Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress.
Gain-of-function mutations in the presenilin-1 (PS-1) promote Alzheimer's disease (AD) by increasing reactive oxygen species, at least part of which is derived by an accompanying increase in generation of amyloid-beta (Abeta). Additional studies indicate that impaired Apolipoprotein E function, which also increases oxidative stress and is also associated with AD, potentiates the deleterious activity of PS-1. Folate deficiency is also associated with AD and potentiates the impact of both ApoE deficiency and beta exposure. More recently, folate deficiency has been shown to increase PS-1 expression. Since dietary supplementation with apple juice provides neuroprotection against ApoE deficiency, Abeta exposure and folate deficiency, we examined the impact of apple juice on PS-1 overexpression. Herein, we demonstrate that dietary deficiency in folate and vitamin E increased PS-1 expression in juvenile and adult normal C57B1/6J and ApoE-/- mice and in aged normal mice. Supplementation with apple juice concentrate (AJC) attenuated or prevent these increases. Prior studies demonstrate that impaired DNA methylation resulting from a deficiency in S-adenosylmethionine (SAM, which is rapidly depleted following folate deprivation) leads to PS-1 overexpression, and that direct supplementation with SAM attenuates PS-1 overexpression. We determined that AJC contained levels of SAM comparable to those capable of suppressing PS-1 overexpression, suggesting that the SAM content of AJC represents a potential mechanism for preventing PS-1 overexpression, and further highlighting the possibility that AJC provides neuroprotection by mechanisms in addition to its antioxidant potential.


Anticipating demand for emergency health services due to medication-related adverse events after rapid mass prophylaxis campaigns.
Mass prophylaxis against infectious disease outbreaks carries the risk of medication-related adverse events (MRAEs). The authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable MRAEs. The authors created a spreadsheet-based computer model that calculates scenario-specific predicted daily MRAE rates from user inputs by applying a probability distribution to the reported timing of MRAEs. A hypothetical two- to ten-day prophylaxis campaign for one million people using recent data from both smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled. The length of a mass prophylaxis campaign plays an important role in determining the subsequent intensity in emergency services utilization due to real or suspected adverse events. A two-day smallpox vaccination scenario would produce an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at 5,246 health care encounters six days after the start of the campaign; in contrast, a ten-day campaign would lead to 41% lower peak surge, with a maximum of 3,106 encounters on the busiest day, ten days after initiation of the campaign. MRAEs with longer lead times, such as those associated with anthrax chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124 out of an estimated 1,400 hospitalizations on day 20 after a two-day campaign versus 103 on day 24 after a ten-day campaign). The duration of a mass prophylaxis campaign may have a substantial impact on the timing and peak number of clinically significant MRAEs, with very short campaigns overwhelming existing emergency department (ED) capacity to treat real or suspected medication-related injuries. While better reporting of both incidence and timing of MRAEs in future prophylaxis campaigns should improve the application of this model to community-based emergency preparedness planning, these results highlight the need for coordination between public health and emergency medicine planning for infectious disease outbreaks to avoid preventable surges in ED utilization.


Histochemical and morphometric observations on the new tissue formed around mammary expanders coated with pyrolytic carbon.
The authors investigated tissue reaction around implanted silicone expanders, focusing on clinical morphological and morphometrical aspects. For use in breast reconstruction in post mastectomy patients, the surface of a medical-grade silicone elastomer was modified, without changing its bulk properties, by the addition of a pyrolytic carbon film. The presence of lipophagy, the number of foreign-body giant cells of histiocytic origin, and the number of MIB-1 positive nuclei (an index of proliferation for the reactive stromal population) were all seen to be influenced by the pyrolytic carbon coating. Indeed, all these parameters were lower in the membrane formed around Carbofilm TM-coated expanders, thus demonstrating the effective protective properties of pyrolytic carbon coating.


Characterization of the mechanical behaviour parameters of the costo-vertebral joint.
This in vitro study introduces a new method to determine quantitative parameters characterizing the mechanical behaviour of the costo-vertebral joint. These parameters are useful in building numerical models of the thoracic spine, taking into account the thoracic cage. Nine thoracic cages were isolated from fresh human cadavers. From each cage, three functional units were tested: T1-T2, T5-T6, T9-T10. Loads were applied according to the joint local coordinate system. Every functional unit was tested first intact and again after section of successive costo-transverse ligaments. We used an opto-electronic system to follow the three-dimensional motion of the joint, and obtained non-linear load/displacement curves according to the primary rotation axis. A statistical analysis of these curves allowed the calculation of parameters describing the joint mechanical behaviour: total range of motion, motion in the low-stiffness zone, and flexibilities in the positive and negative quasi-linear zones. These values can be used as a database for mechanical modeling of the spine.


Role of aberrant IgG glycosylation in the pathogenesis of inflammatory bowel disease.
The intestine is one of the most important organs associated with the immune system. It is thought that disruption of intestinal immunity causes inflammatory bowel disease (IBD). Recent advances in immune glycobiology have provided novel insights into many human diseases. For example, studies of glycosylation remodeling in mice have underscored the importance of oligosaccharides in the pathogenesis of IBD. Furthermore, aberrant glycosylation of IgG is a good serum marker of IBD activity. In this review, we examine current understanding of the role of aberrant glycosylation in the pathogenesis of IBD in terms of our original data and recent reports.


Vitamin A supplementation in early life enhances the intestinal immune response of rats with gestational vitamin A deficiency by increasing the number of immune cells.
Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune response are achieved when vitamin A supplementation occurs during the early postnatal period.


Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1A1*28 polymorphism carriers.
Hyperbilirubinaemia is a frequent complication of atazanavir-containing antiretroviral therapy and its severity is related to UDP-glucuronosyl transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the safety and outcome of unboosted atazanavir-containing regimens based on the genetic constitution. Fifty-one HIV-1-infected patients on boosted atazanavir were prospectively enrolled in the study. Twenty-five patients with a UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. At baseline, UGT1A1 heterozygous and homozygous patients had significantly higher bilirubin levels than wild-type (P = 0.012 and P < 0.001, respectively). After ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82 mg/dL; P < 0.001), γ-glutamyl transpeptidase (P = 0.015), triglycerides (P = 0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell count and no increases in viral load were observed 12 months after unboosting. Plasma drug monitoring after ritonavir removal revealed the presence of therapeutic atazanavir concentrations in all patients except one with poor therapy adherence. UGT1A1*28 is significantly related to hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the initiation of antiretroviral therapy can reduce the emergence of severe hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and efficacious in patients with an undetectable viral load with a UGT1A1*28 polymorphism, allowing the use of atazanavir in patients otherwise likely unable to receive it.


Application of osteoinductive calcium phosphate ceramics in children's endoscopic neurosurgery: report of five cases.
This work aimed at investigating the possibility and effectiveness of osteoinductive calcium phosphate (CaP) ceramics to close the drilled skull holes and prevent the postoperative cerebrospinal fluid (CSF) leaking in children's endoscopic neurosurgery. Five children patients (four boys and one girl, 3- to 8-years old) underwent the surgery, in which the endoscopic third ventriculostomy (ETV) was operated in four cases of hydrocephalus, and biopsy and ETV were both performed in one case of pineal tumor. The drilled skull holes were filled with the commercial osteoinductive CaP ceramics. The patients were followed up by CT scan at 1, 7 days, 3 and 6 months postoperatively. All the five cases were successful, and the holes were closed well after filled with the ceramics. The follow-up survey showed that no CSF leaking or rejection reaction was found. The CT scan indicated that the drilled holes began healing at 7 days postoperatively, and a relatively complete healing happened at 6 months postoperatively. The excellent ability of the CaP ceramics to induce bone regeneration was also confirmed by repairing the skull defects in a monkey model. The results of μ-CT and histological analysis showed that a bony structure with irregular array occurred at the defect area, and the newly formed bone volume density reached 65.7%. In conclusion, the osteoinductive CaP ceramics could be an ideal material to treat the drilled skull holes in children's endoscopic neurosurgery and prevent CSF leaking afterwards. However, further investigation with more cases and longer follow-up was required to evaluate the clinical effect.


[Resuscitation in acute allergic reactions to drugs].
Under analysis were 40 cases of allergic reactions of the immediate type arising in 38 patients following the application of various pharmacological agents. Urticaria and Quincke's edema were observed in 21 cases and anaphylactic shock--in 19 cases. Rare cases of anaphylactic shock following injections of sombrevin, polyglucin and clinical observations of the recurring character of the course of allergic reactions are described.


A simulation study investigating potential diffusion-based MRI signatures of microstrokes.
Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.


