators and energy windows. The MTF of the system was combined with the photon yield and the sensitivity, obtained from the simulations, to form the frequency-dependent DQE of the system. As figure-of-merit (FOM), the integral of the 2D DQE was used. The simulated DQE curves agreed well with published data. As expected, there was a strong dependency of the shape and magnitude of the DQE curve on the collimator, energy window and imaging position. The highest FOM was obtained for a lower energy threshold of 127 keV for objects close to the detector and 131 keV for objects deeper in the phantom, supporting an asymmetric window setting to reduce scatter. The Monte Carlo software SIMIND can be used to determine the DQE of a gamma camera system from a simulated point source alone. The optimal DQE results in the present study were obtained for parameter settings close to the clinically used settings.


Complete androgen insensitivity syndrome: the role of the endocrine surgeon.
Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder characterized by varying degrees of feminization secondary to androgen receptor insensitivity. We report a case of a 34-year-old female with complete androgen insensitivity who presented with a history of primary amenorrhea and two intra-abdominal gonads found on CT scan. The patient underwent successful laparoscopic bilateral gonadectomy without complications. AIS is present in 1:20,000 to 64,000 males; complete androgen insensitivity is seen in 2-5:100,000 phenotypic females and should therefore be considered in any otherwise healthy female with abnormal pubertal development and infertility. Although controversial, most endocrinologists agree that gonadectomy may be performed after puberty with minimal risk of testicular neoplasm.


Features of the Femoral Proximocaudal Joint Capsule Insertion Among Canids.
This observational study was conducted to evaluate the anatomic relationship between the proximocaudal femoral joint capsule insertion and the femoral caudolateral curvilinear osteophyte (CCO), across ancient and modern domestic and non-domestic canids. Museum specimens of proximal femora were screened for presence of remnant enthesophytes of the caudal joint capsule insertion (first inclusion criterion) and then for the CCO (second inclusion criterion). The initially screened population included 267 dry bone specimens: Six Canis species, hybrid coyote × domestic dog, and five vulpines (three Vulpes species, one Urocyon, and one Nyctereutes). Proximocaudal joint capsule insertion remnant enthesophytes were limiting at n = 19 specimens: Seven ancient domestic dogs, four modern coyotes, two ancient coyotes, two modern hybrid coyote × dog, two modern red foxes, and two modern raccoon dogs. The joint capsule enthesophytes are associated with inflammation, but are observed far less frequently than the CCO. The CCO is seen radiographically but is visible more frequently by direct inspection. The primary inclusion criterion necessarily was a visible caudal joint capsule insertion; spatial relationships of the CCO can be assigned with confidence only when a capsule insertion line can be recognized clearly. We demonstrate that the anatomic CCO associates with the joint capsule insertion being nonspecific and species-independent. A joint capsule insertion-CCO spatial relationship across species is an important new observation, strongly indicating that both are pathological features. Our data indicate need for new research to characterize the canid coxofemoral joint and its overt and incipient pathology in a phylogenetic context. Anat Rec, 302:2164-2170, 2019. © 2019 American Association for Anatomy.


Investigation of the protective effects of horse mushroom (Agaricus arvensis Schaeff.) against carbon tetrachloride-induced oxidative stress in rats.
Wild and cultured mushrooms have been extensively used for food and medicinal purposes all around the world. However, there is limited information on chemical composition, health enhancing effects and contributions on diet of some mushrooms (e.g., Agaricus arvensis) widely distributed in many countries including United Kingdom, Australia, Turkey etc. Therefore, the present study was aimed to analyse the bioactive composition and ameliorative effects of A. arvensis via evaluating in vitro and in vivo antioxidant properties in CCl4 induced rat model. The extract exhibited higher antioxidant capacities in vitro than that of the positive control (Reishi-Shiitake-Maitake standardized extract). Administration of the extract had significant regulative effects in the levels of AST, ALT, LDH, Urea and TRIG levels according to CCl4 group. Additionally, lipid peroxidation and GSH in the brain, kidney and liver tissues was regulated by extract treated groups compared to the CCI4 group. The supplementation of the extract at the dose of 100 mg/kg regulated the levels of GST, GR, CAT and GPx enzyme activities in brain and liver, but not in kidney tissue. There was approximately three fold increase in CAT enzyme activity in kidney tissue of extract treated groups compared to Control and CCl4 groups. The extract contained a rich composition of bioactive compounds including phenolics (protocatechuic acid and p-hydroxybenzoic acid), volatile compounds (benzaldehyde, palmitic acid and linoleic acid) and mineral compounds (K, Si, Mg and Na). Data obtained within this study suggests that A. arvensis might be used for food industries in order to obtain nutritional products.


Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness.
Infection may both augment the atherosclerotic process and contribute to later manifestations of overt clinical disease. Chlamydia pneumoniae elementary bodies have been detected in atherosclerotic lesions. The aim of the present study was to investigate whether elevated titers of antibodies and circulating immune complexes to C pneumoniae were associated with ultrasound findings indicating presence of atherosclerosis in the carotid artery. Serum titers of antibodies to C pneumoniae (IgM, IgA, IgG, and circulating immune complex) were related to intima-media thickness (IMT) and plaque status measured by B-mode ultrasound in the carotid artery in 113 men with treated hypertension and at least 1 of the following risk factors: hypercholesterolemia, smoking, or diabetes. Any of the titers was elevated in 56 (50%) men, and common carotid artery IMT was thicker in this group compared with the 57 men without any elevated titers (1.00 versus 0.92 mm, P<0.05). There were no accompanying differences in blood pressure, lipid levels, blood glucose, or smoking. Elevation of separate antibody types and circulation immune complex were also associated with increased IMT. In the latter group, systolic blood pressure was higher among seropositive patients compared with those who had no circulating immune complex. Seropositivity was not related to plaque status. Seropositivity for C pneumoniae was associated with an increased intima-media thickness in the common carotid artery but not plaque status in hypertensive men at high risk for cardiovascular disease.


Searching for a Definition of Refractory Irritable Bowel Syndrome: a Systematic Review and Meta-analysis.
The pathological mechanism of irritable bowel syndrome (IBS) is unclarified, which commonly leads to unresponsiveness to conventional treatments. The diagnostic criteria for refractory IBS are not clearly defined. We performed a systematic review to summarize the key points of the definition of refractory IBS in different studies. We also conducted a meta-analysis to explore whether the diverse definitions for refractory IBS affect the therapeutic effect of gut-directed hypnotherapy (GDH). We searched OVID Medline, Embase and Cochrane (until September 2020) for randomized controlled trials (RCTs) recruiting patients with refractory IBS. We evaluated the definition of refractory IBS through the following aspects: duration of symptoms, unresponsive to dietary intervention, lifestyle modification, pharmacology, psychology, severity assessment and adequate explanation. The effect of the different definitions for refractory IBS on the therapeutic effect of gut-directed hypnotherapy (GDH) was checked by a meta-analysis. Twenty-one RCTs were finally included. Six (28.6%) out of 21 RCTs recruited patients with symptoms lasting for over 12 months; 8 (38.1%) RCTs reported a prior use of dietary intervention; 1 (4.8%) RCT reported the use of lifestyle modification; 11 (52.4%) RCTs recruited patients who were unresponsive to pharmacology; 2 (9.5%) RCTs recruited patients with no response to psychological therapy ; 5 (23.8%) RCTs had symptoms severity assessment; and 8 (38.1%) RCTs recruited patients who were informed adequately. Despite being tested in trials with heterogeneous definition of refractory IBS, GDH had similar effectiveness when compared with supportive treatment [standardized mean difference (SMD)=-0.69, 95%CI: -0.93 to -0.44)] or waiting-list control (SMD=-0.54, 95%CI: -0.98 to -0.10). Varied definitions in refractory IBS were common phenomena in clinical studies. Resistance to symptom severity assessment and psychological treatments should be more explicitly defined. Gut-directed hypnotherapy was efficacious for refractory IBS and was not affected by the diversity in the definition of refractory IBS among RCTs.


