Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection.
Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81-18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21-3.62, P < 0.001) and AFP more than 20 μg/L (HR = 1.49, 95%CI = 1.02-2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76-4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14-6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(-) in both univariate analysis (HR = 4.69, 95%CI = 2.91-7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17-2.64, P = 0.003) and multivariate analysis (P = 0.004). HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically.


An adult case of severe life-threatening Mycoplasma pneumoniae pneumonia due to a macrolide-resistant strain, Japan: a case report.
Until now, the prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) infection among adult patients has been low, and severe MP pneumonia due to a macrolide-resistant strain has seldom been reported. Here, we describe a rare case of severe life-threatening MP pneumonia due to a macrolide-resistant strain in an adult, which was finally treated with fluoroquinolone and tetracycline after failed treatment with macrolide and corticosteroid. A 39-year-old apparently healthy woman complained of fever and productive cough. Three days after onset, she was admitted to a local general hospital. On admission, her vital signs were stable except for high-grade fever. The patient's chest X-ray and chest computed tomography images revealed subsegmental consolidation in her right lower lobe. Treatment with ampicillin/sulbactam, and azithromycin were initiated under a clinical diagnosis of community-acquired pneumonia. After treatment initiation, her fever had not subsided, and the pulmonary lesion had extended to the entire lower lobe. Thus, treatment with prednisolone as steroid pulse therapy was initiated from clinical day 7. However, neither her symptoms nor her pulmonary lesion improved; therefore, she was transferred to our hospital for further examination and treatment. On admission (clinical day 14), her indirect hemagglutination titer for MP was elevated at 1:2560, and bronchoalveolar fluid examination yielded positive results for the mycoplasma antigen. Based on these clinical findings, we confirmed a case of severe life-threatening MP pneumonia. Since her respiratory condition was extremely severe, we initiated levofloxacin and tetracycline. Two days later (clinical day 16), her fever, malaise, and hypoxia resolved, and her pulmonary lesions had significantly improved. Further molecular identification yielded the DNA of MP from her bronchoalveolar fluid, and mutation of A2063G in the 23S rRNA gene was revealed. Based on these results and the clinical course, we confirmed our case as severe MP pneumonia due to a macrolide-resistant strain. More awareness is needed on the emergence of macrolide-resistant MP infection in adults, because severe infection could develop despite initial treatment with macrolide and steroid therapy, which are generally considered as standard therapy for MP.


Three-year tracking of serum fatty acids in Finnish boys and girls.
The composition of fatty acids in serum lipids has been shown to reflect the quality of dietary fat. In order to examine the long-term stability (tracking) of the serum (and hence dietary) fatty acid composition serum cholesteryl ester fatty acids were analysed by gas chromatography in a randomly selected population sample of 1029 Finnish boys and girls aged 3, 6, 9, 12, 15 and 18 years, and again from the same individuals 3 years later. The tracking was evaluated by calculating linear correlation coefficients for the percentages of individual fatty acids between the 2 time points. For all fatty acids the correlations were highly significant, e.g. for linoleate and arachidonate they were 0.58 and 0.61, respectively. In 1980 the means of the percentages of some fatty acids showed certain differences between the various age and sex groups; in 1983 these differences had become smaller and had largely shifted towards three years older age groups, implying that the differences were due to dietary differences between the cohorts rather than to age and sex per se. The present results indicate that serum fatty acid composition has a fairly good biological reproducibility (tracking) and suggest that age and sex as such are only minor determinants of the serum fatty acid composition.


The influence of clonidine on intraocular pressure.
In order to study the influence of clonidine on intraocular pressure (IOP), the drug was administered via different routes. The experiments were performed on chloralose-anaesthetized cats. The rise in IOP observed after administration of clonidine into the external carotid arteries was subjected to a pharmacological analysis. Our experiments suggest that the increase in IOP is due to the contraction of eyelids and extraocular muscles, mediated by the influence of clonidine on alpha-adrenoceptors. The IOP-lowering effect of clonidine was more pronounced after its infusion into the left vertebral artery than after its intravenous injection. This difference would suggest that the clonidine-induced decrease in IOP may be mediated via a central mechanism.


Use of Positive Airway Pressure in the Treatment of Hypoventilation.
The treatment of chronic hypoventilation usually requires noninvasive ventilation. However, upper airway obstruction can lead to hypoventilation in conditions such as obesity-hypoventilation syndrome, or chronic obstructive lung diseases (overlap syndrome). In these situations, continuous positive airway pressure can be an effective therapeutic option. This article reviews the pathophysiology of sleep-related hypoventilation, discusses situations where treatment with continuous positive airway pressure is feasible and briefly outlines noninvasive ventilation modes and settings for the treatment of common sleep-related hypoventilation disorders.


Psychosocial evaluation of bariatric surgery candidates: a survey of present practices.
Successful outcome for bariatric surgery is largely dependent on patients' ability to adhere to postoperative behavior changes. A thorough psychological evaluation is often required before patients' approval for surgery. In addition to a standard psychiatric interview, assessment of behavioral components specific to this surgery seems indicated. No uniform guidelines exist on how to conduct such an evaluation. This survey was designed to collect information on the level of involvement of mental health professionals with bariatric surgery programs and their approach to evaluating bariatric surgery candidates. Surveys about psychological evaluation practices were mailed to 188 bariatric surgery programs. Eighty-one surveys were returned. Eighty-eight percent of programs require patients to undergo a psychological evaluation and almost half require formal standardized psychological assessment. Current illicit drug use, active symptoms of schizophrenia, severe mental retardation, and lack of knowledge about the surgery were the most commonly cited contraindications, preventing patients from gaining approval for surgery. The majority of programs use psychological evaluations; however, the exclusion criteria for surgery vary greatly. Establishing uniform guidelines for the screening of bariatric surgery candidates is necessary. Suggestions on how to begin this process are provided. More research about behavioral and cognitive predictors of postsurgical success is needed.


Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.
Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin-related disorders. We report a patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation. Click https://www.wileyhealthlearning.com/#/online-courses/a6ef1275-8325-4834-89d2-aa18fa31e63f for the corresponding questions to this CME article.


A novel biocontrol agent Bacillus velezensis K01 for management of gray mold caused by Botrytis cinerea.
Gray mold is a destructive plant disease caused by a fungal pathogen Botrytis cinerea. The use of plant growth promoting rhizobacteria (PGPR) has proven to be a promising method to control this disease. Bacillus velezensis K01 was isolated from the rhizosphere of planting tomatoes. Strain K01 has a range of roles, including the ability to solubilize phytate phosphorus, stimulate resistant response, and produce indoleacetic acid (IAA), protease, cellulase, and antimicrobial substances. Strain K01 was found to inhibit 12 phytopathogenic fungi and 5 phytopathogenic bacteria. Specially, strain K01 demonstrated a biocontrol efficiency of over 78% against gray mold caused by B. cinerea on the leaves and fruits of tomato and pepper. Additionally, K01 was found to promote the growth of maize seedlings. Further genomic analysis revealed that K01 belongs to B. velezensis, which is consistent with phylogenetic analysis, average nucleotide polymorphism (ANI), and digital DNA-DNA hybridization (dDDH). The genome of strain K01 had a size of 3,927,799 bp and deduced 3866 predicted genes, with an average guanine-cytosine (GC) content of 46.5%. Based on the analyses of genomic secondary metabolites, over 18.4% of the genome was annotated to 12 gene clusters related to antimicrobial metabolite synthesis. Additionally, genome annotation and comparative genomics identified several genes associated with plant growth promotion and environmental adaption. These findings suggest that B. velezensis K01 has the potential to serve as a new biocontrol agent for management of gray mold on tomato and pepper.


Retinoblastoma: Magnetic Isotope Effects Might Make a Difference in the Current Anti-Cancer Research Strategy.
Human retinoblastoma cells were proven to possess some very unusual DNApolβ species. Being 23.5 kDa monomers, which itself is not common for the DNApolβ superfamily members, these chromatin associated proteins manifests most of the DNApolβ-specifc functional peculiarities making them legitimate targets for DNA repair cytostatic inhibitors. Particularly, these tumor specific enzymes were found to be very sensitive to 25Mg2+-, 43Ca2+- and 67Zn2+-promoted magnetic isotope effects (MIE) caused a marked DNA sequence growth limitation as well as a formation of the size-invalid, i.e. too short in length, DNA fragments, totally inappropriate for the DNA repair purpose. This MIE-DNApolβ match may serve a starting point for further move towards the paramagnetic path in current developments of anti-cancer strategies.


Partial purification and characterization of cyclic nucleotide phosphodiesterases from human bronchial tissue.
DEAE-Sephadex chromatography reveals the presence in extracts of human bronchial tissue of at least three separate cyclic nucleotide phosphodiesterases: a cyclic GMP-specific high affinity enzyme, a non-specific low affinity enzyme, and a high affinity cyclic AMP-specific enzyme. The activity of each fraction was partially characterized with respect to kinetic parameters, thermal stability, and the influence of a number of inhibitors. Each activity was found to resemble the activity of the previously characterized corresponding enzyme from whole lung tissue extracts. A high affinity non-specific phospho-diesterase previously isolated from lung tissue is missing in extracts of bronchial tissue.