Anti-tubercular drug discovery: in silico implications and challenges.
Tuberculosis (TB) has been reported as a major public health concern, especially in the developing countries. WHO report on tuberculosis 2016 shows a high mortality rate caused by TB leading to 1.8 million deaths worldwide (including deaths due to TB in HIV positive individuals), which is one of the top 10 causes of mortality in 2015. However, the main therapy used for the treatment of TB is still the Direct Observed Therapy Short-course (DOTS) that consists of four main first-line drugs. Due to the prolonged and unorganized use of these drugs, Mycobacterium tuberculosis (Mtb) has developed drug-resistance against them. To overcome this drug-resistance, efforts are continuously being made to develop new therapeutics. New drug-targets of Mtb are pursued by the researchers to develop their inhibitors. For this, new methodologies that comprise of the computational drug designing techniques are vigorously applied. A major limitation that is found with these techniques is the inability of the newly identified target-based inhibitors to inhibit the whole cell bacteria. A foremost factor for this limitation is the inability of these inhibitors to penetrate the bacterial cell wall. In this regard, various strategies to overcome this limitation have been discussed in detail in this review, along with new targets and new methodologies. A bunch of in silico tools available for the prediction of physicochemical properties that need to be explored to deal with the permeability issue of the Mtb inhibitors has also been discussed.


Knockdown of lncRNA HULC inhibits proliferation, migration, invasion, and promotes apoptosis by sponging miR-122 in osteosarcoma.
Osteosarcoma is a rare malignant bone tumor with high degree of malignancy. HULC (highly upregulated in liver cancer), a long noncoding RNA (lncRNA) was involved in hepatocellular carcinoma development and progression, but its underlying mechanism in osteosarcoma is unknown. The aim of this study was to explore the functional role of HULC in osteosarcoma. The study was conducted in human osteosarcoma cell lines and the expression of HULC in the cell lines was detected by qRT-PCR. Furthermore, the effects of HULC on tumorigenicity of osteosarcoma cells were evaluated by in vitro assays. Results revealed that HULC was highly expressed in osteosarcoma MG63 and OS-732 cells compared to osteoblast hFOB1.19 cells. Suppression of HULC in osteosarcoma cells inhibited cell viability, migration, invasion, and promoted apoptosis. HULC functioned as an endogenous sponge for miR-122, and its silence functioned through upregulating miR-122. HNF4G was a target of miR-122, and the effect of HNF4G on OS-732 cells was the same as HULC. Furthermore, overexpression of miR-122 inactivated PI3K/AKT, JAK/STAT, and Notch pathways by downregulation of HNF4G. These findings suggest that knockdown of HULC inhibited proliferation, migration, and invasion by sponging miR-122 in osteosarcoma cells. HULC may act as a novel therapeutic target for management of osteosarcoma.


Catalytic hydrogenation enabled by ligand-based storage of hydrogen.
Biology employs exquisite control over proton, electron, H-atom, or H2 transfer. Similar control in synthetic systems has the potential to facilitate efficient and selective catalysis. Here we report a dihydrazonopyrrole Ni complex where an H2 equivalent can be stored on the ligand periphery without metal-based redox changes and can be leveraged for catalytic hydrogenations. Kinetic and computational analysis suggests ligand hydrogenation proceeds by H2 association followed by H-H scission. This complex is an unusual example where a synthetic system can mimic biology's ability to mediate H2 transfer via secondary coordination sphere-based processes.


[Organization of genes (author's transl)].
The organization of genes of animal cells is discussed. The genes for 5S-RNA, rRNA and for histones are examples of the organization of repetitive genes. The interruptions of the coding sequence of the mouse beta-globin gene illustrates the split nature of many eukaryotic genes. It is shown that changes in the organization of genes do occur during the normal development of an organism. The methods used for the analysis of gene structure are of great importance for elucidation of the molecular basis of genetic diseases like the thalassemias.


The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment.
Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.


[The pathogenesis of trehalose dimycolate-induced hemorrhagic pneumonia induced in mice as animal model of human alveolar hemorrhagic syndrome].
Trehalose dimycolate (TDM) is a glycolipid contained in the cell walls of Mycobacteria, Nocardia and Corynebacteria. An intraperitoneal injection of TDM into mice has been known to produce hemorrhagic pneumonia without affecting any other organs. Thus, it provides a unique experimental model for studies of the mechanisms of alveolar hemorrhagic syndrome, including idiopathic pulmonary hemosiderosis. It has been reported that T lymphocytes are essential for the production of TDM-induced hemorrhagic pneumonia, however, the overall cellular mechanism is not yet clear. The purpose of this study is to re-examine and clarify the role of T lymphocytes in the pathogenesis of TDM-induced hemorrhagic pneumonia. To achieve it we considered 1) the dynamics of infiltrating lymphocytes to find out if there is a certain T lymphocyte subpopulation infiltrating predominantly into the lung, 2) the effect of in vivo depletion of T lymphocyte subpopulation by monoclonal antibodies, and 3) the effect of transfer of T lymphocytes into nude mice. The analysis of the dynamic change of the number of lymphocytes showed that the number of L3T4+ cells as well as Lyt2+ cells decreased on day 2 or 3 after TDM injection, thereafter increased, however, neither subpopulation infiltrated predominantly into the lung. Alveolar hemorrhages occurred in L3T4+ cell-depleted and/or Lyt2+ cell-depleted mice, and hemorrhages were enhanced in Lyt2+ cell-deplete mice. Alveolar hemorrhages occurred even in nude mice, and the intensity of hemorrhages or the cell numbers in the lung did not differ from those in T lymphocyte-reconstituted nude mice, however, hemorrhages were enhanced in L3T4+ cell-reconstituted nude mice. These results suggested that T lymphocytes are not primarily involved in the cellular mechanisms of the pathogenesis of TDM-induced hemorrhagic pneumonia, however, L3T4+ cells modify the process of the production of hemorrhagic pneumonia secondarily and enhance it.


Pharmacological management of hypertensive emergencies and urgencies: focus on newer agents.
Hypertensive crises are categorized as hypertensive emergencies and urgencies depending on the presence of acute target-organ damage; the former are potentially life-threatening medical conditions, requiring urgent treatment under close monitoring. Although several short-acting intravenous antihypertensive agents are approved for this purpose, until recently little evidence from proper trials on the relative merits of different therapies was available. This article discusses in brief the pathophysiology, epidemiology and diagnostic approach of hypertensive crises and provides an extensive overview of established and emerging pharmacological agents for the treatment of patients with hypertensive emergencies and urgencies. Agents such as sodium nitroprusside, nitroglycerin and hydralazine have been used for many years as first-line options for patients with hypertensive emergencies, although their potential adverse effects and difficulties in use were well known. With time, equally potent and less toxic alternatives, including nicardipine, fenoldopam, labetalol and esmolol are increasingly used worldwide. Recently, clevidipine, a third-generation dihydropyridine calcium-channel blocker with unique pharmacodynamic and pharmacokinetic properties was added to our therapeutic armamentarium and was shown in clinical trials to reduce mortality when compared with nitroprusside. In view of such evidence, a change in pharmacological treatment practices for hypertensive crises toward newer and safer agents is warranted.


Endodontic Treatment of Primary Molars with Antibiotic Paste: A Report of 38 Cases.
This study presents 38 cases of primary molars with necrotic pulps treated with antibiotics-based paste. The technique consisted of necrotic tissue removal of the pulp chamber, using spoons excavators and low speed drills. Pulp cavity was washed with saline solution and dried with sterile cotton balls. Then an antibiotic paste composed of chloramphenicol, tetracycline, zinc oxide and eugenol - CTZ paste - was inserted at the entrance of root canals. Patients were evaluated clinically and radiographically at different times. The criteria that defined clinical success were the lack of periapical abscess and mobility compatible with chronological age. Radiographic assessments consisted in absence of radiolucency in the region of root bifurcation and pathological bone resorption. There were 100% and 93% of clinical and radiographic success, respectively. The results suggest that the CTZ paste is an optional therapy for pulp of primary molars.


[Distribution of fluoride in the combustion products of coal].
The static distribution characteristic of fluoride in the combustion products of coal was studied by ashing procedure of coal, and the dynamic distribution characteristics of fluorine in the combustion products of coal in pulverized-coal-fired boiler and layer-burning boiler were investigated. Experimental results identified that fluorine in coal belong to volatile elements, fluorine in fly ash and bottom ash were non-rich. About 94.5% of the fluorine in coal emitted as gaseous-fluorine during coal combustion in pulverized-coal-fired boiler, and about 80% of the fluorine in coal emitted as gaseous-fluorine during coal combustion in layer-burning boiler. 55%-60% of the fluorine in fly ash of pulverized-coal-fired boiler were distributed in fly ash particles with a diameter of 74 microns-104 microns.


Relaxation techniques in general practice.
Many common disorders which present in general practice may be treated successfully when patients learn techniques of relaxation. Tension headache, migraine, chronic nervous diarrhoea, pre examination tension and some phobias have a high success rate. The technique is a lifelong asset for both patient and doctor.