Lyme disease in California: interrelationship of ixodid ticks (Acari), rodents, and Borrelia burgdorferi.
The association of immature ixodid ticks, several species of rodents, and the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was studied in two habitats in northern California in spring and summer 1985 and year-round in 1986. A total of 428 rodents were collected from ecotonal chaparral and a woodland-grass-rock outcrop; the former habitat yielded six species, the latter three species. The deer mouse, Peromyscus maniculatus (Wagner), and the piñon mouse, P. truei (Shufeldt), were the dominant species year-round and collectively comprised 78% of rodents captured within chaparral and 87% from the rock outcrop in 1986. In both habitats, rodents were trapped most frequently in winter and spring, and least often in summer and fall. A total of 306 rodent blood films from all six species were assayed for spirochetes by direct immunofluorescence; of these, only one film prepared from P. truei (n = 123 films from 53 individual mice) was found to contain spirochetes. Immature western black-legged ticks, Ixodes pacificus Cooley & Kohls, and Pacific Coast ticks, Dermacentor occidentalis Marx, were collected from each species of rodent. Larvae of I. pacificus infested P. maniculatus and P. truei in low numbers year-round, but nymphs of this tick rarely parasitized these rodents. D. occidentalis larvae infested P. maniculatus and P. truei in spring and particularly in summer; nymphal ticks infested these mice primarily in summer. The efficiency of visual inspection for collecting immatures of these ticks from P. maniculatus ranged from 45 to 69% in spring and summer, whereas the efficiency of a drop-off technique appeared to be 100%. Spirochetes were detected in <1% of D. occidentalis larvae (n = 310) and nymphs (n = 120), and in approximately 4% of I. pacificus larvae (n = 75) derived from these hosts. The potential significance od these findings in the enzootiology of B. burgdorferi is discussed.


Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease.
The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0-0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1-3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7-34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4-74.3%], p < 0.01). Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.


Irrational beliefs in relation to self-esteem and depression.
The joint relationship of depression and self-esteem to Ellis' "irrational beliefs" as measured by the Irrational Beliefs Test (Jones, 1968) was investigated in an Australian sample (N = 268) of students and nonstudents. Analysis that used partial correlation and canonical correlation showed six irrational beliefs to be jointly related to low self-esteem and depression: Demand for Approval, High Self-expectations, Frustration Reactivity, Anxious Overconcern, Problem Avoidance, and Helplessness. The results confirm the findings of previous studies and are consistent with the concept of depressive self-schemas.


Multi-stage surgery for a multiple-level spondylodiscitis caused by multidrug-resistant Mycobacterium avium complex.
The objective of this article is to report a rare case of atypical mycobacterial spinal spondylodiscitis with multiple-level involvement and the successful treatment by multi-stage surgical intervention. Reports on the surgical management of atypical mycobacterial spondylodiscitis are lacking. A 71-year-old woman with a confirmed diagnosis of multiple-level spondylodiscitis of L2-L3 and L5-S1 caused by Mycobacterium avium complex (MAC). The patient underwent a two-stage surgical treatment (first: posterior instrumentation; second: anterior debridement with anterior lumbar interbody fusion). At 1 year after surgery, the patient suffered a proximal junctional failure secondary to a vertebral fracture that was solved with a proximal extension of the fusion using a percutaneous technique. The patient was successfully discharged with good pain control, satisfactory correction, no neurologic complications and an overall satisfactory outcome. A rare case of antibiotic-resistant multi-level spondylodiscitis due to MAC was treated successfully with multi-stage surgical treatment. Surgery in this patient group remains challenging due to the technical complexities and the difficulty of choosing the instrumentation levels.


Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.
Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.


Two-tube test for the rapid identification of prompt lactose-fermenting genera within the family Enterobacteriaceae.
One hundred and fifty-nine prompt lactose-fermenting strains of Enterobacteriaceae were tested for H(2)S production, ornithine decarboxylase activity, motility, and citrate utilization by using two different sets of test media. It was shown that the three tests first mentioned could be carried out in a single tube, the results being as reliable as when each was done separately. Simmons medium was preferred for the detection of citrate utilization. Since these four tests require only two tubes, they are considered more convenient in routine diagnostics. A combined medium for the detection of H(2)S production and motility is described.


The developmental expression dynamics of Drosophila melanogaster transcription factors.
Site-specific transcription factors (TFs) are coordinators of developmental and physiological gene expression programs. Their binding to cis-regulatory modules of target genes mediates the precise cell- and context-specific activation and repression of genes. The expression of TFs should therefore reflect the core expression program of each cell. We studied the expression dynamics of about 750 TFs using the available genomics resources in Drosophila melanogaster. We find that 95% of these TFs are expressed at some point during embryonic development, with a peak roughly between 10 and 12 hours after egg laying, the core stages of organogenesis. We address the differential utilization of DNA-binding domains in different developmental programs systematically in a spatio-temporal context, and show that the zinc finger class of TFs is predominantly early expressed, while Homeobox TFs exhibit later expression in embryogenesis. Previous work, dissecting cis-regulatory modules during Drosophila development, suggests that TFs are deployed in groups acting in a cooperative manner. In contrast, we find that there is rapid exchange of co-expressed partners amongst the fly TFs, at rates similar to the genome-wide dynamics of co-expression clusters. This suggests there may also be a high level of combinatorial complexity of TFs at cis-regulatory modules.


A study of bone marrow failure syndrome in children.
Bone marrow failure syndrome (BMFS), or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. Children with pancytopenia (Hb 9 /L, platelet count<100x10(9)/L) and bone marrow cellularity<25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. Relative risk was estimated by odds ratio (OR) with 95% confidence interval (CI) in matched cases and controls. Of the 53 children studied, 6 (11.3%) were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8%) had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father's occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.


Characterization of retrograde collateral (type II) endoleak using a new canine model.
The clinical significance of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) has not been completely characterized. In this study a canine model was used to analyze intra-aneurysmal pressure, thrombus histologic characteristics, endoleak patency, and radiographic appearance of type II endoleaks originating from single and multiple aneurysm side branches. Prosthetic aneurysms with an intraluminal solid-state strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. A single collateral side branch was reimplanted in 4 animals, multiple side branches were reimplanted in 6 animals, and no side branches were reimplanted in 4 control animals. Intra-aneurysmal and systemic pressure was measured for 60 to 90 days after creation of the type II endoleak. Endoleak patency and flow were assessed with duplex ultrasound scanning and cine-magnetic resonance angiography. Histologic analysis of the intra-aneurysmal thrombus was also performed. Stent-graft exclusion reduced intra-aneurysmal pressure significantly in all animals, as compared with systemic pressure (P < .001). All intra-aneurysmal pressure values are indexed to the systemic pressure, and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. Type II endoleaks originating from multiple side branches exhibited significantly increased intra-aneurysmal systolic pressure, mean pressure, and pulse pressure, as compared with endoleaks derived from either a single side branch (systolic pressure: multiple, 0.70 +/- 0.28 vs single, 0.50 +/- 0.19; P < .001; mean pressure: multiple, 0.78 +/- 0.23 vs single, 0.59 +/- 0.22, P < .001; pulse pressure: multiple, 0.41 +/- 0.25 vs single, 0.17 +/- 0.15, P < .001) or excluded control aneurysms that had no side branches and no endoleak (systolic pressure, 0.17 +/- 0.09; mean pressure, 0.14 +/- 0.10; pulse pressure, 0.098 +/- 0.08; P < .001). Cine-magnetic resonance angiograms and duplex ultrasound scans documented persistent patency of multiple branch endoleaks up to the time of euthanasia. In contrast, single side branch endoleaks thrombosed within 3 days (P < .001). Thrombus in the aneurysm sac in close proximity to the endoleak contained intact red blood cells and limited fibrin. Thrombus distant from the endoleak demonstrated extensive fibrin deposition and degraded red blood cells. The canine model may be used to reliably measure intra-aneurysmal pressure in the presence of patent and thrombosed type II endoleaks. In this model 2 or more side branches are necessary to maintain persistent patency of type II endoleaks. These endoleaks are associated with significantly elevated intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. These results suggest that persistent type II endoleaks have clinical significance. Endoleaks originating from retrograde flow in the side branch vessels of the aneurysm generate significant levels of intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. At least 2 patent side branch vessels appear to be necessary to cause persistent patency of type II endoleak in the canine model. Further studies will be necessary to enable more complete characterization of retrograde endoleaks and to extend these findings to allow clinical application. However, these results suggest that persistently patent type II endoleaks are clinical significance and may require more intensive follow-up intervention.