[Experimental research on the effects of Chinese herb drugs on immune dysfunction in severely scalded rats].
To observe the modulation effect of a concoction of Chinese herb drugs on immune dysfunction in severely burned rats. One hundred healthy Wistar rats were randomly divided into A group (n = 30, with Chinese herb drug feeding after burns), B group (n = 30, with bouillon feeding after burns), C group (n = 30, with ordinary feeding after burns), and D group (n = 10, with sham burns as normal controls). The rats in A, B and C groups were subjected to 30% TBSA full-thickness burns and received conventional treatment. The rats in A group received 2 ml of Chinese herbal drug at 37 degrees C by gavage two times a day beginning from 2 postburn-hours(PBH). The rats in B group received 2 ml bouillon by gavage instead, and otherwise treatment was the same as A group, while the rats in C group were not fed by gavage. The activity of natural killer cell and T lymphocyte, and the levels of IgA, IgG, IgM, C3, C4 in A, B, C groups were examined on 3, 7, 14 PBD, and these indices were also determined in D group. Compared with D group, the amount of the CD3+, CD4+ lymphocyte, the ratio of the CD4+/CD8+, the level of IgA, IgG, IgM, C3, C4, the activity of NK cells, and the density of the sIgA in A, B, C groups were obviously decreased, but the amount of the CD8+ were obviously increased (P < 0.05 or P < 0.01). Furthermore, the above indices in A group improved more quickly when compared with B and C groups. The concoction of Chinese herb drugs can improve the distribution of T lymphocyte subsets, increase the activity of NK cells, promote the secretion of sIgA in intestinal mucous membrane and promote recovery of IgM, IgG, C3, C4 levels, thereby improves the immune function of the body.


Is it Possible to Diagnose "Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features" Preoperatively?
There is no accepted consensus or algorithm for the preoperative diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in patients with thyroid nodules. In this study, we evaluated the importance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in the differential diagnosis of NIFTP. Pathology preparations of 209 patients with a follicular variant of papillary thyroid carcinoma (FVPTC) diagnosed after thyroid surgery in a tertiary health center between January 2010 and January 2020 were re-evaluated. Patients were divided into NIFTP and encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) to compare. Of the patients, 58 (27.7%) were NIFTP, and 151 (72.3%) were EFVPTC. There was no statistically significant difference in terms of age (p = 0.46), tumor size (p = 0.51), gender (p = 0.48), and surgical technique (p = 0.78) between the groups. The probability of the neutrophil-to-lymphocyte ratio (NLR) > 2 is more common in the EFVPTC group. It was statistically significant that the NIFTP group was 1.96 times more likely to have NLR > 2 (OR: 1.96, 95% CI: 1.06-3.63) (p < 0.05). However, there was no risk difference between the groups in terms of the platelet-to-lymphocyte ratio (PLR) (OR: 0.76, 95% CI: 0.41-1.43) (p > 0.05). The diagnosis of NIFTP should be kept in mind in the evaluation of patients whose thyroid fine-needle aspiration (FNA) biopsy results are in the intermediate group. NIFTP exhibits better prognostic findings than classic thyroid papillary cancer and EFVPTC. Therefore, preoperative diagnosis of NIFTP in line with laboratory, ultrasonography, and FNA findings will save the patient from unnecessary overtreatment.


Early events in parvovirus replication: lack of integration by minute virus of mice into host cell DNA.
Viral DNA sequences were not detected in high-molecular-weight host DNA until well after the onset of viral DNA replication.


Significance of serial real-time PCR monitoring of EBV genome load in living donor liver transplantation.
Quantitative analysis of the Epstein-Barr virus (EBV) genome has been recently reported to be helpful for early identification of EBV viremia which could reduce the risk of post-transplantation lymphoproliferative disorder (PTLD). To demonstrate the significance of serial monitoring of EBV genome load by real-time quantitative polymerase chain reaction (PCR) after living donor liver transplantation. From March 1999 to April 2000, the EBV genome load in peripheral blood mononuclear cells (PBMNC) was measured serially in a total of 15 recipients of living donor liver transplantation (LDLT) who had a symptomatic EBV infection. In 15 patients, the mean values of the highest EBV DNA levels from the patients who had fever, URS, diarrhea, ascites, lymphadenopathy and PTLD were 36 232, 16 040, 15 968, 2485, 336 858 and 60 486 copies/microg DNA, respectively. Patients were treated by reduction or discontinuation of immunosuppressives and/or antiviral agents. The EBV DNA levels decreased in all these patients following the recovery from their symptoms. We encountered two cases of PTLD during this study period. One of them was referred to us after the onset of PTLD and one had been undergoing aggressive immunosuppression treatment for severe rejection. Both were successfully treated. Serial quantitative analysis of the EBV genome load by means of real-time PCR are thought to be useful for preventing PTLD through adjustment of the immunosuppression level in response to the viral genome load following symptomatic EBV infection.


[The basic ideas about the use of the Swan-Ganz catheter].
The haemodinamic monitorization through the Swan-Ganz catheter is a valuable source in the assistance of the critically ill patient. This work is a review on the importance, indication, skills and nursing care in order to use this source.


Anomalous tendon slips from the flexor pollicis longus to the flexor digitorum profundus.
Anomalous tendon slips from the flexor pollicis longus to the flexor digitorum profundus are described. Clinical examination of 194 patients suggests that the anomaly is present in at least one extremity of 31% of individuals and in both extremities in 14%. Dissection of 43 cadavers demonstrated the anomaly in at least one extremity of 25% and in both extremities of 6%. Four cases are described in which the anomaly probably was responsible for chronic tenosynovitis. The anomaly was excised surgically in all cases.


Divergent roles of endothelial NF-kappaB in multiple organ injury and bacterial clearance in mouse models of sepsis.
To define the roles of endothelial-intrinsic nuclear factor kappaB (NF-kappaB) activity in host defense and multiple organ injury in response to sepsis, we generated double transgenic (TG) mice (EC-rtTA/I-kappaB alpha mt) that conditionally overexpress a degradation-resistant form of the NF-kappaB inhibitor I-kappaB alpha (I-kappaB alpha mt) selectively on vascular endothelium. The EC-rtTA/I-kappaB alpha mt mice had no basal, but a relatively high level of doxycycline-inducible, I-kappaB alpha mt expression. I-kappaB alpha mt expression was detected in endothelial cells, but not in fibroblasts, macrophages, and whole blood cells, confirming that transgene expression was restricted to the endothelium. When subjected to endotoxemia, EC-rtTA/I-kappaB alpha mt mice showed endothelial-selective blockade of NF-kappaB activation, repressed expression of multiple endothelial adhesion molecules, reduced neutrophil infiltration into multiple organs, decreased endothelial permeability, ameliorated multiple organ injury, reduced systemic hypotension, and abrogated intravascular coagulation. When subjected to cecal ligation and puncture-induced sepsis, the TG mice had less severe multiple organ injury and improved survival compared with wild-type (WT) mice. WT and EC-rtTA/I-kappaB alpha mt mice had comparable capacity to clear three different pathogenic bacteria. Our data demonstrate that endothelial NF-kappaB activity is an essential mediator of septic multiple organ inflammation and injury but plays little role in the host defense response to eradicate invading pathogenic bacteria.


Fibromuscular dysplasia of the superior mesenteric artery and coexisting cerebral berry aneurysms.
Fibromuscular dysplasia of the systemic artery and cerebral "berry" (saccular) aneurysm are nonatheromatous lesions of uncertain etiology. The coexistence of these vascular disorders in the individual reported here is unusual and may provide a possible explanation of their pathogenesis.


A review of applications of metabolomics in osteoarthritis.
Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.


Modeling and simulation studies of human β3 adrenergic receptor and its interactions with agonists.
β3 adrenergic receptor (β3AR) is known to mediate various pharmacological and physiological effects such as thermogenesis in brown adipocytes, lipolysis in white adipocytes, glucose homeostasis and intestinal smooth muscle relaxation. Several efforts have been made in this field to understand their function and regulation in different human tissues and they have emerged as potential attractive targets in drug discovery for the treatment of diabetes, depression, obesity etc. Although the crystal structures of Bovine Rhodopsin and β2 adrenergic receptor have been resolved, to date there is no three dimensional structural information on β3AR. Our aim in this study was to model 3D structure of β3AR by various molecular modeling and simulation techniques. In this paper, we describe a refined predicted model of β3AR using different algorithms for structure prediction. The structural refinement and minimization of the generated 3D model of β3AR were done by Schrodinger suite 9.1. Docking studies of β3AR model with the known agonists enabled us to identify specific residues, viz, Asp 117, Ser 208, Ser 209, Ser 212, Arg 315, Asn 332, within the β3AR binding pocket, which might play an important role in ligand binding. Receptor ligand interaction studies clearly indicated that these five residues showed strong hydrogen bonding interactions with the ligands. The results have been correlated with the experimental data available. The predicted ligand binding interactions and the simulation studies validate the methods used to predict the 3D-structure.


Covalently bonded and adventitious glycans in germin.
Germin was previously shown to contain covalently bonded and adventitious glycans. The object of the present investigation was to characterize the two types of glycan. The presence of N- but not O-glycans in germin is indicated by the biosynthesis of altered forms, including an unglycosylated form of germin when wheat embryos are germinated in the presence of tunicamycin. After treating the doublet of germin pentamers (G and G') from normally germinated embryos with beta-N-acetylglucosaminidase, G is converted to a form that co-migrates with G' during electrophoresis in sodium dodecyl sulfate-polyacrylamide, but G' is unaffected. This suggests that the N-glycans in G contain antennary N-acetylglucosamine but that those in G' do not. This conclusion has been confirmed and elaborated by doubly labeling G and G' in vivo with [3H]glucosamine and [35S]methionine, and by characterizing sugar-labeled glycopeptides from G and G' by gel filtration, before and after their degradation by exoglycosidases. In the context of proven structures for the complex N-glycans in other plant glycoproteins, the findings, when combined with monosaccharide analyses of G and G', permit plausible speculation about the structure of the single N-glycan that is likely present in each G monomer (GlcNAc2(Man)2(Man-Xyl)(GlcNAc)(GlcNAc-Fuc] and G' monomer ((Man)2(Man-Xyl)(GlcNAc)(GlcNAc-Fuc)). The adventitious glycans, which can be removed by phenolic extraction of germin, have a composition similar to that expected for the characteristic hemicelluloses and pectins in monocot cell walls. The possible significance of this finding is discussed in relation to our continuing efforts to define the biochemical involvements of germin. In allied studies, affinity of its N-linked glycans for concanavalin A has been used to concentrate small amounts of germin from large volumes of wheat extract and to fractionate germin from tunicamycin-treated and normally germinated wheat embryos.