Homologous recombination-dependent initiation of DNA replication from DNA damage-inducible origins in Escherichia coli.
Escherichia coli cells induced for the SOS response express inducible stable DNA replication (iSDR) as an SOS function. Initiation of iSDR is independent of transcription, translation and DnaA protein, which are essential for initiation of DNA replication from oriC. We found that a recA mutant that is defective in recombination but proficient in SOS induction could not elicit iSDR. In contrast, iSDR was enhanced by recD and recJ mutations that inactivate the exonuclease V activity of the RecBCD enzyme and the RecJ exonuclease activity, respectively. A mutation in the ruvC gene that blocks the resolution of recombination intermediates (i.e. Holliday structures) also enhanced iSDR. Furthermore, inhibition of branch migration by recG or ruvAB mutations dramatically increased the iSDR activity. recBC mutants are defective in iSDR induction but the defect was suppressed by a mutation in the sbcA gene. The major product of minichromosomes replicated by iSDR was covalently closed circular monomers. We propose that recombination intermediates (i.e. D-loop structures) created by the action of RecA recombinase and RecBC(D) helicase play a central role in initiation of iSDR.


Signal-to-noise ratio behavior of steady-state free precession.
Steady-state free precession (SSFP) is a rapid gradient-echo imaging technique that has recently gained popularity and is used in a variety of applications, including cardiac and real-time imaging, because of its high signal and favorable contrast between blood and myocardium. The purpose of this work was to examine the signal-to-noise ratio (SNR) behavior of images acquired with SSFP, and the dependence of SNR on imaging parameters such as TR, bandwidth, and image resolution, and the use of multi-echo sequences. In this work it is shown that the SNR of SSFP sequences is dependent only on pulse sequence efficiency, voxel dimensions, and relaxation parameters (T1 and T2). Notably, SNR is insensitive to bandwidth unless increases in bandwidth significantly decrease efficiency. Finally, we examined the relationship between pulse sequence performance (TR and efficiency) and gradient performance (maximum gradient strength and slew rate) for several imaging scenarios, including multi-echo sequences, to determine the optimum matching of maximum gradient strength and slew rate for gradient hardware designs. For standard modern gradient hardware (40 mT/m and 150 mT/m/ms), we found that the maximum gradient strength is more than adequate for the imaging resolution that is commonly encountered with rapid scouting (3 mm x 4 mm x 10 mm voxel). It is well matched for typical CINE and real-time cardiac imaging applications (1.5 mm x 2 mm x 6 mm voxel), and is inadequate for optimal matching with slew rate for high-resolution applications such as musculoskeletal imaging (0.5 x 0.8 x 3 mm voxel). For the lower-resolution methods, efficiency could be improved with higher slew rates; this provokes interest in designing methods for limiting dB/dt peripherally while achieving high switching rates in the imaging field of view. The use of multi-echo SSFP acquisitions leads to substantial improvements in sequence performance (i.e., increased efficiency and shorter TR).


Gregor Mendel's classic paper and the nature of science in genetics courses.
The discoveries of Gregor Mendel, as described by Mendel in his 1866 paper Versuche uber Pflanzen-Hybriden (Experiments on plant hybrids), can be used in undergraduate genetics and biology courses to engage students about specific nature of science characteristics and their relationship to four of his major contributions to genetics. The use of primary source literature as an instructional tool to enhance genetics students' understanding of the nature of science helps students more clearly understand how scientists work and how the science of genetics has evolved as a discipline. We offer a historical background of how the nature of science developed as a concept and show how Mendel's investigations of heredity can enrich biology and genetics courses by exemplifying the nature of science.


Mapping the relationship between subgenual cingulate cortex functional connectivity and depressive symptoms across adolescence.
Changes in the functional connectivity of the subgenual anterior cingulate cortex (SGC) have been linked with depressive symptoms. The aim of this study was to map this relationship across mid to late adolescence. Employing a longitudinal functional magnetic resonance imaging (fMRI) design, associations between patterns of resting-state SGC functional connectivity and symptoms of depression were examined at two time points in an initial sample of 72 adolescents. Using a region-of-interest approach, these associations were evaluated cross-sectionally and longitudinally. Cross-sectionally, weaker SGC functional connectivity with the posterior cingulate cortex (PCC), angular gyrus and dorsal prefrontal cortex at baseline, and weaker SGC connectivity with the dorsomedial prefrontal cortex (DMPFC) and ventromedial prefrontal cortex at follow-up, were associated with higher depressive symptoms. Longitudinally, a decrease in SGC functional connectivity with DMPFC, PCC, angular gyrus and middle temporal gyrus was associated with higher depressive symptoms at follow-up. The observation of weaker SGC connectivity predicting increased symptoms contrasts with the majority of resting-state fMRI studies in clinically depressed populations. Taken together with these past studies, our findings suggest depression-related changes in SGC functional connectivity may differ across developmental and illness stages.


Prevalence of HTN in Iran: Meta-analysis of Published Studies in 2004-2018.
Prevalence of hypertension (HTN) is increasing in the developing countries like Iran. Various studies have reported different rates of HTN in Iran. The purpose of this study was to estimate an overall prevalence of HTN in Iran. Using the English and Persian key derived from Mesh, the databases including MagIran, Iran Medex, SID, Web of Sciences, PubMed, Science Direct and Google Scholar as a searching engine were reviewed: from 2004 to 2018. The overall prevalence of MA was estimated using Random effect model. The I2 test was used to assess the heterogeneity of the studies. Additionally, the quality of studies was evaluated using a standard tool. Publication bias was conducted with the Egger test. Meta-regression and analysis of subgroups were analyzed based on variables such as age, marital status, region and tools. Data were analyzed using STATA 12 software. Analysis of 58 primary articles with a sample size of 902580 showed that the prevalence of HTN in Iran was 25% (with 95% CI of 22-28). The highest prevalence of HTN was related to elderly (42%). The prevalence of HTN was 25% (95% CI: 19-31) in women and 24% (95% CI: 20-28) in men with no significant difference (p = 0.758). The results also indicated that the prevalence of HTN was not related to the year of studies (p = 0.708) or sample size (p = 769). Despite the advancements in science and technology, along with health and prevention of diseases, the overall prevalence of HTN raised in Iran. Since HTN is a silent disease with significant health consequences and economic burden, programs designed to better HTN control seem vital to enhance community health.


Thromboxane inhibitors attenuate inflammatory and fibrotic changes in rat liver despite continued ethanol administrations.
Thromboxane levels are increased in rats fed ethanol (EtOH), whereas thromboxane inhibitors reduce alcoholic liver injury. The aim of this study is to determine whether thromboxane inhibitors could attenuate the already established alcoholic liver injury. Rats were fed EtOH and liquid diet for 6 weeks by intragastric infusion to induce liver injury after which EtOH was continued for 2 more weeks, and the rats were treated with either a thromboxane synthase inhibitor (TXSI) or a thromboxane receptor antagonist (TXRA). Liver pathology, lipid peroxidation, nuclear factor-kappa-B (NF-κB) activity, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and transforming growth factor-beta1 (TGF-β(1) ) were evaluated. Administration of fish oil and EtOH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF-κB activity, and expression of TNF-α, COX-2, and TGF-β(1) . Treatment with the thromboxane inhibitors ameliorated a certain level of the pathological and biochemical abnormalities. In particular, TXSI in addition to reducing necrosis, inflammation and fibrosis also decrease the severity of fatty liver. Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued EtOH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease.


Prognostic similarity between ovarian mucinous carcinoma with expansile invasion and ovarian mucinous borderline tumor: A retrospective analysis.
There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.


Role of CD5 molecular-like on hepatocellular carcinoma.
CD5L (CD5 molecular-like) plays an important role in lipid metabolism and immune regulation. This study aimed to investigate the roles of CD5L on liver hepatocellular carcinoma (LIHC). We analyzed the CD5L mRNA expression and its potential prognostic value based on The Cancer Genome Atlas and Gene Expression Omnibus databases. Immunohistochemical analysis was used to investigate the CD5L levels in LIHC tissues. Serum CD5L levels in LIHC were detected by enzyme-linked immunosorbent assay. Cell Counting Kit-8 (CCK-8) assay was used to investigate the effect of CD5L treatment on HepG2 and QSG-7701 cell proliferation. CD5L expression correlated genes were exhumed based on the LinkedOmics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for CD5L associated genes were performed. The correlation between CD5L and tumor immune infiltration was analyzed by using Tumor Immune Estimation Resource (TIMER) 2.0. CD5L mRNA and protein levels were significantly decreased in LIHC tumor tissue compared with non-tumor control tissues. Moreover, serum CD5L levels were significantly lower in LIHC patients than that in healthy subjects. Gene Expression Profiling Interactive Analysis 2 and Kaplan-Meier plotter analysis showed that a high-CD5L expression was correlated with favorable overall survival in LIHC patients, except the LIHC patients with hepatitis virus. CCK-8 results showed that CD5L treatment significantly decreased HepG2 cell proliferation in a concentration-dependent manner, and CD5L treatment had no effect on the proliferation of non-tumor hepatocyte line QSG-7701. CD5L associated genes were enriched in the immune response biological process, and CD5L expression levels were positively correlated with the immune infiltrates of CD8 + T cell and M1 macrophage cells but negatively correlated with CD4 + T cells and M0 macrophage cell infiltration. Exogenous CD5L inhibits cell proliferation of hepatocellular carcinoma. CD5L may act as a role of prognostic marker.