[Complications on minimal access surgery for total hip arthroplasty].
Recently, the surgical approach for total hip replacement has been refined and has been reduced in size. Controversies exist between advantages and complications it can present. To show the complications of total hip arthroplasty by means of minimal access approach. Thirty six patients, 24 women and 12 men (mean age 48 years), grade IV hip arthrosis. Twenty four patients underwent cementless hip arthroplasty and 12 patients hybrid arthroplasty. The preoperative evaluation was done with Harris score. An initial lateral approach of 6 cm (100%) was performed. Complications were grouped on acetabular, femoral and soft tissue complications. Necrosis at the comissure of the wound was seen in 12 patients (33.33%), necrosis at the surface border of the wound in 10 patients (27.77%), mal positioning of the acetabular cup in 3 patients (8.33%), mal positioning of acetabular cup screws in 2 patients (5.55%), eccentric reaming of the acetabulum in one patient (2.77%), and femoral stem malalignment in one patients (2.77%). There are many reports on the advantages of minimal invasion total hip replacement but few on complications which include mal positioning of the acetabular cup, eccentric reaming of the acetabulum and femoral stem malalignment. Nevertheless, advantages include a decreased healing time and postoperative recovery with less pain and reduced blood loss. We recommend that this technique should remain in the hands of experienced orthopaedic surgeons.


Shocking the system: AEDs in military resuscitation.
Automated external defibrillator (AED) devices have been in routine clinical use since the early 1990s to deliver life-saving shocks to appropriate patients in non-clinical environments. As expectations of survival from out-of-hospital cardiac arrest increase, and evidence incontrovertibly points to reduced timelines as the most crucial factor in achieving return of spontaneous circulation, questions regarding the availability and location of AEDs in the UK military need to be readdressed. This article explores the background of AEDs and reviews their history, life-saving potential and defines current and best practice. It goes on to review the evidence surrounding training and looks to identify knowledge gaps that might be addressed effectively by future research. Finally, it makes recommendations regarding training, availability of AEDs on military bases and locations most likely to deliver good outcomes for military personnel in the future.


Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy.
All would agree that hypercalcemia occurs among patients with humoral hypercalcemia of malignancy (HHM) as a result of osteoclastic bone resorption. Some studies suggest that enhanced renal calcium reabsorption, which plays an important pathophysiological role in the hypercalcemia occurring in primary hyperparathyroidism, is also important pathophysiologically in HHM. Other studies have not agreed. In large part, these differences result from the inability to accurately assess creatinine and calcium clearance in critically ill subjects with HHM. To circumvent these issues, we have developed steady state 48-h PTH-related protein (PTHrP) infusion and 8-h hypercalcemic calcium clamp protocols. These techniques allow assessment of the effects of steady state PTHrP and calcium infusions in normal healthy volunteers in a setting in which renal function is stable and measurable and in which the filtered load of calcium can be matched in PTHrP- and calcium-infused subjects. Normal subjects were infused with saline (placebo), PTHrP, or calcium. Subjects receiving PTHrP, as expected, displayed mild hypercalcemia (10.2 mg/dL), suppression of endogenous PTH-(1--84), and phosphaturia. Subjects receiving the hypercalcemic calcium clamp displayed indistinguishable degrees of hypercalcemia and PTH suppression. Despite their matched degrees of hypercalcemia and PTH suppression, the two groups differed importantly with regard to fractional calcium excretion (FECa). The hypercalcemic calcium clamp group was markedly hypercalciuric (FECa averaged 6.5%), whereas FECa in the PTHrP-infused subjects was approximately 50% lower (between 2.5--3.7%), and no different from that in the normal controls, which ranged from 1.5--3.0%. These studies demonstrate that PTHrP is able to stimulate renal calcium reabsorption in healthy volunteers. These studies suggest that PTHrP-induced renal calcium reabsorption, in concert with the well established acceleration of osteoclastic bone resorption, contributes in a significant way to the hypercalcemia observed in patients with HHM.


Assembly of SARS-CoV-2 ribonucleosomes by truncated N∗ variant of the nucleocapsid protein.
The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein serine/arginine (SR) region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N∗ or Δ(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we use mass photometry and negative stain electron microscopy to show that purified Δ(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of Δ(1-209) vRNPs requires the leucine-rich helix of the central disordered region and that this helix promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to Δ(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by phosphorylation.


Beta-endorphin and its congeners in rat pituitary and thyroid: effects of propylthiouracil and thyroid hormone administration.
Immunoreactive beta-endorphin (ir-beta EP) and immunoreactive N-acetyl-endorphin (ir-NacEP) have been demonstrated in the rat thyroid by specific RIA and characterized by reverse phase HPLC. In addition, pituitary and thyroid ir-beta EP and ir-NacEP levels have been determined after manipulation of the pituitary-thyroid axis by chronic (21 days) treatment with 1) propylthiouracil (PTU), 2) L-T4, 3) L-T3, or 4) T3 plus PTU. No difference in anterior pituitary or neurointermediate lobe ir-beta EP was seen between controls and treated groups (n = 8/group). In contrast, levels of ir-NacEP were markedly lower (P less than 0.01) in both hypo- and hyperthyroid groups than in controls, in both anterior pituitary and neurointermediate lobe. In the thyroid, levels of both ir-beta EP and ir-NacEP were profoundly depressed (P less than 0.01) in all treated groups, with no change in calcitonin levels, suggesting that the thyroid effect of PTU and T3/T4 may be specific for the synthesis, processing, and/or release of pro-opiomelanocortin derived peptides. The findings in this study suggest 1) that acetylation of pituitary and thyroid beta EP is similarly sensitive to PTU and thyroid hormone administration and 2) that in the thyroid, but not in the pituitary, both PTU and thyroid hormones markedly lower levels of pro-opiomelanocortin-derived peptides.


Relationship between circulating IGF-1 levels and traumatic brain injury-induced hippocampal damage and cognitive dysfunction in immature rats.
It is well known that traumatic brain injury (TBI) induces the cognitive dysfunction resulting from hippocampal damage. In the present study, we aimed to assess whether the circulating IGF-I levels are associated with cognition and hippocampal damage in 7-day-old rat pups subjected to contusion injury. Hippocampal damage was examined by cresyl violet staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Spatial memory performance was assessed in the Morris water maze. Serum IGF-1 levels decreased in both early and late period of TBI. Decreased levels of serum IGF-1 were correlated with hippocampal neuron loss and spatial memory deficits. Circulating IGF-1 levels may be predictive of cognitive dysfunction resulted from hippocampal damage following traumatic injury in developing brain. Therapy strategies that increase circulating IGF-1 may be highly promising for preventing the unfavorable outcomes of traumatic damage in young children.


Health planning and resources development: an opportunity for optometry.
The American Optometric Association views the goal of the National Health Planning and Resources Development Act of 1974, as the promotion of physical, emotional and environmental health for all. The National Health Planning and Resources Development Act will work towards this goal by identifying problems, preparing reports and studies and developing recommendations for implementation directed toward solving the problems. These functions will be carried out in collaboration with private and governmental individuals and organizations concerned with health care services. Only through this coordinated effort will success be achieved.


Climate change may alter breeding ground distributions of eastern migratory monarchs (Danaus plexippus) via range expansion of Asclepias host plants.
Climate change can profoundly alter species' distributions due to changes in temperature, precipitation, or seasonality. Migratory monarch butterflies (Danaus plexippus) may be particularly susceptible to climate-driven changes in host plant abundance or reduced overwintering habitat. For example, climate change may significantly reduce the availability of overwintering habitat by restricting the amount of area with suitable microclimate conditions. However, potential effects of climate change on monarch northward migrations remain largely unknown, particularly with respect to their milkweed (Asclepias spp.) host plants. Given that monarchs largely depend on the genus Asclepias as larval host plants, the effects of climate change on monarch northward migrations will most likely be mediated by climate change effects on Asclepias. Here, I used MaxEnt species distribution modeling to assess potential changes in Asclepias and monarch distributions under moderate and severe climate change scenarios. First, Asclepias distributions were projected to extend northward throughout much of Canada despite considerable variability in the environmental drivers of each individual species. Second, Asclepias distributions were an important predictor of current monarch distributions, indicating that monarchs may be constrained as much by the availability of Asclepias host plants as environmental variables per se. Accordingly, modeling future distributions of monarchs, and indeed any tightly coupled plant-insect system, should incorporate the effects of climate change on host plant distributions. Finally, MaxEnt predictions of Asclepias and monarch distributions were remarkably consistent among general circulation models. Nearly all models predicted that the current monarch summer breeding range will become slightly less suitable for Asclepias and monarchs in the future. Asclepias, and consequently monarchs, should therefore undergo expanded northern range limits in summer months while encountering reduced habitat suitability throughout the northern migration.