Biodiesel fuel production from waste cooking oil by the inclusion complex of heteropoly acid with bridged bis-cyclodextrin.
The inclusion complex of Cs2.5H0.5PW12O40 with bridged bis-cyclodextrin (CsPW/B) is prepared as a highly efficient catalyst for the direct production of biodiesel via the transesterification of waste cooking oil. CsPW/B is characterized by X-ray diffraction, and the biodiesel is analyzed by Gas Chromatography-Mass Spectrometer. The conversion rate of waste cooking oil is up to 94.2% under the optimum experimental conditions that are methanol/oil molar ratio of 9:1, catalyst dosage of 3 wt%, temperature of 65 °C and reaction time of 180 min. The physical properties of biodiesel sample satisfy the requirement of ASTM D6751 standards. The novel CsPW/B catalyst used for the transesterification can lead to 96.9% fatty acid methyl esters and 86.5% of the biodiesel product can serve as the ideal substitute for diesel fuel, indicating its excellent potential application in biodiesel production.


The Blalock-Hanlon operation: an anachronism?
Some surgeons advocate early correction of dextrotransposition of the great arteries (D-TGA) using hypothermic circulatory arrest when Rashkind balloon atrial septostomy is inadequate. An alternative procedure is a Blalock-Hanlon closed atrial septectomy. From 1971 to 1985, 19 patients underwent the latter procedure for D-TGA at our institution. Three had it as the first procedure, and 16 had undergone Rashkind balloon atrial septostomy, which was unsuccessful. Age at performance of the Blalock-Hanlon closed atrial septectomy ranged from 1 day to 5 months (mean, 2.51 months). There were no operative deaths. Subsequently, 18 children have had a Mustard procedure, and 1, a Rastelli procedure (average age at definitive repair, 25.31 months). One death followed definitive repair (combined mortality, 5%). On room air, average partial pressure of arterial oxygen rose from 23.25 mm Hg prior to closed atrial septectomy to 31.45 mm Hg at discharge. Average hematocrit fell from 58.37% prior to closed atrial septectomy to 53.94% prior to definitive repair. At the time of definitive repair, percentile height ranged from the 3rd to the 95th percentile (mean, 44th percentile) and weight ranged from the 3rd to the 90th percentile (mean, 32.5th percentile). In 1 infant, transient neurological symptoms developed three days following Blalock-Hanlon atrial septectomy. The symptoms were due to multiple cerebral infarctions thought to be caused by emboli. No permanent neurological deficit resulted. We believe that the infant with an inadequate Rashkind balloon atrial septostomy prior to age 6 months should undergo a Blalock-Hanlon septectomy followed by definitive repair timed on the basis of the baby's growth, associated anomalies, and evidence of pulmonary hypertension.


Curated single cell multimodal landmark datasets for R/Bioconductor.
The majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal profiling methods add simultaneous measurement of genomic, proteomic, epigenetic, and/or spatial information on the same cells. The development of new statistical and computational methods in Bioconductor for such data will be facilitated by easy availability of landmark datasets using standard data classes. We collected, processed, and packaged publicly available landmark datasets from important single-cell multimodal protocols, including CITE-Seq, ECCITE-Seq, SCoPE2, scNMT, 10X Multiome, seqFISH, and G&T. We integrate data modalities via the MultiAssayExperiment Bioconductor class, document and re-distribute datasets as the SingleCellMultiModal package in Bioconductor's Cloud-based ExperimentHub. The result is single-command actualization of landmark datasets from seven single-cell multimodal data generation technologies, without need for further data processing or wrangling in order to analyze and develop methods within Bioconductor's ecosystem of hundreds of packages for single-cell and multimodal data. We provide two examples of integrative analyses that are greatly simplified by SingleCellMultiModal. The package will facilitate development of bioinformatic and statistical methods in Bioconductor to meet the challenges of integrating molecular layers and analyzing phenotypic outputs including cell differentiation, activity, and disease.


Is the large-male mating advantege in anurans an epiphenomenon?
This study examines the idea that variation in forelimb length among male anurans influences reproductive success, and does so independently of body size. Analyses of covariance and multivariate analyses of morphological data for five species of explosives breeders are used to test the prediction that for species in which male-male displacements contribute to variation in male reproductive success, amplectant males have longer forelimbs than do non-amplectant males at any body length. The findings for four of five species are in agreement with expectation. The results lend support to the suggestion that for explosive-breeding anurans, the large-male mating advantage may not be a consequence of large body size per se, but rather is due to the fact that large males have longer forelimbs with which to grasp females securely during amplexus and thus resist displacements by competing males.


Mechanism of cinnamic acid-induced trypsin inhibition: a multi-technique approach.
In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol(-1) and 50.70 J mol(-1) K(-1), respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues.


Circulating levels of myocardial proteins predict future deterioration of congestive heart failure.
This study was designed to test whether circulating levels of myocardium-specific proteins serve as useful markers for the prognosis of patients with congestive heart failure. Seventy-eight patients with congestive heart failure from dilated cardiomyopathy but in a stable condition were enrolled, and their blood was sampled for measurements of myosin light chain-I (MLC-I), troponin T (TnT), heart fatty-acid-binding protein (H-FABP), and creatine kinase isoenzyme MB (CK-MB). The patients were then followed up for 951 +/- 68 days, with the endpoint being acute deterioration. A univariate analysis revealed that MLC-I, TnT, H-FABP, and CK-MB were significant predictors for acute deterioration of heart failure. Application of the Kaplan-Meier method using cutoff values determined by analysis of receiver operating characteristics curves demonstrated that the incidence of acute deterioration was significantly higher in patients with higher values of MLC-I (61.9%), TnT (52.4%), H-FABP (50.0%), or CK-MB (38.6%) than in those with lower values of these markers (15.8%, 20.4%, 13.6%, and 16.1%, respectively). Increased circulating levels of the specific myocardial proteins are related to a higher probability of future acute deterioration of congestive heart failure in patients in a stable condition associated with dilated cardiomyopathy.


Altered sensory system activity and connectivity patterns in adductor spasmodic dysphonia.
Adductor-type spasmodic dysphonia (ADSD) manifests in effortful speech temporarily relievable by botulinum neurotoxin type A (BoNT-A). Previously, abnormal structure, phonation-related and resting-state sensorimotor abnormalities as well as peripheral tactile thresholds in ADSD were described. This study aimed at assessing abnormal central tactile processing patterns, their spatial relation with dysfunctional resting-state connectivity, and their BoNT-A responsiveness. Functional MRI in 14/12 ADSD patients before/under BoNT-A effect and 15 controls was performed (i) during automatized tactile stimulus application to face/hand, and (ii) at rest. Between-group differential stimulation-induced activation and resting-state connectivity (regional homogeneity, connectivity strength within selected sensory(motor) networks), as well as within-patient BoNT-A effects on these differences were investigated. Contralateral-to-stimulation overactivity in ADSD before BoNT-A involved primary and secondary somatosensory representations, along with abnormalities in higher-order parietal, insular, temporal or premotor cortices. Dysphonic impairment in ADSD positively associated with left-hemispheric temporal activity. Connectivity was increased within right premotor (sensorimotor network), left primary auditory cortex (auditory network), and regionally reduced at the temporoparietal junction. Activation/connectivity before/after BoNT-A within-patients did not significantly differ. Abnormal ADSD central somatosensory processing supports its significance as common pathophysiologic focal dystonia trait. Abnormal temporal cortex tactile processing and resting-state connectivity might hint at abnormal cross-modal sensory interactions.


Male Akita mice develop signs of bladder underactivity independent of NLRP3 as a result of a decrease in neurotransmitter release from efferent neurons.
Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication that is recalcitrant to glucose control. Using the Akita mouse model (type 1) bred to be NLR family pyrin domain containing 3 (NLRP3)+/+ or NLRP3-/-, we have previously found that females (mild hyperglycemia) progress from an overactive to underactive bladder phenotype and that this progression was dependent on NLRP3-induced inflammation. Here, we examined DBD in the male Akita mouse (severe hyperglycemia) and found by urodynamics only a compensated underactive-like phenotype (increased void volume and decreased frequency but unchanged efficiency). Surprisingly, this phenotype was still present in the NLRP3-/- strain and so was not dependent on NLRP3 inflammasome-induced inflammation. To examine the cause of the compensated underactive-like phenotype, we assessed overall nerve bundle density and afferent nerve bundles (Aδ-fibers). Both were decreased in density during diabetes, but denervation was absent in the diabetic NLRP3-/- strain so it was deemed unlikely to cause the underactive-like symptoms. Changes in bladder smooth muscle contractility to cell depolarization and receptor activation were also not responsible as KCl (depolarizing agent), carbachol (muscarinic agonist), and α,β-methylene-ATP (purinergic agonist) elicited equivalent contractions in denuded bladder strips in all groups. However, electrical field stimulation revealed a diabetes-induced decrease in contractility that was not blocked in the NLRP3-/- strain, suggesting that the bladder compensated underactive-like phenotype in the male Akita mouse is likely through a decrease in efferent neurotransmitter release.NEW & NOTEWORTHY In this study, we show that diabetic bladder dysfunction (the most common diabetic complication) manifests through different mechanisms that may be related to severity of hyperglycemia and/or sex. Male Akita mice, which have severe hyperglycemia, develop bladder underactivity as a result of a decrease in efferent neurotransmitter release that is independent of inflammation. This contrasts with females, who have milder hyperglycemia, where diabetic bladder dysfunction progresses from overactivity to underactivity in an inflammation-dependent manner.


A fatal case of iatrogenic hypercalcemia after calcium channel blocker overdose.
We report a case of a 61-year-old woman treated for a suspected verapamil overdose with continuous calcium chloride infusion, resulting in severe hypercalcemia of 32.3 mg/dL (8.07 mmol/L) with a normal range of 8.6-10.5 mg/dL (2.15-2.63 mmol/L). Treatment with acute hemodialysis rapidly normalized the serum calcium level, but the patient later died of vasoconstrictive complications of hypercalcemia.