Effects of pravastatin on exercise electrocardiography test performance and cardiovascular mortality and morbidity in patients with hypercholesterolemia: Lipid Intervention Study in Kyoto.
The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A reductase inhibitor, pravastatin, on exercise electrocardiography (ECG) test performance and cardiovascular mortality and morbidity were compared with those of conventional lipid-lowering drugs in hypercholesterolemic patients with no history of myocardial infarction or stroke. One thousand two hundred and seventeen patients were randomly assigned with mean serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels of 6.98 +/- 0.91mmol/L, 2.08 +/- 1.87mmol/L, 1.38 +/- 0.44mmol/L, and 5.07 +/- 1.14 mmol/L, respectively, and received either pravastatin at a dose of 10-20mg/day (group P) or one of the conventional lipid-lowering drugs such as fibrates, nicotinic acid, and probucol (group C). The numbers of patients available for analysis in groups P and C were 305 and 278 at year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and 103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in serum LDL cholesterol levels was significantly greater (p<0.01) in group P (-24.3%) than in group C (-16.0%). Serum HDL cholesterol levels increased in group P (+11.6%), but decreased in group C (-0.3%) (p<0.01). There were no significant differences in the rate of patients who exhibited ischemic changes to exercise ECG test (ischemic responders) between the 2 groups. Coronary heart diseases (CHD) occurred in 6 patients in group P and 13 in group C; pravastatin significantly reduced CHD risk (reduction rate 0.369; 95% confidence interval 0.140-0.970; p<0.05). No significant differences existed between the treatment groups in terms of the number of strokes (group P, 6; group C, 7) or deaths unrelated to CHD (group P, 3; group C, 2). Although pravastatin did not improve the proportion of ischemic responders on exercise testing, it reduced CHD risk and serum LDL cholesterol levels more significantly than conventional lipid-lowering drugs without adversely affecting the risk of stroke and non-CHD death in hypercholesterolemic patients.


Search for additional replication terminators in the Bacillus subtilis 168 chromosome.
The Bacillus subtilis 168 chromosome is known to contain at least six DNA replication terminators in the terminus region of the chromosome. By using a degenerate DNA probe for the consensus terminator sequence and low-stringency hybridization conditions, several additional minor hybridizing bands were identified. DNA corresponding to the most intense of these bands was cloned and characterized. Although localized in the terminus region, it could not bind RTP and possibly represents a degenerate terminator. A search of the SubtiList database identified an additional terminator sequence in the terminus region, near glnA. It was shown to bind RTP and to function in blocking replication fork movement in a polar manner. Its orientation conformed to the replication fork trap arrangement of the other terminators. The low-stringency hybridization experiments failed to identify any terminus region-type terminators in the region of the chromosome where postinitiation control sequences (STer sites) are known to reside. The two most likely terminators in STer site regions, in terms of sequence similarity to terminus region terminators, were identified through sequence searching. They were synthesized and were found not to bind RTP under conditions that allowed binding to terminus region terminators. Neither did they elicit fork arrest, when present in a plasmid, under stringent conditions. It is concluded that the STer site terminators, at least the first two to the left of oriC, do not have the typical consensus A+B site makeup of terminus region terminators.


Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.
Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.


Fully scalable one-pot method for the production of phosphonic graphene derivatives.
Graphene oxide was functionalized with simultaneous reduction to produce phosphonated reduced graphene oxide in a novel, fully scalable, one-pot method. The phosphonic derivative of graphene was obtained through the reaction of graphene oxide with phosphorus trichloride in water. The newly synthesized reduced graphene oxide derivative was fully characterized by using spectroscopic methods along with thermal analysis. The morphology of the samples was examined by electron microscopy. The electrical studies revealed that the functionalized graphene derivative behaves in a way similar to chemically or thermally reduced graphene oxide, with an activation energy of 0.014 eV.


Summary of the British Transplantation Society Guidelines for Management of the Failing Kidney Transplant.
The British Transplantation Society "Guideline for Transplantation Management of the Failing Kidney Transplant" was published in May 2014. This is the first national guideline in this field. In line with previous guidelines published by the British Transplantation Society, the guideline has used the GRADE system to rate the strength of evidence and recommendations.This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the management of the failing kidney graft in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.


Crack propagation and arrests in gelatin hydrogels are linked to tip curvatures.
Gelatin hydrogels are attractive scaffold materials for tissue engineering applications as they provide motifs for cell attachment, undergo large deformations, and are tunable. Low toughness and brittle fractures however limit their use in load bearing applications. An investigation of crack tip processes and mechanisms of crack propagation is warranted to link fracture properties with material microstructure. We cross-linked gelatin using glutaraldehyde to obtain low cross-linked control hydrogels and used an additional cross-linker, methylglyoxal, to fabricate MGO hydrogels with higher cross-links. We quantified fractures in the gelatin hydrogels from both groups using pure shear notch tests and characterized strain fields near the crack tip using 2-D digital image correlation. We used a numerical method based on Taylor's series expansion to measure the crack tip curvatures in the hydrogels. This method captures tip curvatures better than the parabolic method routinely used in studies. Results from our study show that cracks in gelatin hydrogels underwent frequent arrests during propagation through the specimen width in both groups. MGO hydrogels had 85% enhanced fracture toughness and a significantly higher number of stalls compared to the control group. Crack initiations following stalls in the sample correlated with low tip curvatures in both hydrogel groups. We also show that mechanical stretching blunts the crack tip before crack propagation; the degree of blunting was independent of the cross-link density and elastic modulus of the gelatin hydrogels. These results show a link between crack growth and the tip curvature in cross-linked gelatin hydrogels, and offer potential insights for the development of tougher hydrogels.


Gene cloning, molecular modeling, and phylogenetics of serine protease P32 and serine carboxypeptidase SCP1 from nematophagous fungi Pochonia rubescens and Pochonia chlamydosporia.
The fungi Pochonia chlamydosporia and Pochonia rubescens are parasites of nematode eggs and thus are biocontrol agents of nematodes. Proteolytic enzymes such as the S8 proteases VCP1 and P32, secreted during the pathogenesis of nematode eggs, are major virulence factors in these fungi. Recently, expression of these enzymes and of SCP1, a new putative S10 carboxypeptidase, was detected during endophytic colonization of barley roots by these fungi. In our study, we cloned the genomic and mRNA sequences encoding P32 from P. rubescens and SCP1 from P. chlamydosporia. P32 showed a high homology with the serine proteases Pr1A from the entomopathogenic fungus Metarhizium anisopliae and VCP1 from P. chlamydosporia (86% and 76% identity, respectively). However, the catalytic pocket of P32 showed differences in the amino acids of the substrate-recognition sites compared with the catalytic pockets of Pr1A and VCP1 proteases. Phylogenetic analysis of P32 suggests a common ancestor with protease Pr1A. SCP1 displays the characteristic features of a member of the S10 family of serine proteases. Phylogenetic comparisons show that SCP1 and other carboxypeptidases from filamentous fungi have an origin different from that of yeast vacuolar serine carboxypeptidases. Understanding protease genes from nematophagous fungi is crucial for enhancing the biocontrol potential of these organisms.


Australia's First Official Illicit Pill Testing at Canberra's Groovin' the Moo Music Festival: Legal Hurdles and Future Prospects.
The first official pill testing at an Australian music festival was conducted at Groovin' The Moo in Canberra on 29 April 2018. As the trial was the first of its kind in Australia, it was not without legal hurdles and uncertainty. Primarily, there was concern over the legal consequences for patrons participating in the pill testing, as well as the legal liability of those facilitating and conducting the testing. This article will discuss the legal hurdles that were overcome in order to facilitate the trial, and the future consequences and position of pill testing at Australian festivals.


In vitro evaluation of chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid: Cytotoxicity, antioxidant activity, and antimicrobial activity.
Chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid (CCAL) was a novel multifunctional nano delivery system exhibited long-term stability at room temperature and high encapsulation efficiency. Which containing two kinds of antioxidants (coenzyme Q10 and alpha-lipoic acid) and two antibacterial agents (chitosan and alpha-lipoic acid). However, the further biocompatibility, such as cytotoxicity and antioxidant activity, and antimicrobial activity of CCAL, has not been systematically evaluated. This study aims to evaluate the cytotoxicity, antioxidant activity and antimicrobial activity of CCAL. This article evaluated the in vitro cytotoxicity and antioxidant activity of CCAL by CCK8 assay, and antimicrobial activity on Staphylococcus aureus and Escherichia coli was investigated. For antioxidant activity study, CCAL displayed significant antioxidant effect when compared with control group (P<.01). Finally, CCAL also exhibited antimicrobial activity, and CCAL showed stronger bactericidal effect with Gram-positive bacteria than Gram-negative bacteria. CCAL could be a potential antioxidant delivery system for cosmetics or pharmaceuticals without cytotoxicity and artificial preservatives free.