Life-threatening intraabdominal arterial embolization after histoacryl injection for bleeding gastric ulcer.
N-butyl-cyanoacrylate (Histoacryl) injection has become the treatment of choice for acutely bleeding esophagogastric varices, and is the only effective option for endoscopic treatment of gastric varices. Recent reports confirm the ability of Histoacryl injection therapy to achieve immediate hemostasis in cases of gastric ulcer bleeding or Dieulafoy ulcer, where conventional endoscopic hemostatic treatment had failed. Although the overall safety record of Histoacryl injection has been relatively good, there have been scattered cases of serious complications. Here, we present two patients showing life-threatening intraabdominal arterial embolization after Histoacryl injection. They had chronic gastric ulcers with active arterial bleeding. In spite of attempts at hemostatic treatment, complete hemostasis was not achieved. We injected Histoacryl, diluted with Lipiodol, into bleeding gastric ulcers, resulting in successful hemostasis. Soon after the procedure, intraabdominal arterial embolization developed in both patients. One patient survived and the other died. Based on these experiences, we would like to warn gastrointestinal endoscopists to be alert to these fatal complications, and we propose that less diluted Histoacryl seems to be preferable in cases of bleeding peptic ulcers.


A sodium afterdepolarization in rat superior colliculus neurons and its contribution to population activity.
The mammalian superior colliculus (SC) is a midbrain structure that integrates multimodal sensory inputs and computes commands to initiate rapid eye movements. SC neurons burst with the sudden onset of a visual stimulus, followed by persistent activity that may underlie shifts of attention and decision making. Experiments in vitro suggest that circuit reverberations play a role in the burst activity in the SC, but the origin of persistent activity is unclear. In the present study we characterized an afterdepolarization (ADP) that follows action potentials in slices of rat SC. Population responses seen with voltage-sensitive dye imaging consisted of rapid spikes followed immediately by a second distinct depolarization of lower amplitude and longer duration. Patch-clamp recordings showed qualitatively similar behavior: in nearly all neurons throughout the SC, rapid spikes were followed by an ADP. Ionic and pharmacological manipulations along with experiments with current and voltage steps indicated that the ADP of SC neurons arises from Na(+) current that either persists or resurges following Na(+) channel inactivation at the end of an action potential. Comparisons of pharmacological properties and frequency dependence revealed a clear parallel between patch-clamp recordings and voltage imaging experiments, indicating a common underlying membrane mechanism for the ADP in both single neurons and populations. The ADP can initiate repetitive spiking at intervals consistent with the frequency of persistent activity in the SC. These results indicate that SC neurons have intrinsic membrane properties that can contribute to electrical activity that underlies shifts of attention and decision making.


The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae.
The key glycolytic HXK2 gene, coding for the enzyme hexokinase 2 (Hxk2p), is expressed when cells of the yeast Saccharomyces cerevisiae are grown on a fermentable medium using glucose, fructose or mannose as a carbon source. After shifting the cells to a non-fermentable carbon source, the HXK2 gene is repressed and the HXK1 and GLK1 genes are rapidly de-repressed, producing the enzymes hexokinase 1 (Hxk1p) and glucokinase (Glk1p) respectively. Because the in vivo functions of the Hxk1p and Glk1p enzymes have remained a mystery so far, we have investigated this glucose-induced regulatory process. Here we demonstrate the involvement of Hxk2p in the glucose-induced repression of the HXK1 and GLK1 genes and the glucose-induced expression of the HXK2 gene. We have also demonstrated the involvement of Hxk1p as a negative factor in the expression of the GLK1 and HXK2 genes. Further experimental evidence, using mutant cells expressing a truncated version of Hxk2p unable to enter the nucleus, shows that nuclear localization of Hxk2p is necessary for glucose-induced repression signalling of the HXK1 and GLK1 genes and for glucose-induced expression of the HXK2 gene. Gel mobility-shift analysis shows that Hxk2p-mediated regulation is exerted through ERA (ethanol repression autoregulation)-like regulatory sequences present in the HXK1 and GLK1 promoters and in two downstream repressing sequences of the HXK2 gene. These findings reveal a novel mechanism of gene regulation whereby the product of a glycolytic gene, normally resident in the cytosol, interacts directly with nuclear proteins to regulate the transcription of the HXK1 and GLK1 genes and to autoregulate its own transcription.


Do fungi need to be included within environmental radiation protection assessment models?
Fungi are used as biomonitors of forest ecosystems, having comparatively high uptakes of anthropogenic and naturally occurring radionuclides. However, whilst they are known to accumulate radionuclides they are not typically considered in radiological assessment tools for environmental (non-human biota) assessment. In this paper the total dose rate to fungi is estimated using the ERICA Tool, assuming different fruiting body geometries, a single ellipsoid and more complex geometries considering the different components of the fruit body and their differing radionuclide contents based upon measurement data. Anthropogenic and naturally occurring radionuclide concentrations from the Mediterranean ecosystem (Spain) were used in this assessment. The total estimated weighted dose rate was in the range 0.31-3.4 μGy/h (5th-95th percentile), similar to natural exposure rates reported for other wild groups. The total estimated dose was dominated by internal exposure, especially from 226Ra and 210Po. Differences in dose rate between complex geometries and a simple ellipsoid model were negligible. Therefore, the simple ellipsoid model is recommended to assess dose rates to fungal fruiting bodies. Fungal mycelium was also modelled assuming a long filament. Using these geometries, assessments for fungal fruiting bodies and mycelium under different scenarios (post-accident, planned release and existing exposure) were conducted, each being based on available monitoring data. The estimated total dose rate in each case was below the ERICA screening benchmark dose, except for the example post-accident existing exposure scenario (the Chernobyl Exclusion Zone) for which a dose rate in excess of 35 μGy/h was estimated for the fruiting body. Estimated mycelium dose rate in this post-accident existing exposure scenario was close to the 400 μGy/h benchmark for plants, although fungi are generally considered to be less radiosensitive than plants. Further research on appropriate mycelium geometries and their radionuclide content is required. Based on the assessments presented in this paper, there is no need to recommend that fungi should be added to the existing assessment tools and frameworks; if required some tools allow a geometry representing fungi to be created and used within a dose assessment.


Passaging of gingival fibroblasts from periodontally healthy and diseased sites upregulates osteogenesis-related genes.
To investigate biological processes of the periodontium, in vitro primary cell models have been established. To study the biology of the gingiva, primary gingival fibroblast cell models are widely used. For such experiments, cells need to be expanded and passaged. A key assumption is that primary cells maintain most of their original characteristics they have in situ. The aim of this research is to explore the impact of early passaging on selected gene expression of human gingival fibroblast cells. For this purpose, gene expression from the outgrowth of the resected tissues until the fourth passage was followed for nine tissue samples, from both healthy and diseased sites. Micrographs were taken from the cultures, RNA was extracted from the samples of each passage and quantitative PCR was performed for selected genes representing various biological processes. Epithelial cells were present during the first outgrowth, but were no longer present in the second passage. Our results indicate that the morphology of the gingival fibroblast cells does not change with passaging and that passages 2-4 contain only gingival fibroblasts. Gene expression of M-CSF, TNF-α, TLR4, POSTN and FAPα was unchanged by passaging, the expression of IL-6, IL-1β and TLR2 decreased due to passaging and the expression of in particular the selected osteogenesis genes (ALP, RUNX2, Osteonectin, COL1A), OPG and MKI67 increased with passaging. Worldwide, use of the same passage in laboratory experiments using primary cell cultures is the standard. Our results support this, since for certain genes, in particular osteogenesis genes, expression may alter solely due to passaging.


Structure of a bifunctional alcohol dehydrogenase involved in bioethanol generation in Geobacillus thermoglucosidasius.
Bifunctional alcohol/aldehyde dehydrogenase (ADHE) enzymes are found within many fermentative microorganisms. They catalyse the conversion of an acyl-coenzyme A to an alcohol via an aldehyde intermediate; this is coupled to the oxidation of two NADH molecules to maintain the NAD(+) pool during fermentative metabolism. The structure of the alcohol dehydrogenase (ADH) domain of an ADHE protein from the ethanol-producing thermophile Geobacillus thermoglucosidasius has been determined to 2.5 Å resolution. This is the first structure to be reported for such a domain. In silico modelling has been carried out to generate a homology model of the aldehyde dehydrogenase domain, and this was subsequently docked with the ADH-domain structure to model the structure of the complete ADHE protein. This model suggests, for the first time, a structural mechanism for the formation of the large multimeric assemblies or `spirosomes' that are observed for this ADHE protein and which have previously been reported for ADHEs from other organisms.