The Food Stamp Program: history, nutrition education, and impact.
The Food Stamp Program has grown from a modest effort to distribute excess farm commodities during the Great Depression to the nation's largest food assistance and nutrition program, serving almost 27 million persons in fiscal year 2006, at a cost of more than 30 billion dollars to federal taxpayers. In 1990 Congress authorized cost sharing for food stamp nutrition education. Since 1992-when only seven states had approved food stamp nutrition education plans totaling 661,076 dollars in federal dollars-the nutrition education program has grown exponentially. In 2007, there were 52 food stamp nutrition education plans for states and territories approved at a total cost of more than 275 million dollars. The purpose of this review is to give an overview of the Food Stamp Program from its inception in May 1939 through 2006, including program milestones, changes that have occurred as the result of legislation, and the growth and effectiveness of nutrition education to Food Stamp Program participants. Future investigations are needed to study processes for development and validation of evaluation measures as required by the US Department of Agriculture Food and Nutrition Service and to examine the effects of food stamp nutrition education on behavior changes affecting health and nutrition of Food Stamp Program participants.


Weekly cumulative extracurricular core training time predicts cadet physical performance: A descriptive epidemiological study.
Core training can enhance athletic performance by enhancing core strength and stability. To achieve this outcome, however, a tailored training program is required; the normal military training curriculum is inadequate. The connection between cumulative weekly extracurricular training time, cumulative weekly extracurricular core training time and cadet performance is unknown. The association between cumulative weekly extracurricular training time, cumulative weekly extracurricular core training time and performance has been discovered using a descriptive epidemiological study methodology. Questionnaires were used to collect information on personal characteristics and weekly cumulative extracurricular (core) training time, as well as the results of the Chinese Army Physical Fitness Test (C-APFT), which included 100-m dash, 5000-m run, 3000-m armed training run, 400-m steeplechase, 800 m breaststroke, horizontal bar pull-ups, 2-min sit-ups, 2-min push-ups, and hand grenade throwing. This study recruited two hundred and twenty male cadets (aged 18 to 23 years, 19.68 ± 0.91) from a military medical university. (a) The correlation between cumulative weekly extracurricular training time and C-APFT score is significant. The 100-m dash, 5000-m run, 3000-m armed training run, 400-m steeplechase, and 2-min push-ups performed the best when participants exercised for 5 to 10 h per week. (b) The number of cadets scoring good or excellent on the C-APFT improves with cumulative weekly extracurricular core training time. The recommended amount of core training for cadets per week is 120 min. (c) The average cumulative weekly extracurricular core training time was a effective predictor of performance on the 400-m steeplechase (R2 = 0.470, F = 10.641, P<0.01), horizontal bar pull-ups (R2 = 0.238, F = 68.191, P<0.01), 2-min sit-ups (R2 = 0.280, F = 84.710, P<0.01), 100-m run (R2 = 0.031, F = 6.920, P<0.01), 3000-m armed training run (R2 = 0.025, F = 5.603, P<0.05), 2-min push-ups (R2 = 0.019, F = 4.295, P<0.05), and hand grenade tossing (R2 = 0.025, F = 5.603, P<0.05). Active participation in extracurricular core training can improve cadets' C-APFT scores. An average cumulative weekly extracurricular training duration of 5-10 h showed the most progress, and more than 120 min per week was ideal for extracurricular core training. The amount of extracurricular time spent on core training exercises each week can be used as a predictor of the C-APFT.


Some legal aspects of epilepsy.
Legal aspects of epilepsy are jurisdiction-dependent, and this analysis has focused on an Australian context;however, the reader can extrapolate to his/her local jurisdiction and/or legal system. The AUSTROADS Guidelines have codified the fitness to drive restrictions to be imposed for both private and commercial drivers. They set out the default positions and the considerations that can be applied to deviate from the default of at least 1year seizure freedom for private license holders and 10years seizure freedom for commercial drivers. People with epilepsy are broadly excluded from all employment requiring the wearing of a uniform. Only where preemployment medical examination mandates disclosure does the person with epilepsy has to disclose epilepsy to a prospective employer. There are specific laws that control workplace and employment standards that cover occupational health and safety, protection for the disabled, and antidiscrimination. Negligence relies on establishing: duty of care; breach of that duty; and damage that is not too remote. Once ascertained, liability is established by the relative causation. The Civil Liability Acts served to redefine negligence, causation, and liability. Added consideration attaches to vicarious liability of the employer for the employee and nondelegable duty of care. This overview has examined three legal aspects of epilepsy, namely, driving, employment, and negligence. The concepts and interpretations should have relative applicability well beyond any narrow confines, limited to a single jurisdiction.


Electrogenerated chemiluminescence detection for deoxyribonucleic acid hybridization based on gold nanoparticles carrying multiple probes.
A novel sensitive electrogenerated chemiluminescence (ECL) method for the detection deoxyribonucleic acid (DNA) hybridization based on gold nanoparticles carrying multiple probes was developed. Ruthenium bis(2,2'-bipyridine)(2,2'-bipyridine-4,4'-dicarboxylic acid)-N-hydroxysuccinimide ester (Ru(bpy)2(dcbpy)NHS) was used as a ECL label and gold nanoparticle as a carrier. Probe single strand DNA (ss-DNA) was self-assembled at the 3'-terminal with a thiol group to the surface of gold nanoparticle and covalently labeled at the 5'-terminal of a phosphate group with Ru(bpy)2(dcbpy)NHS and the resulting conjugate, (Ru(bpy)2(dcbpy)NHS)-ss-DNA-Au, was taken as a ECL probe. When target analyte ss-DNA was immobilized on a gold electrode by self-assembled monolayer technique and then hybridized with the ECL probe to form a double-stranded DNA (ds-DNA), a strong ECL response was electrochemically generated. The ECL intensity was linearly related to the concentration of the complementary sequence (target ss-DNA) in the range from 1.0 x 10(-11) to 1.0 x 10(-8) mol L(-1), and the linear regression equation was S=57301+4579.6 lg C (unit of C is mol L(-1)). A detection limit of 5.0 x 10(-12) mol L(-1) for target ss-DNA was achieved. The ECL signal generated from many reporters of ECL probe prepared is greatly amplified, compared to the convention scheme which is based on one reporter per hybridization event.


Hypoxic airway constriction in infants of very low birth weight recovering from moderate to severe bronchopulmonary dysplasia.
We hypothesized that infants recovering from severe bronchopulmonary dysplasia have airway constriction that is, at least in part, related to borderline hypoxia. If this hypothesis were correct, pulmonary resistance should decrease with the administration of oxygen. To test this hypothesis, we studied 10 infants recovering from severe bronchopulmonary dysplasia (study weight 2490 +/- 275 gm; birth weight 1010 +/- 89 gm; postnatal age 73 +/- 7 days; postconceptional age 38.5 +/- 1.6 weeks) and 10 matched control infants (study weight 2430 +/- 179 gm; birth weight 2320 +/- 195 gm; postnatal age 25 +/- 4 days; postconceptional age 37.5 +/- 0.8 weeks). Resistance and compliance were measured by means of a mask with a flowmeter and an esophageal balloon (with the PEDS computer program). Measurements in both groups were made in quiet sleep, without sedation, during the inhalation of room air and during the fifth minute of oxygen inhalation. We found that (1) total pulmonary resistance, significantly higher in infants with bronchopulmonary dysplasia than in control infants, decreased from 206.1 +/- 47 cm H2O.L-1.sec-1 during inhalation of room air to 106.5 +/- 20.9 during inhalation of 100% oxygen (p less than 0.05) and (2) pulmonary dynamic compliance, lower in infants with bronchopulmonary dysplasia than in control infants, increased significantly with the administration of 100% oxygen. The results suggest that infants with bronchopulmonary dysplasia have airway constriction and that this is alleviated by inhalation of oxygen.


Feasibility of cardiac cryoablation using a transvenous steerable electrode catheter.
We investigated the feasibility of using cryogenic technology in an electrode catheter for percutaneous ablation of cardiac tissue. Despite its high success rate, radiofrequency catheter ablation has important limitations especially with regards to the treatment of ventricular arrhythmias associated with a chronic scar. Arrhythmia surgery experience has shown that freezing with a hand held probe can permanently ablate the arrhythmogenic substrate of ventricular tachycardia associated with an old scar. Moreover, cryosurgery also allows for reversible "ice mapping," in which the area likely responsible for the arrhythmia can be evaluated by suppressing its electrophysiologic properties prior to the creation of an irreversible state. A new steerable cryoablation catheter using Halocarbon 502 as a refrigerant was utilized in six dogs. Serial cryoapplications were performed in the right and left ventricles. In two dogs, we attempted reversible ice mapping of the AV node. Pathological evaluation of the lesions was done acutely in all the animals. Forty-two cryoapplications were delivered at a mean temperature of -45 +/- 9.8 degrees C. No lesion was found at pathological evaluation for 16 cryoapplications which did not achieve a temperature of less (colder) than -30 degrees C. The remaining applications resulted in 26 lesions which were hemorrhagic and sharply demarcated from normal myocardium. Histological evaluation revealed contraction band necrosis. Reversible ice mapping of the AV node was successfully achieved in two animals. Cryoablation is feasible using an electrode catheter with multiple electrodes. This technology has the potential to allow for reversible ice mapping to confirm a successful ablation target before definitive ablation.