[Effects of calcium antagonist, angiotensin-converting enzyme inhibitors and beta-blocker on hemodynamic and sympathetic nerve responses to exercise in essential hypertension].
To investigate the effects of antihypertensive drugs on hemodynamic and sympathetic nerve responses to exercise, graded ergometer exercise tests were performed before and after two-week administration of nifedipine, captopril and metoprolol in 18 patients with essential hypertension. The arterial pressure, heart rates (HR), and left ventricular functions as obtained by echocardiography, and the plasma norepinephrine (PNE) levels, were evaluated at rest and during submaximal exercise before and after two-week treatment with nifedipine (40 mg/day, 5 cases), captopril (37.5-75 mg/day, 6 cases) and metoprolol (60 mg/day, 7 cases). These 3 drugs significantly reduced systolic (SBP) and diastolic (DBP) blood pressures but caused no significant changes in resting PNE levels. Nifedipine produced no significant changes in HR and cardiac output (CO) at rest, but augmented the increase in HR (delta HR) and SBP (delta SBP) during submaximal exercise. The increase in PNE (delta PNE) was also augmented by nifedipine. Captopril reduced left ventricular end-diastolic volume and CO without changes in HR and fractional shortening (FS) at rest; whereas, it did not affect delta HR, delta CO, delta SBP or delta PNE during exercise. Metoprolol reduced HR and CO at rest, and also resulted in a decrease in delta FS and delta CO during submaximal exercise. delta SBP was unchanged and delta PNE was increased by treatment with metoprolol. These results indicate that, in hypertensive subjects, the effects on the hemodynamic and sympathetic nerve responses to exercise are different among these 3 antihypertensive drugs despite their identical effects on blood pressure.


Addressing safeguarding concerns through better communication.
A common theme running through child protection and safeguarding publications concerns the problems and consequences of ineffective communication between agencies. This article looks at why communication may, at times, break down and offers suggestions on how to overcome the barriers that prevent good communication. While the article does not offer definitive solutions, it highlights the potential barriers, with the intention of helping front line staff reflect on their practice and identify ways to improve their communication skills and those of their teams. The article focuses on day surgery, but the issues are relevant to all acute settings in which children receive care.


Relationship between different skeletal facial types and anterior alveolar bone thickness with cone-beam computed tomography in an Asian population.
To investigate the relationship between different skeletal facial types and anterior alveolar bone thickness with cone-beam computed tomography (CBCT) in an Asian population. A total of 130 patients with 1,560 healthy anterior teeth were enrolled. On three-dimensional reconstructed images, Frankfurt-mandibular plane angle (FMA) value and angle formed by subspinale, nasion, and supramental (ANB) value were measured, and subjects were categorized into different groups based on their vertical skeletal patterns as well as sagittal jaw relationships. For each tooth, the thickness of alveolar bone was measured at three locations: 1, 3, and 5 mm apical to alveolar bone crest. Descriptive statistics were used. Kruskal-Wallis test, one-way ANOVA, and independent-samples t-test were used for further analysis. Men's maxillary anterior teeth's lingual alveolar bone thickness was significantly greater than women's (P<0.05). Strong correlations were found between vertical skeletal patterns and lingual alveolar bone thickness of maxillary/mandibular anterior teeth (R2=0.302, P<0.01 in the maxilla; R2=0.311, P<0.01 in the mandible). However, no significant difference was shown in the alveolar bone thickness among people with different sagittal bone profiles. The lingual alveolar bone of the maxillary anterior teeth is thicker in males than in females. With the increase of FMA, the anterior alveolar bone gradually became thinner.


Prevalence of antibodies against Ornithobacterium rhinotracheale in broilers and breeders in Southern Brazil.
In this investigation, we determined the prevalence of the Ornithobacerium rhinotracheale (ORT) infection in broilers and broiler breeders in southern Brazil. We also correlated the presence of antibodies in broilers with performance. Sera from 1550 broilers from 50 flocks were collected during the slaughter time in nine companies with federal veterinary inspection of the state of Rio Grande do Sul. Sera from 480 meat-type breeders of 40 flocks from 14 companies in southern Brazil were also analyzed by enzyme-linked immunosorbent assay, and the prevalence of antibodies was determined. The prevalence of ORT antibodies in broiler flocks was 63.83%, but in each individual flock only 6.52% of the birds were positive. The prevalence in broiler breeder flocks was 100.00%, and in each individual flock 94.62% of the birds were positive. There was a positive correlation between the presence of antibodies to ORT and decreased body weight in broilers. There was no significant correlation between presence of antibodies to ORT and age, lineage, efficiency index, feed conversion, and mortality. There was a positive correlation between the presence of respiratory signs and antibodies to ORT, although the reverse correlation was not significant. These results confirm that ORT is present and widespread in broilers and broiler breeders in southern Brazil.


Zen Mountains: An Illusion of Perceptual Transparency.
The human visual system is usually very successful in segmenting complex natural scenes. During a trip to the Nepalese Himalayas, we observed an impossible example of Nature's beauty: "transparent" mountains. The scene is captured in a photograph in which a pair of mountain peaks viewed in the far distance appear to be transparent. This illusion results from a fortuitous combination of lighting and scene conditions, which induce an erroneous integration of multiple segmentation cues. The illusion unites three classic principles of visual perception: Metelli's constraints for perceptual transparency, the Gestalt principle of good continuation, and depth from contrast and atmospheric scattering. This real-world "failure" of scene segmentation reinforces how ingeniously the human visual system typically integrates complex sources of perceptual information using heuristics based on likelihood as shortcuts to veridical perception.


Relationship between catheter care and catheter-associated urinary tract infection at Japanese general hospitals: a prospective observational study.
The risk factors for catheter-associated urinary tract infections (CAUTIs) that are associated with catheter care have not been examined in detail by prospective studies or randomised clinical trials. To examine the patterns of catheter care and to identify the CAUTI risk factors associated with catheter care. Prospective observational study. Between January and December 2004, 555 adult patients who were catheterised for 3 days in five general hospitals in Japan were surveyed. One researcher collected the following data twice a week: catheter insertion method, catheter management, and signs and symptoms of urinary tract infections. The relative risk exceeding 1 by the Poisson regression were selected for Cox proportional hazard analysis in order to calculate adjusted risks. In addition, expected reductions in the incidence of CAUTIs by elimination of the risk factors were estimated using the population attributable risk percent. The mean duration of catheterisation was 25 days. The overall incidence of CAUTIs was 3.9 cases per 1000-device days; the incidence of CAUTIs ranged from 0.6 to 7.2 cases per 1000-device days among the five hospitals. Only fecal incontinent patients were analysed since they accounted for 94% of the CAUTI cases. In the univariate analysis, the silver-alloy catheter, which contains antimicrobial property, emerged as a potential risk. Since silver-alloy catheters were used in only one hospital, silver-alloy catheter care was compared with that of the other types of catheter, and a significantly higher percentage of inappropriate care was observed. In the final Cox model, two variables remained: 'non-pre-connected closed system (standard system)' (RR 2.35, 95%CI 1.20-4.60, p = 0.013) and 'no daily cleansing of the perineal area' (RR 2.49, 95%CI 1.32-4.69, p = 0.005). The population attributable risk percent suggested that the use of a 'pre-connected closed system' and 'daily cleansing of the perineal area' could reduce the incidence of CAUTIs by nearly 50%. Our investigation identified fecal incontinence as the major risk factor for CAUTIs in the study population. However, attributable risk percent indicates that the implementation of two basic elements of catheter care could reduce CAUTIs by nearly 50%. The hospital using silver-alloy catheters had the highest CAUTI rates, strongly suggesting the hazards of relying on the antimicrobial property of silver and the resultant laxity in care.


[Swyer syndrome. Apropos of a new case of pure gonadal dysgenesis with Karyotype 46 XY].
The authors describe a case they have personally seen of pure gonadal dysgenesis with caryotype 46 XY (Swyers' syndrome) in which they found absence of HY antigen. They analysed the descriptions in the literature about this syndrome and show how this antigen is responsible for testicular differentiation. They show the place this syndrome has in the group of syndromes of bands and once again draw attention that there is a great risk of gonadoblastoma development when the Y chromosome is present and especially when the HY antigen is present. This means that these dysgenetic gonads should be removed surgically.


A Transcriptomic Survey of Ion Channel-Based Conotoxins in the Chinese Tubular Cone Snail (Conus betulinus).
Conotoxins in the venom of cone snails (Conus spp.) are a mixture of active peptides that work as blockers, agonists, antagonists, or inactivators of various ion channels. Recently we reported a high-throughput method to identify 215 conotoxin transcripts from the Chinese tubular cone snail, C. betulinus. Here, based on the previous datasets of four transcriptomes from three venom ducts and one venom bulb, we explored ion channel-based conotoxins and predicted their related ion channel receptors. Homologous analysis was also performed for the most abundant ion channel protein, voltage-gated potassium (Kv; with Kv1.1 as the representative), and the most studied ion channel receptor, nicotinic acetylcholine receptor (nAChR; with α2-nAChR as the representative), in different animals. Our transcriptomic survey demonstrated that ion channel-based conotoxins and related ion channel proteins/receptors transcribe differentially between the venom duct and the venom bulb. In addition, we observed that putative κ-conotoxins were the most common conotoxins with the highest transcription levels in the examined C. betulinus. Furthermore, Kv1.1 and α2-nAChR were conserved in their functional domains of deduced protein sequences, suggesting similar effects of conotoxins via the ion channels in various species, including human beings. In a word, our present work suggests a high-throughput way to develop conotoxins as potential drugs for treatment of ion channel-associated human diseases.