The relationship between hand preference consistency, health, and accidents in a sample of adults over the age of 65 years.
As a result of the Coren and Halpern (1991) hypothesis that left hand preference may be associated with decreased survival fitness, there has been interest in exploring the relationship between hand preference and indices of health status. In a series of studies of university-aged adults, Hicks and his colleagues found a higher prevalence of accidental injuries, falls, and sleep problems among individuals with mixed, rather than left, hand preference. They argued that hand preference consistency, not side, may be a marker for possible reduction in health and well-being. We looked at the relationship between hand preference consistency and the prevalence of sleep problems, accidental injuries, falls, injuries from falls, and the prevalence of autoimmune and other illnesses in a sample of 1277 adults between the ages of 65 and 100 years. Of those participants who reported a recent fall, mixed-handers were more likely to report a higher number of injuries from these falls when compared to the reports of consistent-handers. In contrast to the previous findings of Hicks et al., and highlighting the value of including broader age ranges, all other comparisons showed no differences between the two hand preference types.


Transumbilical catheter intervention of ductus arteriosus in neonatal swine.
The objective of this study is to report a new technique for transcatheter intervention of the ductus arteriosus (DA) through the umbilical artery (UA) in neonatal swine. Transcatheter intervention of the DA in swine is routinely performed via the jugular vein or occasionally the femoral artery accessed via surgical cutdown. Transumbilical catheter intervention is performed in humans. For this study, all procedures were performed under general anesthesia using isoflurane with oxygen for induction and maintenance. Only animals less than 48 h old were used. The UA was cannulated with a 3.5-Fr single-lumen catheter. The catheter was exchanged over a wire for a 4-Fr introducer. A 4-Fr angled catheter was used to cross the DA. Coil occlusion or stent implantation was implemented. UA cannulation was attempted in 30 newborn piglets with the intent to coil occlude or stent the DA. The animals weighed 1.2-1.8 kg (mean 1.49 kg; median 1.4 kg). Umbilical cannulation was successful in 28/30 animals (93%). Successful ductal intervention was achieved in 26 animals (93%). Initially all procedures were performed under general anesthesia and orotracheal intubation; the last 18 were performed using spontaneous mask ventilation. Thus we find that transumbilical DA catheter intervention can be successfully performed. Advantages over traditional methods include avoiding technical problems inherent with traversing right heart structures and surgical wounds. Access to the DA along its natural orientation facilitates intervention.


Characterization of a multigene family undergoing high-frequency DNA rearrangements and coding for abundant variable surface proteins in Mycoplasma agalactiae.
A family of abundant surface proteins (Vpmas [variable proteins of Mycoplasma agalactiae]) undergoing phase variation in M. agalactiae has been characterized using monoclonal antibodies and specific polyclonal sera. Two expressed members of 39 kDa (Vpma39) and 34 kDa (Vpma34), which varied in expression between clones of a lineage, shared a common amino-terminal sequence but were immunologically distinct. An amino-terminal oligonucleotide probe identified multiple vpma genes which were clustered within a 14-kb ClaI genomic fragment. Rearrangements were found to have occurred within the vpma locus between clones which correlated with changes in their Vpma phenotype. Two neighboring vpma genes were cloned and sequenced from one M. agalactiae clonal variant expressing Vpma39. The two genes, vpmaX and vpmaY, were orientated divergently and shared highly homologous 5' untranslated regions, 25-amino-acid (aa) lipoprotein leader sequences, and amino-terminal sequences. The vpmaY gene coded for 346 aa and 84% of the open reading frame, comprised of 1.5 units of a large repeat of 186 aa. Although the sequence for an entire second vpmaY repeat was present, it was prematurely terminated by insertion of two nucleotides. The vpmaX gene encoded 221 aa and possessed 102 aa of the 186-aa repeat of vpmaY. Many of the features in common between the vpma genes were also found to be shared by the vsp genes of M. bovis, which also undergo DNA rearrangements concomitant with phenotypic changes. Since M. bovis is the closest phylogenetic relative to M. agalactiae, the vpma and vsp gene families most probably represent homologous systems.


Alteration of body composition in rats: effect of organic chromium and L-carnitine.
A growth trial was carried out to test the effect of organic, trivalent chromium and L-carnitine on the body composition of growing rats. At the same time, an evaluation of different measurement methods (weight of epididymal fat pad, adipocyte morphometry, total body electrical conductivity) was performed. Outbred Wistar rats of 30 days of age were fed diets of different (0, 10 and 20%) protein level. The diets were supplemented with 4 mg/kg Cr as chromium nicotinate, and 100 mg/kg L-carnitine. The experimental feeding lasted 15 days, after a 5-day-long adjustment period. It was found that Cr addition increased feed intake. Both treatments caused changes in body composition, increasing fat and protein deposition. Organic chromium had no effect at either protein level, while L-carnitine improved the protein retention only at an optimum (20%) protein supply. No statistically significant correlation was found between total body electrical conductivity (TOBEC) and body composition, which could be attributed to the great individual differences. A close correlation was found among total body fat percentage, weight of epididymal fat pad and the adipocyte surface. The data suggest that there is an interaction between dietary protein supply and the effect of repartitioning agents.


Comparison of valsartan and benazepril when combined with atorvastatin in protecting patients with early cardio-renal syndrome (CRS).
The aims to investigate the different protective effects of valsartan and benazepril when combined with atorvastatin in the cardio-renal functions of cardio-renal syndrome (CRS) patients. A total of 200 early CRS patients were enrolled in the present study, including 104 males and 96 females, with an average age of 62.2 ± 7.7 years. The same group of patients were set as the control group prior to treatment, and then randomly divided into two groups; the A group was treated with valsartan (80 mg/d) and atorvastatin (20 mg/d); the B group was treated with benazepril (10 mg/d) and atorvastatin (20 mg/d). The treatment period was 24 months. The clinical efficacy and clinical events were observed and the following parameters of each patient were measured before and after treatment: 24h urine protein; creatinine clearance; serum brain natriuretic peptide (BNP); high sensitivity C-reactive protein (hsCRP); blood lipid level; liver function and ejection fraction (EF) value. Compared with the control group, the clinical symptoms of the treatment groups were improved with decreased blood lipid levels, significantly decreased serum BNP and hsCRP levels and significantly increased EF values and creatinine clearance rates (p < 0.01). The differences between the two treatment groups were not statistically significant. The number of patients that stopped treatment due to the development of a cough was significantly higher in the B group than the A group (p < 0.01). When combined with atorvastatin, both valsartan and benazepril effectively improved the cardio-renal functions of early CRS patients. There was no significant difference between the two treatments however, valsartan appeared to be better tolerated by patients.


Telomeric associations and chromosome instability in ataxia telangiectasia T cells characterized by TCL1 expression.
T-cell tumors in ataxia telangiectasia (AT), such as T-PLL/T-CLL, are first preceded by the development of a large clone of T-lymphocytes, characterized by chromosomal rearrangements, which usually involve specific regions such as the 14q11 region. Malignancy develops years later, after additional chromosomal changes resulting from the genomic instability consequent to ATM disruption and to the activation of the TCL1 oncogene. Here we report the results of a cytogenetic follow-up of an AT patient (AT94-1), still without signs of hematological abnormalities, bearing a T-lymphocyte clone characterized by the t(14;14)(q11;q32) rearrangement and having TCL1 expression. We demonstrated that in clonal cells TCL1 expression correlates with increasing genomic instability and in time this mainly induces chromosomal rearrangements and telomeric associations (tas). Chromosome 21 is not randomly involved; in particular, an i(21q) indicates that it is a subclone prone to additional genetic changes and could represent an early chromosomal rearrangement involved in tumorigenesis. With regard to the increase in tas, we observed that: (i) it is inversely correlated with the proliferative ability of AT94-1 lymphocytes in PHA-stimulated short-term cultures (cell aging in vitro); (ii) this increase is not due to changes either in cell radiosensitivity (measured as bleomycin (BML)-sensitivity) or due to an illegitimate recombination (measured as adriamycin-sensitivity), which may not be sufficient for tumor development.


Monoclonal infection involving Mycobacterium avium presenting with three distinct colony morphotypes.
Recent reports indicate that polyclonal infections may play an important role in multiple drug resistance in Mycobacterium avium infections. We report here on the isolation of a single M. avium strain that appeared to have smooth colony morphology upon initial isolation on a Lowenstein-Jensen slant. Primary subculture onto Middlebrook 7H10, however, revealed three distinct morphotypes representing smooth opaque (SmO), smooth transparent (SmT), and rough (Rg) colony morphologies. All three morphotypes were identified as M. avium by standard biochemical procedures, Genprobe analysis, and mycolic acid patterns. Subsequent restriction fragment length polymorphism analysis, using SalI- and PvuII-digested genomic DNA, revealed identical patterns for hybridization with the IS1245 probe. Thin-layer chromatographic analysis of lipids from the three morphotypes revealed that only the SmT morphotype possessed what appeared to be lipid components similar to, but unlike, previously described serovar-specific glycopeptidolipid antigens. Further analysis of internally radiolabeled deacylated lipids from the SmT morphotype, by high-performance liquid chromatography and thin-layer chromatography, disclosed that some of these components can be internally radiolabeled with [14C] phenylalanine and [14C]mannose. These results suggest that these components are structurally similar to previously described glycopeptidolipid antigens. This is apparently the first report of a monoclonal infection involving a single strain of M. avium presenting with all three colony morphotypes, SmO, SmT, and Rg.