Predictive value of elevated white blood cell count in patients with preexisting coronary heart disease: the Bezafibrate Infarction Prevention Study.
Inflammation is implicated in the pathogenesis of atherosclerosis and acute coronary syndromes. White blood cell (WBC) count increases during infections and inflammatory illnesses and has been shown to predict coronary heart disease (CHD) independent of traditional cardiovascular risk factors. This apparent association may reflect a relationship between the WBC count and other coronary risk factors. Studies in patients with CHD are scarce and give conflicting results. The aim of the present study was to investigate the association between WBC count and subsequent coronary events and total mortality in a large cohort of patients with CHD. We evaluated the relationship between WBC count and 6-year risk of coronary events and mortality in a large cohort of patients with chronic CHD who were enrolled in a secondary prevention study of bezafibrate. In univariate analysis, WBC count was associated with an elevated 6-year risk of myocardial infarction, cardiac death, and total mortality. On multivariate adjustment, the positive association with risk of myocardial infarction and cardiac death was eliminated, but WBC count remained predictive of total mortality: relative risk, 1.47; 95% confidence interval, 1.13 to 1.92, in the upper tertile of WBC count (as compared with the lowest). For every 1000/ microL increase in WBC count, risk of total death increased by 6% (relative risk, 1.06; 95% confidence interval, 1.03-1.10). Elevated WBC count in patients with CHD was associated with higher long-term risk of all-cause mortality. This excess risk of mortality was not due to cardiac causes.


Osteoarthritis of the hip: agreement between joint space width measurements on standing and supine conventional radiographs.
To assess the effect of standing position on joint space width (JSW) measurements of the hips with and without osteoarthritis (OA) on pelvic radiographs. Adult patients aged 18 or more had pelvic anteroposterior conventional radiographs standing and supine performed by a single radiologist in the same radiology unit according to standardised guidelines. JSW measurements in mm were made by a single reader blind to patients' identity and type of view, using a 0.1 mm graduated magnifying glass directly laid over the radiograph, at the narrowest point for OA hips or at the vertical joint space for non-OA hips. Agreement of JSW between both views was assessed using the Bland and Altman graphical analysis. JSW was greater on standing than supine radiographs, for example, 7.1% for OA hips. Mean (SD) differences and limits of agreement (mm) between both views were 0.08 (0.27) and -0.46 to 0.62 for the 70 non-OA hips, 0.02 (0.31) and -0.60 to 0.64 for the 46 OA hips. Corresponding 95% confidence intervals of mean difference were 0.02, -0.14 mm and -0.07, -0.11 mm. Measurements of JSW of the hip on pelvic standing and supine radiographs are concordant. Changes less than or equal to 0.64 mm between the two views are similar or inferior to radiological progression of OA.


Slaying the psychoanalytic dragon: an integrationist's commentary on Yates.
The basis for Yates' (1983) rejection of the case for 'reconciliation and integration' of behaviour therapy and psychodynamic psychotherapy is questioned. His arguments reflect a misunderstanding of the position he rejects and merely establish that those who adopt extreme viewpoints will find their positions irreconcilable. Doubt is cast on his apparent belief that a competition between models will ultimately yield a winner.


Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats.
To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.


Function of hydroxycinnamoyl spermidines in seedling growth of Arabidopsis.
Hydroxycinnamic acid amides are involved in various developmental processes as well as in biotic and abiotic stress responses. Among them, the presence of spermidine derivatives, such as N1,N8-di(coumaroyl)-spermidine and N1,N8-di(sinapoyl)-spermidine, and their biosynthetic genes have been reported in Arabidopsis, but their functions in plants are still unknown. We chemically synthesized the above-mentioned spermidine derivatives to assess their physiological functions in Arabidopsis. We evaluated the growth and development of chemically treated Arabidopsis and demonstrated that these compounds inhibited seed germination, hypocotyl elongation, and primary root growth, which could be due to modulation of plant hormone homeostasis and signaling. The results suggest that these compounds are regulatory metabolites that modulate plant growth and development.


Effect of interferon on assembly of intracellular Moloney murine leukemia virus particles in chronically infected 3T3/NIH cells.
The effect of interferon (IFN) on virus release and on assembly of intracellular virions in 3T3/NIH cells chronically infected with Moloney murine leukemia virus was studied by short labeling with 3H-leucine (viral proteins), 3H-glucosamine (viral glycoproteins) and 3H-uridine (vital RNA). With all of these labels, IFN pretreatment was found to strongly inhibit extracellular virus release. No difference was found between the extent of labeling of viral proteins and glycoproteins of intracellular virions. Incorporation of 3H-uridine into intracellular virions was strongly reduced by the IFN pretreatment. Since it is rather unlikely that encapsidated RNA is significantly degraded during the relatively short time of label incorporation, this finding suggests that IFN interferes with packaging of viral RNA. The effect of IFN on virus release and on 3H-uridine labeling of intracellular virion were found to develop with the same kinetics, though the maximal inhibition of virus release was stronger.


Micrometastasis in gastric cancer.
Circulating tumor cells (CTCs) are a crucial contributor and indicator for cancer metastasis. The presence of CTCs and other two forms of occult disease including circulating tumor microembolus (CTMs) as well as disseminated tumor cells (DTCs) as a sign for micrometastasis has been associated with adverse survival of both localized and metastatic cancers. However, their assignments in micrometastasis are still not well understood. This mini-review is aimed to provide an overview of the biological features and the clinical impact of CTCs, DTCs and CTM in gastric cancer (GC), and to summarize the technical limitations of detection methods in addition to the significance of distinct migration modes in epithelial-mesenchymal transition (EMT) and gastric micrometastasis. Although there are controversies over current CTC identification strategies, both single and collective migration modes as indispensable parts of micrometastasis are influential participants in GC progression, diagnosis and prognosis. CTCs, CTM and DTCs are not separated forms of the occult disease; however available techniques fail to detect all subsets of them. Therefore, micrometastatic detection should be combined with conventional pathological examinations in order to make more accurate predictions of tumor outcomes. Novel markers further defining the features of CTC subsets are warranted.


Abdominal pain as first manifestation of lyme neuroborreliosis in children, case report and review of literature.
Lyme neuroborreliosis can cause a variety of neurological manifestations. European children usually present facial nerve palsy, other cranial nerve palsies and aseptic meningitis. We hereby report a case of Lyme neuroborreliosis in a 9-year-old boy with abdominal pain as first symptom and subsequent onset of attention deficit and ataxia. Diagnosis was made by detection of specific antibody in both serum and cerebrospinal fluid with neuro-radiological images suggestive for this infectious disease. A 12-months follow-up was performed during which no relevant neurological sequelae were revealed. This case report shows that abdominal radiculitis, although extremely rare, could be the first manifestation of early Lyme neuroborreliosis in pediatric patients. Pediatricians must consider Lyme disease in the differential diagnosis of abdominal pain of unknown origin in children, especially in countries where the infection is endemic.


Convergence of multiple sensory inputs onto neurons in the dorsolateral medulla in cats.
The dorsolateral medulla, including the nucleus reticularis parvicellularis, the cuneate nucleus, and the external cuneate nucleus, is an integrative region for a variety of sensory inputs. The purpose of this study was to determine whether individual neurons respond to a variety of different sensory modalities. To this end, responses of 40 neurons in the dorsolateral medulla to multiple sources of sensory input were assessed in cats anesthetized with alpha-chloralose. Neurons were located in the nucleus reticularis parvicellularis (24 cells, 60%), the cuneate nucleus (10 cells, 25%), and the external cuneate nucleus (6 cells, 15%). All neurons were tested for responses to: electrical stimulation of afferents coursing through the left stellate ganglion and afferents in the left cervical vagus nerve, and somatic, auditory, and visual stimulation. No neurons responded to all five stimuli. Three cells (7.5%) responded to four stimuli, 11 (27.5%) responded to three stimuli, 10 (25.0%) responded to two stimuli, and 15 (37.5%) responded to only a single stimulus. The remaining cell was unresponsive to any stimulus. As a group, neurons in the nucleus reticularis parvicellularis received input from the greatest number of sensory modalities, and cuneate nucleus neurons received input predominantly from somatosensory afferents. External cuneate nucleus neurons displayed response profiles intermediate between nucleus reticularis parvicellularis and cuneate nucleus. In addition, eight neurons (20% of the total) were sensitive to changes in blood pressure. Results of the present study support the hypothesis that neurons in the nucleus reticularis parvicellularis receive convergent inputs from different sensory modalities.2+ behaviors.


A unique heterologous fibrin sealant (HFS) as a candidate biological scaffold for mesenchymal stem cells in osteoporotic rats.
The injection of mesenchymal stem cells (MSCs) directly into the bone of osteoporotic (OP) patients for rapid recovery has been studied worldwide. Scaffolds associated with MSCs are used to maintain and avoid cell loss after application. A unique heterologous fibrin sealant (HFS) derived from snake venom was evaluated for the cytotoxicity of its main components and as a three-dimensional biological scaffold for MSCs to repair a critical femur defect in osteoporotic rats. The cytotoxicity of HFS was assessed using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and transmission electron microscopy. The cells were cultured, characterized by flow cytometry and differentiated into the osteogenic lineage. Two-month-old rats underwent ovariectomy to induce OP. After 3 months, a 5 mm critical bone defect was made in the distal end of the rat femurs and filled with HFS; HFS + MSCs; and HFS + MSCs D (differentiated into the osteogenic lineage) to evaluate the effects. An injury control group (injury and no treatment) and blank control group (no injury and no treatment) were also included. The animals were observed at days 14 and 28 by microtomographic (micro-CT) analyses, histologic and biochemical analysis, as well as scanning electron microscopy. The results revealed that one of the compounds of HFS, the thrombin-like enzyme extracted from snake venom, had no cytotoxic effects on the MSCs. OP was successfully induced, as demonstrated by the significant differences in the levels of 17β-estradiol, Micro-CT analyses and alkaline phosphatase between the ovariectomized (OVX) and non-ovariectomized (NOVX) groups. The histological data revealed that at 14 days after surgery in both the OVX and NOVX animals, the HFS + CTMs and HFS + CTMsD showed a higher formation of bone cells at the site in relation to the control group (without treatment). Collagen formation was evidenced through bone neoformation in all treated and control groups. No morphological differences in the femurs of the NOVX and OVX animals were observed after the surgical procedure. Scanning electron microscopy (SEM) confirmed the histological analysis. The new HFS composed of two non-toxic components for MSCs showed capacity to promote the recovery of the bone lesions in OVX and NOVX animals at 14 days after surgery. In addition, the HFS enabled the differentiation of MSCs into MSCs D in the group treated with HFS + MSCs. Using the MSCs and/or MSCs D together with this biopharmaceutical could potentially enable significant advances in the treatment of osteoporotic fractures. Future clinical trials will be necessary to confirm these results.