Evidence for altered configural body processing in women at risk of disorders characterized by body image disturbance.
Two studies were conducted to assess appearance-related visual processing mechanisms in populations at risk of disorders characterized by body image disturbance. Using inverted stimuli, Experiment 1 assessed visual processing mechanisms associated with body, face, and house viewing in adolescents. Experiment 2 applied the same protocol to assess appearance-related configural processing in high- and low-risk adolescent women, and women recovering from disorders characterized by body image disturbance. Experiment 1 found evidence for typical configural face and body processing, although adolescent women reported higher levels of body image concern (BIC) and self-objectified to a greater extent than adolescent men. In Experiment 2, typical body inversion effects were seen in the low-risk group, whilst there was some evidence to suggest a disruption to the configural processing of body stimuli in high-risk adolescents and in women recovering from body image disorders. Women in recovery were also quicker to respond to all stimuli, whilst high-risk adolescents took longer to respond to bodies than to other stimuli. Configural face processing was intact in all groups, and effects did not directly relate to BIC or self-objectification. These findings have implications for future research looking to inform early interventions and treatment, suggesting that there could be a tendency to visually process individual body parts at the expense of the whole-body form in women at risk of developing body image disorders, as well as those in recovery.


An animal model for chronic ulceration.
Few techniques are available for the study of persistent ulceration. In this report we describe a suitable animal model. Intracutaneous injection of sodium tetradecyl sulphate (STD) in guinea-pig flank skin caused a reproducibly sized and shaped superficial ulcer that healed approximately three times more slowly than punch biopsies of comparable size. Histological, immunofluorescent and autoradiographic studies showed that it possesses many of the morphological and kinetic features of human stasis ulceration. STD ulcers treated with a streptokinase/streptodornase solution healed with less slough and tended to re-epithelialize more rapidly than controls, but ulcers treated with dextran polymer beads or a stabilized hydrogen peroxide cream healed at the same rate as their control.


Estimating structure of multivariate systems with genetic algorithms for nonlinear prediction.
Although we can often observe time-series data of many elements, these elements do not always interact with each other. This paper proposes a scheme to estimate the interdependency among observed elements only by time-series data, which is useful for selecting essential elements to optimize multivariate prediction model. Because this estimation is a sort of combinatorial optimization problems, we applied the genetic algorithm as a method to moderate this problem. Through some simulations, we confirmed performance of our method, which can identify interaction of multivariate system and can improve its prediction accuracy. Especially, our method can be applied to predict real foreign-exchange markets even if system has nonstational property and its structure changes dynamically.


Draft Genome Sequences of Thermophiles Isolated from Yates Shaft, a Deep-Subsurface Environment.
The whole-genome sequences of seven thermophiles that could grow at >55°C, but not at 37°C, were generated. These thermophilic bacteria will play a useful role as model microorganisms, and analyzing their genomes will help to understand the observed production of novel bioactive compounds, including thermozymes and macromolecules.


Layperson knowledge of heart attacks in the state of Georgia, USA.
A survey of 200 residents of the state of Georgia, United States was conducted to assess the knowledge of heart attacks. Results depict that Georgia residents have only a basic understanding of heart attack symptoms suggesting the need for medical professionals to spend more time educating their patients on their health in simple terms so that the patients can be knowledgeable on their personal health.


[Space-occupying tumor lesions of the spinal column. An analysis of the material submitted to the Westphalia Bone Tumor Register].
308 tumorous lesions of the spine were identified in the material submitted to the bone tumour register in Münster for recording. Histological examination revealed metastases in 38.6% primary bone tumours in 33.1%, tumour-like lesions in 10% and haematological and lymphatic disease in 13%. 5.3% of all lesions could not be classified in these groups. Primary bone tumours were seen more often than metastases in the cervical spine, the sacrum and the coccyx. 54.9% of the primary bone tumours of the spine were benign. However, only 31.2% of all the tumorous lesions of the spine, metastases included, were benign. The portion of malignant disorders increased with increasing age. The risk of having a malignant spine tumour was 5.9% in patients under 10 years of age but 92.3% in patients in the seventh decade.


Improved Methods for Estimating Flood Depth Exceedances Within Storm Surge Protection Systems.
Contemporary studies conducted by the U.S. Army Corps of Engineers estimate probability distributions of flooding on the interior of ring levee systems by estimating surge exceedances at points along levee system boundaries, calculating overtopping volumes generated by this surface, then passing the resulting volumes of water through a drainage model to calculate interior flood depths. This approach may not accurately represent the exceedance probability of flood depths within the system interior; a storm producing 100-year surge at one point is unlikely to simultaneously produce 100-year surge levels everywhere around the system exterior. A conceptually preferred approach estimates surge and waves associated with a large set of storms. Each storm is run through the interior model separately, and the resulting flood depths are weighted by a parameterized likelihood of each synthetic storm. This results in an empirical distribution of flood depths accounting for geospatial variation in any individual storm's characteristics. This method can also better account for the probability of levee breaches or other system failures. The two methods can produce different estimates of flood depth exceedances and damage when applied to storm surge flooding in coastal Louisiana. Even differences in flood depth exceedances of less than 0.2 m can still produce large differences in projected damage. This article identifies and discusses differences in estimated flood depths and damage produced by each method within multiple Louisiana protection systems. The novel coupled dynamics approach represents a step toward enabling risk-based design standards.


Malignant invasion of the cerebrospinal fluid in adult and paediatric patients with haematological and solid malignancies: a monocentric retrospective study.
In this study, we describe the clinical presentation, the cerebrospinal fluid (CSF) characteristics and outcome of children and adults with leptomeningeal invasion due to haematological and solid malignancies. Routine CSF samples analyzed from 2008 to 2018 at our institution were retrospectively reviewed for the presence of malignant cells based on cytomorphological analysis. Leptomeningeal invasion was identified in 212 patients: 45 children versus 167 adults, and 92 haematological versus 120 solid malignancies. Leukaemic invasion in childhood was mainly due to ALL, and lymphoma invasion was often due to a high-grade B-cell lymphoma in adults. Metastatic invasion by solid tumours was almost exclusively seen in adults. Patients suffered most frequently from cranial neuropathy and headache (both 32%), while asymptomatic presentations were seen mainly in children (33%) and haematological malignancies (17%). Laboratory CSF parameters often showed an elevated WBC count (87%), total protein (74%) and lactate (76%) and a decreased glucose (77%). These deviations were especially found in solid malignancies (>84%) and adults (>82%). Brain and/or spinal cord imaging was more often suggestive for the leptomeningeal invasion in solid than in haematological malignancies (86% vs. 46%). The 5-year overall survival (OS) rates for patients with haematological and solid malignancies were 21.5% and 5.9%, respectively. The 5-year OS rate for children (55.6%) was significantly better than for adults (3.5%). Leptomeningeal invasion is more often asymptomatic, and CSF parameters and imaging are more often normal in children and haematological malignancies than in adults and solid malignancies, possibly leading to underdiagnosis.


An object-oriented tool for the generation and management of multimedia patient folders.
Computer-based patient folders are evolving from the simple reproduction of traditional paper documents toward active tools, able to support the whole diagnostic and therapeutic process. The advent of multimediality has given emphasys to the idea of computerized folder, i.e. a collection of heterogeneous kinds of documents pertaining different media. In this paper we present a tool implementing generation and management of multimedia patient folders showing its architecture and functionalities and the innovative interaction paradigms adopted. The tool realized allows medical users to choose the concepts desired in their target application and generates a customized patient folder management system by means of a friendly interface and without the need of a programming language. The system automatically created can be effectively employed for reporting and storing clinical cases.