Management of turbidity current venting in reservoirs under different bed slopes.
The lifetime and efficiency of dams is endangered by the process of sedimentation. To ensure the sustainable use of reservoirs, many sediment management techniques exist, among which venting of turbidity currents. Nevertheless, a number of practical questions remain unanswered due to a lack of systematic investigations. The present research introduces venting and evaluates its performance using an experimental model. In the latter, turbidity currents travel on a smooth bed towards the dam and venting is applied through a rectangular bottom outlet. The combined effect of outflow discharge and bed slopes on the sediment release efficiency of venting is studied based on different criteria. Several outflow discharges are tested using three different bed slopes (i.e., 0%, 2.4% and 5.0%). Steeper slopes yield higher venting efficiency. Additionally, the optimal outflow discharge leading to the largest venting efficiency with the lowest water loss increases when moving from the horizontal bed to the inclined positions.


Malignant melanoma with neural differentiation: an exceptional case report and brief review of the pertinent literature.
: The term neurotropic melanoma has been used to refer to malignant melanoma with associated infiltration of nerve or "neural differentiation"--that is, melanoma cells exhibiting cytological characteristics of nerve cells. Historically, neurotropic melanoma has generally been discussed within the context of desmoplastic melanoma. We report an exceptional case of melanoma notable for a very well-differentiated neural component that was contiguous with obvious overlying melanoma. After careful consideration of all pertinent histological features, the overall diagnostic impression was that of melanoma with associated "malignant neurotization." We have not encountered a previously reported case with such a well-differentiated neural component. The following article details our exceptional case of melanoma with "malignant neurotization" and presents a discussion of the differential diagnosis and brief review of the pertinent literature.


Liberal Privilege in Academic Psychology and the Social Sciences: Commentary on Inbar & Lammers (2012).
This comment is in two parts. The first presents some implications of Inbar and Lammers' (2012, this issue) findings by making salient many of the advantages and privileges enjoyed by scientists when they extol the moral and intellectual superiority of liberals, liberal beliefs, liberal attitudes, and liberal policy preferences over conservatives, conservative beliefs, conservative attitudes, and conservative policy preferences. The second part of this comment refutes (or, at least, vigorously contests) some of the most common arguments that have attempted to defend social psychology from charges of unscientific and distorting liberal biases.


The clinical significance of metastases to the adrenal glands.
Seven patients, four of whom subsequently proved to have bilateral and three, unilateral adrenal metastases, were evaluated regarding adrenal activity. Three of the patients had clinical signs and symptoms similar to those usually associated with manifest adrenal insufficiency. Massive tumor growth, with less than 20 per cent residual amounts of apparently normal adrenal tissue, was found in three of the four patients with bilateral metastases. The metastases in the fourth patient were smaller and could only be detected microscopically. Evaluation of the adrenal activity included the determination of cortisol levels in plasma at 8 am, 2 pm and 8 pm; single dose dexamethasone suppression test with adrenocorticotropic hormone stimulation, and analysis of 24 hour urinary excretion of epinephrine and norepinephrine. In all seven patients, the plasma cortisol levels, dexamethasone suppression--adrenocorticotropic hormone stimulation test results and urinary excretion of epinephrine and norepinephrine were similar to those found in comparable patients without adrenal metastases. Thus, the metastases did not seem to be of any clinically significant importance for the patients. It was concluded that, apparently, only minimal amounts of residual adrenal tissue are sufficient to maintain, for basic conditions, normal production of cortisol and of epinephrine and to even respond to stress.


Relationship Between Obesity, Physical Activity, and Cardiorespiratory Fitness Levels in Children and Adolescents in Bosnia and Herzegovina: An Analysis of Gender Differences.
This study aimed to examine: (i) the level of physical activity (PA), obesity indices and cardiorespiratory fitness (CRF) among boys and girls in primary school, and (ii) to determine the association of obesity indices and PA with CRF for the total number of participants, and then separately for boys and girls. 753 sixth to ninth grade girls and boys aged 10-14 years took part in this cross-sectional study. The PA was assessed by the "Physical Activity Questionnaire - Children" and CRF was assessed by the Maximal multistage a 20 m shuttle run test. Body mass index (BMI), waist circumferences (WC), and waist to height ratio (WHtR) were considered as obesity indices. Multiple linear regression analyses were performed to explore correlates of CRF. The results obtained showed the prevalence of general overweight and obesity was 25.5% in our sample which was lower than that in the regional estimate (e.g., ∼28%) for Eastern Europe. Among all participants, CRF was associated with male sex, older age, a lower WC percentile, higher WHtR, and higher level of PA. The model accounted for 24% of the variance. CRF was associated with older age and higher level of PA among girls and boys. Lower WC percentile was a significant determinant of CRF among boys. In conclusion, general overweight/obesity was not independently associated with CRF. Those with better CRF were more likely to be male and older, had a higher level of PA and lower central adiposity. These findings emphasize the importance of supporting school age children to take a part in programmed physical activity regardless of their body composition.


Relationships between alcohol-related informal social control, parental monitoring and adolescent problem behaviors among racially diverse urban youth.
The purpose of the present study is to investigate the relationships between alcohol-related informal social control and parental monitoring on alcohol use, behavior and intentions; violent behavior; and delinquent behavior in a racially diverse population of young urban adolescents. Baseline surveys were administered to 6th grade male and female students in 61 urban Chicago schools as part of Project Northland Chicago, a group randomized trial for the prevention/reduction of substance use. A subset of their parents (n = 3,034) was also surveyed regarding alcohol use, violence, and delinquency and related issues. Structural equation modeling was used to assess relationships between alcohol-related informal social control (as measured by parental perceptions of neighborhood action regarding youth drinking) and parental monitoring (as reported by parents), and three adolescent outcomes (alcohol use, behaviors and intentions; violent behavior; and delinquent behavior; as reported by teens). Associations between alcohol-related informal social control and parental monitoring were positive and significant (P < .001). Direct paths from parental monitoring to all three adolescent outcomes were negative and statistically significant (alcohol use, behaviors and intentions, P < .001; violent behavior, P < .001; and delinquent behavior, P < .001). Alcohol-related informal social control was not significantly associated with adolescent outcomes. Efforts to engage parents to be more active in monitoring adolescents' activities may be related to lower levels of underage drinking, violence and delinquency among both female and male urban youth. Neighborhood norms and action against teenage drinking may be too distal to adolescent outcomes to be directly associated.


Subunit interactions in aspartate transcarbamylase. A model for the allosteric mechanism.
The conformational changes in aspartate transcarbamylase upon binding of substrates or regulatory ligands and the effects of alterations in the subunit structure on the allosteric interactions are reviewed. The available information including recent results from studies of the c3r6 complex (c denotes the catalytic polypeptide and r, the regulatory polypeptide) is considered in terms of the existing models for the discrepancies between experimental observations and the present models could be resolved by postulating an important role for r:r interactions in the allosteric mechanism. A new model is presented in which an obligatory conformational change upon binding of substrates results in an alteration in the relative orientation of c versus r. As a consequence of symmetry conservation, the r:r domain is shifted to a position of higher potential energy. By favoring one or the other alternative r:r domains, CTP and ATP can respectively enhance and reduce the sigmoidal character of substrate saturation. The model is shown to be consistent with all of the important known properties of the enzyme. Because the heterotropic effects of CTP or ATP are postulated to operate via a mechanism separate from that for the homotropic effects of the substrates, this model accounts satisfactorily for the observation by Kerbiriou and Herve (Kerbiriou, D., and Herve, G. (1973) J. Mol. Biol. 78, 687-702) that homotropic effects can be abolished whereas heterotropic effects are retained in the altered enzyme from Escherichia coli grown in the presence of 2-thiouracil.