Restoration of acetabular bone loss 2005.
The surgical strategy for revision of the acetabular component is determined by available host bone stock. Contained (cavitary) bone loss is the most common pattern of bone loss and can be addressed by morsellized bone graft. If contact can be made with at least 50% host bone, conventional uncemented cups can be used. If, however, contact with 50% host bone cannot be achieved, a protective cage and a cemented cup is an acceptable option but with a significant complication rate. The use of trabecular metal, which provides a more favorable environment for bone graft remodeling and host bone ingrowth, has allowed us to address larger contained defects without resorting to a cage. For massive contained defects, a combination of a trabecular metal cup protected by a cage has been used.


The mechanism of injury in blunt traumatic rupture of the aorta.
Rupture of the aorta accounts for a significant proportion of fatalities following blunt trauma. A great deal of consensus exists describing the circumstances under which acute traumatic aortic dissection occurs as well as its investigation and management. However, there remains some controversy surrounding the pathogenic aetiology underlying this injury. Univariate and multivariate models of blunt traumatic aortic rupture (BTAR) are discussed. To account for the consistency in the nature of BTAR, despite a range of trauma scenarios, the concepts of dynamic multivariate models and a final common pathway are introduced. Clinical management is described elsewhere. Greater understanding of the mechanism of BTAR could lead to a range of safety systems aimed at a reduction in its incidence and severity.


Association of depressive symptoms with inflammatory biomarkers among pregnant African-American women.
Depression and inflammation are associated with poorer birth outcomes. African-American women have higher levels of inflammatory biomarkers, more depressive symptoms, and a disparate burden of poorer birth outcomes, but the association between depressive symptoms and inflammation within this higher-risk group is unknown. We examined this association among African-American women in the second trimester of pregnancy and additionally tested whether body mass index (BMI) mediates or moderates this relationship. We recruited 187 women from the obstetrics clinics of a large urban health system. Depression symptoms were measured with the Center for Epidemiological Studies Depression (CES-D) scale and inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, IL-10, IL-1β, and tumor necrosis factor-α [TNF-α]) with enzyme immunoassays. Multivariate regression models were fitted to determine the association between CES-D score and each inflammatory biomarker. CES-D was not associated with hs-CRP or TNF-α. CES-D was directly associated with IL-1β (P=0.03). BMI moderated the relationship between CES-D and IL-6 (P<0.01) and IL-10 (P=0.04); in leaner women, depressive symptoms were associated with higher IL-6 and IL-10 levels, whereas in heavier women, depressive symptoms were associated with lower IL-10 levels. BMI did not mediate the relationship between CES-D and inflammation. We conclude that depressive symptoms are associated with increased inflammation among pregnant African-American women. Future studies are needed to examine if depression, mediated through inflammation, increases the risk of adverse pregnancy outcomes in African-American women.


Multiple pathways regulated by the tumor suppressor PP2A in transformation.
Reversible protein phosphorylation plays a central role in regulating intracellular signaling. Dysregulation of the mechanisms that regulate phosphorylation plays a direct role in cancer initiation and maintenance. Although abundant evidence supports the role of kinase oncogenes in cancer development, recent work has illuminated the role of specific protein phosphatases in malignant transformation. Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase in mammalian cells. Inactivation of PP2A by viral oncoproteins, mutation of specific subunits or overexpression of endogenous inhibitors contributes to cell transformation by regulating specific phosphorylation events. Here, we review recent progress in our understanding of how PP2A regulates mitogenic signaling pathways in cancer pathogenesis and how PP2A activity is modulated in human cancers.


Quantification of oxygenates, sulphides, thiols and permanent gases in propylene. A multiple linear regression model to predict the loss of efficiency in polypropylene production on an industrial scale.
This research developed a new methodology using a gas chromatograph, a pulsed discharge helium ionization detector (PDHID), and two mass spectrometric (MSD) detectors. The detectors worked simultaneously, using 8 columns and 7 valves. This new proposal for simultaneous analysis, with a single injection and analysis time of 36 min, allowed the quantification of 10 oxygenated compounds (alcohols, ketones and carboxylic acids), 3 permanent gases, 3 sulphides and 4 thiols, which are aggressive inhibitors of the Ziegler-Natta catalytic systems. The RSD (n = 6) for repeatability of the peak area of the 20 compounds analyzed, and the retention time were less than 0.59 and 0.23% respectively. The RSD (n = 6) for intermediate precision for the peak area was less than 0.85% and, for the retention time, less than 0.35%. 95% of the inhibitors analyzed showed relative errors inter and intra-day less than 3%. The inhibitors detected and quantified were: formic acid (2 to 45.32 ppm), acetic acid (1 to 25.32 ppm), acetone (5 to 72.67 ppm), methanol (1 to 39.93 ppm), isopropyl alcohol (2 to 74.88 ppm), ethanol (0.1 to 57.51 ppm), 1-propanol (0.1 to 92.36 ppm), 1-butanol (5 to 92.36 ppm), 2-butanol (5 to 95.15 ppm), tert-butanol (5 to 90.22 ppm), CO2 (0.5 to 5.0 ppm), CO (0.002 to 5.049 ppm), O2 (0.5 to 6.5 ppm), CH3(CH2)3SH (0.025 to 2.238 ppm), CH3CH2SH (0.025 to 1.595 ppm), COS (0.025 to 1.477 ppm), CH3SH (0.025 to 1.223 ppm), CH3(CH2)2SH (0.025 to 1.880 ppm), CS2 (0.025 to 1.929 ppm), H2S (0.025 to 0.847 ppm) and tert-butylmercaptan (0.025 to 2.283 ppm). These compounds generated reductions of between 5 and 20% in polypropylene production, representing losses of several million dollars. Therefore, a multilinear regression model was developed to predict this percentage of production loss in a fluidized bed reactor, based on the quantified inhibitors. The model has a correlation coefficient of 0.91 and a standard deviation of 1.12, allowing comparisons between actual and predicted experimental values. P values are less than 0.05, indicating that each inhibitor has a statistically significant effect on the model.


Expression of type I and II receptors for transforming growth factor beta in the adult rat testis.
After having established the specificity of the antibodies for the rat testis by western blot analysis, the potential target cells for transforming growth factors (TGFbetas) were identified by immunohistochemical detection of both type I (TbetaRI) and type II (TbetaRII) transducing receptors for TGFbetas in the adult rat testis in situ. Leydig cells showed a strong TbetaRII immunoreactivity whereas the TbetaRI staining was weak. Only TbetaRII was detectable in Sertoli cells. In germ cells, staining for TbetaRI was stronger than for TbetaRII and the expression of both receptors depended on the seminiferous cycle stage. TbetaRI first appeared in pachytene spermatocytes and was absent in elongated spermatids from stage XIV onwards. Labelling for TbetaRII was observed as early as the spermatogonia stage; it increased in pachytene spermatocytes at the onset of TbetaRI and disappeared in elongating spermatids from stage XI onwards. These results show that TGFbetas can affect somatic cells functions and suggest that these factors are involved in the control of meiosis and early spermiogenesis, exerting a direct effect on germ cells.


Integrating intracellular nanovesicles into integrin trafficking pathways and beyond.
Membrane traffic controls the movement of proteins and lipids from one cellular compartment to another using a system of transport vesicles. Intracellular nanovesicles (INVs) are a newly described class of transport vesicles. These vesicles are small, carry diverse cargo, and are involved in multiple trafficking steps including anterograde traffic and endosomal recycling. An example of a biological process that they control is cell migration and invasion, due to their role in integrin recycling. In this review, we describe what is known so far about these vesicles. We discuss how INVs may integrate into established membrane trafficking pathways using integrin recycling as an example. We speculate where in the cell INVs have the potential to operate and we identify key questions for future investigation.


Abrogation of Ref1 retrovirus restriction in human cells.
We have previously described postentry restriction of murine leukemia virus in mammals. Here we characterize the block in human cells. Restricted infection kinetics are multiple hit at high virus dose, and restriction is abrogated by preexposure to restricted virus. We hypothesize that restricted capsid can titrate out the restriction factor.


Effects of Early Vestibular Rehabilitation in Patients With Acute Vestibular Disorder: A Systematic Review and Meta-Analysis.
To investigate the effect of early vestibular rehabilitation on physical function and dizziness in patients with acute vestibular disorders. The electronic databases examined included PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (via Dialog), and PEDro. The inclusion criteria in terms of the study participants were patients 20 years and older with an acute unilateral peripheral vestibular disorder. We included individual randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and crossover trials. The outcomes were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function. Early vestibular rehabilitation was defined as rehabilitation within 14 days of vestibular disorder onset or surgery. Main outcome measures were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function. Twelve trials involving 542 participants were included. Early vestibular rehabilitation improved the Dizziness Handicap Inventory by -7.18 (95% confidence interval [CI], -10.48 to -3.88), balance during eyes close by -1.40 (95% CI, -2.42 to -0.39), and dizziness by -1.47 (95% CI, -2.74 to -0.21) compared with no intervention or placebo. The present study demonstrated that early vestibular rehabilitation improved the Dizziness Handicap Inventory, balance (eyes close), and subjective dizziness in a patient with acute vestibular disorders. This result indicates that early vestibular rehabilitation can promote vestibular compensation.