Altered cerebrovascular responsiveness to N-methyl-D-aspartate after asphyxia in piglets.
We examined effects of prior asphyxia and reventilation on pial arteriolar responses to arterial hypercapnia, topical application of forskolin, and topical application of N-methyl-D-aspartate (NMDA) in newborn pigs. Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. After baseline diameter was determined, the respirator was turned off for 10 min. Then the respirator was turned on, and the piglet was ventilated for 4 h. At 1, 2, and 4 h after asphyxia, arteriolar diameter was determined during control conditions and during arterial hypercapnia (inspiration of 10% CO2 in air; n = 4), topical application of 2.4 x 10(-8) M forskolin (n = 6), and topical application of 10(-5) M NMDA (n = 6). At 1 h after asphyxia, arterial hypercapnia dilated pial arterioles by 39 +/- 3%, topical forskolin dilated pial arterioles by 24 +/- 3%, and NMDA dilated pial arterioles by 10 +/- 1%. For arterial hypercapnia and forskolin application, arteriolar responses were not different from 1 h at 2 and 4 h postasphyxia. In contrast, for NMDA, arteriolar responses were greater at 2 h (23 +/- 6%) and 4 h (30 +/- 5%) than at 1 h. In time-control animals, NMDA dilated arterioles by 20 +/- 5% at 1 h, by 24 +/- 8% at 2 h, and by 21 +/- 4% at 4 h (n = 5). Indomethacin administration (5 mg/kg iv) before asphyxia resulted in a 23 +/- 3% arteriolar dilation in response to NMDA at 1 h (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)


Multirhythmicity generated by slow variable diffusion in a ring of relaxation oscillators and noise-induced abnormal interspike variability.
The deterministic and noise-dependent dynamics of a ring of three Ohmically coupled electronic relaxation oscillators are considered by means of numerical simulations. Each isolated oscillator is described by a set of two ordinary differential equations with very different characteristic times. The emergence of the limit cycle via the Hopf bifurcation results from the N-shaped current-versus-voltage characteristic of the nonlinear resistor. The phase diagram is calculated for a ring of three such oscillators in the presence of small detuning. Special attention is focused on two parameter areas, one near a transition to the homogeneous and the other near the inhomogeneous stable steady state. Along with other nontrivial limit cycles, essentially asymmetrical limit cycles termed dynamic traps may arise in these two areas. A dynamic trap is a regime in which one or two oscillators do not perform full-amplitude oscillations and, correspondingly, do not generate spikes. The interspike interval (ISI) distribution in the presence of noise is calculated as a function of the coupling strength in both areas of the parameter plane. The distributions are extremely polymodal near the homogeneous steady state even if the in-phase limit cycle is dominating. The origins of this abnormal enhancement of ISI variability are discussed in detail. A similar analysis shows that nontrivial periodic attractors are observable in the vicinity of the inhomogeneous stable steady states only if the level of noise is relatively low. In this case, the dominance of the in-phase limit cycle basin results in an almost unimodal distribution of interspike intervals.


Female Chess Players Outperform Expectations When Playing Men.
Stereotype threat has been offered as a potential explanation of differential performance between men and women in some cognitive domains. Questions remain about the reliability and generality of the phenomenon. Previous studies have found that stereotype threat is activated in female chess players when they are matched against male players. I used data from over 5.5 million games of international tournament chess and found no evidence of a stereotype-threat effect. In fact, female players outperform expectations when playing men. Further analysis showed no influence of degree of challenge, player age, nor prevalence of female role models in national chess leagues on differences in performance when women play men versus when they play women. Though this analysis contradicts one specific mechanism of influence of gender stereotypes, the persistent differences between male and female players suggest that systematic factors do exist and remain to be uncovered.


Developmental expression of myelin proteins by oligodendrocytes in the CNS of trout.
Using immunohistochemical techniques, the pattern of cytoplasmic staining and the temporal order of expression of 5 major myelin components of oligodendrocytes were studied in the developing central nervous system of trout. The two myelin glycoproteins, IP1 and IP2, in the cytoplasm of glial cells showed a granular pattern of immunostaining, whereas the 36K protein was homogeneously distributed. Analysis of freshly dissociated cells during early stages of myelinogenesis revealed a constant chronological sequence of expression of myelin proteins by the oligodendrocytes: glycoprotein IP2 was the first protein to appear during glial development together with the galactocerebroside GalC at stage 28 followed by the 36K at stage 30 and finally IP1 at stage 32. The deposition of myelin proteins into the nascent myelin sheath occurred in the same chronological order as their expression by oligodendrocytes. Moreover myelin basic protein, which was not detectable in glial cells, on tissue sections was found to appear in parallel with IP2.


Health and economic costs of physical inactivity.
Physical inactivity has reached epidemic levels in developed countries and is being recognized as a serious public health problem. Recent evidence shows a high percentages of individuals worldwide who are physically inactive, i.e. do not achieve the WHO's present recommendation of 150 minutes of moderate to vigorous intensity per week in addition to usual activities. Living in sedentary lifestyle is one of the leading causes of deaths and a high risk factor for several chronic diseases, like cancer, cardiovascular disease, diabetes type 2, and osteoporosis. This article summarizes evidence for relative risk of the civilization diseases attributable to physical inactivity and the most important conclusions available from the recent investigations computing the economic costs specific to physical inactivity. The findings provide health and economic arguments needed for people to understand the meaning of a sedentary lifestyle. This may be also useful for public health policy in the creation of programmes for prevention of physical inactivity.


Fibrinolytic effect of a particular glycosaminoglycan (endoglycan) per os on normals and in patients with chronic artery disease.
Endoglycan, a heparan-dermatan sulphate association, is a highly purified heparinoid extracted from porcine intestinal mucosa. The aim of our study was to investigate the fibrinolytic system in a group of healthy controls and vascular disease patients, before and after endoglycan administration "per os". All the patients had a reduced basal fibrinolytic activity. The tests carried out were PT, PTT, FDP, Euglobulin Lysis Time (ELT), fibrinogen, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin and t-PA activity assayed with a chromogenic method. After endoglycan administration, we have shown a significant shortening of ELT with complete normalization during the treatment. A fibrinogen decrease and either plasminogen or alpha 2-antiplasmin increase was seen. This was shown in normals too, however to a lesser extent. During therapy most of the healthy subjects, but only some patients, showed increased t-PA levels. Before and during treatment, significantly higher t-PA levels were seen in the control group as compared to the patients group. Reduced t-PA release was seen in our vascular disease patients. In conclusion, endoglycan "per os" appears to exert a stimulatory effect on the fibrinolytic system.


Expression of cancer-testis antigens in esophageal cancer and their progress in immunotherapy.
Esophageal cancer is a common disease in China with low survival rate due to no obvious early symptoms and lack of effective screening strategies. Traditional treatments usually do not produce desirable results in patients with advanced esophageal cancer, so immunotherapy which relies on tumor-related antigens is needed to combat low survival rates effectively. Cancer-testis antigens (CTA), a large family of tumor-related antigens, have a strong in vivo immunogenicity and tumor-restricted expressing patterns in normal adult tissues. These two characteristics are ideal features of anticancer immunotherapy targets and, therefore, promoted the development of some studies of CTA-based therapy. To provide ideas for the role of the cancer-testis antigens MAGE-A, NY-ESO-1, LAGE-1, and TTK in esophageal cancer, we summarized their expression, prognostic value, and development in immunotherapy. The relevant literature from PubMed is reviewed in this study. In esophageal cancer, although the relationship between expression of MAGE-A, NY-ESO-1, LAGE-1, and TTK and prognosis value is still in a controversial situation, MAGE-A, NY-ESO-1, LAGE-1, and TTK are highly expressed and can induce specific CTL cells to produce particular killing effect on tumor cells, and some clinical trials have demonstrated that immunotherapy for esophageal cancer patients is effective and safe, which provides a new therapeutic strategy for the treatment of esophageal cancer in the future. In this review, we summarize expression and prognostic value of MAGE-A, NY-ESO-1, LAGE-1, and TTK in esophageal cancer and point out recent advances in immunotherapy about them.


An association between inflammatory state and left ventricular hypertrophy in hemodialysis patients.
This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1beta, IL-6, TNF-alpha, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r=0.556, p=0.001), diastolic BP (r=0.474, p=0.004), and serum levels of TNF-alpha (r=0.446, p=0.009). Multiple regression analysis showed that systolic BP and TNF-alpha levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 +/- 8.7 vs. 7.3 +/- 0.7 pg/ mL, p=0.001). Predialysis serum levels of TNF-alpha in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 +/- 3 vs. 7 +/- 1.45 pg/mL, respectively, p>0.05). However, serum levels of IL-6 and TNF-alpha significantly elevated after HD, when compared to predialysis levels (from 15.7 +/- 8.7 to 17.8 +/- 9.5 pg/mL, p=0.001 and from 8.3 +/- 3.0 to 9.9 +/- 3.5 pg/mL p=0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-alpha in particular, seem to be associated with LVH in ESRD patients.


Neonatal size and infant mortality at high altitude in the western Himalaya.
A prospective study was undertaken in Ladakh, India, a high-altitude region of the Himalaya, to investigate the effects of small average birth size on neonatal mortality. While such studies exist from high-altitude regions of the New World and shed light on the adaptive status of high-altitude-dwelling populations there, this is the first to examine this relationship in the Himalaya. In a sample of 168 newborns, birthweight and other anthropometric measurements were reduced relative to Andean and Tibetan newborns. Logistic regression and hazard analysis showed that neonatal biological characteristics such as weight, fatness, and circumferences were important predictors of survival probabilities of infants, especially in the neonatal period. Low Rohrer's Ponderal Index (PI) was particularly strongly related to poor survival outcome. Males and females showed no significant differences in mortality risk. Data derived from reproductive histories revealed that neonatal mortality accounted for 70-80% of total infant mortality in Ladakh. Compared to other high-altitude studies, small newborn size in Ladakh was associated with much higher mortality risks; mortality risk rose dramatically with birthweights below the mean (2,764 grams), which characterized 50% of all newborns. It is argued that newborns in Ladakh are subject to strong directional selective forces that favor higher birthweights that incur lower risks of neonatal mortality, while Andean infants are subject to relatively mild selection pressure at both ends of the birthweight distribution. Given the overall small size at birth of Ladakhi newborns and the poor survival outcomes of newborns below the mean, it is suggested that this population is less well adapted in a biological sense to the stresses inherent in this high-altitude environment than are Andean populations, perhaps due to the relatively recent colonization of the area and the substantial genetic admixture that has occurred in the past.