Interventions that prevent or reduce obesity in children from birth to five years of age: A systematic review.
Childhood obesity worldwide affects 5.6% or 38.3 million children under five years of age. The longer children are overweight or obese, the more likely they are to become obese adults with all the contingent morbidity involved. An extensive number of preventive interventions to combat childhood obesity have been carried out worldwide. This article reports a systematic review of interventions aimed to reducing or preventing obesity under-fives. The search was performed with six different databases: Web of Science, PsycINFO, Cochrane, PubMed, Medline, and CINAHL. Studies meeting the inclusion criteria were independently assessed using Joanna Briggs Institute methodology. Thirty studies involving 23,185 children across nine countries were included. Twenty-two were randomised controlled trials, and 8 quasi-experimental pretest/post-test design with comparison. These studies fell into four different categories: home-based interventions with family involvement (n = 12), preschool/early childhood settings (n = 9), multicomponent interventions across multiple settings (n = 6) and healthcare setting (n = 3). Future research should focus on increasing the accessibility of education on diet and physical activity for deprived families as well as the cultural acceptability of interventions to prevent childhood obesity.


Health risk assessment as an approach to manage an old landfill and to propose integrated solid waste treatment: A case study in Italy.
The aim of the present paper is to show how an approach based on human health risk analysis can be used as a decisional tool for the evaluation of impacts on population and for deciding between different waste treatment processes. The situation in which the increasing production of solid wastes cannot be confined in the old existing Municipal Solid Waste landfill (settled in Genoa, Liguria Region, Italy) is used as a case study. Risk assessment for human health due to air, surface water, groundwater and soil contamination is performed in different scenarios for the old landfill and compared with alternative Waste-to-Energy management solutions that consider thermal treatment by gasification of the total waste or gasification of the dry fraction coupled with anaerobic digestion of the wet fraction, plus biogas combustion with or without sludge and bottom ash/slag disposal in the old landfill. Hazard Index (HI) and Cancer Risk (CR) in case of operating landfill and under the suspected situation of failure of the sealing system, were respectively 1.15 and 1.1∗10-7. Unacceptable HI were found due to groundwater contamination, while HI due to river pollution was slightly under the threshold. Vegetables ingestion was the most important pathway and ammonia the most responsible of toxic adverse effects. Fish ingestion and dermal contact with contaminated water were found to be the most important exposure pathways for carcinogenic risk, due mainly to BTEX. HI and CR in the supposed scenario of total waste gasification were respectively 9.4∗10-1 and 1.1∗10-5 while they were respectively 3.2∗10-1 and 6∗10-6 in case of gasification of the dry fraction. CR in both scenarios was over the threshold mainly due to dioxins, where milk and meat ingestion were found to be the highest risk pathways. Inhalation resulted as the highest not-carcinogenic risk exposure pathway, mainly due to NOx. Decision making was made by weighing up the different scenarios, and results suggested to definitively close the landfill and to eliminate gasification of the total waste as a possible waste treatment process.


Methodological concerns and quality appraisal of contemporary systematic reviews and meta-analyses in pediatric urology.
The usefulness of systematic reviews and meta-analyses in influencing clinical practice depends on their quality. We sought to analyze the quality of published systematic reviews and meta-analyses in pediatric urology. We searched PubMed (MEDLINE) and Embase for all systematic reviews and meta-analyses published in the top 5 pediatric urology journals between January 2000 and November 2009. Two reviewers independently selected articles for full text review. Scientific methodological quality was evaluated using the Assessment of Multiple Systematic Reviews 11-item tool. Of 267 initial results 220 articles were excluded because they were surveys, case reports or narrative reviews. Full text evaluation of the remaining 47 articles further excluded 32 series of exclusively adult patients, leaving 15 for final analysis. Seven articles (47%) were published in 2009 (p <0.01). Only 1 review (7%) described a full search strategy and 3 (20%) allowed inclusion of non-English studies. In 8 reviews (53%) selection of studies was performed by 2 reviewers. Five systematic reviews (33%) described some form of quality assessment. Only 5 reviews (33%) described assessment of publication bias, while 8 (53%) checked for heterogeneity among studies. According to AMSTAR criteria, 7 systematic reviews (47%) were considered of less than fair methodological quality, 5 (33%) fair to good quality and 3 (20%) good quality. Despite a recent increase in the number of systematic reviews and meta-analyses published in pediatric urology journals, almost half of these reviews lack good scientific quality, raising concerns about their role in influencing clinical practice. Efforts should be made to improve the methodological quality of systematic reviews and meta-analyses in the pediatric urology literature.


Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucinlike ligand activity distinct from P-selectin glycoprotein ligand-1.
Recent reports have shown that leukocyte-leukocyte adhesion is dependent on L-selectin and that leukocyte recognition of L-selectin may be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). We show that the specific attachment and rolling of human neutrophils and the leukemia cell lines HL-60 and U937 on immobilized, purified L-selectin under continuous shear stress is only partially inhibited by treatment with the PSGL-1 monoclonal antibody (MoAb), KPL1 (41% to 53% inhibition), suggesting that L-selectin ligand activity in addition to PSGL-1 may mediate myeloid cell rolling on L-selectin. K562 cells cotransfected with cDNAs encoding alpha (1,3)fucosyltransferase-VII (FucT-VII) and PSGL-1 rolled on L-selectin. Adhesion of FucT-VII-PSGL-1 transfectants to L-selectin was completely blocked by MoAb KPL1, indicating that both L-selectin and P-selectin bind similar sites on PSGL-1. In support of existence of a non-PSGL-1 L-selectin ligand activity on leukocytes, an HL-60 membrane preparation immunodepleted of PSGL-1 supported rolling of L-selectin, but not P-selectin transfectants. Treatment of HL-60 cells with O-sialoglycoprotein endopeptidase inhibited attachment and rolling on L-selectin and P-selectin. However, neuraminidase treatment completely blocked HL-60 rolling on L-selectin, but not P-selectin, suggesting L-selectin and P-selectin ligand activities have different contributions of sialic acid. These findings indicate that myeloid cells express sialylated, O-linked glycoprotein ligand activity independent of PSGL-1 that supports L-selectin-mediated rolling.


Feeding and reward: perspectives from three rat models of binge eating.
Research has focused on understanding how overeating can affect brain reward mechanisms and subsequent behaviors, both preclinically and in clinical research settings. This work is partly driven by the need to uncover the etiology and possible treatments for the ongoing obesity epidemic. However, overeating, or non-homeostatic feeding behavior, can occur independent of obesity. Isolating the variable of overeating from the consequence of increased body weight is of great utility, as it is well known that increased body weight or obesity can impart its own deleterious effects on physiology, neural processes, and behavior. In this review, we present data from three selected animal models of normal-weight non-homeostatic feeding behavior that have been significantly influenced by Bart Hoebel's 40+-yr career studying motivation, feeding, reinforcement, and the neural mechanisms that participate in the regulation of these processes. First, a model of sugar bingeing is described (Avena/Hoebel), in which animals with repeated, intermittent access to a sugar solution develop behaviors and brain changes that are similar to the effects of some drugs of abuse, serving as the first animal model of food addiction. Second, another model is described (Boggiano) in which a history of dieting and stress can perpetuate further binge eating of palatable and non-palatable food. In addition, a model (Boggiano) is described that allows animals to be classified as having a binge-prone vs. binge-resistant behavioral profile. Lastly, a limited access model is described (Corwin) in which non-food deprived rats with sporadic limited access to a high-fat food develop binge-type behaviors. These models are considered within the context of their effects on brain reward systems, including dopamine, the opioids, cholinergic systems, serotonin, and GABA. Collectively, the data derived from the use of these models clearly show that behavioral and neuronal consequences of bingeing on a palatable food, even when at a normal body weight, are different from those that result from simply consuming the palatable food in a non-binge manner. These findings may be important in understanding how overeating can influence behavior and brain chemistry.


Suppression of F1 Male-Specific Lethality in Caenorhabditis Hybrids by cbr-him-8.
Haldane's Rule and Darwin's Corollary to Haldane's Rule are the observations that heterogametic F1 hybrids are frequently less fit than their homogametic siblings, and that asymmetric results are often obtained from reciprocal hybrid crosses. In Caenorhabditis, Haldane's Rule and Darwin's Corollary have been observed in several hybrid crosses, including crosses of Caenorhabditis briggsae and C. nigoni. Fertile F1 females are obtained from reciprocal crosses. However, F1 males obtained from C. nigoni mothers are sterile and F1 males obtained from C. briggsae die during embryogenesis. We have identified cbr-him-8 as a recessive maternal-effect suppressor of F1 hybrid male-specific lethality in this combination of species. This result implicates epigenetic meiotic silencing in the suppression of F1 male-specific lethality. It is also shown that F1 males bearing a C. briggsae X chromosome are fertile. When crossed to C. briggsae hermaphrodites or F1 females derived from C. briggsae hermaphrodites, viable F2 and backcross (B2) progeny were obtained. Sibling males that possessed a C. nigoni X chromosome were sterile. Therefore, the sterility of F1 males bearing a C. nigoni X chromosome must result from dysgenic interactions between the X chromosome of C. nigoni and the autosomes of C. briggsae. The fertility of F1 males bearing a C. briggsae X chromosome provides an opportunity to identify C. nigoni loci that prevent spermatogenesis, and hence hermaphroditic reproduction, in diplo-X hybrids.