Direct, quantitative, and noninvasive imaging of the transport of active agents through intact brain with positron emission tomography.
Our goal was to use positron emission tomography (PET) to analyze the movement of radiolabeled agents in tissue to enable direct measurement of drug delivery to the brain. Various (11)C- and (18) F-labeled compounds were delivered directly to an agarose phantom or rat striatum. Concentration profiles were extracted for analysis and fitted to diffusion models. Diffusion coefficients ranged from 0.075 ± 0.0026 mm(2)/min ([(18) F]fluoride ion, 18 Da) to 0.0016 ± 0.0018 mm(2)/min ([(18) F]NPB4-avidin, 68 kDa) and matched well with predictions based on molecular weight (R (2) = 0.965). The tortuosity of the brain extracellular space was estimated to be 1.56, with the tissue clearance halftime of each tracer in the brain varying from 19 to 41 min. PET is an effective modality to directly quantify the movement of locally delivered drugs or drug carriers. This continuous, noninvasive assessment of delivery will aid the design of better drug delivery methods.


Perceived stress and E-cigarette use during emerging adulthood: A longitudinal examination of initiation, progression, and continuation.
E-cigarettes are the most commonly used tobacco product among youth and young adults in the US. Limited research has examined how stress impacts e-cigarette use among young people. We examine the longitudinal associations between perceived stress scale (PSS) score and e-cigarette use behaviors among a diverse cohort of emerging adults. We analyzed two waves of data collected in Fall 2019 (baseline) and Spring 2020 (6-month follow-up) of the Texas Adolescent Tobacco and Marketing Surveillance (TATAMS) system. Participants were classified into three mutually exclusive subsamples at baseline: (1) n = 1177 never e-cigarette users; (2) n = 806 ever but not current (past 30-day) e-cigarette users (i.e., ever users); and (3) n = 257 current (past 30-day) e-cigarette users. Three multivariate logistic regression models examined the relationship between PSS at baseline and: (1) initiation among never users; (2) progression to current use among ever users; and (3) continuation among current users, at 6-month follow-up. PSS scores were standardized using z-scores. Models controlled for race/ethnicity, sex, age, ever marijuana use, and ever use of other tobacco products. Mean age ranged from 18.6 to 19.4 among cohorts. Risk for e-cigarette progression among ever users (aOR: 1.30; 95%CI: 1.01-1.69) and e-cigarette continuation among current users (aOR: 1.33 (95%CI: 1.01-1.75) increased with each unit increase in PSS score at baseline. PSS at baseline was not associated with e-cigarette initiation among never users. PSS predicted greater risk of e-cigarette progression and continuation but not initiation among a diverse cohort of emerging adults. E-cigarette prevention and cessation strategies should consider perceived stress an important risk factor for e-cigarette use during emerging adulthood.


The Benefits of Living With Close Others: A Longitudinal Examination of Mental Health Before and During a Global Stressor.
For better or worse, the people one lives with may exert a powerful influence on one's mental health, perhaps especially during times of stress. The COVID-19 pandemic-a large-scale stressor that prompted health recommendations to stay home to reduce disease spread-provided a unique context for examining how the people who share one's home may shape one's mental health. A seven-wave longitudinal study assessed mental health month to month before and during the pandemic (February through September 2020) in two diverse samples of U.S. adults (N = 656; N = 544). Preregistered analyses demonstrated that people living with close others (children and/or romantic partners) experienced better well-being before and during the pandemic's first 6 months. These groups also experienced unique increases in ill-being during the pandemic's onset, but parents' ill-being also recovered more quickly. These findings highlight the crucial protective function of close relationships for mental health both generally and amid a pandemic.


Cortical processing of location and frequency changes of sounds in normal hearing listeners.
Sounds we hear in our daily life contain changes in the acoustic features (e.g., frequency, intensity, and duration or "what" information) and/or changes in location ("where" information). The purpose of this study was to examine the cortical auditory evoked potentials (CAEPs) to the change within a stimulus, the acoustic change complex (ACC), in frequency (F) and location (L) of the sound in normal hearing listeners. Fifteen right-handed young normal hearing listeners participated in the electroencephalographic (EEG) recordings. The acoustic stimuli were pure tones (base frequency at 250 Hz) of 1 s, with a perceivable change either in location (L, 180°), frequency (F, 5% and 50%), or both location and frequency (L+F) in the middle of the tone. Additionally, the 250 Hz tone of 1 sec without any change was used as a reference. The participants were asked to listen passively to the stimuli and not to move their heads during the testing. Compared to the reference tone, by which only the onset-CAEP was elicited, the tones containing changes (L, F, or L+F) elicited both onset-CAEP and the ACC. The waveform analysis of ACCs from the vertex electrode (electrode Cz) showed that, larger sound changes evoked larger peak amplitudes [e.g., (L+50%F)- > L-change; (L+50%F)- > 5%F-change] and shorter the peak latencies ([(L+5%F)- < 5%F-change; 50%F- < 5%F-change; (L+50%F)- < 5%F-change] . The current density patterns for the ACC N1' peak displayed some differences between L-change vs. F-change, supporting different cortical processing for "where" and "what" information of the sound; regardless of the nature of the sound change, larger changes evoked a stronger activation than smaller changes [e.g., L- > 5%F-change; (L+5%F)- > 5%F-change; 50%F- > 5%F-change] in frontal lobe regions including the cingulate gyrus, medial frontal gyrus (MFG), superior frontal gyrus (SFG), the limbic lobe cingulate gyrus, and the parietal lobe postcentral gyrus. The results suggested that sound change-detection involves memory-based acoustic comparison (the neural encoding for the sound change vs. neural encoding for the pre-change stimulus stored in memory) and involuntary attention switch.


Triplex formation by pyrene-labelled probes for nucleic acid detection in fluorescence assays.
Triplex-forming homopyrimidine oligonucleotides containing insertions of a 2'-5' uridine linkage featuring a pyrene moiety at the 3'-position exhibit strong fluorescence enhancement upon binding to double-stranded DNA through Hoogsteen base pairing. It is shown that perfect matching of the new modification to the base pair in the duplex is a prerequisite for strong fluorescence, thus offering the potential to detect single mutations in purine stretches of duplex DNA. The increase in the fluorescence signal was dependent on the thermal stability of the parallel triplex, so a reduction in the pH from 6.0 to 5.0 resulted in an increase in thermal stability from 25.0 to 55.0 degrees C and in an increase in the fluorescence quantum yield (Phi(F)) from 0.061 to 0.179, while the probe alone was fluorescently silent (Phi(F)=0.001-0.004). To achieve higher triplex stability, five nucleobases in a 14-mer sequence were substituted with alpha-L-LNA monomers, which provided a triplex with a T(m) of 49.5 degrees C and a Phi(F) of 0.158 at pH 6.0. Under similar conditions, a Watson-Crick-type duplex formed with the latter probe showed lower fluorescence intensity (Phi(F)=0.081) than for the triplex.


Enzymatic redox cofactor regeneration in organic media: functionalization and application of glycerol dehydrogenase and soluble transhydrogenase in reverse micelles.
An enzymatic system for the regeneration of redox cofactors NADH and NADPH was investigated in nanostructural reverse micelles using bacterial glycerol dehydrogenase (GLD) and soluble transhydrogenase (STH). Catalytic conversion of NAD+ to NADH was realized in the sodium dioctylsulfosuccinate (AOT)/isooctane reverse micellar system harboring GLD and a sacrificial substrate, glycerol. The initial rate of NADH regeneration was enhanced by exogenous addition of ammonium sulfate into the reverse micelles, suggesting that NH4+ acts as a monovalent cationic activator. STH was successfully entrapped in the AOT/isooctane reverse micelles as well as GLD and was revealed to be capable of catalyzing the stoichiometric hydrogen transfer reaction between NADP+ and NADPH in reverse micelles. These results indicate that GLD and STH have potential for use in redox cofactor recycling in reverse micelles, which allows the use of catalytic quantities of NAD(P)H in organic media.


[New employment opportunities: atypical jobs state of the art and general consideration on legislation].
The Authors in this contribute, describe new job opportunities, that are to considered a need for those who are looking for a new employment. Otherwise this new kind of work, called atypical job, offers new possibility in lack of regular job. It also described the law juridical profiles of this new emerging atypical workers.


Detection and quantification of ochratoxin A and deoxynivalenol in barley grains by GC-MS and electronic nose.
Mycotoxin contamination of cereal grains can be detected and quantified using complex extraction procedures and analytical techniques. Normally, the grain odour, i.e. the presence of non-grain volatile metabolites, is used for quality classification of grain. We have investigated the possibility of using fungal volatile metabolites as indicators of mycotoxins in grain. Ten barley samples with normal odour, and 30 with some kind of off-odour were selected from Swedish granaries. The samples were evaluated with regard to moisture content, fungal contamination, ergosterol content, and levels of ochratoxin A (OA) and deoxynivalenol (DON). Volatile compounds were also analysed using both an electronic nose and gas chromatography combined with mass spectrometry (GC-MS). Samples with normal odour had no detectable ochratoxin A and average DON contents of 16 microg kg(-1) (range 0-80), while samples with off-odour had average OA contents of 76 microg kg(-1) (range 0-934) and DON contents of 69 microg kg(-1) (range 0-857). Data were evaluated by multivariate data analysis using projection methods such as principal component analysis (PCA) and partial least squares (PLS). The results show that it was possible to classify the OA level as below or above the maximum limit of 5 microg kg(-1) cereal grain established by the Swedish National Food Administration, and that the DON level could be estimated using PLS. Samples with OA levels below 5 microg kg(-1) had higher concentration of aldehydes (nonanal, 2-hexenal) and alcohols (1-penten-3-ol, 1-octanol). Samples with OA levels above 5 microg kg(-1) had higher concentrations of ketones (2-hexanone, 3-octanone). The GC-MS system predicted OA concentrations with a higher accuracy than the electronic nose, since the GC-MS misclassified only 3 of 37 samples and the electronic nose 7 of 37 samples. No correlation was found between odour and OA level, as samples with pronounced or strong off-odours had OA levels both below and above 5 microg kg(-1). We were able to predict DON levels in the naturally contaminated barley samples using the volatile compounds detected and quantified by either GC-MS or the electronic nose. Pentane, methylpyrazine, 3-pentanone, 3-octene-2-ol and isooctylacetate showed a positive correlation with DON, while ethylhexanol, pentadecane, toluene, 1-octanol, 1-nonanol, and 1-heptanol showed a negative correlation with DON. The root mean square error of estimation values for prediction of DON based on GC-MS and electronic nose data were 16 and 25 microg kg(-1), respectively.