Increased insulin-stimulated Akt pSer473 and cytosolic SHP2 protein abundance in human skeletal muscle following acute exercise and short-term training.
The purpose of the present study was to determine in human skeletal muscle whether a single exercise bout and 7 days of consecutive endurance (cycling) training 1) increased insulin-stimulated Akt pSer(473) and 2) altered the abundance of the protein tyrosine phosphatases (PTPases), PTP1B and SHP2. In healthy, untrained men (n = 8; 24 +/- 1 yr), glucose infusion rate during a hyperinsulinemic euglycemic clamp, when compared with untrained values, was not improved 24 h following a single 60-min bout of endurance cycling but was significantly increased ( approximately 30%; P < 0.05) 24 h following completion of 7 days of exercise training. Insulin-stimulated Akt pSer(473) was approximately 50% higher (P < 0.05) 24 h following the acute bout of exercise, with this effect remaining after 7 days of training (P < 0.05). Insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation were not altered 24 h after acute exercise and short-term training. Insulin did not acutely regulate the localization of the PTPases, PTP1B or SHP2, although cytosolic protein abundance of SHP2 was increased (P < 0.05; main effect) 24 h following acute exercise and short-term training. In conclusion, insulin-sensitive Akt pSer(473) and cytosolic SHP2 protein abundance are higher after acute exercise and short-term training, and this effect appears largely due to the residual effects of the last bout of prior exercise. The significance of exercise-induced alterations in cytosolic SHP2 and insulin-stimulated Akt pSer(473) on the improvement in insulin sensitivity requires further elucidation.


Efficient stimuli for evoking auditory steady-state responses.
To compare the magnitudes of the steady-state responses evoked by several types of stimuli, and the times required to recognize these responses as significant. In the first two experiments, we examined auditory steady-state responses to pure tones, broadband noise and band-limited noise. The stimuli were amplitude modulated in the 75 to 100 Hz range with sinusoidal or exponential envelopes. A third experiment investigated the effects of exponential envelopes on the responses to broadband noise. The final experiment examined auditory steady-state responses evoked by rapidly presented transient stimuli, such as clicks, brief tones and brief noise-bursts. All stimuli were presented dichotically at intensities 30 to 50 dB above behavioral thresholds. The subjects were adults, who drowsed or slept during the recording sessions. The responses to the noise were larger than the responses to the tones. At an intensity of 32 dB nHL, the average amount of time needed to obtain significant responses for the amplitude-modulated noise was 43 sec and the maximum time was 2 minutes. The average time for pure tone stimuli was approximately 2 minutes but 25% of the responses remained undetected after 5 minutes. Combining the responses to all the frequency-specific stimuli showed results similar to using noise stimuli. Using exponential envelopes did not increase response amplitudes for noise stimuli. At 45 dB nHL, the steady-state responses to clicks and other transient stimuli were larger than responses to the broadband noise. The average time to detect steady-state responses to transient stimuli was approximately 20 sec, which was a little faster than for amplitude modulated noise. Auditory steady-state potentials evoked by amplitude modulated noise or transient stimuli might be useful in providing rapid and objective tests of hearing during screening procedures. Another approach might be to record responses to multiple frequency-specific stimuli and to evaluate the combined responses for a rapid indication that some hearing is present.


The role of long non-coding RNAs and downstream signaling pathways in leukemia progression.
The study of long non-coding RNAs (lncRNA) is a newly established field and our knowledge about them is rapidly growing. These kinds of RNAs are unchanged parts of the genome throughout evolution, that modulate cell growth, differentiation, and apoptosis during diverse physiological and pathological processes including leukemia development. They have the capability to be useful biomarkers for the diagnosis, clinical typing, prognosis, as well as potential therapeutic targets. In this study, we summarized the role of lncRNAs in the expression and function of white blood cells and oncogenic transformation into four main types of leukemia.


Expert panels as a reference standard in orthodontic research: An assessment of published methods and reporting.
The aim of this study was to investigate the expert panel methodology applied in orthodontics and its reporting quality. Additionally, the relationship between the reporting quality and a range of variables was explored. PubMed was searched for orthodontic studies in which the final diagnosis or assessment was made by 2 or more experts published up to March 16, 2015. Reporting quality assessment was conducted using an established modified checklist. The relationship between potential predictors and the total score was assessed using univariable linear regression. We identified 237 studies with a mean score of 9.97 (SD, 1.12) out of a maximum of 15. Critical information about panel methodology was missing in all studies. The panel composition differed substantially across studies, ranging from 2 to 646 panel members, with large variations in the expertise represented. Only 17 studies (7.2%) reported sample size calculations to justify the panel size. Panel members were partly blinded in 65 (27.4%) studies. Most studies failed to report which statistic was used to compute intrarater (65.8%) and interrater (66.2%) agreements. Journal type (nonorthodontic: β, 0.23; 95% CI, -0.07 to 0.54 compared with orthodontic), publication year (β, 0; 95% CI, -0.02 to 0.02 for each additional year), number of authors (1-3: β, 0.30; 95% CI, -0.13 to 0.74 compared with at least 6; 4-5: β, 0.18; 95% CI, -0.29 to 0.33 compared with at least 6), and number of centers involved (single: β, 0.20; 95% CI, -0.14 to 0.54 compared with multicenter) were not significant predictors of improved reporting. Studies published in Asia and Australia had significantly lower scores compared with those published in Europe (β, -0.54; 95% CI, -0.92 to -0.17). Formal guidelines on methodology and reporting of studies involving expert panels are required.


Supervised hashing using graph cuts and boosted decision trees.
To build large-scale query-by-example image retrieval systems, embedding image features into a binary Hamming space provides great benefits. Supervised hashing aims to map the original features to compact binary codes that are able to preserve label based similarity in the binary Hamming space. Most existing approaches apply a single form of hash function, and an optimization process which is typically deeply coupled to this specific form. This tight coupling restricts the flexibility of those methods, and can result in complex optimization problems that are difficult to solve. In this work we proffer a flexible yet simple framework that is able to accommodate different types of loss functions and hash functions. The proposed framework allows a number of existing approaches to hashing to be placed in context, and simplifies the development of new problem-specific hashing methods. Our framework decomposes the hashing learning problem into two steps: binary code (hash bit) learning and hash function learning. The first step can typically be formulated as binary quadratic problems, and the second step can be accomplished by training a standard binary classifier. For solving large-scale binary code inference, we show how it is possible to ensure that the binary quadratic problems are submodular such that efficient graph cut methods may be used. To achieve efficiency as well as efficacy on large-scale high-dimensional data, we propose to use boosted decision trees as the hash functions, which are nonlinear, highly descriptive, and are very fast to train and evaluate. Experiments demonstrate that the proposed method significantly outperforms most state-of-the-art methods, especially on high-dimensional data.


Angular Control of Circularly Polarized Emission from Achiral Molecules via Magnetic Dipoles Sustained in a Chiral Metamirror.
Circularly polarized emission (CPE) plays an important role in the designs of advanced displays and photonic integrated circuits. Unfortunately, the control of CPE handedness is limited by the chiral metasurfaces employed to emit chiral light. Particularly, the switching of the handedness with chiral metasurfaces relies on flipping the metasurfaces, which adds some constraints to practical applications. Herein, we propose an angle-sensitive chiral metamirror with Mie resonators to realize handedness switching. The Mie resonator supports a magnetic dipole having large field enhancement. This chiral metamirror is applied to excite CPEs with opposite handedness at emission angles within 10°. In contrast to the conventional methods, this work proposes a more efficient approach to manipulate the handedness of CPE.


Effect of Nutrition Education on the Vegetable Intake of Residents in Okinawa.
Background: Increasing vegetable intake is recommended for promoting health in communities. This study investigated the effects of nutrition education on vegetable intake and the factors associated with changes in vegetable intake among residents of Okinawa. Methods and Results: Subjects (n=1,345; mean [±SD] age 56.8±14.6 years; 40.5% male) were recruited from among local residents participating in the Yui Kenko Project. Subjects completed the brief-type self-administered diet history questionnaire (BDHQ) and questionnaires on socioeconomic demographics and social capital. Subjects were divided into 2 groups according to residential area, namely south Okinawa (n=679), where local health promotion activities have been undertaken since the early 2000s, and central Okinawa (n=666). Survey results were fed back to each subject, and health lectures were then conducted at local community centers. After 1 year, the BDHQ was repeated to investigate changes in vegetable and nutritional parameters. After the intervention, residents of south Okinawa increased their crude and energy-adjusted vegetable intake (P<0.05), whereas residents of central Okinawa showed decreased vegetable intake (P<0.05). Univariable and multivariable regression models indicated that, in south Okinawa, participation in local health promotion activities and agreement with general trust were positively correlated with changes in energy-adjusted vegetable intake, whereas in central Okinawa no correlations were observed. Conclusions: The status of social capital should be taken into account when implementing initiatives to increase vegetable intake in communities.