A cloud computing based 12-lead ECG telemedicine service.
Due to the great variability of 12-lead ECG instruments and medical specialists' interpretation skills, it remains a challenge to deliver rapid and accurate 12-lead ECG reports with senior cardiologists' decision making support in emergency telecardiology. We create a new cloud and pervasive computing based 12-lead Electrocardiography (ECG) service to realize ubiquitous 12-lead ECG tele-diagnosis. This developed service enables ECG to be transmitted and interpreted via mobile phones. That is, tele-consultation can take place while the patient is on the ambulance, between the onsite clinicians and the off-site senior cardiologists, or among hospitals. Most importantly, this developed service is convenient, efficient, and inexpensive. This cloud computing based ECG tele-consultation service expands the traditional 12-lead ECG applications onto the collaboration of clinicians at different locations or among hospitals. In short, this service can greatly improve medical service quality and efficiency, especially for patients in rural areas. This service has been evaluated and proved to be useful by cardiologists in Taiwan.


TAK1 contributes to the enhanced responsiveness of LTB(4)-treated neutrophils to Toll-like receptor ligands.
Pattern-recognition receptors such as Toll-like receptors (TLRs) are essential sensors implicated in the early and efficient innate immune response against pathogens. We have previously demonstrated that leukotriene B(4)(LTB(4)) has the capacity to enhance leukocyte responses to TLR9 ligands and to control viral infection. In this report, we provide evidence that LTB(4) treatment of human neutrophils leads to a potentiation in proinflammatory cytokine secretion induced by various myeloid differentiation factor 88-dependent TLR agonists. LTB(4) failed to enhance TLR mRNA levels as well as expression of TLR2 and TLR4 receptors, suggesting that LTB(4) acts through intracellular mechanism(s) to potentiate neutrophil responses to TLR ligands. We found that while IRAK can be activated by LTB(4), this process is dispensable to LTB(4) to potentiate neutrophil responses to TLR ligands since pretreatment of neutrophils with IRAK1/4 inhibitor did not affect its potentiating effects. However, our data clearly show that LTB(4) treatment of neutrophils led to the phosphorylation of downstream signaling molecules, TAK1 and p38, a process found essential to observe an increased secretion of cytokines by neutrophils activated with TLR ligands. Pretreatment of neutrophils with TAK1 or p38 kinase inhibitors strongly repressed the effect of LTB(4) on cytokine synthesis by neutrophils stimulated with LTA, LPS or CpG. The same pattern was observed in agonist-treated human embryonic kidney 293 cells transfected with TAK1-targeting siRNA where secretion of IL-8 was significantly reduced to basal levels. These results indicate that TAK1 and p38 kinases appear to be central in the 'priming effect' of LTB(4) on neutrophils to enhance response to TLR ligands.


The modulation of somatosensory resonance by psychopathic traits and empathy.
A large number of neuroimaging studies have shown neural overlaps between first-hand experiences of pain and the perception of pain in others. This shared neural representation of vicarious pain is thought to involve both affective and sensorimotor systems. A number of individual factors are thought to modulate the cerebral response to other's pain. The goal of this study was to investigate the impact of psychopathic traits on the relation between sensorimotor resonance to other's pain and self-reported empathy. Our group has previously shown that a steady-state response to non-painful stimulation is modulated by the observation of other people's bodily pain. This change in somatosensory response was interpreted as a form of somatosensory gating (SG). Here, using the same technique, SG was compared between two groups of 15 young adult males: one scoring very high on a self-reported measure of psychopathic traits [60.8 ± 4.98; Levenson's Self-Report Psychopathy Scale (LSRP)] and one scoring very low (42.7 ± 2.94). The results showed a significantly greater reduction of SG to pain observation for the high psychopathic traits group compared to the low psychopathic traits group. SG to pain observation was positively correlated with affective and interpersonal facet of psychopathy in the whole sample. The high psychopathic traits group also reported lower empathic concern (EC) scores than the low psychopathic traits group. Importantly, primary psychopathy, as assessed by the LSRP, mediated the relation between EC and SG to pain observation. Together, these results suggest that increase somatosensory resonance to other's pain is not exclusively explained by trait empathy and may be linked to other personality dimensions, such as psychopathic traits.


"Train how you play": Using representative learning design to train amateur cricketers.
Training task design with amateur female cricketers has typically comprised of deconstructed and monotonous approaches which may not maximise skill development. Clear guidelines to improve these practices in this cohort are lacking. The training environment should provide the same sources of information, decisions and variability as matches in order to prepare players for the match environment, which can be achieved through representative learning design (RLD). An RLD training intervention designed to promote skill development was performed over five weeks with two amateur female cricket teams to provide a framework for community coaches at the foundation stage of cricket. Skill development was recorded as changes in skilled actions for batting and bowling, with cognitions coded as themes for each skill during training. Six of ten batters and seven of eight bowlers exhibited increases in skill development ranging between 7-49%. Changes in batting and bowling behaviour improved substantially between moderately and extensively designed sessions. Batters' thoughts shifted from their own skill execution to objectives, while bowlers focused on their opponent's execution. Moderate to extensive RLD appears to promote skill development in amateur cricketers, making it a viable option for coach education and training design at the foundation level of cricket.


Stereoselective (S)- and (R)-naproxen glucuronosyl transferases of rat liver.
Stereoselective glucuronidation of naproxen, one of the 2-arylpropionic acids that are widely used as anti-inflammatory drugs, was investigated in chromatofocusing fractions of solubilized liver microsomes from 3-methylcholanthrene- (MC) and phenobarbital- (PB) treated rats. On chromatofocusing of solubilized microsomes of PB-treated rats, two naproxen glucuronosyltransferase (GT) fractions were separated. The fraction eluting at pH 8.7 preferentially conjugated (S)-naproxen (S/R ratio = 1.6) and the fraction eluting at pH 7.8 mostly conjugated (R)-naproxen (S/R ratio = 0.7). Chromatofocusing of solubilized microsomes from MC-treated rats also resulted in the separation of two naproxen GT fractions, eluting at pH 9.4 (S/R ratio 0.2) and at pH 8.7 (S/R ratio 0.8). These two fractions coincided with the elution of known MC-inducible GT activities assigned to a GT isozyme variously termed 4-nitrophenol GT or GT-I. Interestingly, kidney microsomes, known to contain a high constitutive expression of GT-I, preferentially glucuronidated (R)-naproxen (S/R ratio 0.2). The S/R ratio of 0.8, observed with the pI 8.7 fraction of MC-treated rat liver, may be explained by the presence of a mixture of naproxen GTs, consisting of (R)-naproxen GT (S/R ratio 0.2) and of (S)-naproxen GT (S/R ratio 1.6). The results suggest that naproxen is conjugated by at least 3 GT isozymes in rat liver; these have been operationally designated (S)-naproxen GTPB (S/R ratio 1.6), (R)-naproxen GTPB (S/R ratio 0.7), and (R)-naproxen GTMC (S/R ratio 0.2). The latter isozyme is probably identical to the previously characterized MC-inducible GT-I. Thus, (S)- and (R)-naproxen represent useful substrates to distinguish different GT isozymes.


[Quantification of residues DNA in animal-derived biological scaffold materials].
Quantification of residual DNA in animal-derived biological scaffold materials is one of technical specifications for evaluating decellularization process and immunotoxicity risk. Up to now, there have been no standard methods available for quantification of residues DNA in animal-derived biological scaffold materials. In this study, a three-step method, including proteinase K digestion, DNA purification and determination of DNA using fluorescence assay, was designed for residual DNA quantification. A parallel recovery experiment of standard DNA using the same protocol to test article determination was used for adjusting final results of residuul DNA amount. DNA purification based on magnetic beads enabled the experiments to get high accuracy and repeatability. The validation experiment showed that the three-step method had high sensitivity up to 6.25ng of DNA per sample with good linearity (recovery curve R2 > 0.99) in the concentration range of 3. 125-100ng, and 25-400ng per sample. This method is useful for determining micro or trace amount DNA remained in the biomaterials.