Diagnosis of dental abnormalities in children using 3-dimensional magnetic resonance imaging.
To assess the feasibility of magnetic resonance imaging (MRI) of dental abnormalities in children. The study included 16 patients (mean age, 10.8 yr) prospectively selected from 1,500 orthodontic patients. The selected patients included 3 with a mesiodens, 9 with supernumerary teeth other than a mesiodens, 1 with gemination, 1 with dilacerations, 1 with transmigration, and 1 with transposition. Three-dimensional (3D) images were acquired on a 1.5-T MRI scanner using a 3D turbo spin echo pulse sequence with a voxel size of 0.8 × 0.8 × 1 mm. The measurement time was 4 to 5 minutes. Using natural MRI contrast, the teeth, dental pulp, mandibular canal, and cortical bone could be clearly delineated. The position and shape of malformed teeth could be assessed in all 3 spatial dimensions. MRI was found to be a well-tolerated imaging modality for the diagnosis of dental abnormalities in children and for orthodontic treatment and surgical planning. Compared with conventional radiography, dental MRI provides the advantage of 3-dimensionality and complete elimination of ionizing radiation, which is particularly relevant for repeated examinations in children.


The effect of glucose on the synthesis of prostaglandins by the renal papilla of the rat in vitro.
Renal pappillae from rats were incubated in vitro. The release of prostaglandin by this tissue was found to be inversely related to the glucose concentration of the buffer. Estimates of prostaglandin release were determined by a rat stomach strip bioassay, and in some instances, gas-chromatography and mass spectrometry. When incubated in the presence of C14-arachidonic acid, the specific activity of prostaglandins E2 and F2 alpha released by the tissue was lower at the lower glucose concentration. Provision of 625 micrograms/ml of exogenous arachidonic acid in the buffer obliterated the effect of glucose on prostalglandin release. These data indicate that increasing amounts of glucose suppresses prostaglandin synthesis in the renal papilla of the rat, and that the mechanism of this phenomenon is related to the release of arachidonic acid from its storage pools in tissue lipids.


Association of retinal sensitivity to integrity of photoreceptor inner/outer segment junction in patients with diabetic macular edema.
To evaluate the relationship between retinal sensitivity and the photoreceptor inner segment/outer segment (IS/OS) layer status in patients with diabetic macular edema (DME). Cross-sectional study. Twenty-five adult patients (37 eyes) diagnosed with DME and managed at the Wilmer Eye Institute, Johns Hopkins University (Baltimore, MD). We obtained simultaneous fundus microperimetry (MP) and optical coherence tomography (OCT) of patients with DME using a combined MP/OCT system. The device recorded retinal sensitivity and retinal thickness on a 3-dimensional tomography map, and we performed a point-by-point analysis of the IS/OS layer integrity at every MP point. We also reviewed OCT scans to determine the type of DME, cystoid macular edema, or diffuse macular edema (absence of any cysts). In addition, fixation stability and fixation location were analyzed. Retinal point sensitivity measured by MP. Twenty-five patients (37 eyes: 29 male and 8 female; mean age, 64.16 years) with DME were enrolled. Fixation was centric in 30 eyes (81%), paracentric in 3 eyes (8%), and eccentric in 4 eyes (11%). Twenty-seven eyes had cystoid macular edema, and 10 eyes had diffuse macular edema. Mean central subfield thickness was 325 μm. We analyzed a total of 1036 individual MP points. Mean point sensitivity was 10.51 dB. A total of 793 points (76.5%) had IS/OS layer present, and 243 points (23.5%) had IS/OS layer disrupted. A mixed linear model, constructed to adjust for potential confounders and account for dependence between retinal points, revealed that the absence of the IS/OS junction was significantly associated with a 3.28-dB decrease in retinal point sensitivity (P<0.001). This novel index study demonstrates that disruption of the IS/OS junction is correlated with a significant decrease in point sensitivity in eyes with DME. Further studies are indicated to confirm and validate this relationship. Proprietary or commercial disclosure may be found after the references.


Rhythmic arm cycling differentially modulates stretch and H-reflex amplitudes in soleus muscle.
During rhythmic arm cycling, soleus H-reflex amplitudes are reduced by modulation of group Ia presynaptic inhibition. This suppression of reflex amplitude is graded to the frequency of arm cycling with a threshold of 0.8 Hz. Despite the data on modulation of the soleus H-reflex amplitude induced by rhythmic arm cycling, comparatively little is known about the modulation of stretch reflexes due to remote limb movement. Therefore, the present study was intended to explore the effect of arm cycling on stretch and H-reflex amplitudes in the soleus muscle. In so doing, additional information on the mechanism of action during rhythmic arm cycling would be revealed. Although both reflexes share the same afferent pathway, we hypothesized that stretch reflex amplitudes would be less suppressed by arm cycling because they are less inhibited by presynaptic inhibition. Failure to reject this hypothesis would add additional strength to the argument that Ia presynaptic inhibition is the mechanism modulating soleus H-reflex amplitude during rhythmic arm cycling. Participants were seated in a customized chair with feet strapped to footplates. Three motor tasks were performed: static control trials and arm cycling at 1 and 2 Hz. Soleus H-reflexes were evoked using single 1 ms pulses of electrical stimulation delivered to the tibial nerve at the popliteal fossa. A constant M-wave and ~6% MVC activation of soleus were maintained across conditions. Stretch reflexes were evoked using a single sinusoidal pulse at 100 Hz given by a vibratory shaker placed over the triceps surae tendon and controlled by a custom-written LabView program. Results demonstrated that rhythmic arm cycling that was effective for conditioning soleus H-reflexes did not show a suppressive effect on the amplitude of the soleus stretch reflex. We suggest this indicates that stretch reflexes are less sensitive to conditioning by rhythmic arm movement, as compared to H-reflexes, due to the relative insensitivity to Ia presynaptic inhibition.


Gangrenous ligamentum teres hepatis causing acute abdominal symptoms.
This unusual case of a gangrenous round ligament manifested by acute abdominal symptoms underscores the importance of the recent radiologic descriptions of the round ligament in computerized tomography and ultrasonography. The cause of the gangrenous process in this case remains unresolved.


ClinCare: improving vascular outcomes through clinical care coordination.
In the current health care environment, increasing emphasis is being placed on the quality and financial outcomes of care by both consumers and third party payors. The ClinCare (registered service mark of Jewish Hospital, Louisville, Ky) program uses an interdisciplinary approach and data-driven decision making to improve the clinical management of specific high-risk patient populations across the continuum of care. The experience of the Vascular and Thoracic Surgery Clinical Practice Team is discussed with emphasis on clinical and financial outcomes.


Effective B cell activation in vitro during viremic HIV-1 infection with surrogate T cell stimulation.
Identifying HIV-1-associated B cell defects and responses to activation may direct interventions to circumvent their impaired antibody responses to infection and vaccines. Among 34 viremic HIV-1-infected and 20 seronegative control adults, we measured baseline frequencies and activation of B and T cell subsets, expression of activation-induced cytidine deaminase (AID), potential determinants of B cell activation in vivo and B and T cell responses in vitro. At baseline, HIV-1 infection was associated with increased IgM memory and decreased anergic cell frequencies, as well as increased activation in all 10 B cell subsets compared with controls. HIV-1 status, TFH activation, and BAFF were significant potential drivers of B cell activation. Despite high baseline activation among HIV-1-infected subjects, stimulation in vitro with combined surrogates for antigen (anti-IgM), cognate (CD40 ligand) and soluble T cell factors (IL-4) elicited comparable B cell activation, transitions from naïve to class-switched memory cells and AID expression in both groups. In summary, viremic HIV-1 infection perturbs circulating B cell subsets and activation at each stage of B cell maturation. However, that appropriate stimulation of B cells elicits effective activation and maturation provides impetus for advancing vaccine development to prevent secondary infections by circumventing early B cell defects.


Optimizing antibody expression by using the naturally occurring framework diversity in a live bacterial antibody display system.
Rapid identification of residues that influence antibody expression and thermostability is often needed to move promising therapeutics into the clinic. To establish a method that can assess small expression differences, we developed a Bacterial Antibody Display (BAD) system that overcomes previous limitations, enabling the use of full-length formats for antibody and antigen in a live cell setting. We designed a unique library of individual framework variants using natural diversity introduced by somatic hypermutation, and screened half-antibodies for increased expression using BAD. We successfully identify variants that dramatically improve expression yields and in vitro thermostability of two therapeutically relevant antibodies in E. coli and mammalian cells. While we study antibody expression, bacterial display can now be expanded to examine the processes of protein folding and translocation. Additionally, our natural library design strategy could be applied during antibody humanization and library design for in vitro display methods to maintain expression and formulation stability.


Management of Bimaxillary Protrusion.
Bimaxillary protrusion is a unique dentofacial deformity trait that can exist in an individual as an isolated problem or in combination with other skeletal and dental-related issues. Orthodontist and oral and maxillofacial surgeons are often the main primary team involved in the management of bimaxillary protrusion. Clinical dilemma often exists as cases can either be treated orthodontically or may require a combination of orthodontic and skeletal segmental orthognathic surgery. This article aims to help clinicians improve their approach to management of bimaxillary protrusion by creating a classification based on the severity that can guide treatment selection.